Reaction Steps
(1S, 55, 65)-5-Benzenesulfonyl-6-methylcyclohex-3-enol (22aMe). To a solution of epoxy-dienyl sulfone SS-9a (0.377 g, 1.6 mmol) in THF (10 mL) at −78° C. was slowly added LiHMDS (1.8 mL, 1.8 mmol). The solution was stirred for 30 min, followed by addition of sat'd solution of NH4Cl (5 mL). Et2O (5 mL) was added to the mixture and separated. The aqueous layer was extracted with Et2O (2×5 mL) and the organic layers are combined, dried over MgSO4 and concentrated. The resulting solid was dissolved in THF (10 mL) at −78° C. was added MeLi (3.4 mL, 4.8 mmol) in Et2O over a period of 15 min, addition must be done slowly to minimize aromatization. The orange solution was stirred for 20 min and then quenched by slowly adding a solution of sat'd NH4Cl (5 mL). The temperature was allowed to rise to 25° C. and diethyl ether was added (10 mL). The organic layer was separated and the aqueous layer was extracted with diethyl ether (2×10 mL). The organic layers were combined, dried over MgSO4, and concentrated. The resultant mixture was filtered through a one inch silica gel plug eluting with a 3:1 mixture of ethyl acetate/hexanes to give 0.370 g of the desired sulfone as an oil in 92% yield and a 9:1 ratio of diastereomers. 1H NMR (CDCl3): δ 7.88 (m, 2H), 7.61 (m, 3H), 5.97 (m, 1H), 5.54 (m, 1H), 4.17 (m, 1H), 3.62 (m, 1H), 2.47 (m, 1H), 2.28 (m, 1H), 2.05 (m,1H), 1.77 (m, 1H), 1.07 (d, J=6.9 Hz, 3H). 13C NMR (CDCl3): δ137.9 133.7, 132.3, 129.1, 128.9, 117.5, 68.6, 66.2, 32.7, 30.3, 15.5. LRMS: (CI) highest mass 253 (M+H), base peak 143. HRMS: (CI) calculated for C13H16O3S 253.0898, found 253.0905 (1S, 55, 65)-5-Benzenesulfonyl-6-isopropylcyclohex-3-enol (22aPr). To a solution of epoxy-dienyl sulfone SS-9a (0.350 g, 1.5 mmol) in THF (10 mL) at −78° C. was slowly added LiHMDS (1.6 mL, 1.6 mmol). The solution was stirred for 30 min, followed by addition of a sat'd solution of NH4Cl (5 mL). Et2O (5 mL) was added to the mixture and separated. The aqueous layer was extracted with Et2O (2×5 mL) and the organic layers are combined, dried over MgSO4 and concentrated. To the resulting solid in THF (10 mL) at −78° C. was slowly added iPrMgCl (3.7 mL, 7.4 mmol) over a period of 15 min, addition must be done slowly to minimize aromatization. The orange solution was stirred for 20 min and the temperature allowed to slowly rise to −10° C. over a period of 1 h. The solution was quenched by slowly adding a solution of sat'd NH4Cl (10 mL). The temperature was allowed to rise to 25° C. and diethyl ether was added (10 mL). The organic layer was separated and the aqueous layer was extracted with diethyl ether (2×10 mL). The organic layers were combined, dried over MgSO4, and concentrated. The resultant mixture was filtered through a one inch silica gel plug eluting with a 3:1 mixture of ethyl acetate:hexanes to give 0.375 g of the desired sulfone as an oil in 89% yield and a 30:1 ratio of diastereomers. 1H NMR (CDCl3): δ 7.88 (m, 2H), 7.59 (m, 3H), 5.99 (m, 1H), 5.66 (m, 1H), 4.31 (m, 1H), 3.77 (m, 1H), 2.17 (m, 4H), 0.81 (d, J=6.9 Hz, 3H), 0.76 (d, J=6.9 Hz, 3H). 13C NMR (CDCl3): δ 137.6, 133.7, 133.2, 129.1, 129.0, 118.5, 65.6, 63.9, 42.6, 31.5, 24.8, 22.1, 19.7. LRMS: (CI) highest mass 281 (M+H), base peak 143. HRMS: (CI) calculated for C15H20O3S 281.1211, found 281.1199. (2R, 3S, 4S)-(3-Benzenesulfonyl-2-methylcyclohept-4-enyloxy)-tert-butyldimethylsilane (30). To a solution of dienyl sulfone 2 (FIG. 1) (0.322 g, 0.89 mmol) in THF (9 mL) at −78° C. was slowly added MeLi (1.8 mL, 1.95 mmol) in Et2O over a period of 10 min. The orange solution was stirred for 20 min and was then quenched by slowly adding a solution of sat'd NH4Cl (10 mL). The temperature was allowed to rise to 25° C. and diethyl ether was added (10 mL). The organic layer was separated and the aqueous layer was extracted with diethyl ether (2×10 mL). The organic layers were combined, dried over MgSO4, and concentrated. The resultant mixture was filtered through a one inch silica gel plug eluting with a 3:1 mixture of ethyl acetate:hexanes to give 0.317 g of the desired sulfone as an oil in 94% yield and a 20:1 ratio of diastereomers. 1H NMR (CDCl3): δ7.87 (m, 2H), 7.58 (m, 3H), 6.03 (m, 1H), 5.87 (m, 1H), 4.60 (m, 1H), 3.83 (m, 1H), 2.42 (m, 4H), 1.77 (m, 1H), 1.63 (m, 1H), 1.41 (m, 1H), 1.09 (d, J=7.0 Hz, 3H), 0.85 (s, 9H), −0.02 (s, 3H), −0.08 (s, 3H). 13C NMR (CDCl3): δ 139.0, 134.9, 133.4, 129.1, 128.5, 123.2, 73.6, 62.3, 35.9, 27.1, 25.7, 20.0, 17.9, 12.3, −5.1. LRMS: (CI) highest mass 381 (M+H), base peak 249. HRMS: (CI) calculated for C20H32O3SSi 381.1920, found 381.1917.
