Dynamic Kinetic Resolution of beta-Substituted alpha-Diketones via Asymmetric Transfer Hydrogenation

摘要

Developing innovative dynamic kinetic resolution (DKR) modes and achieving the highly regio-and enantioselective semihydrogenation of unsymmetrical alpha-diketones are two formidable challenges in the field of contemporary asymmetric (transfer) hydrogenation. In this work, we report the highly regio-and stereoselective asymmetric semi-transfer hydrogenation of unsymmetrical alpha-diketones through a unique DKR mode, which features the reduction of the carbonyl group distal from the labile stereocenter, while the proximal carbonyl remains untouched. Moreover, the protocol affords a variety of enantioenriched acyclic ketones with alpha-hydroxy-alpha '-C(sp2)-functional groups, which represent a new product class that has not been furnished in known arts. The utilities of the products have been demonstrated in a series of further transformations including the rapid synthesis of drug molecules. Density functional theory calculations and plenty of control experiments have also been conducted to ga i n more mechanistic insights into the highly selective semihydrogenation.