Catalyst-Free Electro-photochemical Hydroalkylation of N‑Aryl Maleimides via Alternate Electrode Electrolysis: A Sustainable Route to N‑Aryl Succinimides with Quaternary Center

Abstract

We report a dual electrochemical-photochemical platform that enables selective hydroalkylation of N-aryl maleimides for the construction of C4-functionalized N-aryl succinimides in the presence of alcohol (as a solvent) and aryl diazo esters. Alternate electrode electrolysis (AEE) selectively promotes electrochemical reduction of N-aryl maleimides which undergoes cyclopropanation with a carbene (generated by blue LED irradiation of diazo esters), subsequent ketyl radical-mediated ring opening, and electro-oxidative nucleophilic attack by alcohol afford the densely substituted hydroalkylated succinimide derivative. No cross-reactivity or degradation of intermediates was observed. The protocol showcases high functional group tolerance, affording over 26 structurally diverse N-aryl succinimide derivatives, including the late-stage functionalization of aromatic amine-containing pharmaceutical scaffolds. A gram-scale synthesis underscores the scalability and operational simplicity of the process. Control experiments highlight the orthogonal yet complementary nature of the activation modes and provide mechanistic evidence supporting a stepwise paired electrolysis process aided with photochemical carbene generation pathway.

Introduction

Succinimides are valuable five-membered nitrogen-containing heterocycles widely recognized for their presence in pharmaceuticals, agrochemicals, and natural products. They exhibit diverse biological activities, with clinically approved drugs such as ethosuximide and phensuximide used to treat absence seizures by modulating calcium channels (Figure A). Succinimide derivatives also possess anticancer, anti-inflammatory, and analgesic properties, and N-hydroxysuccinimide (NHS) esters are extensively used in bioconjugation and protein labeling. − While less common in natural products, succinimide motifs appear in fungal metabolites and polyketide–peptide hybrids. Their rigid, dipolar structure enhances receptor binding, and their synthetic accessibility through condensation, hydrogenation, or modern electro/photochemical oxidation of maleimides makes them a privileged scaffold in medicinal chemistry. −

1.

Selected succinimide-containing natural products and pharmaceutical compounds.

N-Aryl maleimides represent a synthetically valuable class of substrates in succinimide chemistry. Maleimides are well-known electron-deficient olefins due to the presence of two conjugated carbonyl groups and an N-substituent, which strongly withdraw electron density from the alkene, lowering its LUMO energy. This electronic polarization makes maleimides highly reactive toward nucleophilic and radical species, similar to other activated olefins such as acrylates or acrylonitriles. − Leveraging this property, we envision a tandem electro-photochemical strategy that enables modular hydroalkylation of N-aryl maleimides to generate N-aryl succinimides with a stereogenic quaternary carbon center.

Hydroalkylation of electron-deficient olefins, such as acrylates, acrylonitriles, fumarates, etc., is a powerful strategy to forge C­(sp³)–C­(sp²) bonds across the alkene via radical or polar mechanisms. − These olefins possess low-lying LUMOs due to electron-withdrawing groups, enabling facile nucleophilic or radical addition at the β-carbon which involve metal catalysis. Recent advances use photoredox catalysis or electrochemistry to enable hydrofunctionalization of electron-deficient olefins, forming valuable β-substituted products under mild, oxidant-free conditions. − Such transformations are increasingly favored for green synthesis, medicinal chemistry, and late-stage functionalization.

Electrosynthesis has become now a corner stone in organic synthesis, by which a wide number of chemical transformations are being accomplished, which are not feasible in other ways. In this line, different electrolysis techniques have been evolved to enhance the efficiency and chemoselectivity of electro–organic reactions. Among them, pulse electrolysis applies pulses of electricity instead of a constant potential/current as in direct current (DC) electrolysis, whereas rapid alternating polarity (rAP) involves reversal of electrode polarity (i.e., anode becomes cathode and cathode becomes anode at a given frequencya square wave version of AC electrolysis) (Figure B). These methods have been proven to be distinctly efficient in performing chemoselective electrosynthesis, which are not practical under conventional DC processes. Alternate electrode electrolysis (AEE) is a recently developed platform that allows rapid alternation of anodic and cathodic current between dual electrode pairs, where pulse electrolysis can be achieved while maintaining a constant potential/current in an electrolysis process through complementary action by two pairs of electrodes (Figure B). Unlike rAP electrolysis, the electrodes in AEE do not undergo reversal of polarity, subsequently different anodic and cathodic materials could be chosen according to the requirement. This is not possible in rAP where both the electrode materials should be the same. Additionally, AEE has been proven to offer distinct advantages including enhanced current density, reduced solution internal resistance, shorter reaction time, improved mass transport, and higher energy efficiency by the electrochemical cell.

Blue light-induced photolysis of diazo carbonyl compounds has emerged as a sustainable strategy for accessing electron-deficient carbenes under mild conditions. − These photogenerated carbenes readily engage in diverse transformations, including cyclopropanation, ylide formation, and substitution reactions, when paired with suitable reaction partners. − The use of blue light not only minimizes thermal degradation and byproduct formation but also enhances the reaction selectivity and yield. Recently, photoelectrochemical organic reactions have introduced sustainability and selectivity in the synthesis of chemical building blocks. , Our recent advances have demonstrated the synergistic integration of blue light photochemistry to generate carbene with AEE-mediated electrochemical activation of 1,4-quinones to selectively generate anion radical intermediate which could trap the carbene efficiently, offering orthogonal reactivity modes that enable highly efficient and selective bond-forming processes. ,

Our approach centers on AEE, which delivers a highly efficient platform for activating electron-deficient N-aryl maleimides in alcohol-rich media. Under AEE conditions, N-aryl maleimide is selectively reduced to its radical anion, while an aryl diazoester generates a carbene under blue-light irradiation. The carbene undergoes cyclopropanation with the maleimide, followed by radical-mediated ring opening to form a tertiary radical. This radical is then oxidized at the anode and is subsequently attacked by methanol. This metal-free, operationally straightforward protocol exhibits broad functional-group tolerance, accommodating diverse N-aryl maleimides, diazoesters, and primary alcohols, and establishes a distinctive photoelectrochemical hydroalkylation manifold that sets it apart in contemporary synthetic methodology. Control experiments and intermediate analysis point toward a paired electrolysis and highlight the role of AEE and blue light in enabling efficient hydroalkylation of N-aryl maleimides.

Results and Discussion

It is noteworthy that under purely photochemical conditions, the electron-deficient maleimide and the carbene generated from the diazo ester remain electronically mismatched, leading predominantly to cyclopropanation or dimerization to diazine forming pathways, respectively (Scheme a). However, under electro-photochemical conditions, the maleimide could undergo electroreduction which could be significantly more reactive toward the photogenerated carbene species. This reduction step therefore overcomes the intrinsic mismatch and enables productive C–C bond formation to deliver the hydroalkylated succinimide (Scheme b). Our plan exploits a three-component functionalization in which the aryl diazo ester engages (i) a solvent-level alkoxy nucleophile and (ii) a maleimide-derived radical anion to forge the C–O and C–C bonds in one pot (Scheme c).

1. (a) Conventional Reaction of Diazoester and Maleimide Under Light, (b) Synthesis Hypothesis for Dual Activation of Substrates by Electricity and Light, and (c) This Work of Hydroalkylation of Maleimide with Dual Activation by Light and Electricity with Photo-electrochemical Setup.

Building on our retrosynthetic analysis (Scheme b) and after the initial experiments were done, we undertook systematic optimization of the electro-photochemical hydroalkylation of N-aryl maleimide 1a with aryl diazoester 2a in methanol (3a) for the synthesis of substituted N-aryl succinimide derivative 4a (Table ). Key reaction parametersincluding electrode materials, electrochemical settings, and use of supporting electrolyteswere rigorously evaluated to establish the optimal conditions.

1. Optimization of the AEE-Mediated EPC Reaction to Generate Substituted N-Aryl Succinimide, 4a ^,

entry	deviation from above condition	yield (4a)	comments
1	no deviation	94%	4 h reaction time
2	2C(+), 2Pt(−)	56%	6.5 h reaction time
3	2C(+), 2Al(−)	68%	6 h reaction time
4	2Al(+), 2Al(−)	32%	5.5 h reaction time
5	blue light only, no electricity	trace	overnight (12 h) reaction time, 1a unreacted, 2a decomposition
6	rAP, C+/C- (@ 50 ms)	75%	5 h reaction time
7	DC, C+/Ni- (9 V)	23%	decomposition of reactants
8	nBu4NCl as supporting electrolyte	64%	7 h reaction time
9	Me4NBF4 as supporting electrolyte	73%	6 h reaction time
10	constant current @ 4.17 mA/cm2	53%	8.5 h reaction time
11	constant current @ 8.33 mA/cm2	70%	8 h reaction time
12	constant voltage @ 2 V	88%	prolonged reaction time
13	constant voltage @ 5 V	61%	7 h reaction time, more byproducts
14	constant voltage @ 10 V	32%	decomposed 2a
15	DC, constant current @ 16.66 mA/cm2	trace 4a	decomposed 2a
16	no light, in dark	nil	2a remained unreacted

^aReactions were monitored through TLC for checking completion; yields mentioned are isolated yields.

^bReaction conducted with 50 mg of 1a.

^cIsolated yield.

Initial electrode screening included graphite, platinum, nickel, and aluminum (Table , entries 1–4). The highest yield was obtained using blue light with graphite as the anode and nickel (Ni) as the cathode with a constant current of 20 mA for 50 ms in tetra-n-butyl hexafluorophosphate (nBu₄NPF₆) as supporting electrolyte in 4 h (Table , entry 1). Control experiments revealed that photochemical activation alone (blue light, 34 W) in the absence of electricity produced only trace amounts of 4a (Table , entry 5), while other electrode combinations under identical conditions gave inferior yields (Table , entries 2–4).

The reaction performed under photochemical and rapid alternating polarity (rAP) (50 ms) conditions delivered 4a in 75% yield (Table , entry 6), whereas traditional DC (9 V) electrolysis with the photochemical condition afforded 4a in only 40% yield (Table , entry 7). Various other supporting electrolytes such as tetra-n-butylammonium chloride ( ⁿ Bu₄NCl) and tetramethylammonium tetrafluoroborate (Me₄NBF₄) were tested and afforded 4a in 64% and 73% yield, respectively, but required extended reaction times of 6–7 h (Table , entries 8 and 9), compared to 4 h under the optimized AEE conditions (Table , entry 1).

Further modulation of electrochemical parameters demonstrated that decreasing the current to 4.17 mA/cm² significantly reduced the yield and prolonged the reaction time (45% yield, 8.5 h; Table , entry 10), while increasing it to 8.33 mA/cm² led to only 70% yield over nearly 8 h (Table , entry 11). Constant voltage conditions (2, 5, and 10 V; Table , entries 12–14) were also less efficient, both in terms of yield and duration, relative to the constant current of 20 mA. Finally, keeping all the other conditions same the reaction in DC at a constant current of 16.66 mA/cm² yielded a trace amount of product with majority of the decomposed 2a as the byproducts.

When the reaction was conducted without blue light under dark conditions, 4a was not formed, and 2a remained unreacted in the reaction mixture after electrolysis. Taken together, these results establish that the optimal conditions for this AEE-driven electro-photochemical transformation involve the use of graphite as anode and nickel as cathode under a nitrogen atmosphere, in dry, degassed methanol, irradiated with blue light (34 W), and operated at a constant current of 16.66 mA/cm². These parameters ensure the highest efficiency and reproducibility of the synthesis of 4a.

It is noteworthy that methanol (or any alcohol) alone is used as both the solvent and nucleophile in all subsequent reactions. All experiments reported in this manuscript beyond Scheme were therefore carried out in alcohol.

With the optimized reaction conditions established, the scope and robustness of the protocol were systematically evaluated through the reaction of a diverse set of N-aryl maleimides 1 with structurally varied aryl diazo esters 2, predominantly in methanol (3a) as the solvent (Scheme ). As a model substrate, N-phenyl maleimide (1a) exhibited broad reactivity with both electron-rich and electron-deficient aryl diazo esters (2b–2f), delivering the corresponding succinimide adducts 4b–4f in excellent yields (80–94%) and moderate diastereoselectivity (dr = 75:25–82:18), attributable to the absence of chiral induction in the current system. The general structure of the desired products was confirmed by single-crystal X-ray of compound 4d (CCDC#2466424) (Scheme ).

2. Substrate Scope of N-Aryl Succinimides 4 with Quaternary Stereogenic Center from Hydroalkylation of N-Aryl Maleimide 2 .

Substitution of methanol with higher homologues such as ethanol and n-butanol led to reduced reaction efficiency, with the corresponding succinimide derivatives 4g and 4h isolated in 69% and 58% yield, respectively. The methodology also accommodated variation at the ester moiety of the diazo compound. For instance, the reaction of benzo­[d]­[1,3]­dioxol-5-yl methyl esters bearing 4-chlorophenyl and 4-bromophenyl diazo motifs (2g and 2h) with 1a in methanol yielded the corresponding succinimides 4j and 4k in 70% and 76% yield, respectively.

To further probe the generality of the transformation, a series of N-aryl maleimides bearing electron-donating and electron-withdrawing substituents on the aromatic ring, including 3-Cl (1b), 4-Cl (1c), 4-Br (1d), 4-SMe (1e), 2 F (1f), 3-CF₃ (1g), 4-tert-butyl (1h), and 4-cyano (1i), were reacted with representative diazo esters 2a, 2c, and 2i to furnish the corresponding succinimides derivatives 4o–4x. These transformations proceeded with moderate to good yields and diastereoselectivities (75:25–82:18) under the standard conditions (Scheme ).

When N-benzyl maleimide 1j was reacted with 2a and methanol 3a, the resulting succinimides 4y was obtained in ∼45% and in 2:1 diastereomeric ratio (Scheme ). The moderate yield and poor diastereoselectivity reflected the incompatibility of the reaction with N-alkyl maleimides, as N-methyl and N-ethylmaleimides 1x and 1y afforded 1, 4-product (instead of desired 1,2-) as discussed in Scheme below. It is noteworthy that the potential range in this generic synthesis is between 0.8 and 3 V, and the amount of electricity ranges from 4.08 to 14.96 F mol^–1 (refer to the Supporting Information, Table S1).

3. Control Experiments to Understand the Mechanism of AEE-Induced EPC Hydroalkylation of N-Aryl Maleimides 1 to N-Aryl Succinmides 4. ^a0.1 M ⁿ Bu₄PF₆ Solution in MeOH Was Used for this Experiment; ^bYields Were Measured by ¹H NMR Using Mesitylene as the Internal Standard, 2a Decomposition Corresponds to Diazine Formation; ^CEnergy Expended by the Electrochemical Power Supply during the Standard Reaction Generating 4a in AEE and DC (Detail Calculation Given in the Supporting Information).

Finally, the synthetic utility of this protocol was demonstrated through a late-stage functionalization of the nonsteroidal anti-inflammatory drug (NSAID) felbinac. The carboxylic acid functionality of felbinac was converted to the corresponding diazo ester (2k), which underwent hydroalkylation with 1a under the optimized conditions to afford succinimide-functionalized felbinac analogue 4z in 75% yield (Scheme ). Similarly, reaction of 2k and 1k in MeOH afforded the desired compound 4aa in 75% yield with a d. r. of 78:22 (Scheme ). Both 4z and 4aa were obtained in 80:20 and 78:22 diastereoselectivity, respectively.

To further demonstrate the versatility of our strategy, we explored the union of felbinac-derived diazo acetate 2k with maleimides 1l and 1m, which were synthesized from the local anesthetics benzocaine and butamben, respectivelyboth known sodium channel blockers. This approach enabled the covalent fusion of two pharmacologically distinct drug scaffolds to afford chimeric succinimide-based small molecules 4ab and 4ac (Scheme ). To demonstrate the robustness of the strategy, we investigated the reaction among 2k, 1k, and methanol on a 1 g scale. To our utmost gratification, the desired product 4y was obtained in 64% yield (refer the Supporting Information). Finally, we used our strategy for the late-stage functionalization of antibiotic sulphamethaoxazole to generate 4ad (Scheme ).

Though premature, the resulting hybrids represent interesting lead molecules highlighting scaffold fusion as a compelling strategy in contemporary drug discovery.

It is noteworthy that, while extending the strategy to dimethyl and diethyl maleate, the reaction resulted in the insertion of the methoxy moiety at the carbene anion, leading to the formation of 8a (Scheme S4). This could be because such substrates lack the redox-responsive behavior of N-arylmaleimides and may not undergo efficient olefin activation under our AEE protocol.

While this study primarily utilizes alcohols as nucleophiles for the hydroalkylation of N-aryl maleimides under electro-photochemical conditions, we briefly explored the potential of other nucleophiles including amines, silyl enol ethers, and electron-rich arenes. These attempts were largely unsuccessful under the current conditions, resulting in either the decomposition or recovery of starting materials. The lack of reactivity may stem from either insufficient nucleophilicity or incompatibility with the redox environment. In particular, phthalimide, tested as a possible alternative substrate, was unreactive under AEE-blue light (34 W) conditions, likely due to its lower redox reactivity and the absence of an electron-deficient alkene motif required for radical cation formation. These observations reinforce the unique redox-responsive behavior of N-aryl maleimides in this transformation and underscore the need for precise electronic tuning of both the nucleophile and electrophilic partner in future developments of this methodology.

We agree that broader exploration of nucleophiles and redox-active substrates is a promising direction and forms part of our ongoing research toward extending the synthetic utility of the AEE-electro-photochemical platform.

To elucidate the reaction mechanism underlying our AEE-induced electro-photochemical (EPC) strategy for the hydroalkylation of N-aryl maleimides 1, a series of control experiments were conducted (Scheme ).

Initially, N-phenylmaleimide 1a was irradiated under blue light in methanol (3a) in the presence of phenyl diazoacetate 2a. This reaction furnished the bicyclic cyclopropane intermediate 5a in 78% yield (Scheme a) in an overnight reaction. Subjecting 5a to AEE under the optimized conditions for 5 h led to no observable conversion (Scheme b­(i)), indicating that AEE does not facilitate nucleophilic ring opening of this cyclopropane intermediate. To confirm there is any role of blue light to initiate the ring opening of 5a, we attempted a reaction of 5a with standard electrochemical condition in the presence of blue light. However, we did not observe the formation of product 4a under this condition (Scheme bii). This indicated that the cyclopropyl product would not be the intermediate of the standard reaction.

Subsequently, when 1a was first subjected to AEE in methanol, an electron-deficient olefin intermediate 6 was obtained in 78% yield (Scheme c). This observation suggests that in methanol, N-aryl maleimides in the absence of blue light undergo electro-reduction to the olefin intermediate 6.

A potential alternative pathway involving direct nucleophilic attack by methoxide generated via cathodic methanol reduction was examined. However, stirring 5a with two equivalents of sodium methoxide in methanol (in the absence of electrolysis) failed to yield the succinimide intermediate 4a (Scheme d), thereby ruling out nonelectrochemical nucleophilic addition. We have also conducted another experiment using sodium methoxide replacing electricity from the beginning with 1a and 2a, to check whether the reaction is proceeding via formation of electrogenerated methanolate from methanol at cathode and then subsequent trapping of carbene by the methanolate generating a carbanion to react with maleimide. Here too, we found no formation of product 4a, which eliminates this possibility (Scheme S5).

Diazo ester-derived carbenes undergo OH-insertion in the presence of alcohols. Subsequently, we investigated the scope of 8a as a potential intermediate in the reaction. Accordingly, when 8a and 1a are reacted under the optimized condition, no formation of 4a was observed, instead the formation of ring-opened amide 6 was observed (Scheme e). This ruled out the possibility of OH-insertion in the reaction (Scheme e). Next, when N-methyl and N-ethyl maleimides (1x and 1y) were subjected to the optimized conditions in methanol, the corresponding 1,4-addition products 7a and 7b were isolated in 76% and 80% yield, respectively (Scheme f). This divergence from the N-aryl substrates highlights the electronic influence of the N-substituent, with electron-donating alkyl groups directing electron density toward the C4 position, in contrast to electron-withdrawing aryl groups that localize it more at C2. Cyclic voltammetry (CV) experiments further supported this mechanistic sequence. In CV, the first reduction peak of 1a was observed at 1.0 V vs Ag/Ag⁺, and second one at 1.50 V vs Ag/Ag⁺, whereas the reduction of 2a was observed with a peak at 1.75 V vs Ag/Ag⁺ (Scheme g). We have also conducted the CV experiment under blue light irradiation where we could find that the reduction peaks appeared at similar potentials as under normal conditions (Figure S7), which indicated that blue light has no role to induce the electro-reduction of the substrates.

Next, we conducted a divided cell experiment, with phenyl diazoester 2a and phenyl maleimide 1a in the presence of methanol in the anodic chamber while keeping the cathodic chamber reactant-free (Scheme h). Herein, we had kept all other parameters unchanged in both compartments, i.e., nickel foam cathode and graphite anode. The solution was stirred under blue LED, and the electricity was applied with 20 mA constant current. We monitored the reaction solution of the anodic chamber for 2 h, after which LCMS and HPLC analysis indicated the formation of a trace amount of product 4a and substantial amount of decomposed 2a. Almost a similar observation was witnessed when polarity was reversed, i.e., where both the substrates were in the cathodic chamber while keeping all other parameters unchanged (Scheme h). Here too, a trace product formation of 4a was observed after 2 h of electrolysis under blue LED. These two experiments strongly suggest that both cathodic and anodic reactions were essential for the desired transformation in the presence of the blue LED.

It is noteworthy that the possibility of nickel leaching is ruled out in the observed transformations. In the optimization experiments using inert cathodes such as platinum and aluminum (Table , entries 2 and 3), these setups gave lower yields (56% and 68%, respectively) but still led to product formation, suggesting nickel plays a role as a physical cathode material rather than a leached homogeneous catalyst. Additionally, the Ni electrodes were weighed before and after electrolysis, and no measurable weight loss was observed, indicating negligible electrode degradation under the reaction conditions.

To understand why AEE enhances reaction efficiency relative to DC electrolysis, we measured the solution resistance over a low-potential window (0 to −1.0 V vs Ag/Ag⁺), a critical parameter governing effective current delivery under dynamic conditions. Notably, AEE exhibited significantly lower solution resistance than DC electrolysis (Scheme i), consistent with improved ion and solute diffusion near the electrodes and, consequently, enhanced mass transfer. This observation aligns with the optimization studies, where DC electrolysis proved to be largely ineffective for the desired transformation (Table , entry 7).

Both AEE and rAP benefit from transient electrode polarization; however, polarity reversal in rAP (Table , entry 6) is inferior to the pulsed potential profile intrinsic to AEE (Table , entry 1). The superior kinetic responsiveness of the system under AEE is reflected in higher yields and reduced competitive decomposition pathways, which are prevalent under DC and, to a lesser extent, rAP conditions. Indeed, applying a constant current of 20 mA under DC electrolysis resulted in extensive decomposition of diazoester 2a and only trace formation of the desired product (Table , entry 15; Scheme j), highlighting that reaction efficiency depends not merely on current magnitude but critically on waveform and electrode-switching dynamics.

Finally, energy consumption analysis revealed that AEE is at least 4.5 times more energy-efficient than DC electrolysis for the synthesis of 4a (Scheme k and the Supporting Information). Collectively, these blue light-driven electrochemical studies establish AEE as a finely tunable, kinetically favorable, and energy-efficient platform for orchestrating redox-driven transformations.

Orchestrating this redox-driven transformation critically depends on the fate of the photogenerated carbene within the electrochemical environment. Once generated under blue-light irradiation, the carbene can engage in three distinct reaction pathways: (i) productive interception by the one-electron-reduced N-aryl maleimide (radical anion) to deliver the desired hydroalkylation product under electro-photochemical conditions; (ii) competitive cyclopropanation with unreduced neutral maleimide to afford bicyclic cyclopropane 5a (Scheme a); or (iii) dimerization via reaction with unreacted diazo ester to form the corresponding diazine byproduct 9 (Scheme ), a well-documented deactivation pathway in diazo-carbene chemistry. The latter two pathways become dominant only when the steady-state concentration of the maleimide radical anion is insufficient to efficiently trap the highly reactive carbene.

4. Putative Mechanism for the AEE-Mediated EPC Hydroalkylation of N-Aryl Maleimide 1 to N-Aryl Succinimide 4 .

This scenario is clearly manifested under conventional DC electrolysis, where poor yields of 4a are accompanied by substantial formation of cyclopropane and diazine side products. In contrast, AEE markedly suppresses these undesired pathways. Under AEE conditions, a higher effective current density and enhanced mass transport facilitate more efficient and sustained electroreduction of the maleimide, thereby maintaining a higher concentration of the reactive radical anion. Moreover, the presence of two cathodes immersed in the reaction medium ensures superior spatial distribution of the maleimide radical anion, increasing the probability of productive carbene capture before deleterious side reactions can occur.

On the basis of the optimization studies and comprehensive control experiments, a plausible mechanism is proposed (Scheme ). Initial cathodic reduction of N-aryl maleimide 1a furnishes the corresponding radical anion B. In parallel, blue-light irradiation of aryl diazoester 2a generates singlet carbene C, which undergoes rapid, concerted cyclopropanation with B to form cyclopropanated radical intermediate D. Subsequent radical-mediated ring opening of D delivers intermediate E, which upon protonation affords tertiary radical F. Anodic oxidation of F generates the corresponding carbocation G, which is intercepted by methanol to form intermediate H; final deprotonation furnishes hydroalkylated succinimide 4a.

Under DC electrolysis, following the initial one-electron reduction of 1a, a second reduction event (observed at −1.50 V vs Ag/Ag⁺) becomes accessible, leading to over-reduction and decomposition of both the maleimide and the photogenerated carbene (Table and Scheme j). The pulsed current profile inherent to AEE likely suppresses this undesired second reduction, thereby preserving radical anion B for productive coupling with carbene C. In contrast, rapid alternating polarity (rAP) electrolysis may inhibit downstream chemical steps (B → D → E → F) by oxidizing transient radical intermediates (D or E) during polarity reversal. Additionally, the use of dual electrode pairs in AEE further enhances the homogeneous distribution of reactive intermediates throughout the solution.

Notably, singlet carbenes typically undergo cyclopropanation through a concerted pathway, often resulting in diastereoselective outcomes. − In the present system, cyclopropanation occurs with a singly reduced maleimide radical anion yet still follows a concerted trajectory, accounting for the observed diastereoselectivity. This behavior strongly supports the involvement of a photogenerated singlet carbene in the key C–C bond-forming step.

Collectively, these findings substantiate an electrophotolytic mechanism involving a paired sequence of cathodic reduction and anodic oxidation, as further corroborated by divided-cell experiments (Scheme h). The transformation thus exemplifies a dual-activation strategy wherein electrochemical generation of a maleimide radical anion and photochemical carbene formation from aryl diazoesters operate in concert to enable selective hydroalkylation.

Conclusion

Herein, we disclose an unprecedented hydroalkylation of N-aryl maleimides for the synthesis of N-aryl succinimides substituted with a stereogenic quaternary carbon via a sustainable electro-photochemical (EPC) strategy enabled by AEE. This protocol employs N-aryl maleimides 1, aryl diazo esters 2, and alcohols 3 as readily available starting materials to deliver the corresponding diastereoselective succinimides 4 in moderate to excellent yields. The transformation demonstrates a broad functional group tolerance across a range of aryl substrates and is applicable to the late-stage functionalization of drug molecules. Notably, the strategy facilitates the synthesis of succinimide-based chimeric scaffolds derived from pharmaceuticals such as felbinac, sulfamethoxazole, benzocaine, and butamben.

Succinimides are privileged structural motifs in both organic synthesis and medicinal chemistry, and their synthesis from readily available precursors remains a valuable goal. The challenge lay in orchestrating a precise sequence of events under electro-photochemical conditions: first, electroreductive activation of the maleimide followed by cyclopropanation by the carbene generated by the blue LED irradiation of the aryl diazo esters and subsequent ring opening and oxidation at the anode to generate the tertiary carbocation which reacts with the primary alcohols to afford the desired product. AEE played a pivotal role in selective generation of radical anion intermediate from N-phenyl maleimide which could trap photoinduced carbene in a balanced dual electro-photochemical process which was not practical under DC electrolysis. This dual electro-photochemical platform introduces an orthogonal activation paradigm for hydroalkylation of electron deficient olefins, allowing one-pot construction of succinimides from otherwise unreactive maleimide precursors without using any catalyst/base. Furthermore, the use of AEE enhances operational scalability and energy efficiency while circumventing limitations typically associated with conventional diazo and carbene chemistry.

Our AEE-EPC strategy enabled the hydroalkylation of electron-deficient alkenes such as the N-arylmaleimides, which represents a challenging yet strategically valuable transformation in modern synthetic chemistry. Unlike their electron-rich counterparts, electron deficient alkenes exhibit diminished reactivity toward conventional carbenoid or metal-carbene intermediates, necessitating the development of AEE-EPC. The current protocol focuses on N-aryl maleimides not only as substrates but also as precursors to reactive radical anion via AEE-electrolytic reduction. This dual role sets them apart mechanistically from externally added alkenes. Overall, this work establishes a robust and sustainable framework for the synthesis of functionalized succinimide architectures under mild and practical conditions.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacsau.5c01681.

• Additional experimental details, materials, and methods, including photographs of the experimental setup (PDF)

All authors have given approval to the final version of the manuscript. CRediT: Shweta Singh data curation, investigation, validation; Vaibhav Cholke investigation, validation; Rakesh Ganguly formal analysis; Debajit Maiti supervision, visualization, writing - review & editing; Subhabrata Sen conceptualization, funding acquisition, project administration, resources, supervision, writing - original draft, writing - review & editing.

The authors declare no competing financial interest.