Advancement in Catalytic Asymmetric Hydrogenation of Ketones and Imines, and Development of Asymmetric Isomerization of Allylic Alcohols

Abstract

Catalytic asymmetric hydrogenation of ketones through the "metal-ligand cooperative mechanism" has been improved in terms of the efficiency, stereoselectivity, and scope of substrates by varying the arrangement of the catalyst structure and reaction conditions. Imino compounds are also smoothly converted to the optically active amines with appropriate catalysts. This type of catalyst exhibits excellent performance on the asymmetric isomerization of primary allylic alcohols into the optically active aldehydes. This personal account describes recent progress on these topics.

Double Asymmetric Hydrogenation of Linear β,β‐Disubstituted α,β‐Unsaturated Ketones into γ‐Substituted Secondary Alcohols using a Dual Catalytic System

“…The catalytic species (type ( I )) is a Ru hydride coordinated by a diamine derivative that has at least one NH 2 group (Scheme a). The catalyst type ( I ) smoothly hydrogenates C=O groups through a six‐membered transition structure in which the H δ− ‐Ru δ+ ‐N δ− ‐H δ+ quadrupole fits with the C δ+ =O δ− dipole . The less polar C=C groups are not significantly reduced by this catalytic system.…”

“…The presence of another coordinative functionality (X) in the molecule promotes the alkene hydrogenation with formation of a stable chelate intermediate . In general, the σ‐coordinative C=O groups are much more slowly reduced with the catalyst ( II ) . We expected that, when type ( I ) and ( II ) were reversibly formed as shown in Scheme a, both polar C=O and less polar C=C groups would be smoothly hydrogenated through the dual catalysis process.…”

“…Generally, chiral catalysts for this transformation are appropriately designed according to the chemical features of the substrates. We have reported asymmetric hydrogenation of ketones catalyzed by chiral Ru complexes . The catalytic species (type ( I )) is a Ru hydride coordinated by a diamine derivative that has at least one NH 2 group (Scheme a).…”

“…The diastereo‐ and enantioselectivity were somewhat decreased in the reaction with the ( S )‐DM‐SEGPHOS/( S )‐DEAPEN/Ru II complex ( S P , S N )‐ 6 b (entry 6). The mono‐hydrogenation product 3 a was obtained quantitatively with the complex ( S P , S N )‐ 7 bearing the strongly binding diamine DPEN (entry 7) . Double hydrogenation of 1 a was observed in tert ‐butyl alcohol, but the yield and stereoselectivity of 2 a were lower than those in 2‐propanol (entry 8).…”

“…A plausible mechanism for the double hydrogenation of α,β‐unsaturated ketone 1 a with the ( S P , S N )‐ 6 a / t ‐C 4 H 9 OK catalyst system consisting of dual catalytic cycles ( I ) and ( II ) is shown in Scheme . The catalytic cycle ( I ) hydrogenates α,β‐unsaturated ketone 1 a to the allylic alcohol ( R )‐ 3 a , and the cycle ( II ) converts ( R )‐ 3 a into the saturated alcohol (2 R ,4 S )‐ 2 a . Catalytic cycle ( I ): ( S P , S N )‐ 6 a is converted to the catalytic cycle species with the hydride source, H 2 , in a base containing alcoholic solvent.…”