Dual Pathway for the Asymmetric Transfer Hydrogenation of α‐Ketoimides to Chiral α‐Hydroxy Imides or Chiral α‐Hydroxy Esters

Abstract

In an enantioselective reaction, we expect to obtain two types of chiral products through a controllable strategy in asymmetric catalysis. Herein, we develop Ru‐catalysed asymmetric transfer hydrogenation of α‐ketoimides to realise an enantioselective construction of chiral α‐hydroxy imides or chiral α‐hydroxy esters. The transformation of α‐ketoimides catalysed by (S,S)‐[RuCl(η6‐mesitylene)diamine] can afford various chiral α‐hydroxy imides with high yields and enantioselectivities, whereas that catalysed by (S,S)‐[RuCl(η6‐hexamethylbenzene)diamine] gives the desirable chiral α‐hydroxy esters through a slight adjustment of the reaction conditions. The method described here is a controllable organic transformation with sodium formate as a hydrogen source under mild reaction conditions, and the benefit of this transformation is that various chiral α‐hydroxy imides or α‐hydroxy esters can be obtained selectively from α‐ketoimides.

Asymmetric Transfer Hydrogenation of α-Keto Amides; Highly Enantioselective Formation of Malic Acid Diamides and α-Hydroxyamides

“…A report by Bhanage and Mishra, using the 3C tethered catalyst 2 , demonstrated a practical approach to the synthesis of asymmetric mandelimides, (Figure A). ATH of α-keto/enol lactams, coupled to dynamic kinetic resolution (DKR), using catalyst 3 , gave products in high dr and ee (Figure B). , Other catalytic methods have also been used for the asymmetric reduction of α-keto amides, including biocatalysis, Cu-catalyzed hydrosilylation, and asymmetric hydrogenation. − ATH of the closely related α-keto imides in high ee, using Noyori–-Ikariya catalysts (Figure C) was reported by Liu et al The ATH of analogous α-keto esters, using the same class of catalyst, has also been reported in detail …”