The increasing demand for stable isotopically labeled compounds has led to an increased interest in H/D-exchange reactions at carbon centers. Today deuterium-labeled compounds are used as internal standards in mass spectrometry or to help elucidate mechanistic theories. Access to these deuterated compounds takes place significantly more efficiently and more cost effectively by exchange of hydrogen by deuterium in the target molecule than by classical synthesis. This Review will concentrate on the preparative application of the H/D-exchange reaction in the preparation of deuterium-labeled compounds. Advances over the last ten years are brought together and critically evaluated.

The renaissance of H/D exchange.

Hydrogen isotopes are unique tools for identifying and understanding biological and chemical processes. Hydrogen isotope labelling allows for the traceless and direct incorporation of an additional mass or radioactive tag into an organic molecule with almost no changes in its chemical structure, physical properties, or biological activity. Using deuterium-labelled isotopologues to study the unique mass-spectrometric patterns generated from mixtures of biologically relevant molecules drastically simplifies analysis. Such methods are now providing unprecedented levels of insight in a wide and continuously growing range of applications in the life sciences and beyond. Tritium (3 H), in particular, has seen an increase in utilization, especially in pharmaceutical drug discovery. The efforts and costs associated with the synthesis of labelled compounds are more than compensated for by the enhanced molecular sensitivity during analysis and the high reliability of the data obtained. In this Review, advances in the application of hydrogen isotopes in the life sciences are described.

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Deuterium- and Tritium-Labelled Compounds: Applications in the Life Sciences

In this contribution, we provide a comprehensive overview of C-H activation methods promoted by NHC-transition metal complexes, covering the literature since 2002 (the year of the first report on metal-NHC-catalyzed C-H activation) through June 2019, focusing on both NHC ligands and C-H activation methods. This review covers C-H activation reactions catalyzed by group 8 to 11 NHC-metal complexes. Through discussing the role of NHC ligands in promoting challenging C-H activation methods, the reader is provided with an overview of this important area and its crucial role in forging carbon-carbon and carbon-heteroatom bonds by directly engaging ubiquitous C-H bonds.

N-Heterocyclic Carbene Complexes in C–H Activation Reactions

The use of deuteration in medicinal chemistry has exploded in the past years, and the FDA has recently approved the first deuterium-labeled drug. Precision deuteration goes beyond the pure and simple amelioration of the pharmacokinetic parameters of a drug and might provide an opportunity when facing problems in terms of metabolism-mediated toxicity, drug interactions, and low bioactivation. The use of deuterium is even broader, offering the opportunity to lower the degree of epimerization, reduce the dose of coadministered boosters, and discover compounds where deuterium is the basis for the mechanism of action. Nevertheless, designing, synthesizing, and developing a successful deuterated drug is far from straightforward, and the translation from concept to practice is often unpredictable. This Perspective provides an overview of the recent developments of deuteration, with a focus on deuterated clinical candidates, and highlights both opportunities and challenges of this strategy.

Applications of Deuterium in Medicinal Chemistry

N-Heterocyclic carbenes (NHC) are nowadays ubiquitous and indispensable in many research fields, and it is not possible to imagine modern transition metal and main group element chemistry without t...

N-Heterocyclic Carbene Adducts of Main Group Elements and Their Use as Ligands in Transition Metal Chemistry.

The various applications of hydrogen isotopes (deuterium, D, and tritium, T) in the physical and life sciences demand a range of methods for their installation in an array of molecular architectures. In this Review, we describe recent advances in synthetic C-H functionalisation for hydrogen isotope exchange.

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C-H Functionalisation for Hydrogen Isotope Exchange.

Die steigende Nachfrage nach stabil isotopenmarkierten Verbindungen fuhrt zu einem verstarkten Interesse an H/D-Austauschreaktionen an Kohlenstoffatomen. Heutzutage werden Deuterium-markierte Verbindungen als interne Standards in der Massenspektrometrie eingesetzt oder helfen dabei, mechanistische Theorien zu untermauern. Der Zugang zu diesen deuterierten Verbindungen erfolgt uber einen Austausch von Wasserstoff gegen Deuterium im Zielmolekul deutlich effizienter und preiswerter als uber die klassische Synthese. Schwerpunkt dieses Aufsatzes sind praparative Anwendungen der H/D-Austauschreaktion zur Herstellung Deuterium-markierter Substanzen. Die Fortschritte der letzten zehn Jahre werden zusammengefasst und kritisch bewertet.

Die Renaissance des H/D-Austausches

The wide range of applications involving hydrogen isotopes in drug discovery and beyond dictates that their selective and efficient installation continues to present an important and continuing challenge to synthetic chemists. In this review advances in the field of hydrogen isotope exchange over the last ten years and related hydrogen isotope applications in a broad spectrum of disciplinary areas are brought together.

Jens Atzrodt

Papers

Deuterium- and Tritium-Labelled Compounds: Applications in the Life Sciences

C-H Functionalisation for Hydrogen Isotope Exchange.

Die Renaissance des H/D-Austausches

Deuterium- und tritiummarkierte Verbindungen: Anwendungen in den modernen Biowissenschaften

Iridium-catalysed ortho-H/D and -H/T exchange under basic conditions: C–H activation of unprotected tetrazoles