Abstract
Deuterium incorporation is crucial in organic synthesis and has wide applications in the pharmaceutical industry. State-of-the-art H/D isotope exchange and chemical defunctionalization for deuterium incorporation suffer from significant drawbacks, including expensive deuterium sources, low deuteration efficiency and poor selectivity. In this perspective, we highlight an alternative pathway for forming C-D bonds by electrocatalytic heavy water splitting (D2O) under mild conditions. In addition, the intrinsic mechanism and examples of the synthesis of deuterated pharmaceuticals are discussed in detail. Finally, we present the challenges facing this field and provide an overall perspective on future research directions.
Highlights
Since the discovery of deuterium by Urey et al.[1] in 1932, deuterated compounds have been extensively employed in various applications
The growing interest in catalytic C-H activation and deuterated compounds as references in mass spectrometry led to the rapid development of this field in the mid1990s[2,3,4]
Tremendous efforts have been devoted to the synthesis of deuterated pharmaceuticals, including the first US Food and Drug www.energymaterj.com
Summary
Since the discovery of deuterium by Urey et al.[1] in 1932, deuterated compounds have been extensively employed in various applications. In line with the defunctionalization strategy, deuterium labelling by electrochemical heavy water (D2O) splitting affords a greener, safer and more efficient method [Figure 1C][33] than conventional H/D exchanges or difunctionalization-based deuteration with strong reductive reagents This electrochemical method allows the use of electrons as a green reductant source and can be readily controlled by adjusting external parameters, such as the electrolytes and applied voltages, as well as by materials engineering of the catalyst. While significant advances have been made in electrochemical deuteration, the energy-related aspects of the entire electrochemical process need to be considered for their successful translation to industrial applications This includes the suppression of side reactions to improve the FE, recycling of unused heavy water for cost reduction and better reactor designs that integrate with state-of-the-art electrolyzer technologies to reduce electricity consumption. This underscores the importance of integrating flow cell technologies and modular operations for translating laboratorial practice to industrial applications
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