A Protocol for the Ortho-Deuteration of Acidic Aromatic Compounds in D 2 O Catalyzed by Cationic Rh III

Org Lett. 2019 Sep 6;21(17):7044-7048. doi: 10.1021/acs.orglett.9b02618. Epub 2019 Aug 27.

Abstract

Methods to catalytically introduce deuterium in synthetically useful yields ortho to a carboxylic acid directing group on arenes typically requires D2 or high catalyst loadings, which makes using these approaches cost prohibitive for large-scale synthesis (equipment and reagent costs respectively). Herein, we present a simplified approach using low catalyst loadings of cationic RhIII and D2O as both deuterium source and solvent and show its application to H/D exchange on various carboxylic acid substrates.