Aza-Ortho-Quinone Methides as Reactive Intermediates: Generation and Utility in Contemporary Asymmetric Synthesis

The aza-ortho-quinone methide (aza-o-QM) chemistry has overwhelmingly progressed in the past few decades. This review aims to integrate various transition metal-catalyzed and organocatalytic strategies in taming aza-o-QM intermediates, including the aza-ortho-vinylidene quinone methide (aza-o-VQM), aza-ortho-alkynyl quinone methide (aza-o-AQM), aza-para-quinone methide (aza-p-QM), and indole-based aza-o-QM analog. These transient species are often utilized for the direct and enantioselective synthesis of complex (hetero)polycyclic or fused-ring molecular scaffolds such as tetrahydroquinoline and indoline, among others, which are abundant in many natural products, bioactive compounds, and pharmaceuticals.

Automated summary

This review presents the progress of aza-ortho-quinone methide (aza-o-QM) chemistry in the past few decades. Various catalytic strategies using transition metals and organocatalysts are discussed for controlling aza-o-QM intermediates, leading to the synthesis of complex molecular scaffolds.