Mechanism-driven approaches to site- and enantioselective C−H amidation reactions by developing robust nitrene precursors

Abstract

Catalytic functionalization of a carbon-hydrogen to carbon-nitrogen bond is one of the most efficient synthetic transformation to prevalent nitrogen-containing molecules. Although a number of innovative methodologies have been devised for the last decade, fundamental understanding of catalytic mechanism is still infancy and further improvement of the reaction still lie ahead. This dissertation describes the reaction mechanism-guided discovery of novel nitrene precursors and their applications in catalytic C–H amidation protocols, which displayed excellent level of efficiency and selectivity. The important results are (i) development of 1,4,2-dioxazol-5-one compounds as efficient amide agents for (pentamethylcyclopentadienyl)rhodium- and iridium catalysis, (ii) integrated experimental and computational mechanism study for an origin of the reactivity, (iii) leveraging the reactivity of a transient intermediate to envision catalytic C–H insertion reactions and their asymmetric variant, and (iv) applying statistical tools to analyze site- and enantioselectivity of C–H functionalization reactions.