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

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Ide, Takafumi and Barham, Joshua P. and Fujita, Masashi and Kawato, Yuji and Egami, Hiromichi and Hamashima, Yoshitaka (2018) Regio- and chemoselective Csp3-H arylation of benzylamines by single electron transfer/hydrogen atom transfer synergistic catalysis. Chemical Science, 9 (44). pp. 8453-8460. ISSN 2041-6539 (https://doi.org/10.1039/c8sc02965b)

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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.

ORCID iDs

Ide, Takafumi, Barham, Joshua P. ORCID logoORCID: https://orcid.org/0000-0003-1675-9399, Fujita, Masashi, Kawato, Yuji, Egami, Hiromichi and Hamashima, Yoshitaka;
  • Item type:Article
    ID code:92108
    Dates:
    Date
    Event
    28 November 2018
    Published
    12 September 2018
    Published Online
    10 September 2018
    Accepted
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:20 Feb 2025 11:11
    Last modified:20 Feb 2025 11:11
    URI:https://strathprints.strath.ac.uk/id/eprint/92108
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