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

Michael Shevlin, Max R. Friedfeld, Huaming Sheng, Nicholas A. Pierson, Jordan M. Hoyt, Louis Charles Campeau, Paul J. Chirik

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)3562-3569
Number of pages8
JournalJournal of the American Chemical Society
Volume138
Issue number10
DOIs
StatePublished - Mar 16 2016

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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