Enantioselective Divergent Total Syntheses of Cycloaurenones and Dysiherbols

Abstract 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).