Enantioselective Synthesis of cis‐Decalins by Merging the Birch Reduction and Inverse‐Electron‐Demand Diels–Alder Reaction

Herein, we show that the combination of the Birch reduction of readily available anisole derivatives and the catalytic asymmetric inverse-electron-demand Diels-Alder reaction of 2-pyrones can serve as a powerful platform for the diverse synthesis of synthetically important cis-decalin scaffolds. Enabled by a well-modified chiral bis(oxazoline) ligand/CuII complex, a wide range of polysubstituted cis-decalin scaffolds with up to six contiguous stereocenters were generated efficiently. The synthetic potential of this method is demonstrated by the concise synthesis of the sesquiterpene (+)-occidentalol and a key intermediate for seven triterpenes. Mechanistic studies suggest the 1,3-cyclohexadienes formed in situ are the key intermediates, and efficient kinetic resolution occurs when C2- and/or C3-substituted 1,4-cyclohexadienes are utilized as substrates. DFT calculations elucidated that the Diels-Alder reaction proceeds in a stepwise fashion and revealed the origins of the stereoselectivities.