To optimize reaction conditions, the cross-coupling of N-methylaniline (1) and methyl 4-bromobenzonate (2) was picked as the model reaction. Catalytic tests with different conditions were carried out in an undivided PEC cell with a three-electrode configuration (Supplementary Figs. 1–3). The BiVO4 photoanode was successfully prepared (Supplementary Fig. 4) using the previously reported method36. Concurrently, a Ni foam electrode and a Ag/AgNO3 electrode were employed as the cathode and the reference electrode, respectively. In a typical test, the experiment was performed in N2 atmosphere under the irradiation of a 465 nm blue light emitting diode with a constant external bias of –0.4 V vs. Ag/AgNO3 (Fig. 1b).Initially, the reaction was conducted using acetone as the solvent and LiBr as the electrolyte. NiBr2 glyme and the ligand 4,4′-Di-tert-butyl-2,2′-dipyridyl (dtbppy) were added to the reaction system simultaneously for the formation of Ni catalyst. 1,4-Diazabicyclo[2.2.2]octane (DABCO), a HAT mediator, was introduced to the PEC cell to facilitate the electron transfer between the photoanode and amine (Fig. 1c, entry 1). Such recipe led to a high yield of 82% towards the target product methyl 4-(methyl(phenyl)amino)benzoate (3). To investigate the solvent effect, acetone was in turn replaced by acetonitrile (MeCN), dimethylacetamide (DMA) and dichloroethane (DCE), but poor results were observed (Fig. 1c, entry 2–4). As for the influence of electrolyte, when LiBr was changed to nBu4NBr or nBu4NBF4, the yield dropped below 60% (Fig. 1c, entry 5–6). Reducing the amount of either HAT mediator or electrolyte had negative effects on the yield (Supplementary Fig. 5). Additionally, trace product was obtained when Pt plate was employed as the cathode (Fig. 1c, entry 7). Changing Ni precatalyst or reducing the ligand loading amount exhibited limited impact on the reaction, with yields consistently exceeding 70% (Fig. 1c, entry 8–9). However, replacing dtbppy with 2,2’-bipyridine (bpy) almost stopped the reaction from proceeding (Fig. 1c, entry 10). Recycling experiments were carried out to test the stability of the photoanode (Supplementary Fig. 6), and the catalytic performance of BiVO4 slightly decreased after five cycles of experiments.The role of each component in the reaction was explored. As expected, no reaction happened when Ni precatalyst or ligand was omitted (Fig. 1c, entry 11). Similarly, only trace product was found in the absence of DABCO (Fig. 1c, entry 12) or electricity (Fig. 1d, left column). These results demonstrated that Ni catalyst, DABCO and electricity all played crucial roles in the catalysis. Electrocatalysis under dark condition was also carried out (Fig. 1d, middle column), and no product was detected until the potential was raised up to +1.5 V vs. Ag/AgNO3. Furthermore, due to the high overpotential of electrocatalysis, the yield and selectivity of product 3 were merely 16% and 62% at +1.5 V vs. Ag/AgNO3, respectively (Supplementary Table 1). Notably, introducing light to the electrocatalysis dramatically lowered the potential to –0.4 V vs. Ag/AgNO3, consequently improving the yield and selectivity of product 3 to 82% and 89% (Fig. 1d, right column).Linear sweep voltammetry (LSV) and cyclic voltammetry (CV) were applied to investigate the EC and PEC properties of the reaction systems (See Supplementary Figs. 7–10 for more details). The onset potential on BiVO4 photoanode in PEC cell was much lower than that on glassy carbon (GC) anode in EC cell (Supplementary Fig. 7), suggesting the PEC approach significantly lowered the overpotential. As shown in Fig. 2a, the LSV diagram of BiVO4 anode showed significant onset potential decrease in the presence of light, which highlighted the superiority of PEC cell. Adding DABCO also contributed to the reduction of onset potential (Fig. 2a, pink curve vs. blue curve), indicating that DABCO served as a mediator to promote the charge transfer between the anode and the substrate. The function of DABCO was further revealed by CV curves (Fig. 2b). The considerably lower oxidation potential of DABCO (EOx,DABCO = +0.41 V vs. Ag/AgNO3) than that of the substrate N-methylaniline (EOx,N-methylaniline = +0.53 V vs. Ag/AgNO3) demonstrated that it was easier to be oxidized by the anode, which well accorded with LSV results. Moreover, in the presence of N-methylaniline (Fig. 2b, pink curve), the intensity of DABCO oxidation peak obviously exceeded the original one (Fig. 2b, orange curve), suggesting the interactions between oxidized DABCO and N-methylaniline. Furthermore, the EC properties of Ni catalyst were studied via CV tests. As illustrated in the right diagram of Fig. 2c, the CV curve of Ni catalyst displayed a reduction peak at Ered,1 = –1.73 V vs. Ag/AgNO3, which is attributed to the Ni(II/I) redox couple (orange curve). After the inclusion of aryl bromide, the intensity of reduction peak increased significantly (pink curve). The change in reduction signal reveals the oxidation addition of aryl bromide on Ni(I) catalyst. Meanwhile, the concurrent observation of enhanced Ni(I/0) redox signals (Ered,2 = –2.24 V vs. Ag/AgNO3) and the emergence of a new pair of reversible redox peaks at –2.0 V vs. Ag/AgNO3 fortified the existence of Ni(I)-participated oxidation addition15,47.Fig. 2: Photoelectrochemical performances and cyclic voltammograms studies.a LSV curves of BiVO4 photoanode under irradiation (pink), dark (black) and in the absence of DABCO (blue). b CV curves of blank electrolyte (black), in the presence of DABCO (orange), N-methylaniline (blue) and the mixture of DABCO and N-methylaniline (pink). c CV curves of blank electrolyte (black), methyl 4-bromobenzonate (denoted as Ar-Br, blue), NiBr2 glyme + dtbbpy (denoted as NiL, orange) and the mixture of Ar-Br and NiL (pink). Note that the CV curves are recorded on the glass carbon electrodes owing to its inert nature and wide electrochemical window compared with BiVO4.To dig deep into the reaction pathway, several control experiments and radical trapping experiment were designed and carried out. When the control experiment was conducted in a divided cell where all the reagents except for LiBr were placed in the cathode chamber (Fig. 3a, top), only trace 3 was obtained, displaying the importance of anode oxidation reaction. The addition of butylated hydroxytoluene (BHT), a radical-scavenging agent, greatly suppressed the generation of 3 (Fig. 3a, middle). Instead, BHT adduct 4 was detected by high-resolution mass spectrometry (HR-MS), demonstrating that the nitrogen-centered radical was an important intermediate in the PEC process. Control experiment in the absence of Ni catalyst led to 1,2-dimethyl-1,2-diphenylhydrazine (5) from coupling of 1 (Fig. 3a, bottom), offering another evidence about the existence of radical intermediate. This result indicated that the Ni catalyst played a critical role in the cross-coupling of 1 and 2. Further getting rid of DABCO from the reaction system resulted in the vanishment of 5, showing that DABCO took part in the generation of amine radical.Fig. 3: Mechanistic studies and proposal.a Control experiments and radical trapping experiment. b Proposed reaction mechanism. c Computed energy profile of Ni-catalytic cycle.Based on the experimental results above, a plausible reaction mechanism of PEC C–N coupling was proposed (Fig. 3b). Under light irradiation, the electron in the valence band (VB) of BiVO4 photoanode was excited to the conduction band (CB) and left a hole behind. After migrating to the surface, the photogenerated hole oxidized DABCO (6) to DABCO cation radical (7) via a single-electron transfer reaction. The HAT between DABCO amine radical and the aniline substrate gave rise to the protonated DABCO (8) and the aniline radical (9). The deprotonation of the former accomplished the organocatalytic cycle and the latter participated in the Ni-catalytic cycle. Meanwhile, the Ni-catalytic cycle started from the reduction of NiII catalyst 10 at the Ni foam cathode. As-generated NiI intermediate 11, confirmed by high-resolution electrospray ionization mass spectrometry (ESI-HRMS) (Supplementary Fig. 11), involves the oxidative addition of aryl bromide to form NiIII intermediate 12 followed by receiving an electron from the cathode to generate NiII intermediate 13. Afterwards, the NiII intermediate was added by the aniline radical to produce NiIII intermediate 14. Finally, a reductive elimination occured and the coupling product was formed.Density functional theory (DFT) simulations were performed (See Supplementary Information for details) to verify the rationality of the proposed reaction mechanism. The HAT from aniline to DABCO cation radical had a low activation energy of ∆G‡HAT-TS = +9.4 kcal mol–1 (Supplementary Fig. 12), indicating the fast kinetics of this process. As shown in Fig. 3c, the oxidative addition step of aryl bromide on 11 was proven to be a fast step (∆G‡11→TS1 = +9.4 kcal mol–1) with a Gibbs free energy change of ∆G11→12 = –4.4 kcal mol–1. The reduction step for the intermediate 12 was calculated to be endothermic (∆G12→13 = +22.9 kcal mol–1). Once NiII intermediate 13 was formed, it was possible to be attacked by N-methylaniline or its radical. Noteworthily, DFT simulation elucidated that compared with the traditional amine attacking pathway (13 → TS2’ → 15) in electrocatalysis, the radical attacking pathway (13 → TS2 → 14) had a much lower energy barrier (∆G‡13→TS2 = +5.0 kcal mol–1 vs. ∆G‡13→TS2’ = +9.9 kcal mol–1) and was more thermodynamically favorable (∆G13→14 = –9.2 kcal mol–1 vs. ∆G13→15 = –2.8 kcal mol–1), revealing the intrinsic advantage of PEC approach. Finally, the reductive elimination was a thermodynamically favorable step (∆G14→3 = –23.5 kcal mol–1) with an energy barrier of ∆G‡14→TS3 = +11.3 kcal mol–1.Armed with mechanistic insights, we set out to explore the generality of our PEC C–N cross-coupling method. The scope of aryl bromide substrate was first investigated. As displayed in Fig. 4, the para-position exhibited excellent group tolerance under the standard condition. When the ester group was replaced by ketocarbonyl, phenyl and trifluoromethyl groups, good yields were obtained (16–18). Employing 1-bromo-4-chlorobenzene as substrate resulted in the selective production of 19, implying that the Ni-catalytic cycle had a high selectivity on activating halide groups. Thio- and cyano-containing substrates were also successfully coupled with N-methylaniline with slightly lower yields (20, 21). Even for bulky substituent such as tert-butyl or carbazole, the reaction took place with moderate yields (22, 23). Similar tolerance was observed for the meta- and multi-substituted substrates (24–31). Bromobenzene, bromonaphthalene and some more complicated bromated (hetero) aromatic compounds were further tested and fair to good yields were observed (32–38). In regard to the scope of amine substrate, aniline derivatives including para- and meta-substituted N-methylaniline, N-methyl-2-naphthylamine, cyclic amines, primary aryl amines and morpholine were tried (39–53). The catalytic performance varied greatly among different substrates, likely because the stability of amine radical was sensitive to the electronic effect and the steric hinderance.Fig. 4: Scope of photoelectrochemical Ni-catalyzed system.aReaction condition: BiVO4 photoanode (1.2 cm × 2.5 cm), Ni foam cathode (1.0 cm ×3.0 cm), Ag/AgNO3 as reference electrode, amine (0.4 mmol), aryl bromide (0.2 mmol), LiBr (0.2 M), NiBr2·glyme (0.02 mmol), dtbbpy (0.03 mmol), DABCO (2 equiv), acetone (5.0 mL), E= –0.4 V vs Ag/AgNO3, 12 h, N2. bE = 0.2 V vs Ag/AgNO3. cE = 0.0 V vs Ag/AgNO3. Corresponding yields are shown.Last but not least, we showcased the synthetic applicability of this synergistically catalytic approach with a few examples of late-stage functionalization. Impressively, the analog of phytol and L-menthol, two types of important natural product, were readily synthesized using this method (54, 55). Bromides derived from pharmaceutical chemicals (canagliflozin, bedaquiline and celecoxib precursor) also incorporated well into this protocol (56-58). Additionally, fenofibrate, indomethacin and etoricoxib, three famous drugs with aryl chloride moiety, were found to be compatible with this system, evincing that it is promising to apply the PEC mode to other halides (59-61).
