Deep Electroreductive Chemistry: Harnessing Carbon- and Silicon-based Reactive Intermediates in Organic Synthesis

Abstract

This Viewpoint outlines our recent contribution in electroreductive synthesis. Specifically, we leveraged deeply reducing potentials provided by electrochemistry to generate radical and anionic intermediates from readily available alkyl halides and chlorosilanes. Harnessing the distinct reactivities of radicals and anions, we have achieved several challenging transformations to construct C–C, C–Si, and Si–Si bonds. We highlight the mechanistic design principle that underpinned the development of each transformation and provide a view forward on future opportunities in growing area of reductive electrosynthesis.

Graphical Abstract

1. INTRODUCTION

The development of general and selective methods to generate and transform reactive intermediates such as radicals, cations, and anions remains an important objective in modern organic chemistry.¹ In the realm of two-electron chemistry, reactive ionic intermediates have been traditionally accessed using organometallic reagents or strong Lewis/Brönsted acids, which are often highly reactive but can be limited by functional group tolerance and selectivity. Complimentary to two-electron chemistry, the unique electronic configuration and distinct reactivity of radicals enable their use for challenging transformations. Early work on radical intermediates employed potentially hazardous initiators, such as tin reagents and peroxides, hampering the broad adoption of radical reactions in organic synthesis.² To address the challenges associated with highly reactive intermediates and further advance their chemistry, transition metal catalysis,³ organocatalysis,⁴ photoredox chemistry,⁵ and biocatalysis⁶ have emerged as increasingly powerful tools in organic synthesis. Nevertheless, the continued development of complementary approaches that can provide controlled access to both one- and two-electron paradigms remains highly desirable.

Electrochemistry can promote the formation of both radical and ionic intermediates by applying sufficient activating potentials to common organic functional groups.7 In contrast to canonical chemical redox reactions, electrochemistry provides access to a wide potential window, which is limited only by stability of the solvent and electrolyte. Importantly, modulation of the electric potential and current allows for precise control over the identity and concentration of the reactive intermediates generated at the electrodes. These attributes make electrochemistry an efficient method for accessing and controlling the reactivity of both radical and ionic intermediates. Indeed, pioneering studies over the last several decades have demonstrated the versatility of this approach in guiding unstable intermediates through reaction pathways with high chemofidelity. ⁸ Not surprisingly, in the past several years synthetic electrochemistry has rapidly expanded into a major subfield of modern organic chemistry and been adopted by many sectors of academic and industrial research. However, while there is a large and increasing body of literature on oxidative electrosynthesis, reductive electrochemical reactions are substantially less reported.⁹ We attribute this striking difference to the intrinsic challenges associated with reductive electrosynthesis. In general, electroreductive reactions require the use of sacrificial anodes or reductants, which may cause electrode fouling or interfere with desired cathodic reactions. Moreover, the low overpotentials for hydrogen and oxygen reduction often require such reactions to be run under strictly anhydrous and anaerobic conditions. Nevertheless, the prospect of gaining convenient and controlled access to reactive intermediates at deep reductive potentials has driven a renewed interest in expanding the scope of reductive electrosynthesis in recent years.

The earliest example of an electroreductive reaction was the dehalogenation of trichloromethanesulfonic acid developed by Schoebein,¹⁰ reported shortly before the venerable Kolbe electrolysis.¹¹ Since then, other noteworthy reductive electrochemical reactions, such as the Tafel rearrangement,¹² the reductive coupling of ketones,¹³ and the carboxylation of organohalides¹⁴ have been developed. Today, several commodity chemicals are produced via electroreductive syntheses, including 1,4-dihydronaphthalene, adiponitrile, 4-aminomethylpyridine, succinic acid, and azobenzene (Figure 1).¹⁵ Interestingly, these industrial reactions are operated at potentials ranging from −1.0 to −2.6 V, highlighting the wide potential window available to synthetic chemists.

Figure 1.

Electroreductive synthesis: (A) Select early examples of electroreductive reactions. (B) Select fine chemicals produced by reductive electrolysis in industry.

Inspired by these precedents, our laboratory is particularly interested in leveraging radicals and anions generated from common electrophilic functional groups in organic electrosynthesis. In this Viewpoint, we highlight our recent campaign in this field (Figure 2). First, we discuss our strategy for the selective electrochemical reduction of alkyl halides and its utility towards alkene carbofunctionalization and cross-electrophile coupling reactions. We then summarize our contribution to the synthesis of organosilicon compounds via electrochemical reduction of chlorosilanes. We conclude with a view forward and discuss future opportunities in reductive electrosynthesis.

Figure 2.

Electroreductive chemistry of alkyl halides and chlorosilanes contributed by our group.

2. ELECTROCHEMICAL REDUCTION OF ALKYL HALIDES

Alkyl halides are among the most prevalent functional groups in organic molecules.¹⁶ In addition to being excellent electrophiles, alkyl halides are also used as precursors for alkyl radicals (Figure 3). Unactivated alkyl halides often exhibit significantly negative single-electron reduction potentials that are challenging to access in a selective manner using traditional chemical reagents. To circumvent this issue, tin, silicon, or boron-based initiators have been used to transform alkyl halides into alkyl radicals, often via a halogen atom transfer mechanism (XAT).¹⁷ Likewise, transition metals such as Ni have also been shown to undergo oxidative addition to alkyl halides.¹⁸ Recently, these activation approaches have been integrated with photoredox catalysis to further diversify the radical transformations of alkyl halides.¹⁹

Figure 3.

Strategies and select reagents used to generate alkyl radicals from alkyl halides.

Advantageously, the highly biased potentials accessible with electrochemistry offer an efficient means to directly reduce alkyl halides to alkyl radicals without the use of additional activating agents.²⁰ Furthermore, depending on the substrate structure and applied potential, electrochemistry can also turn on two-electron reduction pathways, thus granting access to alkyl anions and the reactions associated with these intermediates. The electroreductive activation of alkyl halides has been extensively studied using cyclic voltammetry,²¹ which laid the foundation for a number of pioneering contributions by Perichon and others²⁰ to the development of Giese,²² carboxylation,²³ and alkylation reactions.²⁴ Nevertheless, the types of transformations enabled by this strategy remain limited, and the exploration of these methods in complex environments relevant to medicinal and materials applications is rare.

2.1. Reductive Carbofunctionalization of Alkenes

Our initial research focused on the electroreductive carbofunctionalization of alkenes with alkyl bromides. Electrochemistry has been explored as an efficient approach for the difunctionalization of alkenes,²⁵ but prior work has primarily interrogated oxidative transformations by activating nucleophile reagents.^25,26 We envisioned a radical-polar crossover mechanism for the desired carbofunctionalization by means of an electrochemical-chemical-electrochemical-chemical (ECEC) process (Figure 4A).²⁷ Specifically, selective cathodic reduction of an alkyl bromide would form an alkyl radical capable of adding into an alkene to deliver a new carbon-centered radical (4–4). This radical would be further reduced at the cathode to generate a carbanion (4–5), which could then be intercepted by a second electrophile (E⁺) to afford the product 4–6. To achieve this reaction in high regio- and chemo-selectivity, possible side products (4–7 to 4–10) derived from the radical and anion intermediates must be inhibited. Thus, the choice of E⁺ is key so that the alkyl bromide is selectively reduced (instead of E⁺) and so that resultant carbanion (4–5) selectively reacts with E⁺ (instead of the alkyl bromide). In addition, the alkene substrate should stabilize both radical and anionic intermediates to facilitate the initial radical addition and subsequent reduction over radical dimerization. With these criteria in mind, knowledge of the reduction potentials of various electrophiles and radicals is critical to reagent selection (Figure 4B).

Figure 4.

Electroreductive carbofunctionalization of alkenes with alkyl bromides.²⁷ (A) Reaction design princeple. (B) Reduction potentials of some relevant reagents and intermediates.

Following these criteria, we developed various reductive carbofunctionaliztion reactions of terminal alkenes (Figure 5A).²⁷ These reactions typically employ graphite as the working electrode and a sacrificial magnesium anode that releases Mg²⁺ into the solution during electrolysis (Figure 5A). For example, using N,N-dimethylformamide (DMF) as both the solvent and a formyl group donor allowed us to realize the intermolecular carboformylation of alkenes (Figure 5B, box a). This reaction is compatible with various electronically disparate conjugated alkenes, including styrenes and vinyl-N-heteroarenes. Acyclic and cyclic secondary and tertiary alkyl bromides were tolerated. Using a solvent with acidic protons, such as acetonitrile (MeCN), further allowed us to access anti-Markovnikov hydroalkylated products (Figure 5B, box b). Although several transition-metal based catalysts are available for similar transformations,²⁸ this electrochemical reaction provides a complementary approach to hydroalkylation of alkenes via a distinct mechanism. Owing to the radical or anion stabilization effect, non-styrenyl alkenes such as vinyl pinacol boronic esters and 2-acetamidoacrylate could also be used (products 5–9 and 5–10, respectively).

Figure 5.

Electroreductive carbofunctionalization of alkenes: reaction development. (A) Optimal reaction condition. (B) Representative reaction scope. (C) Synthesis of precursor of bioactive molecules.

Finally, motivated by prior work demonstrating that CO₂ can be used in electrochemical carboxylation,^{14, 23, 29} in particular the dicarboxylation³⁰ and hydrocarboxylation³¹ of alkenes, we extended this approach to the carbocarboxylation of alkenes using CO₂ as the second electrophile (Figure 5B, box c)²⁷. Of note, the resultant α-arylacetic acid products (5–11, 5–14, 5–15) are prevalent scaffolds in bioactive molecules.³² The diversity and availability of alkenes and alkyl bromides further allowed us to synthesize a series of analogs to bioactive molecules and their precursors in a modular and expedient manner³³ (Figure 5C), highlighting the benefit of this electrochemical method.

2.2. Cross-Electrophile Coupling for C(sp³)–C(sp³) Bond Formation

In recent years, cross-electrophile coupling (XEC) has become a versatile and efficient approach for the construction of C–C bonds from readily available electrophiles, such as organohalides³⁴ Despite advances in Ni-catalyzed XEC reactions for C(sp²)–C(sp²)³⁵ and C(sp²)–C(sp³) bond formation³⁶, selective XEC of two alkyl halides to construct C(sp³)–C(sp³) bonds remains challenging.³⁷ Current methods relying on transition metal catalysis are frequently plagued by undesired competitive homocoupling^{37a, b, c} in addition to other side reactions associated with metal–alkyl intermediates.

Taking advantage of the marked differences in the electronic and steric properties of alkyl halides with disparate (i.e., primary, secondary, or tertiary) substitution patterns, we envisioned an electrochemically driven XEC (e-XEC) as a new and complementary approach to achieve selective substrate activation toward the desired cross coupling.³⁸ Specifically, a more substituted alkyl bromide (secondary or tertiary; 6–1) could undergo two successive one-electron reductions at the cathode preferentially in the presence of a more reductively inert primary alkyl halide (6–4), generating a carbanion intermediate (6–3) after loss of Br⁻. This intermediate would then preferentially react with a sterically more accessible primary alkyl bromide (6–4) in an S_N2 pathway to furnish the XEC product (Figure 6A).

Figure 6.

Electrochemically driven XEC reaction.³⁸ (A) Reaction design principle. (B) Initial trial with unactivated alkyl bromides: alkyl radical reduction is in competition with radical side reactions. (C) The use of anion stabilizing substituents promotes the desired reactivity.

Cognizant of the difficulty of reducing simple alkyl radicals to carbanions (Figure 6B), we strategically employed tertiary alkyl halides with an anion-stabilizing substituent at the α position to ensure the success of this reaction design (Figure 6C). Density functional theory (DFT) calculations and cyclic voltammetry (CV) measurements suggested that groups such as boryl, aryl, and alkenyl facilitate the overall two-electron reduction by means of conjugative or hyperconjugative stabilization of the resultant carbanions. Importantly, these substituents, such as Bpin, could be further elaborated into other useful functional groups.³⁹

Mechanistically, our design principle is fundamentally different from previously reported Ni-XEC reactions,^{37a, b, c} allowing us to bypass the traditional limitations associated with Ni catalysis. Indeed, when we monitored the reaction of a tertiary α-bromoboronate ester (7–1) with a primary alkyl bromide (7–2) (Figure 7A), the e-XEC reaction showed excellent chemoselectivity, with no evidence of homocoupling (a typical side reaction in Ni catalyzed systems) and only traces (≤5%) of hydrodehalogenation and elimination products. Notably, decreasing the amount of primary alkyl bromide to 1.05 equivalents, the reaction still proceeded in good yield (68%) with excellent chemoselectivity.

Figure 7.

Electrochemical XEC of alkyl halides: reaction development. (A) Optimal reaction conditions. (B) Representative reaction scope. (C) Formal benzylic C-H bond methylation

Following optimization of the reaction conditions, we extended the scope of the transformation to a broad range of alkyl halides (Figure 7B). Functional groups such as alkyl chloride, carbamate, ester, nitrile, and heteroarenes are preserved under these highly reducing reaction conditions. In tandem with initial photochemical benzylic C–H chlorination,⁴⁰ we further applied our e-XEC methodology to achieve the formal benzylic C–H methylation of 7–14 in good yield (Figure 7C).

Control experiments with radical and anion probes supported our proposed mechanism for the e-XEC reaction (Figures 8A–8B). For instance, when the radical probe substrate 8–1 with a cyclopropyl ring was employed, the ring opening product 8–3 was observed, supporting the presence of a radical intermediate under the reaction conditions. Furthermore, subjecting chiral alkyl bromide 8–5 to the reaction conditions led to enantioenriched product 8–6, suggesting C–C bond formation via a concerted S_N2 mechanism operating through a carbanion intermediate. Finally, we successfully carried out the e-XEC reaction on a 20-mmol scale using a modified procedure with dimethoxyethane (DME) as a co-solvent, producing nearly 4 g of 8–8 in excellent yield (Figure 8C).

Figure 8.

(A) and (B) Control experiments to probe the mechanism of electrochemical XEC of alkyl halides, (C) synthesis scale-up, and (D) development of deuterohalogenation.

The same reaction strategy has recently been applied to the development of a deuterodehalogenation reaction of benzylic halides (Figure 8D).⁴¹ Through systematic optimization of homogenous reductants, it was found that diisopropylethyl amine (DIPEA) could undergo anodic oxidation on a carbon electrode to counterbalance the desired cathodic reduction of alkyl halides, thus avoiding the use of a sacrificial metal anode. Under this parallel paired electrolysis system, a variety of simple and complex benzylic bromides and chlorides were efficiently deuterated using D₂O as the deuterium source.

3. ELECTROCHEMICAL REDUCTION OF CHLOROSILANES

Having achieved electroreductive transformations of alkyl halides, we were interested in extending this mechanistic platform to the reductive activation of chlorosilanes to construct Si–R (R = C, Si) bonds. Silicon-containing compounds have attracted great interest in organic chemistry, medicinal chemistry, and materials science.⁴² For example, organosilanes are more stable alternatives to organoboranes in cross-coupling reactions (i.e., Hiyama coupling).⁴³ In addition, the strategic incorporation of silicon bioisosteres into bioactive compounds has become a common strategy to optimize the lipophilicity, biological activity, and overall therapeutic potential of drug molecules.⁴⁴ Oligosilanes are also key intermediates in the preparation of industrially valuable materials such as silicon carbide.⁴⁵ As such, practical methods to synthesize Si–C or Si–Si bonds from abundant feedstocks are highly desirable.

Chlorosilanes are among the most available silyl reagents in organic synthesis and are traditionally used as electrophiles to construct Si–O, Si–Si, or Si–C bonds.⁴⁶ In comparison, the reductive activation of chlorosilanes to generate silyl radicals and silyl anions remains challenging due to the strength of the Si–Cl bond (BDE = 110 kcal/mol) and its low single-electron reduction potential (–3.1 V vs SCE).⁴⁷ We envisioned that reduction of chlorosilane could be achieved using electrochemistry and the resultant radical intermediate could then be interfaced in a radical-polar crossover mechanism to achieve either alkene difunctionalization or cross-electrophile coupling, in a manner akin to the alkyl halide reactivity described in Section 2 (see Figure 2). In particular, depending on the structure of the chlorosilane and the reaction conditions, one could selectively access either one-electron or two-electron reduction pathways to yield either silyl radicals or anions. In the following sections, we highlight our contributions in developing a general and mild approach for the synthesis of organosilanes and oligosilanes via the electrochemical reduction of chlorosilanes.

3.1. Reductive Disilylation of Alkenes

Silyl radicals are typically strongly nucleophilic and can react with various π-electrophiles such as alkenes, providing an expedient approach to generating Si–C bonds.⁴⁸ Typically, silyl radicals have been generated by hydrogen atom abstraction from hydrosilanes via chemical⁴⁹or photochemical^{47, 50} initiation, but these methods are often limited by the availability of hydrosilanes.⁵¹ Activation of Si–X (X = Si,⁵² B,⁵³ or P⁵⁴, etc.⁵⁵) bonds has emerged as an alternative approach to access silyl radicals, though these precursors are often synthesized from chlorosilanes. The electroreductive generation of silyl radicals directly from readily available chlorosilanes is an attractive alternative to these methods, but there are few examples in organic synthesis. In an early report, Hengge⁵⁶ and Shono⁵⁷ demonstrated the overall two-electron reduction of chlorosilanes to generate silyl anions via silyl radicals, but the interception of intermediate silyl radicals for C-Si bond formation remained underexplored.⁵⁸

In our design, reduction of chlorosilanes would enable an ECEC mechanism similar to the one encountered with alkyl halides (Figure 9A).⁵⁹ Specifically, chlorosilane reduction would generate a silyl radical (9–2) capable of rapidly adding across an alkene to furnish a new carbon-centered radical (9–4). Reduction of this new radical species to form anion 9–5 followed by termination with a suitable electrophile (E⁺) would then generate the desired product.

Figure 9.

Electroreductive disilylation of alkenes.⁵⁸ (A) Reaction design principle. (B) Optimal reaction conditions. (C) Representative reaction scope.

We first developed the electroreductive disilylation of styrenes using two equivalents of trimethylsilyl chloride (TMSCl) as both silyl radical precursor and anion-terminating electrophile (Figures 9B–9C). A wide range of electron-withdrawing or electron-donating groups were found to be tolerated on the alkene (e.g., 9–9 and 9–10), and heterocycles such as vinylpyridine were also suitable substrates (9–11). Allenes were smoothly converted to disilanes (e.g., 9–12). In addition to styrenes, vinyl boronates also proved to be excellent radical acceptors, undergoing disilylation to yield gem-(B, Si) substitution (9–13). By using dichlorodisilanes as reagents, we could access silacycles (e.g., 9–14 and 9–15), which are often challenging to synthesize.⁶⁰

Cyclic voltammetry studies revealed that reduction of TMSCl occurs at a higher potential than styrene and should be favored under the experimental conditions. Further, the use of radical probe 10–1 or anion probe 10–4 as substrates resulted in ring opening of the cyclopropane (10–3) and formation of an allylic silane (10–6), respectively, suggesting the formation of both radical and anionic intermediates along the reaction path (Figure 10A). Multivariate linear regression analysis revealed that the reaction rate is dependent on both the electronic properties of the alkene and the stability of the benzylic radical. Altogether, these observations support that dual C–Si bond formation occurs via the proposed radical-polar crossover mechanism (Figure 9A).

Figure 10.

(A) Radical and anion probe substrates used to investigate the mechanism of reductive alkene disilylation. (B) Extension of this reactivity to other substrates.

We envisioned that in the presence of a judiciously selected second electrophile (E⁺) other than TMSCl, other silylation reactions may be achieved (Figure 10B). Specifically, if the chosen electrophile is more challenging to reduce than chlorosilane but is highly reactive towards quenching the carbanion (9–5 in Figure 9) generated upon radical-polar crossover, a diverse range of cross-selective alkene difunctionalizations could be possible. For example, when MeCN (or MeCN-d₃) was used as solvent instead of THF, hydro- and deuteron-silylation products (e.g., 10–7 to 10–9) could be obtained by capturing the resultant benzylic anion with a proton (or a deuterium).⁶¹ Additionally, when a leaving group was attached either adjacent or distal to the site of the benzylic anion, intramolecular elimination or substitution took place to deliver silyl-substituted cyclic alkanes (e.g., 10–12) or allylsilanes (e.g., 10–15).

Cross-Electrophile Coupling for Si(sp³)–Si(sp³) Bond Formation

Disilanes and oligosilanes have received increasing interest in organic synthesis and materials science.⁶²For example, disilanes are useful reagents to construct C–Si bonds.⁶³ Materials containing oligosilanes exhibit unique electronic and luminescent characteristics as a result of σ-bond electron delocalization along the Si–Si chains.⁶⁴ Even still, methods to construct Si–Si bonds are underdeveloped. Classic Wurtz coupling of halosilanes using alkali metals (i.e., Na or Li) remains the most practiced method to form Si–Si bonds, but the functional group tolerance and reaction selectivity are limited under the harsh conditions employed.⁶⁵ Dehydrogenative coupling of silanes has emerged as an attractive alternative, although current methods are limited to homodimerization and polymerization.⁶⁶ Silylboranates have also been used for Si–Si bond formation, yet methods for preparing of these reagents remain limited.⁶⁷

We were interested in applying the principles of e-XEC to achieve Si–Si cross-electrophile coupling, starting from chlorosilanes with distinct redox potentials and steric properties (Figure 11A).⁶⁸ For example, a chlorosilane with an aromatic stabilizing group (11–1) would preferentially undergo an overall two-electron reduction to form a silyl anion (11–4) in the presence of a di- or tri-alkylchlorosilane (11–3); the ensuing silyl anion would then selectively attack the sterically less encumbered di- or tri-alkylchlorosilane to complete the Si–Si bond formation (11–5). It should be noted that the electrochemical activation of chlorosilanes was previously explored in a few pioneering studies,^{55, 56} but the reaction scope and its synthetic applications were not established, particularly in the context of cross coupling and oligosilane synthesis.

Figure 11.

Electroreductive silyl cross-electrophile coupling.⁶⁸ (A) Reaction design of electroreductive disilylation of alkenes and DFT calculations support for the proposed mechanism. (B) Optimal reaction conditions. (C) Representative reaction scope.

We developed optimal reaction conditions (Figure 11B) for several silyl cross-coupling reactions between a variety of chlorosilanes (Figure 11C). We found that the combination of a molybdenum cathode and tetrabutylammonium tetraphenylborate or perchlorate (TBABPh₄ or TBAClO₄) as electrolyte affords desired products in high yield with excellent selectivities, under otherwise similar conditions to those used for the disilylation of alkenes. For example, using a nearly 1:1 ratio of the precursor chlorosilanes, the formation of heterocoupling products over the homocoupling products was favored with >20:1 selectivity (e.g., 11–9 and 11–10). The reaction scope was further expanded to Si–Ge bond formation using Me₃Ge–Cl (11–11). Notably, supersilyl chloride (TMS₃SiCl) could also be preferentially reduced and coupled with TMSCl to afford TMS₄Si (11–12) in nearly quantitative yield.

We next sought to extend this approach to the synthesis of more challenging compounds including acyclic and cyclic oligosilanes. In particular, to generate and control the reactivity of multivalent silyl anion intermediates (e.g., dianions) from polychlorosilanes (e.g., 12–1) is difficult using the canonical Wurtz method.⁶⁹ We envisioned that electrochemistry could provide a complementary synthetic logic to oligosilane synthesis by bypassing this restriction (Figure 12). For example, dichlorosilanes such as 12–1 could serve as a silyl dianion equivalent via sequential reduction (12–2) and reaction with monochlorosilanes (12–3) to form one Si–Si bond (12–4). This reductive coupling step could be repeated for 12–4 to form a second Si–Si bond (12–5). Following reaction optimization (Figure 12B), this concept was successfully demonstrated in the synthesis of various oligosilanes via multiple consecutive Si–Si bond-forming events (e.g., 12–8 to 12–10) from corresponding di- and tri-chlorosilanes (Figure 12C). Furthermore, the concept was adapted for the synthesis of cyclic oligosilanes such as cyclopentasilane 12–14 and cyclohexasilane 12–15 and 12–16. These compounds are either synthesized using excess Li metal (12–15)⁷⁰ or, to our knowledge, have not been previously isolated (12–14 and 12–16),⁷¹ highlighting the usefulness of electroreductive chemistry in organosilane synthesis.

Figure 12.

Extension of electroreductive silyl cross-electrophile coupling to oligosilanes and cyclic silanes. (A) Reaction design principle. (B) Optimal reaction conditions. (C) Representative reaction scope.

SUMMARY AND OUTLOOK

In recent years, reductive electrochemistry has drawn substantial interest as a valuable tool in organic synthesis. Our contributions in this area have focused on leveraging deeply reducing potentials to access radical and anionic intermediates that can engage in the formation of C–C, C–Si, and Si–Si bonds. To this end, electrochemically enabled radical-polar crossover has proven to be a general and effective strategy for the successful development of various alkene difunctionalization and cross coupling reactions. Despite these early successes, several outstanding questions remain. For example, further mechanistic studies are needed to elucidate the factors that govern one- and two-electron reduction of alkyl halides and chlorosilanes. Additionally, expansion of electroreductive chemistry to include electrophiles such as ketones,⁷² epoxides,⁷³ imines,⁷⁴ and heterocyclic arenes⁷⁵ is desirable. Further, the development of enantioselective variants⁷⁶ remains an attractive yet challenging objective. Finally, interfacing electroreductive chemistry with transition metal catalysis⁷⁷ and electrode modification⁷⁸ are also promising directions for exploration. We anticipate that the recent renewed interest in reductive electrosynthesis in the organic chemistry community will continue to improve our ability to synthesize complex molecules and enrich our understanding of the activities of reactive intermediates.