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

• Published in: Organic & biomolecular chemistry 2023-11, Vol.21 (46), p.9159-9172
• Main Authors: He, Xinwei, Wang, Demao, Liu, Yanan, Wu, Mengdi, Kong, Yangzilin, Tang, Qiang, Wang, Yiping, Fan, Chenli, Shang, Yongjia
• Format: Article
• Language: English
• Subjects: Cascade chemical reactions; Chemical reactions; Chemical synthesis; Conjugates; Functional groups; Organic chemistry; Phenolic compounds; Phenols; Quinones; Regioselectivity; Scaffolds
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d3ob01572f

Facile access to furan fused heterocyclic scaffolds through a regioselective cascade reaction of propargylamines with 4-hydroxy-2 H -pyran-2-ones and 4-hydroxy-6-methylpyridin-2(1 H )-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(5 H )-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 4 H -furo[3,2- c ]pyran-4-ones were also performed.