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

Carboxylic acids are highly abundant in bioactive molecules. In this study, we describe the late-stage beta-C(sp(3))-H deuteration of free carboxylic acids. On the basis of the finding that C-H activation with our catalysts is reversible, the dedeuteration process was first optimized. The resulting method uses ethylenediamine-based ligands 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 and enables the functionalization of nonactivated methylene beta-C(sp(3))-H bonds for the first time.