Studies on the regioselectivity of the cyclization of tryptophanol-derived oxazolopiperidone lactams

Abstract

Cyclization of the lactam carbonyl on the indole ring in tryptophanol-derived oxazolopiperidone lactams 2 and 6, under the classical POCl3-promoted Bischler-Napieralski conditions and under neutral conditions via the corresponding thiolactam, has been studied. Whereas tricyclic lactam 2 only leads to products coming from an α-amidoalkylation process, bicyclic lactam 6 undergoes cyclization on the lactam carbonyl, leading to the expected indolo[2,3-a]quinolizidine derivatives. Cyclizations on the lactam carbonyl from tryptophanol-derived oxazolopiperidone lactams have been studied. A pyridine ring fused to the piperidone moiety exerts a dramatic effect on the regioselectivity of the cyclization, leading exclusively to α- amidoalkylation products. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.