Tandem Palladium-Catalyzed 6-<i>exo</i>-<i>dig</i> Oxocyclization Coupling of δ-Acetylenic β-Ketoesters with Aryl Bromides and Chlorides: Route to Substituted Dihydropyrans

Abstract

We report an efficient and functional group-tolerant method for the synthesis of substituted dihydropyrans, based on tandem Pd-catalyzed cyclization/coupling of δ-acetylenic β-ketoesters with aryl halides. The reaction proceeds cleanly through 6- exo-dig oxocyclizaton mode, delivering products with very good yields and complete control of regio- and stereoselectivity. Due to mild conditions, the transformation offers exceptional tolerance of functionalities, including NHR, formyl, enolizable ketone, free OH and NH₂ groups, as well as a range of N-heterocyclic moieties of potential biological relevance.