Highly enantioselective hydrogenation of tetra- And tri-Substituted α,β-unsaturated carboxylic acids with oxa-spiro diphosphine ligands

Abstract

We herein present the design and synthesis of a structurally unique oxa-spirocyclic diphosphine ligand, termed as O-SDP. The diphosphine ligand O-SDP derived from oxa-spirocyclic diphenols (O-SPINOL) has a relatively larger bite angle compared with that of SDP, and O-SDP has been successfully applied in the ruthenium-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic acids under mild reaction conditions. High yields and enantioselectivities were generally achieved for a wide range of substrates (up to 99% yield and >99% ee), and many of the resulting products are key intermediates of important drugs such as Sacubitril, Artemisinin, and Paroxetine.