M C. White, Chem 153 Hydrogenation -158 Week of october 15. 2002 BINAP-Ru complexes: Noyori increases the substrate scope for asymmetric hydrogenations The first demonstration of high asymmetric induction in the hydrogenation of substrates lacking an acylamino group asymmetric hydrogenation of a, B-unsaturated carborylic acids CO,H HRc CH The degree of asymmetric induction is significantly affected by the H2 pressure in a substrate specif H2(4am91%e manner. The implication of this is that a range of H2 H,(101 atm): 50%ee pressures must be screened to achieve optimal CO,H (S)-10.5-1mol%) asymmetric induction on a substrate by substrate basis. O,H No trend was observed and no rationale for the MeOH,H2,15-30°℃ emperical observation was given. (S o ee H2(112 atm) 2h COH leOH,H2(135atm)15-30 HcO HyCO (S)-Naproxen NoyoriJOC 1987(52)3174M.C. White, Chem 153 Hydrogenation -158- Week of October 15, 2002 BINAP-Ru complexes: Noyori increases the substrate scope for asymmetric hydrogenations The first demonstration of high asymmetric induction in the hydrogenation of substrates lacking an acylamino group: asymmetric hydrogenation of α,β-unsaturated carboxylic acids The degree of asymmetric induction is significantly affected by the H2 pressure in a substrate specific manner. The implication of this is that a range of H2 pressures must be screened to achieve optimal asymmetric induction on a substrate by substrate basis. No trend was observed and no rationale for the emperical observation was given. H3C CH3 CO2H P Ph2 Ru(II) Ph2 P O O O O (0.5-1 mol%) MeOH, H2, 15-30oC (S)-1 H3C CH3 CO2H (S) H2 (4 atm): 91% ee H2 (101 atm): 50% ee CO2H Ph CO2H (S) H2 (4 atm): 48% ee H2 (112 atm): 92% ee Asymmetric Synthesis of (S)-Naproxen: H3CO CO2H (0.5 mol%) MeOH, H2 (135 atm), 15-30oC (S)-1 H3CO CO2H (S)-Naproxen 92% yield 97% ee Noyori JOC 1987 (52) 3174