Mechanistic insights on C(acyl)–N functionalisation mediated by late transition metals

Abstract

The carboxamide functional group has a privileged role in organic and biological chemistry due to its prevalence and utility across synthetic and natural products. Due to n_N → π*_CO delocalisation, amides and related functional groups are typically kinetically resistant to degradation. Nonetheless, over the past decade, transition metal catalysis has transformed our ability to utilise molecules featuring C(acyl)–N units as reactants. Alongside the burgeoning catalytic applications ranging from CO_x utilisation to small molecule synthesis, elucidation of the underlying mechanisms remains a critical ongoing effort. Herein, we aggregate and analyse current understanding of the mechanisms for C(acyl)–N functionalisation of amides and related functional groups with a focus on recent developments involving mechanisms unique to the late transition metals. Discussion is organized around three general mechanistic manifolds: redox-neutral mechanisms, 2e⁻ redox-cycling mechanisms, and mechanisms involving 1e⁻ redox steps. For each class, we focus on reactions that directly involve a transition metal mediator/catalyst in the C(acyl)–N cleavage step. We conclude with an outlook on the outstanding ambiguities and opportunities for innovation.