Shaping Chirality via Stereoselective, Organocatalytic [4+2] Cycloadditions involving Heterocyclic ortho-Quinodimethanes.

Abstract

Polycyclic compounds bearing a complex heterocyclic core such as an aromatic heterocycle "fused" with one or more functionalized rings, are widespread leading molecules in the domain of synthetic organic chemistry and pharmaceuticals. Although many synthetic methodologies have been devised to access achiral, fused heteroaromatic scaffolds, or related chiral variants adorned with out-of-cycle stereogenic elements, equally efficient strategies to afford chiral heterocycles featuring in-cycle stereocenters, exist to a lesser extent and presently represent a growing field of investigation. The mild, organocatalytic generation of elusive ortho-quinodimethane intermediates (oQDMs), derived from suitable heteroaromatic carbonyl- or carbonyl-like pronucleophiles has recently proved successful in the synthesis of such peculiar chiral architectures via stereoselective [4+2] cycloadditions. This review provides an overview of the most important advances attained in this field over the last decade.