Enantioselective Total Synthesis of (-)-Bisabosqual F via N-Heterocyclic Carbene Catalyzed (4+2) Annulation

In 2001, a family of meroterpenoids, the bisabosquals, were isolated from the Stachybotrys fungi during studies focused on the discovery of antifungals. Although they share biosynthetic precursors with more common Stachbotrys merotepenoids, their cyclization is reminiscent of the cannabinoid family thereby providing their unique densely functionalized benzopyran/benzofuran core. Despite interest in their total synthesis, to date only racemic bisabosqual A has been prepared, with the enantioselective total synthesis of any bisabosqual yet to be realized. Herein, we report the successful completion of the first enantioselective total synthesis of a bisabosqual with the 16-step synthesis of (-)-bisabosqual F. Key aspects include an enantioselective N-heterocyclic carbene (NHC) catalyzed (4 + 2) annulation to construct the D-ring; stereoinvertive cyclization at a tertiary alcohol to produce an advanced benzochromene; and late stage oxidative NHC-mediated lactonization to assemble the pentasubstituted aromatic.