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

Abstract

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(sp 2 )-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.

Rhodium‐Catalyzed Asymmetric Transfer Hydrogenation of Heterocyclic Diaryl Ketones: Facile Access to Key Intermediate of Baloxavir†

“…[ 10 ] Subsequently, the tethered rhodium has been applied in the dynamic kinetic asymmetric transfer hydrogenation of α‐cyano ketones [ 11 ] and 3‐hydroxy‐4‐substituted‐maleimide derivatives [ 12 ] by our group and β‐substituted α‐diketones by Fang and coworkers. [ 13 ] As a continuation of investigation on asymmetric transfer hydrogenation, herein, we disclose a highly enantioselective asymmetric hydrogenation of heterocyclic diaryl ketones catalyzed by tethered rhodium catalyst (Scheme 1d).…”

Rhodium-Catalyzed Asymmetric Transfer Hydrogenation of Heterocyclic Diaryl Ketones: Facile Access to Key Intermediate of Baloxavir

“…[10] Subsequently, the tethered rhodium has been applied in the dynamic kinetic asymmetric transfer hydrogenation of α-cyano ketones [11] and 3-hydroxy-4-substituted-maleimide derivatives [12] by our group and β-substituted α-diketones by Fang and coworkers. [13] As a continuation of investigation on asymmetric transfer hydrogenation, herein, we disclose a highly enantioselective asymmetric hydrogenation of heterocyclic diaryl ketones catalyzed by tethered rhodium catalyst (Scheme 1c). We initiated our investigation with the optimization of the reaction conditions for the asymmetric transfer hydrogenation of 1a , and the results were summarized in Table 1.…”

Asymmetric Transfer Hydrogenation of Cyclobutenediones

“…The challenges arise first from the regioselectivity control, wherein the two carbonyls are both reactive and the double bond could be attacked from either side; the second reason is that CBDs have been reported to undergo facile ring-opening reactions, leading to linear or ring-expanded compounds . Our group has been interested in both kinetic resolution and 1,2-diketone chemistry, with a recent focus on the asymmetric transfer hydrogenation (ATH) of various ketone molecules . In this article, we describe the first ATH of CBDs in a highly regio- and stereoselective fashion.…”