Reaction Steps
[(3R,5R)-3,5-Bis[(tert-Butyldimethylsilyl)oxy]-4-[3′-(methoxymethoxy)propylidene]cyclohexanone (11). To a solution of hydroxy ketone 9 (40 mg, 117 μmol) in anhydrous CH2Cl2 (0.4 mL) at −50° C. was added 2,6-lutidine (32 μL, 274 μmol) and t-butyldimethylsilyl triflate (56 μL, 240 μmol). The mixture was stirred for 5 min at −50° C., then it was allowed to warm up to −15° C. and stirred at this temperature for additional 30 min. Benzene and water was added and the mixture was poured into water and extracted with benzene. The extract was washed with saturated CuSO4 and water, dried (MgSO4), and evaporated. The oily residue was redissolved in hexane, and purified by flash chromatography on silica. Elution with hexane/ethyl acetate (95:5) gave pure protected ketone 11 as a colorless oil (30 mg, 57%; 66% based on recovered substrate) and unreacted 9 (6 mg). 11: [α]24D−26° (c 0.30 CHCl3); 1H NMR (400 MHz, CDCl3) δ 0.019 and 0.065 (3H and 9H, each s, 4×SiCH3), 0.838 and 0.912 (9H and 9H, each s, 2×Si-t-Bu), 2.32 (1H, dd, J=14.1, 10.4 Hz, 2α-H), 2.45 (3H, br m, ═C—CH2 and 6α-H), 2.53 (1H, ddd, J=14.4, 3.2, 2.1 Hz, 6β-H), 2.75 (1H, ddd, J=14.1, 5.6, 2.1 Hz, 21-H), 3.36 (3H, s, O—CH3), 3.58 (2H, m, CH2—CH2—O), 4.62 (2H, s, O—CH2—O), 4.75 (1H, ddd, J=10.4, 5.6, 1.4 Hz, 3β-H), 5.01 (1H, t, J˜3.2 Hz, 5α-H), 5.70 (1H, dt, J=1.7, 7.8 Hz, ═CH); 13C NMR (125 MHz) δ −5.08 (Si—CH3), −5.06 (Si—CH3), −5.05 (Si—CH3), −5.00 (Si—CH3), 17.9 [C(CH3)3], 25.5 [C(CH3)3], 27.7 (CH2—CH2—C═), 50.2 (C6), 52.4 (C2), 55.2 (O—CH3), 65.8 (C3), 67.1 (O—CH2—CH2), 67.8 (C5), 96.4 (O—CH2—O), 118.5 (═C—CH2), 141.5 (C4), 207.5 (C1); MS (EI) m/z (relative intensity) 443 (M++H, 2), 427 (M+−CH3, 5), 401 (55), 371 (15), 339 (20), 75 (100); exact mass calcd for C12H43O4Si2 (M+−CH3) 427.2700, measured 427.2701.
