Total Synthesis of the Cephalotaxus Norditerpenoids (±)-Cephanolides A–D

Concise syntheses of the Cephalotaxus norditerpenoids cephanolides A-D (8-14 steps from commercial material) using a common late-stage synthetic intermediate are described. The success of our approach rested on an early decision to apply chemical network analysis to identify the strategic bonds that needed to be forged, as well as the efficient construction of the carbon framework through iterative Csp²-Csp³ cross-coupling, followed by an intramolecular inverse-demand Diels-Alder cycloaddition. Strategic late-stage oxidations facilitated access to all congeners of the benzenoid cephanolides isolated to date.