Organic compounds labeled with hydrogen isotopes play a crucial role in numerous areas, from materials science to medicinal chemistry. Indeed, while the replacement of hydrogen by deuterium gives rise to improved absorption, distribution, metabolism, and excretion (ADME) properties in drugs and enables the preparation of internal standards for analytical mass spectrometry, the use of tritium-labeled compounds is a key technique all along drug discovery and development in the pharmaceutical industry. For these reasons, the interest in new methodologies for the isotopic enrichment of organic molecules and the extent of their applications are equally rising. In this regard, this Review intends to comprehensively discuss the new developments in this area over the last years (2017-2021). Notably, besides the fundamental hydrogen isotope exchange (HIE) reactions and the use of isotopically labeled analogues of common organic reagents, a plethora of reductive and dehalogenative deuteration techniques and other transformations with isotope incorporation are emerging and are now part of the labeling toolkit.

Isotope labelling, particularly deuteration, is an important tool for the development of new drugs, specifically for identification and quantification of metabolites. For this purpose, many efficient methodologies have been developed that allow for the small-scale synthesis of selectively deuterated compounds. Due to the development of deuterated compounds as active drug ingredients, there is a growing interest in scalable methods for deuteration. The development of methodologies for large-scale deuterium labelling in industrial settings requires technologies that are reliable, robust and scalable. Here we show that a nanostructured iron catalyst, prepared by combining cellulose with abundant iron salts, permits the selective deuteration of (hetero)arenes including anilines, phenols, indoles and other heterocycles, using inexpensive D₂O under hydrogen pressure. This methodology represents an easily scalable deuteration (demonstrated by the synthesis of deuterium-containing products on the kilogram scale) and the air- and water-stable catalyst enables efficient labelling in a straightforward manner with high quality control.

The development of improved catalysts for highly selective hydrogenation of nitroarenes is described. For this purpose Co nanoparticles were supported on ordered mesoporous carbon CMK-3 and characterized in detail. The optimal CMK-3-CoPc catalyst exhibits excellent hydrogenation activity for several (hetero)aromatic nitro compounds and yielded the corresponding anilines under mild conditions (40 °C, 20 bar H₂).

A practical and stable heterogeneous copper catalyst has been developed for dehalogenative deuteration via water–gas shift reaction at low temperature, allowing deuteration of diverse (hetero)aryl halides with good functional group tolerance.