D. A. Evans Enantioselective c=o Addition Ketone Reduction -2 Chem 115 Improved Enantioselectivity with Alphatic Ketones Miscellaneous Chiral Borohydride Reagents chem.1989,54, Rxn time Brown, J. Org. Chem. 1988, 53, 1231 Ketone THF,23°℃)%conV.%ee Brown. J. Am. Chem. Soc. 1988. 110 1539 7 day 3-methyl-2-butanone 2 days 100%88% cyclohexyl methyl ketone 4 days 86% R=t-Bu 87%ee. 92%ee. 4 days 72% cyclohexenone 4 days 50%79% THF,-78°C Brown Tetrahedron Let. 1991. 32 6691 PhCoHN-+H HT NHCOP LiBH4/EtOH Rxn time (1:3:13) Ketone (THF,-25°℃)%com.%ee >99% 78°C.THF 2, 2-dimethylcyclopentanone trans-4-phenyl-3-buten-2-one 14d 2-cyclohexenone 60%74% -BuOH replacing EtOH OH 83%e e (R) 4-phenyl-3-butyn-2-one 5h 82%33% Soai. Chem. Commun. 1987. 801: Chem. Commun. 1986. 1018 19A-06- Asym Red-21/19001:48PMLiBH4 EtOH ( 1 : 3 : 1.3 ) -78°C, THF 73% 84% e.e. 83% e.e. (R) * 72% * t-BuOH replacing EtOH Soai, Chem. Commun. 1987, 801; Chem. Commun. 1986, 1018 Brown, J. Am. Chem. Soc. 1988, 110, 1539 Brown, J. Org. Chem. 1988, 53, 1231 Brown, J. Org. Chem. 1986, 51, 1934 Miscellaneous Chiral Borohydride Reagents 86 - 98% e.e. R = alkyl, aryl THF, -78°C 75 - 85% 97% e.e. 87% e.e. 92% e.e. R = t-Bu = i-Pr = Et THF, -78°C 90 - 95% K - + Brown, Tetrahedron Let. 1991, 32, 6691 Ketone Rxn time (THF, -25°C) % Conv. % ee Brown, J. Org. Chem. 1989, 54, 4504 % Conv. % ee Rxn time Ketone (THF, 23°C) acetophenone 3-methyl-2-butanone cyclohexyl methyl ketone 2,2-dimethylcyclopentanone trans-4-phenyl-3-buten-2-one 2-cyclohexenone 4-phenyl-3-butyn-2-one 24 h 2 d 3 d 24 h 14d 7 d 5 h 80% 65% 65% 80% 60% 60% 82% >99% 95% 97% >99% 82% 74% 33% 2 Improved Enantioselectivity with Alphatic Ketones 72% 88% 86% 76% 72% 79% 50% 100% 60% 30% 40% 50% 7 days 2 days 4 days 14 days 4 days 4 days acetophenone 3-methyl-2-butanone cyclohexyl methyl ketone cyclohexyl ethyl ketone cyclopentyl methyl ketone cyclohexenone D. A. Evans Enantioselective C=O Addition: Ketone Reduction-2 Chem 115 B Cl B O Cl tBu Bzl B O H O O O O O S Ph R O Ph R OH OEt R O O O OH R OEt S PhCOHN NHCOPh CO2H CO2H H H N Me O OH Me N Cl O OH Cl 19A-06-Asym Redn-2 1/19/00 1:48 PM