Mechanistic Exploitations of the Asymmetric ?-Allylation of an ?-CF3 Amide Enabled by Cu/Pd Synergistic Dual Catalysis

DFT computational investigations were carried out to explore the mechanism of enantioselective Cu/Pd-catalyzed allylation of an alpha-CF3 amide. A kinetically favored chiral Cu(I)-enolate species undertakes facile allylation with racemic pi-allyl-Pd(II) species to stereoconvergently deliver a stereocenter. Computational models and distortion/interaction analyses unveil versatile modes of stereoinduction wherein the reactive site of (R,Rp)-Walphos/copper(I)-enolate cis to the -PPh2 moiety has more space for the nucleophilic reaction, and can face-selectively capture pi-allyl-palladium(II) intermediates using sterically affected distortions.

Automated summary

DFT computational investigations were conducted on the mechanism of enantioselective Cu/Pd-catalyzed allylation of an alpha-CF3 amide. The results revealed that a kinetically favored chiral Cu(I)-enolate species can react with racemic pi-allyl-Pd(II) species to deliver a stereocenter with stereoconvergence. The study also provided insight into the versatile modes of stereoinduction and the selective capture of pi-allyl-palladium(II) intermediates.