Iridium-catalysed asymmetric hydrogenation of allylic alcohols via dynamic kinetic resolution

Abstract

Dynamic kinetic resolutions (DKRs) allow for the conversion of both enantiomers of starting material into a single enantiomer of product, hence avoiding the 50% yield limit observed in traditional kinetic resolutions. Transition-metal-catalysed variants have become an important and useful method in asymmetric synthesis. Here we report an asymmetric hydrogenation of allylic alcohols using an Ir–N,P-ligand complex via DKR. In contrast to the many DKRs involving carbonyl reduction, this methodology allows for DKR during alkene reduction. Mechanistic studies support the hypothesis that racemization of the substrate is achieved by cleavage and reforming of the oxygen–carbon bond. Under the cooperative dynamic kinetic asymmetric hydrogenation, a broad range of chiral alcohols containing two stereogenic centres were produced with excellent diastereoselectivities (up to 95:5) and enantioselectivities (up to 99%). Dynamic kinetic resolution (DKR) allows the conversion of both enantiomers of a racemic mixture into a single enantiomer of product, and requires both a stereoselective reaction and a means of rapidly racemizing the starting materials. Here, a highly stereoselective iridium-catalysed DKR of secondary allylic alcohols is reported, with mechanistic studies implying that substrate racemization is achieved through carbon–oxygen bond cleavage.