Reaction Steps
A solution of sodium carbonate (281 mg, 2.65 mmol) in water (5 mL) was added whilst stirring to a solution of (3R, 3aR, 6S, 6aS)-3-hydroxyhexahydro-2H-furo[3,2-b]pyrrol-6-yl 4-methylbenzenesulfonate in 1,4-dioxane (5 mL). A solution of benzyl chloroformate (0.225 mL, 1.96 mmol) in 1,4-dioxane (2.5 mL) was added over 20 minutes then the mixture stirred for 35 minutes, then water (50 mL) was added and the product extracted into dichloromethane (2×50 mL). The organic layer was washed with brine (50 mL), then dried (Na2SO4), filtered and reduced in vacuo to leave a residue. Flash chromatography over silica, eluting with ethyl acetate:heptane mixtures 25:75 to 50:50 gave bicyclic alcohol (34) (518 mg, 95%) as a white solid. TLC (Rf=0.25, EtOAc:heptane 3:2), analytical HPLC single main peak, Rt=17.86 min., HPLC-MS 434.2 [M+H]+, 456.1 [M+Na]+, 889.3 [2M+Na]+; [α]D16.5−23.1° (c=1.190, CHCl3); δH (500 MHz, CDCl3) mixture of rotamers major:minor 3:2; 1.96 (0.4H, d, J=4.11 Hz, OH minor), 2.43 (1.8H, s, aryl-CH3 major), 2.44 (1.2H, s, aryl-CH3 minor), 2.59 (0.6H, d, J=3.42 Hz, OH major), 3.35 (0.4H, dd, J=13.43 and 3.71 Hz, CbzNCH2 minor), 3.41 (0.6H, dd, J=13.31 and 3.80 Hz, CbzNCH2 major), 3.74-3.88 (3H, m, 2×OCH2CHOH and 1×CbzNCH2), 4.29 (0.4H, s, CbzNCHminor), 4.31 (0.6H, s, CbzNHCH major), 4.37 (0.4H, brs, OCH2CHOH minor), 4.49 (0.6H, brs, OCH2CHOH major), 4.51 (0.6H, d, J=4.59 Hz, TsOCHCH major), 4.64 (0.4H, brd, J=4.44 Hz, TsOCHCH minor), 4.77 (0.4H, d, J=3.43 Hz, TsOCHCH minor), 4.79 (0.6H, d, J=3.53 Hz, TsOCHCH major), 5.06-5.13 (1.6H, m, CH2Ph), 5.21 (0.4H, d, J=12.22 Hz, CH2Ph minor), 7.30 (7H, m, aromatic-CH and CH3CCH), 7.75-7.79 (2H, m, aromatic OSO2CCH); δC (125 MHz, CDCl3) 21.658 (aryl-CH3), 51.015/51.082 (CbzNCH2), 67.511/67.622 (CH2Ph), 67.953/68.902 (CbzNCH), 74.375/74.420 (OCH2CHOH), 75.322/76.156 (OCH2CHOH), 79.944/80.600 (TsOCHCH), 83.537/84.651 (TsOCHCH), 127.791, 127.837, 127.942, 128.011, 128.382, 128.485, 128.558, 128.703 and 130.102 (aromatic CH), 133.021/133.087 (CHOSO2C quaternary), 135.895/136.018 (Cbz quaternary), 145.441 (CH3C quaternary), 153.976/154.591 (Cbz C═O).
