Supramolecular catalysis in the dearomative Michael addition involving nitro-group-activated benzofurans†

Abstract

In this manuscript, the application of supramolecular catalysis utilizing the combination of a cinchona-alkaloid-derived squaramide and an acidic co-catalyst in the vinylogous, dearomative Michael addition is described. The appropriate selection of reaction promotors allowing for the self-assembly of a well-defined transition state resulted in the formation of biologically relevant heterocycles bearing three contiguous stereocenters with high stereoselectivity. The synthetic potential of the methodology was confirmed in selected post-functionalizations including removal of the nitro group with concomitant aromatization and the thia-Michael reaction. Furthermore, the mechanism of the reaction has been studied using DFT calculations indicating the importance of supramolecular interactions for the reaction outcome.