Synthetic approaches to dysiherbaine via electrophile-promoted cyclization

Abstract

The furopyran core of dysiherbaine 1 was successfully synthesized via intramolecular epoxide opening in conjunction with electrophile-promoted cyclization. Our synthetic approach commenced in a palladium-catalyzed cross coupling under Stille conditions of cis-vinyl iodide 65 and tributyltin derivative 76 accessible from commercially-available starting materials, tris(hydroxymethyl)aminomethane $(TRIZMA^{\{cicledR})$ hydrochloride and D-mannitol, respectively. The resulting cis, cis diene intermediate 68 served as the precursor to epoxy alcohol 85. Protecting group modification of 68 followed by epoxidation afforded epoxy alcohol 85 which was designed to be the template for the ensuing cyclization reactions. The bicyclic framework was then assembled in sequence through a facile intramolecular epoxide opening of 85 to furnish tricyclic triol 88 bearing the requisite furan ring followed by mercurioetherification to undergo a six-membered ring cyclization thereby completing the furopyran ring to provide organomercurial product 96. Bicyclic diol 51 precursory to oxazolidinone 50, the chosen key intermediate to dysiherbaine was achieved upon reductive demercuration of 96. The key features in our synthetic strategy include the facile and efficient cyclization reactions and its convergence to provide the crucial intermediate prior to cyclization. Noteworthy also is the satisfactory yields in all key steps.