1,1-Difluorinated sulfonamides are known to have better anti-inflammatory activity and enzyme inhibitory potency than their nonfluorinated counterparts. Two geminal fluorine atoms cause electronic perturbation of the nearby polar groups enhanced the biological activity of the 1,1-difluorinated sulfonamides. However, because methods for their stereoselective synthesis are scarce, such entities remain entirely unexplored. Here, we outline an efficient method for the stereoselective introduction of the difluoro(aminosulfonyl)methyl group (CF₂SO₂NH₂) into carbonyls, imines, and alkyl halides with a new (R)-2-pyridyl difluoromethyl sulfoximine reagent, which provides a unique solution for the synthesis of chiral α,α-difluorinated sulfonamides with a quaternary stereocenter. Its potency is illustrated by the synthesis of fluorinated analogues of bioactive compounds such as 2-OH-SA, an antagonist for the GABA_B receptor in guinea pig ileum, and the late-stage modification of complex molecules such as haloperidol, ebastine, cholesterol, and (+)-δ-tocopherol derivatives. Stereoselective difluoro(aminosulfinyl)methylation to yield chiral sulfinylamides is presented, showcasing other uses of this new reagent.

已知 1,1-二氟磺胺类药物比其非氟磺胺类药物具有更好的抗炎活性和酶抑制效力。两个孪生氟原子引起附近极性基团的电子扰动增强了1,1-二氟磺胺类药物的生物活性。然而，由于它们的立体选择性合成方法很少，这些实体仍然完全未被探索。在这里，我们概述了一种将二氟（氨基磺酰基）甲基（CF ₂ SO ₂ NH ₂）立体选择性引入羰基、亚胺和卤代烷的有效方法)-2-吡啶基二氟甲基亚砜亚胺试剂，它为合成具有四元立体中心的手性 α,α-二氟磺酰胺提供了独特的解决方案。其效力通过合成生物活性化合物的氟化类似物（例如 2-OH-SA，豚鼠回肠中 GABA _B受体的拮抗剂）以及复杂分子（例如氟哌啶醇、依巴斯汀、胆固醇、 (+)-δ-生育酚衍生物。提出了立体选择性二氟（氨基亚磺酰基）甲基化以产生手性亚磺酰胺，展示了这种新试剂的其他用途。