Unified Total Synthesisof Benzenoid and Troponoid Cephalotaxus Diterpenoids Enabled by RegiocontrolledPhenol-to-Tropone Ring Expansion

Herein, we present a unified strategy for the total synthesis of benzenoid and troponoid Cephalotaxus diterpenoids, specifically cephanolides A and B (benzenoids) and harringtonolide and cephinoid H (troponoids), in 13 to 19 longest linear steps. This synthesis relies on a palladium-catalyzed Csp²–Csp³ cross–coupling followed by an intramolecular doubly electron-deficient Diels–Alder reaction to establish the core skeleton and complete the synthesis of the Cephalotaxus benzenoids. A late-stage regioselective phenol-to-tropone ring expansion was developed to convert the benzenoids to the corresponding troponoid congeners. This work provides a regiocontrolled approach for achieving the synthetic connectivity between benzenoid and troponoid Cephalotaxus diterpenoids.