Hydrogen isotope exchange (HIE) has played an increasingly important role in deuteration and tritiation of compounds in the pharmaceutical industry. Transition metal-catalyzed HIE methods have gained considerable attention in the past decades, and most of these methods were comprehensively reviewed in 2010 in a special JLCR issue. It covered a wide variety of HIE catalysis systems involving precious metal catalysts, and a relatively small percentage of base metal catalysts, with a major focus on heterogeneous nickel. While base metal catalysts have remained underdeveloped for HIE chemistry relative to second and third row transition metal catalysts, in recent years, the first examples of homogeneous iron, nickel, and cobalt catalysts have been introduced to the field. Hence, in this review, we describe the recent development of base metal catalysts for HIE and their applications in isotopic labeling of pharmaceutical compounds. These research efforts have resulted in the development of labeling approaches that complement traditional methods in terms of activity and selectivity, thus diversifying the methodologies available for isotope chemists.
Keywords: Base metal catalysis; Deuterium; Iron; Nickel.
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