Electrochemical/Cobalt Dual Catalysis for Regioselective Tetramerization of Indoles

Abstract Indoles are critically important heterocyclic building blocks with broad applications in pharmaceuticals, fragrances, agrochemicals, pigments, and materials. Recent advancements have highlighted bis‐indole derivatives and oligomerized indoles as promising scaffolds for anticancer compounds and materials in organic semiconductors. Despite the challenges in forming C−C bonds in indoles, we developed a novel method combining electrochemical and cobalt complex dual catalysis to achieve regioselective C3−C3/C2−C3 coupling. Using 1‐methylindole as a model substrate, we optimized reaction conditions to achieve a 90 % yield of the tetramerized product. The method proved effective for various substituted indoles, with satisfactory yields for 6‐position substituents and poorer results for 5‐position due to steric hindrance, as confirmed by DFT calculations. The proposed mechanism involves initial C3−C3 coupling facilitated by cobalt catalysis, followed by C2−C3 coupling under electrochemical conditions, providing an efficient and environmentally benign strategy for synthesizing complex indole derivatives.