Ligand-Controlled Palladium-Catalyzed Stereodivergent Hydrocyanation of Yne-Sulfonamides: En Route to E- and Z-Trisubstituted α-Enamidonitriles.

Hydrofunctionalization of ynamides has emerged as a powerful strategy for the synthesis of trisubstituted alkenes. Herein, we report a palladium-catalyzed, ligand-controlled stereodivergent hydrocyanation of ynamides that enables selective access to either E- or Z-configured trisubstituted α-enamidonitriles from the same starting materials. Through judicious selection of ligands─DPEphos favoring the formation of E-isomers and Phox-type ligand L3 promoting high selectivity toward Z-isomers─the stereochemical outcome can be reliably controlled. Mechanistic studies indicate that the reaction proceeds without isomerization of the resulting E- or Z-alkenes. The method exhibits good functional group tolerance, including aryl halides and high step economy. Moreover, downstream transformations reveal distinct reactivity patterns between E- and Z-isomers, highlighting the critical influence of alkene geometry in synthetic applications.