These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Late-Stage β-C(sp3)–H Deuteration of Carboxylic Acids
preprintrevised 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.