Supporting Information

© Wiley-VCH 2008

69451 Weinheim, Germany

High-Pressure Entry into Platencin

D. C. J. Waalboer, M. C. Schaapman, F. L. van Delft, F. P. J. T. Rutjes*

Institute for Molecules and Materials, Radboud University Nijmegen Heyendaalseweg 135, NL-6525 AJ Nijmegen, The Netherlands

Supporting Information

General Information ........................................................................................................1

Experimental protocol .....................................................................................................1

Reference ........................................................................................................................4

NMR spectra for compounds...........................................................................................5

General Information Solvents were distilled from appropriate drying agents prior to use and stored under nitrogen. Chemicals were

purchased from Sigma-Aldrich and used as received, unless stated otherwise. Reactions were carried out under

inert atmosphere of argon using flame dried glassware. Hyperbaric reactions were carried out in a high pressure

apparatus. Reactions were followed using thin layer chromatography (TLC) on silica gel-coated plates (Merck 60

F254). IR spectra were recorded on an ATI Mattson Genesis Series FTIR spectrometer, or a Bruker Tensor 27

FTIR spectrometer. NMR spectra were recorded on a Bruker DMX 300 (300 MHz), and a Varian 400 (400 MHz)

spectrometer in CDCl3 solutions. Proton chemical shifts are internally referenced to the residual solvent resonance

signal (CDCl3 d 7.26). Carbon chemical shifts are internally referenced to the residual solvent resonance signal

(CDCl3 d 77.0). Column or flash chromatography was carried out using Silicycle silica gel (60 Å, 230-400 mesh).

Optical rotations were determined with a Perkin Elmer 241 polarimeter. High resolution mass spectra were

recorded on a JEOL AccuTOF (ESI), or a MAT900 (EI, CI, and ESI).

Experimental protocol Aldehyde (5)

A Teflon vial was loaded with (S)-(–)-perillaldehyde (3.56 g, 23.7 mmol), Danishefsky’s diene (4.50 g, 26.1 mmol) and a catalytic amount of 5-tert-butyl-4-hydroxy-2-methylphenyl sulfide (3.0 mg, 0.008 mmol). The vial was filled with MeCN (5 mL) so that no air remained and was then sealed with a stainless steel screw cap. The contents were mixed by shaking and the vial was placed in the high pressure apparatus. The stainless steel cylinder containing the reaction vial was filled with petroleum ether after which the contents were pressurized to 15 kbar by a piston. Subsequently, the reaction mixture was warmed to 50 °C in 1 h. After 15 h,

the solvent was evaporated and the crude product redissolved in toluene (350 mL). The solution was cooled to 0 °C

H

O

CHO

and a suspension of Yb(OTf)3 (0.385 g, 0.621 mmol) and MeOTMS (0.259 g, 2.48 mmol) in toluene (50 mL) was added via a pipette. The initially yellow mixture was stirred for 6 h, during which time the reaction color changed to dark red. The reaction was quenched with cold water and the water layer was extracted with EtOAc (× 3). The combined organic layers were washed with brine, dried over Na2SO4, and the solvent evaporated. The crude product was purified by flash column chromatography (silica gel, ethyl acetate : heptane 1:10 ? 1:3) to give 5 (4.21 g, 81%) as a colorless oil. Note: The reaction time of the Lewis acid workup with Yb(OTf)3 may vary significantly depending on the quality of Yb(OTf)3. Reactions with fresh Yb(OTf)3 proceed within 30 min. whereas older batches give slower, though cleaner conversion. [a]d25 = +147.1 (c = 0.84 CH2Cl2). 1H NMR (CDCl3, 400MHz) d = 9.59 (br s, 1 H), 6.61 (d, J = 10.1 Hz, 1 H), 6.09 (dd, J = 10.1, 0.7 Hz, 1 H), 4.75-4.76 (m, 1 H), 4.69-4.70 (m, 1 H), 2.78-2.84 (m, 1 H), 2.66 (dd, J = 16.5, 13.9 Hz, 1 H), 2.40 (dd, J = 16.5, 4.3 Hz, 1 H) 2.22 (td, J = 14.0, 3.6 Hz, 1 H), 2.11 (tt, J = 11.7, 3.5 Hz , 1 H), 1.72-1.78 (m, 1H), 1.68-1.70 (m, 3H), 1.64-1.69 (m, 1H), 1.61-1.63 (m, 1H), 1.57-1.59 (m, 1H), 1.24 (dq, J = 13.1, 3.4 Hz, 1H). 13C NMR (75 MHz, CDCl3) d = 201.6, 198.5, 148.2, 147.9, 129.9, 109.7, 52.7, 39.2, 38.0, 32.8, 32.6, 28.1, 27.1, 20.9. IR (neat) ? 3079, 2930, 2860, 2708, 1725, 1674, 1643 cm–1. HRMS (EI) calcd. for C14H18O2 (M+) 218.1307, found 218.1313. Alkene (10)

To a suspension of methyltriphenylphosphonium bromide (11.05 g, 30.93 mmol) in THF (250 mL) at 0 °C was added KOtBu (2.89 g, 25.75 mmol). After stirring for 10 min the resulting yellow suspension was added via a cannula to a solution of 5 (3.75 g, 17.17 mmol) in THF (100 mL) at 0 °C until the reaction mixture retained its indicative yellow color due to excess Wittig reagent (approximately 1.1 equiv.). The reaction was quenched with sat. aq. NH4Cl and diluted with ether. The organic layer was separated and the waterlayer extracted with ether (× 2). The combined organic layers were washed with water (× 2) and brine, dried over MgSO4 and

concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel, ether : pentane 1:10) to give 10 (3.20 g, 86%) as a colorless oil. [a]d25 = +91.2 (c = 1.03 CH2Cl2). 1H NMR (CDCl3, 400MHz) d = 6.58 (d, J = 10.1 Hz, 1 H), 5.93, (d, J = 10.1 Hz, 1 H), 5.91 (dd, J = 17.7, 10.8 Hz, 1 H), 5.26, (d, J = 10.8 Hz, 1 H), 5.17, (d, J = 17.7 Hz, 1 H), 4.76 (br s, 1 H), 4.72 (br s, 1 H), 2.60-2.67 (m, 1 H), 2.30-2.40 (m, 2 H), 2.15 (tt, J = 10.9, 3.4 Hz, 1 H), 1.75-1.82 (m, 2H), 1.72 (br s, 3 H), 1.61-1.68 (m, 2 H), 1.46-1.57 (m, 2 H). 13C NMR (CDCl3, 75 MHz) d = 200.2, 157.2, 148.8, 143.3, 127.0, 115.8, 109.3, 42.3, 40.0, 38.3, 38.1, 32.0, 30.6, 25.9, 21.1. IR (CH2Cl2) ? 2931, 2859, 1676, 1642 cm–1 HRMS (EI) calcd. for C15H20O (M+) 216.1514, found 216.1519.

Ketal (11)

To 10 (3.00 g, 13.87 mmol) in dry benzene (300 mL) were added ethylene glycol (8.61 g, 138.74 mmol) and PPTS (0.87 g, 3.47 mmol). The flask was fitted to a Dean-Stark condensor and the set up was purged with argon. After refluxing for 16 h, the reaction was cooled to RT and quenched with anhydrous Na2CO3 (3.00 g, 28.30 mmol). The reaction was stirred for 30 min and diluted with ether. Subsequently, the reaction mixture was washed with sat. aq. NaHCO3, (× 2), water and brine, dried over Na2SO4 and concentrated in vacuo to give 11 (3.70 g, quant.) as a colorless oil, which required no further purification. [a]d25 = +23.8 (c = 2.03 CH2Cl2). 1H NMR (CDCl3, 400MHz) d = 5.86 (dd, J = 17.5, 11.0 Hz, 1 H), 5.59 (d, J = 10.0 Hz, 1 H), 5.49 (dd, J = 10.0, 1.7

Hz, 1 H), 5.15 (dd, J = 11.0, 1.0 Hz, 1 H), 5.13 (dd, J = 17.5, 1.0 Hz, 1 H), 4.68-4.69 (m, 1 H), 4.66-4.67 (m, 1 H), 3.97-4.05 (m, 3 H), 3.88-3.95 (m, 1 H), 2.15-2.22 (m, 1 H), 2.12 (dd, J = 14.0, 11.9 Hz, 1 H) 2.04 (tt, J = 12.2, 3.0 Hz, 1 H), 1.73 (dd, J = 13.4, 4.4 Hz, 1 H), 1.69-1.70 (m, 3 H), 1.65-1.68 (m, 1H), 1.64 (td, J = 11.8, 1.6 Hz, 1 H), 1.52-1.60 (m, 2 H), 1.39-1.47 (m, 2 H). 13C NMR (CDCl3, 75 MHz) d = 150.2, 144.4, 140.9, 124.6, 114.3, 108.5, 106.7, 64.7, 64.4, 41.3, 39.1, 36.7, 36.0, 33.4, 30.8, 26.9, 20.9. IR (neat) ? 3079, 3023, 2922, 2877, 1642 cm–1. HRMS (ESI+) calcd. for C17H24O2Na (M+Na+) 283.1674, found 283.1667. Aldehyde (4)

A solution of 11 (98 mg, 0.38 mmol) and pyridine (0.119 g, 1.50 mmol) in CH2Cl2/MeOH (1:1, 5 mL) was cooled to -78 °C and ozone was bubbled through the solution. When the reaction was complete according to TLC the reaction mixture was purged with argon for 30 min at –78 °C. Subsequently, the reaction was quenched with triphenyl phosphine (0.300 g, 1.14 mmol) and the reaction was allowed to warm to RT. After stirring for 1.5 h the solvent was evaporated and the crude product purified by flash column chromatography (silica gel,

H

CHO

O

OO

H

OO

H

O

ethyl acetate : heptane 1:6, 1% Et3N ? 1:2, 1% Et3N) to yield 4 (90 mg, 91%) as a colorless oil, which solidifies upon storage in the freezer. [a]d25 = +122.5 (c = 1.00 CH2Cl2). 1H NMR (CDCl3, 400MHz) d = 9.41 (d, J = 1.0 Hz, 1 H), 5.75 (dd, J = 10.0, 1.5 Hz, 1 H), 5.53 (d, J = 10.0 Hz, 1 H), 3.98-4.08 (m, 3 H), 3.91-3.97 (m, 1 H), 2.60-2.66 (m, 1 H), 2.41 (tt, J = 11.8, 3.7 Hz, 1 H), 2.10-2.16 (m, 1 H), 2.12 (s, 3 H), 2.02 (t, J = 13.5 Hz, 1 H), 1.79-1.85 (m, 1 H), 1.66-1.76 (m, 3 H), 1.44 (ddt, J = 13.6, 3.6, 0.9 Hz, 1 H), 1.29-1.36 (m, 1 H). 13C NMR (CDCl3, 75 MHz) d = 210.9, 202.4, 131.2, 130.0, 105.5, 64.9, 64.6, 51.9, 45.3, 35.0, 30.7, 30.6, 27.8, 26.9, 24.8. IR (neat) ? 2944, 2925, 2883, 2859, 1703, 1643 cm–1. HRMS (ESI) calcd. for C15H20O4Na (M+Na+) 287.1259, found 287.1250. Diol (8)

To a solution of 4 (70.0 mg, 0.265 mmol) in THF (1 mL) at RT was added methanol (45 mg, 1.4 mmol) under an argon atmosphere. A samarium iodide solution (0.1 M in THF, 9.5 mL) was added via syringe until the solution retained its blue color for more than 5 min. The reaction mixture was diluted with ether and sat. aq. NH4Cl was added. The organic layer was washed with brine, dried over Na2SO4. After evaporation of the solvent, the crude product was redissolved in CH2Cl2 (5 mL) and one drop of water was added followed by a catalytic amount of PTSA. The reaction mixture was stirred

vigorously for 30 min after which the solvent was evaporated and the crude product purified by flash column chromatography (silica gel, ethyl acetate : heptane 1:10 ? 1:2) to give 8 (50.2 mg, 85%) as a white solid. [a]d25 = +40.4 (c = 0.99 CH2Cl2). 1H NMR (CDCl3, 400MHz) d = 7.04 (d, J = 10.2 Hz, 1H), 5.92 (dd, J = 10.2, 0.9 Hz, 1H), 3.32-3.35 (m, 1H), 3.12 (dd, J = 5.2, 1.3 Hz, 1H), 2.46 (ddd, J = 17.0, 5.2, 0.9 Hz, 1H), 2.34-2.41 (m, 2H), 1.94-2.04 (m, 3H), 1.73-1.82 (m, 1H), 1.63-1.68 (m, 1H), 1.38-1.47 (m, 2H), 1.36 (s, 3H), 1.09-1.17 (m, 1H). 13C NMR (75 MHz, CDCl3) d = 199.6, 155.0, 128.1, 76.8, 70.0, 41.1, 39.8, 36.9, 32.8, 30.8, 29.4, 20.7, 17.3. IR (neat) ? 3330, 2948, 2875, 1675, 1666 cm–1. HRMS (ESI+) calcd. for C13H18O3Na (M+Na+) 245.1154, found 245.1158. Acetate (12)

Acetic anhydride (1.41 g, 13.8 mmol) was added to a solution of 8 (0.613 g, 2.76 mmol) and DMAP (5.8 mg, 0.05 mmol) in CH2Cl2/pyridine (20 mL, 20:1) at 0 °C. After stirring for 5 min the reaction was warmed to RT and stirred for 1 h. The reaction was cooled to 0 °C and quenched with sat. aq. NaHCO3. Subsequently, the reaction mixture was stirred vigorously at RT for 30 min after which the reaction mixture was diluted with CH2Cl2 and the water layer extracted with CH2Cl2 (× 2). The combined organic layers were washed with aq. HCl (0.1 M), water and brine, dried over Na2SO4 and

the solvent evaporated. The crude product was purified by flash column chromatography (silica gel, ethyl acetate : heptane 1:4 ? 1:2) to give 12 (0.729 g, quant.) as a white solid. [a]d25 = +64.7 (c = 1.02 CH2Cl2). 1H NMR (CDCl3, 400MHz) d = 6.68 (d, J = 10.2 Hz, 1H), 5.91 (dd, J = 10.2, 0.9 Hz, 1H), 4.23 (d, J = 1.5 Hz, 1H), 2.48 (ddd, J = 16.7, 5.1, 0.9 Hz, 1H), 2.38 (dd, J = 16.7, 12.9 Hz, 1H), 2.20 (s, 3H), 1.98-2.13 (m, 3H), 1.93 (br s, 1H), 1.76-1.82 (m, 1H), 1.65-1.68 (m, 1H), 1.51-1.57 (m, 1H), 1.44-1.50 (m, 1H), 1.43 (s, 3H), 1.12 (ddd, J = 9.4, 7.4, 1.5 Hz, 1H). 13C NMR (75 MHz, CDCl3) d = 198.8, 172.0, 152.6, 128.6, 79.1, 70.0, 40.6, 38.2, 36.6, 32.6, 30.6, 29.2, 20.9, 20.4, 18.2. IR (neat) ? 3451, 2967, 2932, 2870, 1713, 1684, 1669 cm–1. HRMS (ESI+) calcd. for C15H20O4Na (M+Na+) 287.1259, found 287.1254. Allylic acetate (9)

Burgess reagent (47.0 mg, 0.197 mmol)[1] was added to a solution of 12 (21.0 mg, 0.079 mmol) in toluene (1.5 mL) and the reaction mixture was warmed to 70 °C. After 15 min the reaction mixture was cooled to RT and the solvent evaporated. The crude product was purified by flash column chromatography (silica gel, ethyl acetate : heptane 1:10) to give 9 (9.4 mg, 48%) as a colorless oil, which solidified upon storage in the freezer. [a]d25 = +96.2 (c = 1.25 CH2Cl2). 1H NMR (CDCl3, 400MHz) d = 6.61 (d, J = 10.2 Hz, 1H), 5.93 (dd, J = 10.2, 0.9 Hz, 1H), 5.24-5.26 (m, 1H), 5.12 (t, J

= 1.2 Hz, 1H), 5.06, (t, J = 1.3 Hz, 1H), 2.51, (ddd, J = 16.8, 5.2, 0.9 Hz, 1H), 2.39-2.42 (m, 1H), 2.39 (dd, J = 16.8, 13.3 Hz, 1H), 2.15 (s, 3H), 2.01-2.11 (m, 1H), 1.96 (dddd, J = 14.6, 9.9, 4.4, 2.2 Hz, 1H), 1.84-1.91 (m, 1H), 1.78-1.83 (m, 1H), 1.72-1.77 (m, 1H), 1.60-1.70 (m, 1H), 1.22 (ddd, J = 12.5, 7.8, 1.4 Hz, 1H). 13C NMR (75 MHz, CDCl3) d = 198.8, 172.0, 152.6, 128.6, 79.1, 70.0, 40.6, 38.2, 36.6, 32.6, 30.6, 29.2, 20.9, 20.4, 18.2. IR (neat) ? 2938, 2864, 1736, 1683 cm–1. HRMS (ESI+) calcd. for C15H18O3Na (M+Na+) 269.1154, found 269.1145.

O

OHOH

O

OAcOH

O

OAc

Enone (3)

To a solution of 9 (67.9 mg, 0.276 mmol) in THF (4.5 mL) was added a premixed solution of Pd2dba3 (12.6 mg, 0.014 mmol), PBu3 (22.4 mg, 0.111 mmol), Et3N (0.167 g, 1.66 mmol) and formic acid (76.2 mg, 1.66 mmol) in THF (0.5 mL). After 18 h the reaction mixture was cooled to RT, diluted with ether and washed with water, aq. HCL (2 M), sat. aq. NaHCO3 and brine. The organic layer was dried over MgSO4, the solvent evaporated and the crude product purified by flash column

chromatography (silica gel, ether : pentane 100% ? 1:10) to give 3 (31.0 mg, 60%) as a colorless oil. [a]d25 = +24.1 (c = 1.20 CHCl3) 1H NMR (CDCl3, 400MHz) d = 6.56 (d, J = 10.0 Hz, 1H), 5.87 (dd, J = 10.0, 1.0 Hz, 1H), 4.83 (dt, J = 3.0, 1.7 Hz, 1H), 4.68 (m, 1H), 2.45 (dd, J = 16.7, 4.9 Hz, 1H), 2.43 (dt, J = 16.2, 2.6 Hz, 1H), 2.32 (dd, J = 16.8, 13.6 Hz, 1H), 2.30-2.32 (m, 1H), 2.07-2.19 (m, 2H), 1.96-2.03 (m, 1H), 1.68-1.83 (m, 3H), 1.47-1.54 (m, 1H), 1.20 (ddd, J = 12.6, 7.8, 1.3 Hz, 1H). 13C NMR (75 MHz, CDCl3) d = 200.1, 156.7, 148.9, 127.8, 106.9, 41.6, 40.9, 36.0, 35.6, 35.5, 34.9, 26.4, 24.5. IR (CHCl3) ? 2936, 2864, 1429, 1681, 1392 cm–1. HRMS (ESI+) calcd. for C13H17O (M+H+) 189.1279, found 189.1268. [Matched with literature][2]

Reference [1] E. M. Burgess, H. R. Penton, E. A. Taylor, J. Org. Chem. 1973, 38, 26 – 31. [2] a) K. C. Nicolaou, G. S. Tria, D. J. Edmonds, Angew. Chem. 2008, 120, 1804 – 1807; Angew. Chem. Int.

Ed. 2008, 47, 1780 – 1783; b) J. Hayashida, V. H. Rawal, Angew. Chem. 2008, 120, 4445 – 4448; Angew. Chem. Int. Ed. 2008, 47, 4373 – 4376; c) S. Y. Yun, J.-C. Zheng, D. Lee, Angew. Chem. 2008 Early view; Angew. Chem. Int. Ed. 2008, Early view.

O

NMR spectra for

compounds