Desymmetrization-Based Enantiodivergent Total Syntheses of Cycloaurenones and Dysiherbols

Cycloaurenones and dysiherbols are naturally occurring sesquiterpene quinones/quinols that share a 6/6/5/6 tetracyclic carbon skeleton with either a cis- or trans-decalin system containing four contiguous stereocenters, including three contiguous all-carbon quaternary stereocenters. No total syntheses of cycloaurenones have been reported. Herein, we report the first divergent protecting-group-free syntheses of cycloaurenones and dysiherbols based on desymmetrization reactions of a chiral cyclohexadienone intermediate: namely, a Giese–Baran-type intramolecular cyclization and a new copper-catalyzed enantioselective conjugate addition. Moreover, we began our syntheses by installing the two 1,4-nonadjacent stereocenters via an unprecedented desymmetric enantioselective hydrogenation of a bis-α,β-unsaturated Weinreb amide intermediate (>99:1 d.r. and 99% e.e.).