Phosphine-catalyzed remote α-C–H bond activation of alcohols or amines triggered by the radical trifluoromethylation of alkenes: reaction development and mechanistic insights

Abstract

Intramolecular hydrogen atom transfer (HAT) for the remote functionalization of C(sp³)–H bonds has emerged as a powerful strategy, but its asymmetric diversification remains a great challenge because of the requirement of harsh reaction conditions and less enantiotopic discrimination. To overcome this, we described a general and efficient radical protocol for the concomitant functionalization of both alkenes and the remote α-C–H bonds of alcohols or amines via 1,5(6,7)-HAT triggered by the addition of a trifluoromethyl radical to alkenes in a highly controlled site-selective manner. Furthermore, such an approach could be developed for late-stage asymmetric diversification at the remote sp³-hydridized positions of alcohols or amines via a cascade sequence for the facile construction of chiral CF₃-containing homoallylic alcohols or secondary amines with good to excellent enantioselectivities. Mechanistic experiments and DFT calculations revealed that 1,5(6,7)-HAT is a kinetically relevant process and provided a rationale for the observed different reactivities between the linear alkenyl alcohol or amine and alkenyl ketone or amide.