Efficient Synthesis of α-Alkyloxy and α-Aryloxy Esters via Cobaloxime Catalyzed Carbene Insertion into O‒H Bonds

The formation of C–O bonds represents a significant area of research in synthetic chemistry, particularly for the preparation of α-alkyloxy and α-aryloxy esters, which serve as key structural motifs in many biologically active molecules. Despite considerable progress in this field, the development of efficient and general methods for C–O bond construction remains a pressing challenge. Transition metal-catalyzed carbene insertion into O–H bonds has emerged as a powerful strategy for C–O bond formation; however, these transformations have predominantly relied on noble metal catalysts. While base metal catalysts have been explored to a limited extent, cobalt-catalyzed O–H insertion reactions have not been reported to date. Herein, we report the first cobalt-catalyzed O–H insertion reaction using diazo compounds as carbene precursors. A broad range of nucleophilic O–H substrates—including alcohols, phenols, carboxylic acids, benzoic acids, and even water—are well tolerated under the optimized conditions, affording the corresponding α-alkoxy and α-aryloxy esters in yields of up to 97%. Furthermore, the applicability of this methodology to O-containing bioactive molecules highlights its potential for late-stage functionalization. Finally, a plausible reaction mechanism is proposed to account for the observed reactivity and selectivity.