Jump to main content
Jump to site search

Issue 25, 2018
Previous Article Next Article

Direct heterobenzylic fluorination, difluorination and trifluoromethylthiolation with dibenzenesulfonamide derivatives

Author affiliations

Abstract

Functionalization of heterocyclic scaffolds with mono- or difluoroalkyl groups provides unique opportunities to modulate drug pKa, influence potency and membrane permeability, and attenuate metabolism. While advances in the addition of fluoroalkyl radicals to heterocycles have been made, direct C(sp3)–H heterobenzylic fluorination is comparatively unexplored. Here we demonstrate both mono- and difluorination of a range of alkyl heterocycles using a convenient process that relies on transient sulfonylation by the electrophilic fluorinating agent N-fluorobenzenesulfonimide. We also report heterobenzylic trifluoromethylthiolation and 18F-fluorination, providing a suite of reactions for late-stage C(sp3)–H functionalization of drug leads and radiotracer discovery.

Graphical abstract: Direct heterobenzylic fluorination, difluorination and trifluoromethylthiolation with dibenzenesulfonamide derivatives

Back to tab navigation

Supplementary files

Publication details

The article was received on 15 Mar 2018, accepted on 25 May 2018 and first published on 07 Jun 2018


Article type: Edge Article
DOI: 10.1039/C8SC01221K
Chem. Sci., 2018,9, 5608-5613
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    Direct heterobenzylic fluorination, difluorination and trifluoromethylthiolation with dibenzenesulfonamide derivatives

    M. Meanwell, B. S. Adluri, Z. Yuan, J. Newton, P. Prevost, M. B. Nodwell, Chadron M. Friesen, P. Schaffer, R. E. Martin and R. Britton, Chem. Sci., 2018, 9, 5608
    DOI: 10.1039/C8SC01221K

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements