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Synlett 2024; 35(19): 2201-2206
DOI: 10.1055/a-2239-6965
letter
Isotopic Labeling

Directing Hydrogen Isotope Exchange with Aryl Carboxylic Acids

Richard J. Mudd 
a   Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, Scotland, UK, G1 1XL
,
Marc Reid 
a   Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, Scotland, UK, G1 1XL
,
Laura C. Paterson 
a   Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, Scotland, UK, G1 1XL
,
Jens Atzrodt
b   Sanofi Germany, R&D Operations, Industriepark Höchst, 65926 Frankfurt am Main, Germany
,
Volker Derdau 
c   Sanofi Germany, R&D, Integrated Drug Discovery, Isotope Chemistry, Industriepark Höchst, 65926 Frankfurt am Main, Germany
,
William J. Kerr  ∗
a   Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, Scotland, UK, G1 1XL
› Author AffiliationsThe work was funded by postgraduate studentship provision from the University of Strathclyde (R.J.M.) and the Carnegie Trust for the Universities of Scotland (M.R.).
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Abstract

A highly effective and selective ortho-directed hydrogen isotope exchange process for aryl carboxylic acids has been achieved by using an iridium(I) N-heterocyclic carbene/phosphine complex under mild and neutral conditions. Good levels of deuterium incorporation have been delivered across a wide array of examples, including a number of biologically active drug compounds.

Key words

iridium catalysis - hydrogen isotope exchange - deuteration - carboxylic acids - benzoic acids

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2239-6965.
  • Supporting Information


Publication History

Received: 24 November 2023

Accepted after revision: 05 January 2024

Accepted Manuscript online:
05 January 2024

Article published online:
05 February 2024

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  • References and Notes

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