Herein, the first catalytic protocol for nickel-catalyzed ortho or para position difluoromethylation of various aromatic amines has been developed with the assistance of a bidentate phosphine ligand, offering an invaluable synthesis means to construct extensive p-difluoromethylated products and difluorooxindole derivatives with significant functional fragments. Furthermore, the gram-scale reaction, broad substrate scope, excellent functional-group compatibility, late-stage difluoromethylation of pesticides, and even formal synthesis of HDAC6 inhibitors further demonstrate the usefulness of this method.Letter pubs.acs.org/OrgLett

This paper reports a concise and efficient synthesis method, namely copper-catalyzed direct hydrocarbon dehydrogenation coupling of sulfonamides and aliphatic cyclic tertiary amines, to realize the highly regioselective synthesis of (E)-N-sulfonylformamidines. The reaction is accomplished without any corrosive acid or base as an additive. It tolerates a broad scope of substrates, good functional group compatibility, and generates exclusive (E)-stereoselectivity. Moreover, this utility of the protocol is successfully demonstrated in a late-stage functionalization of medicinally active molecules and gram-scale synthesis. Keywords copper catalysis; aliphatic cyclic tertiary amines; regioselective; sulfonylformamidines 磺酰基脒类片段作为一类独特的分子砌块, 广泛地 存在于生物活性分子和天然产物分子中 [1] . 特别是近年 来它在不同领域具有重要的应用价值. 例如, 它作为重 要的药效团用于药物研发 [2] , 作为关键合成中间体构建 杂环化合物 [3] , 以及作为配体用于过渡金属催化 [4] 等. 因此, 发展高效构建磺酰基脒类骨架的合成方法具有重 要的意义.