Dynamic Kinetic Resolution of β-Substituted α-Diketones via Asymmetric Transfer Hydrogenation

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.

Automated summary

In this study, a unique dynamic kinetic resolution (DKR) mode was used to achieve the highly selective semi-transfer hydrogenation of unsymmetrical alpha-diketones. The distal carbonyl group was reduced while the proximal carbonyl remained untouched, resulting in the synthesis of enantioenriched acyclic ketones with alpha-hydroxy-alpha'-C(sp2)-functional groups. These products represent a new class of compounds that have not been previously reported. The utility of the synthesized compounds was demonstrated through further transformations, including the rapid synthesis of drug molecules. DFT calculations and control experiments were conducted to gain mechanistic insights into the highly selective semihydrogenation.