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

Abstract

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