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.

Organic chemistry Z 0200The Renaissance of H/D Exchange -[282 refs.]. -(ATZRODT, J.; DERDAU, V.; FEY, T.; ZIMMERMANN, J.; Angew. Chem., Int. Ed. 46 (2007) 41, 7744-7765; Isotope Chem. Metab. Synth., Sanofi-Aventis Dtschl. GmbH, D-65926 Frankfurt/M., Germany; Eng.) -Bartels 51-243

Die steigende Nachfrage nach stabil isotopenmarkierten Verbindungen führt zu einem verstärkten 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 über einen Austausch von Wasserstoff gegen Deuterium im Zielmolekül deutlich effizienter und preiswerter als über die klassische Synthese. Schwerpunkt dieses Aufsatzes sind präparative Anwendungen der H/D‐Austauschreaktion zur Herstellung Deuterium‐markierter Substanzen. Die Fortschritte der letzten zehn Jahre werden zusammengefasst und kritisch bewertet.

trans-7,8-dimethoxy-11,12-dehydrocalamenene, a projected intermediate for the total synthesis of marine serrulatane and amphilectane diterpenes, was efficiently synthesized. Starting from a styrene, asymmetric Rh-catalyzed hydroboration using a novel chiral P,P-bidentate ligand afforded an organoboron intermediate (93% ee) which was directly used for C-C bond formation (double homologation, Suzuki coupling). The 1,4-trans-disubstituted tetralin skeleton was selectively formed by a Friedel-Crafts-type cationic cyclization under strictly aprotic conditions (Me2AlCl) to suppress a remarkable proton-catalyzed disproportionation via diastereoselective hydride transfer.

Based on a general modular synthetic scheme, a variety of chiral bidentate P/P‐, P/S‐, P/N‐, and P/Se‐ligands is accessible in an efficient divergent manner starting from phenol or naphthol derived backbone systems. A library of 20 selected ligands was tested in the Rh‐catalyzed asymmetric hydroboration of styrene to give 1‐phenylethanol in up to 91% ee after oxidative work‐up. It was demonstrated that small variations of the ligand structures lead to pronounced, unpredictable differences in the performance of the in situ generated rhodium complexes. The modular approach should be applicable for the identification and optimization of suitable ligands for other transition metal‐catalyzed transformations with comparably low effort.