Isoquinolinones, a class of aromatic N-heterocycles, are often found in natural products and bioactive molecules. Straightforward synthetic access to functionalized isoquinolin-1(2H)-ones is, thus, useful. Different functional groups have been introduced into the C3/C4/C8 positions using transition-metal-catalyzed C–H functionalizations.

Guo-Li Huang, Yunnan Normal University, Kunming, China, and colleagues have developed a metal-free, green, simple, and efficient iodine-promoted method for the synthesis of 4-arylthioisoquinolin-1(2H)-ones under solvent-free conditions. The team used inexpensive and commercially available aryl sulfonyl chlorides as the sulfur source. Iodine (I₂) and diethyl phosphite ((EtO)₂P(O)H) allow the generation of electrophilic ArSI species, which can be converted to ArS^· radical intermediates by homolysis. These intermediates can couple with the substrate and form the desired products.

 

The reaction proceeds smoothly in air and gives moderate to good yields of the C-4 sulfenylated products. The process has high regioselectivity, a broad substrate scope, and good functional group tolerance. Overall, the method provides simple, time-efficient, scalable, and low-cost access to 4-arylthio-substituted isoquinolin-1(2H)-one derivatives.

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• I₂-promoted direct C-H sulfenylation of isoquinolin-1(2H)-ones with sulfonyl chlorides,
  Cai-Yun Yang, Xia Li, Bo Liu, Guo-Li Huang,
  Eur. J. Org. Chem. 2020.
  https://doi.org/10.1002/ejoc.202001371