Electrochemical Trideuteromethylation with AcOD- <i>d</i> <sub>4</sub> : A Route to CD <sub>3</sub> -Labeled Building Blocks
Deuterium substitution (CH 3 → CD 3 ) can enhance metabolic stability via the kinetic isotope effect and enable bioanalytical mass shifts. We report an electrochemical Kolbe heterocoupling that installs CD 3 at aliphatic positions by coupling carboxylic acids with AcOD- d 4 . The reaction proceeds at room temperature under constant current with Pt electrodes and base. Diverse CD 3 -labeled building blocks are obtained in moderate to good yields, and the method avoids CD 3 I and deuterated solvents.
Authors
- M Garreau
- Katherine M. P. Wheelhouse (ORCID: https://orcid.org/0000-0002-1963-1465)
- Kevin Lam (ORCID: https://orcid.org/0000-0003-1481-9212)
- Lee J. Edwards (ORCID: https://orcid.org/0000-0002-5645-746X)
- Federico Paccoia
- Conall Molloy
- Serena Xhihani
Institutions
- University of Pisa (IT)
- University of Hertfordshire (GB)
- University of Perugia (IT)
- University of Greenwich (GB)
Publication Details
- Journal
- Organic Letters
- Published
- 2026-06-17
- DOI
- https://doi.org/10.1021/acs.orglett.6c02508
- Primary Topic
- Chemical Reactions and Isotopes
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- GlaxoSmithKline
- Innovate UK
- Erasmus+
- HORIZON EUROPE European Innovation Council