Divergent Total Syntheses of Rearranged Steroids Swinhoeisterols A–C

Swinhoeisterols A-C are 13(14→8),14(8→7)-diabeo-steroids possessing an intriguing 6/6/5/7 tetracyclic core framework and potent inhibitory activity against the histone acetyltransferase p300. Herein we report their divergent total syntheses from readily available (S)-Wieland-Miescher ketone. A tandem Negishi/Heck cross-coupling of a chloroenol triflate was developed to install the labile methylenecyclopentene motif using a silyl-tethered homoallylic zinc reagent that was carefully designed to suppress undesired [Pd]-H insertion. Furthermore, a Baran reductive olefin coupling of a diene, a rarely used radical donor, with a tethered acrylonitrile group allowed for the simultaneous construction of the seven-membered ring and two contiguous stereocenters, including a quaternary carbon center.