Mechanism-Based Classification of Carbon–Oxygen Bond Functionalization by Transition Metal Catalysis

Abstract In this review, we categorize C–O bond functionalization reactions according to their underlying mechanisms, encompassing both C(sp²)–O and C(sp³)–O bond activations. While nickel-based catalysts have dominated the early and continuing developments in this area, recent efforts have expanded the scope to include a broader range of transition metals. Although molecular transformations catalyzed by these alternative metals are still in their infancy, they have yielded valuable mechanistic insights that are essential for future advancements. Moreover, it has become increasingly clear that traditional mechanistic frameworks are insufficient to fully explain the activation of inherently unreactive C–O bonds. This has led to a surge of interest in alternative activation paradigms, particularly dual activation strategies that exploit the synergistic roles of multiple catalytic components. By systematically summarizing current strategies for C–O bond activation, this review seeks to accelerate progress in the field and offer conceptual guidance for the broader activation of otherwise inert bonds.