Four-Component Cascade Heteroannulation of Heterocyclic Ketene Aminals: Synthesis of Functionalized Tetrahydroimidazo[1,2?a]pyridine Derivatives

摘要

An efficient and straightforward four-component synthetic protocol has been developed to synthesizenimidazo[1,2-a]pyridines and imidazo[1,2,3-ij][1,8]naphthyridine derivatives incorporating medicinally privileged heterosystemsnfrom heterocyclic ketene aminals, aldehydes, diketene, and amines via cascade reactions, including diketene ring-opening,nKnoevenagel condensation, aza−ene reaction, imine−enamine tautomerization, cyclocondensation, and intramolecular SNAr.nThis strategy can provide an alternative approach for easy access to the highly substituted imidazo[1,2-a]pyridine derivatives innmoderate to good yields using four simple and readily available building blocks under mild conditions. Importantly, the unusualnsplitting peaks in the 1H NMR spectra of the products derived from heterocyclic ketene aminals with an o-halogen atom on thenaryl ring were explained reasonably by varying the temperature in NMR analysis.