TY - JOUR
T1 - Nickel-Catalyzed Asymmetric Alkene Hydrogenation of α,β-Unsaturated Esters
T2 - High-Throughput Experimentation-Enabled Reaction Discovery, Optimization, and Mechanistic Elucidation
AU - Shevlin, Michael
AU - Friedfeld, Max R.
AU - Sheng, Huaming
AU - Pierson, Nicholas A.
AU - Hoyt, Jordan M.
AU - Campeau, Louis Charles
AU - Chirik, Paul J.
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/3/16
Y1 - 2016/3/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84961282411&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84961282411&partnerID=8YFLogxK
U2 - 10.1021/jacs.6b00519
DO - 10.1021/jacs.6b00519
M3 - Article
C2 - 26890979
AN - SCOPUS:84961282411
SN - 0002-7863
VL - 138
SP - 3562
EP - 3569
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 10
ER -