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

Abstract

Herein, we show 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/Cu(II) complex, a wide range of polysubstituted cis-decalin scaffolds with up to six continuous stereocenters was generated efficiently. The synthetic potential of this method is demonstrated by the concise synthesis of sesquiterpene (+)-occidentalol and a key intermediate for seven triterpenes. Mechanistic studies suggest the in situ formed 1,3-cyclohexadienes are the key intermediates, and efficient kinetic resolution occurs when C2 and/or C3 substituted 1,4-cyclohexadienes are utilized as substrates. DFT calculations elucidate the Diels-Alder reaction proceeds in a stepwise fashion, and reveal the originations of the stereoselectivities.