Luo Yuping, He Xiujuan, Jiang Yike, Li Jie, Wu Leifang, Cai Zhihua, He Lin
School of Chemistry and Chemical Engineering/State Key Laboratory Incubation Base for Green Processing of Chemical Engineering, Shihezi University, Shihezi 832003, P. R. China.
Analysis and Testing Center of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, P. R. China.
J Org Chem. 2024 Aug 16;89(16):11766-11776. doi: 10.1021/acs.joc.4c01033. Epub 2024 Aug 3.
A direct and practical three-component tandem reaction of arynes, -methyl- sulfonothioate with sulfonamides or amides is developed. The reaction is highly efficient and chemoselective, which allows mild synthesis of trideuteromethylated sulfilimines with broad substrate scope and good functional group compatibility, giving the products in good to excellent yields with 92%-99% deuterium incorporation. Mechanism studies disclosed sulfenamide that generated in is the key intermediate for the reaction. This protocol provides potential method for introduction of -SCD moiety for deuteration of marked drugs and drug candidates containing sulfilimine skeleton.
开发了一种芳烃、α-甲基硫代磺酸酯与磺酰胺或酰胺的直接且实用的三组分串联反应。该反应高效且具有化学选择性，能够温和地合成具有广泛底物范围和良好官能团兼容性的三氘代甲基化亚磺酰亚胺，产物收率良好至优异，氘掺入率为92% - 99%。机理研究表明反应中生成的亚磺酰胺是关键中间体。该方法为在含有亚磺酰亚胺骨架的标记药物和候选药物的氘代中引入 -SCD 部分提供了潜在方法。
