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.

Few methods permit the hydrogenation of alkenes to a thermodynamically favored configuration when steric effects dictate the alternative trajectory of hydrogen delivery. Dissolving metal reduction achieves this control, but with extremely low functional group tolerance. Here we demonstrate a catalytic hydrogenation of alkenes that affords the thermodynamic alkane products with remarkably broad functional group compatibility and rapid reaction rates at standard temperature and pressure.

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Simple, Chemoselective Hydrogenation with Thermodynamic Stereocontrol

The catalytic transformations of 1,2-dichlorobenzene, chlorobenzene, 4-chlorobiphenyl, γ-hexachlorocyclohexane (Lindane), naphthalene and phenanthrene were studied over palladium on alumina in hydrogen-saturated water (Pd/Al2O3/H2) at room temperature and ambient pressure. The chlorinated benzenes were rapidly hydrodechlorinated and Lindane was dehydrochlorinated to benzene. Partial or complete hydrogenation was observed for biphenyl and the polycyclic aromatic hydrocarbons. The phenanthrene ring was cleaved at the 9,10-position. In general dechlorination reactions were faster than hydrogenation reactions.

Hydrodechlorination and hydrogenation of aromatic compounds over palladium on alumina in hydrogen-saturated water

This review addresses method developments both homogeneous and heterogeneous Pd- and Pt-catalyzed exchange, including catalyst activation principles and recent practical applications together with example procedures. Specific requirements for isotopically labelled internal MS standard preparation are discussed from a Sanofi-Aventis perspective on recent examples. Copyright © 2010 John Wiley & Sons, Ltd.

Pd- and Pt-catalyzed H/D exchange methods and their application for internal MS standard preparation from a Sanofi-Aventis perspective

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.

A.W. Weitkamp

Papers

Deuteriation and deuterogenation of naphthalene and two octalins