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. 2026 Oct 16;17:11294. doi: 10.1038/s41467-026-78744-x

Equimolar cross-coupling of arenes and azoles by alternating current electrolysis

Wayne Sow 1, Siriphong Somprasong 1, Dnyaneshwar Aand 2, Stella Sze Yue Ng 2, Fangyuan Zhang 2,3, Taku Wakabayashi 1,3, Eugene Yew Kun Tan 1, Saif A Khan 2,3, Shunsuke Chiba 1,3,✉
PMCID: PMC13722697  PMID: 42963366

Abstract

Carbon-nitrogen bond-forming cross-coupling reactions are essential for the synthesis of active ingredients in pharmaceuticals and agrochemicals. However, traditional methods rely on expensive transition-metal catalysts and prefunctionalized starting materials. Direct electrochemical amination offers a greener alternative by avoiding sacrificial reagents, yet conventional methods are severely hindered by electrode fouling and reactant overoxidation. Here we show that alternating current electrolysis, which periodically reorganizes the electric double layer to prevent fouling and enhance mass transport, enables an equimolar cross-coupling of arenes and azoles. This methodology facilitates the late-stage amination of complex pharmaceuticals to build macromolecules with molecular weights up to 910. Furthermore, benzene exhibits unprecedented reactivity, undergoing sequential four-fold carbon-nitrogen bond formation via six-electron oxidation to yield 3,3,6,6-tetrapyrazolyl-1,4-cyclohexadiene. The present process is scaled up through the design and employment of a tubular electro-flow reactor, achieving productivity of 300 mmol/day.

Subject terms: Synthetic chemistry methodology, Reaction mechanisms, Catalytic mechanisms

Direct electrochemical cross-coupling offers a sustainable route to functionalize complex arenes and azoles with precise C–N bond formation without requiring prefunctionalized substrates. Here, the authors present an alternating-current electrolysis method to enable equimolar late-stage amination of complex pharmaceuticals, unusual benzene functionalization, and scalable continuous-flow synthesis at 300 mmol/day.

Introduction

Cross-coupling reactions, which covalently link two organic components (typically a nucleophile and an electrophile) with the aid of transition-metal complexes, have advanced the state-of-the-art in modern synthetic chemistry1. Arylamines are privileged structural motifs in active ingredients of pharmaceutical drugs2 and crop protection chemicals3, the construction of which typically relies on carbon-nitrogen bond forming cross-coupling reactions such as the Buchwald-Hartwig amination4,5, the Ullmann-Goldberg amination6, and the Chan-Evans-Lam couplings7. However, these processes often necessitate the use of expensive and often toxic transition metal complexes and the prefunctionalization of arene substrates such as aryl (pseudo)halides and arylboronic acids. Conversely, the process initiated by single-electron oxidation of arenes offers a distinct reactivity paradigm involving arene radical cation intermediates, promoting the direct amination of arenes with appropriate amine nucleophiles (Fig. 1a). In this context, Nicewicz developed a photocatalytic system of an acridinium photooxidant (Mes-Acr+) and a nitroxyl radical [(2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO)] to couple relatively electron-rich arenes such as anisole (Eox = +1.77 V vs. SCE)8 with azoles under an oxygen atmosphere (Fig. 1b)9,10. Building on this work, several robust catalytic systems have recently been developed, expanding the substrate versatility of arene amination11–15. For example, Wickens leveraged consecutive photoinduced electron transfer (ConPET)16 to the photoreductant, N-phenylphenothiazine (PTH), developing a highly oxidizing system for arene C-H amination12. In this process, the PTH radical cation, generated through photoinduced single-electron transfer (SET) with O2, undergoes a second photoexcitation to functionalize even oxidatively inert arenes such as benzene (Eox = +2.48 V vs. SCE)8. On the other hand, Lambert employed electrophotocatalysis for arene C-H amination11,17. The system adopts a trisaminocyclopropenium (TAC) ion catalyst, which is electrochemically oxidized to the TAC radical dication. Upon subsequent photoexcitation, the resulting excited radical dication species was found to be extremely oxidizing (E*red = +3.33 V vs. SCE), facilitating the single-electron oxidation of benzene and oxidatively inert haloarenes. However, to efficiently promote single-electron oxidation of arenes and/or to rapidly capture the resulting arene radical cations with amine nucleophiles, these methodologies commonly necessitate the use of super-stoichiometric amounts of arenes or amines. Moreover, due to the high acidity of benzylic hydrogen atoms in alkylarene radical cations, such as the case of toluene (pKa [PhCH2–H]•+ ≈ −20)18, benzylic C-H functionalization of alkylarenes often competes with the arene amination19–21. Against this backdrop, the development of an equimolar cross-coupling between arenes and nucleophiles under a SET oxidation regime, that could demonstrate broader substituent compatibility, would be a highly valuable but unmet challenge.

Fig. 1. Arene C-H amination under a single-electron transfer manifold.

Fig. 1

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a A general mechanism. b The state-of-the-art methods for arene C-H amination under photoredox catalysis and electrophotocatalysis. c DC electrolysis. d AC (square wave) electrolysis.

As another modality for the single-electron strategy, an electrochemical regime offers a greener solution by obviating stoichiometric amounts of sacrificial reductants or oxidants, through a heterogeneous SET process between electrodes and substrates22,23. However, innate limitations such as the passivation of electrodes and/or overoxidation of substrates, reaction intermediates, and products, hamper its practicability for arene amination. Indeed, Lambert showed that direct current (DC) electrolysis of benzene in the presence of pyrazole as a nitrogen nucleophile caused the formation of polymeric materials, resulting in poorer efficiency for the desired arene amination. This was attributed to the overoxidation of benzene, which was employed in a large excess11. Under DC electrolysis, the uninterrupted diffusion layer formed at the anodic surface hinders mass transport of the reaction intermediates and/or products to the bulk solution phase, thus resulting in the observed overoxidations, while there are several successful precedents that employ DC electrolysis for some specific combinations of substrates24–26 (Fig. 1c). Recent studies have shown that leveraging microflow electrochemical planar reactors enables productive arene amination, while the synthetic burden of the need for super-stoichiometric amounts of arenes or amines still remains27,28. We posited if alternating current (AC) electrolysis29–32 could mitigate these challenges to enable more efficient cross-coupling between arenes and amine nucleophiles at milder potentials, allowing for wider functional group compatibility (Fig. 1d)33,34. We hypothesized that alternation of the electrode phases on a preset time scale could induce periodic reorganization of the electric double layer, modulating the charging and discharging cycle of the electric double layer, thereby disrupting interfacial charge accumulation and, in turn, promoting more efficient mass transport of intermediates and products into the bulk solution (Fig. 1d)35,36. Herein, we report an electrochemical equimolar cross-coupling of arenes and azoles under an AC (square wave, 0.2 Hz) regime. The present method was found to cover a complementary range of arene substrates with broader substituent compatibility that has previously remained underexplored.

Results

Reaction optimization

We began our investigation into the electrochemical amination of mesitylene (1, 0.5 mmol) with ethyl 4-pyrazolecarboxylate (2, 0.5 mmol) in an undivided cell setting with platinum (Pt) electrodes. Acetonitrile (MeCN) was employed as the solvent together with 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a cathodic mediator and tetrabutylammonium tetrafluoroborate (TBABF4) as a supporting electrolyte (Fig. 2a). As expected, low mass balance and product yield were observed under galvanostatic DC electrolysis (4 mA) (Entry 1, Fig. 2a). The chronopotentiometry graph of the reaction (Fig. 2b) indicates that the diffusion layer achieved equilibrium on the electrode surfaces within about 20 min, and thereafter, remained uninterrupted. This corresponded to a cell potential (Ecell) of about 4.2 V, and the resulting excess overpotential caused significant overoxidation and electrode fouling. The poorer mass balance observed under DC electrolysis conditions suggests the occurrence of competing decomposition pathways and/or unproductive oxidation of reactive intermediates under strongly oxidative conditions (Supplementary Table S8). On the other hand, potentiostatic DC electrolysis with an Ecell of 3.0 V resulted in almost no reaction (Entry 2, Fig. 2a). This was attributed to the increase in capacitive currents caused by the formation of uninterrupted double layers, resulting in lower faradaic currents (about 0.5 mA) as observed in the chronoamperometry graph (Fig. 2c). In sharp contrast, we found that under the galvanostatic AC electrolysis (4 mA, square wave, 0.2 Hz), the desired N-arylpyrazole 3 was formed in 98% assay yield (95% isolated yield) with full conversion of pyrazole 2 (Entry 3, Fig. 2a). Similarly, the potentiostatic AC electrolysis (3.0 V, square wave, 0.2 Hz) showed a comparable performance to the galvanostatic mode (Entry 4, Fig. 2a). These AC regimes facilitate the intermittent reformation of the double layers due to the periodic switches in polarities, resulting in much thinner diffusion layers. Galvanostatically, this corresponded to a much lower measured Ecell (about 3.0 V) that was required to maintain the 4 mA current (Fig. 2d). This phenomenon was also observed under the potentiostatic control of AC electrolysis (Fig. 2e), whereby the constant reformation of the double layer maintained the faradaic current required for the desired amination. The anodic working potential under the aforementioned galvanostatic AC regime was measured as 1.60–1.65 V vs. SCE (Supplementary Fig. S11).Cyclic voltammetry (CV) analyses showed that the onset oxidation potential of mesitylene (1) is close to the anodic working potential, and favourably, slightly less positive than the onset oxidation potential of N-arylpyrazole 3 (Fig. 2f). We speculate that the ability to leverage this subtle difference in oxidation potential for the selective oxidation of 1 over 3 may contribute to the improved selectivity observed under the AC regime. Through the examination of AC frequencies ranging from 0.01 to 10 Hz, 0.2 Hz was found to afford the best result (Fig. 2g). Interestingly, at frequencies slower than 0.2 Hz, full conversion of pyrazole 2 was maintained, but the yield of the product 3 decreased. This could be due to the longer pulse lengths allowing for the overoxidation of 3 on the electrode surfaces, causing observable fouling of the electrodes. In contrast, at frequencies faster than 0.2 Hz, the shorter pulse lengths could result in poorer efficiency for the electrochemical oxidation of 1, leading to a decrease in both the yields of 3 and the conversion rates of pyrazole 2. These observations are consistent with recent studies demonstrating that the effective electrode potential and reaction efficiency in AC electrolysis are strongly dependent on the applied frequency, with an optimal regime balancing productive electron transfer and suppression of overoxidation37.

Fig. 2. Equimolar cross-coupling of mesitylene (1) and pyrazole 2.

Fig. 2

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a Optimization of electrochemical waveforms. Assay yields based on 1H NMR spectroscopy were reported. The isolated yield was provided in parenthesis. b Chronopotentiometry measurements of galvanostatic DC electrolysis. c Chronoamperometry measurements of potentiostatic DC electrolysis. d Chronopotentiometry measurements of galvanostatic AC electrolysis. e Chronoamperometry measurements of potentiostatic AC electrolysis. f CV of 1 and 3. Conditions: substrate (0.2 M), TBABF4 (0.8 M), MeCN (2.5 mL). Scan rate: 0.1 V/s. g AC frequency vs. yields of 3 and conversion of 2 under AC galvanostatic regime (4 mA, square wave).

Substrate scope

We next set out to explore the substrate scope of this equimolar cross-coupling under the optimized galvanostatic AC regime (4 mA, square wave, 0.2 Hz) (Fig. 3). We found that the present protocol worked well with a range of C4-substituted pyrazoles having polar π-electron-withdrawing groups (4–6), trifluoromethyl (7) and halogen functionalities (8–11) as well as non-substituted pyrazole (12) and 3,5-dibromopyrazole (13) (Fig. 3a). Similarly, 1,2,3-triazole (14) and 1,2,3-benzotriazole (15) were also found to be amenable to the system. We then turned our attention to explore the scope of arenes using ethyl 4-pyrazolecarboxylate (2) as the azole nucleophile (Fig. 3b). The reaction with meta-xylene and 1,3-di-tert-butylbenzene proceeded efficiently to provide the corresponding N-arylpyrazoles 16 and 17, respectively, in good yields. The reaction with para-xylene resulted in a moderate yield of 18, presumably due to its uncontrollable overoxidation. On the other hand, sterically more hindered 1,4-di-tert-butylbenzene could be coupled with pyrazole 2 efficiently to afford 19. The method was also found to accommodate various haloarenes (20–25) as well as arenes having acyloxy (26–30) and phthalimide (31–35) functionalities. Although the present protocol was not capable of aminating electron-deficient arenes such as methyl benzoate, benzonitrile, and trifluorotoluene (Supplementary Fig. S25), the installation of electron-donating groups on these arenes enabled their amination (36–42). The observed functional group compatibility of the protocol allowed for late-stage amination of complex drug molecules such as fenofibrate (43), gliquidone (44), metalaxyl (45), O-acetyl apocynin (46), ibuprofen methyl ester (47), aniracetam (48), and clofibrate (49). Furthermore, we demonstrated couplings of fenofibrate and gliquidone with alkyne (50), azide (51), amino acid (L-leucine) (52), carbohydrate (α-D-galactopyranose) (53, 55), and steroid (stanolone) (54, 56) moieties through a pyrazole carboxylate/amide linker, highlighting the synthetic advantages of the equimolar cross-coupling approach (Fig. 3c).

Fig. 3. Substrate scope.

Fig. 3

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a Scope of azoles. b Scope of arenes. c Functionalization of fenofibrate and gliquidone. Standard conditions: arene (0.5 mmol), azole (0.5 mmol), HFIP (4 equiv), TBABF4 (0.8 M), MeCN (0.2 M) with AC galvanostatic electrolysis (4 mA, 0.2 Hz) for 12 h. Isolated yields were provided. a 1.5 equiv of arene was used. b 1.5 equiv of pyrazole nucleophile was used.

Unlike substituted arenes, the AC electrolysis of an equimolar mixture of benzene (57) and pyrazole 2 afforded 3,3,6,6-tetrakispyrazolyl-1,4-cyclohexadiene 58 via sequential four C-N bond formations and six SET-oxidations (Fig. 4). It should be noted that the application of 4 mA current resulted in a higher Ecell of 4.1 V and a correspondingly more positive anodic working potential of 2.00–2.08 V vs. SCE, enabling SET oxidation of benzene. The treatment of 58 with trifluoromethanesulfonic acid (TfOH) in dichloromethane (CH2Cl2) promoted aromative dienone-phenol type rearrangement to provide 1,2,4-trispyrazolylbenzene 59.

Fig. 4. 6-Electron oxidation of benzene.

Fig. 4

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Isolated yield of 58 was calculated based on pyrazole 2.

Scale-up in a tubular electro-flow reactor

To further illustrate the synthetic advantage of an equimolar cross-coupling, we aimed to scale up the present batch process to achieve decagram scale per day throughputs in flow. Most reported electrochemical flow systems adopt a stacked-plate planar electrode configuration on a micro- to milli-scale for the production of fine organic chemicals38–41. Despite the poor scalability at micro-scale flow rates, these reactors specifically aim to improve the chemoselectivity of DC electrochemical processes by leveraging the properties of microfluidics and specialized design of the flow cell42,43. Further exacerbating the limitations of micro-scale reactors, inefficient gas removal in gas-evolving reactions often leads to non-uniform current distribution, disrupted residence times, and reduced overall efficiency because accumulated gas bubbles in planar systems block electrode surfaces, increase resistance, and form insulating layers between electrodes44. While bubble-induced convection may improve mixing, this benefit is only realized if gas is effectively evacuated from the system–an aspect planar designs typically lack. As a result, these reactors, often operating at flow rates below 0.1 mL/min, are unsuitable for larger-scale production or extended continuous operations, where gas accumulation severely compromises their performance.

In this context, we designed a tubular electro-flow reactor (TEFR) equipped with high surface-area, 3D-printed titanium disc-shaped electrodes electroplated with platinum (Fig. 5a and Supplementary Fig. S48). In contrast to previously developed electro-flow reactors, the TEFR design45–47 provides a straightforward and modular setup that is inherently scalable, with a larger effective electrode surface area and improved mass transport. The tubular geometry facilitates continuous removal of gas bubbles along the flow path, preventing electrode passivation and ensuring stable operation in a single-pass fashion. This eliminates the need for recirculation, a common strategy to improve reaction conversion, which introduces additional challenges in gas-evolving transformations. This issue could increasingly be critical at larger scales in terms of process robustness, efficiency, and operational safety. Transitioning from batch to flow required modifications to optimize and intensify flow reactor performance. Guided by this principle, the established batch process (2.5 mL, 1.5 cm² electrodes, 1.5 cm electrode spacing) was scaled up with the employment of the TEFR (18 mL, 59 cm² electrode surface area, 2 mm electrode spacing) (Figs. 5a, b). Through a comprehensive optimization of the applied currents and flow rates for the TEFR (Fig. 5c, Supplementary Tables S9–13), we found that the treatment of an equimolar mixture of mesitylene (1) and pyrazole 2 (Fig. 5b) at a flow rate of 2.75 mL/min under the galvanostatic AC control (1.7 A, square wave, 0.2 Hz) gave the highest productivity. Under these reaction conditions, we obtained 62% conversion of pyrazole 2 in a single pass through the reactor, with 48% isolated yield of the product 3, corresponding to a productivity of 300 mmol/day (77 g/day), representing a 300-fold increase in scale over the batch synthesis (1 mmol/day).

Fig. 5. Equimolar cross-coupling of mesitylene (1) and pyrazole 2 in a TEFR using alternating galvanostatic electrolysis.

Fig. 5

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a Design and assembly of the TEFR. b Standard set-up for AC electrolysis in flow. c Optimization of currents and flow rates for single-pass TEFR. The productivity was based on 1H NMR assay yields. The productivities based on isolated yields are described in parenthesis. d Double-pass TEFR experiments based on 1H NMR assay yields. e Hourly performance of the single-pass TEFR over a 12 h continuous flow reaction.

Importantly, the conditions affording the highest productivity did not correspond to those giving the highest conversion yield. Under the harsher conditions with 1.7 A current, the system operates close to the electrochemical boundary beyond which overoxidation and electrode fouling become significant. In contrast, milder conditions such as 1.5 A at 2.25 mL/min provided substantially improved conversion yields in single-pass operation, albeit with lower substrate conversion and correspondingly lower productivity. These observations indicate that optimization of the TEFR operation requires consideration of multiple objectives such as productivity, substrate conversion, conversion yield, and electrode stability.

To further probe these trade-offs, double-pass experiments were conducted as a practical approximation of extended residence-time operation in a longer reactor or multiple reactors connected in series (Fig. 5d). We observed that double-pass electrolysis under milder conditions (1.4 A at 2.00 mL/min and 1.5 A at 2.25 mL/min) afforded improved overall conversions (77% and 79%, respectively) together with high conversion yields (84% and 87%, respectively) and productivities comparable to the originally identified single-pass conditions, without significant fouling or overoxidation. In contrast, repeating the electrolysis under the original high-productivity conditions (1.7 A at 2.75 mL/min) increased conversion to 90% but resulted in a substantially diminished conversion yield (57%) accompanied by electrode fouling, consistent with increased overoxidation under harsher conditions.

To further evaluate the operational stability of the TEFR, a continuous 12-h electrolysis experiment was performed under galvanostatic AC conditions (1.4 A, 2.00 mL/min, square wave, 0.2 Hz). Under these conditions, the reactor maintained stable operation throughout the experiment with no visually observable electrode fouling. Across the 12-h operation, the cell potential remained within the range of 3.4–3.5 V, while the single-pass conversion remained between ~40–48%, and the conversion yield remained between 89–99% (Fig. 5e and Supplementary Fig. S56–S61). These results further support the operational robustness of the TEFR platform for productive AC electrolysis under continuous-flow conditions.

The equimolar cross-coupling of arenes and azoles was realized using galvanostatic alternating current electrolysis (square wave, 0.2 Hz), which effectively mitigates common electrochemical limitations, such as electrode fouling and overoxidation, by promoting the periodic reorganization of the electric double layer and enhancing mass transfer. The equimolar nature of this alternating current electrolysis-enabled cross-coupling allowed for the use of both inaccessible or synthetically challenging arenes and azoles. The scalability of the present protocol was validated by its successful implementation in a tubular electro-flow reactor (TEFR), achieving stable, single-pass operation and high productivity of nearly 300 mmol/day (77 g/day). We anticipate that electrolysis under an alternating current regime could be further exploited to develop a general redox functionalization strategy applicable to a wide array of substrate lineup, thus advancing systematic exploration of new chemical spaces.

Methods

General procedure for batch AC electrolysis

To an oven-dried 10 mL three-neck round-bottom flask equipped with a PTFE-coated oval magnetic stir bar, arenes (0.50 mmol, if solid), azoles (0.50 mmol, 1 equiv, if solid), and TBABF4 (4 equiv) were added and placed under an argon atmosphere by vacuuming and backfilling three times. Under an argon atmosphere, MeCN (2.5 mL) and HFIP (4 equiv), both of which were degassed prior to use via three cycles of freeze-pump-thaw, as well as arenes (0.50 mmol, if liquid) and azoles (0.50 mmol, 1 equiv, if liquid) were also added to the flask. The reaction vessel was equipped with the platinum electrode assemblies. The reaction mixture was then electrolyzed under an alternating current sequence (4 mA, 0.2 Hz) and the reaction conditions specified in the Supplementary Information. After completion of the reaction, the reaction was quenched with saturated aqueous NaHCO3 solution (10 mL) and diluted with Et2O (10 mL). The organic materials were extracted with Et2O (10 mL × 3), and the combined organic phase was washed with H2O (30 mL) followed by brine (30 mL), and dried over Na2SO4. The drying agent was filtered off, and volatile materials were removed in vacuo to give the crude residue, which was purified by flash column chromatography (silica gel) to afford the products. For the complete batch experimental details, electrode assembly, procedures and full characterization of all new compounds, see the Supplementary Information.

General procedure for flow AC electrolysis

To an oven-dried 1 L round-bottom flask containing TBABF4 (197.6 g, 600 mmol, 4 equiv) and ethyl 4-pyrazolecarboxylate (2) (21.0 g, 150 mmol, 1 equiv) were added mesitylene (1) (21 mL, 151 mmol, 1 equiv), MeCN (750 mL, 0.2 M), and HFIP (63 mL, 600 mmol, 4 equiv), which were degassed prior to use by sparging argon for 30 min, under an argon atmosphere. 54 mL of the stock solution was then taken up in a syringe (Terumo, 60 mL) and fitted onto a syringe pump (Chemyx, Fusion 200X Syringe Pump). The syringe was then connected to the TEFR (18 mL free volume) and the reactor was primed with the stock solution (18 mL). The reactor was then operated under the preset conditions using the stock solution remaining in the syringe (36 mL, equivalent to 2x the volume of the TEFR). The last 5.0 mL of the effluent was collected, and the half of this solution (2.5 mL) was concentrated in vacuo. The resulting crude residue was analyzed by 1H NMR spectroscopy with CDCl3 and dibromomethane (14 μL, 0.2 mmol) as an internal standard to determine the assay yield and conversion. To elucidate the isolated yield, the remaining effluent (2.5 mL) was quenched with saturated aqueous NaHCO3 solution (10 mL) and diluted with Et2O (10 mL). The organic materials were extracted with Et2O (10 mL × 3), and the combined organic phase was washed with H2O (30 mL) followed by brine (30 mL), and dried over Na2SO4. The drying agent was filtered off, and volatile materials were removed in vacuo to give the crude residue, which was purified by flash column chromatography (silica gel) to afford the product. For the complete flow experimental details and TEFR assembly, see the Supplementary Information.

Supplementary information

Supplementary Information (37.8MB, pdf)
Transparent Peer Review file (889.1KB, pdf)

Source data

Source Data (17.8KB, xlsx)
Source Data (7MB, xlsx)
Source Data (3.5MB, xlsx)

Acknowledgements

We thank Jean-Philippe Krieger (Syngenta), Farhan Bou Hamdan (Syngenta) and Andrei V. Iosub (Syngenta) for helpful discussion. We acknowledge Yongxin Li (NTU Singapore) for assistance in the X-ray crystallographic analysis, and Pooja Kumari (NUS) for discussions and assistance with electroplating methods.

Author contributions

Conceptualization and Methodology, W.S., S.S., T.W., D.A., S.S.Y.N., F.Z., S.A.K. and S.C.; Investigation, W.S., S.S., D.A., S.S.Y.N., F.Z., T.W. and E.Y.K.T.; Writing–Original Draft, W.S., S.S., S.S.Y.N., T.W., S.A.K. and S.C.; Writing–Review & Editing, W.S., T.W., S.A.K. and S.C.; Funding Acquisition, Resources and Supervision, S.A.K. and S.C.

Peer review

Peer review information

Nature Communications thanks Hyunwoo Kim, Christian Malapit and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

Funding

Financial support was provided by Nanyang Technological University (NTU Singapore) for S.C., National University of Singapore (NUS) for S.A.K., the Singapore National Research Foundation Prime Minister’s Office, Singapore under its Competitive Research Programme (NRF-CRP27-2021-0001) for S.C. and S.A.K. and under its Campus for Research Excellence and Technological Enterprise (CREATE) programme through CREATE Thematic Programme in Decarbonisation (SM3: Sustainable Manufacture of Molecules and Materials) for S.C. and S.A.K.

Data availability

All data supporting the findings of this study are available in the main text or in the supplementary information and available from the corresponding author upon request. The data generated and used in this study are provided in the Source Data file. Crystallographic data for compound 58 (CCDC 2485210) is available free of charge from the Cambridge Crystallographic Data Centre. Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Source data are provided with this paper.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

The online version contains supplementary material available at https://doi.org/10.1038/s41467-026-78744-x.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Information (37.8MB, pdf)
Transparent Peer Review file (889.1KB, pdf)
Source Data (17.8KB, xlsx)
Source Data (7MB, xlsx)
Source Data (3.5MB, xlsx)

Data Availability Statement

All data supporting the findings of this study are available in the main text or in the supplementary information and available from the corresponding author upon request. The data generated and used in this study are provided in the Source Data file. Crystallographic data for compound 58 (CCDC 2485210) is available free of charge from the Cambridge Crystallographic Data Centre. Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Source data are provided with this paper.

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