Copper-Catalyzed Regioselective C(sp³)—H Sulfonimidization of Aliphatic Cyclic Tertiary Amines

Abstract

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.

The regioselective annulation of N-methylpyridinium ylides with alkenes enabled by palladium catalysis: access to 3-unsubstituted indolizine derivatives

“…Afterward, unstable annulation intermediate 8 a ( A9 , −44.3 kcal mol −1 ) is generated by the reductive elimination of intermediate A7 . After the ligand exchange of A9 , Pd-catalysed dehydrogenation of A10 occurs with a barrier of 4.0 kcal mol −1 releasing 9.7 kcal mol −1 to form A12 , followed by the oxidative aromatization 8 j ,21 with the assistance of oxidant NaBrO 3 and copper salt to access the annulation product 3a . Meanwhile, Pd 0 released from the catalytic cycle is reoxidized to Pd II to achieve catalytic turnover.…”

Mechanochemical Metal‐free N‐Sulfonyl Transfer Reaction: Expedient Synthesis of N‐Sulfonyl Amidines

“…[33][34][35] With sulfonamides various metal catalysts and iodine reagents were deployed to afford the N-sulfonyl amidines (Scheme 1d-f). [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] In general, the reported synthesis of N-sulfonyl amidines requires organic solvents, excess Lewis acids/bases, metal catalysts, high temperature, pressure, and multiple equipment. It is noteworthy that usage of these contribute to the contamination of the environment subsequently making the strategies less sustainable.…”

Metal-Free Direct Access toN-Sulfonyl Amidines from Sulfonamides and Secondary Amines Involving Tandem C–N Bond Formations

“…Reactions of sulfonamides with secondary amines were investigated with CuBr at 100 °C to furnish N -sulfonyl amidines (Scheme f) . In addition, other methods have also been developed for the synthesis of N -sulfonyl amidines. Most of these methods require stoichiometric or catalytic amounts of transition metal catalysts, potentially explosive sulfonyl azides, hazardous reagents, environmentally unfriendly solvents, elevated temperatures, limited substrate scope, expensive catalysts, relatively long reaction times, and harsh reaction conditions.…”