Short and Protecting-Group-Free Approach to the (-)-Δ8-THC-Motif: Synthesis of THC-Analogues, (-)-Machaeriol B and (-)-Machaeriol D.

Friedel-Crafts alkylation of resorcinols with ( S)- cis-verbenol and subsequent cyclization allows the construction of the tetrahydrodibenzopyran core of (-)-Δ8-THC which is also found in other natural products in one step. Using a benzofuryl substituted resorcinol, followed by diastereoselective hydroboration and oxidative or reductive workup, directly provides (-)-machaeriol B and D in 42% and 43% overall yields. Bromoresorcinol as a coupling partner delivers Br-THC that can be applied for late-stage diversification by Suzuki-Miyaura cross-coupling to readily access (-)-Δ8-THC analogues.