D. A. Evans Enantioselective c=o Addition other methods Chem 115 Enantioselective Hydrosilylation The Meenwein-Ponndorf-Verley reduction Nishiyama, Organometallics, 1989, 8, 846 Nishiyama, Organometallics, 1991, 10, 508 Nishiyama, J. Org. Chem, 1992, 57, 4306 Rhcl Me2HC CHMe2 CHMez The Ligand The Catalyst (1 he Oppenauer Oxidation Woodward: 1945 W. von E Doering: 1950 1, Ph2 SiH 10%+-Buo-Sml2 Kagan 1984 65°C Additve catalyst conditions Kagan, J.Org. Chem, 1984, 48, 2045 R^R210%m 17% 25°C F3OE235% 0°C,14h82% Kagan, Nouv. J. Chim. 1986, 10, 229-232 AgBF4 5C,5h93%(90%yed) 1.0mo% DEIPSO PMBO PMBO a Representative Reductions A 25°C,30min Hydride Eq: AX ROH YId Eq ROH 95%ee(91% yield) 27% ee(60% yield) 70% ee(94% yield) Na/NH3 40% Sml2 /i-Pr 98% with S Kaldor, J. Am. Chem. Soc. 1990. 112.7001 19A-09-other Methods-1 1/19/00 1: 48 PMwith S. Kaldor, J. Am. Chem. Soc., 1990, 112, 7001 SmI2 /i-PrOH 98.5 : 1.5 98% Na/NH3 60 : 40 40% LiAlH4 0 : 100 0% Hydride Eq : Ax ROH Yld Eq ROH Kagan, Nouv. J. Chim. 1986, 10, 229-232. 25°C, 30 min. SmI2 0.1 equiv Me2CHOH A Kagan, Tet. Lett, 1991, 32, 2355 Kagan, J. Org. Chem, 1984, 48, 2045 10 % SmI2 25 °C Kagan 1984 10 % t-BuO-SmI2 65 °C Woodward: 1945 W. von E. Doering: 1950 The Oppenauer Oxidation Al(O-iPr)3 80 °C 80 °C Al(O-iPr)3 The Meerwein-Ponndorf-Verley Reduction Exercise: Work out a rational methanism which explains the stereochemical outcome. Assume that the resting state of the the catalyst is in the +1 oxidation state. 95% ee (91% yield) 27% ee (60% yield) 70% ee (94% yield) AgBF4 4 % -5°C, 5h 93% (90% yield) 1.0 mol% BF3•OEt2 1.7 mol% 3.5 % 0 °C, 14h 82% 1.7 % rm temp no rxn catalyst conditions ee, % none Additve H3O+ additive 1, Ph2SiH ■ Representative Reductions ■ The Reaction: The Catalyst (1) RhCl3 The Ligand Nishiyama, J. Org. Chem, 1992, 57, 4306 Nishiyama, Organometallics, 1991, 10, 508 Nishiyama, Organometallics, 1989, 8, 846 D. A. Evans Enantioselective C=O Addition: Other Methods Chem 115 Enantioselective Hydrosilylation N O N N O Me2HC CHMe2 Me2HC CHMe2 O N N O N Rh Cl Cl Cl Me Ph O OSiR3 Me Me Ph Ph OH Me OEt OH O O OH Me OEt OH Me Me Me R1 R2 O OH R1 R2 Me Me OH O Me Me R1 R2 OH O R1 R2 R1 R2 O OH R1 R2 OH H Me H Me DEIPSO PMBO H H O Et O H O O Et H H PMBO DEIPSO Me H Me H O 19A-09-Other Methods-1 1/19/00 1:48 PM