Alkene/Alkyne Hydrozirconation - Harvard Universitysites.fas.harvard.edu/~chem153/lectures/week9a.pdf · Alkene/Alkyne Hydrozirconation Zr IV H Cl C 6 H 13 (stoichiometric) benzene,

M.C. White, Chem 153 Hydrozirconation -292- Week of November 18, 2002

Alkene/Alkyne Hydrozirconation

ZrI V

H

ClC6H13

(stoichiometric)benzene, rt, N2

ZrI V

H

Cl

R

18e - (d0)

Schwartz's reagent, 16e - (d0)

ZrI VCl

16e - (d0)

R

Moisture and O2 sensitive alkylzirconiumproduct. Olefin insertion into the Zr-C bond has never been observed.

Internally metalated alkylzirconiumcomplexes rapidly isomerize at rt via β-hydride elimination, reinsertionsequences to the least stericallyhindered 1o alkylzirconium product.Schwartz JACS 1974 (96) 8115.

Morokuma OM 1993 (12) 2777.

Olefin binds weakly to vacant d orbital on Zr via σ-donation (π-backbonding is not possible because the complex has no d electrons).

ZrIV

H

Cl

benzene, rt, N2

H Zr(Cl)Cp2

+

Zr(Cl)Cp2 H

84:16

1 eq

ZrI V

H

Cl

benzene, rt, N2

catalytic

Cp2(Cl)Zr

H

H

Zr(Cl)Cp2

H Zr(Cl)Cp2

+

Zr(Cl)Cp2 H

98:2

Stereospecific cis hydrometalation occurs with highregioselectivity in formation of the least sterically hinderedvinylzirconium species. The use of excess Schwartz's reagentresults in higher regioselectivities via formation of a dimetalated alkyl intermediate that preferentially β-hydride eliminates at themore sterically hindered Zr center.

Schwartz JACS 1975 (97) 679.


Functionalization

Br2

O

Cl

BrR

HR

R

O

ZrIVCl

R

ZrIVCl

RBrBr

ZrI V

Br

Cl

Schwartz ACIEE 1976 (15) 333.

H2O2, NaOHHO

R

ZrI VCl

R

Electrophilic functionalization

CO insertion/ Zr acyl functionalization

ZrI VCl

R

O

Br2, MeOH

O

HR'

H2O2, NaOH

O

H R

O

MeO ROH

R'

O

R

O

HO RSchwartz JACS 1975 (97) 228.Hanzawz ACIEE 1998 (37) 1696.

16e - (d0)

CO (1.5 atm), rt

16e - (d0)

HCl (dilute) >99% n-heptanal

insertion proceedswith retention ofconfiguration at C.

51% methyl n-heptanoate

BF3· OEt2

-HC=CH-, R = C4H9, R'= Ph , 69%-CH2CH2 -, R = (CH2 )2 OBn, R'= Ph, 74%

n-heptanoic acid, 77%

HCl (dilute)

alkylzirconium and alkenylzirconiumcompounds react readily with a range of electrophiles.

>99% octane

96%

80%

16e - (d0) 16e - (d0)

Reaction of Br2 with chiral alkylzirconium complexes affords alkyl bromides with retention of configurationat the stereogenic carbon center. Likewise,alkenylzirconium complexes react with Br2 to givevinyl bromides with retention of olefin geometry.Because the alkylzirconium complex is formally d0,product formation via an oxidative addition/ reductiveelimination sequence is not reasonable.Functionalization is thought to proceed via a σ-bondmetathesis mechanism.

+

69%

(note :NBS and NCS also work)

Transmetallation of alkenylzirconocenes

ZrIVCl

R

16e - (d0)

LnM-Xtransmetalation

M = Al, B, Cu, Hg, Ni, Pd, Sn, Zn

R

LnMZrIV

X

Cl+

Wipf Tetrahedron 1996 (52) 12853.


Synthetic applications

Oi-PrO

HMe

O

OZrIV

Me

Cl

Me2Zn

MeO

OR

ZnMe

R

Zr(Cl)Cp2 Oi-PrO

OH

O1. [Cp2Zr(H)Cl], CH2Cl2

2. Me2Zn (-78oC), 10 min

3.

R ~ 45%

Hydrozirconation/transmetalation sequence in the total synthesis of Fostriecin. Jacobsen ACIEE 2001 (40) 3667.

Hydrozirconation/bromination sequence in the total synthesis of FK 506. Schreiber JACS 1990 (112) 5583.

Me

MeO

TIPSO

MeO

TIPSO

Br

Me

MeO

TIPSO

Zr(Cl)Cp2

Me1. [Cp2Zr(H)Cl](3 eq),

benzene, 30-40oC

2. NBS, rt, 25 minR

86%

Hydrozirconation/Negishi coupling sequence in the total synthesis of FR901464. Jacobsen JACS 2000 (122) 10482.

OI

H

O

TESO

OI

O

TESO

Cp2(Cl)Zr2. ZnCl2, THF, 0oC3. Pd(PPh3)4 (6.5mol%)

O

N3

I

obtained via hydrozirconation/iodination sequence

OI

O

TESO

O

N3

1. [Cp2Zr(H)Cl],

THF, 0oC

80%


Hydridic character of Schwartz’s reagent

Reduction of 3o amides directly to aldehydes.

O

R NEt3

ZrIV

H

Cl

O

R H

R = p-CNC6H4-, 90% p-NO2C6H4-, 81% p-OMeC6H4-, 99% MeOC(O)C8H16-, 74%

O

NO

O

H3CPh

MeO

O

H

MeO

Direct reduction of Evan's N-acyl oxaolidinone (generally a 2 step procedureinvolving transamination to the Weinreb amide followed by LAH reduction to the aldehyde).

Cp2Zr(H)Cl (1.5-2.0 eq)THF, rt, 20-30 min

92%

(1.5-2 eq)

THF, rt, 20-30 min

Why don't the product aldehydes become reduced in situ? According to the proposed mechanism, the aldehyde is masked as iminium ion intermediate which decomposes upon aqueous workup to release the aldehyde product.

R

O

NR'

R''

Cp2Zr(H)ClR

OZr(H)Cp2

NR'

R''

Cl

R

OZrCp2

NR'

R''

ClH

R

H

NR'

R''

Cl

H2OR

H

O

Cp2Zr(O)Georg JACS 2000 (122) 11995.

ZrI V

H

Cl

O

R H

O

R R'

O

R OR'

OZr(Cl)Cp2

R R'H

H3O+

OH

R R'H

H3O+

H3O+

OH

R HH

OH

R HH

The hydridic character of the highly ionic Zr-H bond is demonstrated in its ability to reduce a variety ofcarbonyl functionalities to Zr alkoxides at a ratecompetative with olefin hydrozirconation.

δ+

δ-

Schwartz ACIEE 1976 (15) 333.

M.C. White, Chem 153 Alkene/C-M insertions -296- Week of November 18, 2002

LnMn H + R'K1

LnMn H

R'

K1 has been found to depend on thenumber and size of alkylsubstituents on the olefin. Increased substitution and steric bulk of theolefin leads to decreased rates ofbinding to the metal complex.

LnMn H

R' ‡

LnMn

R'

H

K2

β-hydride addition

β-hydrideelimination

It has been observed that with early, high-valent metals(e.g. Zr(IV), d0) the equilibrium lies to the left (K2 >1)whereas with late, low-valent metals (e.g. Pd(II), d8)the equilibrium lies to the right (K2 < 1). Electron density at the metal is thought to favor the hydrido-alkenespecies via stabilizing π-backbonding into the olefin π*. Hoffmann JACS 1976 (98) 1729.

Labinger ACIEE 1976 (15) 333.

Dimerization, Oligomerization, Polymerization

LnMn R

R = CH3, H

LnMn R

LnMn

LnMn

LnMn

R

R

R

H

R

LnMn

R

LnMn

R

n

H

Rn

oligomer, n= 3-100polymer, n > 100

termination viaβ-hydride elimination

propagationvia insertion

note that there is nooxidation state changeto the metal throughout the cycle

LnMn

H

R

dimer


M.C. White, Chem 153 EM Polymerization -297- Week of November 18, 2002

Ziegler Natta Polymerization

Natta Angew. Chem. 1956 (68) 393.

"What has guided my research has been solely the wish to do something that gave me joy,that is a joy from finding, somehow or somewhere, something really novel...At least at the outset, the only thing of value aimed for is an accretion in knowledge, rather than newapplications." Karl Ziegler.

Li ∆ LiH

Li∆ LiH

Al H 100oCAl Al

Al Al H

If traces of Ni salts could make such a dramatic impact on thecourse of ethylene oligermerizations, Ziegler wondered what othermetals may do... An exploration of this curiosity led to theTiCl3/Et2AlCl catalyzed Zeigler Natta polymerization (Nobel Prize, 1963) which is currently used commercially to produce ~ 15million tons of polyethylene and polypropylene annually.

Ziegler's original process for ethylene polymerization:

TiCl4/AlR3n

polyethylene

Ziegler Angew. Chem. 1955 (67) 541.

Natta extends this to propylene polymerization. He finds that by using crystalline TiCl3, the regularity of the surface of theheterogeneous catalyst is increased. This results in a greaterstereospecificity in polymerization with the amount of desiredisotactic polypropylene inreasing from 40% to 90%.

TiCl3/AlR3n

polypropylene

The stereochemistry of polypropylene significantly influences its physical properties. Isotactic polymers are the most useful commercially with such physical properties as high tensilestrength and high melting points (~165oC).

In an attempted distillation of ethyllithium, Zieglerobserved ethylene and higher α-olefins. He reasoned that the following process was occuring:

+β-hydride

eliminationpropagation

β-hydrideelimination

+

Organoaluminum compounds such as Et2AlH displayed even higher activities towards ethylene resulting in higher aluminum alkyls that could be readilyhydrolyzed to produce higher alcohols.

Ziegler found that traces of Ni salts (accidentlyincorporated during cleaning the reactor) resulted only in butene and R2AlH.

Ni salts+

Eisch J. Chem. Edu. 1983 (60) 1009.

isotactic: stereoregular material, long sequences having the samestereochemistry at adjacent carbons.Physical properties: crystallinethermoplastic.

syndiotactic: long sequences havingthe opposite stereochemistry atadjacent carbons. Physical properties:semicrystalline with a meltingtemperature ~ 100oC.

atactic: stereorandom polymer that behaves as an amorphous gum elastomer.

For other polymer tacticities see: Coates Chem. Rev. 2000 (100) 1223.


Cossee mechanism for Ziegler Natta polymerizations

TiCl Cl

Cl

Cl Ti

Ti

Cl

TiCl Cl

Cl

Cl Ti

Ti

Cl

TiCl Cl

Cl

Cl Ti

Ti

Cl

TiCl Cl

Cl

Cl Ti

Ti

Cl

Representation of aTiCl3 lattice with anopen coordination site on the surface

According to the Cossee mechanism, propagation of the polymer occurs exclusively at the Ti center. The role of the alkyl aluminum species is thought to be that of initiator by alkylating the TiCl3.

olefin coordination

cis-carbometalation via aconcerted 4-membered TS.

Cossee TL 1960 (17) 12.

Cossee mechanism for Ziegler Natta heterogeneous polymerization.

Cossee stereochemical model for isotactic polypropylene formation:

TiCl Cl

Cl

Cl Ti

Ti

PolymerCl

si-facefavored

TiCl Cl

Cl

Cl Ti

Ti

PolymerCl

re-facedisfavored

Representation of a stereogenic Ti center on the edge of a chiral TiCl3crystal. The growing polymer occupies the open quadrant. The olefinpreferentially binds via its si-face placing its methyl substituent trans to the bulky polymer chain. Modern MgCl2-supported Ziegler Nattacatalysts are highly stereoselective resulting in formation of essentiallyonly the isotactic polymer.

Cossee TL 1960 (17) 17.Brintzinger ACIEE 1995 (34) 1143.


Metallocenes as homogeneous polymerization catalysts

TiIV

Cl

Cl

Et2AlCln

polyethylene

No reaction is observed in the absence of Et2AlCl or Et3Al. Both Et2AlCl and Et3Al alone produce onlyoligomers. Unlike the heterogeneous Ziegler-Natta polymerization catalysts, these catalysts are ineffective at polymerizing α-olefins (propylene).

Natta JACS 1957 (79) 2975.Breslow JACS 1957 (79) 5072.

Breslow's proposed mechanism:

Breslow JACS 1959 (81) 81.

TiIV

Cl

AlClδ+ δ-

TiIV

Cl

Cl Et2AlCl

σ-bond metathesis?

Cl

TiIV

Cl

AlCl

Cl

TiIV

Cl

AlCl

δ+

δ-

Cl

cis- migratoryinsertion

propagation

TiIV

Cl

AlCl

Cl

P

Hβ-hydrideelimination

P

TiIV

H

Cl

AlCl

Cl

TiIV

H

Cl

AlCl

δ+

Cl

(termination)

Polarization of the Ti-Cl bond by the Lewis acidic Al center promotesethylene coordination/insertion.

P


Activation by MAO

In situ formation of MAO (methylalumino oxane). Hydrolysis ofAlMe3 by water results in the formation of a mixture of oligomericaluminoxanes (exact compositions and structures are still not known). Preformed MAO is equally effective as an activator of Cp2ZrMe2 andCp2ZrCl2 catalysts towards olefin polymerizations.

nAlMe3

nH2OAl

Me

O

n

O Al

Al O

O Al

Al O

Me

Me

Me

Me

n

MAO (methlylalumino oxane)

Barron JACS 1995 (117) 6465.

Activation by MAO:

ZrIV

Me

Me

It is postulated that the highly Lewis acidic Al centers in MAO "abstract" CH3_ resulting

in a cationic Zr complex and a weakly coordinating (CH3-MAO)- counterion that may or

may not be weakly associated with the metal.

MAOZrI V

Me

H3C Al(MAO)

ZrI V

Me

H3C Al(MAO)

ZrI V

H3C Al(MAO)

δ-

δ+

δ-

δ+

polypropylene

Dichlorozirconium complex

Dimethylzirconium complex

ZrI V

Cl

Cl MAO ZrI V

Me

Me

ligand exchange (viaσ-bond metathesis?)

MAO as above

Kaminsky ACIEE 1976 (15) 630.Kaminsky ACIEE 1980 (19) 390.Brintzinger ACIEE 1995 (34) 1143.

atactic polypropylene

ZrIV

R'

R'

R3Al

+ H2O

n

R' = Me or ClNo polymerization activity

Water is generally considered a poison for early transition metalpolymerization catalysts. Trace amounts of water were reported to cause a significant increase in the rates of ethylene polymerization byCp2TiEtCl/AlEtCl2 system. It was later found that water activatedanalogous Zr complexes which were typically unreactive towards evenethylene polymerizations to highly active catalysts for both ethylene andpropylene polymerization.

or

orn


Cationic metallocene catalysts

ZrI V

CH3

CH3 AgBPh4 (1 eq)

THF

ZrIV

CH3

O

BPh4

First preformed and spectroscopically characterized cationic complex capable of ethylenepolymerization. This work supports the proposal that cationic Zr and Ti complexes formed upon olefin binding are the active polymerization catalysts.The low polymerization activity was attributed to thecoordinated THF which competes with ethylene for binding.

Jordan JACS 1986 (108) 7410.

First well-characterized cationic zirconocene catalyst capable of propylene polymerization at high rates.

ZrIV

CH3

CH3B(C6F5)3 (1 eq)

C6H6

ZrI V

CH3

H3C B(C6F5)3

Marks JACS 1991 (113) 3623.

M.C. White Chem 153 EM Polymerization -302- Week of November 18, 2002

Chiral metallocene catalysts

ZrCl Cl

Brintzinger's C2-symmetric catalysts/ enantiomorphic site control

ZrCl Cl

MAOMAO

Me2Si Zr

1-Naphthyl

1-Naphthyl

Me

MeClCl

MAO

polymer chain-end control: the stereochemistry of the newest stereogenic center on the growingpolymer controls the stereochemistry of monomeraddition. enantiomorphic site control: chiral ligandoverrides the influence of the polymer chain endand controls the stereochemistry of monomeraddition.

LnM P

LnM P

polymer chain-end control:stereoerror is propagated.

enantiomorphic site control:stereoerror is corrected by the catalyst.

(±) ethylenebis(indenyl)zirconium dichloride

(±) ethylenebis(tetrahydroindenyl)zirconium dichloride

60oC50oC

91% isotacticity, 7700 activity (kg pol/molZr·h),Mw = 12,000.Brintzinger ACIEE 1985 (6) 507.

78% isotacticity, 188 activity (kg pol/molZr·h),Mw =24,000.Paulus OM 1994 (13) 954.

50oC

>99% isotacticity, 875 activity (kg pol/molZr·h),Mw = 920,000.Paulus OM 1994 (13) 954.

Zr

Proposed model for isospecific polymerization

P

HH

polymer chain is in open quadrant

olefin binds such that itsα-substituent is trans to thebulky substituent on the growing polymer chain

ZrP

H

H

‡

stabilizing α-agostic interaction in theTS is thought to rigidify the TS for olefin insertion thereby increasing thestereospecificity of insertion.

ZrP

Zr ClCl

meso ligands give atactic polymers.

Ewan JACS 1984 (106) 6355.Grubbs Acc. Chem. Res. 1996 (29) 85.Coates Chem. Rev. 2000 (100) 1223.


R*

*R

Me

ZrCl

R* =

R* =

neoisomenthyl

neomenthyl

this catalyst led to the formation of highly isotactic, high molecularweight polypropylene, with purelyenantiomorphic site control at lowtemperature.

in contrast, polymerizations withthe neomenthyl-substitutedmetallocene catalyst were "much less selective"

MAO

Cl

Torsional isomers in stereoselective propylene polymerization

13C NMR and 1H NMR studies at -50 oC showed that

in solution the neoisomenthyl-substituted metallocenes

exist primarily as a single, C2-symmetric species. In

contrast, the neomenthyl-substituted catalysts exist as a

4:1 ratio of C2:C1-symmetric metallocene species. The

authors speculate that with the neomenthyl-substituted

catalysts the switching between C2 and C1-symmetric

metallocene species may have given rise to the

formation of alternating isotactic and nearly atactic

sequences along the growing polymer chain.

R*

R*

R*

R*

ZrR

Me

ZrR

Me

C2-symmetric C1-symmetric

R* =

Isotactic Atactic

neomenthyl

Erker JACS 1993 (115) 4590.


Recall:

ZrP

ZrP

chiral- racemic achiral-meso

Atactic polymer 6.25 % isotactic pentad

(fraction of stereosequences containing 5 adjacent

isotactic centers)

Isotactic polymer Often up to 100 % isotactic pentad

(fraction of stereosequences containing 5 adjacent isotactic

centers)

The bridge between the indenyl ligands is removed to allow rotation about themetal ligand bond axis. Bulky phenylsubstituents are incorporated into theindene ligand to inhibit the rate ofligand rotation such that it is slowerthan monomer insertion but faster thanpropagation/termination. The result isproduction of an isotactic-atacticstereoblock copolymer.

Observation of both theracemic-like and meso-likecompounds in the crystal unit cellindicates that the torsional isomers are energetically similar.

note: another way in whichpolymer tacticity is oftendescribed is by thestereochemical relationshipbetween adjacentstereogenic centers: "m" for meso and "r" for racemic .For example, an isotacticpentad would be [mmmm] Waymouth Science 1995 267 217-219.

Torsional isomers in stereoselective propylene polymerization

Zr ZrP P

ki

k-i

Me Me

Chiral racemic-like Achiral meso-like

kpi kpa

Isotactic pentad Atactic block Isotactic pentad

Isotactic pentad content = 6.3-28.1 %

Block copolymer is produced with alternating isotactic-atactic domains

M.C. White/ Chem 153 Oligomerization -305- Week of November 18, 2002

SHOP (Shell Higher Olefin Process)

P

O

NiIIPh

PPh3SHOP process is operated on a 1 million ton capacity and constitutes one of the largestapplications of homogeneous catalysis by atransition metal.(40 atm) 50 oC, toluene

n99% linear

98% α-olefinsup to C30

late metal is highlytolerant of oxygenated functionality

activity = 6000 mol ethylene/mol Ni

Keim and Kruger ACIEE 1978 (17) 466.Keim ACIEE 1990 (29) 235.

Catalyst activation:

Ph2P

O

NiII

Ph

Ph

PPh3

Ph2P

O

NiII

Ph

Ph

PPh3

Ph2P

O

NiII

PhPh

H

Ph2P

O

NiII

Ph

H

Ph2P

O

NiII

Ph

H

Ph2P

O

NiII

Ph

Ph2P

O

NiII

Ph

H

Ph2P

O

NiII

Ph

H

n

n

hydride migratory insertion/ethylene association

alkyl migratory insertion/ethylene assocation, repeat..

(propagation)


n associativedisplacement

If there is β-hydride elimination, why don't we seesignificant branching? Possibilities include 1.associative displacement of the α-olefin oligomer israpid relative to cis hydrometallation to the branched alkyl 2. branched alkyl insertion into ethylene isunfavorable.

Ph2P

O

NiII

Phn

Ph2P

O

NiII

Phn

etc..

branching pathway

Proposed mechanism:

(can be run in acetone or EtOH)

Ph2P

O

NiII

Ph

Ph2P

OPh

Formation of the bis ligandcomplex results in irreversible catalyst inactivation.

Ittel J. Mol. Catal. 1987 (41) 123.

M.C. White, Chem 153 LM Polymerization -306- Week of November 18, 2002

Brookhart’s cationic Ni(II) polymerization catalyst

(1 atm) toluene, 25oC Mw = 410,000

activity = 1.53 x 105 TO/h· mol Ni, 1.8 g PE

71 methyls (branches)/1000 C

branched polyethylene (PE)

nm

N

N

NiIIBr

Br

MAO

Brookhart JACS 1995 (117) 6414.Excellent review: Brookhart Chem. Rev. 2000 (100) 1169.

The rate of associative displacement ofthe olefin (leading to chain terminationand oligomeric products as in the SHOP process) is retarded in these systems bythe steric bulk of the ligand whichblocks the axial positions above andbelow the plane of the Ni complex (seeMechanism, pg 46,47).

NiIIN Br

N Br

NiIIN

N

NiIIN CH3

N

NiII

N

N

NiII

N

N

MAO CH3Al(MAO)

H

NiII

N

N HNiII

N

N

CH3

NiII

N

N

H

H

NiIIN

N

NiII

N

N HNiII

N

N H

NiIIN

N

H

CH3Al(MAO)

see EM Polymerization,pg 300

n

n

n

nm

catalyst activation

insertion

propagation

Linear high Mw

polymers

β-hydride elimination

re-insertion w/opposite

regioselectivity

propagation

Branched

high Mw

polymers

n

termination

associativedisplacement

etc...

etc...

Low Mw polymers

nm

Low Mw polymers

branching

propagation

Proposed catalytic cycle:


Grubbs’neutral Ni(II) polymerization catalyst

N

O

i-Pr

NiII

Ph

PPh3i-Pr

(~7 atm)toluene, 10oC external bath n

Mw > 250,000

activity = 3.7x 106 g PE/mol Ni/hr

>10 branches/1000 C's

linear polyethylene (PE)

cat.1

+

(~7 atm)

OH

toluene,

10oC external bath

1, cat

(225 eq.)OH

n m

incorporation of polar monomer: 22 Wgt %Branch/1000 C = 9Mw = 73, 800

Unlike heterogeneous Ziegler Natta and homogeneous cationic metallocenepolymerization catalysts (poisoned by O,N, and S heteroatom functionality),neutral Ni(II) catalyst 1 is highly tolerant of oxygenated functionality. Ethlene polymerizations with 1 can be run in the presence of up to 1500 eq. of ether,ketone, and ester additives without significantly inhibiting catalyst activity.

Unlike the Brookhart cationic Ni(II) polymerization catalysts, catalyst 1produces highly linear PE.

NiII

N Ph

O PPh3styrene, PR3(as in SHOP)

NiII

N

O

H

NiII

N

O HNiII

N

O

NiII

N

O

PR3NiII

N

O PR3

observed by 31P NMR

propagation

NiII

N

O

H

n

NiII

N

O

H

n

PR3NiII

N

O

H

PR3

observed by 31P NMR

n

Grubbs Science 2000 (287) 460.

Proposed catalytic cycle: The rate of associative displacement of the olefin (leading tochain termination and oligomeric products) may be retardedin these systems (as in the Brookhart system) by the stericbulk of the ligand which blocks the axial positions above andbelow the plane of the Ni complex. The resting state of thecatalyst appears to be the phosphine complex (observed byNMR at various stages throughout the cycle). Neutral Ni(II)complexes are less prone to β-hydride elimination thatcationic Ni(II). This may account for the more linear PEobserved in these systems vs. the cationic Brookhart systems.


A crystal structure of 3 was obtained. The nearly identical bond distances between Ni and the 2 N atoms (1.91Å,1.94Å) and the elongated C-O bond suggests thatresonance structure B is a significant contributor to 3'sstructure.

Ligand mediated activation

N

NO

R1 R1

R2 R2

Ni(C6F3)3B

N

NO

R1 R1

R2 R2

NiCH2Ph

PMe3

N

NO

R1 R1

R2 R2

Ni(C6F3)3B

Neutral Ni (II) complex is activated via formation of a borane carbonyl adduct on the ligand towards oligomerization and polymerization of ethylene. Upon formation of a hypervalent boron"ate" complex which places a positive charge on the coordinated carbonyl oxygen, induction via the ligand's π-system is translated into a loss ofelectron density at the Ni center. At one extreme, resonance structure B may be draw with a full positive charge at the Ni center. As seen in the Brookhart and Grubbssystems, ligand steric bulk in the axial positions is required to effect high Mw polymerization rather than SHOP type oligermerization with Ni.

B(C6F5)3

PMe3

(7 atm)

toluene

1: R1, R2 = H2: R1 = i-Pr, R2 = H 3: R1, R2 = i-Pr

A B

n

1: oligomers , activity = 1500 kg/molNi·h2: PE, Mw = 119,000; activity = 550 kg/molNi·h3: PE, Mw = 508,000; activity = 350 kg/molNi·h

(7 atm)

toluene

NDP Bazan JACS 2001 (123) 5352.

M.C. White, Chem 153 Dimerization -309- Week of November 18, 2002

Nickel promoted olefin dimerizations

NiCl

ClNi

(i-Pr)2P(t-Bu) = PR3 NiIIR3P

Cl

EtAlCl2

NiIIR3P

EtCl2AlClδ+

NiIIR3P

EtCl2AlClδ+

NiIIR3P

EtCl2AlClδ+

δ-δ-

δ-

NiIIR3P

EtCl2AlClδ+δ-

H

NiIIR3P

EtCl2AlClδ+

H

δ-

NiIIR3P

EtCl2AlClδ+δ-

NiIIR3P

EtCl2AlClδ+δ- H

catalyst activationcatalytic cycle

Proposed mechanism:

Wilke ACIEE 1988 (27) 185.

NiCl

ClNi

cat.

EtAlCl2, chlorobenzene, -45oC

R3P+

(i-Pr)2P(t-Bu) P(Et)3

Product distribution of propylene dimersformed depends heavily on the phosphineligand. Diisopropyl-tert-butylphosphine givespredominantly 2,3-dimethyl-1-butene and alsoshowes the highest catalytic activity fordimerization. In the analogous process withethylene, the choice of bulky phosphine effects whether dimerization or polymerizationoccurs.

Ligand effects...

Very subtle...

NiCl

ClNi

cat.

EtAlCl2, chlorobenzene, -45oC

R3P+

(i-Pr)2P(t-Bu), dimer

n

(t-Bu)3P, polyethylene

trace

+

M.C. White, Q. Chen Chem 153 Dimerization -310- Week of November 18, 2002

ZrI V

Cl

Cl MAO ZrIV

ClAl(MAO)

Me

δ-

?

EtZrI V

ClAl(MAO)

Meδ-

Et

ZrI V

ClAl(MAO)δ-

Et

δ+ δ+

ZrI V

ClAl(MAO)

Hδ- Et

ZrIV

ClAl(MAO)

Hδ-

Et

δ+

ZrIV

ClAl(MAO)δ-δ+

Et

ZrIV

ClAl(MAO)δ-

Et

δ+

Et

ZrI V

ClAl(MAO)δ-δ+

EtEt

H

Et

Et

Bergman JACS 1996 (118) 4715.

Et

Et

Et

In zirconocene/MAO catalyzed polymerizations, a large excess of MAO is necessary toeffect an efficient process (Al/Zr ratios of 500:1 up to 10,000:1). The Cp2ZrCl2/MAO(Al/Zr ratio 1:1) system is very selective for the dimerization of terminal olefins overoligomerization and polymerization. One rationale for this is that an associated Cl promotes β-hydride elimination over insertion. The reason for this is unclear.

Cp2ZrCl2/MAO 0.5 mol %

(1:1 Zr:Al)

Cp2Zr(Cl)/MAO (Zr:Al, 1:1) leads to dimerization

M.C. White, Chem 153 Cyclodimerization -311- Week of November 18, 2002

Ni(0) catalyzed 1,3-diene cyclodimerization

Ni0R3P NiIIR3P

NiII

R3PNiII

R3P

NiII

PR3HNiII

PR3

NiII

H

PR3

PR3NiII

Ni0(COD)2PR3

2 COD

η1,η3-bis allyl

LnNi(0)

sterically unfavorable

favored when PR3 is bulky

Proposed mechanism:

Weimann ACIEE 1980 (19) 569, 570.Houk JACS 1994 (116) 330.

Once again, the dimerization product distribution is heavily dependent on the phosphine ligand used. Basic phosphinesare known to stabilize the 16e- η1,η3-bis-allyl intermediatewhich leads to the vinylcyclohexene product. Less basicphosphites are thought to stabilize the 18e- bis-η3-allylforms.

LnMn

oxidative coupling

reductive fragmentation (rare)LnMn+2

Note that thismechanism operatesfor metals in ligandenviroments that can increase theiroxidation state by 2units.

LnMn+2

concerted stepwise

LnMn LnMn+2

Oxidative coupling

Ni0(COD)2, PR3

basic phosphines(PPhEt2)

less basic phosphites

bulky e.g. P(OPh)3

non-bulky e.g. P(OMe)3

M.C. White, Chem 153 [4+4] -312- Week of November 18, 2002

Wender’s intramolecular cyclodimerization: [4+4]

EtO2C

EtO2C

Ni(COD)2 (11 mol%)

PPh3 (33 mol%), tol

60oC

H

H

EtO2C

EtO2C

H

H

EtO2C

EtO2C

H

H

70% (19:1)

+EtO2C

EtO2C

2.6% (if P(OTol)3 is used, the vinyl cyclohexene analog is the main product (37% yield)

3 carbon tether:

H

H

Ni0

PPh3NiII

PPh3

H

H

Ni

PPh3

H

H

NiIIPPh3

Ni0Ln

oxidative coupling

Ln(PPh3)Ni0

CO2Me

Ni(COD)2 (11 mol%)

PPh3 (33 mol%), tol

60oC

H

H

MeO2C

95:5 (trans:cis)99:1 (dr)

84%

H

H

Ni0

PPh3 H

H

NiIIPPh3

Ln(PPh3)Ni0

oxidative coupling

etc...

An analogous homoallylic substituted substratealso gave predominantly the trans fused productbut very poor dr (1:2.2). When the allylic ester is replaced with other bulky functionality, thediastereoselectivity remains high: CH2OAc (dr21:1) and CH3 (dr 20:1).

Wender JACS 1986 (108) 4678.Wender TL 1987 (28) 2451.

4 carbon tether:


Applications of [4+4] in TOS

Ni(COD)2 (11 mol%)

PPh3 (33 mol%), tol

60oC

O

O

H

67%H

O

O

H H

H

O

O

H HH

O

(+)-Asteriscanolide

First application of the [4+4] methodology in the total synthesis of (+)-Asteriscanolide. Wender JACS 1988 (110) 5904.

TBSO Ni(COD)2 (11 mol%)

PPh3 (33 mol%), tol

110oC

52%

TBSO

CO2CH3

Ni(COD)2 (11 mol%)

PPh3 (33 mol%), tol

110oCH

CO2CH3

92% yield97% de

AcO O

RO

OH OR

H

OH

O

OAc

Taxol

Model studies for the taxane skeleton. Wender TL 1987 (28) 2221.


Intramolecular dienyne cycloaddition: [4+2]

O

Ni(COD)2 (10 mol%)

P(O-o-biphenyl)3 (30 mol%), THF

rt

O

H

H H

rxn proceeds with complete stereocontrol in C-C bond formations: 99% yield, (trans: cis, >99:1)

H

O

Ni0

PR3

O

NiII

H

Me

H

R3P

ONiII

H

Me

H

R3P

Ln(PR3)Ni0Ln(PR3)Ni0

Proposed mechanism

Wender JACS 1989 (111) 6432.

Ni(COD)2 (10 mol%)

P(O-o-biphenyl)3 (30 mol%), THF

rtX

R'

R

R'X

HR

R'X

HR

R= CH2OTBS, R'= Me, X= CH2, >99%; (2:1), thermal 160oC

R= CH2OTBS, R'= TMS, X= CH2, 98% (1.2:1), thermal 140oC

R= CH2OAc, R'= Me, X = CH2CH2, 85% (1.8:1), thermal 200oC

The low reactivity of unactivated alkynesas dienophiles in thermal DA rxns requires extreme temperatures to effectcycloadditions. Elevated temperaturesoften lead to decomposition, particularlyfor substrates with remote functionality.Alternatively, the Ni(0) promotedcyclization proceeds at rt with outstandingyields.

3 and 4 carbon tethers used. 2 and 5 carbon tethers donot cyclize.

Unlike the Ni(0) catalyzed[4+4], PPh3 ligand results in slow reactions that areattended by substratedecomposition and productaromatization.


Intramolecular diene-allene cycloaddition: [4+2]

·

OTBS

RhIR3P

Cl

PR3

L

H

TBSO

RhICl

R3P

H

OTBS

RhI

R3P

R3PCl

RhIII

OTBS

R3P

Cl

HRhIII

OTBS

R3P

Cl

H

RhIII

OTBS

R3P

Cl

H

OTBS

HRhI

R3P

R3P Cl

OTBS

H

Proposed mechanism:

Wender JACS 1995 (117)1843.

Ni(COD)2 (10mol%)P(O-o-biphenyl)3 (30 mol%)

THF, rt97%

[Rh(COD)Cl]2 (5 mol%)

P(O-o-biphenyl)3 (48 mol%)

THF, 45oC

90%

OTBS

OTBS

H

OTBS

H

H

TBSO

RhICl

R3P

H

TBSO

H

Ni0R3P

Metal mediated reversal in chemoselectivity...

A complete reversal of chemoselectivityoccurs in the metal-mediated [4+2]diene-allene cycloaddition in switchingfrom a Ni(COD)2 catalyst to[Rh(COD)Cl]2. The known preference for Ni0 coordination to the less stericallyhindered π-bond of allenes is given as arationale for the observed difference inselectivities.

·


X

R

RhCl(PPh3)3 (0.1 mol% -0.5 mol%)

AgOTf (0.1 mol% - 0.5 mol%)

tol, 110oCX

R

Efficient route to 7 membered rings via 5+2 cycloadditions of vinylcyclopropanes and...

MeO2C

MeO2C

H

O

R

R'

MeO2C

MeO2C

Me

H

alkenes/alkynes

allenes

X

·

R

RhCl(PPh3)3 (1 mol%)

tol, 110oC

X

R

H

H

t-Bu

H

H

MeO2C

MeO2C

83% R = Me, 88% TMS, 83% CO2Me, 74%

92%

exclusive formation of the cis-fused product for the 5,7 ring system. Trans-fused product observed for the 6,7 ring system.

96%

XRhI PPh3

PPh3

oxidativecoupling

X RhIII

H

H

exclusive formation of the cis-fusedproduct is consistent with thepreferential formation of a cis-fused metallocyclopentane intermediate

PPh3

PPh3

ring-expansion X

H

Hvinylcyclopropanes are thought tohave diene-like properties becauseof significant p orbital character in the strained σ bond

RhIII

PPh3PPh3

reductiveelimination

X

H

H

-OTf -OTf -OTf

[LnRhI]+ (OTf-)

XRhIII

PPh3

PPh3 -OTf

or...

Wender JACS 1995 (117) 4720.Wender JACS 1998 (120) 1940.Wender JACS 1999 (121) 5348.for an intermolecular [5+2] w/ alkynes see: Wender JACS 1998 (120) 10976.

Proposed mechanism:

Wender’s [5+2] cycloadditions

M.C. White, Chem 153 [5+2]-317- Week of November 18, 2002

Applications of [5+2] in TOS Me

OHMe

CHO(+)-Allocyathin B2

·

OBn

[Rh(CO)2Cl]2

Toluene

100 oC

RhLn

OBnH

H

LnRh

OBn HOBn

Asymmetric total synthesis of (+)-Aphanamol I. Wender OL 2000 2:15 2323-2326.

93%

H

O

OBn

(+)-Aphanamol

Asymmetric synthesis of tricyclic core of (+)-Allocyathin B2. Wender OL 2001 3:13 2105-2108.

Me

HO

MeO O

OHMe

RhLn

Me

H

OOHMe Me

H

RhLn

Me

HO

O

Me

H

[Rh(CO)2Cl]2

DCE, 80 oC

5 mol%

90%


Question 1Propose a mechanism for the following transformation:

O O

+

O CH3

Et

[Rh(CO)2Cl]2 (2.5 mol%)

CO (1-2 atm), dioxane, 60oC

H3O+

C(O)CH3

Et

H

OH

O

M.C. White, Chem 153 Cycloisomerization -319- Week of November 18, 2002

CO2CH3RTBDMSO

CO2CH3

RTBDMSO

CO2CH3RTBDMSO

Ru(II)Cp

Ru(IV)Cp

CO2CH3TBDMSOR

CO2CH3R

TBDMSO

Ru(IV)Cp

H

TBDMSOR

CO2CH3

Ru(IV)CpH

A

BC

TBDMSO R

CO2CH3

Ru(IV)Cp

TBDMSO R

H

R = CH3R = H

Cycle A Cycle B

CpRu(CH3CN)3PF6

10 mol%

acetone, rt

CpRu(CH3CN)3PF6

10 mol%

acetone, rt

R = H

R = Me

A1,3-type strain if R = Me

RuII

H3CNCCNCH3

CNCH3

(PF6-)

CO2CH3

R = H

R = Me

CO2CH3

CD3

RTBDMSOD

TBDMSO R

D

D

CO2CH3

The allylic C-H activation mechanism is supported by the following deuterium-labelling experiment

CpRu(CH3CN)3PF6

To rationalize the observed divergence in reaction course, the authors

suggest that when R = Me the oxidative coupling of A to form B is

disfavored due to steric congestion in the form of A1,3-type strain between

the quaternary center and the ester. Alternatively, allylic C-H activation

leads to the formation of intermediate C, which subsequently cyclizes to a

seven-membered ring

Trost JACS 1999 121 9728-9729.

Ru mediated cycloisomerization

M.C. White Chem 153 Cycloisomerization -320- Week of November 18, 2002

CO2CH3

N NPh Ph

CO2CH3

CO2CH3

PdII(OAc)2Ln

Nu

CO2CH3

PdII(OAc)Ln

Nu

H CO2CH3Nu PdIILn

AcO

HAcOH

CO2CH3Pd0Ln PdIILn

CO2CH3

H PdIILn

CO2CH3

H

Pd(OAc)2 (5 mol%)

6 mol% 83%

Trost JACS 1987 (109) 3484.

in situ generation of Pd(0) via Wacker type process:

+ Pd0Ln

Pd0Ln Pd0Ln

Pd mediated cycloisomerization

Pd2(dba)2 (2.5 mol%)

P(o-tol)3 (5 mol%)

AcOH (5 mol%)MeO2C

MeO2C

Cy

Cy

95%

MeO2C

MeO2C

Pd0Ln

AcOH

PdIILnAcO

H

MeO2C

MeO2C

CyPd OAc

H

MeO2C

MeO2C

CyPd OAc

Cy

MeO2C

MeO2CPd(OAc)Ln

H

When AcOD was used thedideuterated product is observed.The first deuterium isincorporated via exchange withacetylene H and the second via the proposed hydropalladation.

Cy

MeO2C

MeO2C

D

D

Trost JACS 1994 (116) 4268.

M.C. White, Q. Chen Chem 153 [2+2+2] -321- Week of November 18, 2002

[2+2+2] cycloaddition of diynes with isocyanates to give bicyclic pyridones

NPh

O

RuIICp*Cl

RuIVCp*Cl

PhNCORu

N

·O

Ph

NPh

RuCp*Cl

O

NPh

O

+

Cp*Ru(COD)Cl5 mol%

DCE, reflux, 2h

16e-

Cp*RuCl

Cp*Ru(COD)Cl

Cp*

Cl

· ON

Ph

Itoh. OL 2001 (3) 2117.


Ph Nt-Bu + CO

Ru3(CO)12 2 mol%

toluene, 180 oCNt-Bu

O

Ph

Although α,β-unsaturated imines react readily with early transition metals such as Ti and Zr to form the corresponding metallacyclopentenes, this is the first example of such a reaction with a latetransition metal complex.

(10 atm)

the authors propose that initialcoordination of a nitrogen to ruthenium facilitates the oxidative cyclization toyield the metallacycle intermediate

for the reaction of imines which contain a β-hydrogen, olefin isomerization occursto give the thermally more stableα,β-unsaturated γ-lactam

Ru0(CO)4

Ph Nt-Bu

Ru (CO)4

RuII (CO)4

Nt-Bu

Ru (CO)3

Nt-Bu

O

Nt-Bu

O

Ph

PhNt-Bu

O

Ph

oxidativecyclizationCO insertion

CO

Murai JACS 1999 (121) 1758.

Carbonylative [4+1]

M.C. White, M.W. Kanan Chem 15 Cycloisomerization -323- Week of November 18, 2002

TsN

H

H

CO2H

TsN

TsN NiLn

TsN

H

H

NiII

TsN

H

H

O

O

NiLn

TsN

H

H

O

OZnEt

LnNi

Et

TsN

H

H

O

OZnEt

NiLn

H

TsN

H

H

CO2ZnEt

Et2Zn

ZnEt2

TsN

H

H

CO2H

LnNi

Me

TsN

H

H

O

OZnMe

TsN

H

H

CO2ZnMe

NiII(acac)2

LnNi0

Mori JACS 2002 (124) 10008.

Ni(acac)2 5 mol%

PPh3, 10 mol%

CO2, 1 atm Me2Zn, 4.5 eq.

HF, 0°C

Ni(acac)2 5 mol%

PPh3, 10 mol%

CO2, 1 atm Et2Zn, 4.5 eq.

HF, 0°C

reductiveelimination

β-hydride elimination

reductive elimination

this intermediate has no β-hydrogens

·O

O

TsN

oxidativecoupling

insertion

transmetalation

Cycloisomerization/carboxylation of bis-1,3-dienes

M.C. White/Q. Chen Chem 153 Question -324- Week of November 18, 2002

TBDPSO TBDPSO

OH

TBDPSO TBDPSOH

O

Beginning with 1 propose a synthetic route to 2. Indicate all reagents and show intermediates.

1 2

3 4

Beginning with 3 propose a synthetic route to 4. Indicate all reagents and show intermediates.

Question 2

M.C. White, M.S. Taylor Chem 153 Question -325- Week of November 18, 2002

MeO2C

MeO2C Ph3SiD

Pd2(dba)3 (5 mol%)THF, 25°C, 2 hours

SiPh3

DH2C

MeO2C

MeO2CCH2D

MeO2C

MeO2C

Ph3Si

A B6:1 A:B

Provide a mechanism for the following transformation

Question 3

Documents

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