Coupling of Sterically Hindered Trisubstituted Olefins and Benzocyclobutenones by CC Activation: Total Synthesis and Structural Revision of Cycloinumakiol

Abstract

AbstractThe first total syntheses of the proposed structure of cycloinumakiol (1) and its C5 epimer (18) are achieved in a concise and efficient fashion. Starting from the known 3‐hydroxybenzocyclobutenone, 1 and 18 are obtained in nine and five steps with overall yields of 15 % and 33 %, respectively. The key for the success of this approach is the use of a catalytic CC activation strategy for constructing the tetracyclic core of 1 through carboacylation of a sterically hindered trisubstituted olefin with benzocyclobutenone. In addition, the structure of the natural cycloinumakiol was reassigned to 19‐hydroxytotarol (7) through X‐ray diffraction analysis. This work demonstrates the potential of CC activation for streamlining complex natural product synthesis.