Synthesis, Table of Contents Synthesis 2022; 54(22): 4907-4916DOI: 10.1055/a-1859-8012 feature Palladium-Catalyzed Ligand-Free ortho-Deuteration of Aromatic Carboxylic Acids with D2O Ziyin Zhang‡ a School of Biological and Chemical Engineering, NingboTech University, Ningbo 315100, P. R. of China b School of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, P. R. of China , Zhi-Jiang Jiang ‡ a School of Biological and Chemical Engineering, NingboTech University, Ningbo 315100, P. R. of China , Yiwei Cao a School of Biological and Chemical Engineering, NingboTech University, Ningbo 315100, P. R. of China , Jia Chen∗ a School of Biological and Chemical Engineering, NingboTech University, Ningbo 315100, P. R. of China c Ningbo Cuiying Chemical Technology Co. Ltd., Ningbo 315100, P. R. of China , Zhanghua Gao a School of Biological and Chemical Engineering, NingboTech University, Ningbo 315100, P. R. of China› Author AffiliationsRecommend Article Abstract Buy Article All articles of this category Abstract A ligand-free, palladium-catalyzed ortho-deuteration of aromatic carboxylic acids was developed using D2O as the deuterium source. Compared to their meta-substituted analogues, an unusually lower reactivity in para- and ortho-substituted benzoic acids toward hydrogen isotope exchange was observed. Further investigation revealed that the reaction temperature is a critical parameter for the reactivity, and the modified conditions can afford deuterated products with good to excellent deuterium incorporation. Key words Key wordsbenzoic acids - heavy water - deuteration - hydrogen isotope exchange - palladium - ligand-free Full Text References References 1a Yang J. Deuterium: Discovery and Applications in Organic Chemistry. Elsevier; Amsterdam: 2016 1b Atzrodt J, Derdau V, Kerr WJ, Reid M. Angew. Chem. Int. Ed. 2018; 57: 3022 1c Atzrodt J, Derdau V, Kerr WJ, Reid M. Angew. Chem. 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