Organocatalytic Asymmetric Annulation of 2-Aminophenyl-Derived α,β-Unsaturated Systems: Access to Chiral Benzene-fused Nitrogen-containing Heterocycles

Nitrogen-containing heterocycles are ubiquitous structural motifs in biologically active natural products, pharmaceuticals, and functional molecules. Among them, benzene-fused nitrogen-containing heterocycles, particularly quinoline-derived frameworks, have attracted considerable attention because of their diverse biological activities and broad therapeutic potential. As a result, the development of efficient and enantioselective methods for constructing these architectures has become an important objective in contemporary organic synthesis. This account summarizes the contributions of our group, together with those of other research groups, to the development of organocatalytic asymmetric annulation strategies for the enantioselective construction of aromatic-fused nitrogen-containing heterocycles. Particular emphasis is placed on the use of 2-aminophenyl-derived α,βunsaturated compounds-especially 2-aminocinnamaldehydes, 2aminochalcones, and 2-amino-β-nitrostyrenes-as versatile bifunctional synthons. Owing to the presence of both a nitrogencentered nucleophile and an activated π-system, these substrates readily participate in a variety of cascade annulation and cycloaddition processes, enabling the efficient construction of structurally diverse benzene-fused nitrogen-containing heterocycles with high levels of stereocontrol.