One-pot Site-Selective Synthesis of 7-Arylidenefuro[3,4-b]pyridin-5(7H)-one Hybrids

A robust and sustainable one-pot, two-step, Cu(I)-mediated protocol has been introduced for the stereoselective synthesis of 7-arylidenefuro[3,4-b]pyridin-5(7H)-one derivatives by involving the 2-chloronicotinic acid and terminal alkynes through Sonogashira/intramolecular 5-exo-dig cyclization. The present method is more advanced due to its higher atom economy and environmentally compatible conditions than those previously reported for the synthesis of related structures. Moreover, this approach provided a wider tolerance for functional groups, enabled rapid synthetic conversion, yielded better to moderate isolated yields (87-66%), and produced Z-configured derivatives with alkyne coupling partners by in situ oxacyclization. Mechanistic investigation has disclosed the consequence of the Cu(I) catalyst in the tandem Sonogashira coupling and subsequent 5-exo-dig cyclization, enabling a versatile route for complex heterocycle synthesis. This operatively simple and greener synthetic route may contribute to current process development, which can be advantageous for its potential utility.