1: With n-butyllithium in tetrahydrofuran; hexane T=-75°C; 2 h; Large scale reaction; 2: With tri-isopropoxy-borane in tetrahydrofuran; hexane T=-75 - -10°C; 3 h; Enzymatic reaction; 3: With sulfuric acid; water in tetrahydrofuran; hexane T=40°C; 4 h; Enzymatic reaction;

2: 90 percent / LiOH*H2O / dioxane; H2O / 1) RT, 5 h, ultrasound, 2) 50 deg C, 15 h 3: 1-chloro-1-(N,N-dimethylamino)-2-methyl-1-propene / CH2Cl2 / 0.25 h / 0 °C 4: 1) n-BuLi / 1) THF, hexane, -70 deg C, 20 min, 2a) -70 deg C to RT, 2b) RT, 15 h 5: H2 / <(R)-(RuCl(p-cymene)BINAP>Cl / methanol; CH2Cl2 / 72 h / 50 °C / 37503 Torr 6: 97 percent / aq. HOAc / 3 h / 50 °C 7: 95 percent / tetramethylguanidine / tetrahydrofuran / 1) -70 to -30 deg C, 5 h, 2) -30 deg C, 2 d, 3) RT, 15 h 8: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 9: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 10: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 11: 71 percent / HOAc / H2O / 4 h / 50 °C 12: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 13: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 14: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 15: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 16: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 17: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme

1: With n-butyllithium in tetrahydrofuran; hexane T=-75°C; 2 h; Large scale reaction; 2: With tri-isopropoxy-borane in tetrahydrofuran; hexane T=-75 - -10°C; 3 h; Enzymatic reaction; 3: With sulfuric acid; water in tetrahydrofuran; hexane T=40°C; 4 h; Enzymatic reaction;

2: 74 percent / N-bromosuccinimide (NBS), 2,6-lutidine, H2O / acetonitrile / 0.08 h / 0 °C 3: 99 percent / LiCl, 1,8-diazabicyclo<5.4.0>undec-7-ene (DBU) / acetonitrile / 1 h / Ambient temperature 4: 95 percent / NEt3/C / ethanol; CHCl3 / 48 h / Ambient temperature 5: 100 percent / LiOH, H2O / dioxane / 12 h / Ambient temperature 6: 100 percent / H2, <Rh<cycloocta-1,5-diene><(R,R)-1,2-bis<2-(2-methoxyphenyl)phenylphosphino>ethane>>+*BF4- / methanol / 72 h / Ambient temperature 7: 82 percent / dicyclohexylcarbodiimide (DCC), 4-dimethylaminopyridine (DMAP) / ethyl acetate / 12 h / -15 - 20 °C 8: 84 percent / pyridinium-p-toluene sulphonate, H2O / acetone / 6 h / Heating 9: 93 percent / LiCl, 1,8-diazabicyclo<5.4.0>undec-7-ene (DBU) / acetonitrile / 2 h / Ambient temperature 10: NEt3/C / ethanol; CHCl3 / 48 h / Ambient temperature 11: H2, <Rh<cycloocta-1,5-diene><(R,R)-1,2-bis<2-(2-methoxyphenyl)phenylphosphino>ethane>>+*BF4- / methanol / 72 h / Ambient temperature 12: 100 percent / 6 M HCl / dioxane / 2 h / 20 °C 13: 71 percent / N-(3-dimethylaminopropyl)-N'-ethylcarboimide hydrochloride (EDC), hydroxybenzotriazole / CH2Cl2 / 14 h / 15 - 20 °C 14: 85 percent / AcOH, H2O / 7 h / 50 °C 15: Bu4NF / dimethylformamide / 1 h / Ambient temperature 16: 95 percent / N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) / CH2Cl2 / 14 h / -15 - 20 °C 17: 1.) 6 M HCl, 2.) NaHCO3 / 1.) dioxane, CH2Cl2, 0 deg C, 2.) CHCl3, 20 deg C, 5 min 18: 70 percent / trimethylsilyl trifluoromethane sulphonate, thioanisole, CF3CO2H / 0.5 h / Ambient temperature View Scheme