Catalytic Asymmetric Inverse‐Electron‐Demand Diels–Alder Reactions of 2‐Pyrones with Indenes: Total Syntheses of Cephanolides A and B

Abstract An inverse‐electron‐demand Diels–Alder (IEDDA) reaction could complement the conventional normal‐electron‐demand Diels–Alder reaction in the synthesis of six‐membered carbocycles. However, catalytic asymmetric all‐carbon‐based IEDDA reactions are underdeveloped. Herein, we disclosed a copper‐catalyzed asymmetric IEDDA reaction using electron‐deficient 3‐carboalkoxyl‐2‐pyrones and electronically unbiased indenes as reactants. This method enables the rapid and enantioselective construction of a wide range of hexahydrofluorenyl bridged‐lactone scaffolds. Using this method, asymmetric total syntheses of cephanolides A and B were accomplished.