D. A. Evans Enantioselective c=o Addition Ketone reduction Chem 115 Stoichiometric Chloroborane Reducing Agents Enantioselective Reducing Agent N-Methylephedrine LIAIH4, (3, 5-Xylenol)2 2 [LiAl(ig)(OAr)2H] 5090% (R)-Alpine borane Me (S)-BINAL-H Darvon alcohol, LIAIH4 LIAl(ig)2H Reviews: Midland, Asymmetric Synthesis, Vol 2, p 45. 3, 3-dimethyl-2-butanone 25.C, 12 days 5% Granbois, Asymmetric Synthesis, Vol 2, p 71 Brown. Accts. Chem. Res. 1992. 25. 16-24 25°C,2days 91% Singh, Synthesis 1992, 605-617 Reductions of Representative Carbonyl Compounds Brown's model Alpine-Borane 72-92%ee 59.89%ee.78%ee.R=Me 90%e e R=CO Me d Large ligand (RU) BINAL-H 84.96%ee.>95%ee.95-100%ee. (57%ee, R=i-Pr) (71%ee,R=-Pr) Rs Favored TS Small ligand(Rs) Darvon-LiAIH4 34-90%e e. 25% 15-75%ee Less hindered aliphatic ketones are not reduced with useful Brown, J. Org. Chem. 1986, 51, 3394 N-Methylephedrine-75-90%ee. 78-98%ee levels of enantioselectivity 19A-05 Asym Red-11/19001:48PM00 00 000 000 Brown's Model D. A. Evans Enantioselective C=O Addition: Ketone Reduction Chem 115 (R)-Alpine Borane Li + (S)-BINAL-H Enantioselective Reducing Agents Darvon alcohol, LiAlH4 [LiAl(lig)2H] N-Methylephedrine, LiAlH4, (3,5-xylenol)2 [LiAl(lig)(OAr)2H] - Reviews: Midland, Asymmetric Synthesis, Vol 2, p 45- Granbois, Asymmetric Synthesis, Vol 2, p 71- Brown, Accts. Chem. Res. 1992, 25, 16-24 Singh, Synthesis 1992, 605-617 78% e.e. R=Me 90% e.e. R=CO2Me 95 - 100% e.e. (71% ee, R=i-Pr) 15 - 75% e.e. ---- 59 - 89% e.e. >95% e.e. 25% e.e. 78 - 98% e.e. (cyclic ketones) 72 - 92% e.e. 84 - 96% e.e. (57% ee, R=i-Pr) 34 - 90% e.e. 75 - 90% e.e. Alpine-Borane BINAL-H Darvon-LiAlH4 N-Methylephedrine- LiAlH4 Reagent Reductions of Representative Carbonyl Compounds THF 50 - 90% Less hindered aliphatic ketones are not reduced with useful levels of enantioselectivity 2 Brown, J. Org. Chem. 1985, 50, 5446 98% 98% 79% 95% 91% -25 °C -25 °C -25 °C 25°C, 12 days 25°C, 2 days acetophenone butyrophenone 2,2-dimethylpropiophenone 3,3-dimethyl-2-butanone 2,2-dimethylcyclohexanone Ketone Reaction Conditions % ee Brown, J. Org. Chem. 1986, 51, 3394 Brown, J. Org. Chem. 1988, 53, 2916 Stoichiometric Chloroborane Reducing Agents Small ligand (Rs) Large ligand (RL) Favored TS Me B O O Al H OEt Bn Ph Ph Me Me2N OH NMe2 OH Me O R R O R O Me B Cl RL RS O OH RL RS X B Me Me Me H H O RL RS Y 19A-05-Asym Redn-1 1/19/00 1:48 PM