Bimolecular Homolytic Substitution (S_H2) and Radical Ligand Transfer (RLT): Emerging Paradigms in Radical...

Inspired by biological rebound processes, radical ligand transfer (RLT) has emerged as a powerful and versatile strategy for the selective functionalization of alkyl radicals. RLT enables direct C-X bond formation through homolytic substitution at a metal-bound ligand (M-X) and demonstrates broad functional group tolerance and high potential for catalysis. Despite growing interest and mechanistic understanding, including recent insights into asynchronous concerted ion-electron transfer (cIET), the broader application of RLT strategies remains underdeveloped. In parallel, the closely related S_H2 (bimolecular homolytic substitution) mechanism has gained increasing utility in C-C bond formation, where low-valent metals capture transient radicals and facilitate selective coupling with persistent radical partnersa process referred to as radical sorting. Herein, we present a comprehensive perspective of the evolving landscape of RLT and S_H2 chemistry, emphasizing recent advances. We highlight key bioinspired and computationally guided approaches that have enhanced mechanistic understanding and broadened the substrate scope, including landmark contributions by Kochi, Groves, Shaik, MacMillan, and others. To complement these studies and encourage further development, we also report DFT-based thermodynamic analyses of radical ligand transfer across first-row transition metal complexes bearing porphyrin and BOX ligands. By unifying these mechanistic frameworks, this perspective aims to provide a roadmap for designing novel, selective, and sustainable radical-based transformations.