Biomimetic Total Synthesis of Clavicipitic Acid: A DDQ-Mediated Intramolecular Cross-Dehydrogenative Coupling Approach.

Clavicipitic acid, a communesin alkaloid precursor, has attracted significant attention due to its unique azepino[5,4,3-cd]indole framework. Herein, we report a novel biomimetic synthesis of clavicipitic acid diastereomers by utilizing a DDQ-mediated cross-dehydrogenative coupling (CDC) reaction. The synthesis involves Suzuki coupling for the prenylation of a 4-bromotryptophan derivative, followed by an intramolecular CDC reaction to construct the azepinoindole core. The trans isomer was obtained as the major product, and the two diastereomers were separable. The CDC reaction conditions, including temperature, solvent, and protecting groups, were investigated, and a plausible mechanism for the observed diastereoselectivity was proposed.