Efficient synthesis and mechanistic insights for the formation of imidazo[1,2-a]pyridines via multicomponent decarboxylative coupling using chitosan-supported copper catalysts

Abstract

An efficient multicomponent decarboxylative coupling of 2-aminopyridines, aldehydes and alkynoic acids for the synthesis of imidazo[1,2-a]pyridines was developed using recyclable chitosan-supported copper (chit@CuSO4) as a heterogeneous catalyst. Computational and experimental evidence revealed that in situ generated propargylamine undergoes cyclization to the desired imidazopyridine via prototropic isomerization involving allene type intermediates. Control experiments on isolated propargylamine demonstrated that cyclization could proceed without any metal catalyst. In literature, the cyclization step is assumed to be facilitated by metal catalyst and experimental proof for the involvement of actual intermediates is not available. The synthesized imidazopyridines were further evaluated for antiproliferative activity against human neuroblastoma cells (SHSY-5Y) using MTT assay.