Metal-free synthesis of 4-(methylthio)-3-phenylisoquinolines

Herein, we report a straightforward protocol for synthesizing 4-(methylthio)-3-phenylisoquinolines, which are valuable compounds in medicinal chemistry for their biological activities. This method uses 1-(azidomethyl)-2-(phenylethynyl)benzenes and dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTSM) under mild, metal-free conditions. Notably, it tolerates diverse aromatic functional groups, enabling derivative preparation. The reaction proceeds smoothly, affording products in good to excellent yields. By avoiding hazardous and malodorous methylthio radical reagents as well as methylthio nucleophile precursors, this protocol provides a practical and eco-friendly route to sulfur-containing heterocycles.