Development of a C-C Bond Cleavage/Vinylation/Mizoroki-Heck Cascade Reaction: Application to the Total Synthesis of 14- and 15-Hydroxypatchoulol.

ABSTRACT

A C-C bond cleavage/vinylation/Mizoroki-Heck cascade reaction has been developed to provide access to densely functionalized bicyclo[2.2.2]octane frameworks. The sequence proceeds through the coupling of dihydroxylated pinene derivatives, prepared from carvone, with gem-dichloroalkenes. The method was applied to 12-step total syntheses of both 14- and 15-hydroxypatchoulol, which provided unambiguous support for the structure of the natural products and corrects a misassignment in the isolation report.