Synthesis of 4-(arylthio)isoquinolin-1(2 <i>H</i> )-ones <i>via</i> TBHP-mediated sequential amidation/thioetherification of <i>N</i> -alkylisoquinolinium salts

Here, a simple, efficient, and practical method for the assembly of 4-(arylthio)isoquinolin-1(2<i>H</i>)-ones <i>via</i> TBHP-mediated 1,4-difunctionalization of <i>N</i>-alkylisoquinolinium iodide salts under metal-free conditions is reported. This strategy features readily available starting materials, operational simplicity, and metal-free conditions. Remarkably, a variety of (hetero)aryl/alkyl thiols, diphenyl disulfide, diphenyl diselenide, and <i>N</i>-alkylisoquinolinium bromides or chlorides are compatible with this method, which generates the desired 4-(arylthio)isoquinolin-1(2<i>H</i>)-ones in 30-92% yields. The potential synthetic utility is demonstrated by its gram-scale synthesis and derivatizations. The mechanistic experiments indicate that the iodide plays a key role in this transformation.