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Issue 44, 2018
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Regio- and chemoselective Csp3–H arylation of benzylamines by single electron transfer/hydrogen atom transfer synergistic catalysis

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Abstract

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.

Graphical abstract: Regio- and chemoselective Csp3–H arylation of benzylamines by single electron transfer/hydrogen atom transfer synergistic catalysis

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Publication details

The article was received on 05 Jul 2018, accepted on 10 Sep 2018 and first published on 12 Sep 2018


Article type: Edge Article
DOI: 10.1039/C8SC02965B
Citation: Chem. Sci., 2018,9, 8453-8460
  • Open access: Creative Commons BY license
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    Regio- and chemoselective Csp3–H arylation of benzylamines by single electron transfer/hydrogen atom transfer synergistic catalysis

    T. Ide, J. P. Barham, M. Fujita, Y. Kawato, H. Egami and Y. Hamashima, Chem. Sci., 2018, 9, 8453
    DOI: 10.1039/C8SC02965B

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