Contra-thermodynamic hydrogen atom abstraction in the selective C−H functionalization of trialkylamine N‑CH3 groups

Barham, Joshua P. and John, Matthew P. and Murphy, John A. (2016) Contra-thermodynamic hydrogen atom abstraction in the selective C−H functionalization of trialkylamine N‑CH3 groups. Journal of the American Chemical Society, 138 (47). pp. 15482-87. ISSN 1520-5126 (https://doi.org/10.1021/jacs.6b09690)

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Abstract

We report a simple one-pot protocol that affords functionalization of N-CH3 groups in N-methyl-N,N-dialkylamines with high selectivity over N-CH2R or N-CHR2 groups. The radical cation DABCO+•, prepared in situ by oxidation of DABCO with a triarylaminium salt, effects highly selective and contra-thermodynamic C−H abstraction from N-CH3 groups. The intermediates that result react in situ with organometallic nucleophiles in a single pot, affording novel and highly selective homologation of N-CH3 groups. Chemoselectivity, scalability, and recyclability of reagents are demonstrated, and a mechanistic proposal is corroborated by computational and experimental results. The utility of the transformation is demonstrated in the late-stage site-selective functionalization of natural products and pharmaceuticals, allowing rapid derivatization for investigation of structure−activity relationships.

ORCID iDs

Barham, Joshua P. ORCID logoORCID: https://orcid.org/0000-0003-1675-9399, John, Matthew P. and Murphy, John A.;
  • Item type:Article
    ID code:58859
    Dates:
    Date
    Event
    30 November 2016
    Published
    18 November 2016
    Published Online
    3 November 2016
    Accepted
    Notes:This is an open access article published under an ACS AuthorChoice License (https://pubs.acs.org/page/policy/authorchoice_termsofuse.html), which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:28 Nov 2016 16:48
    Last modified:11 Nov 2024 11:34
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/58859
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