Accepted Manuscript

Syntheses of 2-Silicon-Substituted 13-Dienes

Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi Mark EWelker

PII S0022-328X(13)00927-3

DOI 101016jjorganchem201312046

Reference JOM 18432

To appear in Journal of Organometallic Chemistry

Received Date 25 October 2013

Revised Date 23 December 2013

Accepted Date 24 December 2013

Please cite this article as PP Choudhury CS Junker RR Pidaparthi ME Welker Synthesesof 2-Silicon-Substituted 13-Dienes Journal of Organometallic Chemistry (2014) doi 101016jjorganchem201312046

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Abstract

A number of 2-silicon substituted 13ndashdienes have been prepared by one of three routes 1) Reactions of 13-dienyl Grignard reagents with silyl electrophiles or silyl Grignard reagents with 13-dienyl electrophiles 2) Hydrosilylation of enynes 3) Enyne cross metathesis The strengths and limitations of each preparative method are discussed

Keywords 13-dienes metal dienyls Grignard reactions hydrosilylation enyne cross metathesis 1 Introduction

We have been interested in the preparation and reaction chemistry of metal substituted dienes

for over 15 years Initially we prepared a number of transition metal substituted dienes1 for

these studies but more recently we have been interested in the investigation of silicon and boron

substituted dienes2 We have reported the preparation of 2-silicon substituted 13-butadienes by

one of three different routes and demonstrated that they could be used in sequential Diels-

Aldercross coupling reactions but we have never discussed the strengths and limitations of these

different silicon substituted diene preparative routes3 Here we report the preparation of new 2-

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silicon substituted 13-dienes by one of three different routes and focus our discussion on a

comparison of those routes

2 Results and discussion

21 Preparation of 2-silicon substituted 13-dienes via Grignard chemistry

Preparation of 2-silicon substituted 13 dienes via Grignard chemistry can be accomplished by

one of two methods i) preparation of a dienyl Grignard reagent and its addition to a silicon

electrophile or ii) preparation of a silicon containing Grignard reagent and its addition to a dienyl

electrophile (Scheme 1) In our prior work we have been successful in preparing Grignard

reagents from simple halodienes like chloroprene (1) followed by treatment of those reagents

with boron substituted electrophiles4 or alkoxy silyl electrophiles3a but had always encountered

some difficulties in attempting to use Grignard reagents prepared from more highly substituted

13-dienes5 We have found the same trends to hold for silicon substituted diene synthesis with

alkyl or aryl silyl reagents So while a Grignard reagent prepared from chloroprene (1) reacts

with dimethylphenylsilyl chloride or dichlorodimethylsilane (followed by hydrolysis)6 to

provide new dienes (2 amp 3) we found it most convenient to use trimethylsilylmagnesium

chloride addition to the more highly substituted halodienes (4 and 6) to produce the trimethylsilyl

substituted dienes 57 and 7 Attempts to prepare Grignard reagents from dienes 4 and 6 and react

them with TMSCl produced diene dimerization and decomposition products rather than 5 and 7

Diene 2 participated in a Diels-Alder reaction cleanly with N-phenylmaleimide in high yield to

produce 8

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Cl ClMg

PhMe2SiCl 05M HClMg

PhMe2Si

1 2 97

Br

4

Br

6

Ph

+ TMSMgCl

+ TMSMgCl

TMS

5 85

Ph

TMS

7 47

1) Me2SiCl2

2) 1M acetate

buffer

Me2(OH)Si

3 46

NPh

Si

O

O

H

H

NPM

4h

THF

8 98

Scheme 1 Preparation of Silyl Dienes via Grignard Chemistry

22 Preparation of 2-silicon substituted 13-dienes via hydrosilylation of enynes

Our next attempts at the synthesis of 4-substituted 2-silyl dienes involved the cis-

hydrosilylation of 13-enynes (Scheme 2) (E)-4-phenyl-3-buten-1-yne (9) was synthesized from

trans-cinnamaldehyde via the Colvin rearrangement8 Ruthenium-catalyzed hydrosilylation of

enyne (9) with triethoxysilane (10) was performed with Grubbs 1st generation catalyst and

cyclopentadienyl ruthenium salt (11) These reactions produced mixtures of 2- and 1-siloxy

substituted dienes (12 and 13) We also investigated a copper(I)-catalyzed hydrosilylation

protocol employing silyl boranes and this method also leads to a mixture of 2-silicon and 1-

silicon substituted 13 diene products (1516)9 The authors who first reported this method

hypothesized a mechanism involving transmetallation to a cupric silane species and subsequent

silylcupration of an alkyne Under these conditions we were able to effect hydrosilylation using

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(dimethylphenylsilyl)boronic acid pinacol ester (14) to yield dienes (15 amp 16) in moderate yield

and regioselectivity

Scheme 2 Enyne Cis-Hydrosilylation

In addition to these enyne hydrosilylation reactions we also executed new examples of Leersquos

protocol10 which utilizes an initial silylation of a terminal alkyne followed by a carbonyl

condensation (Scheme 3) The overall reaction is an example of an unusual trans hydrosilylation

of an alkyne With commercially available 3-methyl-3-buten-1-yne (17 R1 = H R2 = Me) the

yield for 2 steps (condensation with diisopropylchlorosilane to yield 18a followed by

condensation with acetone to yield 19a) was an acceptable 72 Silylation of that same alkyne

(17 R1 = H R2 = Me) with dimethylchlorosilane also yields an alkyne (18b) in good yield The

crude product after condensation with acetone contains 19b (by 1H NMR) but this compound did

not survive chromatographic purification on silica or alumina 4-Phenyl-3-buten-1-yne (9) also

condenses with diisopropylchlorosilane to yield 18c in acceptable yield and that alkyne

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condenses with formaldehyde to produce another example of a siloxycyclopentene (19c) in good

yield

Scheme 3 Enyne Trans-Hydrosilylation

23 Preparation of 2-silicon substituted-13-dienes via enyne metathesis

In the past we had also reported the use of intermolecular enyne cross metathesis to prepare 2-

trialkoxysilyl substituted 13 dienes3de but had not tried this method for triaryl or trialkyl silyl

substituted alkynes or for any intramolecular enyne cross metathesis We first tried this reaction

with triphenylsilylacetylene (20) and styrene (21) however we only isolated 2-triphenylsilyl-13-

butadiene (23) in good yield (69) along with trans-stilbene (24) (Scheme 4) We hypothesized

that the ethylene atmosphere typically used in these reactions contributed to the formation of 23

however in the absence of ethylene the reaction still resulted in formation of 23 Given that

observation it appears that ruthenium benzylidene catalyst must react much faster with styrene

(21) to produce trans-stilbene (24) and methylidene catalyst (25) than it reacts with

tripheynylsilylacetylene (20) so it is the methylidene catalyst (25) that reacts with 20 and leads to

the isolated silyl substituted diene product (23)

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Scheme 4 Enyne Metathesis of Triphenylsilylacetylene

We also tried enyne metathesis on a commercially available internal alkyne (26) which bears a

trialkylsilyl group on the alkyne (Scheme 5)11 This reaction resulted in low yield and the use of

an internal alkyne changed the regiochemistry of the metathesis reaction to yield 123-

trisubstituted diene (27)

Scheme 5 Enyne Metathesis of an Internal Trimethylsilyl Substituted Alkyne

We had never attempted an intramolecular version of this enyne cross metathesis reaction but

we found that it could be effected for a benzyldimethyl substituted heptenyne (29) to produce

silyl substituted diene (30) (Scheme 6) However when we went to the next higher homolog ie

an octenyne (32) we could prepare the enyne (32) in good yield but we noted only enyne

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decomposition with different ruthenium catalysts catalyst loadings and solvents in attempts to

produce 33 by enyne metathesis The observed product 30 is most easily rationalized through an

yne then ene cross metathesis mechanism rather than an ene then yne mechanism12

SiSi

Li

DMSODean-Stark

nBu-Li

SiCl

Bn

THF

Hoveyda-Grubbs Catalyst2nd Generation 15 mol

DCM reflux

H2N

NH2

-78 oC RT

12 h

12 h

Br

X

31

32 65 33

Scheme 6 Intramolecular Silyl Enyne Cross Metathesis

3 Conclusions

In cases where 2-halo-13 dienes are commercially available or synthetically accessed easily

using Grignard chemistry to make 2-silyl-13 dienes is the preferred method of synthesis When

the 2-halo-13-dienes are not readily available cis-hydrosilylation of enynes containing terminal

alkynes leads to mixtures of regioisomeric products Compare for instance the preparation of

diene 5 using Grignard chemistry to the preparation of structurally related diene 15 by

hydrosilylation to note the advantages of the Grignard approach when feasible Trans-

hydrosilylation of enynes in conjunction with carbonyl compound trapping is a viable synthetic

route to siloxy substituted alkenyl cyclopentenes (19) Intermolecular enyne cross metathesis

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can be used to make 4-alkyl or 4-aryl-2-silicon substituted dienes if the terminal alkynes used for

cross metathesis bear small substituents on silicon3d The reaction fails as a route to make 4-

substituted-2-silicon dienes if the terminal alkyne used bears silicon with large substituents such

as 20 Intramolecular enyne cross metathesis can be used to make additional silyl substituted

alkenyl cyclopentenes such as 30 but fails as a route to make a silyl substituted alkenyl

cyclohexenes such as 33

4 Experimental

41 General Procedures are part of the Supplementary Material

421 Synthesis of (Buta-13-dien-2-yl)dimethyl(phenyl)silane (2) Chloroprene (458 g 517

mmol) and phenyldimethylchlorosilane (803 g 471 mmol) were used according to the general

procedure to yield a light yellow colored crude product (144 g) as a mixture of diene and

xylenes The crude product was subjected to fractional distillation at reduced pressure (20 mm

45 ⁰C) which resulted in a brown colored liquid which was further purified by flash

chromatography (100 pentanes) to yield the title compound (2) as a light yellow liquid (836 g

444 mmol 97) Rf 063 (100 pentanes) 1H NMR (500 MHz CDCl3) δ 749minus755 (m 2H)

731minus737 (m 3H) 646 (dd J = 177 109 Hz 1H) 588 (d J = 32 Hz 1H) 551 (d J = 32

Hz 1H) 510 (d J = 177 Hz 1H) 500 (d J = 109 Hz 1H) 043 (s 6H) 13C NMR (75 MHz

CDCl3) δ 1476 1411 1382 1339 1304 1290 1278 1167 minus23 HRMS calcd for C12H16Si

(M+) 1881021 found 1881020

422 Synthesis of (Buta-13-dien-2-yl) dimethylsilanol (3) Chloroprene in 50 xylenes

(10mL 515 mmol) and dichlorodimethylsilane (0645 g 5 mmol) were used according to the

general procedure above (1M acetate buffer of pH 5 was used instead of 05M HCl for the

quench) to yield a light yellow colored liquid 1H NMR of the crude product (11g) showed a

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mixture of xylenes diene and the corresponding disiloxane dimer Kugelrohr distillation at 60˚C

(4mm Hg) of the crude product yielded the target compound (3) (0300g 23 mmol 46) 1H

NMR (300 MHz CDCl3) δ 646 (dd J = 178 108 Hz 1H) 577 (d J = 30 Hz 1H) 556 (d J =

29 Hz 1H) 537 (d J = 182 Hz 1H) 512 (d J = 108 Hz 1H) 225 (bs 1H) 030 (s 6H) 13C

NMR (75 MHz CDCl3) δ 14865 14088 12958 11656 032 EIMS calcd for C6H13OSi

(M+H)+ 12906 found 1290

431 Synthesis of Trimethyl[(E)-4-phenyl-13-butadien-2-yl]silane (5) 1-[(E)-3-Bromobuta-13-

dienyl]benzene13 (4) (199 g 949 mmol) and trimethylsilylchloride (137 g 126 mmol) were

used according to the general method producing the crude compound as a dark brown liquid

Purification by flash chromatography (hexanes Et2O 91) yielded compound 5 as a brown-

yellow oil (156 g 773 mmol 85) This compound has been reported previously by a

different route but no characterization data were provided14 Rf 015 (hexanesEt2O 91) 1H

NMR (500 MHz CDCl3) δ 743 (d J = 77 Hz 2H) 734 (t J = 77 Hz 2H) 724 (t J = 74 Hz

1H) 694 (d J = 165 Hz 1H) 664 (d J = 165 Hz 1H) 589 (d J = 30 Hz 1H) 553 (d J =

30 Hz 1H) 027 (s 9H) 13C NMR (75 MHz CDCl3) δ 1489 1377 1340 1305 1286 1285

1273 1263 08

432 Synthesis of (1-Cyclohexylideneprop-2-en-2-yl)trimethylsilane (7) Chlorotrimethylsilane

(0685 g 630 mmol) and (2-bromoallylidene)cyclohexene15 (6) (0929 g 464 mmol) were used

according to the general procedure The resulting dark brown crude residue after purification by

flash chromatography (hexanes Et2O 151 rarr 91) yielded compound 7 as a brown-yellow oil

(0483 g 249 mmol 47) Rf 084 (hexanesEt2O 151) 1H NMR (500 MHz CDCl3) δ 571 (s

1H) 540minus549 (m 2H) 210minus223 (m 4H) 154minus160 (m 4H) 141minus150 (m 2H) 007 (s

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9H) 13C NMR (75 MHz CDCl3) δ 1503 1405 1251 1235 374 293 290 283 269

minus195 HRMS calcd for C12H22Si (M+) 1941491 found 1941489

44 Diels-Alder Reactions

441 Synthesis of 3a477a-Tetrahydro-5-[dimethyl(phenyl)silyl]-2-phenyl-2H-isoindole-13-

dione (8) Diene (2) (0302 g 160 mmol) and N-phenylmaleimide (0103 g 0595 mmol) were

dissolved in THF (5mL) and degassed in a sealed tube After heating for 4h at 90 ⁰C the reaction

mixture was filtered through a cotton plug and volatiles were removed by rotary evaporation

The resulting yellow colored residue was purified by flash chromatography with the excess diene

(2) eluting (0151 g 0802 mmol 78 recovery Rf 084 pentanediethyl ether 11) followed by

the cycloadduct 8 as a colorless clear viscous liquid (0204 g 0564 mmol 98) Rf 029

(pentanediethyl ether 11) 1H NMR (500 MHz CDCl3) δ 741minus754 (m 4H) 729minus741 (m

4H) 709minus720 (m 2H) 634 (m 1H) 318minus330 (m 2H) 271minus288 (m 2H) 222minus236 (m

2H) 036 (s 3H) 035 (s 3H) 13C NMR (75 MHz CDCl3) δ 1791 1787 1407 1384 1370

1339 1320 1292 1290 1284 1278 1263 393 392 264 250 -388 -389 HRMS calcd

for C22H23NO2Si (M+) 3611498 found 3611490 Anal calcd for C22H23NO2Si C 7310 H

642 Found C 7263 H 638

45 Cis-Hydrosilylation Reactions

452 Copper-catalyzed hydrosilylation of (E)-4-phenyl-3-buten-1-yne (9) To a 5-mL sealable

microwave tube equipped with a stir bar copper(I) chloride (0031 g 031 mmol) JohnPhos

(0037 g 012 mmol) and sodium tert-butoxide (0015 g 016 mmol) were suspended in THF

(26 mL) and degassed with argon (Dimethylphenylsilyl)boronic acid pinacol ester (14) (234

microL 086 mmol) was added to the reaction vessel the tube was sealed with a crimp cap and

placed in a circulating chiller at 0 degC After 30 min (E)-4-phenyl-3-buten-1-yne (9) (0108 g

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

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Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

1

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silicon substituted 13-dienes by one of three different routes and focus our discussion on a

comparison of those routes

2 Results and discussion

21 Preparation of 2-silicon substituted 13-dienes via Grignard chemistry

Preparation of 2-silicon substituted 13 dienes via Grignard chemistry can be accomplished by

one of two methods i) preparation of a dienyl Grignard reagent and its addition to a silicon

electrophile or ii) preparation of a silicon containing Grignard reagent and its addition to a dienyl

electrophile (Scheme 1) In our prior work we have been successful in preparing Grignard

reagents from simple halodienes like chloroprene (1) followed by treatment of those reagents

with boron substituted electrophiles4 or alkoxy silyl electrophiles3a but had always encountered

some difficulties in attempting to use Grignard reagents prepared from more highly substituted

13-dienes5 We have found the same trends to hold for silicon substituted diene synthesis with

alkyl or aryl silyl reagents So while a Grignard reagent prepared from chloroprene (1) reacts

with dimethylphenylsilyl chloride or dichlorodimethylsilane (followed by hydrolysis)6 to

provide new dienes (2 amp 3) we found it most convenient to use trimethylsilylmagnesium

chloride addition to the more highly substituted halodienes (4 and 6) to produce the trimethylsilyl

substituted dienes 57 and 7 Attempts to prepare Grignard reagents from dienes 4 and 6 and react

them with TMSCl produced diene dimerization and decomposition products rather than 5 and 7

Diene 2 participated in a Diels-Alder reaction cleanly with N-phenylmaleimide in high yield to

produce 8

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Cl ClMg

PhMe2SiCl 05M HClMg

PhMe2Si

1 2 97

Br

4

Br

6

Ph

+ TMSMgCl

+ TMSMgCl

TMS

5 85

Ph

TMS

7 47

1) Me2SiCl2

2) 1M acetate

buffer

Me2(OH)Si

3 46

NPh

Si

O

O

H

H

NPM

4h

THF

8 98

Scheme 1 Preparation of Silyl Dienes via Grignard Chemistry

22 Preparation of 2-silicon substituted 13-dienes via hydrosilylation of enynes

Our next attempts at the synthesis of 4-substituted 2-silyl dienes involved the cis-

hydrosilylation of 13-enynes (Scheme 2) (E)-4-phenyl-3-buten-1-yne (9) was synthesized from

trans-cinnamaldehyde via the Colvin rearrangement8 Ruthenium-catalyzed hydrosilylation of

enyne (9) with triethoxysilane (10) was performed with Grubbs 1st generation catalyst and

cyclopentadienyl ruthenium salt (11) These reactions produced mixtures of 2- and 1-siloxy

substituted dienes (12 and 13) We also investigated a copper(I)-catalyzed hydrosilylation

protocol employing silyl boranes and this method also leads to a mixture of 2-silicon and 1-

silicon substituted 13 diene products (1516)9 The authors who first reported this method

hypothesized a mechanism involving transmetallation to a cupric silane species and subsequent

silylcupration of an alkyne Under these conditions we were able to effect hydrosilylation using

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(dimethylphenylsilyl)boronic acid pinacol ester (14) to yield dienes (15 amp 16) in moderate yield

and regioselectivity

Scheme 2 Enyne Cis-Hydrosilylation

In addition to these enyne hydrosilylation reactions we also executed new examples of Leersquos

protocol10 which utilizes an initial silylation of a terminal alkyne followed by a carbonyl

condensation (Scheme 3) The overall reaction is an example of an unusual trans hydrosilylation

of an alkyne With commercially available 3-methyl-3-buten-1-yne (17 R1 = H R2 = Me) the

yield for 2 steps (condensation with diisopropylchlorosilane to yield 18a followed by

condensation with acetone to yield 19a) was an acceptable 72 Silylation of that same alkyne

(17 R1 = H R2 = Me) with dimethylchlorosilane also yields an alkyne (18b) in good yield The

crude product after condensation with acetone contains 19b (by 1H NMR) but this compound did

not survive chromatographic purification on silica or alumina 4-Phenyl-3-buten-1-yne (9) also

condenses with diisopropylchlorosilane to yield 18c in acceptable yield and that alkyne

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condenses with formaldehyde to produce another example of a siloxycyclopentene (19c) in good

yield

Scheme 3 Enyne Trans-Hydrosilylation

23 Preparation of 2-silicon substituted-13-dienes via enyne metathesis

In the past we had also reported the use of intermolecular enyne cross metathesis to prepare 2-

trialkoxysilyl substituted 13 dienes3de but had not tried this method for triaryl or trialkyl silyl

substituted alkynes or for any intramolecular enyne cross metathesis We first tried this reaction

with triphenylsilylacetylene (20) and styrene (21) however we only isolated 2-triphenylsilyl-13-

butadiene (23) in good yield (69) along with trans-stilbene (24) (Scheme 4) We hypothesized

that the ethylene atmosphere typically used in these reactions contributed to the formation of 23

however in the absence of ethylene the reaction still resulted in formation of 23 Given that

observation it appears that ruthenium benzylidene catalyst must react much faster with styrene

(21) to produce trans-stilbene (24) and methylidene catalyst (25) than it reacts with

tripheynylsilylacetylene (20) so it is the methylidene catalyst (25) that reacts with 20 and leads to

the isolated silyl substituted diene product (23)

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Scheme 4 Enyne Metathesis of Triphenylsilylacetylene

We also tried enyne metathesis on a commercially available internal alkyne (26) which bears a

trialkylsilyl group on the alkyne (Scheme 5)11 This reaction resulted in low yield and the use of

an internal alkyne changed the regiochemistry of the metathesis reaction to yield 123-

trisubstituted diene (27)

Scheme 5 Enyne Metathesis of an Internal Trimethylsilyl Substituted Alkyne

We had never attempted an intramolecular version of this enyne cross metathesis reaction but

we found that it could be effected for a benzyldimethyl substituted heptenyne (29) to produce

silyl substituted diene (30) (Scheme 6) However when we went to the next higher homolog ie

an octenyne (32) we could prepare the enyne (32) in good yield but we noted only enyne

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decomposition with different ruthenium catalysts catalyst loadings and solvents in attempts to

produce 33 by enyne metathesis The observed product 30 is most easily rationalized through an

yne then ene cross metathesis mechanism rather than an ene then yne mechanism12

SiSi

Li

DMSODean-Stark

nBu-Li

SiCl

Bn

THF

Hoveyda-Grubbs Catalyst2nd Generation 15 mol

DCM reflux

H2N

NH2

-78 oC RT

12 h

12 h

Br

X

31

32 65 33

Scheme 6 Intramolecular Silyl Enyne Cross Metathesis

3 Conclusions

In cases where 2-halo-13 dienes are commercially available or synthetically accessed easily

using Grignard chemistry to make 2-silyl-13 dienes is the preferred method of synthesis When

the 2-halo-13-dienes are not readily available cis-hydrosilylation of enynes containing terminal

alkynes leads to mixtures of regioisomeric products Compare for instance the preparation of

diene 5 using Grignard chemistry to the preparation of structurally related diene 15 by

hydrosilylation to note the advantages of the Grignard approach when feasible Trans-

hydrosilylation of enynes in conjunction with carbonyl compound trapping is a viable synthetic

route to siloxy substituted alkenyl cyclopentenes (19) Intermolecular enyne cross metathesis

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can be used to make 4-alkyl or 4-aryl-2-silicon substituted dienes if the terminal alkynes used for

cross metathesis bear small substituents on silicon3d The reaction fails as a route to make 4-

substituted-2-silicon dienes if the terminal alkyne used bears silicon with large substituents such

as 20 Intramolecular enyne cross metathesis can be used to make additional silyl substituted

alkenyl cyclopentenes such as 30 but fails as a route to make a silyl substituted alkenyl

cyclohexenes such as 33

4 Experimental

41 General Procedures are part of the Supplementary Material

421 Synthesis of (Buta-13-dien-2-yl)dimethyl(phenyl)silane (2) Chloroprene (458 g 517

mmol) and phenyldimethylchlorosilane (803 g 471 mmol) were used according to the general

procedure to yield a light yellow colored crude product (144 g) as a mixture of diene and

xylenes The crude product was subjected to fractional distillation at reduced pressure (20 mm

45 ⁰C) which resulted in a brown colored liquid which was further purified by flash

chromatography (100 pentanes) to yield the title compound (2) as a light yellow liquid (836 g

444 mmol 97) Rf 063 (100 pentanes) 1H NMR (500 MHz CDCl3) δ 749minus755 (m 2H)

731minus737 (m 3H) 646 (dd J = 177 109 Hz 1H) 588 (d J = 32 Hz 1H) 551 (d J = 32

Hz 1H) 510 (d J = 177 Hz 1H) 500 (d J = 109 Hz 1H) 043 (s 6H) 13C NMR (75 MHz

CDCl3) δ 1476 1411 1382 1339 1304 1290 1278 1167 minus23 HRMS calcd for C12H16Si

(M+) 1881021 found 1881020

422 Synthesis of (Buta-13-dien-2-yl) dimethylsilanol (3) Chloroprene in 50 xylenes

(10mL 515 mmol) and dichlorodimethylsilane (0645 g 5 mmol) were used according to the

general procedure above (1M acetate buffer of pH 5 was used instead of 05M HCl for the

quench) to yield a light yellow colored liquid 1H NMR of the crude product (11g) showed a

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mixture of xylenes diene and the corresponding disiloxane dimer Kugelrohr distillation at 60˚C

(4mm Hg) of the crude product yielded the target compound (3) (0300g 23 mmol 46) 1H

NMR (300 MHz CDCl3) δ 646 (dd J = 178 108 Hz 1H) 577 (d J = 30 Hz 1H) 556 (d J =

29 Hz 1H) 537 (d J = 182 Hz 1H) 512 (d J = 108 Hz 1H) 225 (bs 1H) 030 (s 6H) 13C

NMR (75 MHz CDCl3) δ 14865 14088 12958 11656 032 EIMS calcd for C6H13OSi

(M+H)+ 12906 found 1290

431 Synthesis of Trimethyl[(E)-4-phenyl-13-butadien-2-yl]silane (5) 1-[(E)-3-Bromobuta-13-

dienyl]benzene13 (4) (199 g 949 mmol) and trimethylsilylchloride (137 g 126 mmol) were

used according to the general method producing the crude compound as a dark brown liquid

Purification by flash chromatography (hexanes Et2O 91) yielded compound 5 as a brown-

yellow oil (156 g 773 mmol 85) This compound has been reported previously by a

different route but no characterization data were provided14 Rf 015 (hexanesEt2O 91) 1H

NMR (500 MHz CDCl3) δ 743 (d J = 77 Hz 2H) 734 (t J = 77 Hz 2H) 724 (t J = 74 Hz

1H) 694 (d J = 165 Hz 1H) 664 (d J = 165 Hz 1H) 589 (d J = 30 Hz 1H) 553 (d J =

30 Hz 1H) 027 (s 9H) 13C NMR (75 MHz CDCl3) δ 1489 1377 1340 1305 1286 1285

1273 1263 08

432 Synthesis of (1-Cyclohexylideneprop-2-en-2-yl)trimethylsilane (7) Chlorotrimethylsilane

(0685 g 630 mmol) and (2-bromoallylidene)cyclohexene15 (6) (0929 g 464 mmol) were used

according to the general procedure The resulting dark brown crude residue after purification by

flash chromatography (hexanes Et2O 151 rarr 91) yielded compound 7 as a brown-yellow oil

(0483 g 249 mmol 47) Rf 084 (hexanesEt2O 151) 1H NMR (500 MHz CDCl3) δ 571 (s

1H) 540minus549 (m 2H) 210minus223 (m 4H) 154minus160 (m 4H) 141minus150 (m 2H) 007 (s

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9H) 13C NMR (75 MHz CDCl3) δ 1503 1405 1251 1235 374 293 290 283 269

minus195 HRMS calcd for C12H22Si (M+) 1941491 found 1941489

44 Diels-Alder Reactions

441 Synthesis of 3a477a-Tetrahydro-5-[dimethyl(phenyl)silyl]-2-phenyl-2H-isoindole-13-

dione (8) Diene (2) (0302 g 160 mmol) and N-phenylmaleimide (0103 g 0595 mmol) were

dissolved in THF (5mL) and degassed in a sealed tube After heating for 4h at 90 ⁰C the reaction

mixture was filtered through a cotton plug and volatiles were removed by rotary evaporation

The resulting yellow colored residue was purified by flash chromatography with the excess diene

(2) eluting (0151 g 0802 mmol 78 recovery Rf 084 pentanediethyl ether 11) followed by

the cycloadduct 8 as a colorless clear viscous liquid (0204 g 0564 mmol 98) Rf 029

(pentanediethyl ether 11) 1H NMR (500 MHz CDCl3) δ 741minus754 (m 4H) 729minus741 (m

4H) 709minus720 (m 2H) 634 (m 1H) 318minus330 (m 2H) 271minus288 (m 2H) 222minus236 (m

2H) 036 (s 3H) 035 (s 3H) 13C NMR (75 MHz CDCl3) δ 1791 1787 1407 1384 1370

1339 1320 1292 1290 1284 1278 1263 393 392 264 250 -388 -389 HRMS calcd

for C22H23NO2Si (M+) 3611498 found 3611490 Anal calcd for C22H23NO2Si C 7310 H

642 Found C 7263 H 638

45 Cis-Hydrosilylation Reactions

452 Copper-catalyzed hydrosilylation of (E)-4-phenyl-3-buten-1-yne (9) To a 5-mL sealable

microwave tube equipped with a stir bar copper(I) chloride (0031 g 031 mmol) JohnPhos

(0037 g 012 mmol) and sodium tert-butoxide (0015 g 016 mmol) were suspended in THF

(26 mL) and degassed with argon (Dimethylphenylsilyl)boronic acid pinacol ester (14) (234

microL 086 mmol) was added to the reaction vessel the tube was sealed with a crimp cap and

placed in a circulating chiller at 0 degC After 30 min (E)-4-phenyl-3-buten-1-yne (9) (0108 g

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

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1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

1

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Cl ClMg

PhMe2SiCl 05M HClMg

PhMe2Si

1 2 97

Br

4

Br

6

Ph

+ TMSMgCl

+ TMSMgCl

TMS

5 85

Ph

TMS

7 47

1) Me2SiCl2

2) 1M acetate

buffer

Me2(OH)Si

3 46

NPh

Si

O

O

H

H

NPM

4h

THF

8 98

Scheme 1 Preparation of Silyl Dienes via Grignard Chemistry

22 Preparation of 2-silicon substituted 13-dienes via hydrosilylation of enynes

Our next attempts at the synthesis of 4-substituted 2-silyl dienes involved the cis-

hydrosilylation of 13-enynes (Scheme 2) (E)-4-phenyl-3-buten-1-yne (9) was synthesized from

trans-cinnamaldehyde via the Colvin rearrangement8 Ruthenium-catalyzed hydrosilylation of

enyne (9) with triethoxysilane (10) was performed with Grubbs 1st generation catalyst and

cyclopentadienyl ruthenium salt (11) These reactions produced mixtures of 2- and 1-siloxy

substituted dienes (12 and 13) We also investigated a copper(I)-catalyzed hydrosilylation

protocol employing silyl boranes and this method also leads to a mixture of 2-silicon and 1-

silicon substituted 13 diene products (1516)9 The authors who first reported this method

hypothesized a mechanism involving transmetallation to a cupric silane species and subsequent

silylcupration of an alkyne Under these conditions we were able to effect hydrosilylation using

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(dimethylphenylsilyl)boronic acid pinacol ester (14) to yield dienes (15 amp 16) in moderate yield

and regioselectivity

Scheme 2 Enyne Cis-Hydrosilylation

In addition to these enyne hydrosilylation reactions we also executed new examples of Leersquos

protocol10 which utilizes an initial silylation of a terminal alkyne followed by a carbonyl

condensation (Scheme 3) The overall reaction is an example of an unusual trans hydrosilylation

of an alkyne With commercially available 3-methyl-3-buten-1-yne (17 R1 = H R2 = Me) the

yield for 2 steps (condensation with diisopropylchlorosilane to yield 18a followed by

condensation with acetone to yield 19a) was an acceptable 72 Silylation of that same alkyne

(17 R1 = H R2 = Me) with dimethylchlorosilane also yields an alkyne (18b) in good yield The

crude product after condensation with acetone contains 19b (by 1H NMR) but this compound did

not survive chromatographic purification on silica or alumina 4-Phenyl-3-buten-1-yne (9) also

condenses with diisopropylchlorosilane to yield 18c in acceptable yield and that alkyne

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condenses with formaldehyde to produce another example of a siloxycyclopentene (19c) in good

yield

Scheme 3 Enyne Trans-Hydrosilylation

23 Preparation of 2-silicon substituted-13-dienes via enyne metathesis

In the past we had also reported the use of intermolecular enyne cross metathesis to prepare 2-

trialkoxysilyl substituted 13 dienes3de but had not tried this method for triaryl or trialkyl silyl

substituted alkynes or for any intramolecular enyne cross metathesis We first tried this reaction

with triphenylsilylacetylene (20) and styrene (21) however we only isolated 2-triphenylsilyl-13-

butadiene (23) in good yield (69) along with trans-stilbene (24) (Scheme 4) We hypothesized

that the ethylene atmosphere typically used in these reactions contributed to the formation of 23

however in the absence of ethylene the reaction still resulted in formation of 23 Given that

observation it appears that ruthenium benzylidene catalyst must react much faster with styrene

(21) to produce trans-stilbene (24) and methylidene catalyst (25) than it reacts with

tripheynylsilylacetylene (20) so it is the methylidene catalyst (25) that reacts with 20 and leads to

the isolated silyl substituted diene product (23)

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Scheme 4 Enyne Metathesis of Triphenylsilylacetylene

We also tried enyne metathesis on a commercially available internal alkyne (26) which bears a

trialkylsilyl group on the alkyne (Scheme 5)11 This reaction resulted in low yield and the use of

an internal alkyne changed the regiochemistry of the metathesis reaction to yield 123-

trisubstituted diene (27)

Scheme 5 Enyne Metathesis of an Internal Trimethylsilyl Substituted Alkyne

We had never attempted an intramolecular version of this enyne cross metathesis reaction but

we found that it could be effected for a benzyldimethyl substituted heptenyne (29) to produce

silyl substituted diene (30) (Scheme 6) However when we went to the next higher homolog ie

an octenyne (32) we could prepare the enyne (32) in good yield but we noted only enyne

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decomposition with different ruthenium catalysts catalyst loadings and solvents in attempts to

produce 33 by enyne metathesis The observed product 30 is most easily rationalized through an

yne then ene cross metathesis mechanism rather than an ene then yne mechanism12

SiSi

Li

DMSODean-Stark

nBu-Li

SiCl

Bn

THF

Hoveyda-Grubbs Catalyst2nd Generation 15 mol

DCM reflux

H2N

NH2

-78 oC RT

12 h

12 h

Br

X

31

32 65 33

Scheme 6 Intramolecular Silyl Enyne Cross Metathesis

3 Conclusions

In cases where 2-halo-13 dienes are commercially available or synthetically accessed easily

using Grignard chemistry to make 2-silyl-13 dienes is the preferred method of synthesis When

the 2-halo-13-dienes are not readily available cis-hydrosilylation of enynes containing terminal

alkynes leads to mixtures of regioisomeric products Compare for instance the preparation of

diene 5 using Grignard chemistry to the preparation of structurally related diene 15 by

hydrosilylation to note the advantages of the Grignard approach when feasible Trans-

hydrosilylation of enynes in conjunction with carbonyl compound trapping is a viable synthetic

route to siloxy substituted alkenyl cyclopentenes (19) Intermolecular enyne cross metathesis

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can be used to make 4-alkyl or 4-aryl-2-silicon substituted dienes if the terminal alkynes used for

cross metathesis bear small substituents on silicon3d The reaction fails as a route to make 4-

substituted-2-silicon dienes if the terminal alkyne used bears silicon with large substituents such

as 20 Intramolecular enyne cross metathesis can be used to make additional silyl substituted

alkenyl cyclopentenes such as 30 but fails as a route to make a silyl substituted alkenyl

cyclohexenes such as 33

4 Experimental

41 General Procedures are part of the Supplementary Material

421 Synthesis of (Buta-13-dien-2-yl)dimethyl(phenyl)silane (2) Chloroprene (458 g 517

mmol) and phenyldimethylchlorosilane (803 g 471 mmol) were used according to the general

procedure to yield a light yellow colored crude product (144 g) as a mixture of diene and

xylenes The crude product was subjected to fractional distillation at reduced pressure (20 mm

45 ⁰C) which resulted in a brown colored liquid which was further purified by flash

chromatography (100 pentanes) to yield the title compound (2) as a light yellow liquid (836 g

444 mmol 97) Rf 063 (100 pentanes) 1H NMR (500 MHz CDCl3) δ 749minus755 (m 2H)

731minus737 (m 3H) 646 (dd J = 177 109 Hz 1H) 588 (d J = 32 Hz 1H) 551 (d J = 32

Hz 1H) 510 (d J = 177 Hz 1H) 500 (d J = 109 Hz 1H) 043 (s 6H) 13C NMR (75 MHz

CDCl3) δ 1476 1411 1382 1339 1304 1290 1278 1167 minus23 HRMS calcd for C12H16Si

(M+) 1881021 found 1881020

422 Synthesis of (Buta-13-dien-2-yl) dimethylsilanol (3) Chloroprene in 50 xylenes

(10mL 515 mmol) and dichlorodimethylsilane (0645 g 5 mmol) were used according to the

general procedure above (1M acetate buffer of pH 5 was used instead of 05M HCl for the

quench) to yield a light yellow colored liquid 1H NMR of the crude product (11g) showed a

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mixture of xylenes diene and the corresponding disiloxane dimer Kugelrohr distillation at 60˚C

(4mm Hg) of the crude product yielded the target compound (3) (0300g 23 mmol 46) 1H

NMR (300 MHz CDCl3) δ 646 (dd J = 178 108 Hz 1H) 577 (d J = 30 Hz 1H) 556 (d J =

29 Hz 1H) 537 (d J = 182 Hz 1H) 512 (d J = 108 Hz 1H) 225 (bs 1H) 030 (s 6H) 13C

NMR (75 MHz CDCl3) δ 14865 14088 12958 11656 032 EIMS calcd for C6H13OSi

(M+H)+ 12906 found 1290

431 Synthesis of Trimethyl[(E)-4-phenyl-13-butadien-2-yl]silane (5) 1-[(E)-3-Bromobuta-13-

dienyl]benzene13 (4) (199 g 949 mmol) and trimethylsilylchloride (137 g 126 mmol) were

used according to the general method producing the crude compound as a dark brown liquid

Purification by flash chromatography (hexanes Et2O 91) yielded compound 5 as a brown-

yellow oil (156 g 773 mmol 85) This compound has been reported previously by a

different route but no characterization data were provided14 Rf 015 (hexanesEt2O 91) 1H

NMR (500 MHz CDCl3) δ 743 (d J = 77 Hz 2H) 734 (t J = 77 Hz 2H) 724 (t J = 74 Hz

1H) 694 (d J = 165 Hz 1H) 664 (d J = 165 Hz 1H) 589 (d J = 30 Hz 1H) 553 (d J =

30 Hz 1H) 027 (s 9H) 13C NMR (75 MHz CDCl3) δ 1489 1377 1340 1305 1286 1285

1273 1263 08

432 Synthesis of (1-Cyclohexylideneprop-2-en-2-yl)trimethylsilane (7) Chlorotrimethylsilane

(0685 g 630 mmol) and (2-bromoallylidene)cyclohexene15 (6) (0929 g 464 mmol) were used

according to the general procedure The resulting dark brown crude residue after purification by

flash chromatography (hexanes Et2O 151 rarr 91) yielded compound 7 as a brown-yellow oil

(0483 g 249 mmol 47) Rf 084 (hexanesEt2O 151) 1H NMR (500 MHz CDCl3) δ 571 (s

1H) 540minus549 (m 2H) 210minus223 (m 4H) 154minus160 (m 4H) 141minus150 (m 2H) 007 (s

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9H) 13C NMR (75 MHz CDCl3) δ 1503 1405 1251 1235 374 293 290 283 269

minus195 HRMS calcd for C12H22Si (M+) 1941491 found 1941489

44 Diels-Alder Reactions

441 Synthesis of 3a477a-Tetrahydro-5-[dimethyl(phenyl)silyl]-2-phenyl-2H-isoindole-13-

dione (8) Diene (2) (0302 g 160 mmol) and N-phenylmaleimide (0103 g 0595 mmol) were

dissolved in THF (5mL) and degassed in a sealed tube After heating for 4h at 90 ⁰C the reaction

mixture was filtered through a cotton plug and volatiles were removed by rotary evaporation

The resulting yellow colored residue was purified by flash chromatography with the excess diene

(2) eluting (0151 g 0802 mmol 78 recovery Rf 084 pentanediethyl ether 11) followed by

the cycloadduct 8 as a colorless clear viscous liquid (0204 g 0564 mmol 98) Rf 029

(pentanediethyl ether 11) 1H NMR (500 MHz CDCl3) δ 741minus754 (m 4H) 729minus741 (m

4H) 709minus720 (m 2H) 634 (m 1H) 318minus330 (m 2H) 271minus288 (m 2H) 222minus236 (m

2H) 036 (s 3H) 035 (s 3H) 13C NMR (75 MHz CDCl3) δ 1791 1787 1407 1384 1370

1339 1320 1292 1290 1284 1278 1263 393 392 264 250 -388 -389 HRMS calcd

for C22H23NO2Si (M+) 3611498 found 3611490 Anal calcd for C22H23NO2Si C 7310 H

642 Found C 7263 H 638

45 Cis-Hydrosilylation Reactions

452 Copper-catalyzed hydrosilylation of (E)-4-phenyl-3-buten-1-yne (9) To a 5-mL sealable

microwave tube equipped with a stir bar copper(I) chloride (0031 g 031 mmol) JohnPhos

(0037 g 012 mmol) and sodium tert-butoxide (0015 g 016 mmol) were suspended in THF

(26 mL) and degassed with argon (Dimethylphenylsilyl)boronic acid pinacol ester (14) (234

microL 086 mmol) was added to the reaction vessel the tube was sealed with a crimp cap and

placed in a circulating chiller at 0 degC After 30 min (E)-4-phenyl-3-buten-1-yne (9) (0108 g

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

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(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

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1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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(dimethylphenylsilyl)boronic acid pinacol ester (14) to yield dienes (15 amp 16) in moderate yield

and regioselectivity

Scheme 2 Enyne Cis-Hydrosilylation

In addition to these enyne hydrosilylation reactions we also executed new examples of Leersquos

protocol10 which utilizes an initial silylation of a terminal alkyne followed by a carbonyl

condensation (Scheme 3) The overall reaction is an example of an unusual trans hydrosilylation

of an alkyne With commercially available 3-methyl-3-buten-1-yne (17 R1 = H R2 = Me) the

yield for 2 steps (condensation with diisopropylchlorosilane to yield 18a followed by

condensation with acetone to yield 19a) was an acceptable 72 Silylation of that same alkyne

(17 R1 = H R2 = Me) with dimethylchlorosilane also yields an alkyne (18b) in good yield The

crude product after condensation with acetone contains 19b (by 1H NMR) but this compound did

not survive chromatographic purification on silica or alumina 4-Phenyl-3-buten-1-yne (9) also

condenses with diisopropylchlorosilane to yield 18c in acceptable yield and that alkyne

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condenses with formaldehyde to produce another example of a siloxycyclopentene (19c) in good

yield

Scheme 3 Enyne Trans-Hydrosilylation

23 Preparation of 2-silicon substituted-13-dienes via enyne metathesis

In the past we had also reported the use of intermolecular enyne cross metathesis to prepare 2-

trialkoxysilyl substituted 13 dienes3de but had not tried this method for triaryl or trialkyl silyl

substituted alkynes or for any intramolecular enyne cross metathesis We first tried this reaction

with triphenylsilylacetylene (20) and styrene (21) however we only isolated 2-triphenylsilyl-13-

butadiene (23) in good yield (69) along with trans-stilbene (24) (Scheme 4) We hypothesized

that the ethylene atmosphere typically used in these reactions contributed to the formation of 23

however in the absence of ethylene the reaction still resulted in formation of 23 Given that

observation it appears that ruthenium benzylidene catalyst must react much faster with styrene

(21) to produce trans-stilbene (24) and methylidene catalyst (25) than it reacts with

tripheynylsilylacetylene (20) so it is the methylidene catalyst (25) that reacts with 20 and leads to

the isolated silyl substituted diene product (23)

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Scheme 4 Enyne Metathesis of Triphenylsilylacetylene

We also tried enyne metathesis on a commercially available internal alkyne (26) which bears a

trialkylsilyl group on the alkyne (Scheme 5)11 This reaction resulted in low yield and the use of

an internal alkyne changed the regiochemistry of the metathesis reaction to yield 123-

trisubstituted diene (27)

Scheme 5 Enyne Metathesis of an Internal Trimethylsilyl Substituted Alkyne

We had never attempted an intramolecular version of this enyne cross metathesis reaction but

we found that it could be effected for a benzyldimethyl substituted heptenyne (29) to produce

silyl substituted diene (30) (Scheme 6) However when we went to the next higher homolog ie

an octenyne (32) we could prepare the enyne (32) in good yield but we noted only enyne

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decomposition with different ruthenium catalysts catalyst loadings and solvents in attempts to

produce 33 by enyne metathesis The observed product 30 is most easily rationalized through an

yne then ene cross metathesis mechanism rather than an ene then yne mechanism12

SiSi

Li

DMSODean-Stark

nBu-Li

SiCl

Bn

THF

Hoveyda-Grubbs Catalyst2nd Generation 15 mol

DCM reflux

H2N

NH2

-78 oC RT

12 h

12 h

Br

X

31

32 65 33

Scheme 6 Intramolecular Silyl Enyne Cross Metathesis

3 Conclusions

In cases where 2-halo-13 dienes are commercially available or synthetically accessed easily

using Grignard chemistry to make 2-silyl-13 dienes is the preferred method of synthesis When

the 2-halo-13-dienes are not readily available cis-hydrosilylation of enynes containing terminal

alkynes leads to mixtures of regioisomeric products Compare for instance the preparation of

diene 5 using Grignard chemistry to the preparation of structurally related diene 15 by

hydrosilylation to note the advantages of the Grignard approach when feasible Trans-

hydrosilylation of enynes in conjunction with carbonyl compound trapping is a viable synthetic

route to siloxy substituted alkenyl cyclopentenes (19) Intermolecular enyne cross metathesis

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can be used to make 4-alkyl or 4-aryl-2-silicon substituted dienes if the terminal alkynes used for

cross metathesis bear small substituents on silicon3d The reaction fails as a route to make 4-

substituted-2-silicon dienes if the terminal alkyne used bears silicon with large substituents such

as 20 Intramolecular enyne cross metathesis can be used to make additional silyl substituted

alkenyl cyclopentenes such as 30 but fails as a route to make a silyl substituted alkenyl

cyclohexenes such as 33

4 Experimental

41 General Procedures are part of the Supplementary Material

421 Synthesis of (Buta-13-dien-2-yl)dimethyl(phenyl)silane (2) Chloroprene (458 g 517

mmol) and phenyldimethylchlorosilane (803 g 471 mmol) were used according to the general

procedure to yield a light yellow colored crude product (144 g) as a mixture of diene and

xylenes The crude product was subjected to fractional distillation at reduced pressure (20 mm

45 ⁰C) which resulted in a brown colored liquid which was further purified by flash

chromatography (100 pentanes) to yield the title compound (2) as a light yellow liquid (836 g

444 mmol 97) Rf 063 (100 pentanes) 1H NMR (500 MHz CDCl3) δ 749minus755 (m 2H)

731minus737 (m 3H) 646 (dd J = 177 109 Hz 1H) 588 (d J = 32 Hz 1H) 551 (d J = 32

Hz 1H) 510 (d J = 177 Hz 1H) 500 (d J = 109 Hz 1H) 043 (s 6H) 13C NMR (75 MHz

CDCl3) δ 1476 1411 1382 1339 1304 1290 1278 1167 minus23 HRMS calcd for C12H16Si

(M+) 1881021 found 1881020

422 Synthesis of (Buta-13-dien-2-yl) dimethylsilanol (3) Chloroprene in 50 xylenes

(10mL 515 mmol) and dichlorodimethylsilane (0645 g 5 mmol) were used according to the

general procedure above (1M acetate buffer of pH 5 was used instead of 05M HCl for the

quench) to yield a light yellow colored liquid 1H NMR of the crude product (11g) showed a

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mixture of xylenes diene and the corresponding disiloxane dimer Kugelrohr distillation at 60˚C

(4mm Hg) of the crude product yielded the target compound (3) (0300g 23 mmol 46) 1H

NMR (300 MHz CDCl3) δ 646 (dd J = 178 108 Hz 1H) 577 (d J = 30 Hz 1H) 556 (d J =

29 Hz 1H) 537 (d J = 182 Hz 1H) 512 (d J = 108 Hz 1H) 225 (bs 1H) 030 (s 6H) 13C

NMR (75 MHz CDCl3) δ 14865 14088 12958 11656 032 EIMS calcd for C6H13OSi

(M+H)+ 12906 found 1290

431 Synthesis of Trimethyl[(E)-4-phenyl-13-butadien-2-yl]silane (5) 1-[(E)-3-Bromobuta-13-

dienyl]benzene13 (4) (199 g 949 mmol) and trimethylsilylchloride (137 g 126 mmol) were

used according to the general method producing the crude compound as a dark brown liquid

Purification by flash chromatography (hexanes Et2O 91) yielded compound 5 as a brown-

yellow oil (156 g 773 mmol 85) This compound has been reported previously by a

different route but no characterization data were provided14 Rf 015 (hexanesEt2O 91) 1H

NMR (500 MHz CDCl3) δ 743 (d J = 77 Hz 2H) 734 (t J = 77 Hz 2H) 724 (t J = 74 Hz

1H) 694 (d J = 165 Hz 1H) 664 (d J = 165 Hz 1H) 589 (d J = 30 Hz 1H) 553 (d J =

30 Hz 1H) 027 (s 9H) 13C NMR (75 MHz CDCl3) δ 1489 1377 1340 1305 1286 1285

1273 1263 08

432 Synthesis of (1-Cyclohexylideneprop-2-en-2-yl)trimethylsilane (7) Chlorotrimethylsilane

(0685 g 630 mmol) and (2-bromoallylidene)cyclohexene15 (6) (0929 g 464 mmol) were used

according to the general procedure The resulting dark brown crude residue after purification by

flash chromatography (hexanes Et2O 151 rarr 91) yielded compound 7 as a brown-yellow oil

(0483 g 249 mmol 47) Rf 084 (hexanesEt2O 151) 1H NMR (500 MHz CDCl3) δ 571 (s

1H) 540minus549 (m 2H) 210minus223 (m 4H) 154minus160 (m 4H) 141minus150 (m 2H) 007 (s

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9H) 13C NMR (75 MHz CDCl3) δ 1503 1405 1251 1235 374 293 290 283 269

minus195 HRMS calcd for C12H22Si (M+) 1941491 found 1941489

44 Diels-Alder Reactions

441 Synthesis of 3a477a-Tetrahydro-5-[dimethyl(phenyl)silyl]-2-phenyl-2H-isoindole-13-

dione (8) Diene (2) (0302 g 160 mmol) and N-phenylmaleimide (0103 g 0595 mmol) were

dissolved in THF (5mL) and degassed in a sealed tube After heating for 4h at 90 ⁰C the reaction

mixture was filtered through a cotton plug and volatiles were removed by rotary evaporation

The resulting yellow colored residue was purified by flash chromatography with the excess diene

(2) eluting (0151 g 0802 mmol 78 recovery Rf 084 pentanediethyl ether 11) followed by

the cycloadduct 8 as a colorless clear viscous liquid (0204 g 0564 mmol 98) Rf 029

(pentanediethyl ether 11) 1H NMR (500 MHz CDCl3) δ 741minus754 (m 4H) 729minus741 (m

4H) 709minus720 (m 2H) 634 (m 1H) 318minus330 (m 2H) 271minus288 (m 2H) 222minus236 (m

2H) 036 (s 3H) 035 (s 3H) 13C NMR (75 MHz CDCl3) δ 1791 1787 1407 1384 1370

1339 1320 1292 1290 1284 1278 1263 393 392 264 250 -388 -389 HRMS calcd

for C22H23NO2Si (M+) 3611498 found 3611490 Anal calcd for C22H23NO2Si C 7310 H

642 Found C 7263 H 638

45 Cis-Hydrosilylation Reactions

452 Copper-catalyzed hydrosilylation of (E)-4-phenyl-3-buten-1-yne (9) To a 5-mL sealable

microwave tube equipped with a stir bar copper(I) chloride (0031 g 031 mmol) JohnPhos

(0037 g 012 mmol) and sodium tert-butoxide (0015 g 016 mmol) were suspended in THF

(26 mL) and degassed with argon (Dimethylphenylsilyl)boronic acid pinacol ester (14) (234

microL 086 mmol) was added to the reaction vessel the tube was sealed with a crimp cap and

placed in a circulating chiller at 0 degC After 30 min (E)-4-phenyl-3-buten-1-yne (9) (0108 g

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

1

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condenses with formaldehyde to produce another example of a siloxycyclopentene (19c) in good

yield

Scheme 3 Enyne Trans-Hydrosilylation

23 Preparation of 2-silicon substituted-13-dienes via enyne metathesis

In the past we had also reported the use of intermolecular enyne cross metathesis to prepare 2-

trialkoxysilyl substituted 13 dienes3de but had not tried this method for triaryl or trialkyl silyl

substituted alkynes or for any intramolecular enyne cross metathesis We first tried this reaction

with triphenylsilylacetylene (20) and styrene (21) however we only isolated 2-triphenylsilyl-13-

butadiene (23) in good yield (69) along with trans-stilbene (24) (Scheme 4) We hypothesized

that the ethylene atmosphere typically used in these reactions contributed to the formation of 23

however in the absence of ethylene the reaction still resulted in formation of 23 Given that

observation it appears that ruthenium benzylidene catalyst must react much faster with styrene

(21) to produce trans-stilbene (24) and methylidene catalyst (25) than it reacts with

tripheynylsilylacetylene (20) so it is the methylidene catalyst (25) that reacts with 20 and leads to

the isolated silyl substituted diene product (23)

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Scheme 4 Enyne Metathesis of Triphenylsilylacetylene

We also tried enyne metathesis on a commercially available internal alkyne (26) which bears a

trialkylsilyl group on the alkyne (Scheme 5)11 This reaction resulted in low yield and the use of

an internal alkyne changed the regiochemistry of the metathesis reaction to yield 123-

trisubstituted diene (27)

Scheme 5 Enyne Metathesis of an Internal Trimethylsilyl Substituted Alkyne

We had never attempted an intramolecular version of this enyne cross metathesis reaction but

we found that it could be effected for a benzyldimethyl substituted heptenyne (29) to produce

silyl substituted diene (30) (Scheme 6) However when we went to the next higher homolog ie

an octenyne (32) we could prepare the enyne (32) in good yield but we noted only enyne

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decomposition with different ruthenium catalysts catalyst loadings and solvents in attempts to

produce 33 by enyne metathesis The observed product 30 is most easily rationalized through an

yne then ene cross metathesis mechanism rather than an ene then yne mechanism12

SiSi

Li

DMSODean-Stark

nBu-Li

SiCl

Bn

THF

Hoveyda-Grubbs Catalyst2nd Generation 15 mol

DCM reflux

H2N

NH2

-78 oC RT

12 h

12 h

Br

X

31

32 65 33

Scheme 6 Intramolecular Silyl Enyne Cross Metathesis

3 Conclusions

In cases where 2-halo-13 dienes are commercially available or synthetically accessed easily

using Grignard chemistry to make 2-silyl-13 dienes is the preferred method of synthesis When

the 2-halo-13-dienes are not readily available cis-hydrosilylation of enynes containing terminal

alkynes leads to mixtures of regioisomeric products Compare for instance the preparation of

diene 5 using Grignard chemistry to the preparation of structurally related diene 15 by

hydrosilylation to note the advantages of the Grignard approach when feasible Trans-

hydrosilylation of enynes in conjunction with carbonyl compound trapping is a viable synthetic

route to siloxy substituted alkenyl cyclopentenes (19) Intermolecular enyne cross metathesis

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can be used to make 4-alkyl or 4-aryl-2-silicon substituted dienes if the terminal alkynes used for

cross metathesis bear small substituents on silicon3d The reaction fails as a route to make 4-

substituted-2-silicon dienes if the terminal alkyne used bears silicon with large substituents such

as 20 Intramolecular enyne cross metathesis can be used to make additional silyl substituted

alkenyl cyclopentenes such as 30 but fails as a route to make a silyl substituted alkenyl

cyclohexenes such as 33

4 Experimental

41 General Procedures are part of the Supplementary Material

421 Synthesis of (Buta-13-dien-2-yl)dimethyl(phenyl)silane (2) Chloroprene (458 g 517

mmol) and phenyldimethylchlorosilane (803 g 471 mmol) were used according to the general

procedure to yield a light yellow colored crude product (144 g) as a mixture of diene and

xylenes The crude product was subjected to fractional distillation at reduced pressure (20 mm

45 ⁰C) which resulted in a brown colored liquid which was further purified by flash

chromatography (100 pentanes) to yield the title compound (2) as a light yellow liquid (836 g

444 mmol 97) Rf 063 (100 pentanes) 1H NMR (500 MHz CDCl3) δ 749minus755 (m 2H)

731minus737 (m 3H) 646 (dd J = 177 109 Hz 1H) 588 (d J = 32 Hz 1H) 551 (d J = 32

Hz 1H) 510 (d J = 177 Hz 1H) 500 (d J = 109 Hz 1H) 043 (s 6H) 13C NMR (75 MHz

CDCl3) δ 1476 1411 1382 1339 1304 1290 1278 1167 minus23 HRMS calcd for C12H16Si

(M+) 1881021 found 1881020

422 Synthesis of (Buta-13-dien-2-yl) dimethylsilanol (3) Chloroprene in 50 xylenes

(10mL 515 mmol) and dichlorodimethylsilane (0645 g 5 mmol) were used according to the

general procedure above (1M acetate buffer of pH 5 was used instead of 05M HCl for the

quench) to yield a light yellow colored liquid 1H NMR of the crude product (11g) showed a

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mixture of xylenes diene and the corresponding disiloxane dimer Kugelrohr distillation at 60˚C

(4mm Hg) of the crude product yielded the target compound (3) (0300g 23 mmol 46) 1H

NMR (300 MHz CDCl3) δ 646 (dd J = 178 108 Hz 1H) 577 (d J = 30 Hz 1H) 556 (d J =

29 Hz 1H) 537 (d J = 182 Hz 1H) 512 (d J = 108 Hz 1H) 225 (bs 1H) 030 (s 6H) 13C

NMR (75 MHz CDCl3) δ 14865 14088 12958 11656 032 EIMS calcd for C6H13OSi

(M+H)+ 12906 found 1290

431 Synthesis of Trimethyl[(E)-4-phenyl-13-butadien-2-yl]silane (5) 1-[(E)-3-Bromobuta-13-

dienyl]benzene13 (4) (199 g 949 mmol) and trimethylsilylchloride (137 g 126 mmol) were

used according to the general method producing the crude compound as a dark brown liquid

Purification by flash chromatography (hexanes Et2O 91) yielded compound 5 as a brown-

yellow oil (156 g 773 mmol 85) This compound has been reported previously by a

different route but no characterization data were provided14 Rf 015 (hexanesEt2O 91) 1H

NMR (500 MHz CDCl3) δ 743 (d J = 77 Hz 2H) 734 (t J = 77 Hz 2H) 724 (t J = 74 Hz

1H) 694 (d J = 165 Hz 1H) 664 (d J = 165 Hz 1H) 589 (d J = 30 Hz 1H) 553 (d J =

30 Hz 1H) 027 (s 9H) 13C NMR (75 MHz CDCl3) δ 1489 1377 1340 1305 1286 1285

1273 1263 08

432 Synthesis of (1-Cyclohexylideneprop-2-en-2-yl)trimethylsilane (7) Chlorotrimethylsilane

(0685 g 630 mmol) and (2-bromoallylidene)cyclohexene15 (6) (0929 g 464 mmol) were used

according to the general procedure The resulting dark brown crude residue after purification by

flash chromatography (hexanes Et2O 151 rarr 91) yielded compound 7 as a brown-yellow oil

(0483 g 249 mmol 47) Rf 084 (hexanesEt2O 151) 1H NMR (500 MHz CDCl3) δ 571 (s

1H) 540minus549 (m 2H) 210minus223 (m 4H) 154minus160 (m 4H) 141minus150 (m 2H) 007 (s

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9H) 13C NMR (75 MHz CDCl3) δ 1503 1405 1251 1235 374 293 290 283 269

minus195 HRMS calcd for C12H22Si (M+) 1941491 found 1941489

44 Diels-Alder Reactions

441 Synthesis of 3a477a-Tetrahydro-5-[dimethyl(phenyl)silyl]-2-phenyl-2H-isoindole-13-

dione (8) Diene (2) (0302 g 160 mmol) and N-phenylmaleimide (0103 g 0595 mmol) were

dissolved in THF (5mL) and degassed in a sealed tube After heating for 4h at 90 ⁰C the reaction

mixture was filtered through a cotton plug and volatiles were removed by rotary evaporation

The resulting yellow colored residue was purified by flash chromatography with the excess diene

(2) eluting (0151 g 0802 mmol 78 recovery Rf 084 pentanediethyl ether 11) followed by

the cycloadduct 8 as a colorless clear viscous liquid (0204 g 0564 mmol 98) Rf 029

(pentanediethyl ether 11) 1H NMR (500 MHz CDCl3) δ 741minus754 (m 4H) 729minus741 (m

4H) 709minus720 (m 2H) 634 (m 1H) 318minus330 (m 2H) 271minus288 (m 2H) 222minus236 (m

2H) 036 (s 3H) 035 (s 3H) 13C NMR (75 MHz CDCl3) δ 1791 1787 1407 1384 1370

1339 1320 1292 1290 1284 1278 1263 393 392 264 250 -388 -389 HRMS calcd

for C22H23NO2Si (M+) 3611498 found 3611490 Anal calcd for C22H23NO2Si C 7310 H

642 Found C 7263 H 638

45 Cis-Hydrosilylation Reactions

452 Copper-catalyzed hydrosilylation of (E)-4-phenyl-3-buten-1-yne (9) To a 5-mL sealable

microwave tube equipped with a stir bar copper(I) chloride (0031 g 031 mmol) JohnPhos

(0037 g 012 mmol) and sodium tert-butoxide (0015 g 016 mmol) were suspended in THF

(26 mL) and degassed with argon (Dimethylphenylsilyl)boronic acid pinacol ester (14) (234

microL 086 mmol) was added to the reaction vessel the tube was sealed with a crimp cap and

placed in a circulating chiller at 0 degC After 30 min (E)-4-phenyl-3-buten-1-yne (9) (0108 g

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

1

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Scheme 4 Enyne Metathesis of Triphenylsilylacetylene

We also tried enyne metathesis on a commercially available internal alkyne (26) which bears a

trialkylsilyl group on the alkyne (Scheme 5)11 This reaction resulted in low yield and the use of

an internal alkyne changed the regiochemistry of the metathesis reaction to yield 123-

trisubstituted diene (27)

Scheme 5 Enyne Metathesis of an Internal Trimethylsilyl Substituted Alkyne

We had never attempted an intramolecular version of this enyne cross metathesis reaction but

we found that it could be effected for a benzyldimethyl substituted heptenyne (29) to produce

silyl substituted diene (30) (Scheme 6) However when we went to the next higher homolog ie

an octenyne (32) we could prepare the enyne (32) in good yield but we noted only enyne

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decomposition with different ruthenium catalysts catalyst loadings and solvents in attempts to

produce 33 by enyne metathesis The observed product 30 is most easily rationalized through an

yne then ene cross metathesis mechanism rather than an ene then yne mechanism12

SiSi

Li

DMSODean-Stark

nBu-Li

SiCl

Bn

THF

Hoveyda-Grubbs Catalyst2nd Generation 15 mol

DCM reflux

H2N

NH2

-78 oC RT

12 h

12 h

Br

X

31

32 65 33

Scheme 6 Intramolecular Silyl Enyne Cross Metathesis

3 Conclusions

In cases where 2-halo-13 dienes are commercially available or synthetically accessed easily

using Grignard chemistry to make 2-silyl-13 dienes is the preferred method of synthesis When

the 2-halo-13-dienes are not readily available cis-hydrosilylation of enynes containing terminal

alkynes leads to mixtures of regioisomeric products Compare for instance the preparation of

diene 5 using Grignard chemistry to the preparation of structurally related diene 15 by

hydrosilylation to note the advantages of the Grignard approach when feasible Trans-

hydrosilylation of enynes in conjunction with carbonyl compound trapping is a viable synthetic

route to siloxy substituted alkenyl cyclopentenes (19) Intermolecular enyne cross metathesis

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can be used to make 4-alkyl or 4-aryl-2-silicon substituted dienes if the terminal alkynes used for

cross metathesis bear small substituents on silicon3d The reaction fails as a route to make 4-

substituted-2-silicon dienes if the terminal alkyne used bears silicon with large substituents such

as 20 Intramolecular enyne cross metathesis can be used to make additional silyl substituted

alkenyl cyclopentenes such as 30 but fails as a route to make a silyl substituted alkenyl

cyclohexenes such as 33

4 Experimental

41 General Procedures are part of the Supplementary Material

421 Synthesis of (Buta-13-dien-2-yl)dimethyl(phenyl)silane (2) Chloroprene (458 g 517

mmol) and phenyldimethylchlorosilane (803 g 471 mmol) were used according to the general

procedure to yield a light yellow colored crude product (144 g) as a mixture of diene and

xylenes The crude product was subjected to fractional distillation at reduced pressure (20 mm

45 ⁰C) which resulted in a brown colored liquid which was further purified by flash

chromatography (100 pentanes) to yield the title compound (2) as a light yellow liquid (836 g

444 mmol 97) Rf 063 (100 pentanes) 1H NMR (500 MHz CDCl3) δ 749minus755 (m 2H)

731minus737 (m 3H) 646 (dd J = 177 109 Hz 1H) 588 (d J = 32 Hz 1H) 551 (d J = 32

Hz 1H) 510 (d J = 177 Hz 1H) 500 (d J = 109 Hz 1H) 043 (s 6H) 13C NMR (75 MHz

CDCl3) δ 1476 1411 1382 1339 1304 1290 1278 1167 minus23 HRMS calcd for C12H16Si

(M+) 1881021 found 1881020

422 Synthesis of (Buta-13-dien-2-yl) dimethylsilanol (3) Chloroprene in 50 xylenes

(10mL 515 mmol) and dichlorodimethylsilane (0645 g 5 mmol) were used according to the

general procedure above (1M acetate buffer of pH 5 was used instead of 05M HCl for the

quench) to yield a light yellow colored liquid 1H NMR of the crude product (11g) showed a

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mixture of xylenes diene and the corresponding disiloxane dimer Kugelrohr distillation at 60˚C

(4mm Hg) of the crude product yielded the target compound (3) (0300g 23 mmol 46) 1H

NMR (300 MHz CDCl3) δ 646 (dd J = 178 108 Hz 1H) 577 (d J = 30 Hz 1H) 556 (d J =

29 Hz 1H) 537 (d J = 182 Hz 1H) 512 (d J = 108 Hz 1H) 225 (bs 1H) 030 (s 6H) 13C

NMR (75 MHz CDCl3) δ 14865 14088 12958 11656 032 EIMS calcd for C6H13OSi

(M+H)+ 12906 found 1290

431 Synthesis of Trimethyl[(E)-4-phenyl-13-butadien-2-yl]silane (5) 1-[(E)-3-Bromobuta-13-

dienyl]benzene13 (4) (199 g 949 mmol) and trimethylsilylchloride (137 g 126 mmol) were

used according to the general method producing the crude compound as a dark brown liquid

Purification by flash chromatography (hexanes Et2O 91) yielded compound 5 as a brown-

yellow oil (156 g 773 mmol 85) This compound has been reported previously by a

different route but no characterization data were provided14 Rf 015 (hexanesEt2O 91) 1H

NMR (500 MHz CDCl3) δ 743 (d J = 77 Hz 2H) 734 (t J = 77 Hz 2H) 724 (t J = 74 Hz

1H) 694 (d J = 165 Hz 1H) 664 (d J = 165 Hz 1H) 589 (d J = 30 Hz 1H) 553 (d J =

30 Hz 1H) 027 (s 9H) 13C NMR (75 MHz CDCl3) δ 1489 1377 1340 1305 1286 1285

1273 1263 08

432 Synthesis of (1-Cyclohexylideneprop-2-en-2-yl)trimethylsilane (7) Chlorotrimethylsilane

(0685 g 630 mmol) and (2-bromoallylidene)cyclohexene15 (6) (0929 g 464 mmol) were used

according to the general procedure The resulting dark brown crude residue after purification by

flash chromatography (hexanes Et2O 151 rarr 91) yielded compound 7 as a brown-yellow oil

(0483 g 249 mmol 47) Rf 084 (hexanesEt2O 151) 1H NMR (500 MHz CDCl3) δ 571 (s

1H) 540minus549 (m 2H) 210minus223 (m 4H) 154minus160 (m 4H) 141minus150 (m 2H) 007 (s

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9H) 13C NMR (75 MHz CDCl3) δ 1503 1405 1251 1235 374 293 290 283 269

minus195 HRMS calcd for C12H22Si (M+) 1941491 found 1941489

44 Diels-Alder Reactions

441 Synthesis of 3a477a-Tetrahydro-5-[dimethyl(phenyl)silyl]-2-phenyl-2H-isoindole-13-

dione (8) Diene (2) (0302 g 160 mmol) and N-phenylmaleimide (0103 g 0595 mmol) were

dissolved in THF (5mL) and degassed in a sealed tube After heating for 4h at 90 ⁰C the reaction

mixture was filtered through a cotton plug and volatiles were removed by rotary evaporation

The resulting yellow colored residue was purified by flash chromatography with the excess diene

(2) eluting (0151 g 0802 mmol 78 recovery Rf 084 pentanediethyl ether 11) followed by

the cycloadduct 8 as a colorless clear viscous liquid (0204 g 0564 mmol 98) Rf 029

(pentanediethyl ether 11) 1H NMR (500 MHz CDCl3) δ 741minus754 (m 4H) 729minus741 (m

4H) 709minus720 (m 2H) 634 (m 1H) 318minus330 (m 2H) 271minus288 (m 2H) 222minus236 (m

2H) 036 (s 3H) 035 (s 3H) 13C NMR (75 MHz CDCl3) δ 1791 1787 1407 1384 1370

1339 1320 1292 1290 1284 1278 1263 393 392 264 250 -388 -389 HRMS calcd

for C22H23NO2Si (M+) 3611498 found 3611490 Anal calcd for C22H23NO2Si C 7310 H

642 Found C 7263 H 638

45 Cis-Hydrosilylation Reactions

452 Copper-catalyzed hydrosilylation of (E)-4-phenyl-3-buten-1-yne (9) To a 5-mL sealable

microwave tube equipped with a stir bar copper(I) chloride (0031 g 031 mmol) JohnPhos

(0037 g 012 mmol) and sodium tert-butoxide (0015 g 016 mmol) were suspended in THF

(26 mL) and degassed with argon (Dimethylphenylsilyl)boronic acid pinacol ester (14) (234

microL 086 mmol) was added to the reaction vessel the tube was sealed with a crimp cap and

placed in a circulating chiller at 0 degC After 30 min (E)-4-phenyl-3-buten-1-yne (9) (0108 g

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

1

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decomposition with different ruthenium catalysts catalyst loadings and solvents in attempts to

produce 33 by enyne metathesis The observed product 30 is most easily rationalized through an

yne then ene cross metathesis mechanism rather than an ene then yne mechanism12

SiSi

Li

DMSODean-Stark

nBu-Li

SiCl

Bn

THF

Hoveyda-Grubbs Catalyst2nd Generation 15 mol

DCM reflux

H2N

NH2

-78 oC RT

12 h

12 h

Br

X

31

32 65 33

Scheme 6 Intramolecular Silyl Enyne Cross Metathesis

3 Conclusions

In cases where 2-halo-13 dienes are commercially available or synthetically accessed easily

using Grignard chemistry to make 2-silyl-13 dienes is the preferred method of synthesis When

the 2-halo-13-dienes are not readily available cis-hydrosilylation of enynes containing terminal

alkynes leads to mixtures of regioisomeric products Compare for instance the preparation of

diene 5 using Grignard chemistry to the preparation of structurally related diene 15 by

hydrosilylation to note the advantages of the Grignard approach when feasible Trans-

hydrosilylation of enynes in conjunction with carbonyl compound trapping is a viable synthetic

route to siloxy substituted alkenyl cyclopentenes (19) Intermolecular enyne cross metathesis

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can be used to make 4-alkyl or 4-aryl-2-silicon substituted dienes if the terminal alkynes used for

cross metathesis bear small substituents on silicon3d The reaction fails as a route to make 4-

substituted-2-silicon dienes if the terminal alkyne used bears silicon with large substituents such

as 20 Intramolecular enyne cross metathesis can be used to make additional silyl substituted

alkenyl cyclopentenes such as 30 but fails as a route to make a silyl substituted alkenyl

cyclohexenes such as 33

4 Experimental

41 General Procedures are part of the Supplementary Material

421 Synthesis of (Buta-13-dien-2-yl)dimethyl(phenyl)silane (2) Chloroprene (458 g 517

mmol) and phenyldimethylchlorosilane (803 g 471 mmol) were used according to the general

procedure to yield a light yellow colored crude product (144 g) as a mixture of diene and

xylenes The crude product was subjected to fractional distillation at reduced pressure (20 mm

45 ⁰C) which resulted in a brown colored liquid which was further purified by flash

chromatography (100 pentanes) to yield the title compound (2) as a light yellow liquid (836 g

444 mmol 97) Rf 063 (100 pentanes) 1H NMR (500 MHz CDCl3) δ 749minus755 (m 2H)

731minus737 (m 3H) 646 (dd J = 177 109 Hz 1H) 588 (d J = 32 Hz 1H) 551 (d J = 32

Hz 1H) 510 (d J = 177 Hz 1H) 500 (d J = 109 Hz 1H) 043 (s 6H) 13C NMR (75 MHz

CDCl3) δ 1476 1411 1382 1339 1304 1290 1278 1167 minus23 HRMS calcd for C12H16Si

(M+) 1881021 found 1881020

422 Synthesis of (Buta-13-dien-2-yl) dimethylsilanol (3) Chloroprene in 50 xylenes

(10mL 515 mmol) and dichlorodimethylsilane (0645 g 5 mmol) were used according to the

general procedure above (1M acetate buffer of pH 5 was used instead of 05M HCl for the

quench) to yield a light yellow colored liquid 1H NMR of the crude product (11g) showed a

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mixture of xylenes diene and the corresponding disiloxane dimer Kugelrohr distillation at 60˚C

(4mm Hg) of the crude product yielded the target compound (3) (0300g 23 mmol 46) 1H

NMR (300 MHz CDCl3) δ 646 (dd J = 178 108 Hz 1H) 577 (d J = 30 Hz 1H) 556 (d J =

29 Hz 1H) 537 (d J = 182 Hz 1H) 512 (d J = 108 Hz 1H) 225 (bs 1H) 030 (s 6H) 13C

NMR (75 MHz CDCl3) δ 14865 14088 12958 11656 032 EIMS calcd for C6H13OSi

(M+H)+ 12906 found 1290

431 Synthesis of Trimethyl[(E)-4-phenyl-13-butadien-2-yl]silane (5) 1-[(E)-3-Bromobuta-13-

dienyl]benzene13 (4) (199 g 949 mmol) and trimethylsilylchloride (137 g 126 mmol) were

used according to the general method producing the crude compound as a dark brown liquid

Purification by flash chromatography (hexanes Et2O 91) yielded compound 5 as a brown-

yellow oil (156 g 773 mmol 85) This compound has been reported previously by a

different route but no characterization data were provided14 Rf 015 (hexanesEt2O 91) 1H

NMR (500 MHz CDCl3) δ 743 (d J = 77 Hz 2H) 734 (t J = 77 Hz 2H) 724 (t J = 74 Hz

1H) 694 (d J = 165 Hz 1H) 664 (d J = 165 Hz 1H) 589 (d J = 30 Hz 1H) 553 (d J =

30 Hz 1H) 027 (s 9H) 13C NMR (75 MHz CDCl3) δ 1489 1377 1340 1305 1286 1285

1273 1263 08

432 Synthesis of (1-Cyclohexylideneprop-2-en-2-yl)trimethylsilane (7) Chlorotrimethylsilane

(0685 g 630 mmol) and (2-bromoallylidene)cyclohexene15 (6) (0929 g 464 mmol) were used

according to the general procedure The resulting dark brown crude residue after purification by

flash chromatography (hexanes Et2O 151 rarr 91) yielded compound 7 as a brown-yellow oil

(0483 g 249 mmol 47) Rf 084 (hexanesEt2O 151) 1H NMR (500 MHz CDCl3) δ 571 (s

1H) 540minus549 (m 2H) 210minus223 (m 4H) 154minus160 (m 4H) 141minus150 (m 2H) 007 (s

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9H) 13C NMR (75 MHz CDCl3) δ 1503 1405 1251 1235 374 293 290 283 269

minus195 HRMS calcd for C12H22Si (M+) 1941491 found 1941489

44 Diels-Alder Reactions

441 Synthesis of 3a477a-Tetrahydro-5-[dimethyl(phenyl)silyl]-2-phenyl-2H-isoindole-13-

dione (8) Diene (2) (0302 g 160 mmol) and N-phenylmaleimide (0103 g 0595 mmol) were

dissolved in THF (5mL) and degassed in a sealed tube After heating for 4h at 90 ⁰C the reaction

mixture was filtered through a cotton plug and volatiles were removed by rotary evaporation

The resulting yellow colored residue was purified by flash chromatography with the excess diene

(2) eluting (0151 g 0802 mmol 78 recovery Rf 084 pentanediethyl ether 11) followed by

the cycloadduct 8 as a colorless clear viscous liquid (0204 g 0564 mmol 98) Rf 029

(pentanediethyl ether 11) 1H NMR (500 MHz CDCl3) δ 741minus754 (m 4H) 729minus741 (m

4H) 709minus720 (m 2H) 634 (m 1H) 318minus330 (m 2H) 271minus288 (m 2H) 222minus236 (m

2H) 036 (s 3H) 035 (s 3H) 13C NMR (75 MHz CDCl3) δ 1791 1787 1407 1384 1370

1339 1320 1292 1290 1284 1278 1263 393 392 264 250 -388 -389 HRMS calcd

for C22H23NO2Si (M+) 3611498 found 3611490 Anal calcd for C22H23NO2Si C 7310 H

642 Found C 7263 H 638

45 Cis-Hydrosilylation Reactions

452 Copper-catalyzed hydrosilylation of (E)-4-phenyl-3-buten-1-yne (9) To a 5-mL sealable

microwave tube equipped with a stir bar copper(I) chloride (0031 g 031 mmol) JohnPhos

(0037 g 012 mmol) and sodium tert-butoxide (0015 g 016 mmol) were suspended in THF

(26 mL) and degassed with argon (Dimethylphenylsilyl)boronic acid pinacol ester (14) (234

microL 086 mmol) was added to the reaction vessel the tube was sealed with a crimp cap and

placed in a circulating chiller at 0 degC After 30 min (E)-4-phenyl-3-buten-1-yne (9) (0108 g

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

1

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can be used to make 4-alkyl or 4-aryl-2-silicon substituted dienes if the terminal alkynes used for

cross metathesis bear small substituents on silicon3d The reaction fails as a route to make 4-

substituted-2-silicon dienes if the terminal alkyne used bears silicon with large substituents such

as 20 Intramolecular enyne cross metathesis can be used to make additional silyl substituted

alkenyl cyclopentenes such as 30 but fails as a route to make a silyl substituted alkenyl

cyclohexenes such as 33

4 Experimental

41 General Procedures are part of the Supplementary Material

421 Synthesis of (Buta-13-dien-2-yl)dimethyl(phenyl)silane (2) Chloroprene (458 g 517

mmol) and phenyldimethylchlorosilane (803 g 471 mmol) were used according to the general

procedure to yield a light yellow colored crude product (144 g) as a mixture of diene and

xylenes The crude product was subjected to fractional distillation at reduced pressure (20 mm

45 ⁰C) which resulted in a brown colored liquid which was further purified by flash

chromatography (100 pentanes) to yield the title compound (2) as a light yellow liquid (836 g

444 mmol 97) Rf 063 (100 pentanes) 1H NMR (500 MHz CDCl3) δ 749minus755 (m 2H)

731minus737 (m 3H) 646 (dd J = 177 109 Hz 1H) 588 (d J = 32 Hz 1H) 551 (d J = 32

Hz 1H) 510 (d J = 177 Hz 1H) 500 (d J = 109 Hz 1H) 043 (s 6H) 13C NMR (75 MHz

CDCl3) δ 1476 1411 1382 1339 1304 1290 1278 1167 minus23 HRMS calcd for C12H16Si

(M+) 1881021 found 1881020

422 Synthesis of (Buta-13-dien-2-yl) dimethylsilanol (3) Chloroprene in 50 xylenes

(10mL 515 mmol) and dichlorodimethylsilane (0645 g 5 mmol) were used according to the

general procedure above (1M acetate buffer of pH 5 was used instead of 05M HCl for the

quench) to yield a light yellow colored liquid 1H NMR of the crude product (11g) showed a

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mixture of xylenes diene and the corresponding disiloxane dimer Kugelrohr distillation at 60˚C

(4mm Hg) of the crude product yielded the target compound (3) (0300g 23 mmol 46) 1H

NMR (300 MHz CDCl3) δ 646 (dd J = 178 108 Hz 1H) 577 (d J = 30 Hz 1H) 556 (d J =

29 Hz 1H) 537 (d J = 182 Hz 1H) 512 (d J = 108 Hz 1H) 225 (bs 1H) 030 (s 6H) 13C

NMR (75 MHz CDCl3) δ 14865 14088 12958 11656 032 EIMS calcd for C6H13OSi

(M+H)+ 12906 found 1290

431 Synthesis of Trimethyl[(E)-4-phenyl-13-butadien-2-yl]silane (5) 1-[(E)-3-Bromobuta-13-

dienyl]benzene13 (4) (199 g 949 mmol) and trimethylsilylchloride (137 g 126 mmol) were

used according to the general method producing the crude compound as a dark brown liquid

Purification by flash chromatography (hexanes Et2O 91) yielded compound 5 as a brown-

yellow oil (156 g 773 mmol 85) This compound has been reported previously by a

different route but no characterization data were provided14 Rf 015 (hexanesEt2O 91) 1H

NMR (500 MHz CDCl3) δ 743 (d J = 77 Hz 2H) 734 (t J = 77 Hz 2H) 724 (t J = 74 Hz

1H) 694 (d J = 165 Hz 1H) 664 (d J = 165 Hz 1H) 589 (d J = 30 Hz 1H) 553 (d J =

30 Hz 1H) 027 (s 9H) 13C NMR (75 MHz CDCl3) δ 1489 1377 1340 1305 1286 1285

1273 1263 08

432 Synthesis of (1-Cyclohexylideneprop-2-en-2-yl)trimethylsilane (7) Chlorotrimethylsilane

(0685 g 630 mmol) and (2-bromoallylidene)cyclohexene15 (6) (0929 g 464 mmol) were used

according to the general procedure The resulting dark brown crude residue after purification by

flash chromatography (hexanes Et2O 151 rarr 91) yielded compound 7 as a brown-yellow oil

(0483 g 249 mmol 47) Rf 084 (hexanesEt2O 151) 1H NMR (500 MHz CDCl3) δ 571 (s

1H) 540minus549 (m 2H) 210minus223 (m 4H) 154minus160 (m 4H) 141minus150 (m 2H) 007 (s

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9H) 13C NMR (75 MHz CDCl3) δ 1503 1405 1251 1235 374 293 290 283 269

minus195 HRMS calcd for C12H22Si (M+) 1941491 found 1941489

44 Diels-Alder Reactions

441 Synthesis of 3a477a-Tetrahydro-5-[dimethyl(phenyl)silyl]-2-phenyl-2H-isoindole-13-

dione (8) Diene (2) (0302 g 160 mmol) and N-phenylmaleimide (0103 g 0595 mmol) were

dissolved in THF (5mL) and degassed in a sealed tube After heating for 4h at 90 ⁰C the reaction

mixture was filtered through a cotton plug and volatiles were removed by rotary evaporation

The resulting yellow colored residue was purified by flash chromatography with the excess diene

(2) eluting (0151 g 0802 mmol 78 recovery Rf 084 pentanediethyl ether 11) followed by

the cycloadduct 8 as a colorless clear viscous liquid (0204 g 0564 mmol 98) Rf 029

(pentanediethyl ether 11) 1H NMR (500 MHz CDCl3) δ 741minus754 (m 4H) 729minus741 (m

4H) 709minus720 (m 2H) 634 (m 1H) 318minus330 (m 2H) 271minus288 (m 2H) 222minus236 (m

2H) 036 (s 3H) 035 (s 3H) 13C NMR (75 MHz CDCl3) δ 1791 1787 1407 1384 1370

1339 1320 1292 1290 1284 1278 1263 393 392 264 250 -388 -389 HRMS calcd

for C22H23NO2Si (M+) 3611498 found 3611490 Anal calcd for C22H23NO2Si C 7310 H

642 Found C 7263 H 638

45 Cis-Hydrosilylation Reactions

452 Copper-catalyzed hydrosilylation of (E)-4-phenyl-3-buten-1-yne (9) To a 5-mL sealable

microwave tube equipped with a stir bar copper(I) chloride (0031 g 031 mmol) JohnPhos

(0037 g 012 mmol) and sodium tert-butoxide (0015 g 016 mmol) were suspended in THF

(26 mL) and degassed with argon (Dimethylphenylsilyl)boronic acid pinacol ester (14) (234

microL 086 mmol) was added to the reaction vessel the tube was sealed with a crimp cap and

placed in a circulating chiller at 0 degC After 30 min (E)-4-phenyl-3-buten-1-yne (9) (0108 g

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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mixture of xylenes diene and the corresponding disiloxane dimer Kugelrohr distillation at 60˚C

(4mm Hg) of the crude product yielded the target compound (3) (0300g 23 mmol 46) 1H

NMR (300 MHz CDCl3) δ 646 (dd J = 178 108 Hz 1H) 577 (d J = 30 Hz 1H) 556 (d J =

29 Hz 1H) 537 (d J = 182 Hz 1H) 512 (d J = 108 Hz 1H) 225 (bs 1H) 030 (s 6H) 13C

NMR (75 MHz CDCl3) δ 14865 14088 12958 11656 032 EIMS calcd for C6H13OSi

(M+H)+ 12906 found 1290

431 Synthesis of Trimethyl[(E)-4-phenyl-13-butadien-2-yl]silane (5) 1-[(E)-3-Bromobuta-13-

dienyl]benzene13 (4) (199 g 949 mmol) and trimethylsilylchloride (137 g 126 mmol) were

used according to the general method producing the crude compound as a dark brown liquid

Purification by flash chromatography (hexanes Et2O 91) yielded compound 5 as a brown-

yellow oil (156 g 773 mmol 85) This compound has been reported previously by a

different route but no characterization data were provided14 Rf 015 (hexanesEt2O 91) 1H

NMR (500 MHz CDCl3) δ 743 (d J = 77 Hz 2H) 734 (t J = 77 Hz 2H) 724 (t J = 74 Hz

1H) 694 (d J = 165 Hz 1H) 664 (d J = 165 Hz 1H) 589 (d J = 30 Hz 1H) 553 (d J =

30 Hz 1H) 027 (s 9H) 13C NMR (75 MHz CDCl3) δ 1489 1377 1340 1305 1286 1285

1273 1263 08

432 Synthesis of (1-Cyclohexylideneprop-2-en-2-yl)trimethylsilane (7) Chlorotrimethylsilane

(0685 g 630 mmol) and (2-bromoallylidene)cyclohexene15 (6) (0929 g 464 mmol) were used

according to the general procedure The resulting dark brown crude residue after purification by

flash chromatography (hexanes Et2O 151 rarr 91) yielded compound 7 as a brown-yellow oil

(0483 g 249 mmol 47) Rf 084 (hexanesEt2O 151) 1H NMR (500 MHz CDCl3) δ 571 (s

1H) 540minus549 (m 2H) 210minus223 (m 4H) 154minus160 (m 4H) 141minus150 (m 2H) 007 (s

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9H) 13C NMR (75 MHz CDCl3) δ 1503 1405 1251 1235 374 293 290 283 269

minus195 HRMS calcd for C12H22Si (M+) 1941491 found 1941489

44 Diels-Alder Reactions

441 Synthesis of 3a477a-Tetrahydro-5-[dimethyl(phenyl)silyl]-2-phenyl-2H-isoindole-13-

dione (8) Diene (2) (0302 g 160 mmol) and N-phenylmaleimide (0103 g 0595 mmol) were

dissolved in THF (5mL) and degassed in a sealed tube After heating for 4h at 90 ⁰C the reaction

mixture was filtered through a cotton plug and volatiles were removed by rotary evaporation

The resulting yellow colored residue was purified by flash chromatography with the excess diene

(2) eluting (0151 g 0802 mmol 78 recovery Rf 084 pentanediethyl ether 11) followed by

the cycloadduct 8 as a colorless clear viscous liquid (0204 g 0564 mmol 98) Rf 029

(pentanediethyl ether 11) 1H NMR (500 MHz CDCl3) δ 741minus754 (m 4H) 729minus741 (m

4H) 709minus720 (m 2H) 634 (m 1H) 318minus330 (m 2H) 271minus288 (m 2H) 222minus236 (m

2H) 036 (s 3H) 035 (s 3H) 13C NMR (75 MHz CDCl3) δ 1791 1787 1407 1384 1370

1339 1320 1292 1290 1284 1278 1263 393 392 264 250 -388 -389 HRMS calcd

for C22H23NO2Si (M+) 3611498 found 3611490 Anal calcd for C22H23NO2Si C 7310 H

642 Found C 7263 H 638

45 Cis-Hydrosilylation Reactions

452 Copper-catalyzed hydrosilylation of (E)-4-phenyl-3-buten-1-yne (9) To a 5-mL sealable

microwave tube equipped with a stir bar copper(I) chloride (0031 g 031 mmol) JohnPhos

(0037 g 012 mmol) and sodium tert-butoxide (0015 g 016 mmol) were suspended in THF

(26 mL) and degassed with argon (Dimethylphenylsilyl)boronic acid pinacol ester (14) (234

microL 086 mmol) was added to the reaction vessel the tube was sealed with a crimp cap and

placed in a circulating chiller at 0 degC After 30 min (E)-4-phenyl-3-buten-1-yne (9) (0108 g

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

1

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9H) 13C NMR (75 MHz CDCl3) δ 1503 1405 1251 1235 374 293 290 283 269

minus195 HRMS calcd for C12H22Si (M+) 1941491 found 1941489

44 Diels-Alder Reactions

441 Synthesis of 3a477a-Tetrahydro-5-[dimethyl(phenyl)silyl]-2-phenyl-2H-isoindole-13-

dione (8) Diene (2) (0302 g 160 mmol) and N-phenylmaleimide (0103 g 0595 mmol) were

dissolved in THF (5mL) and degassed in a sealed tube After heating for 4h at 90 ⁰C the reaction

mixture was filtered through a cotton plug and volatiles were removed by rotary evaporation

The resulting yellow colored residue was purified by flash chromatography with the excess diene

(2) eluting (0151 g 0802 mmol 78 recovery Rf 084 pentanediethyl ether 11) followed by

the cycloadduct 8 as a colorless clear viscous liquid (0204 g 0564 mmol 98) Rf 029

(pentanediethyl ether 11) 1H NMR (500 MHz CDCl3) δ 741minus754 (m 4H) 729minus741 (m

4H) 709minus720 (m 2H) 634 (m 1H) 318minus330 (m 2H) 271minus288 (m 2H) 222minus236 (m

2H) 036 (s 3H) 035 (s 3H) 13C NMR (75 MHz CDCl3) δ 1791 1787 1407 1384 1370

1339 1320 1292 1290 1284 1278 1263 393 392 264 250 -388 -389 HRMS calcd

for C22H23NO2Si (M+) 3611498 found 3611490 Anal calcd for C22H23NO2Si C 7310 H

642 Found C 7263 H 638

45 Cis-Hydrosilylation Reactions

452 Copper-catalyzed hydrosilylation of (E)-4-phenyl-3-buten-1-yne (9) To a 5-mL sealable

microwave tube equipped with a stir bar copper(I) chloride (0031 g 031 mmol) JohnPhos

(0037 g 012 mmol) and sodium tert-butoxide (0015 g 016 mmol) were suspended in THF

(26 mL) and degassed with argon (Dimethylphenylsilyl)boronic acid pinacol ester (14) (234

microL 086 mmol) was added to the reaction vessel the tube was sealed with a crimp cap and

placed in a circulating chiller at 0 degC After 30 min (E)-4-phenyl-3-buten-1-yne (9) (0108 g

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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084 mmol) and MeOH (65 microL 161 mmol) were injected into the reaction vessel After 24 h at

0degC the reaction mixture was filtered through a plug of celite with DCM (100 mL) The organic

solution was then condensed by rotary evaporation and dried under reduced pressure to yield a

greenish brown liquid (0386 g) The crude product was purified on silica gel with 201

hexanesethyl acetate resulting in dienes 1516 as a yellow liquid (0091 g 034 mmol 41) Rf

05 (hexanesethyl acetate 201) 15 (major product) 1H NMR (300 MHz CDCl3) δ 759-714

(m 10H) 692 (d J = 164 Hz 1H) 648 (d J = 162 Hz 1H) 600 (d J = 29 Hz 1H) 557 (d

J = 29 Hz 1H) 049 (s 6H) 13C NMR (755 MHz CDCl3) δ 1468 (C) 1381 (C) 1375 (C)

1339 (CH) 1335 (CH) 1315 (CH) 1305 (CH2) 1291 (CH) 1285 (CH) 1279 (CH) 1273

(CH) 1262 (CH) -21 (CH3) GCMS mz (relative ) 2652 (2) [M+1] 2641 (8) [M+]

2041 (2) 1731 (3) 1710 (3) 1450 (4) 1371 (4) 1361 (14) 1351 (100) 1281 (27) 1210

(4) 1070 (6) 1050 (8) 911 (4) 781 (7) 511 (3) 21 ratio of αβ regio isomers was

determined by the integrations of vinyl resonances in the 1H NMR spectrum

46 Trans-Hydrosilylation Reactions

461 Trans-hydrosilylatoncarbonyl condensation of enynes to prepare siloxycyclopentenes

(19) In a 100 mL flame dried flask equipped with a magnetic stir bar 3-methyl-3-buten-1-yne

(139 g 209 mmol) was added followed by anhydrous THF (20 mL) The solution was cooled

to -78oC and nBuLi (150 mL of a 16 M soln in hexanes 230 mmol) was added slowly and

stirred for 20 min Chlorodiisopropylsilane (344 g 230 mmol) in THF (10 mL) was added drop

wise to the above reaction mixture After stirring for 30 min at -78 ˚C it was allowed to warm

and stirred 12 h at RT The milky white reaction mixture was diluted with diethyl ether (100 mL)

and washed with half saturated NH4Cl solution (100 mL) The organic layer was dried over

MgSO4 and the solvent was evaporated under reduced pressure to give a light yellow colored

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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liquid (18a) (3279 g 1818 mmol 87) 1H NMR (300 MHz CDCl3) δ 537 ndash 538 (m 1H)

527 (p J = 166 Hz 1H) 375 (bs 1H) 190 (t J = 114 Hz 3H) 106 (m 14 H) 13C NMR

(75MHz CDCl3) δ 12679 12304 10917 8668 2388 1849 1824 1086 HRMS calcd for

C11H20Si (M+) 1801333 found 1801333

In a 20 mL flame dried flask anhydrous THF (5 mL) was added followed by acetone (0269 g

464 mmol) To that solution the silylation product (18a) (092 g 511 mmol) was added

followed by 95 KOtBu (0052 g 0464 mmol) The solution was stirred for 40 min at RT and

then washed with half saturated NH4Cl solution (20 mL) and diethyl ether (20 mL) and the

organics dried over MgSO4 Upon removal of the solvent under reduced pressure and flash

chromatography with 4 diethyl ether in pentane (Rf 044) the target compound (19a) was

isolated as a clear liquid (0918 g 385 mmol 83 ) 1H NMR (300 MHz CDCl3) δ 651 (s

1H) 498 (bs 1H) ) 479 (bs 1H) ) 191 (s 3H) ) 135 (s 6H) ) 098 (m 14H) 13C NMR

(75MHz CDCl3) δ 15104 14212 13793 11631 8243 2973 207 1784 174 1319

HRMS calcd for C14H26OSi (M+) 2381753 found 2381755

463 Preparation of 19c(E)-4-phenyl-3-buten-1-yne (9) was synthesized from trans-

cinnamaldehyde as described previously8 Enyne 9 (1361 g 1061 mmol) nBu-Li (73 mL of a

16 M soln in hexanes 117 mmol) and chlorodiisopropylsilane (176 g 117 mmol) were

combined and worked up as described above to yield crude 18c (2343 g) as a dark brown liquid

Flash chromatography using 3 triethylamine in pentane (Rf 06) produced 18c as a light yellow

colored oil (1906 g 786 mmol 74) 1H NMR (300 MHz CDCl3) δ 728 ndash 740 (m 5H) 703

(d J = 163 Hz 1H) 620 (dd J = 163 104 Hz) 380 (bs 1H) 108 ndash 112 (m 14H) 13C NMR

(75 MHz CDCl3) δ 14275 13605 12882 12871 12631 10796 10793 9956 1853 1830

1093 HRMS calcd for C16H12Si (M+) 2421490 found 2421486 Compound 18c (005 g 0206

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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mmol) paraformaldehyde (00051 g 017 mmol) and 95 KOtBu (0002 g 017 mmol)) were

combined and worked up as described above for 19a to yield a crude product which was purified

by preparative silica gel chromatography and eluted with (33 96) triethylaminediethyl

etherpentane mixture (Rf 04) An orange colored liquid (19c) was isolated (0030 g 011 mmol

53) 1H NMR (300 MHz CDCl3) δ 723 -743 (m 5H) 713 (d J = 1598 Hz 1H) 685 (bs

1H) 640 (d J = 1598 Hz 1H) 106 ndash 112 (m 14 H) 13C NMR (75 MHz CDCl3) δ (14644

13745 13740 13271 12861 12748 12624 7263 17 36 1696 1327

47 Enyne Cross Metathesis

472 (Z)-3-methylene-5-phenyl-4-(trimethylsilyl)pent-4-en-2-one (27) To a dried 50-mL round

bottom flask equipped with a stir bar HoveydandashGrubbs 2nd generation catalyst (0165 g 026

mmol) was added dissolved in DCM (365 mL) and degassed with argon 4-(Trimethylsilyl)-3-

butyn-2-one (26) (292 microL 178 mmol) and styrene (21) (10 mL 87 mmol) were then added

successively to the reaction flask The flask was then fitted with a condenser and heated to 40 degC

After 24 h the reaction was cooled to room temperature condensed by rotary evaporation and

dried under reduced pressure to yield a brown liquid (042 g) The crude product was then

purified on silica gel with 51 hexanesethyl acetate as eluent resulting in a yellow oil 27 (0041

g 017 mmol 9) Rf 03 (hexanesethyl acetate 51) 1H NMR (300 MHz CDCl3) δ 730 (m

5H) 716 (s 1H) 594 (d J = 09 Hz 1H) 575 (d J = 09 Hz 1H) 239 (s 3H) -005 (s 9H)

13C NMR (755 MHz CDCl3) δ 2000 (C=O) 1557 (C) 1448 (C) 1445 (CH) 1394 (C) 1285

(CH) 1278 (CH) 1273 (CH) 1230 (CH2) 264 (CH3) 048 (CH3) HRMS [M+Na]+ calcd for

C15H20NaOSi 2671181 found 2671194 Regiochemistry supported by HMBC spectroscopy

Double bond isomer supported by NOE spectroscopy

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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473 Intramolecular enyne cross metathesis6-Hept-1-yne (28) was synthesized from 5-bromo-

1-pentene as described previously16 The enyne (28) (06 g 637 mmol) was treated with nBu-Li

(45 mL of a 16 M soln in hexanes 7 mmol) and benzylchlorodimethylsilane (1404 g 75

mmol) as described above for 18a-c A light yellow colored liquid (29) was obtained (1377 g

568 mmol 89) 1H NMR (500 MHz CDCl3) δ 722 (t J = 804 Hz 2H) 709 (m 3H) 58

(ddt J = 17 1025 67 Hz 1H) 5045 (dd J = 171 172 Hz 1H) 500 (m 1H) 224 (t J = 71

Hz 2H) 219 (s 2H) 214 (q J = 744 Hz 2H) 161 (p J = 804 Hz 2H) 011 (s 6H) 13C

NMR (75 MHz CDCl3) δ 13922 13774 12833 12806 12421 11519 10855 8310 3268

2768 2651 1923 - 191 HRMS calcd for C16H22Si (M+) 2421491 found 2421492

474 Preparation of diene 30 Hoveyda-Grubbs second generation catalyst (0045g

0053mmol) was added to a flame dried flask equipped with stir bar and 4 Aring molecular sieves

(40 ww) DCM (3mL) was added and the solution was degassed Silylenyne (29) (0080g

0353 mmol) was added and refluxed for 12h under Ar The reaction was monitored by 1H NMR

spectroscopy Upon completion of the reaction solvent was removed under vacuum and the

crude product was purified by preparative silica gel TLC (Rf 066 (triethylamine Et2O pentane

1150) to yield 30 (0034 g 0140 mmol 40) 1H NMR ((500 MHz CDCl3) δ 719 (t J=754

Hz 2H) 706 (t J=738 Hz 1H) 698 (d J = 81 Hz 2H) 58 (bs 1H) 566 (d J= 266 Hz

1H) 536 (d J = 265 Hz 1H) 248-251 (m 4H) 226 (s 2H) 19 (p J= 764 Hz 2H)

0133 (s 6H) 13C NMR (75 MHz CDCl3) δ 14515 14419 14011 12940 12827 12800

12566 12396 3368 3307297 2596 2244 HRMS calcd for C16H22Si (M+) 2421491 found

2421494

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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Supporting Information

General experimental procedures used to prepare many of the compounds and 1H and 13C NMR

spectral data for all new compounds reported

Acknowledgements

We thank the National Science Foundation for their support of this work (CHE-0749759) and

the NMR and X-ray instrumentation used to characterize the compounds reported here The

UNC Mass Spectrometry facility and Mass Spectrometry Lab School of Chemical Sciences

University of Illinois at Urbana-Champaign performed high resolution mass spectral analyses

References

(1) (a) Welker M E Adv Cycloaddn 1997 4 149 (b) Welker M E Curr Org Chem 2001 5 785

(2) (a) Welker M E Tetrahedron 2008 64 11529 (b) Lim D S W Anderson E A Synthesis-Stuttgart 2012 44 983 (c) Herndon J W Coord Chem Rev 2012 256 1281 (d) Sore H F Galloway W Spring D R Chem Soc Rev 2012 41 1845 (e) Puri J K Singh R Chahal V K Chem Soc Rev 2011 40 1791

(3) (a) Pidaparthi R R Welker M E Day C S Wright M W Org Lett 2007 9 1623 (b) Pidaparthi R R Welker M E Tet Lett 2007 48 7853 (c) Pidaparthi R R Junker C S Welker M E Day C S Wright M W J Org Chem 2009 74 8290 (d) Junker C S Welker M E Day C S J Org Chem 2010 75 8155 (e) Junker C S Welker M E Tetrahedron 2012 68 5341

(4) De S Welker M E Org Lett 2005 7 2481 (5) De S Day C Welker M E Tetrahedron 2007 63 10939 (6) (a) Denmark S E Werner N S J Am Chem Soc 2008 130 16382 (b) Zhou H

Moberg C Org Lett 2013 15 1444 (7) (a) Hyuga S Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 16

1757 (b) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 17 809 (8) (a) Miwa K Aoyama T Shioiri T Synlett 1994 107 (b) Albert B J

Sivaramakrishnan A Naka T Czaicki N L Koide K J Am Chem Soc 2007 129 2648

(9) Wang P Yeo X-L Loh T-P J Am Chem Soc 2011 133 1254 (10) Maifeld S V Lee D Org Lett 2005 7 4995 (11) Kim M Park S Maifeld S V Lee D J Am Chem Soc 2004 126 10242 (12) Dieltiens N Moonen K Stevens C V Chem ndash Eur J 2007 13 203 (13) (a) Ma S Wang G Tet Lett 2002 43 5723 (b) Ma S Hou H Zhao S Wang G

Synthesis 2002 2002 1643 (14) (a) Hyuga S Yamashina N Hara S Suzuki A Chem Lett 1988 809 (b) Hyuga S

Chiba Y Yamashina N Hara S Suzuki A Chem Lett 1987 1757

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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(15) Horvaacuteth A Baumlckvall J-E J Org Chem 2001 66 8120 (16) Negishi E Holmes S J Tour J M Miller J A Cederbaum F E Swanson D R

Takahashi T J Am Chem Soc 1989 111 3336

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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Syntheses of 2-Silicon-Substituted 13-Dienes Partha P Choudhury Christopher S Junker Ramakrishna R Pidaparthi and Mark E Welker Department of Chemistry Wake Forest University PO Box 7486 Winston-Salem NC 27109 (USA) email welkerwfuedu FAX (336)-758-4656 Highlights

bull Three different synthetic routes to 2-silyl substituted 13-dienes are presented bull Hydrosilylaton of enynes yields mixtures of regiosiomers bull Grignard chemistry is the best synthetic route when 2-halo-13-dienes are available

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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Syntheses of 2-Silicon-Substituted 13-Dienes

Partha Choudhury Christopher S Junker Ranlakrishna Pidaparthi and Mark E Welker

Department ofChemistry Wake Forest University P O Box 7486 Winston-Salem NC 27109 (USA) email

welkerwfuedu FAX (336)-758-4656

Supporting Information

Table of Contents Page

41 General Procedures 2 4 2 General Procedure for Grignard Reactions with Chloroprene 2 43 General Procedure for Reactions ofSilyl Grignard Reagents with Halodienes 3 451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane 4 462 Attempted Preparation of19 b 5 4 71 Enyne metathesis to produce silyl substituted dienes 5 475 Attempted preparation ofdiene 33 6 NMR Spectra of 2 7 NMR Spectra of3 9 NMR Spectra of 5 11 NMR Spectra of 7 13 NMR Spectraof8 15 NMR Spectra of 18b 17 NMR Spectra of 18c 19 NMR Spectra of 19a 21 NMR Spectra of 19c 23 NMR Spectra of 27 26 NMR Spectra of 29 31 NMR Spectra of30 33 NMR Spectra of32 35 NMR Spectra of 18a 38

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41 TIJIr]1 Procedures The 1ItfItn 111-1 U FTHVLAV resonance (lH NMR) were

-LULU using a Broker A vance 300 operating at 3001

spectrometer n~middott1lcr at 1 MHz BC NMR 11gt(gt1 VLUu usmg

a Avance 300 MHz spectr()mtteroperating at 755 MHz IH and lt1gt were

to the residual proton or carbon v~~~ of the respective 101ltgt(1 solvents All

O~ analyses were performed Microlabs Inc Norcross High-resolution

mass was performed at Spectrometry NC

-UVi were carried out ofnitrogen was

argon and then two 4 x 36 inch columns

(8 x mesh activated a at 350degC for 3 hr) to remove water Toluene

was degassed with N2 Water was and distilled were

1- from Cambridge Isotope and dried over molecular Sodium

sodium hydroxide lllsect 12-dibromoethane were purchased from

-UbullUl Company 2-Chloro-l

was purchased Inc and used as

Procedure for i7YUrrfl LU HJl with Chloroprene 100 2shy

round-bottom flask equipped with a stir bar addition condenser

was with magnesium (16 eq) followed by the addition (110 mol )

After stirring -ca 5 (initiation of magnesium can be noticed by

and ethane gas 30 mol of anhydrous THF (5 mL) was

mixture was (30 mL) a whitish-grey

was brought to over a period of 15 50

(10 eq) and dibromoethane 0 mol ) in THF (25 mL) was added drop-wise to the

2

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mixture over 30 min After the addition 1TII11VIII was continued for another

Agreenish-grey colored Grignard solution was rt by cannula into a 250 mL

om-mCK round-bottomed flask containing chlorosilane (095 in THF (25 mL) at room

reaction mixture was refluxed (1 h) poured 05M Hel solution (100 mL)

and VT1fTrt pentane (2 x 75 mL) The combined organic layers were

with 05M He (75 mL) water After drying over MgS04

reduced to diene with xylenes as

a

43 Tt~TJtCJ Procedure for Reactions ofSilyl rinIrrrf YpoundJJCTontlt with Halodienes Substituted

d middot h l 12middotthsHyl UUUI 7) were prepared according to a pn)ceQur reporte m t e lterature WI

mCIQIJt1cfttlcfns Magnesium turnings (30eq) and were taken into a 2-neck 100

mL rotmQ-b(mOlm(~Q flask fitted with a reflux v addition funnel and stir-bar After

adding (20 mL) and stirring for ca~ 2 dibromoethane (15 mol) in THF (50 mL) was

added at room temperature After cessation of 141 the reaction flask was

to 0 an lce-02ltn and stirring Ih Silylchloride (l3eq) in (10

over 15 min followed auUVU ofa mixture of halodiene

(10eq) dibromoethane (30 mol) in (20 over a period of45 min After

addition vv stirring was continued for 1 h at 0 at room temperature

~tgt The reaction mixture was quenched 06 M Hel (50 mL) and extlact(~a

(3 x 30 mL) The combined were washed with brine x 50

dried over and volatiles were removed rotary evaporation The crude product was

chromatography

3

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451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane To a 10-mL round

bottom (E)-4-phenyl-3-buten-l-yne (9) (1 eq) hydrosilane (1 equiv) were dissolved

(2-5 mL) purged with N2 gas Ruthenium catalyst (5-10 was then

added to reaction mixture to 50 in an oil After amount of

time the reaction was cooled to room temperature condensed by evaporation and dried

under reduced Using Grubbs 1st generation catalyst (E)-4-phenyl-3-buten-l-yne8 (9)

(0067 mmol) triethoxysilane (0104 g 0633 mmol) Grubbs 1st generation

(0023 g 003 mmol) and v (5 were rp~1prl according to general oroceaur for

h to a brown (0181 g) Analysis product vinyl which

correspond to double bond isomers diene Integration shifts indicates a 1

of the desired (l isomer (12) to unwanted ~ isomers (13)

12 NMR diagnostic alkene LjOJlVU (300 CDCh) (app q 150 Hz 602 (d

33 Hz 589 (d J Hz 1

Using ruthenium catalyst 11 a dry 10-mL round bottom flask (E)-4-phenyl-3-buten-1-yne

(9) (0064 05 mmol) (113 mmol) DCM (25 were and

with while cooled to ooe in an bath After 10 minutes catalyst 11

(0030 005 mmol) was added the reaction was wanned to room temperature Ar(g)

After 19 h analysis revealed no remaining The mixture was COrlCeltltnlted

reduced to an oil (01 g 05mmol) which was a 1 mixture of ~XJ

1213 by NMR

4 Attempted Preparation of19 b Similarly 3-methyl-3-but-l-yne (17

Me)(L38 g 209 mmol) (150 roL of a 16 M III uugt

dimethylchlorosilane g 25 was to as a liquid 8 g

4

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145 mmol IH NMR (300 MHz CDCh) 0 (slH) IH)418 J = 37

Hz 1 189 (s 3H) (d J = 37 6 BC NMR MHz CDCh) 0 1 12335

107678991 HRMS for C7H 1 1230630 found 1230632

Compound ISb (0400 mmol) acetone (0 27 and 95 (0032 g

were the diene yntnesls as described above for 19a NMR of the

product mOllCatea (19b) iVraquoUltVH but it not purified by alumina or

chromatography

471 Enyne metathesis to produce silyl substituted 23 To a 15-mL round

bottom Grubbs-Hoyeda generation (0060 0088 mmol) was aUUliu

dissolved in DCM (2 mL) purged with Ar(g) and septum In a dry vial

triphenylsilylacetylene (20) (0255 088 mmol) was dissolved in DCM (1 mL) This

solution was injected the round bottom The round bottom was then fitted with a

balloon Styrene mmol) was dropwise at

approximately 1 10 minutes analysis

Another equivalent of (01 mL 088 mmol) was then added dropwise another 10

uu ~u TLC analysis showed no bull ~LUJLEgt alkyne reaction mixture was then

concentrated under reduced to yield a brown residue Purification on silica

gel cyclohexane as eluent diene (23) as a white powder (0191 g061

mmol 69) Juu by spectroscopic comparison to reported 15

475 Attempted preparation ofdiene 33 -yne (31) was as i

16 (31)(100 mmol) (65 mL a 16M soin in

hexaneslO mmol) and benzylchlorodimethylsilane (1877 g 1016 mmol) were combined

ltUJVLUlll- to the general procedure used to 18a-c to A-~ a crude product which was

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mixture over 30 min After the addition 1TII11VIII was continued for another

Agreenish-grey colored Grignard solution was rt by cannula into a 250 mL

om-mCK round-bottomed flask containing chlorosilane (095 in THF (25 mL) at room

reaction mixture was refluxed (1 h) poured 05M Hel solution (100 mL)

and VT1fTrt pentane (2 x 75 mL) The combined organic layers were

with 05M He (75 mL) water After drying over MgS04

reduced to diene with xylenes as

a

43 Tt~TJtCJ Procedure for Reactions ofSilyl rinIrrrf YpoundJJCTontlt with Halodienes Substituted

d middot h l 12middotthsHyl UUUI 7) were prepared according to a pn)ceQur reporte m t e lterature WI

mCIQIJt1cfttlcfns Magnesium turnings (30eq) and were taken into a 2-neck 100

mL rotmQ-b(mOlm(~Q flask fitted with a reflux v addition funnel and stir-bar After

adding (20 mL) and stirring for ca~ 2 dibromoethane (15 mol) in THF (50 mL) was

added at room temperature After cessation of 141 the reaction flask was

to 0 an lce-02ltn and stirring Ih Silylchloride (l3eq) in (10

over 15 min followed auUVU ofa mixture of halodiene

(10eq) dibromoethane (30 mol) in (20 over a period of45 min After

addition vv stirring was continued for 1 h at 0 at room temperature

~tgt The reaction mixture was quenched 06 M Hel (50 mL) and extlact(~a

(3 x 30 mL) The combined were washed with brine x 50

dried over and volatiles were removed rotary evaporation The crude product was

chromatography

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451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane To a 10-mL round

bottom (E)-4-phenyl-3-buten-l-yne (9) (1 eq) hydrosilane (1 equiv) were dissolved

(2-5 mL) purged with N2 gas Ruthenium catalyst (5-10 was then

added to reaction mixture to 50 in an oil After amount of

time the reaction was cooled to room temperature condensed by evaporation and dried

under reduced Using Grubbs 1st generation catalyst (E)-4-phenyl-3-buten-l-yne8 (9)

(0067 mmol) triethoxysilane (0104 g 0633 mmol) Grubbs 1st generation

(0023 g 003 mmol) and v (5 were rp~1prl according to general oroceaur for

h to a brown (0181 g) Analysis product vinyl which

correspond to double bond isomers diene Integration shifts indicates a 1

of the desired (l isomer (12) to unwanted ~ isomers (13)

12 NMR diagnostic alkene LjOJlVU (300 CDCh) (app q 150 Hz 602 (d

33 Hz 589 (d J Hz 1

Using ruthenium catalyst 11 a dry 10-mL round bottom flask (E)-4-phenyl-3-buten-1-yne

(9) (0064 05 mmol) (113 mmol) DCM (25 were and

with while cooled to ooe in an bath After 10 minutes catalyst 11

(0030 005 mmol) was added the reaction was wanned to room temperature Ar(g)

After 19 h analysis revealed no remaining The mixture was COrlCeltltnlted

reduced to an oil (01 g 05mmol) which was a 1 mixture of ~XJ

1213 by NMR

4 Attempted Preparation of19 b Similarly 3-methyl-3-but-l-yne (17

Me)(L38 g 209 mmol) (150 roL of a 16 M III uugt

dimethylchlorosilane g 25 was to as a liquid 8 g

4

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145 mmol IH NMR (300 MHz CDCh) 0 (slH) IH)418 J = 37

Hz 1 189 (s 3H) (d J = 37 6 BC NMR MHz CDCh) 0 1 12335

107678991 HRMS for C7H 1 1230630 found 1230632

Compound ISb (0400 mmol) acetone (0 27 and 95 (0032 g

were the diene yntnesls as described above for 19a NMR of the

product mOllCatea (19b) iVraquoUltVH but it not purified by alumina or

chromatography

471 Enyne metathesis to produce silyl substituted 23 To a 15-mL round

bottom Grubbs-Hoyeda generation (0060 0088 mmol) was aUUliu

dissolved in DCM (2 mL) purged with Ar(g) and septum In a dry vial

triphenylsilylacetylene (20) (0255 088 mmol) was dissolved in DCM (1 mL) This

solution was injected the round bottom The round bottom was then fitted with a

balloon Styrene mmol) was dropwise at

approximately 1 10 minutes analysis

Another equivalent of (01 mL 088 mmol) was then added dropwise another 10

uu ~u TLC analysis showed no bull ~LUJLEgt alkyne reaction mixture was then

concentrated under reduced to yield a brown residue Purification on silica

gel cyclohexane as eluent diene (23) as a white powder (0191 g061

mmol 69) Juu by spectroscopic comparison to reported 15

475 Attempted preparation ofdiene 33 -yne (31) was as i

16 (31)(100 mmol) (65 mL a 16M soin in

hexaneslO mmol) and benzylchlorodimethylsilane (1877 g 1016 mmol) were combined

ltUJVLUlll- to the general procedure used to 18a-c to A-~ a crude product which was

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451 Reactions of(E)-4-phenyl-3-buten-1-yne (9) with Triethoxysilane To a 10-mL round

bottom (E)-4-phenyl-3-buten-l-yne (9) (1 eq) hydrosilane (1 equiv) were dissolved

(2-5 mL) purged with N2 gas Ruthenium catalyst (5-10 was then

added to reaction mixture to 50 in an oil After amount of

time the reaction was cooled to room temperature condensed by evaporation and dried

under reduced Using Grubbs 1st generation catalyst (E)-4-phenyl-3-buten-l-yne8 (9)

(0067 mmol) triethoxysilane (0104 g 0633 mmol) Grubbs 1st generation

(0023 g 003 mmol) and v (5 were rp~1prl according to general oroceaur for

h to a brown (0181 g) Analysis product vinyl which

correspond to double bond isomers diene Integration shifts indicates a 1

of the desired (l isomer (12) to unwanted ~ isomers (13)

12 NMR diagnostic alkene LjOJlVU (300 CDCh) (app q 150 Hz 602 (d

33 Hz 589 (d J Hz 1

Using ruthenium catalyst 11 a dry 10-mL round bottom flask (E)-4-phenyl-3-buten-1-yne

(9) (0064 05 mmol) (113 mmol) DCM (25 were and

with while cooled to ooe in an bath After 10 minutes catalyst 11

(0030 005 mmol) was added the reaction was wanned to room temperature Ar(g)

After 19 h analysis revealed no remaining The mixture was COrlCeltltnlted

reduced to an oil (01 g 05mmol) which was a 1 mixture of ~XJ

1213 by NMR

4 Attempted Preparation of19 b Similarly 3-methyl-3-but-l-yne (17

Me)(L38 g 209 mmol) (150 roL of a 16 M III uugt

dimethylchlorosilane g 25 was to as a liquid 8 g

4

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145 mmol IH NMR (300 MHz CDCh) 0 (slH) IH)418 J = 37

Hz 1 189 (s 3H) (d J = 37 6 BC NMR MHz CDCh) 0 1 12335

107678991 HRMS for C7H 1 1230630 found 1230632

Compound ISb (0400 mmol) acetone (0 27 and 95 (0032 g

were the diene yntnesls as described above for 19a NMR of the

product mOllCatea (19b) iVraquoUltVH but it not purified by alumina or

chromatography

471 Enyne metathesis to produce silyl substituted 23 To a 15-mL round

bottom Grubbs-Hoyeda generation (0060 0088 mmol) was aUUliu

dissolved in DCM (2 mL) purged with Ar(g) and septum In a dry vial

triphenylsilylacetylene (20) (0255 088 mmol) was dissolved in DCM (1 mL) This

solution was injected the round bottom The round bottom was then fitted with a

balloon Styrene mmol) was dropwise at

approximately 1 10 minutes analysis

Another equivalent of (01 mL 088 mmol) was then added dropwise another 10

uu ~u TLC analysis showed no bull ~LUJLEgt alkyne reaction mixture was then

concentrated under reduced to yield a brown residue Purification on silica

gel cyclohexane as eluent diene (23) as a white powder (0191 g061

mmol 69) Juu by spectroscopic comparison to reported 15

475 Attempted preparation ofdiene 33 -yne (31) was as i

16 (31)(100 mmol) (65 mL a 16M soin in

hexaneslO mmol) and benzylchlorodimethylsilane (1877 g 1016 mmol) were combined

ltUJVLUlll- to the general procedure used to 18a-c to A-~ a crude product which was

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145 mmol IH NMR (300 MHz CDCh) 0 (slH) IH)418 J = 37

Hz 1 189 (s 3H) (d J = 37 6 BC NMR MHz CDCh) 0 1 12335

107678991 HRMS for C7H 1 1230630 found 1230632

Compound ISb (0400 mmol) acetone (0 27 and 95 (0032 g

were the diene yntnesls as described above for 19a NMR of the

product mOllCatea (19b) iVraquoUltVH but it not purified by alumina or

chromatography

471 Enyne metathesis to produce silyl substituted 23 To a 15-mL round

bottom Grubbs-Hoyeda generation (0060 0088 mmol) was aUUliu

dissolved in DCM (2 mL) purged with Ar(g) and septum In a dry vial

triphenylsilylacetylene (20) (0255 088 mmol) was dissolved in DCM (1 mL) This

solution was injected the round bottom The round bottom was then fitted with a

balloon Styrene mmol) was dropwise at

approximately 1 10 minutes analysis

Another equivalent of (01 mL 088 mmol) was then added dropwise another 10

uu ~u TLC analysis showed no bull ~LUJLEgt alkyne reaction mixture was then

concentrated under reduced to yield a brown residue Purification on silica

gel cyclohexane as eluent diene (23) as a white powder (0191 g061

mmol 69) Juu by spectroscopic comparison to reported 15

475 Attempted preparation ofdiene 33 -yne (31) was as i

16 (31)(100 mmol) (65 mL a 16M soin in

hexaneslO mmol) and benzylchlorodimethylsilane (1877 g 1016 mmol) were combined

ltUJVLUlll- to the general procedure used to 18a-c to A-~ a crude product which was

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purified by flash chromatography (RrOA 2 diethyl ether in pentane) to yield a clear liquid 32

(0899g35 65) NMRCDCb (500 MHz) 0 (tJ 81 Hz 709-7

(m 584 (ddt J 1711028 HzIH) J= 171 18 Hz IH)498 (m

IH) (t J 675 1 (s2H) 1 (q J 715 2 H) 146 - 159 (m 4H) 013

(s6H) l3C NMR (300 MHz 013924 13853 12834 12805 12420 11457 10880

8258 192796 2653 - 191 HRMS for (~)

found 2561 Intramolecular enyne metathesis of32 was attempted with amerent catalysts

( Hoveyda-Grubbs generation Zhan catalyst) different loadings

from 10 - 30mol in different (DCM THF LVLY

isolated and the NMR of the V-U mixture indicated decomposition of material

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34

a~Ra

N~~~~ bullbull MMNO~~OO~~~NNN~~rn t(V)NCl~O ~~~~MMMMMM~~~~~OOOO~mMMMOorn I~Ior MM

middot0 ~~~~~~~~~~~w~~~~~~m~~~~~~ 0000001

F

~~P V~~~ ~ LX-) Current Data Parameters NAME Ra-5134 EXPNO 1 PROCNO 1

F2 - Acquisition ParametersIt Oate_ 20070315 ~~NOG Time 1343

INSTRUM speetI( ~ J PROBHO 5 mm TXI 13C Z

PULPROG zg30 ~I-l- 5middot TO 32768 SOLVENT COC13-16 NS 16 OS 4(9s SWH 4340278 Hz FlORES 0132455 Hz AQ 37750387 see

Co WtpOv--nJ 2shy RG 32 OW 115200 usee OE 600 usee TE 3000 K 01 1 00000000 see MCREST 000000000 see MCWRK 001500000 see

======== CHANNEL fl ======== NUCl 1H PI 830 usee PL1 000 dB SF01 5001319199 MHz

F2 - Processing parameters SI 16384 SF 5001300500 MHz WOW EM SSB 0 LB 030 Hz GB 0 PC 100

I I ~f~ ~f~- ~f~Tf~ f

a 7 6 543 2 1 o ppm

(~y~ I~ (~I (sectI (sectr~ r~1

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en shy ~ - ~ --1476

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~ --138200 ~ 51 _____ 13392 - 13362 ~ _____ 13039

CN - - ~ _12901 shy

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L I) shy0 --11666

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(X) - ~7742o _______ 770 0 7658

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592--[

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bull I bull bull I

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Current Data Parameters NANE Ra-4064 EXPNO J PROCNO J

2 - Acquisition Parameters Date_ 20051207 Time 1206 INSTRUM spect PROSHO 5 mm TXI 13C Z PULPROG zg30 TD 32768 SOLVENT coelJ NS 16 DS 4 SIIH 4496403 Hz nORES 0137219 Hz AQ 36439629 sec RG 905 OW 111200 use DE 600 use TE 3000 K 01 100000000 sec flCREST 000000000 sec MCNRK 001500000 sec

======== CHANNEL fl ======= NUC1 IH PI 830 user PL1 000 dB SFOl 5001317481 KHz

F2 - Processing par2meters S1 16384 SF 5001300127 HHz JDN SSB L8 G8 PC

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N 1 cgt exgt CI 01 0 co rl N l) M MOC)O cgt U) cgt cgt fll) U) f - I (I r-r-ill rshy OlCOCOD rlt

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current Oato) ParltlJJlOtor NAME Occ06-2QOS EXPNO 2 PROCNU 1

F2 ~ Acqui~ it io1 PllranoterB Date_ 2005 1 201 Time 1126 INSTRIJl1 spect PROBf(O 5 mrn QNP IH PU1PROO jmod 10 65536 SOLVENT CDC) NS 4096 OS lt SI-IH 1883239] Hz FlORES 0287360 Hz 1gt0 17II00)OS sec RG 096 Dil 26 550 usee DE 6 00 Ulec TE 3000 K CNSI2 1450000000 CNSTll 10000000 Dl 200000000 cae d13 000000300 cc d20 O006B9655 lGC DELTA 000001592 SIX

11gt CHANNEL f l = ==c NUCI 11C PI 12 SO usee p2 250 0 usee PL1 000 dB SFOI 754760200 MHz

========gt= CHANNEL f2 = CPDPRG2 al tz1 6 NUC2 1H pePD 110 SO usee PL2 000 lt1D PL12 2000 dB SF02 JOOIJ1200S 101Hz

2 - Proces9in9 peramettr$ SI 32769 Sf 754677475 tlllz DJ pound11 SS8 0 LB 100 Hz CB 0 PC 1 ( 0

~~r I I n I I TT~n I I ~n I ~I I I I I I I I

150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

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Current Data Parameters NANE Ra-4064 EXPNO J PROCNO J

2 - Acquisition Parameters Date_ 20051207 Time 1206 INSTRUM spect PROSHO 5 mm TXI 13C Z PULPROG zg30 TD 32768 SOLVENT coelJ NS 16 DS 4 SIIH 4496403 Hz nORES 0137219 Hz AQ 36439629 sec RG 905 OW 111200 use DE 600 use TE 3000 K 01 100000000 sec flCREST 000000000 sec MCNRK 001500000 sec

======== CHANNEL fl ======= NUC1 IH PI 830 user PL1 000 dB SFOl 5001317481 KHz

F2 - Processing par2meters S1 16384 SF 5001300127 HHz JDN SSB L8 G8 PC

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current Oato) ParltlJJlOtor NAME Occ06-2QOS EXPNO 2 PROCNU 1

F2 ~ Acqui~ it io1 PllranoterB Date_ 2005 1 201 Time 1126 INSTRIJl1 spect PROBf(O 5 mrn QNP IH PU1PROO jmod 10 65536 SOLVENT CDC) NS 4096 OS lt SI-IH 1883239] Hz FlORES 0287360 Hz 1gt0 17II00)OS sec RG 096 Dil 26 550 usee DE 6 00 Ulec TE 3000 K CNSI2 1450000000 CNSTll 10000000 Dl 200000000 cae d13 000000300 cc d20 O006B9655 lGC DELTA 000001592 SIX

11gt CHANNEL f l = ==c NUCI 11C PI 12 SO usee p2 250 0 usee PL1 000 dB SFOI 754760200 MHz

========gt= CHANNEL f2 = CPDPRG2 al tz1 6 NUC2 1H pePD 110 SO usee PL2 000 lt1D PL12 2000 dB SF02 JOOIJ1200S 101Hz

2 - Proces9in9 peramettr$ SI 32769 Sf 754677475 tlllz DJ pound11 SS8 0 LB 100 Hz CB 0 PC 1 ( 0

~~r I I n I I TT~n I I ~n I ~I I I I I I I I

150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

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Current Data Parameters NANE Ra-4064 EXPNO J PROCNO J

2 - Acquisition Parameters Date_ 20051207 Time 1206 INSTRUM spect PROSHO 5 mm TXI 13C Z PULPROG zg30 TD 32768 SOLVENT coelJ NS 16 DS 4 SIIH 4496403 Hz nORES 0137219 Hz AQ 36439629 sec RG 905 OW 111200 use DE 600 use TE 3000 K 01 100000000 sec flCREST 000000000 sec MCNRK 001500000 sec

======== CHANNEL fl ======= NUC1 IH PI 830 user PL1 000 dB SFOl 5001317481 KHz

F2 - Processing par2meters S1 16384 SF 5001300127 HHz JDN SSB L8 G8 PC

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current Oato) ParltlJJlOtor NAME Occ06-2QOS EXPNO 2 PROCNU 1

F2 ~ Acqui~ it io1 PllranoterB Date_ 2005 1 201 Time 1126 INSTRIJl1 spect PROBf(O 5 mrn QNP IH PU1PROO jmod 10 65536 SOLVENT CDC) NS 4096 OS lt SI-IH 1883239] Hz FlORES 0287360 Hz 1gt0 17II00)OS sec RG 096 Dil 26 550 usee DE 6 00 Ulec TE 3000 K CNSI2 1450000000 CNSTll 10000000 Dl 200000000 cae d13 000000300 cc d20 O006B9655 lGC DELTA 000001592 SIX

11gt CHANNEL f l = ==c NUCI 11C PI 12 SO usee p2 250 0 usee PL1 000 dB SFOI 754760200 MHz

========gt= CHANNEL f2 = CPDPRG2 al tz1 6 NUC2 1H pePD 110 SO usee PL2 000 lt1D PL12 2000 dB SF02 JOOIJ1200S 101Hz

2 - Proces9in9 peramettr$ SI 32769 Sf 754677475 tlllz DJ pound11 SS8 0 LB 100 Hz CB 0 PC 1 ( 0

~~r I I n I I TT~n I I ~n I ~I I I I I I I I

150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

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Current Data Parameters NANE Ra-4064 EXPNO J PROCNO J

2 - Acquisition Parameters Date_ 20051207 Time 1206 INSTRUM spect PROSHO 5 mm TXI 13C Z PULPROG zg30 TD 32768 SOLVENT coelJ NS 16 DS 4 SIIH 4496403 Hz nORES 0137219 Hz AQ 36439629 sec RG 905 OW 111200 use DE 600 use TE 3000 K 01 100000000 sec flCREST 000000000 sec MCNRK 001500000 sec

======== CHANNEL fl ======= NUC1 IH PI 830 user PL1 000 dB SFOl 5001317481 KHz

F2 - Processing par2meters S1 16384 SF 5001300127 HHz JDN SSB L8 G8 PC

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ACCEPTED MANUSCRIPT or Ra-4064 Ctl~fY~ 1 C13APT 4hrs C13 and 1 I) I - B~F

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current Oato) ParltlJJlOtor NAME Occ06-2QOS EXPNO 2 PROCNU 1

F2 ~ Acqui~ it io1 PllranoterB Date_ 2005 1 201 Time 1126 INSTRIJl1 spect PROBf(O 5 mrn QNP IH PU1PROO jmod 10 65536 SOLVENT CDC) NS 4096 OS lt SI-IH 1883239] Hz FlORES 0287360 Hz 1gt0 17II00)OS sec RG 096 Dil 26 550 usee DE 6 00 Ulec TE 3000 K CNSI2 1450000000 CNSTll 10000000 Dl 200000000 cae d13 000000300 cc d20 O006B9655 lGC DELTA 000001592 SIX

11gt CHANNEL f l = ==c NUCI 11C PI 12 SO usee p2 250 0 usee PL1 000 dB SFOI 754760200 MHz

========gt= CHANNEL f2 = CPDPRG2 al tz1 6 NUC2 1H pePD 110 SO usee PL2 000 lt1D PL12 2000 dB SF02 JOOIJ1200S 101Hz

2 - Proces9in9 peramettr$ SI 32769 Sf 754677475 tlllz DJ pound11 SS8 0 LB 100 Hz CB 0 PC 1 ( 0

~~r I I n I I TT~n I I ~n I ~I I I I I I I I

150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

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Current Data Parameters NANE Ra-4064 EXPNO J PROCNO J

2 - Acquisition Parameters Date_ 20051207 Time 1206 INSTRUM spect PROSHO 5 mm TXI 13C Z PULPROG zg30 TD 32768 SOLVENT coelJ NS 16 DS 4 SIIH 4496403 Hz nORES 0137219 Hz AQ 36439629 sec RG 905 OW 111200 use DE 600 use TE 3000 K 01 100000000 sec flCREST 000000000 sec MCNRK 001500000 sec

======== CHANNEL fl ======= NUC1 IH PI 830 user PL1 000 dB SFOl 5001317481 KHz

F2 - Processing par2meters S1 16384 SF 5001300127 HHz JDN SSB L8 G8 PC

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ACCEPTED MANUSCRIPT or Ra-4064 Ctl~fY~ 1 C13APT 4hrs C13 and 1 I) I - B~F

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N 1 cgt exgt CI 01 0 co rl N l) M MOC)O cgt U) cgt cgt fll) U) f - I (I r-r-ill rshy OlCOCOD rlt

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current Oato) ParltlJJlOtor NAME Occ06-2QOS EXPNO 2 PROCNU 1

F2 ~ Acqui~ it io1 PllranoterB Date_ 2005 1 201 Time 1126 INSTRIJl1 spect PROBf(O 5 mrn QNP IH PU1PROO jmod 10 65536 SOLVENT CDC) NS 4096 OS lt SI-IH 1883239] Hz FlORES 0287360 Hz 1gt0 17II00)OS sec RG 096 Dil 26 550 usee DE 6 00 Ulec TE 3000 K CNSI2 1450000000 CNSTll 10000000 Dl 200000000 cae d13 000000300 cc d20 O006B9655 lGC DELTA 000001592 SIX

11gt CHANNEL f l = ==c NUCI 11C PI 12 SO usee p2 250 0 usee PL1 000 dB SFOI 754760200 MHz

========gt= CHANNEL f2 = CPDPRG2 al tz1 6 NUC2 1H pePD 110 SO usee PL2 000 lt1D PL12 2000 dB SF02 JOOIJ1200S 101Hz

2 - Proces9in9 peramettr$ SI 32769 Sf 754677475 tlllz DJ pound11 SS8 0 LB 100 Hz CB 0 PC 1 ( 0

~~r I I n I I TT~n I I ~n I ~I I I I I I I I

150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

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ACCEPTED MANUSCRIPT~~-----------~ F------

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Current Data Parameters NANE Ra-4064 EXPNO J PROCNO J

2 - Acquisition Parameters Date_ 20051207 Time 1206 INSTRUM spect PROSHO 5 mm TXI 13C Z PULPROG zg30 TD 32768 SOLVENT coelJ NS 16 DS 4 SIIH 4496403 Hz nORES 0137219 Hz AQ 36439629 sec RG 905 OW 111200 use DE 600 use TE 3000 K 01 100000000 sec flCREST 000000000 sec MCNRK 001500000 sec

======== CHANNEL fl ======= NUC1 IH PI 830 user PL1 000 dB SFOl 5001317481 KHz

F2 - Processing par2meters S1 16384 SF 5001300127 HHz JDN SSB L8 G8 PC

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75 70 65 60 55 50 45 40 35 30 25 20 15 10 05 ppm

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N 1 cgt exgt CI 01 0 co rl N l) M MOC)O cgt U) cgt cgt fll) U) f - I (I r-r-ill rshy OlCOCOD rlt

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current Oato) ParltlJJlOtor NAME Occ06-2QOS EXPNO 2 PROCNU 1

F2 ~ Acqui~ it io1 PllranoterB Date_ 2005 1 201 Time 1126 INSTRIJl1 spect PROBf(O 5 mrn QNP IH PU1PROO jmod 10 65536 SOLVENT CDC) NS 4096 OS lt SI-IH 1883239] Hz FlORES 0287360 Hz 1gt0 17II00)OS sec RG 096 Dil 26 550 usee DE 6 00 Ulec TE 3000 K CNSI2 1450000000 CNSTll 10000000 Dl 200000000 cae d13 000000300 cc d20 O006B9655 lGC DELTA 000001592 SIX

11gt CHANNEL f l = ==c NUCI 11C PI 12 SO usee p2 250 0 usee PL1 000 dB SFOI 754760200 MHz

========gt= CHANNEL f2 = CPDPRG2 al tz1 6 NUC2 1H pePD 110 SO usee PL2 000 lt1D PL12 2000 dB SF02 JOOIJ1200S 101Hz

2 - Proces9in9 peramettr$ SI 32769 Sf 754677475 tlllz DJ pound11 SS8 0 LB 100 Hz CB 0 PC 1 ( 0

~~r I I n I I TT~n I I ~n I ~I I I I I I I I

150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

MANUSCRIP

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ACCEPTED MANUSCRIPT

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Current Data Parameters NANE Ra-4064 EXPNO J PROCNO J

2 - Acquisition Parameters Date_ 20051207 Time 1206 INSTRUM spect PROSHO 5 mm TXI 13C Z PULPROG zg30 TD 32768 SOLVENT coelJ NS 16 DS 4 SIIH 4496403 Hz nORES 0137219 Hz AQ 36439629 sec RG 905 OW 111200 use DE 600 use TE 3000 K 01 100000000 sec flCREST 000000000 sec MCNRK 001500000 sec

======== CHANNEL fl ======= NUC1 IH PI 830 user PL1 000 dB SFOl 5001317481 KHz

F2 - Processing par2meters S1 16384 SF 5001300127 HHz JDN SSB L8 G8 PC

Et1 o

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Lf)rlt)rlOIOOlaquoJiCOMCOO rlONN mror-MIOOLOlaquoJiMr-O rlmr-o rlrlrlrlLf)LOLOLOLf)~ltjl rl 0 00

NNNNrlrlrlrlrlrlrl 0000

~ ~ ~

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1 11

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75 70 65 60 55 50 45 40 35 30 25 20 15 10 05 ppm

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ACCEPTED MANUSCRIPT or Ra-4064 Ctl~fY~ 1 C13APT 4hrs C13 and 1 I) I - B~F

U) I II III

N 1 cgt exgt CI 01 0 co rl N l) M MOC)O cgt U) cgt cgt fll) U) f - I (I r-r-ill rshy OlCOCOD rlt

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I 1 I ~

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current Oato) ParltlJJlOtor NAME Occ06-2QOS EXPNO 2 PROCNU 1

F2 ~ Acqui~ it io1 PllranoterB Date_ 2005 1 201 Time 1126 INSTRIJl1 spect PROBf(O 5 mrn QNP IH PU1PROO jmod 10 65536 SOLVENT CDC) NS 4096 OS lt SI-IH 1883239] Hz FlORES 0287360 Hz 1gt0 17II00)OS sec RG 096 Dil 26 550 usee DE 6 00 Ulec TE 3000 K CNSI2 1450000000 CNSTll 10000000 Dl 200000000 cae d13 000000300 cc d20 O006B9655 lGC DELTA 000001592 SIX

11gt CHANNEL f l = ==c NUCI 11C PI 12 SO usee p2 250 0 usee PL1 000 dB SFOI 754760200 MHz

========gt= CHANNEL f2 = CPDPRG2 al tz1 6 NUC2 1H pePD 110 SO usee PL2 000 lt1D PL12 2000 dB SF02 JOOIJ1200S 101Hz

2 - Proces9in9 peramettr$ SI 32769 Sf 754677475 tlllz DJ pound11 SS8 0 LB 100 Hz CB 0 PC 1 ( 0

~~r I I n I I TT~n I I ~n I ~I I I I I I I I

150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

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ACCEPTED MANUSCRIPT or Ra-4064 Ctl~fY~ 1 C13APT 4hrs C13 and 1 I) I - B~F

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CHlINNEL f1 ~C~~~ NUCl lH PI 1115 usee p2 2230 uIec PL1 000 dB SFOl 500 1317505 MHz

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PIE 1 500 00 usee

Fl - Acqul31tion pCJcameters NDO 1 TO 110 SFOl 5001 310 M8z FlORES 36 310111 Hz 51 1199 ppm rIiMODE Slaleg-TPPI

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m12 - Acquisition Parameters ~_______________________ J L ~~~_ 201~~~~~ ~ U J L pp

in INSTRUM spect

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k 100 ~~2 2~g~ ~~ec IJ ~ H p Sro2 1257716224 MHz

GRAD I ENT CHANNEL bullbullbullbullbull GPNlIMl SINE100 GPNlIM2 SINEl00

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fi 5101 1257716 MHz ~ Q FIORES 122838051 Hz

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Date_ 20110614 Time 1255 INSTRUM spect PROBHO 5 men Multinucl PULPROG hrilqcgpqf ~ 0 TD 2048

20

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r 40 CNsrl 14 50000000~

dO 000000300 sec Dl 150000000 sec d2 000344828 sec d12 000002000 sec d13 000000400 sec 016 0 00010000 sec

60 DELTAl 000182426 sec INO 0 00001590 sec

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cc==== CHANNEL pound2 0==== CPDPRG2 garpNue2 13C p3 2100 usee100 PCPD2 6 7 00 usee PL2 000 dB PL12 1000 dB Sf02 125 7 716224 MJlz

=gt=r== GRADIENT CHANNEL wcoc c

GPNAM1 SINE 100 GPNAM2 SINE 100 GPNAM3 SINE 100 GPZl 50 00 GPZ2 3000 GPZ3 4010 P16 150000 usec

r120

140 n - Acquisition parameters NOD 2 TO 256 SFOI 1257716 MHz FIDRES 122838051 Hz sw 2500 29 ppm1-160 FnfgtlODE OF

F2 - P[ocessinq parameters S1 512 SF 5001300000 Hllz wow QSINE

~180 SSB 2 LB 000 Hz GB 0 PC 100

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CHlINNEL f1 ~C~~~ NUCl lH PI 1115 usee p2 2230 uIec PL1 000 dB SFOl 500 1317505 MHz

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PIE 1 500 00 usee

Fl - Acqul31tion pCJcameters NDO 1 TO 110 SFOl 5001 310 M8z FlORES 36 310111 Hz 51 1199 ppm rIiMODE Slaleg-TPPI

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CJ0460a_HMBC ei

Current Data Paramemiddotters NAME CJ0460a EXPNO 22 ~ 1

m12 - Acquisition Parameters ~_______________________ J L ~~~_ 201~~~~~ ~ U J L pp

in INSTRUM spect

o Q PROSHO 5 mm Hultinucl PULPROG hmbcgplpndgf

-- 0 TO 20480bull SOLVENT CDC13o IIgt NS 64

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GRAD I ENT CHANNEL bullbullbullbullbull GPNlIMl SINE100 GPNlIM2 SINEl00

l---I reg(A~ 000 J 1 120

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Current Data Parameters tlAME CJ0460a EXPNO 21 PROCNO 1Jt U J ~J A ppm f 2 _ Acquisition Parameters

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Date_ 20110614 Time 1255 INSTRUM spect PROBHO 5 men Multinucl PULPROG hrilqcgpqf ~ 0 TD 2048

20

SOLVENT COCl3 NS 32 DS 16 SWH 5000000 Hz FlORES 2441406 Hz AO 0 2049500 sec RG 4096 ow 100000 usee DE 600 usee TE 2942 K

r 40 CNsrl 14 50000000~

dO 000000300 sec Dl 150000000 sec d2 000344828 sec d12 000002000 sec d13 000000400 sec 016 0 00010000 sec

60 DELTAl 000182426 sec INO 0 00001590 sec

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cc==== CHANNEL pound2 0==== CPDPRG2 garpNue2 13C p3 2100 usee100 PCPD2 6 7 00 usee PL2 000 dB PL12 1000 dB Sf02 125 7 716224 MJlz

=gt=r== GRADIENT CHANNEL wcoc c

GPNAM1 SINE 100 GPNAM2 SINE 100 GPNAM3 SINE 100 GPZl 50 00 GPZ2 3000 GPZ3 4010 P16 150000 usec

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F2 - P[ocessinq parameters S1 512 SF 5001300000 Hllz wow QSINE

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F2 - Acqui3itlon Parameters Dote 701 00706 Time 936 INSTRUM spect PROSHO mm Nulcinucl PULPROG noesygpph Tn 20 48 SOLVENT CDeD NS 16 DS 4 SWH 4 006 410 H~ FlORES I 956255 cl AQ O ~57557 sec RG 228 1 DW 1 24000 U3ec nE 600 usee tE 2982 K dO 0 00011 078 sec D1 7 00000000 sec De 075000000 gt cc DIE 0 00010000 INO 0 00 02lt 995 STleNT 64 TAU O J 7HOUIJO sec

CHlINNEL f1 ~C~~~ NUCl lH PI 1115 usee p2 2230 uIec PL1 000 dB SFOl 500 1317505 MHz

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PIE 1 500 00 usee

Fl - Acqul31tion pCJcameters NDO 1 TO 110 SFOl 5001 310 M8z FlORES 36 310111 Hz 51 1199 ppm rIiMODE Slaleg-TPPI

F2 - Pro~e3inq ptlraneter3 51 512 5F ~OO l]OOll-1 Mlh WDW QSINE 558 2 LB 000 Hz GB o PC ]00

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CJ0460a_HMBC ei

Current Data Paramemiddotters NAME CJ0460a EXPNO 22 ~ 1

m12 - Acquisition Parameters ~_______________________ J L ~~~_ 201~~~~~ ~ U J L pp

in INSTRUM spect

o Q PROSHO 5 mm Hultinucl PULPROG hmbcgplpndgf

-- 0 TO 20480bull SOLVENT CDC13o IIgt NS 64

OS 16 SWH 6510417 Hz fIORES 3178914 Hz

20 AQ 01574132 secrfl ~ RG 23170 5

~ i(J ~ OW 76800 usee DE 600 usee TE 2952 K

l f-- 40 g~~i~3 li~ g~~~ggg

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60 ~~~ gggg~~~~~ ~~ CHANNEL fl ---_-shy

NUCI lH Pl 1115 usee(iiY~ I 80 p2 2230 useeNyl ~ PLI 000 dB

IfW ~ H Srol 5001320005 MHz

~__L- l CHANNEL i3~middotmiddotmiddotmiddotmiddot~ NUC2 f2

k 100 ~~2 2~g~ ~~ec IJ ~ H p Sro2 1257716224 MHz

GRAD I ENT CHANNEL bullbullbullbullbull GPNlIMl SINE100 GPNlIM2 SINEl00

l---I reg(A~ 000 J 1 120

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fi 5101 1257716 MHz ~ Q FIORES 122838051 Hz

160 ~~OOE 25006~ ppm

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75 70 65 60 55 50 45 40 35 30 25 20 15 10 05 00 ppm GB 0

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ACCEPTED MANUSCRIPT

--I

CJ0460a_HMQC

f)

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Current Data Parameters tlAME CJ0460a EXPNO 21 PROCNO 1Jt U J ~J A ppm f 2 _ Acquisition Parameters

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-----l- lt0 e-

Date_ 20110614 Time 1255 INSTRUM spect PROBHO 5 men Multinucl PULPROG hrilqcgpqf ~ 0 TD 2048

20

SOLVENT COCl3 NS 32 DS 16 SWH 5000000 Hz FlORES 2441406 Hz AO 0 2049500 sec RG 4096 ow 100000 usee DE 600 usee TE 2942 K

r 40 CNsrl 14 50000000~

dO 000000300 sec Dl 150000000 sec d2 000344828 sec d12 000002000 sec d13 000000400 sec 016 0 00010000 sec

60 DELTAl 000182426 sec INO 0 00001590 sec

80

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cc==== CHANNEL pound2 0==== CPDPRG2 garpNue2 13C p3 2100 usee100 PCPD2 6 7 00 usee PL2 000 dB PL12 1000 dB Sf02 125 7 716224 MJlz

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F2 - P[ocessinq parameters S1 512 SF 5001300000 Hllz wow QSINE

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CHlINNEL f1 ~C~~~ NUCl lH PI 1115 usee p2 2230 uIec PL1 000 dB SFOl 500 1317505 MHz

GRADIENT CHANNEL =~~~ GPNIIHI SIfl~100 GPNlJ42 SINE100 GPZl 10 00 ttl GPZ2 -1000 S

PIE 1 500 00 usee

Fl - Acqul31tion pCJcameters NDO 1 TO 110 SFOl 5001 310 M8z FlORES 36 310111 Hz 51 1199 ppm rIiMODE Slaleg-TPPI

F2 - Pro~e3inq ptlraneter3 51 512 5F ~OO l]OOll-1 Mlh WDW QSINE 558 2 LB 000 Hz GB o PC ]00

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CJ0460a_HMBC ei

Current Data Paramemiddotters NAME CJ0460a EXPNO 22 ~ 1

m12 - Acquisition Parameters ~_______________________ J L ~~~_ 201~~~~~ ~ U J L pp

in INSTRUM spect

o Q PROSHO 5 mm Hultinucl PULPROG hmbcgplpndgf

-- 0 TO 20480bull SOLVENT CDC13o IIgt NS 64

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~ i(J ~ OW 76800 usee DE 600 usee TE 2952 K

l f-- 40 g~~i~3 li~ g~~~ggg

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60 ~~~ gggg~~~~~ ~~ CHANNEL fl ---_-shy

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k 100 ~~2 2~g~ ~~ec IJ ~ H p Sro2 1257716224 MHz

GRAD I ENT CHANNEL bullbullbullbullbull GPNlIMl SINE100 GPNlIM2 SINEl00

l---I reg(A~ 000 J 1 120

~~~~3 SINO IggQ f1I ( GPZ2 3000

GPZ3 4010 P16 1500 00 usee

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fi 5101 1257716 MHz ~ Q FIORES 122838051 Hz

160 ~~OOE 25006~ ppm

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75 70 65 60 55 50 45 40 35 30 25 20 15 10 05 00 ppm GB 0

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CJ0460a_HMQC

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Date_ 20110614 Time 1255 INSTRUM spect PROBHO 5 men Multinucl PULPROG hrilqcgpqf ~ 0 TD 2048

20

SOLVENT COCl3 NS 32 DS 16 SWH 5000000 Hz FlORES 2441406 Hz AO 0 2049500 sec RG 4096 ow 100000 usee DE 600 usee TE 2942 K

r 40 CNsrl 14 50000000~

dO 000000300 sec Dl 150000000 sec d2 000344828 sec d12 000002000 sec d13 000000400 sec 016 0 00010000 sec

60 DELTAl 000182426 sec INO 0 00001590 sec

80

=C= CHANNEL f 1 =__ NUel 1H PI )115 usee p2 2230 usee PL1 000 dB srOl SOD 1320005 MlIz

cc==== CHANNEL pound2 0==== CPDPRG2 garpNue2 13C p3 2100 usee100 PCPD2 6 7 00 usee PL2 000 dB PL12 1000 dB Sf02 125 7 716224 MJlz

=gt=r== GRADIENT CHANNEL wcoc c

GPNAM1 SINE 100 GPNAM2 SINE 100 GPNAM3 SINE 100 GPZl 50 00 GPZ2 3000 GPZ3 4010 P16 150000 usec

r120

140 n - Acquisition parameters NOD 2 TO 256 SFOI 1257716 MHz FIDRES 122838051 Hz sw 2500 29 ppm1-160 FnfgtlODE OF

F2 - P[ocessinq parameters S1 512 SF 5001300000 Hllz wow QSINE

~180 SSB 2 LB 000 Hz GB 0 PC 100

Fl - Ptocessing parameters 512~200 SI

OFMC2 SF 1257577890 MHz wow OSINE1 1 1 1 1 1 I 1 SSB 2 LB 000 Hz

07 6 5 4 3 2 1 0 ppm GB

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F2 - Acqui3itlon Parameters Dote 701 00706 Time 936 INSTRUM spect PROSHO mm Nulcinucl PULPROG noesygpph Tn 20 48 SOLVENT CDeD NS 16 DS 4 SWH 4 006 410 H~ FlORES I 956255 cl AQ O ~57557 sec RG 228 1 DW 1 24000 U3ec nE 600 usee tE 2982 K dO 0 00011 078 sec D1 7 00000000 sec De 075000000 gt cc DIE 0 00010000 INO 0 00 02lt 995 STleNT 64 TAU O J 7HOUIJO sec

CHlINNEL f1 ~C~~~ NUCl lH PI 1115 usee p2 2230 uIec PL1 000 dB SFOl 500 1317505 MHz

GRADIENT CHANNEL =~~~ GPNIIHI SIfl~100 GPNlJ42 SINE100 GPZl 10 00 ttl GPZ2 -1000 S

PIE 1 500 00 usee

Fl - Acqul31tion pCJcameters NDO 1 TO 110 SFOl 5001 310 M8z FlORES 36 310111 Hz 51 1199 ppm rIiMODE Slaleg-TPPI

F2 - Pro~e3inq ptlraneter3 51 512 5F ~OO l]OOll-1 Mlh WDW QSINE 558 2 LB 000 Hz GB o PC ]00

11 - IrocEJs ing paramoters S1 517 HC2 Sta tes-TPll SF 5001300116 1H z wow QSJNE 558 2 L8 000 Hz GB 0

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CJ0460a_HMBC ei

Current Data Paramemiddotters NAME CJ0460a EXPNO 22 ~ 1

m12 - Acquisition Parameters ~_______________________ J L ~~~_ 201~~~~~ ~ U J L pp

in INSTRUM spect

o Q PROSHO 5 mm Hultinucl PULPROG hmbcgplpndgf

-- 0 TO 20480bull SOLVENT CDC13o IIgt NS 64

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~ i(J ~ OW 76800 usee DE 600 usee TE 2952 K

l f-- 40 g~~i~3 li~ g~~~ggg

dO 000000300 sec 01 150000000 sec d2 0003l4828 sec d6 005000000 sec

60 ~~~ gggg~~~~~ ~~ CHANNEL fl ---_-shy

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IfW ~ H Srol 5001320005 MHz

~__L- l CHANNEL i3~middotmiddotmiddotmiddotmiddot~ NUC2 f2

k 100 ~~2 2~g~ ~~ec IJ ~ H p Sro2 1257716224 MHz

GRAD I ENT CHANNEL bullbullbullbullbull GPNlIMl SINE100 GPNlIM2 SINEl00

l---I reg(A~ 000 J 1 120

~~~~3 SINO IggQ f1I ( GPZ2 3000

GPZ3 4010 P16 1500 00 usee

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fi 5101 1257716 MHz ~ Q FIORES 122838051 Hz

160 ~~OOE 25006~ ppm

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75 70 65 60 55 50 45 40 35 30 25 20 15 10 05 00 ppm GB 0

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ACCEPTED MANUSCRIPT

--I

CJ0460a_HMQC

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Current Data Parameters tlAME CJ0460a EXPNO 21 PROCNO 1Jt U J ~J A ppm f 2 _ Acquisition Parameters

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Date_ 20110614 Time 1255 INSTRUM spect PROBHO 5 men Multinucl PULPROG hrilqcgpqf ~ 0 TD 2048

20

SOLVENT COCl3 NS 32 DS 16 SWH 5000000 Hz FlORES 2441406 Hz AO 0 2049500 sec RG 4096 ow 100000 usee DE 600 usee TE 2942 K

r 40 CNsrl 14 50000000~

dO 000000300 sec Dl 150000000 sec d2 000344828 sec d12 000002000 sec d13 000000400 sec 016 0 00010000 sec

60 DELTAl 000182426 sec INO 0 00001590 sec

80

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cc==== CHANNEL pound2 0==== CPDPRG2 garpNue2 13C p3 2100 usee100 PCPD2 6 7 00 usee PL2 000 dB PL12 1000 dB Sf02 125 7 716224 MJlz

=gt=r== GRADIENT CHANNEL wcoc c

GPNAM1 SINE 100 GPNAM2 SINE 100 GPNAM3 SINE 100 GPZl 50 00 GPZ2 3000 GPZ3 4010 P16 150000 usec

r120

140 n - Acquisition parameters NOD 2 TO 256 SFOI 1257716 MHz FIDRES 122838051 Hz sw 2500 29 ppm1-160 FnfgtlODE OF

F2 - P[ocessinq parameters S1 512 SF 5001300000 Hllz wow QSINE

~180 SSB 2 LB 000 Hz GB 0 PC 100

Fl - Ptocessing parameters 512~200 SI

OFMC2 SF 1257577890 MHz wow OSINE1 1 1 1 1 1 I 1 SSB 2 LB 000 Hz

07 6 5 4 3 2 1 0 ppm GB

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140 130 120 110 100 90 80 70 60 50 40 30 20 10 o f1 (ppm)

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F2 - Acqui3itlon Parameters Dote 701 00706 Time 936 INSTRUM spect PROSHO mm Nulcinucl PULPROG noesygpph Tn 20 48 SOLVENT CDeD NS 16 DS 4 SWH 4 006 410 H~ FlORES I 956255 cl AQ O ~57557 sec RG 228 1 DW 1 24000 U3ec nE 600 usee tE 2982 K dO 0 00011 078 sec D1 7 00000000 sec De 075000000 gt cc DIE 0 00010000 INO 0 00 02lt 995 STleNT 64 TAU O J 7HOUIJO sec

CHlINNEL f1 ~C~~~ NUCl lH PI 1115 usee p2 2230 uIec PL1 000 dB SFOl 500 1317505 MHz

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PIE 1 500 00 usee

Fl - Acqul31tion pCJcameters NDO 1 TO 110 SFOl 5001 310 M8z FlORES 36 310111 Hz 51 1199 ppm rIiMODE Slaleg-TPPI

F2 - Pro~e3inq ptlraneter3 51 512 5F ~OO l]OOll-1 Mlh WDW QSINE 558 2 LB 000 Hz GB o PC ]00

11 - IrocEJs ing paramoters S1 517 HC2 Sta tes-TPll SF 5001300116 1H z wow QSJNE 558 2 L8 000 Hz GB 0

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ACCEPTED MANUSCRIPT6shy

CJ0460a_HMBC ei

Current Data Paramemiddotters NAME CJ0460a EXPNO 22 ~ 1

m12 - Acquisition Parameters ~_______________________ J L ~~~_ 201~~~~~ ~ U J L pp

in INSTRUM spect

o Q PROSHO 5 mm Hultinucl PULPROG hmbcgplpndgf

-- 0 TO 20480bull SOLVENT CDC13o IIgt NS 64

OS 16 SWH 6510417 Hz fIORES 3178914 Hz

20 AQ 01574132 secrfl ~ RG 23170 5

~ i(J ~ OW 76800 usee DE 600 usee TE 2952 K

l f-- 40 g~~i~3 li~ g~~~ggg

dO 000000300 sec 01 150000000 sec d2 0003l4828 sec d6 005000000 sec

60 ~~~ gggg~~~~~ ~~ CHANNEL fl ---_-shy

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IfW ~ H Srol 5001320005 MHz

~__L- l CHANNEL i3~middotmiddotmiddotmiddotmiddot~ NUC2 f2

k 100 ~~2 2~g~ ~~ec IJ ~ H p Sro2 1257716224 MHz

GRAD I ENT CHANNEL bullbullbullbullbull GPNlIMl SINE100 GPNlIM2 SINEl00

l---I reg(A~ 000 J 1 120

~~~~3 SINO IggQ f1I ( GPZ2 3000

GPZ3 4010 P16 1500 00 usee

-4- O~ 0 nfQl ~ I 140 ~~o - Acquisition param~ters IJIiJ 1 J TO 256

fi 5101 1257716 MHz ~ Q FIORES 122838051 Hz

160 ~~OOE 25006~ ppm

F2 - Processing parameters Sl 512 SI 5001300036 HHz

f-- 180 ~~~ SIN~ LB 000 Hz GB 0

tor ~ I 200 i~ -Processing par~ers~ D r MC2 OF

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75 70 65 60 55 50 45 40 35 30 25 20 15 10 05 00 ppm GB 0

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--I

CJ0460a_HMQC

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-----l- lt0 e-

Date_ 20110614 Time 1255 INSTRUM spect PROBHO 5 men Multinucl PULPROG hrilqcgpqf ~ 0 TD 2048

20

SOLVENT COCl3 NS 32 DS 16 SWH 5000000 Hz FlORES 2441406 Hz AO 0 2049500 sec RG 4096 ow 100000 usee DE 600 usee TE 2942 K

r 40 CNsrl 14 50000000~

dO 000000300 sec Dl 150000000 sec d2 000344828 sec d12 000002000 sec d13 000000400 sec 016 0 00010000 sec

60 DELTAl 000182426 sec INO 0 00001590 sec

80

=C= CHANNEL f 1 =__ NUel 1H PI )115 usee p2 2230 usee PL1 000 dB srOl SOD 1320005 MlIz

cc==== CHANNEL pound2 0==== CPDPRG2 garpNue2 13C p3 2100 usee100 PCPD2 6 7 00 usee PL2 000 dB PL12 1000 dB Sf02 125 7 716224 MJlz

=gt=r== GRADIENT CHANNEL wcoc c

GPNAM1 SINE 100 GPNAM2 SINE 100 GPNAM3 SINE 100 GPZl 50 00 GPZ2 3000 GPZ3 4010 P16 150000 usec

r120

140 n - Acquisition parameters NOD 2 TO 256 SFOI 1257716 MHz FIDRES 122838051 Hz sw 2500 29 ppm1-160 FnfgtlODE OF

F2 - P[ocessinq parameters S1 512 SF 5001300000 Hllz wow QSINE

~180 SSB 2 LB 000 Hz GB 0 PC 100

Fl - Ptocessing parameters 512~200 SI

OFMC2 SF 1257577890 MHz wow OSINE1 1 1 1 1 1 I 1 SSB 2 LB 000 Hz

07 6 5 4 3 2 1 0 ppm GB

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Current Data Paramemiddotters NAME CJ0460a EXPNO 22 ~ 1

m12 - Acquisition Parameters ~_______________________ J L ~~~_ 201~~~~~ ~ U J L pp

in INSTRUM spect

o Q PROSHO 5 mm Hultinucl PULPROG hmbcgplpndgf

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~ i(J ~ OW 76800 usee DE 600 usee TE 2952 K

l f-- 40 g~~i~3 li~ g~~~ggg

dO 000000300 sec 01 150000000 sec d2 0003l4828 sec d6 005000000 sec

60 ~~~ gggg~~~~~ ~~ CHANNEL fl ---_-shy

NUCI lH Pl 1115 usee(iiY~ I 80 p2 2230 useeNyl ~ PLI 000 dB

IfW ~ H Srol 5001320005 MHz

~__L- l CHANNEL i3~middotmiddotmiddotmiddotmiddot~ NUC2 f2

k 100 ~~2 2~g~ ~~ec IJ ~ H p Sro2 1257716224 MHz

GRAD I ENT CHANNEL bullbullbullbullbull GPNlIMl SINE100 GPNlIM2 SINEl00

l---I reg(A~ 000 J 1 120

~~~~3 SINO IggQ f1I ( GPZ2 3000

GPZ3 4010 P16 1500 00 usee

-4- O~ 0 nfQl ~ I 140 ~~o - Acquisition param~ters IJIiJ 1 J TO 256

fi 5101 1257716 MHz ~ Q FIORES 122838051 Hz

160 ~~OOE 25006~ ppm

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f-- 180 ~~~ SIN~ LB 000 Hz GB 0

tor ~ I 200 i~ -Processing par~ers~ D r MC2 OF

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75 70 65 60 55 50 45 40 35 30 25 20 15 10 05 00 ppm GB 0

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ACCEPTED MANUSCRIPT

--I

CJ0460a_HMQC

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Current Data Parameters tlAME CJ0460a EXPNO 21 PROCNO 1Jt U J ~J A ppm f 2 _ Acquisition Parameters

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-----l- lt0 e-

Date_ 20110614 Time 1255 INSTRUM spect PROBHO 5 men Multinucl PULPROG hrilqcgpqf ~ 0 TD 2048

20

SOLVENT COCl3 NS 32 DS 16 SWH 5000000 Hz FlORES 2441406 Hz AO 0 2049500 sec RG 4096 ow 100000 usee DE 600 usee TE 2942 K

r 40 CNsrl 14 50000000~

dO 000000300 sec Dl 150000000 sec d2 000344828 sec d12 000002000 sec d13 000000400 sec 016 0 00010000 sec

60 DELTAl 000182426 sec INO 0 00001590 sec

80

=C= CHANNEL f 1 =__ NUel 1H PI )115 usee p2 2230 usee PL1 000 dB srOl SOD 1320005 MlIz

cc==== CHANNEL pound2 0==== CPDPRG2 garpNue2 13C p3 2100 usee100 PCPD2 6 7 00 usee PL2 000 dB PL12 1000 dB Sf02 125 7 716224 MJlz

=gt=r== GRADIENT CHANNEL wcoc c

GPNAM1 SINE 100 GPNAM2 SINE 100 GPNAM3 SINE 100 GPZl 50 00 GPZ2 3000 GPZ3 4010 P16 150000 usec

r120

140 n - Acquisition parameters NOD 2 TO 256 SFOI 1257716 MHz FIDRES 122838051 Hz sw 2500 29 ppm1-160 FnfgtlODE OF

F2 - P[ocessinq parameters S1 512 SF 5001300000 Hllz wow QSINE

~180 SSB 2 LB 000 Hz GB 0 PC 100

Fl - Ptocessing parameters 512~200 SI

OFMC2 SF 1257577890 MHz wow OSINE1 1 1 1 1 1 I 1 SSB 2 LB 000 Hz

07 6 5 4 3 2 1 0 ppm GB

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Current Data Parameters tlAME CJ0460a EXPNO 21 PROCNO 1Jt U J ~J A ppm f 2 _ Acquisition Parameters

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-----l- lt0 e-

Date_ 20110614 Time 1255 INSTRUM spect PROBHO 5 men Multinucl PULPROG hrilqcgpqf ~ 0 TD 2048

20

SOLVENT COCl3 NS 32 DS 16 SWH 5000000 Hz FlORES 2441406 Hz AO 0 2049500 sec RG 4096 ow 100000 usee DE 600 usee TE 2942 K

r 40 CNsrl 14 50000000~

dO 000000300 sec Dl 150000000 sec d2 000344828 sec d12 000002000 sec d13 000000400 sec 016 0 00010000 sec

60 DELTAl 000182426 sec INO 0 00001590 sec

80

=C= CHANNEL f 1 =__ NUel 1H PI )115 usee p2 2230 usee PL1 000 dB srOl SOD 1320005 MlIz

cc==== CHANNEL pound2 0==== CPDPRG2 garpNue2 13C p3 2100 usee100 PCPD2 6 7 00 usee PL2 000 dB PL12 1000 dB Sf02 125 7 716224 MJlz

=gt=r== GRADIENT CHANNEL wcoc c

GPNAM1 SINE 100 GPNAM2 SINE 100 GPNAM3 SINE 100 GPZl 50 00 GPZ2 3000 GPZ3 4010 P16 150000 usec

r120

140 n - Acquisition parameters NOD 2 TO 256 SFOI 1257716 MHz FIDRES 122838051 Hz sw 2500 29 ppm1-160 FnfgtlODE OF

F2 - P[ocessinq parameters S1 512 SF 5001300000 Hllz wow QSINE

~180 SSB 2 LB 000 Hz GB 0 PC 100

Fl - Ptocessing parameters 512~200 SI

OFMC2 SF 1257577890 MHz wow OSINE1 1 1 1 1 1 I 1 SSB 2 LB 000 Hz

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