Understanding Off-Cycle and Deactivation Pathways in Radical-Type Carbene Transfer Catalysis.

Transition metal radical-type carbene transfer catalysis is a sustainable and atom-efficient method to generate C-C bonds, especially to produce fine chemicals and pharmaceuticals. A significant amount of research has therefore been devoted to applying this methodology, which resulted in innovative routes toward otherwise synthetically challenging products and a detailed mechanistic understanding of the catalytic systems. Furthermore, combined experimental and theoretical efforts elucidated the reactivity of carbene radical complexes and their off-cycle pathways. The latter can imply the formation of N-enolate and bridging carbenes, and undesired hydrogen atom transfer by the carbene radical species from the reaction medium which can lead to catalyst deactivation. In this concept paper, we demonstrate that understanding off-cycle and deactivation pathways not only affords solutions to circumvent them, but can also uncover novel reactivity for new applications. In particular, considering off-cycle species involved in metalloradical catalysis can stimulate further development of radical-type carbene transfer reactions.