A Robust [Pd(BIAN-IPr#)Cl2(H2O)] Catalyst Employing Water as a Disposable Ligand for C–S Cross Coupling of Aryl Chlorides and Thiols

Abstract

Aryl thioethers represent versatile synthetic intermediates with extensive applications spanning medicinal, biological, and agricultural chemistry. Herein, we report a highly efficient Pd-catalyzed cross-coupling protocol for the reaction of thiols with readily availabe and inexpensive aryl chlorides, enabled by a newly prepared and well-defined Pd(BIAN-IPr#)Cl2(H2O) catalyst. Notably, a distinctive feature of this catalyst is the incorporation of H2O as a benign, throw-away ligand, rendering it a greener and more pratical alternative to commonly employed cinnamyl- or PEPPSI-type precatalysts. The developed protocol operates under mild conditions (50 °C, air), eliminates the necessity for inert-atmosphere protection, and demonstrates exceptional tolerance toward a wide range of electronically and sterically diverse substrates, affording aryl thioethers in excellent yields. The utility of this methodology was further demonstrated through its successful extension to benzylic chlorides, where both Pd-catalyzed cross-coupling and direct nucleophilic substitution pathways operate concurrently to deliver the corresponding thioethers in good to excellent yields.