Electrochemical and photocatalytic generation of cis-olefin-bridged carbodication for umpolung [4+1] cycloaddition

Domain: chemistry
Published: 2026-02-02
Editorial outcome: major_revision

Abstract
Carbodications, bearing two positive charges on carbon atoms, are emerging as powerful superelectrophiles in organic synthesis. Traditionally formed through single-electron oxidation of overcrowded electron-rich alkenes or acid-mediated dehydration of diols, these species show high reactivity toward carbon-based nucleophiles. However, their reactivities with heteroatom nucleophiles like amines and water remain underexplored, largely due to difficulties in controlling oxidation and undesirable acid–base interactions. Here, we report that carbodication species, generated under mild electrochemical or photocatalytic conditions in the presence of heteroatom nucleophiles, display remarkable electrophilic reactivity toward primary amines and water. This enables an intermolecular umpolung [4+1] cycloaddition, proceeding via a cis-olefin-bridged dicationic intermediate, energetically favored over its trans-isomer, yielding a class of thioxanthene-based dispirocycles with 2,5-dihydro-1H-pyrrole or 2,5-dihydrofuran central cores. Theoretical studies of electrochemical cycloaddition with aniline suggest that hydrogen bonding between aniline and the fluorine atom of the nBu4NPF6 electrolyte stabilizes the transition state, promoting nucleophilic addition.

Introduction
Dicationic species carrying two positive charges within a single molecule have garnered significant attention in synthetic chemistry and materials science due to their pronounced superelectrophilic reactivity and pronounced redox activity1–11. Among these, carbodications with spatially separated charges on two carbon atoms are particularly notable. Their stability is typically achieved through extended π-conjugation and incorporation of electron-donating groups, which not only enhance their electrophilic behavior in carbon–carbon bond-forming reactions but also impart distinctive electrochromic properties. For instance, the Suzuki group has isolated highly stable carbodications based on overcrowded ethylene scaffolds such as tetraaryl-9,10-anthraquinodimethane (Ar4AQD) and its bridged diol analog12,13.

These carbodications exhibit reversible redox behavior and can be generated by either two-electron oxidation of electron-rich alkenes (e.g., with Magic Blue) or via Brønsted acid-promoted dehydration of diols (Fig. 1a). In parallel, our group and others have reported that fluorene end-capped 1,3-dienes (DFDPE) and 11,12-dihydroindeno[2,1-a]fluorene-11,12-diols ([2,1-a]-IFOH) undergo two-fold Friedel–Crafts cyclizations to form dispirocyclic π-systems (e.g., DSFIIF) and thiophene-fused polycycles (e.g., [2,1-a]-IF-Th), respectively (Fig. 1b)14,15. These transformations are proposed to proceed via superelectrophilic carbodication intermediates generated either through FeCl3-mediated two-step single-electron oxidations or Brønsted acid-promoted dehydration of diols. While these carbodications exhibit notable reactivity toward weak carbon-based nucleophiles, their reactivity with heteroatom nucleophiles such as amines or water remains largely unexplored. This limitation is likely due to competing oxidation of electron-rich dication precursors in the presence of heteroatom nucleophiles. In addition, unfavorable acid–base interactions between strong Brønsted acids and these heteroatoms suppress efficient diol dehydration process and also reduce the nucleophilicity of the heteroatoms. Furthermore, products sensitive to strongly acidic conditions may revert to stable carbodication intermediates, leading to undesirable side reactions. Consequently, developing methods for heteroatom-based bifunctionalization of carbodications remains a significant synthetic challenge.

Recently, mild oxidative strategies such as electrosynthesis and photocatalysis have emerged as promising alternatives, offering precise redox control and improved environmental compatibility16–24. We assumed that these methods could enable the selective formation of stable dicationic species in the presence of nucleophilic heteroatoms under neutral and mild oxidative conditions, thereby avoiding the harshness associated with traditional oxidants and strong acids. Indeed, previous studies have shown that carbodications can be generated via the cation pool method through oxidative C–C bond cleavage under low-temperature electrolysis in the absence of nucleophiles, and that the resulting carbodications display remarkable electrophilic reactivity toward various carbon nucleophiles24. As illustrated in Fig. 1b, our previous work on the formation of dispirocyclic DSFIIF revealed that its construction is facilitated by a trans-olefin-bridged carbodication conformer, which promotes intramolecular two-fold Friedel–Crafts cyclization14. Building on this, we considered whether a cis-olefin-bridged carbodication, thermodynamically more stable than its trans counterpart, could be selectively accessed via single-electron oxidation of electron-rich 1,3-dienes under electrochemical or photocatalytic conditions in the presence of heteroatom nucleophiles (Fig. 1c). If successful, this would enable an intermolecular umpolung [4+1] cycloaddition between electronically mismatched 1,3-dienes and simple heteroatom nucleophiles such as primary amines or water. Although [4+1] cycloadditions of 1,3-dienes with one-atom synthons such as CO, isocyanides, carbenes, nitrenes, or silylenes are well established, often via transition-metal catalysis (Fig. 1c)25–30, the use of primary amines or water as heteroatom nucleophiles in this context has not been reported to date31. Herein, we report an umpolung [4+1] cycloaddition of thioxanthene-end-capped 1,3-dienes with primary amines or water, acting as N1 or O1 synthons, respectively (Fig. 1d). This transformation proceeds via a cis-dicationic intermediate formed under mild oxidative conditions enabled by electrosynthesis or photocatalysis, ultimately affording structurally unique thioxanthene-based dispirocycles incorporating central 2,5-dihydro-1H-pyrrole or 2,5-dihydrofuran cores.

Results
Electrochemical [4+1] cycloaddition of thioxanthene end-capped dienes with primary amines

Building on our previous studies of the oxidative ring expansion of biphenyl-tethered methylene thioxanthenes to thiepine-embedded polyaromatics, we observed that the methylene moiety undergoes selective oxidation to a radical cation, owing to its high electron density32. Drawing from these findings and our prior work on carbodication reactivity (Fig. 1b)14, we designed and synthesized a thioxanthene end-capped 1,3-diene substrate, 1a, to explore a potential [4+1] cycloaddition pathway (Fig. 2). Cyclic voltammetry (CV) of 1a in DCM/HFIP (5:1 v/v) mixture revealed a single oxidation wave and two distinct one-electron reduction peaks (Fig. 2a). To gain further insight into the oxidation process, differential pulse voltammetry (DPV) was conducted under identical solvent system. The DPV trace showed a slight separation of the oxidation wave into two closely spaced peaks (Fig. 2a, inset), suggesting that 1a undergoes a two-electron oxidation with nearly identical first and second oxidation potentials. These electrochemical features are consistent with density functional theory (DFT) calculations, which predict first and second oxidation potentials of 0.78 V and 0.59 V vs SCE, respectively, supporting the nearly simultaneous formation of the dicationic species 1a2+ (Table S4, SI). This behavior can be rationalized by the preferential two-electron oxidation to yield the thermodynamically stable aromatic thioxanthylium dication, rather than the less stable radical cation formed by single-electron oxidation. The stability of the cis-dication 1a2+ is further enhanced by intramolecular π–π interactions between the two thioxanthylium polyaromatic units. The large peak-to-peak separation (~0.5 V) between oxidation and reduction in the CV trace indicates the high stability of the dicationic intermediate12,13. Moreover, the oxidation potential of 1a (0.79 V vs Ag/AgNO3) is 0.15 V lower than that of aniline (0.94 V), confirming that 1a is more easily oxidized under anodic conditions. DFT analysis of 1a2+ in the presence of the PF6‒ counteranion reveals that the cis conformer is 3.4 kcal/mol more stable than the trans form, supporting the proposed two-step electrophilic [4+1] cycloaddition pathway (Fig. 2b and Fig. S7, SI). In contrast, when the PF6⁻ anion is omitted, the trans-dication becomes 3.6 kcal/mol more stable than the cis form. These findings suggest that the PF6⁻ counteranion mitigates charge–charge repulsion between the two cationic centers by cation-anion interactions, thereby stabilizing the cis configuration. An electrostatic potential (MEP) map of the cis-dication indicates delocalization of positive charge across the individual bis(thioxanthylium) 14π-aromatic systems (Fig. 2c). Furthermore, non-covalent interaction (NCI) analysis confirms additional stabilization of the cis conformer through intramolecular π–π interactions between the parallel thioxanthylium π-surfaces (Fig. S8, SI)33,34.

Guided by these electrochemical and theoretical insights, we optimized the electrochemical [4+1] cycloaddition of 1a with aniline using an undivided electrochemical cell (Table 1). The optimal setup employed graphite electrodes (anode and cathode), a constant current of 3 mA, and nBu4NPF6 in DCM/HFIP (5:1) at room temperature for 3 h, yielding dispirocycle 2a in 98% yield (entry 1). The dispirocyclic structure of 2a was determined unambiguously by X-ray crystallographic analysis. HFIP proved critical for product selectivity35; replacing it with isopropanol or omitting it led to formation of the reduced byproduct 1a′ instead of 2a (entries 2 and 3). Among various electrolytes, those containing fluorine, nBu4NPF6 (98%), nBu4NBF4 (97%), and nBu4NOTf (97%), outperformed nBu4NClO4 (86%) and nBu4NBr (75%), suggesting a beneficial role of fluorine (entries 1, 4–7). Switching the graphite cathode for platinum had minimal effect, but using platinum at both electrodes significantly reduced the yield, underscoring the importance of the graphite anode in the two-electron oxidation (entries 8 and 9)36. Lowering the current to 1 mA extended the reaction time to 9 h to maintain high yield (entry 10), while increasing the current to 5 mA led to decreased yield (entry 11), likely due to over-oxidation and partial decomposition of 2a, which itself shows a relatively low oxidation peak at 0.94 V vs Ag/AgNO3 (Fig. 2a). No product formation was observed in the absence of electric current, confirming the necessity of the electrochemical approach. During optimization, it was noted that no dispirocyclic analogues such as DSFIIF (Fig. 1b)14 were detected.

Given the remarkable electrochemical performance observed, a broad range of primary amines was evaluated under the optimized electrochemical conditions (Fig. 3a). Primary aryl amines with electron-donating substituents such as methyl, tert-butyl, and methoxy at the para-position of the phenyl ring showed excellent compatibility, delivering the corresponding dispirocycles 2b–2d in high yields. Notably, the reaction between 1a and para-methoxy-substituted arylamine yielded product 2d in high yield when 10 mol% nBu4NI was added as an additive, likely due to suppression of over-oxidation of the electron-rich product 2d. Aryl amines bearing electron-withdrawing groups such as Br, Cl and CF3 also furnished the corresponding products 2e–2g in good to high yields, despite their decreased nucleophilicity. The aryl amine with two methyl groups at the 3,5-positions of the phenyl ring, owing to its enhanced nucleophilicity, afforded dispirocycle 2h in 86% yield. Primary alkyl amines such as 1-hexylamine and benzylamine were also compatible with the reaction conditions, providing dispirocycles 2i and 2j in good to high yields. However, substrates like p-tosylamide and tert-butyl carbamate, which possess electron-withdrawing substituents on nitrogen, failed to react due to their low nucleophilicity. Subsequently, the effect of substituents on the 1,3-diene moiety of substrates 1 was investigated (Fig. 3b). Aryl-substituted dienes with electron-donating groups at the para-position of the phenyl ring exhibited high reactivity, delivering the corresponding dispirocycles 2k–2n in good to high yields. Similarly, dienes bearing halogens such as fluorine or chlorine at the para-position gave products 2o and 2p in moderate to good yields, without any observable dehalogenation. For the sterically hindered 1,3-diene bearing a 3,5-dimethylphenyl group, an elevated temperature (50 °C) was required to drive the cycloaddition with aniline, resulting in a 65% yield of product 2q. Additionally, a 1,3-diene substituted with two n-butyl groups reacted smoothly, affording product 2r in good yield. Frontier molecular orbital (FMO) analysis of dispirocycle 2a revealed a clear spatial separation between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) (Fig. S5, SI). The HOMO is primarily localized on the two electron-rich thioxanthene units and the nitrogen atom, whereas the LUMO is distributed over the two phenyl rings and the bridged C=C bond in the dihydro-1H-pyrrole core. The HOMO energy level of compound 2a, determined by CV analysis, was −5.09 eV, which correlates well with the calculated value of −5.29 eV.

Considering the pronounced selectivity and reactivity enhancement imparted by HFIP as a cosolvent in the electrochemical transformation (Table 1), we further investigated the oxidation potentials of aniline and compound 1a to elucidate HFIP’s role. CV analysis revealed that aniline exhibits an oxidation peak at 0.94 V (vs Ag/AgNO3) in a DCM/HFIP (5:1 v/v) solvent mixture, anodically shifted compared to its peak in pure DCM (0.83 V vs Ag/AgNO3) (Fig. 4a). This shift likely arises from hydrogen bonding interactions between aniline and HFIP. In contrast, compound 1a displays similar reversible redox behavior in both solvents; however, its oxidation wave undergoes a cathodic shift in DCM/HFIP (0.79 V vs Ag/AgNO3) compared to DCM (0.83 V vs Ag/AgNO3) (Fig. 4b). As a result, the oxidation potential gap between 1a and aniline is widened by 0.15 V in the presence of HFIP, favoring the selective two-electron oxidation of 1a over aniline during the electrochemical process. To obtain more precise oxidation information at the anode, we monitored the real-time anodic potentials of the reaction of 1a under standard electrolysis conditions using an Ag/AgNO3 reference electrode (Fig. 4c). The anodic potential gradually increased from 1.22 V to 1.48 V over 110 min, at which point product 2a was obtained in 92% yield, with 7% of unreacted 1a remaining. The potential then rose rapidly to 1.66 V, and after an additional 70 min, 2a was obtained in 98% yield. These applied potentials are higher than the oxidation potentials of both 1a and aniline, enabling efficient oxidation of both species. Moreover, the sharp increase in potential after 110 min suggests the onset of aniline oxidation, further supporting the selective anodic oxidation driven by the difference in oxidation potentials between 1a and aniline.

To directly observe the dicationic species 1a2+, anodic oxidation of 1a was carried out under standard electrolysis conditions in the absence of amine using a divided cell (Fig. 4d). The resulting red solid was analyzed by 1H NMR spectroscopy in CD3CN, which showed complete consumption of 1a (Fig. S11, SI). High-resolution mass spectrometry (HRMS) detected signals at m/z 285.0732 and 715.1112, corresponding to 1a2+ and [1a2+]PF6⁻, respectively (Fig. S12, SI). The 1H NMR spectrum of 1a²⁺ recorded in CD3CN displayed a single set of signals (Fig. S11, SI), indicating the formation of a single stereoisomer of the dicationic species. Furthermore, cathodic reduction of this red solid (1a2+) under identical electrolysis conditions in a divided cell regenerated 1a in 75% yield, as determined by 1H NMR analysis (Fig. S11, SI). Collectively, these spectroscopic and redox property provide strong evidence for the efficient generation of the dicationic species 1a2+ under anodic oxidation conditions.

To investigate the intrinsic reactivity of 1a2+ toward amines, the in situ generated 1a2+ was treated with aniline in the absence of applied current (Fig. 4e). The reaction afforded 2a in 63% yield, along with 23% recovered 1a (Fig. S13, SI). When the solvent was switched to DCM, 2a was obtained in 33% yield with 37% recovered 1a. These results demonstrate that 1a2+ is indeed a reactive intermediate capable of [4+1] cycloaddition with amines, even without electrolysis. The moderate efficiency observed under these conditions likely arises from the reducing nature of aniline toward 1a2+, as well as the generation of PhNH3+ species during product formation. In contrast, reactions in undivided cells proceed more efficiently, likely due to selective anodic oxidation of 1a and facilitated proton transfer enabled by aniline deprotonation and the cathodic reduction of PhNH3+ (Fig. 4f). Notably, during the investigation of substrate scope, no dispirocyclic analogues such as DSFIIFs (Fig. 1b), which are proposed to arise from a trans-dicationic intermediate (Fig. 2b), were detected. Together, these experimental observations and theoretical analysis suggest that the observed dicationic species 1a2+ adopts a cis-geometry.

To compare our electrochemical oxidation with a chemical approach, we tested molecular iodine (I2) (Figs. S14 and SI), which has been previously used to generate 1,2-ethylenedications2. When I2 (1.5 equiv) was used to the reaction of 1a with aniline in CHCl3 or CHCl3/HFIP (5:1), the desired product 2a was formed in only 55% and 52% yield, respectively, and a significant amount of 1a was recovered. In contrast, I2 was completely ineffective with alkylamines such as n-hexylamine, producing no detectable products, including the targeted cycloadduct 2i. These results demonstrate the superior oxidation efficiency of electrochemical method in promoting the [4+1] cycloaddition.

The proposed electrochemical cycloaddition mechanism is depicted in Fig. 4f. Initially, 1a undergoes a two-step, one-electron anodic oxidation at its 1,3-diene moiety, preferentially over aniline, yielding the cis-dication intermediate B (1a2+) via the cis-radical cation intermediate A. To gain insight into the subsequent intermolecular nucleophilic addition of aniline to dication B (1a2+), DFT calculations were conducted to identify energetically favorable transition states (TSs). These calculations indicate that the formation of an intermolecular N–H⋯F hydrogen bond between aniline and a fluorine atom from the nBu4NPF6 electrolyte significantly stabilizes transition state TSb–c, reducing the activation free energy (ΔG‡) to 3.4 kcal/mol (Fig. 4g). In the absence of this hydrogen bond, the corresponding TS′b–c has a substantially higher ΔG‡ of 7.5 kcal/mol. Similarly, the TS′c–d, stabilized by an intramolecular N–H⋯F hydrogen bond, shows a ΔG‡ of 6.8 kcal/mol, whereas TSc–d, lacking this interaction, exhibits a higher ΔG‡ of 13.8 kcal/mol (Fig. 4h). Despite this, the intermediates C′ and D′ that feature the hydrogen bonds are thermodynamically less stable than C and D, which do not involve such interactions. These computational results highlight the crucial role of hydrogen bonding, especially involving the electrolyte, in facilitating both the nucleophilic addition and cycloaddition steps under mild conditions. Finally, deprotonation of the cationic intermediate D or D′ by aniline produces the cycloadduct 2a along with PhNH3+. Subsequent cathodic reduction of PhNH3+ generates hydrogen gas and regenerates aniline.

Photocatalytic [4+1] cycloaddition of thioxanthene end-capped dienes with H2O

Encouraged by the remarkable reactivity of the cis-dication species 1a2+ toward primary amines, we next investigated its potential reactivity with water (H2O) as a hetero-nucleophile. We anticipated a comparable [4+1] cycloaddition, leading to the formation of a 2,5-dihydrofuran core. However, under previously optimized electrochemical conditions, the desired cycloaddition between 1a and H2O did not occur, as water was preferentially electrolyzed to produce H2 and O2 gases. To suppress this competing electrolysis of water, we examined the oxidative electrolysis of 1a in the presence of H2O under acidic conditions. When 0.01 M HCl or an aqueous KCl/HCl buffer (pH 2.0) was used under standard electrolysis conditions, no desired product 3a was detected, and 1a was largely recovered unchanged (Fig. S15, SI). To further overcome the competing electrolysis of water while still enabling generation of the active cis-dication intermediate, we turned to a photocatalytic strategy. After screening several conditions, we found that irradiation of a mixture containing Ru(bpy)3Cl2·6H2O (photocatalyst) and (NH4)2S2O8 (oxidant) in a 9:1 DCE/H2O solvent system under blue light (440 nm) at room temperature for 2 h afforded the desired dispirocycle 3a in 98% yield (Table 2, entry 1). The selected irradiation wavelength effectively excites the Ru-photocatalyst. Notably, compounds 1a and 3a have absorption onsets at 395 nm and 330 nm, respectively, and thus do not interfere with the excitation of the photocatalyst (Fig. 5a). No product formation was observed in the absence of (NH4)2S2O8 (entry 2), confirming its essential role as the oxidant. Alternative photocatalysts, including Ru(bpz)3PF6, Ir(ppy)3, and MesAcrMe+ClO4–, showed reduced or negligible activity in promoting 3a formation when paired with (NH4)2S2O8 (entries 3–5). Replacing (NH4)2S2O8 with K2S2O8 enabled the reaction, albeit with a reduced yield of 80% (entry 6), while other oxidants such as AgNO3 and H2O2 proved largely ineffective (entries 7 and 8), underscoring the unique role of the persulfate (S2O82–) anion. Control experiments further demonstrated that no product was formed in the absence of Ru(bpy)3Cl2·6H2O, either under light irradiation with (NH4)2S2O8 or under thermal conditions at 55 °C without light (entries 9 and 10). Together, these results establish Ru(bpy)3Cl2·6H2O and (NH4)2S2O8 as an effective and synergistic photoredox system for generating the cis-dication intermediate and facilitating the [4+1] cycloaddition with water. Interestingly, when the previously described [4+1] cycloaddition of 1a with aniline was performed under these optimized photocatalytic conditions, only a low yield (24%) of product 2a was obtained. This outcome is likely due to oxidative degradation of aniline, which may act as a reductive quencher of the Ru(bpy)3Cl2·6H2O photocatalyst. For comparison with common chemical oxidants, I2 was used in the cycloaddition of 1a with H2O at room temperature (Fig. S14c, SI). However, no desired product 3a was obtained, and 1a was recovered in 72% yield. This result highlights the superior efficiency of the present photocatalytic oxidation in promoting the [4+1] cycloaddition.

We next evaluated the substrate scope of this photocatalytic [4+1] cycloaddition using the optimized conditions. As shown in Fig. 5b, thioxanthene end-capped substrates bearing electron-donating aryl groups on the 1,3-diene moiety, such as tolyl and tert-butylphenyl groups, afforded the corresponding products 3b and 3c in high yields. In contrast, substrates with electron-rich alkoxy substituents (e.g., methoxy and decyloxy) gave lower yields of 3d and 3e, likely due to partial decomposition via competing single-electron oxidation pathways facilitated by the high electron density of the alkoxy groups. Substrates bearing sterically bulky 3,5-dimethylphenyl groups afforded the corresponding spirocycle 3f in 75% yield. Electron-withdrawing haloaryl groups such as fluorine and chlorine were also well tolerated, delivering products 3g and 3h in good yields with halogen substituents intact. Additionally, alkyl-substituted substrates containing n-butyl or bulky cyclohexyl groups underwent efficient [4+1] cycloaddition to form 3i and 3j in 73% and 68% yields, respectively. Structural confirmation of the spirocyclic framework was provided by X-ray crystallographic analysis of compound 3a. DFT calculations indicate that 3a possesses a similar electronic structure to 2a: its HOMO is delocalized over the two thioxanthene moieties and the oxygen atom, while the LUMO is localized over the two phenyl rings across the C=C bond of the 2,5-dihydrofuran ring (Fig. S5, SI). The HOMO energy of 3a is estimated to be –5.35 eV from CV analysis, which is slightly lower than that of 2a, likely due to the nitrogen atom present in the latter.

To elucidate the mechanism of the present photocatalytic cycloaddition, the redox potentials of the photocatalysts and reactants were analyzed. The oxidation potential of compound 1a is estimated to be 1.01 V (vs. SCE), based on CV data (Fig. 4b). Therefore, 1a can be oxidized by the Ru(bpy)33+ species (E1/2 Ⅲ/Ⅱ=1.29 V vs SCE)21–23,37. In contrast, the excited-state Ru(bpy)32+* species (E1/2 Ⅱ*/Ⅰ=0.77 V vs SCE) lacks sufficient oxidative ability to effectively oxidize 1a. The persulfate ion (S2O82–) is known to oxidatively quench the excited Ru(bpy)32+* species, yielding Ru(bpy)33+ and generating sulfate ions (SO42–) along with highly reactive sulfate radical anions (SO4•–), which are strong oxidants (E⁰=2.5–3.1 V vs. SCE) and may also oxidize 1a38,39. Photocatalytic on/off experiments for the reaction of 1a with H2O revealed that no product formation occurred during periods without light irradiation (Fig. 6a). This observation indicates that the Ru(bpy)32+/S2O82– system is not an effective oxidant in the dark. Instead, the reactive oxidant species formed under light irradiation are short-lived and highly reactive, underscoring the essential role of photoactivation in enabling the cycloaddition process. A plausible reaction mechanism is proposed in Fig. 6b. Upon blue light irradiation, the Ru(bpy)32+ catalyst is excited to its photoactive state, Ru(bpy)32+*22,23. This excited species undergoes oxidative quenching by S2O82–, producing Ru(bpy)33+, SO42–, and SO4•–. The substrate 1a undergoes a two-step, one-electron oxidation, mediated by either Ru(bpy)33+ and/or SO4•–, to form the cis-radical cation intermediate A, which is further oxidized to the cis-dication intermediate B. These oxidation steps proceed smoothly and concomitantly, as illustrated in Fig. 2a, with concurrent regeneration of the Ru(bpy)32+ catalyst. Subsequently, water undergoes an intermolecular nucleophilic addition to the cis-dication B, yielding the cationic intermediate C. This intermediate then undergoes an intramolecular nucleophilic cyclization to afford the dispirocyclic product 3a, which features a 2,5-dihydrofuran central core.

In conclusion, we have demonstrated that a carbodication species, generated through either electrosynthesis or photocatalysis, exhibits high electrophilic reactivity toward heteroatom nucleophiles such as primary amines and water. This reactivity enables an intermolecular umpolung [4+1] cycloaddition reaction that has not been developed to date. The key to this transformation lies in the formation of a reactive cis-olefin-bridged dicationic intermediate derived from thioxanthene end-capped 1,3-dienes. This intermediate selectively undergoes cycloaddition with primary amines under electrochemical conditions and with water under photoredox catalytic conditions, yielding a class of dispirocyclic π-molecules that feature 2,5-dihydro-1H-pyrrole and 2,5-dihydrofuran cores, respectively. Given the established optoelectronic performance of structurally related dispirocyclic π-systems as hole-transporting and light-emitting materials40–43, these newly synthesized compounds are expected to exhibit high potential in future optoelectronic applications. Further studies in this direction are currently underway in our laboratory. This work highlights the synthetic potential of carbodicationic intermediates in enabling selective and mild incorporation of heteroatom nucleophiles, broadening the scope of dication chemistry and offering effective strategies for constructing complex and valuable heterocyclic frameworks.

Methods
General procedure for the electrochemical [4+1] cycloaddition with primary amines

To an undivided ElectraSyn cell (5 mL) vial equipped with a stirring bar was added 1a (57 mg, 0.1 mmol) and nBu4NPF6 (116.2 mg, 0.3 mmol, 0.1 M). The cell was equipped with (+) graphite/(–) graphite electrodes and sealed with a cap. The cell was charged with argon via a balloon. A mixture of DCM/HFIP (v/v = 5:1, 3.0 mL) and aniline (14 mg, 0.15 mmol) were added to the cell via a syringe. The reaction mixture was subjected to the programmed electrolysis at room temperature for 3 h at a constant current of 3 mA and a stirring speed of 400 rpm. Upon completion, the electrodes were washed with DCM, which was combined with the reaction mixture. After concentration in vacuo, the residue was purified by flash column chromatography using hexane/DCM (5/1) as an eluent to give desired product 2a in 98% yield (64.8 mg, 0.098 mmol) as white solid.

General procedure for the photocatalytic [4+1] cycloaddition with H2O

To a transparent test tube (Ø15 × 05 mm) was added substrate 1a (57 mg, 0.1 mmol), Ru(bpy)3Cl2·6H2O (3.7 mg, 5.0 mol%), anhydrous (NH4)2S2O8 (45.6 mg, 0.2 mmol) and anhydrous DCE/H2O (v/v = 9:1, 2 mL, 0.05 M). The test tube was stirred for 2 h under an Ar atmosphere under irradiation of a Kessil lamp (440 nm, 100% intensity) placed 5–7 cm away from the test tube. A regular fan was equipped to maintain the ambient temperature at 25 °C. Upon completion, the reaction mixture was diluted with DCM (10 mL), poured into water (20 mL) and extracted with DCM (2 × 10 mL). The combined organic layer was washed with brine (3 × 10 mL) and dried over MgSO4. After filtration and concentration in vacuo, the residue was purified by flash column chromatography using hexane/DCM (5/1) as an eluent to give desired product 3a in 98% yield (57.4 mg, 0.098 mmol) as white solid.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "In this manuscript, the authors prepared a series of aryl-substituted 1,3-dienes and carried out electrochemical and photocatalytic oxidations to generate dicationic species. The resulting ethylene dications are highly stabilized by two or four aryl groups, with primary stabilization from two thioxanthene ring systems. When done in the presence of anilines and amines, the dication reacts to form a novel spirocycle from 4+1 cycloaddition (electrochemical oxidation). Photocatalytic oxidation provides a spirocyclic ether from 4+1 cycloaddition with water. The redox characteristics have been characterized by CV and the structures of the dications studied by DFT calculations. Interestingly, the optimized dication structure prefers a cis-conformation (favored by 3.4 kcal/mol) over the trans. The cyclization products have been characterized by X-ray crystallography. Yields of the aniline/amine spirocycles are ca. 50-97% while the water spirocycles are formed in 68-93% yields. Mechanisms are proposed for the oxidation sequences and the cyclizations.\nIn general, this is an interesting study of dicationic electrophiles. The authors are correct in noting that dicationic electrophiles are usually generated under harsh conditions which precludes their use in reactions with strong nucleophiles. This methodology allows such chemistry to be performed. The products formed are also rather unusual aryl spirocycles – ones that should be further studied for in optoelectronic applications.\nThe methodology would be more interesting (and wider in scope) if the authors could extend it to a 4+2 cycloaddition. In this regard, the study should include a reaction with hydrazine or its derivatives.\nThe authors should also include studies of chemical oxidants, especially those used previously in the generation of ethylene dication systems (see Chapter 5, Superelectrophiles and Their Chemistry, Olah, 2008). For example, iodine has been previously used to generate 1,2-ethylene dications. Will it work with this system? The authors’ use of electrochemical and photochemical catalysis is outstanding. However, the results should still be compared to the chemical oxidants.\nThe study would be further improved by direct observation of the dicationic species using low temperature NMR techniques. Even more spectacular, it would be a great achievement to obtain an XRD of a crystal of the dication, although there are big technical challenges to this type of work.\nThe authors should try to develop a better hypothesis for the cis-conformation of the dication. It is more common to see cationic rings stack with neutral rings, or two neutral ring stacking, but it seems rather remarkable to have two cationic rings having pi-stacking. Indeed, the authors have noted that the ring are even parallel - suggesting a strong interaction or bonding. Most dicationic systems tend to have strong charge-charge repulsive effects, which should tend to favor the trans-stereoisomer. So why does this prefer otherwise?\nIt is not exactly clear on the fate of the protons during the cyclization steps. Shouldn’t the excess aniline or amine be the proton carrier? If so, can these ions provide the H2 gas upon reduction at the cathode?\nSome specific comments from the text:\nLine 29 carbodications have been previously generated from electrochemical oxidation; see, Yoshida, JACS 2005, 127, 6930; in general, the manuscript would be improved with a little more summary of other electrochemical routes to cationic electrophiles; the cation pool method, in particular should be mentioned.\nLine 30 it is not unusual for electrophiles to react with amines or water – even Mother Nature can do this; it is unusual to be able to generate a species with electrophilic centers in the presence of the strong nucleophiles.\nLine 35 Throughout the manuscript, there is the typo nBu4PF6. It should be: nBu4NPF6\nSupporting Information\nAn alternative synthesis of compound 1a has been reported, please cite: CN116947758 A", "reviewer_2": "The manuscript convincingly demonstrates that a cis‐olefin‐bridged carbodication—generated via a combination of electrosynthesis and photocatalysis—displays high electrophilic reactivity toward underexplored heteroatom nucleophiles. This reactivity facilitates an unusual umpolung [4+1] cycloaddition between thioxanthene-end-capped 1,3-dienes and either primary amines or water, thereby affording dispirocyclic π-systems featuring either a central 2,5-dihydro-1H-pyrrole or 2,5-dihydrofuran core. SUbstrate scope is broad. The mechanistic proposal with the DFT studies and mechanistic experiments are consistent and convincing. However, still there are some clarifications/corrections in manuscript and supporting data are required. Therefore, this work is suitable for publication in this journal only after addressing the following concerns:\n1. In CV discussion “Cyclic voltammetry (CV) of 1a in a DCM/HFIP (5:1 v/v) mixture revealed a one-wave, two- electron oxidation and a two-step, one-electron reduction”- author proposed one/two electron oxidation/reduction from CV observation only, however, more details measurement like DPV/SWV is required to support such phenomenon.\n2. “..oxidation potentials of 0.78 V and 0.59 V vs SCE, respectively,..”- this is interesting that the 2nd oxidation is happening at lower potential than the 1st one (means a cation is oxidizing more readily than a neutral species), authors may include possible rational behind this.\n3. Author could measure and include the real time anodic potential of the standard reaction with respect to a reference electrode to get more precise idea of the oxidation phenomenon at anode.\n4. CV experimental details should be mentioned, including concentration of electrolyte, substrates, solvent used, reference electrode solution composition etc. Ideally there should be separate sections in SI describing experimental details on all the mechanistic experiments.\n5. For light setup parameters should be mentioned: wattage/intensity of the light source, distance of the light source from the reaction chamber etc.\n6. Have the authors attempted electrochemical reaction with water as nucleophile under acidic condition with/without a buffer to avoid water oxidation to get the product 3?\n7. For the light on/off experiment the how the yield was measured should be mentioned.\n8. 19F NMRs should be included for relevant products.\n9. Few 13C NMRs peaks are too small to understand, need to be replaced after thorough checking.\n10. Some of the NMRs showing grease/impurity (1a-1d, 1f-1i, 2c, 2d, 2h,….) required to replace and recalculation of yield after re-purifications.\n11. The number of protons is not matching between the data and the structure (e.g. 1c), all NMR data should be thoroughly checked and corrected.", "reviewer_3": "The Jin group reported an innovative solution for the synthesis of dispirocyclic π-systems featuring 13 central 2,5-dihydro-1H-pyrrole or 2,5-dihydrofuran cores. Divergent synthetic routes were developed by either electrochemical or photoredox methodology to accomplish the formal 4+1 cycloaddition. An important carbodication intermediate was proposed and supported by DFT calculation. The reaction displayed a broad substrate scope, and mechanistic investigations were well executed. However, my major concern is the significance of this manuscript. From the methodology point of view, this reaction is predictable because hetero-nucleophile attacking a carbocation is a common decomposition pathway for carbocation formed during proton-initiated electrophilic addition of alkenes, which has been well documented in classic organic textbooks; examples of oxidative alkene activation via electrochemical and photoredox methods are also abundant. In addition, I didn’t find the unique advantage of the carbodication intermediate for facilitating this transformation, which is heteroatom-stabilized carbocation with attenuated reactivity. From the application point of view, although the authors claimed these novel spirocyclic aromatic compounds may exhibit promising optoelectronic effect, no supporting data was listed in this manuscript. Therefore, I will recommend rejection of this manuscript in its current form due to lack of significance. If such optimal optoelectronic effect of these compound can be added, I would be happy to reconsider this manuscript.\nIn addition, regarding the DFT calculation, these questions should be addressed:\nQ1. Regarding the DFT calculations performed to evaluate the stability energy difference between the cis- and trans-carbodication conformers, the authors should provide additional computational details:\n(1) Were the geometries of these conformers optimized in solvent? If not, it is recommended to reoptimize them using an appropriate solvent model.\n(2) If hexafluoroisopropanol (HFIP) was used as the solvent, please specify the corresponding computational treatment within Gaussian (e.g., implicit solvation model and relevant parameters).\n(3) For cationic species, the use of a basis set including diffuse functions is highly recommended. The def2-SVP basis set may not adequately capture the interactions in cationic systems.\nQ2. The authors are requested to clarify why the functional and basis set were switched to B3LYP/6-31G(d,p) for analyzing the HOMO and LUMO distributions of products 2a and 3a. Please provide a justification for this choice of method.\nQ3. In Section S9.5, the comparison of stability between cis- and trans-radical cation conformers is discussed. Have the authors considered an alternative conformer in which the PF₆⁻ anion is positioned closer to the phenyl group? If not, it would be valuable to include such a structure in the conformational analysis."}, "author_response": "Tohoku University\nTienan Jin, Associate Professor\nResearch and Analytical Center for Giant Molecules\nGraduate School of Science\n6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan\nPhone: +81-22-795-5707; Email: tetsuo.kin.a6@tohoku.ac.jp\nReviewer 1:\nComment 1:\nThe methodology would be more interesting (and wider in scope) if the authors could extend it to a\n4+2 cycloaddition. In this regard, the study should include a reaction with hydrazine or its derivatives.\nResponse:\nWe sincerely appreciate this valuable suggestion. In response, we examined the reaction of substrate\n1a with anhydrous hydrazine under the standard electrolysis conditions. However, no reaction\noccurred, and 1a was recovered in 96% yield. Furthermore, we investigated the reactivity of the\ndicationic species 1a2+, generated by anodic oxidation of 1a in a divided cell, with hydrazine under\ncurrent-free conditions. Again, no desired [4+2] cycloaddition product was obtained, and 1a2+ was\ncompletely reduced back to 1a.\nIn addition, preliminary studies revealed that secondary amines were unreactive under the present\n[4+1] cycloaddition conditions. Based on these negative results, we did not further explore substituted\nhydrazine derivatives. Given that the main focus of this work is the development and mechanistic\nstudy of the [4+1] cycloaddition, we decided not to include these unsuccessful trials in the revised\nmanuscript or Supplementary Information.\nComment 2:\nThe authors should also include studies of chemical oxidants, especially those used previously in the\ngeneration of ethylene dication systems (see Chapter 5, Superelectrophiles and Their Chemistry, Olah,\n2008). For example, iodine has been previously used to generate 1,2-ethylene dications. Will it work\nwith this system? The authors’ use of electrochemical and photochemical catalysis is outstanding.\nHowever, the results should still be compared to the chemical oxidants.\nResponse:\nWe appreciate the reviewer’s insightful suggestion to include studies with chemical oxidants for\ncomparison with our electrochemical and photochemical oxidation systems. Accordingly, we have\nexamined the reactivity of molecular iodine (I ), which has been previously used to generate 1,2-\n2\nethylene dications (see Olah, Superelectrophiles and Their Chemistry, 2008, Chapter 5). The results\nhave been added to the revised manuscript as follows:\nOn page 9, we describe the oxidation of 1a with amines:\n“To compare our electrochemical oxidation with a chemical approach, we tested molecular iodine (I )\n2\n(Fig. S14, SI), which has been previously used to generate 1,2-ethylene dications.2 When I (1.5 equiv)\n2\nwas used to the reaction of 1a with aniline in CH Cl or CH Cl /HFIP (5:1), the desired product 2a\n2 2 2 2\nwas formed in only 55% and 52% yield, respectively, and a significant amount of 1a was recovered.\nIn contrast, I was completely ineffective with alkylamines such as n-hexylamine, giving no desired\n2\nproduct 2i. These results demonstrate the superior oxidation efficiency of electrochemical method in\npromoting the [4+1] cycloaddition.”\nOn page 12, we describe the oxidation of 1a with H O:\n2\n“For comparison with common chemical oxidants, I was used in the cycloaddition of 1a with H O at\n2 2\nroom temperature (Fig. S14c, SI). However, no desired product 3a was obtained, and 1a was\nrecovered in 72% yield. This result highlights the superior efficiency of the present photocatalytic\noxidation in promoting the [4+1] cycloaddition.”\nThe corresponding reaction schemes are provided in Fig. S14 of the revised Supplementary\nInformation. The relevant literature source has been cited as reference 2 in the revised manuscript.\nComment 3:\ntemperature NMR techniques. Even more spectacular, it would be a great achievement to obtain an\nXRD of a crystal of the dication, although there are big technical challenges to this type of work.\nResponse:\nWe thank the reviewer for this insightful suggestion regarding the direct observation of the dicationic\nspecies and the use of low-temperature NMR techniques. In response, we have conducted additional\nexperiments to characterize the dicationic species 1a2+ generated by anodic oxidation of 1a in a\ndivided cell. The formation of 1a2+ was confirmed by high-resolution mass spectrometry (HRMS), 1H\nNMR analysis, and redox studies, as well as by its direct reactivity toward aniline.\nThe isolated dicationic species 1a2+ is soluble in DMSO-d but poorly soluble in other common\n6\nwere not feasible under these conditions. Nevertheless, 1a2+ exhibited remarkable stability in the solid\nstate for over one month under an argon atmosphere at room temperature, allowing us to obtain\nreproducible ¹H NMR spectra at ambient temperature. The ¹H NMR spectrum showed multiple\nunresolved peaks, indicating that 1a2+ likely exists as a mixture of cis- and trans-isomers. Due to this\nisomeric mixture, we were unable to obtain high-quality single crystals suitable for X-ray diffraction\n(XRD) analysis, despite repeated crystallization attempts.\nIn the revised manuscript, we have included the results of these experiments and additional\ndiscussion to clarify the generation, stability, and spectroscopic characteristics of 1a2+ (page 9).\nSpecifically, we describe the anodic oxidation of 1a to 1a2+, its redox behavior, and supporting\nanalytical data:\nOn page 9, we describe the anodic oxidation of 1a to 1a2+, redox property, and data analysis:\n“To directly observe the dicationic species 1a2+, anodic oxidation of 1a was carried out under standard\nelectrolysis conditions in the absence of amine using a divided cell (Fig. 4d). The resulting red solid\nwas analyzed by 1H NMR spectroscopy in DMSO-d , which showed complete consumption of 1a (Fig.\ncorresponding to 1a2+ and [1a2+]PF₆⁻, respectively (Fig. S12, SI). The 1H NMR spectrum of 1a2+\ndisplayed multiple unresolved peaks rather than a single set of signals (Fig. S11, SI), suggesting the\ncoexistence of a mixture of cis- and trans-dicationic isomers in the reaction system. We infer that\nduring the cycloaddition reactions conducted in an undivided cell (Fig. 3), the unreactive trans-1a2+\nmay undergo reduction at the cathode to regenerate 1a, which is then reoxidized at the anode to form\nboth cis- and trans-1a2+. This redox cycling likely enhances the overall reaction efficiency.\nFurthermore, cathodic reduction of this red solid (1a2+) under identical electrolysis conditions in a\ndivided cell regenerated 1a in 75% yield, as determined by 1H NMR analysis (Fig. S11, SI).\nCollectively, these spectroscopic and redox property provide strong evidence for the efficient\ngeneration of the dicationic species 1a2+ under anodic oxidation conditions.”\nWe have also examined the reactivity of 1a2+ with aniline under current-free conditions (page 9):\n“To investigate the intrinsic reactivity of 1a2+ toward amines, the in situ generated 1a2+ was treated\nwith aniline in the absence of applied current (Fig. 4e). The reaction afforded 2a in 40% yield, along\nwith 29% recovered 1a (Fig. S13, SI). When the solvent was switched to DCM, 2a was obtained in\n33% yield with 37% recovered 1a. These results demonstrate that 1a2+ is indeed a reactive\nintermediate capable of [4+1] cycloaddition with amines, even without electrolysis. The moderate\nefficiency likely arises from the presence of the unreactive trans-isomer and the reducing nature of\naniline toward 1a2+, as well as the generation of PhNH + species during product formation. In contrast,\n3\nreactions in undivided cells proceed more efficiently, likely due to continuous redox cycling and\nfacilitated proton transfer enabled by aniline deprotonation and the cathodic reduction of PhNH + (Fig.\n3\n4f).”\nThe new reaction schemes have been added as Figs. 4d and 4e in the revised manuscript.\nCorresponding experimental details (Sections 10.7–10.8), 1H NMR spectra (Figs. S11, S13), and\nHRMS data (Fig. S12) are provided in the revised Supplementary Information.\nComment 4:\nThe authors should try to develop a better hypothesis for the cis-conformation of the dication. It is\nmore common to see cationic rings stack with neutral rings, or two neutral ring stacking, but it seems\n2\nrather remarkable to have two cationic rings having pi-stacking. Indeed, the authors have noted that\nthe ring are even parallel - suggesting a strong interaction or bonding. Most dicationic systems tend to\nhave strong charge-charge repulsive effects, which should tend to favor the trans-stereoisomer. So\nwhy does this prefer otherwise?\nResponse:\nWe thank the reviewer for this insightful comment and valuable discussion. As correctly pointed out,\nthe presence of two cationic π-systems in a parallel orientation is indeed remarkable, as charge–charge\nrepulsion would generally favor the trans-conformation rather than the cis-form. To further understand\nthis phenomenon, we performed additional DFT calculations on the dicationic species without the\nPF ‒ counteranions. Interestingly, in contrast to the dicationic species with PF ‒ counteranions, where\n6 6\nthe cis-isomer is more stable (3.4 kcal/mol) than the trans-isomer, the calculations without\ncounteranions showed that the trans-isomer is more stable (3.6 kcal/mol). This result clearly indicates\nthat the PF ‒ anions play a crucial role in stabilizing the cis-conformation by mitigating the\n6\nelectrostatic repulsion between the two cationic centers through cation–anion interactions.\nA brief description of these findings has been added to the revised manuscript (page 5):\n“DFT analysis of 1a2+ in the presence of the PF₆‒ counteranion reveals that the cis conformer is 3.4\nkcal/mol more stable than the trans form, supporting the proposed two-step electrophilic [4+1]\ncycloaddition pathway (Fig. 2b, Table S7 and Fig. S7, SI). In contrast, when the PF₆⁻ anion is omitted,\nthe trans-dication becomes 3.6 kcal/mol more stable than the cis form. These findings suggest that the\nPF₆⁻ counteranion mitigates charge–charge repulsion between the two cationic centers by cation-anion\ninteractions, thereby stabilizing the cis configuration.”\nThe corresponding DFT results have been incorporated into Fig. 2b in the revised manuscript, and\nthe detailed computational data are provided in Table S7 and Fig. S7 of the revised Supplementary\nInformation.\nComment 5:\nIt is not exactly clear on the fate of the protons during the cyclization steps. Shouldn’t the excess\naniline or amine be the proton carrier? If so, can these ions provide the H2 gas upon reduction at the\ncathode?\nResponse:\nWe thank the reviewer for this insightful comment regarding the fate of protons during the cyclization\nsteps and the possible role of excess aniline or amine as proton carriers. We fully agree with the\nreviewer’s suggestion that the excess aniline (or amine) can serve as a proton carrier by deprotonating\nthe cationic cycloadduct intermediates, thereby generating PhNH + (or the corresponding ammonium\n3\nspecies). These protonated amines can then undergo cathodic reduction to release hydrogen gas and\nregenerate the neutral amine.\nThis mechanistic aspect has now been clarified and illustrated in the revised manuscript.\nSpecifically, the deprotonation and subsequent reduction process have been incorporated into Fig. 4f,\nwith a brief mechanistic description added on page 11:\n“Finally, deprotonation of the cationic intermediate D or D′ by aniline produces the cycloadduct 2a\nalong with PhNH +. Subsequent cathodic reduction of PhNH + generates hydrogen gas and regenerates\n3 3\naniline.”\nWe also note that this explanation is consistent with our response to Comment 3, which discusses\nthe reactivity of 1a2+ and aniline under current-free conditions.\nComment 6:\nLine 29: carbodications have been previously generated from electrochemical oxidation; see, Yoshida,\nJACS 2005, 127, 6930; in general, the manuscript would be improved with a little more summary of\nother electrochemical routes to cationic electrophiles; the cation pool method, in particular should be\nmentioned.\nResponse:\nthis important literature on the electrochemical generation of carbodication species. In response, we\nhave now included a summary of relevant electrochemical approaches to cationic electrophiles, with\nparticular emphasis on the cation pool method. Specifically, the generation of carbodication species\nvia the cation pool method has been described in the Introduction section (page 3) as follows:\n“Indeed, previous studies have shown that carbodications can be generated via the cation pool method\nthrough oxidative C–C bond cleavage under low-temperature electrolysis in the absence of\nnucleophiles, and that the resulting carbodications display remarkable electrophilic reactivity toward\nvarious carbon nucleophiles.24”\nThe relevant literature (Yoshida, J. Am. Chem. Soc. 2005, 127, 6930) has been cited as reference 24\nin the revised manuscript.\nComment 7:\nLine 30: it is not unusual for electrophiles to react with amines or water – even Mother Nature can do\nthis; it is unusual to be able to generate a species with electrophilic centers in the presence of the\nstrong nucleophiles.\nResponse:\nWe thank the reviewer for this insightful comment emphasizing that electrophiles commonly react\nwith nucleophiles such as amines and water. We fully agree that the unusual aspect of our study lies in\nthe generation of highly electrophilic carbodication species in the presence of such strong nucleophiles.\nTo clarify this point, we have revised the corresponding sentence in the Abstract (line 30) as follows:\n“Here, we report for the first time that carbodication species, generated under mild electrochemical or\nphotocatalytic conditions in the presence of heteroatom nucleophiles, display remarkable\nelectrophilic reactivity toward primary amines and water.”\nComment 8:\nLine 35: Throughout the manuscript, there is the typo nBu4PF6. It should be: nBu4NPF6.\nResponse:\nWe thank the reviewer for pointing out the typographical error in nBu PF . We apologize for this\n4 6\noversight. In the revised manuscript and Supplementary Information, all instances of nBu PF have\n4 6\nbeen corrected to nBu NPF in both the text and the schemes.\n4 6\nComment 9:\nSupporting Information: An alternative synthesis of compound 1a has been reported, please cite:\nCN116947758 A.\nResponse:\nWe thank the reviewer for this helpful comment. The suggested patent (CN116947758 A) describing\nan alternative synthesis of compound 1a has been cited as reference 4 in the revised Supplementary\nInformation (page S5).\nReviewer 2:\nComment 1:\nIn CV discussion “Cyclic voltammetry (CV) of 1a in a DCM/HFIP (5:1 v/v) mixture revealed a one-\nwave, two-electron oxidation and a two-step, one-electron reduction”- author proposed one/two\nelectron oxidation/reduction from CV observation only, however, more details measurement like\nDPV/SWV is required to support such phenomenon.\nResponse:\nWe thank the reviewer for this insightful comment. As pointed out, the cyclic voltammetry (CV)\nmeasurement alone does not unambiguously confirm a one-wave, two-electron oxidation process. To\nprovide solid experimental support, we conducted differential pulse voltammetry (DPV) of 1a under\nidentical solvent system. The DPV trace revealed a slight separation of the oxidation wave into two\nclosely spaced peaks, which supports the assignment of a two-electron oxidation process with nearly\n4\nidentical first and second oxidation potentials. This new DPV result and discussion have been added\non page 5 of the revised manuscript, and Fig. 2a has been updated to include the DPV trace as an inset.\nThe revised description reads as follows:\n“Cyclic voltammetry (CV) of 1a in a DCM/HFIP (5:1 v/v) mixture revealed a single oxidation wave\nand two distinct one-electron reduction peaks (Fig. 2a). To gain further insight into the oxidation\nprocess, differential pulse voltammetry (DPV) was conducted under identical solvent system. The\nDPV trace showed a slight separation of the oxidation wave into two closely spaced peaks (Fig. 2a,\ninset), suggesting that 1a undergoes a two-electron oxidation with nearly identical first and second\noxidation potentials.”\nComment 2:\n“..oxidation potentials of 0.78 V and 0.59 V vs SCE, respectively,..”- this is interesting that the 2nd\noxidation is happening at lower potential than the 1st one (means a cation is oxidizing more readily\nthan a neutral species), authors may include possible rational behind this.\nResponse:\nWe appreciate the reviewer’s insightful comment regarding the unusual oxidation behavior. Indeed,\nthe observation that the second oxidation occurs at a lower potential than the first suggests that the\ncationic intermediate is more easily oxidized than the neutral species. Although a definitive\nexplanation remains challenging, this phenomenon can be rationalized by considering the overall\nthermodynamics of the oxidation process. The system preferentially undergoes a two-electron\noxidation to form the highly stabilized aromatic thioxanthylium dication, rather than remaining as a\nless stable radical cation after single-electron oxidation. Furthermore, the stability of the resulting cis-\ndication (1a²⁺) is likely enhanced by intramolecular π–π interactions between the two thioxanthylium\npolyaromatic units. A brief discussion has been added on page 5 of the revised manuscript as follows:\n“This behavior can be rationalized by the preferential two-electron oxidation to yield the\nthermodynamically stable aromatic thioxanthylium dication, rather than the less stable radical cation\nformed by single-electron oxidation. The stability of the cis-dication 1a2+ is further enhanced by\nintramolecular π–π interactions between the two thioxanthylium polyaromatic units.”\nComment 3:\nAuthor could measure and include the real time anodic potential of the standard reaction with respect\nto a reference electrode to get more precise idea of the oxidation phenomenon at anode.\nResponse:\nWe sincerely appreciate this valuable and insightful suggestion to measure the real-time anodic\npotential with respect to a reference electrode, which indeed provides a more precise understanding of\nthe oxidation process occurring at the anode. In response, we performed the electrochemical\ncycloaddition of 1a with aniline under the standard conditions using an Ag/AgNO reference electrode\n3\nto monitor the real-time anodic potential.\nThe measured anodic potentials were found to be higher than the oxidation potentials of both 1a and\naniline, confirming that both species can undergo anodic oxidation. As shown in the newly added Fig.\n4c in the revised manuscript, the anodic potential gradually increased from 1.22 V to 1.48 V over 110\nmin, during which product 2a was obtained in 92% yield with 7% of unreacted 1a. The potential then\nrose sharply to 1.66 V, and after an additional 70 min, 2a was produced in 98% yield. This sharp rise\nin potential after 110 min indicates the onset of aniline oxidation, supporting that the anodic oxidation\nproceeds selectively based on the difference in oxidation potentials between 1a and aniline.\nThis discussion has been added on page 9 of the revised manuscript as follows, and Fig. 4c has been\nadded accordingly:\n“To obtain more precise oxidation information at the anode, we monitored the real-time anodic\npotentials of the reaction of 1a under standard electrolysis conditions using an Ag/AgNO reference\n3\nelectrode (Fig. 4c). The anodic potential gradually increased from 1.22 V to 1.48 V over 110 min, at\nwhich point product 2a was obtained in 92% yield, with 7% of unreacted 1a remaining. The potential\nthen rose rapidly to 1.66 V, and after an additional 70 min, 2a was obtained in 98% yield. These\napplied potentials are higher than the oxidation potentials of both 1a and aniline, enabling efficient\noxidation of both species. Moreover, the sharp increase in potential after 110 min suggests the onset of\n5\naniline oxidation, further supporting the selective anodic oxidation driven by the difference in\noxidation potentials between 1a and aniline.”\nThe detailed method has been added to Section 10.6 of the revised Supplementary Information.\nComment 4:\nCV experimental details should be mentioned, including concentration of electrolyte, substrates,\nsolvent used, reference electrode solution composition etc. Ideally there should be separate sections in\nSI describing experimental details on all the mechanistic experiments.\nResponse:\nWe thank the reviewer for this valuable comment, which has helped us improve the clarity and\ncompleteness of our manuscript. The detailed experimental conditions for the CV and DPV\nmeasurements, including the concentrations of electrolytes and substrates, solvents used, and the\ncomposition of the reference electrode solution, have been added in Section 10.2 of the revised\nSupplementary Information.\nFurthermore, in accordance with the reviewer’s suggestion, we have reorganized the Supplementary\nInformation to include a dedicated Section 10 summarizing all mechanistic studies. This section now\ncontains detailed descriptions of the DFT calculations (for dications, intermediates, and transition\nstates), electrochemical measurements (CV and DPV), spectroscopic analyses (1H NMR and\nHRMS), and experimental studies (generation of dications, redox reactions, and reactions of\ndications with aniline).\nComment 5:\nFor light setup parameters should be mentioned: wattage/intensity of the light source, distance of the\nlight source from the reaction chamber etc.\nResponse:\nIn response to Comment 5, we have added detailed light setup parameters including pictures of the\nphoto-reactor to Section 6 of the revised Supplementary Information, as follows:\n“Two parallel blue LED lamps (Kessil PR160L, 440 nm, 40 W maximum, 100% intensity) were\npositioned obliquely on either side of the test tubes, with each test tube placed 8 cm from the\ncorresponding lamp.”\nComment 6:\nHave the authors attempted electrochemical reaction with water as nucleophile under acidic condition\nwith/without a buffer to avoid water oxidation to get the product 3?\nResponse:\nWe have investigated the electrochemical reaction of 1a with water as the nucleophile under acidic\nconditions, both with and without a buffer, to obtain the corresponding product 3a. However, the\ndesired product 3a was not formed under these conditions. The detailed reaction scheme has been\nincluded in Section 12 of the revised Supplementary Information and a brief discussion has been\nadded on page 11 of the revised manuscript, as follows:\n“To suppress this competing electrolysis of water, we examined the oxidative electrolysis of 1a in the\npresence of H O under acidic conditions. When 0.05 M HCl or an aqueous KCl/HCl buffer was used\n2\nunder standard electrolysis conditions, no desired product 3a was detected, and 1a was largely\nrecovered unchanged (Fig. S15, SI).”\nComment 7:\nFor the light on/off experiment the how the yield was measured should be mentioned.\nResponse:\nWe thank the reviewer for this comment. The light on/off experiments for 1a were conducted under\nthe standard photocatalytic conditions described in Section 6 of the Supplementary Information\nBecause the reaction mixture contains water, it is not practical to acquire 1H NMR spectra directly\nfrom the same reaction mixture at multiple time points without first removing the water, a step that\ncould introduce analytical variability. To ensure accurate and reproducible yield measurements, we\n6\ntherefore performed six independent reactions in parallel, all under identical photocatalytic conditions.\nAt each designated time point, the reaction corresponding to that time point was quenched, and the\nyield of 3a was determined by 1H NMR analysis using CH Br as an internal standard. This detailed\n2 2\nprocedure has been added to Section 13 of the revised Supplementary Information. In addition, a brief\nexplanatory note has been included in Fig. 6 (page 14) of the revised manuscript, which now reads:\n“The reaction yields of 3a at various time intervals were measured by 1H NMR analysis (see SI in\ndetail) and determined using dibromomethane as an internal standard”\nComment 8:\n19F NMRs should be included for relevant products.\nResponse:\nIn response to Comment 8, we have now included the 19F NMR spectra for the relevant compounds.\nSpecifically, the 19F NMR data for the starting substrate 1f and the products 2g, 2o, and 3g are\nprovided in the revised Supplementary Information.\nComment 9:\nFew 13C NMRs peaks are too small to understand, need to be replaced after thorough checking.\nResponse:\nDue to the low solubility of the compounds in various deuterated solvents, obtaining new high-quality\n13C NMR spectra was not feasible. However, to address the concern, we have added magnified insets\nof the aromatic regions for all compounds in the revised Supplementary Information, allowing the\nrelevant peaks to be clearly observed.\nComment 10:\nSome of the NMRs showing grease/impurity (1a-1d, 1f-1i, 2c, 2d, 2h,….) required to replace and\nrecalculation of yield after re-purifications.\nResponse:\nWe apologize for the contamination observed in the previously reported NMR spectra. In response, all\naffected compounds were re-synthesized and re-purified. The new samples provided clean 1H NMR\nspectra, which are now included in the revised Supplementary Information. Importantly, the yields of\nthese compounds remained consistent with the originally reported values.\nComment 11:\nThe number of protons is not matching between the data and the structure (e.g. 1c), all NMR data\nshould be thoroughly checked and corrected.\nResponse:\nWe thank the reviewer for pointing this out. We apologize for the discrepancy in the proton count for\ncompound 1c. In response, we have carefully reviewed and corrected not only the NMR data for 1c\nbut also all other NMR data in the manuscript. The revised and verified NMR spectra are now\nincluded in the updated Supplementary Information.\nReviewer 3:\nComment 1:\nRegarding the DFT calculations performed to evaluate the stability energy difference between the cis-\nand trans-carbodication conformers, the authors should provide additional computational details:\n(1) Were the geometries of these conformers optimized in solvent? If not, it is recommended to\nreoptimize them using an appropriate solvent model.\nResponse: Yes. All conformer geometries were optimized under an implicit representation of HFIP\nusing the SMD model in Gaussian 16.\n(2) If hexafluoroisopropanol (HFIP) was used as the solvent, please specify the corresponding\ncomputational treatment within Gaussian (e.g., implicit solvation model and relevant parameters).\nResponse: A reference is added to the revised Supplementary Information (page S4) on the\ncomputational treatment (Cheng, Y.-X., Yang, X.-G., Du, F.-H. & Zhang, C. Green Chem. 26, 5914-5920\n(2024)). When reading custom solvent parameters, we used scrf = read.\n(3) For cationic species, the use of a basis set including diffuse functions is highly recommended. The\ndef2-SVP basis set may not adequately capture the interactions in cationic systems.\nResponse: Our DFT analysis targets relative stabilities between closely related conformers. In this\nregime, basis-set incompleteness and the absence of diffuse functions are expected to be largely\ncancelled in delta-E, so the qualitative ordering remains unchanged under the present protocol.\nComment 2:\nThe authors are requested to clarify why the functional and basis set were switched to B3LYP/6-\n31G(d,p) for analyzing the HOMO and LUMO distributions of products 2a and 3a. Please provide a\njustification for this choice of method.\nResponse:\nThe frontier-orbital plots are for qualitative visualization only; no quantitative conclusion relies on\nthem. We chose B3LYP/6-31G(d,p) for stability, cost, and comparability with prior literature.\nComment 3:\nIn Section S9.5, the comparison of stability between cis- and trans-radical cation conformers is\ndiscussed. Have the authors considered an alternative conformer in which the PF ‒ anion is positioned\n6\ncloser to the phenyl group? If not, it would be valuable to include such a structure in the\nconformational analysis.\nResponse:\nOur mechanistic analysis focuses on the intrinsic conformational preference (cis vs trans) of the\ndication intermediate. The preceding radical cation is assumed to undergo rapid one-electron oxidation\nto the dication, and our conclusions are drawn from the relative ordering at the dication stage. To\nmaintain consistency across comparisons, PF ‒ was kept in the same distal arrangement in both stages,\n6\nand a survey of specific ion-pair orientations at the radical-cation stage was kept out of scope. Under\nthis modeling rationale, the conclusions regarding the cis/trans ordering of the dication are not\nexpected to be materially affected.\nTienan Jin, Associate Professor\nResearch and Analytical Center for Giant Molecules\nGraduate School of Science\n6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan\nPhone: +81-22-795-5707; Email: tetsuo.kin.a6@tohoku.ac.jp\nDecember 26, 2025\nManu script I D: NCOMMS-25-43648A\nReviewer 1:\nComment:\nThe only remaining issue regards the experiment described on page 9, wherein the dication was\ngenerated in a DMSO solution as part of an effort to observe the species by NMR. It is well known\nthat DMSO itself will react with carbocation centers - forming a new C-O bond and generating the\nrelatively stable sulfoxonium ion. It is uncertain what is being observed in their NMR spectra of these\nproducts. In addition to the possibility of the cis/trans dication being observed, DMSO adduct may\nalso be the observed ion. The authors should address this chemistry in their discussion. After this\nminor edit, the manuscript is acceptable for publication.\nResponse:\nWe sincerely thank the reviewer for this insightful and technically precise comment. We fully agree\nthat DMSO is a potentially reactive solvent toward carbocationic centers, and that this chemistry must\nbe explicitly addressed to avoid ambiguity in the interpretation of the NMR data.\nFirst, we clarify that the dication was generated under standard electrolysis conditions in a divided\ncell using a DCM/HFIP solvent system. After removal of the solvents, the resulting red solid was\ntransferred to an NMR tube, and the 1H NMR spectrum was initially recorded in DMSO-d6.\nUpon careful reexamination, we fully agree with the reviewer that DMSO-d6 can act as a\nnucleophile toward the dication. Indeed, the previously reported 1H NMR spectrum contains signals\narising from both the dication (1a2+) and its DMSO-d6 adduct(s). In the previous version of the\nmanuscript, these signals were incorrectly assigned to a mixture of cis/trans dication isomers, and this\ninterpretation has now been corrected.\nConsistent with the reviewer’s concern, we observed that when the NMR sample in DMSO-d6 was\nleft at room temperature for 12 h, the downfield signals attributable to the dication gradually\ndisappeared, and the spectrum converged to a single remaining set of signals. This species is assigned\nto the DMSO-d6 adduct of 1a2+, although we cannot currently distinguish between mono- and bis-\naddition. Importantly, this DMSO-d6 adduct could not be reduced by n-Bu NI, whereas freshly\n4\nprepared samples containing intact 1a2+ were readily reduced back to 1a under otherwise identical\nconditions. This difference in redox behavior supports the assignment of the persistent species as a\nsolvent-trapped sulfoxonium-type adduct rather than the free dication.\nTo avoid ambiguity arising from DMSO reactivity, we additionally recorded the 1H NMR spectrum\nin CD CN. When measured within 30 min after NMR tube preparation, a single new and well-defined\n3\nset of signals was observed, which we assign to a single stereoisomer of the dication 1a2+. However,\nupon standing at room temperature for 24 h, these signals gradually evolved into multiple unresolved\npeaks. We attribute this behavior to the slow formation of CD CN adduct(s) of 1a2+, further\n3\nhighlighting the sensitivity of the dication toward nucleophilic solvents.\nThese results have now been explicitly discussed in the revised manuscript and Supplementary\nInformation (SI) to clarify the role of solvent participation and to avoid overinterpretation of NMR\ndata obtained in nucleophilic media. The description of the trans-dication intermediates on page 7 of\n1\nthe revised manuscript has been corrected accordingly, and the relevant experimental observations\nhave been incorporated.\n(a)\nOriginal:\n“The 1H NMR spectrum of 1a2+ displayed multiple unresolved peaks rather than a single set of signals\n(Fig. S11, SI), suggesting the coexistence of a mixture of cis- and trans-dicationic isomers in the\nreaction system. We infer that during the cycloaddition reactions conducted in an undivided cell (Fig.\n3), the unreactive trans-1a2+ may undergo reduction at the cathode to regenerate 1a, which is then\nreoxidized at the anode to form both cis- and trans-1a2+. This redox cycling likely enhances the overall\nreaction efficiency.”\nCorrected to:\n“The 1H NMR spectrum of 1a2+ recorded in CD CN displayed a single set of signals (Fig. S11, SI),\n3\nindicating the formation of a single stereoisomer of the dicationic species.”\n(b)\nOriginal:\n“The moderate efficiency likely arises from the presence of the unreactive trans-isomer and the\nreducing nature of aniline toward 1a2+, as well as the generation of PhNH + species during product\n3\nformation. In contrast, reactions in undivided cells proceed more efficiently, likely due to continuous\nredox cycling and facilitated proton transfer enabled by aniline deprotonation and the cathodic\nreduction of PhNH + (Fig. 4f).”\n“The moderate efficiency observed under these conditions likely arises from the reducing nature of\naniline toward 1a2+, as well as the generation of PhNH + species during product formation. In contrast,\n3\nreactions in undivided cells proceed more efficiently, likely due to selective anodic oxidation of 1a\nand facilitated proton transfer enabled by aniline deprotonation and the cathodic reduction of PhNH +\n3\n(Fig. 4f). Notably, during the investigation of substrate scope, no dispirocyclic analogues such as\nDSFIIFs (Fig. 1b), which are proposed to arise from a trans-dicationic intermediate (Fig. 2b), were\ndetected. Together, these experimental observations and theoretical analysis suggest that the observed\ndicationic species 1a2+ adopts a cis-geometry.”\n(c)\nOn pages S37 and S39 of the revised Supplementary Information (SI), Figures S11 and S13 show the\n1H NMR spectra recorded in CD CN, which replace the corresponding 1H NMR spectra previously\n3\nrecorded in DMSO-d . In response to the reviewer’s comment, the 1H NMR assignment of 1a2+ in\n3 3\nd has also been added.\n1a2+: red solid; 1H NMR (CD CN, 400 MHz) δ 9.23 (d, J = 8.8 Hz, 4H), 8.83 (d, J = 8.0 Hz, 4H), 8.40\n3\n(dt, J = 8.8, 1.2 Hz, 4H), 8.30-8.25 (m, 4H), 6.99-6.95 (m, 2H), 6.87-6.80 (m, 8H).\nDiscussion (page S35-S36):\nIt was noted that, when the 1H NMR spectrum in CD CN was measured within 30 min after NMR\n3\ntube preparation, a single new and well-defined set of signals was observed (Fig. S11b), which we\nassign to a single stereoisomer of the dication 1a2+. However, upon standing at room temperature for\n24 h, these signals gradually evolved into multiple unresolved peaks (Fig. S11c). We attribute this\nbehavior to the slow formation of CD CN adduct(s) of 1a2+, further highlighting the sensitivity of the\n3\ndication toward nucleophilic solvents.\nSimilarly, when the 1H NMR spectrum of 1a2+ was measured in DMSO-d within 30 min after\nof signals. Upon standing at room temperature for 12 h, the downfield resonances attributable to the\ndication gradually disappeared, and the spectrum converged to a single remaining set of signals.\nAlthough the structure has not yet been unambiguously determined, it is currently assigned as the\nDMSO-d bisadduct of 1a2+. Importantly, this DMSO-d adduct could not be reduced by n-Bu NI,\n6 6 4\nwhereas freshly prepared samples containing intact 1a2+ were readily reduced back to 1a under\notherwise identical conditions. This difference in redox behavior supports the assignment of the\npersistent species as a solvent-trapped sulfoxonium-type adduct rather than the free dication.\n3\nand CD Cl were unsuccessful due to the very poor solubility of the dication in these media.\n2 2\nReviewer 2:\nComment 1:\nFor compounds whose NMR spectra were recorded on a 600 MHz instrument, the corresponding 13C\nNMR frequency should be 150 MHz (not 101 MHz). This should be corrected for the relevant\ncompounds (e.g., 2p–2r). Also the 19F frequency in a 400 MHz instrument should be 376 MHz as per\nthe gyromagnetic ratio.\nResponse:\nWe clarify that for compounds 2p–2r, the reported 13C NMR spectra at 101 MHz were recorded on a\nspectrometer.\nRegarding 19F NMR, the spectra were recorded on a 600 MHz instrument. Based on the gyromagnetic\nratio, the corresponding 19F frequency is 565 MHz, not 376 MHz. This has been clarified in the\nGeneral Information section of the Supplementary Information as follows: “19F NMR spectra were\nrecorded on a JEOL JNM-ECA 600 spectrometer (565 MHz).”\nComment 2:\nAdditionally, the authors are requested to verify whether the manuscript length meets the journal’s\ncriteria and, if necessary, to adjust the size accordingly while keeping the scientific content unchanged.\nResponse:\nThe manuscript length has been carefully checked against the journal’s criteria in accordance with the\nAuthor Checklist. The manuscript currently meets the required length, and the scientific content has\nbeen kept unchanged. If the Editorial Office considers further adjustment necessary, we would be\npleased to revise the manuscript length accordingly.\nReviewer 3:\nNo Comments\nAll the reviewers' comments were insightful and valuable for improving the quality of our\nmanuscript. We sincerely thank them for their time and constructive feedback. We believe that the\nrevised manuscript addresses their concerns and meets the high standards expected by Nature\nCommunications.\n3"}]

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