Synthesis of Furfural Sulfides and 4-Alkylthiopyridines via Heterocyclization of a-Acyl Ketene Dithioacetals

Herein, we devised a synthetic approach for skeletally diversified furfuryl sulfides and 4-alkylthiopyridines involving the heterocyclization of flexible a-acyl ketene dithioacetals, enabled by cooperative Pd/Cu catalysis. The overall transformation was initiated by acyl-directed desulfurative Sonogashira coupling, which was proposed as the key step in surmounting the competitive carbothiolation pathway. This step was followed by 1,6-addition of either a S- or N-nucleophile and intramolecular cyclization. Notably, the two different annulation reactions featured readily accessible starting materials, selective cleavage and reassembly of multiple chemical bonds, broad functional group tolerance, pharmacologically significant heterocyclic products with high regio- and chemoselectivities, and high atom economy.