Formal [4+1] heteroannulative coupling of Knoevenagel adducts derived from 2-heteroaryl acetonitriles with isocyanides: subsequent Pd-catalyzed intramolecular N-arylation to 6-5-5-5-6 pentacyclic cores

Abstract

A concise and practical approach for expedient synthesis of substituted benzoxazolpyrroles, benzothiazolpyrroles and indolizines by three-component cascade annulative coupling of an aldehyde, 2-heteroaryl acetonitrile and an isocyanide in the presence of 10 mol% 2-(hydroxymethyl)pyrrolidinium acetate has been devised in high yields for the first time. The compatibility with a wide range of functional groups makes this domino formation of one C–C and two C–N bonds interesting. In particular, the heterocycles derived from 2-bromobenzaldehydes are further converted into indole-fused novel pentacyclic (6-5-5-5-6) heteroaromatic compounds by Pd(II)-catalyzed intramolecular N-arylation via a cross-dehydrobromination reaction. This annulative protocol not only provides an efficient method to access tricyclic heteroaromatics, but also enriches the research domain of pentacyclic scaffolds.