Enantioselective Hydrogenation of tetra-Substituted α,β-Unsaturated Carboxylic Acids Enabled by Cobalt(II) Catalysis: Scope and Mechanistic Insights.

Chiral carboxylic acids are important compounds because of their prevalence in pharmaceuticals, natural products and agrochemicals. Asymmetric hydrogenation of α , β -unsaturated carboxylic acids has been widely recognized as one of the most efficient synthetic approaches to afford such compounds. Although related asymmetric hydrogenation of di - and tri -substituted unsaturated acids with noble metals has been well established, asymmetric hydrogenation of challenging tetra -substituted α , β -unsaturated carboxylic acids is rarely reported. Herein, we demonstrate enantioselective hydrogenation of both cyclic and acyclic tetra -substituted α , β -unsaturated carboxylic acids via cobalt(II) catalysis. This protocol showed broad substrate scope and gave chiral carboxylic acids in good yields with excellent enantiocontrol (up to 98% yield and 99% ee). The combined experimental and computational mechanistic studies collectively support a Co(II) catalytic cycle involving migratory insertion and sigma-bond metathesis processes. In addition, our DFT calculations revealed that the enantioselectivity may origin from the steric effect between the phenyl groups of the ligand and the substrate.