Mechanistic and Kinetic Studies of the Direct Alkylation of Benzylic Amines: A Formal C(sp³)–H Activation Proceeds Actually via a C(sp²)–H Activation Pathway

Abstract

Mechanistic investigations of a Rh(I)-catalyzed direct C-H alkylation of benzylic amines with alkenes, formally an C(sp³)-H activation, reveal this reaction to proceed via imine intermediates and, hence, via C(sp²)-H activation. The reaction shows a primary kinetic isotope effect of 4.3 at the benzylic C-H position together with a reversible H-D exchange at the same position, which indicates that there are at least two distinct steps in which the corresponding C-H bonds are broken. The imine intermediates are shown to be converted to the final product under the reaction conditions, and a time course analysis of the alkylated imine intermediate shows that it is formed before the final amine product in the course of the reaction.