Regio- and chemoselective Csp3–H arylation of benzylamines by single electron transfer/hydrogen atom transfer synergistic catalysis†,Chemical Science

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Regio- and chemoselective Csp3–H arylation of benzylamines by single electron transfer/hydrogen atom transfer synergistic catalysis†
Chemical Science ( IF 7.6 ) Pub Date : 2018-09-12 00:00:00 , DOI: 10.1039/c8sc02965b
Takafumi Ide ₁ , Joshua P Barham ₁ , Masashi Fujita ₁ , Yuji Kawato ₁ , Hiromichi Egami ₁ , Yoshitaka Hamashima ₁

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We present a highly regio- and chemoselective Csp³–H arylation of benzylamines mediated by synergy of single electron transfer (SET) and hydrogen atom transfer (HAT) catalysis. Under well precedented SET catalysis alone, the arylation reaction of N,N-dimethylbenzylamine proceeded via aminium radical cation formation and selectively targeted the N-methyl group. In contrast, addition of PhC(O)SH as a HAT catalyst precursor completely switched the regioselectivity to Csp³–H arylation at the N-benzylic position. Measurement of oxidation potentials indicated that the conjugate base of PhC(O)SH is oxidized in preference to the substrate amine. The discovery of the thiocarboxylate as a novel HAT catalyst allowed for the selective generation of the sulfur-centered radical, so that the N-benzyl selectivity was achieved by overriding the inherent N-methyl and/or N-methylene selectivity under SET catalysis conditions. While visible light-driven α-C–H functionalization of amines has mostly been demonstrated with aniline derivatives and tetrahydroisoquinolines (THIQs), our method is applicable to a variety of primary, secondary and tertiary benzylamines for efficient N-benzylic C–H arylation. Functional group tolerance was high, and various 1,1-diarylmethylamines, including an α,α,α-trisubstituted amine, were obtained in good to excellent yield (up to 98%). Importantly, the reaction is applicable to late-stage functionalization of pharmaceuticals.

中文翻译：

通过单电子转移/氢原子转移协同催化对苯甲胺进行区域和化学选择性 Csp3–H 芳基化†

我们提出了通过单电子转移（SET）和氢原子转移（HAT）催化的协同作用介导的苄胺的高度区域和化学选择性Csp ³ -H芳基化。仅在先例的 SET 催化下， N , N-二甲基苄胺的芳基化反应通过铵自由基阳离子的形成进行，并选择性地靶向N-甲基。相比之下，添加PhC(O)SH作为HAT催化剂前体将区域选择性完全转变为N-苄基位置处的Csp ³ –H芳基化。氧化电位的测量表明，PhC(O)SH 的共轭碱优先于底物胺被氧化。硫代羧酸酯作为新型 HAT 催化剂的发现允许选择性生成以硫为中心的自由基，从而通过在 SET 催化条件下超越固有的N-甲基和/或N-亚甲基选择性来实现N-苄基选择性。虽然可见光驱动的胺 α-C-H 官能化主要是用苯胺衍生物和四氢异喹啉 (THIQ) 来证明的，但我们的方法适用于各种伯、仲和叔苄胺，以实现有效的N-苄基 C-H 芳基化。官能团耐受性高，各种 1,1-二芳基甲胺（包括 α,α,α-三取代胺）的产率良好至优异（高达 98%）。重要的是，该反应适用于药物的后期功能化。

更新日期：2018-09-12

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