Mechanism-guided development of nitrenoid transfer catalysts for selective formation of N-heterocycles

Abstract

Transition-metal catalyzed nitrene transfer is the most desirable strategies to introduce nitrogen functionality into organic molecules, which allows straightforward and shortcut access to many N-heterocycles. Although tremendous progress has been made in the past decade, the formation of cyclic amides has traditionally been hindered by competing isocyanate formation. This dissertation describes how the reaction mechanism guided to provide an innovative solution to the unmet challenge in contemporary catalysis. Based on the mechanistic understanding derived from a seamless collaboration between theory and experiment, we developed customized transition metal catalysts, which enable to insert metal-nitrenoid into diverse functional groups with the exceptional selectivity. The approach was successfully utilized to develop several synthetic methodologies: (i) selective formation of 5-membered amides via C−H amidation, (ii) stereoselective haloamidation of alkynes by ligand participation, (iii) harnessing Ir-nitrenoid as a motif of 1,3-dipole for stereodefined procedure via olefin difunctionalization, (iv) oxidative cyclization based on the intermediacy of carbocation for allyl amide synthesis and its asymmetric variant, (v) [4+2] and [4+1] annulations.