Organocatalytic synthesis of optically active heteroaromatic compounds

Abstract

This perspective presents recently developed enantioselective organocatalytic strategies for the formation of hydroxyalkyl- and aminoalkyl-substituted heteroaromatic compounds. These novel methodologies rely on multi-bond forming one-pot [3+2]-annulation reaction cascades applying 2,3-epoxy and 2,3-aziridine aldehydes as key intermediates. The possibility to employ 1,3-dinucleophilic reagents, i.e. 1,3-dicarbonyl compounds, thioamides, amidines, ureas, thioureas or 2-aminopyridines, leading to the formation of optically active furans, thiophenes, imidazoles, oxazoles, thiazoles or imidazo[1,2-a]pyridines is discussed. Furthermore, studies on the application of the methodology for the synthesis of 2,3-dihydrofurans and 2,3-dihydrobenzofurans, via either interruption of the sequence before dehydrative aromatization or structural modification of key intermediates, are also described. Finally, challenges related to regio-, chemo-, enantio- and diastereoselectivity and main benefits of the reaction sequences are outlined.