The Renaissance of H/D Exchange

Abstract

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.

Mild and Selective H/D Exchange at the β Position of Aromatic α‐Olefins by N‐Heterocyclic Carbene–Hydride–Rhodium Catalysts

“…[2] Organometallic catalysts offer the potential for mild reaction conditions with a high degree of regio-and chemoselectivity. [3,4] Although the study of H/D exchange reactions has tended to concentrate on aromatic [2,3a-i] or aliphatic [2,3a-d,j] compounds, there is an increasing interest in the deuteration of vinylic derivatives.…”

New Gateways to the Platinum Group Metal-Catalyzed Direct Deuterium-Labeling Method Utilizing Hydrogen as a Catalyst Activator

“…Based on these useful properties of C-D bonds, deuterium-labeled organic compounds have traditionally been utilized in various scientific fields, such as the elucidation of reaction mechanisms, investigation of metabolism, microanalysis tracers, etc. [1][2][3][4][5][6] Recently, the delay effects of the metabolism of heavy drugs, which are partially deuterium-labeled original drugs, have been in the spotlight. [7][8][9][10][11][12][13][14][15] Therefore, the development of various preparation methods of deuterium-labeled medicines and synthetic precursors are eagerly awaited in order to contribute to the progress of a wide variety of scientific fields.…”

Application of Iridium Catalysts in the Fine Chemicals Industry

“…Besides preparative applications, Ir complexes such as Ir(cod)(acac) or [cp * Ir(PMe 3 )H 3 ]OTf have successfully been applied for hydrogen/deuterium ( H/ D ) exchange reactions, which are important for producing labeled compounds for kinetic and metabolic studies in the pharmaceutical industries [44] . While we do not know of any ' real world ' applications, it has been shown that both selective as well as extensive deuteration are possible, depending on the Ir catalyst and the deuterating agent.…”