Recent Advances in the Synthesis of Deuterium‐Labeled Compounds

Abstract

Deuterium‐labeled compounds are of importance in chemical, environmental, and biological fields. Preparation methods for deuterium‐labeled compounds have been studied extensively in response to increasing demand for these chemicals. In this review, we summarize recent advances in synthetic methods and present a comprehensive overview of diverse routes, including conventional deuteration and hydrogen‐deuterium exchange. Deuteration by the classical process, which starts from appropriate available labeled precursors, is introduced for different reaction types. Key features of hydrogen‐deuterium exchange are elaborated in detail from the perspective of the catalyst and the chemical structure of the substrate. Regioselective deuteration at the target position is discussed because of the role of stereospecific deuterium labeling in medicine. Finally, challenges and future prospects of these processes are discussed to provide a general guideline for the synthesis of deuterium‐labeled compounds.

Calcium Aluminate Induced Pt(0)‐Pt(δ+) Coupling Boost Catalyzed H−D Exchange Reaction of Arenes with Deuterium Oxide

“…Although inverse DÀ H exchange reactions are also possible, in the case of excess D 2 O, the HÀ D exchange reaction proceeds preferentially due to isotopic effects (CÀ D bonds are more stable than CÀ H bonds). [48]…”

“…The Ar−H bond activated by Pt(δ+) continues with D* for H−D exchange (D→E), and finally, Pt(0)‐Pt(δ+) separates the hydrogen‐deuterium exchange product HOD and deuterated aromatics (E→A), and these reaction pathways are considered to proceed simultaneously in multiple steps to obtain deuterated aromatics. Although inverse D−H exchange reactions are also possible, in the case of excess D 2 O, the H−D exchange reaction proceeds preferentially due to isotopic effects (C−D bonds are more stable than C−H bonds) [48] …”

Cu‐catalyzed vinylamination of S‐alkylisothiouronium salts with maleimide and alkylamines

“…Since 2000, the deuteration strategy has been widely used in innovative drug research. [ 22 ] Up to now, more than 10 deuterated drugs have entered the clinical trial stage, and hundreds of patent applications have been authorized by the State Intellectual Property Office. As illustrated in Scheme 5C, we designed and prepared an effective deuteriomethylthioation reagent for aminotrideuteromethylthiolation of maleimide.…”

Mild and selective hydrogen–deuterium exchange for aromatic hydrogen of amines

“…Deuterated organic compounds have been used as probes for mechanistic studies of biologically active compounds and pharmaceuticals and in chemical and biological processes 2–4 . Hydrogen–deuterium exchange (H–D exchange) is one of the methods used for preparation of deuterium‐labeled compounds 4–9 . The introduction of deuterium by H–D exchange is beneficial as the final step in the construction of bioactive compounds 10 .…”