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Late-Stage β-C(sp3)–H Deuteration of Carboxylic Acids

preprint
revised on 10.05.2021, 07:23 and posted on 11.05.2021, 08:05 by Alexander Uttry, Sourjya Mal, Manuel van Gemmeren
Carboxylic acid moieties are highly abundant in bioactive molecules. In this study we describe the late-stage β-C(sp3)–H deuteration of free carboxylic acids. Based on our finding that the C–H activation with our catalyst systems is reversible, the de-deuteration process was first optimized. The resulting conditions involve ethylenediamine-based ligands, which, amongst other positions, for the first time enables the functionalization of non-activated methylene β-C(sp3)–H bonds and can be used to achieve the desired deuteration when using a deuterated solvent. The reported method allows for the functionalization of a wide range of free carboxylic acids with diverse substitution patterns, as well as the late-stage deuteration of bioactive molecules and related frameworks.

Funding

Deutsche Forschungsgemeinschaft (SFB 858 and Emmy-Noether-Programme)

History

Email Address of Submitting Author

mvangemmeren@uni-muenster.de

Institution

Westfälische Wilhelms-Universität Münster

Country

Germany

ORCID For Submitting Author

0000-0003-3080-3579

Declaration of Conflict of Interest

no conflict of interests