Meldrum's Acid-Derived Thione Dienophile in a Convergent and Stereoselective Synthesis of a Tetracyclic Quassinoid Intermediate

An advanced intermediate toward anti-cancer quassinoids has been synthesized using a quadruple diene-transmissive [4+2]-cycloaddition strategy. High convergence is achieved thanks to a regio- and stereoselective hetero-Diels−Alder reaction using a thione. The relative stereochemistry of the final Diels−Alder adduct was controlled by tethered substituents introduced via a highly syn- and γ-selective vinylogous Mukaiyama aldol.