As the breadth of radical chemistry grows, new means to promote and regulate single-electron redox activities play increasingly important roles in driving modern synthetic innovation. In this regard, photochemistry and electrochemistry—both considered as niche fields for decades—have seen an explosive renewal of interest in recent years and gradually have become a cornerstone of organic chemistry. In this Outlook article, we examine the current state-of-the-art in the areas of electrochemistry and photochemistry, as well as the nascent area of electrophotochemistry. These techniques employ external stimuli to activate organic molecules and imbue privileged control of reaction progress and selectivity that is challenging to traditional chemical methods. Thus, they provide alternative entries to known and new reactive intermediates and enable distinct synthetic strategies that were previously unimaginable. Of the many hallmarks, electro- and photochemistry are often classified as “green” technologies, promoting organic reactions under mild conditions without the necessity for potent and wasteful oxidants and reductants. This Outlook reviews the most recent growth of these fields with special emphasis on conceptual advances that have given rise to enhanced accessibility to the tools of the modern chemical trade.

Interest in deuterated active pharmaceutical ingredients (APIs) is increasing as deuteration holds promise for kinetic isotope effect (KIE) regulated finetuning of API performance. Moreover, deuterium isotope labeling is frequently carried out to study organic and bioorganic reaction mechanisms and to facilitate complex target synthesis. As such, methods for highly selective deuteration of organic molecules are highly desirable. Herein, we present an electrochemical method for the selective deuterodehalogenation of benzylic halides via a radical-polar crossover mechanism, using inexpensive deuterium oxide (D 2 O) as the deuterium source. We demonstrate broad functional group compatibility across a range of aryl and heteroaryl benzylic halides. Furthermore, we uncover a sequential paired electrolysis regime, which permits switching between net reductive and overall redox-neutral reactions of sulfurcontaining substrates simply by changing the identity of the sacrificial reductant employed.Methods that achieve site-specific incorporation of deuterium atom are desirable in many research areas spanning physical organic chemistry, target-oriented synthesis, medicinal chemistry, and chemical biology. Deuterium isotope labeling is often employed to probe the mechanism of organic reactions in chemical and enzymatic settings by tracking the fate of the D atom or elucidating the kinetic profile through the kinetic isotope effect (KIE). [1] In addition, deuterated intermediates have demonstrated utility in the synthesis of various complex natural products such as norzoanthamine, [2] welwitindolinones, [3] and taxol [4] by decelerating undesirable side reactions. In the realm of pharmaceutical development, extensive research has been devoted to understanding how active pharmaceutical ingredients (APIs) behave in vivo [5] and how to prevent oxidative degradation, which is a major pathway in drug metabolism. [6] Recent reports suggest that efficacy [7] and toxicity metrics [8] for certain APIs can be improved by deuteration of metabolically oxidizable [9] CÀ H bonds. [10] KIE could be leveraged without compromising the conformational structure or reactivity of an API, thus allowing efficacy to be tuned to improve the pharmacokinetic profile. [11][12] Further-more, deuteration can be employed to decrease the rate at which APIs react with off-target enzymes. For example, a major metabolite of gemfibrozil reacts irreversibly with heme in P450 2C8 (Scheme 1A), [13] but the rate of this

Interest in deuterated active pharmaceutical ingredients (APIs) is increasing as deuteration holds promise for kinetic isotope effect (KIE) regulated fine‐tuning of API performance. Moreover, deuterium isotope labeling is frequently carried out to study organic and bioorganic reaction mechanisms and to facilitate complex target synthesis. As such, methods for highly selective deuteration of organic molecules are highly desirable. Herein, we present an electrochemical method for the selective deuterodehalogenation of benzylic halides via a radical‐polar crossover mechanism, using inexpensive deuterium oxide (D2O) as the deuterium source. We demonstrate broad functional group compatibility across a range of aryl and heteroaryl benzylic halides. Furthermore, we uncover a sequential paired electrolysis regime, which permits switching between net reductive and overall redox‐neutral reactions of sulfur‐containing substrates simply by changing the identity of the sacrificial reductant employed.

Herein a bimetallic radical redox-relay strategy is employed to generate alkyl radicals under mild conditions with titanium(III) catalysis and terminated via hydrogen atom transfer with cobalt(II) catalysis to enact base-free isomerizations of N-Bz aziridines to N-Bz allylic amides. This reaction provides an alternative strategy for the synthesis of allylic amides from alkenes via a three-step sequence to accomplish a formal transpositional allylic amination.

Interest in deuterated de novo active pharmaceutical ingredients (APIs) is increasing due to the release of the first FDA approved deuterated drug, deutetrabenazine. Deuteration also holds promise for kinetic isotope effect (KIE) regulated fine-tuning of active pharmaceutical ingredient performance. As such, methods for highly selective deuteration of organic molecules—particularly at positions that are prone to undergoing biochemical reactions—are highly desirable. Herein, we present an electrochemical method for the selective deuterodehalogenation of benzylic halides via a radical-polar crossover mechanism, using inexpensive deuterium oxide (D2O) as the deuterium source. We demonstrate broad functional group compatibility across a range of aryl and heteroaryl benzylic halides. Furthermore, we uncover a sequential paired electrolysis regime, which permits switching between net reductive and overall redox-neutral reactions of sulfur-containing substrates simply by changing the identity of the sacrificial reductant employed.