Regio- and stereoselective synthesis of functionalized tetrahydro-benzochromenes and hexahydrochromenochromenones via [4 + 2] annulation of curcumins with nitrochromenes

Abstract

A base-mediated regio- and stereoselective synthesis of functionalized tetrahydro-6H-benzo[c]chromenes and hexahydro-1H,6H-chromeno[6,5-c]chromenone is disclosed here. It involves a [4 + 2] annulation via cascade double and triple Michael reactions between curcumins and nitrochromenes in the presence of Cs₂CO₃ and DBU, respectively, at room temperature, and it offers a diverse array of products as single regio- and diastereomers in excellent yields under mild conditions. Preliminary studies towards developing an enantioselective version under organocatalytic conditions met with only limited success but revealed a potentially interesting kinetic resolution pathway.