Recent Advances in Deuteration Reactions†

Abstract

Comprehensive SummaryThe deuteration of organic compounds has attracted more attentions in recent years for the potential applications in new drug discovery and synthetic chemistry. For this purpose, many efficient deuterium labeling methodologies have been developed, including hydrogen isotope exchange (HIE), reductive deuteration, and dehalogenative deuteration that allow for the synthesis of selectively deuterated compounds. In the last few years, great breakthroughs in selective isotope labeling have been achieved and the interest in new methodologies for the deuteration of organic molecules is rising. In this review, we summarized the recent developments in the selective deuteration of organic molecules since 2021. Several types of key processes in deuterium incorporation reactions, including H/D exchange, reductive deuteration and dehalogenative deuteration, are introduced and discussed. Key ScientistsIn the 2000s, Derdau and Atzrodt's group have made great contributions to the directing group assisted noble‐metal catalyzed hydrogen isotope exchange of arenes and applications of labeled compounds. During the same period, Sajiki and co‐workers completed a series of deuteration reactions by heterogeneous platinum‐group metal catalysts. Since 2015, Gregory Pieters and co‐workers have developed ruthenium catalysts for selective hydrogen isotope exchange. In 2016, Chirik's group achieved hydrogen isotope exchange in the presence of a homogeneous iron complex. David MacMillan and coworkers have made breakthroughs in photocatalyzed HIE reactions for α‐amino C(sp3)–H bonds. From 2020, a series of nanoelectrodes were designed for selective dehalogenative deuterations and reductive deuteration of unactivated unsaturated bonds by Zhang's group. Recently, Beller's group developed several efficient strategies for isotopic labeling using heterogeneous earth‐abundant catalysts. Our review summarized the latest and important developments since 2021.