Cobalt-catalyzed highly enantioselective hydrogenation of α,β-unsaturated carboxylic acids

Asymmetric hydrogenation of alpha,beta -unsaturated acids catalyzed by noble metals has been well established, whereas, the asymmetric hydrogenation with earth-abundant-metal was rarely reported. Here, we describe a cobalt-catalyzed asymmetric hydrogenation of alpha,beta -unsaturated carboxylic acids. By using chiral cobalt catalyst bearing electron-donating diphosphine ligand, high activity (up to 1860 TON) and excellent enantioselectivity (up to >99% ee) are observed. Furthermore, the cobalt-catalyzed asymmetric hydrogenation is successfully applied to a broad spectrum of alpha,beta -unsaturated carboxylic acids, such as various alpha -aryl and alpha -alkyl cinnamic acid derivatives, alpha -oxy-functionalized alpha,beta -unsaturated acids, alpha -substituted acrylic acids and heterocyclic alpha,beta -unsaturated acids (30 examples). The synthetic utility of the protocol is highlighted by the synthesis of key intermediates for chiral drugs (6 cases). Preliminary mechanistic studies reveal that the carboxy group may be involved in the control of the reactivity and enantioselectivity through an interaction with the metal centre. A large number of marketed drugs contains a chiral carboxylic acid scaffold. Here, the authors report the asymmetric hydrogenation of alpha,beta -unsaturated carboxylic acids to alpha -chiral carboxylic acids using a cobalt catalyst bearing an electron-donating chiral diphosphine ligand.