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

11 May 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


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.


C–H activation
hydrogen isotope exchange
late-stage functionalization
carboxylic acids

Supplementary materials

Uttry et al Deuteration SI


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