Total Synthesis and Assignment of the Absolute Configuration of (+)-Omphalic Acid

Abstract

Omphalane diterpenoids usually contain a cyclohexane-fused bicyclo[3.2.1]octane scaffold embedded with two continuous quaternary carbon centers, which pose considerable challenges to synthetic chemists. Herein, we reported the first total synthesis of omphalic acid with high stereochemical control, featuring an intermolecular Diels-Alder cycloaddition, ring reorganization through Criegee oxidative cleavage and programmed aldol condensations, conformationally controlled hydrogenation, and Pd-catalyzed carboxylation. The absolute configuration of omphalic acid was defined for the first time via the asymmetric total synthesis facilitated by a derivatization resolution protocol.