“Green” Oxidant (Oxygen) Mediated Synthesis of N-(2-(Methylsulfonyl)ethyl)amide Derivatives Using DMSO as a Dual Synthon and Solvent

Sulfone derivatives are important components of many pharmaceuticals. This Letter reports an efficient method for synthesizing N-(2-(methylsulfonyl)ethyl)amide compounds with sulfone skeletons from amide compounds and dimethyl sulfoxide (DMSO) using an environmentally benign oxidant (oxygen). This metal-free protocol features operational simplicity, a low-cost and nonhazardous oxidant mediator, good functional group tolerance, and scalability to gram-scale. Notably, DMSO acts as a dual synthon donor, providing both methylene (−CH2−) and methylsulfonyl (−SO2Me) groups to form C(sp3)–N and C(sp3)–C(sp3) bonds while serving as the solvent. A radical mechanism is proposed based on control experiments and EPR spectroscopy.