Short and Divergent Total Synthesis of ()-Machaeriol B, ()-Machaeriol D, ()-Δ(8)-THC, and Analogues.
Short and highly efficient stereoselective syntheses provide machaeriols and cannabinoids in a divergent approach starting from a common precursor, commercially available (S)-perillic acid. Key features of the novel strategy are a stereospecific palladium-catalyzed decarboxylative arylation and a one-pot sequence comprising a stereoselective hydroboration followed by oxidation or reduction of the corresponding intermediary boranes. The divergent approach is convincingly demonstrated by the five-step syntheses of ()-machaeriol B, ()-machaeriol D, and related analogues, and the four-step synthesis of ()-Δ(8)-THC and an analogue.