Multicomponent cascade reactions of HKAs: synthesis of highly functionalized 5H-chromeno[4,3-d]pyrimidines

Abstract

A novel protocol was developed for the construction of highly functionalized 5H-chromeno[4,3-d]pyrimidines (CMPDs) from 3-formylchromones, heterocyclic ketene aminals (HKAs), and amidine hydrochlorides via a novel cascade reaction involving ring-opening and 1,3-H shift reactions. As a result, a series of CMPDs was produced by exploitation of the cascade reaction, which involved the formation of three bonds and the cleavage of one bond through multiple reactions in one pot. This protocol can be used in combinatorial and parallel syntheses of various CMPD derivatives with the potential to exhibit biological activities against clinically relevant pharmacological targets and will be widely used for designing and synthesizing various novel chromene-containing heterocycles in the future.