Nickel-Catalyzed Asymmetric Alkene Hydrogenation of α,β-Unsaturated Esters: High-Throughput Experimentation-Enabled Reaction Discovery, Optimization, and Mechanistic Elucidation

• DOI: 10.1021/jacs.6b00519
• Publication Date: 2016-02-18T16:57:03Z
• Authors: Michael Shevlin; Max R. Friedfeld; Huaming Sheng; Nicholas A. Pierson; Jordan M. Hoyt; Louis-Charles Cam...; Paul J. Chirik
• Keywords: Alkene

A highly active and enantioselective phosphine-nickel catalyst for the asymmetric hydrogenation of α,β-unsaturated esters has been discovered. The coordination chemistry catalytic behavior nickel halide, acetate, mixed halide-acetate with chiral bidentate phosphines have explored deuterium labeling studies, method continuous variation, nonlinear kinetic measurements provided mechanistic understanding. Activation molecular hydrogen by a trimeric (Me–DuPhos)3Ni3(OAc)5I complex was established as turnover limiting followed rapid conjugate addition hydride nonselective protonation to release substrate. In reaction discovery optimization, previously unreported utility high-throughput experimentation elucidation is also described.