Synthesis of arene-functionalized fused heterocyclic scaffolds via a regioselective cascade 1,4-conjugate addition/5-exo-dig annulation strategy

Abstract

Facile access to furan fused heterocyclic scaffolds through a regioselective cascade reaction of propargylamines with 4-hydroxy-2H-pyran-2-ones and 4-hydroxy-6-methylpyridin-2(1H)-one has been achieved. This cascade reaction presumably involves the formation of ortho-alkynyl quinone methide (o-AQM), 1,4-conjugate addition, followed by regioselective 5-exo-dig annulation, and a 1,3-H shift process. Moreover, the reaction provides a new and efficient method for the synthesis of highly sterically congested 3-phenolic furo[3,2-c]pyran-4-ones and furo[3,2-c]pyridin-4(5H)-ones by the formation of a furan ring from readily available starting materials in good to high yields (50–82%) with broad functional group compatibility in a single step. Significantly, the strategy described here is easily scalable and several useful synthetic transformations of the prepared arene-functionalized 4H-furo[3,2-c]pyran-4-ones were also performed.