Dinuclear zinc-catalyzed enantioselective formal [3 + 2] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with low reactivity aurone derivatives

Abstract

Highly enantioselective formal [3 + 2] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with aurone derivatives of low reactivity using chiral dinuclear zinc catalysts has been developed via a Brønsted base and Lewis acid cooperative activation model. These transformations involving a domino Michael/Mannich reaction sequence led to efficient construction of a range of chiral spiro[benzofuran-pyrrolidine] scaffolds bearing three biologically relevant heterocyclic moieties and two adjacent spiro quaternary stereocenters in high yields (up to 95%) and with good enantioselectivities (up to 99% ee).