Enantioselective Divergent 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. Total syntheses of cycloaurenones have not been reported. Herein, we present the first enantiodivergent syntheses of cycloaurenones and dysiherbols based on manipulation of a common cyclohexadienone intermediate: namely, a local desymmetric Giese-Baran-type cyclization for cycloaurenones and a copper-catalyzed enantioselective conjugate addition for dysiherbols. Moreover, the key cyclohexadienone intermediate was readily accessible by a bidirectional approach from a chiral bis-Weinreb amide. The 1,4-nonadjacent stereocenters were installed by an unprecedented enantioselective hydrogenation of the corresponding bis-α,β-unsaturated Weinreb amide (>99:1 chiral/meso ratio, >99% enantiomeric excess).