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

• Published in: Journal of the American Chemical Society 2023-01, Vol.145 (1), p.585-599
• Main Authors: Chen, Ting, Liu, Wenjun, Gu, Wei, Niu, Shengtong, Lan, Shouang, Zhao, Zhifei, Gong, Fan, Liu, Jinggong, Yang, Shuang, Cotman, Andrej Emanuel, Song, Jinshuai, Fang, Xinqiang
• Format: Article
• Language: English
• Subjects: Catalysis; Hydrogenation; Ketones; Kinetics; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.2c11149

Developing innovative dynamic kinetic resolution (DKR) modes and achieving the highly regio- and enantioselective semihydrogenation of unsymmetrical α-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 α-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 α-hydroxy-α′-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 gain more mechanistic insights into the highly selective semihydrogenation.