Regiospecific and Enantioselective Arylvinylcarbene Insertion of a C-H Bond of Aniline Derivatives Enabled by a Rh(I)-Diene Catalyst

Asymmetric insertion of an arylvinylcarbenoid into the C-H bond for direct enantioselective C(sp(2))-H functionalization of aniline derivatives catalyzed by a rhodium(I)-diene complex was developed for the first time. The reaction occurred exclusively at the uncommon vinyl terminus site with excellent E selectivity and enantioselectivities, providing various chiral gamma,gamma-gem-diarylsubstituted alpha,beta-unsaturated esters with broad functional group compatibility under simple and mild conditions. It provides a rare example of the asymmetric C-H insertion of arenes with selective vinylogous reactivity. Synthesis applications of this protocol were featured by several versatile product transformations. Systematic DFT calculations were also performed to elucidate the reaction mechanism and origin of the uncommon enantio- and regioselectivity of the Rh(I)-catalyzed C(sp(2))-H functionalization reaction. The measured and computed inverse deuterium kinetic isotope effect supports the C-C bond-formation step as the rate-determining step. Attractive interactions between the chiral ligand and substrates were also proposed to control the enantioselectivity.

Automated summary

This study introduces for the first time the asymmetric insertion of an arylvinylcarbenoid into the C-H bond catalyzed by a rhodium(I)-diene complex, providing various chiral compounds with excellent enantioselectivity. Systematic DFT calculations were used to elucidate the reaction mechanism and origin of the uncommon enantioselectivity.