M C. White Chem 153 Hydrogenation-157 Week of october 15. 2002 BINAP-Ru complexes: Noyori increases the substrate scope for asymmetric hydrogenations The first report: asymmetric hydrogenation of (2r-enamides Interestingly, E-enamides are completely unreactive towards these hydrogenation conditions. No air-sensitive rationale for this has been presented Ph HICO HcO NCOCH3 NCOCH3 AcO Aco OAc(R-1(0.5-1mo) EtOH: CH CI(5: 1 ) H,(4 atm), 23C NCH3 OCH3 OCH NoyoriJACS 1986(108)7117 Noyori ACEE 2002 (41)2008 92% yield 95%ee morphine Asymmetric hydrogenation of allylic and homoallylic alcohols regioselectivity: allylic and homoallylic alcohols are hydrogenated whereas bis homoallylic and higher analogues are left untouched. E-olefin (S}1001mol% allylic olefin geometry may dictate stereochemical outcome of the 97 to >99% yields hydrogenation. Practical consequence Z-olefin to obtain high ee's must start with (S}102mol% stereochemically pure olefins MeOH,H,18-20°℃ (S)-citronellol NoyoriJACS 1987(109)1596M.C. White, Chem 153 Hydrogenation -157- Week of October 15, 2002 BINAP-Ru complexes: Noyori increases the substrate scope for asymmetric hydrogenations The first report: asymmetric hydrogenation of (Z)-enamides NCOCH3 H3CO AcO OAc OCH3 P Ph2 Ru(II) Ph2 P O O O O (0.5-1 mol%) EtOH:CH2Cl2 (5:1), H2 (4 atm), 23oC NCOCH3 H3CO AcO OAc OCH3 NCH3 HO HO O H morphine 92% yield 95% ee Interestingly, E-enamides are completely unreactive towards these hydrogenation conditions. No rationale for this has been presented. Noyori JACS 1986 (108) 7117. Noyori ACIEE 2002 (41) 2008. (R)-1 air-sensitive Asymmetric hydrogenation of allylic and homoallylic alcohols: P Tol2 Ru(II) Tol2 P O O O O 0.01 mol% MeOH, H2, 18-20oC (S)-1 OH OH geraniol nerol 0.2 mol% MeOH, H2, 18-20oC (S)-1 OH OH (R)-citronellol 97 to >99% yields (S)-citronellol 96% ee 98% ee allylic olefin geometry may dictate the stereochemical outcome of the hydrogenation. Practical consequence: to obtain high ee's must start with stereochemically pure olefins. E-olefin Z-olefin regioselectivity: allylic and homoallylic alcohols are hydrogenated whereas bis homoallylic and higher analogues are left untouched. Noyori JACS 1987 (109) 1596