Thiolation of 1,3‐Diynes as a Regio‐ and Stereoselective Route to Z ‐Thioenynes

ABSTRACT A regio‐ and stereoselective method for the synthesis of Z ‐thioenynes from 1,3‐diynes has been developed using in situ‐generated lithium thiolates under mild conditions. The transformation proceeds with excellent Z ‐selectivity and broad functional‐group tolerance, enabling the efficient preparation of both symmetrical and unsymmetrical thioenynes. Mechanistic studies, including reactions performed with deuterium‐labeled ethanol, demonstrated that ethanol essentially acts as the hydrogen source for vinyl protonation, supporting an anti‐addition pathway followed by selective quenching of the vinyl anion. The presence of a propargyl hydroxyl group was shown to strongly influence the regiochemical outcome, favoring thiolate addition at C‐2 of the diyne. The method was scalable, and the resulting Z‐ thioenynes could be further transformed into functionalized thiophenes via copper‐catalyzed cyclization with diphenyl diselenide. This study provides a practical, selective, and mechanistically informed strategy for constructing sulfur‐containing enyne frameworks of synthetic utility.