Hydrophobic Amplification Enabled High-Turnover Phosphazene Superbase Catalysis

beta-Sulfido sulfonyl fluoride and its derivatives have been gaining attention recently in the fields of medicinal chemistry and material science. The conventional method for the synthesis of functionalized alkyl sulfonyl fluorides requires several chemical transformations. Therefore, a direct establishment of such chemical structures remains challenging, and an efficient catalytic approach is highly desired. Herein a significant on-water hydrophobic amplification was achieved, enabling a high-turnover catalytic thia-Michael addition to produce unprecedented beta-arylated-beta-sulfido sulfonyl fluorides. Amounts as low as 100 ppm (0.01 mol %) of the phosphazene superbase were sufficient to successfully catalyze the reaction with excellent chemo-/site-selectivity and with optimal functional group tolerance. Several beta-arylated ethene sulfonyl fluorides were converted into thia-Michael adducts up to >99 % yields. The mild conditions, high turnover, neutral pH, and scalability of the sustainable catalytic process benefit the preparation of potential pharmaceuticals (e. g., polyisoprenylated methylated protein methyl esterase inhibitors) and organic materials (e. g., electrolyte additives).

Automated summary

Beta-Sulfido sulfonyl fluoride and its derivatives have gained attention in medicinal chemistry and material science. A direct establishment of such chemical structures remains challenging, motivating the development of an efficient catalytic approach. This study achieved a high-turnover catalytic thia-Michael addition, leading to the production of unprecedented beta-arylated-beta-sulfido sulfonyl fluorides.