Photo-induced selective N-N bond construction via harnessing nitrene release and transfer

Domain: chemistry
Published: 2026-01-27
Editorial outcome: minor_revision

Abstract
Nitrogen incorporation is fundamental in organic synthesis for functional materials, pharmaceuticals, and agrochemicals. While C–N bond formation has gained great progress, N-N bond construction remains challenging: existing methods rely on prefunctionalized precursors, and direct coupling is hindered by narrow substrate scope and poor reactivity control. Although transition-metal-catalyzed nitrene strategies exhibit high efficacy for intermolecular N–H insertion, nitrene-mediated N–N coupling under metal-free conditions has rarely been explored. Herein, we report a broadly applicable sulfilimine-based approach for selective N–N coupling. By leveraging sulfilimines as nitrene precursors, we achieve controlled release of highly reactive nitrene intermediates, enabling intermolecular N-N coupling with amines. This strategy provides an alternative pathway for nitrene-mediated N-H insertion reaction over conventional methods, providing a streamlined route for constructing complex N–N-containing architectures.

Introduction
Nitrogen incorporation is fundamental in organic synthesis for functional materials, pharmaceuticals, and agrochemicals. While significant progress has been made in this process via C-N bond construction, forming nitrogen–nitrogen (N-N) bonds, which are prevalent motifs in diverse natural products, remains challenging (Fig. 1a)1–6. Current strategies for constructing N-N-containing scaffolds predominantly rely on the modification of N-N or N=N precursors, such as hydrazine and diazo compounds7–9. However, direct N-N coupling holds the promise of a more streamlined and convergent synthetic approach, offering enhanced retrosynthetic flexibility and the potential for the rapid assembly of complex N-N-containing architectures. The inherent high electronegativity of nitrogen pose a significant barrier to non-polar N–N bond construction4,10–13, particularly in intermolecular reactions12–14. Although several elegant N-N cross-coupling methods have been developed, which employed oxidative, reductive or radical cross-coupling pathways to form hydrazines, these pioneer methods were often restricted to the synthesis of specific classes of compounds, such as N-N linked bicarbazoles and tetra-aryl substituted hydrazines11,15–19. A promising route for intermolecular N-N coupling is electron-deficient nitrene transfer to amines. Transition-metal-catalyzed nitrene insertion, using Ag and Rh20,21, Fe/Ir/Cu22,23, and Ni catalysts24 to regulate the reactivity of nitrenes (Fig. 1b), perform well for sulfonyl/acetyl nitrenes, pave the path to the diversified N-N coupling products. Building on these advancements, we sought to explore whether nitrene-mediated N-N coupling could be successfully achieved by selecting appropriate nitrene precursors under metal-catalyst-free condition, thus a potential approach that would enable access to a broader range of hydrazine products.

Photochemistry presents an equally important and complementary approach for the generation of nitrene species and enables some unbelievable transformations25–34. In these cases, most of these photochemical reactions are associated with unsaturated bonds or intramolecular processes. Applying photo-induced nitrene generation to N-N bond construction is still fraught with challenges. Several issues need to be aware of: Firstly, free nitrenes are highly reactive and short-lived species, harsh reaction conditions for their generation often leads to undesired side reactions21,22,35,36. Secondly, the selectivity of N-H cleavage is influenced by the spin state of nitrenes, with triplet and singlet nitrenes participating in different reaction pathways. Specifically, singlet nitrenes may be involved in the direct nucleophilic attack process and N-H insertion, while triplet nitrenes undergo hydrogen atom transfer. Thirdly, controlling the concentration of nitrenes is a significant hurdle, as many previous methods involve gas liberation for nitrene generation37–39, and high nitrene concentrations exacerbate the occurrence of side reactions (Fig. 1c).

Building on previous research into photochemical nitrene-involved amination reactions, we aimed to identify a readily accessible, photoactive nitrene precursor that could achieve the aforementioned N-N coupling. Sulfilimines emerged as a particularly promising candidate: owing to their diverse reactivity profiles and ease of structural modification, these compounds have already found widespread application in amination processes36–40. Notably, diarylsulfoneimine—a well-documented member of the sulfilimine family-exhibits intrinsic photochemical activity and has been shown to undergo efficient amination reactions under light-irradiation conditions28,40–47. This inherent photochemical activity, coupled with the modular nature of sulfilimine structures, offers two key advantages: first, it facilitates the controlled generation of nitrene intermediates upon photoexcitation, and second, it allows for the precise tuning of nitrene reactivity through structural modifications of the sulfilimine scaffold. Here, we propose sulfilimines as nitrene precursor, with the potential to pave the way for efficient, metal-free, nitrene-mediated N–N coupling reactions (Fig. 1d).

Results
Condition optimizations
Our investigation commenced by preparing a series of sulfilimines 1a-1–1a-4 with the goal to implement N-N bond construction of an aniline moiety with sulfilimines (see Supplementary information Section 2 for the synthesis of these reagents). After screening of conditions, N-(5λ4-dibenzo[b,d]thiophen-5-ylidene)−4-methylbenzamide 1a-1 showed optimal reactivity in the N-N coupling reaction, for the sulfilimines derived from other diaryl sulfides 3”−2–3”−4 (entries 2-5, Table 1), lower yields were obtained. Subsequently, solvents were tested detailly, when chloroform was chosen as solvent, best outcomes in yield and selectivity were achieved and byproduct 4-methylbenzamide produced using DMSO, CH3CN and DMF as solvent (entries 6-13, Table 1). Finally, the light parameters were screened, the wavelength of light was 365 nm, 50 W turned out to be the best choice (entries 14-16, Table 1). Additionally, under air atmosphere, the target product was obtained in 31% yield (entry 17, Table 1). And further control experiment without light irradiation, the two reaction reactants were remained and no reaction occurred (entry 18, Table 1).

Scope of substrate
With the optimal reaction conditions established, we systematically evaluated the substrate scope of amine reactants in their coupling with N-(5λ⁴-dibenzo[b,d]thiophen-5-ylidene)−4-methylbenzamide (1a-1). As illustrated in Fig. 2, N-monosubstituted aniline derivatives efficiently furnished the corresponding N-N coupling products (3–10) with isolated yields ranging from 50% to 72%, demonstrating slight influence of substituent electronic properties on the phenyl ring. Notably, arylamines bearing five-, six-, or seven-membered ortho-fused aliphatic rings underwent smooth coupling, affording N-N motifs (11–16) with excellent operational compatibility. Additionally, cyclohexyl and isopropylanilines were viable substrates, delivering hydrazide molecules (17–19) in moderate yields.

Next, we assessed the reactivity of aliphatic amines under standard conditions. Remarkably, this method exhibited compatibility with aliphatic amines: various alkylamines, including diethyl-, dipropyl-, isopropyl-, cyclohexyl-, and allylamines (20–24), provided products in moderate yields with high selectivity. Both ethylbutylamine and methylbenzylamine (25–26) were successfully incorporated, and cyclic alkylamines demonstrated broad tolerance, yielding hydrazide products (27–30). Diarylamines also served as viable substrates, although slightly reduced yield was observed for product 31. The reaction with primary arylamine did not give the desired hydrazide products 32 under our optimized reaction condition, the reaction with aliphatic amine became messy and we could not detect desired hydrazide 33.

The scope of sulfilimine partners was subsequently explored. A series of N-arylbenzoyl derivatives (1) bearing electron-donating or electron-withdrawing substituents afforded corresponding products (34–43) in good yields (Fig. 3). Polyfluoro-benzoyl, 1-naphthyl, furan-2-yl, and thiophen-2-yl analogs performed comparably, delivering hydrazide products (44–48) in moderate yields. Extension to non-aromatic acyl groups revealed pivaloyl, (E)-but-2-enoyl, and acryloyl derivatives (49–51) were competent coupling partners. Meanwhile, octadecanoyl-cyclopropyl-, cyclopentyl-, and cyclohexyl-acyl compounds exhibited similar reactivity profiles, furnishing hydrazide products (52–54). Formate acyl derivatives (56–59) also engaged smoothly with high reaction efficiency. The scope of sulfonyl-based sulfilimines were further explored: methylsulfonyl-, 1-propanesulfonyl-, cyclopropylsulfonyl-sulfilimines were also candidate substrates, 44-53% yield of target products was furnished (60-62). Next, aryl-, and 8-quinoline sulfonyl derivatives underwent successful coupling to afford target hydrazides in 44-69 yield (63–70).

To demonstrate the synthetic utility of this N-N bond coupling strategy in late-stage functionalization, we applied this methodology to a diverse set of bioactive molecules (Fig. 3c). Notable applications included site-selective modification of clinically relevant compounds such as ibuprofen 71, indomethacin (COX inhibitor) 72, and probenecid (anti-gout drug) 73, as well as advanced intermediates like L(-)-10-camphorsulfonyl chloride 74 and (-)-camphanic acid 75. The protocol efficiently introduced nitrogen-based moieties into structurally complex frameworks, including hydro-1H-benzo[b]azepine (neuroactive scaffold) and a glycine derivative (76), showcasing broad compatibility with heterocyclic systems and chiral centers.

Synthetic applications
To detect the utilization potential of our strategy, a series of synthetic applications were carried out. This method is easy to operate and could be carried at 3 mmol scale with 73% isolated yields (668 mg). In addition, methylation was also smoothly achieved to form the desired product 67 in high yields. Further derivatizations of products exhibited the potential value of such photochemical transformation to synthesize various hydrazines molecules. For example, with Lawesson’s reagent, thioacyl hydrazines can be accessible in a direct way. Furthermore, the palladium-catalyzed arylation and amination reaction of 67 pave the pathway towards functionalized hydrazines (Fig. 4).

Mechanistic studies
To gain more details of this photochemical nitrene-mediated N-N coupling reaction, mechanistic studies were carried out to shed light on the process of this transformation. Firstly, TEMPO and BHT were added as additives under the standard reaction, the target product yield of this reaction decreased, which means that the reaction may involve the radical process partially (Fig. 4a). When we used deuterium substrate 2a-D (98% D) as substrate, 3-D (66% D) was obtained. To further determined the hydrogen source, the reaction with deuterated methylaniline (2a-CD3) was performed under standard reaction condition and 22% deuterium incorporation on N-D moiety of 3-CD3. These results collectively support the mechanism involving hydrogen atom abstraction from the methyl group of N-methylaniline by the generated triplet nitrene (Fig. 4b). Then, the reaction of 1a-1 with alkene containing cyclopropyl groups substrate was carried out, ring-open product was detected by High Resolution Mass Spectrometer (HR-MS) (Fig. 4c), and SPh2, PPh3 and cyclohexa-1,4-diene were selected as nitrene-trapping agent, corresponding nitrene insertion adducts were also detected by HR-MS, these results directly verify the generation of free nitrene intermediates. Additionally, electron paramagnetic resonance (EPR) experiments were carried out to capture radical species with the addition of radical scavenger 5,5-Dimethyl-1-pyrroline N-oxide (DPMO), a weak and messy radical signal was observed using sulfilimine 1a-1 under 1-h 365 nm LED irradiation (Supplementary Fig. 5), confirming the triplet nitrene may generated. Further spin-trapping experiments suggest that the triplet nitrene generated from light-irradiation of sulfilimine 1a-1, reacts with morpholine to yield the corresponding nitrogen-centered radical (g=2.0072, AN1=14.3 G, AH=17.1 G, AN2=1.8 G), these results indicated possibility of triplet nitrene-mediated hydrogen atom transfer (HAT) process (Fig. 4d).

Theoretically, the production of the nitrene intermediate requires the excitation of sulfilimine, which means that continuous light irradiation should be necessary. The light on/off experiments verified this viewpoint (Fig. 5a). Subsequently, the UV-Vis absorption spectra reveal that all tested sulfilimines display a strong absorption band below 360 nm, where absorbance intensifies with decreasing wavelength. What’s more, a prominent absorption tail is observed in the range of ca. 360-500 nm (Fig. 5b and Supplementary Fig. 2), this is the reason why this strategy is also efficient under blue light (Table 1, entry 14). The UV-Vis absorption spectra showed no significant bathochromic shift for the mixture of 1-16 and 2a compared to the individual components, and no noticeable absorbance enhancement with the mixture of 1-16 and 2a, indicating there are no intermolecular interactions involving two starting materials (Fig. 5b). The Stern-Volmer quenching study further illustrated that amine substrate 2a could effectively quench the excited sulfilimine substrate 1-16 (Fig. 5d). Cyclic voltammetry experiments were carried to gain more details, sulfilimine molecule 1a-1 showed one irreversible reduction peak (Ep = -1.48 V vs Ag/AgCl) which refers to the S-N bond cleavage (Fig. 5c). And a reversible reduction peak (Ep/2 = -2.48 V vs Ag/AgCl) was observed which refers to the redox process of dibenzo[b,d]thiophene (DBT). These CV results indicated that 1a-1 showed remarkable reactivity (Fig. 5c).

To elucidate the transient species driving this transformation, we employed time-resolved absorption (ns-TA) spectroscopy. We selected a 355 nm laser to selectively photoexcite the sulfilimine, closely mimicking the 365 nm irradiation used synthetically. Upon excitation of sulfilimine 1-16 in CHCl3, a broad transient absorption signal (360–500 nm) centered at ca. 450 nm forms immediately (Fig. 5e). This initial feature evolves rapidly: the 450 nm band decays within 1 µs, concurrent with intensity growth in the 360–420 nm region over 10 µs timescale. Drawing on literature regarding acyl nitrene precursors48, we assign these phases to sequential nitrene intermediates. The short-lived species around 450 nm is assigned to the triplet acyl nitrene. Kinetic analysis reveals its decay is a first-order process sensitive to molecular oxygen (τ=312 ns under air vs. τ=1194 ns under deoxygenated conditions), but unaffected by methanol (Fig. 5f and Supplementary Fig. 3a-3b). Conversely, the growth at 360–420 nm corresponds to the decay reactions of the singlet acyl nitrene, which is the energetic ground state, stabilized by an interaction between the carbonyl oxygen and the hypervalent nitrogen48–52. As shown in Supplementary Fig. 3a, kinetic analysis at 370 nm confirm the reaction process of the singlet acyl nitrene is insensitive to oxygen but is accelerated by methanol, consistent with the characteristic reactivity of singlet acyl nitrenes: their decay is insensitive to molecular oxygen, but their lifetime is significantly shortened by methanol due to a O–H insertion reaction48.

In the presence of amine 2a, the kinetics of the triplet nitrene at 450 nm remained unchanged (Fig. 5g). In stark contrast, increasing concentrations of amine 2a accelerated the decay of the singlet nitrene (Fig. 5h), demonstrating effectively quenching of the singlet species by amine in competition with its intrinsic decay. Similar spectral results were obtained with other sulfilimine and amine substrates (Supplementary Fig. 3 and Supplementary Fig. 4). A kinetic comparison revealed that aromatic amines are more effective quenchers of the singlet acyl nitrene than aliphatic amines (Fig. 5i), which may rationalize the higher selectivity observed for N-N coupling with arylamine substrates. The sens-TA results establish the ground-state singlet acyl nitrene as the key reactive intermediate responsible for the productive N–N bond formation. The reaction proceeds via photoexcitation of the sulfilimine, S=N bond cleavage to generate dual-state (singlet and triplet) nitrenes, and subsequent nucleophilic attack of the amine on the singlet nitrene. Besides, the extended lifetime of the triplet nitrene under anaerobic conditions is expected to permit a secondary interaction with the amine, thereby accessing an additional reaction channel. Furthermore, the continuous irradiation employed in the synthetic protocol maintains a non-zero steady-state concentration of triplet nitrenes, which consequently would serve as supplementary intermediates for the overall transformation.

To gain deeper mechanistic insights, density functional theory (DFT) calculations were performed (see Supplementary information Section 6 for more details.). As depicted in Fig. 6, upon photoexcitation at 365 nm, substrate 1CS 1a-1 is promoted to its singlet excited state (1CS 1a-1*). This singlet state undergoes intersystem crossing to generate the triplet state nitrene (3 1a-1), which undergoes S-N cleavage and transforms into the singlet closed-shell state 1CS B1', which is susceptible to nucleophilic attack by the lone-pair electrons of N-methyl aniline to form 1CS D. Notably, an intramolecular hydrogen transfer pathway via the ternary-ring transition state 1CS TS D-E was calculated to have a significantly higher energy barrier of 29.3 kcal/mol, highlighting the kinetic preference for the secondary reaction pathway: intermediate 1CS D undergoes intramolecular hydrogen transfer through two sequential transition states—1CS TS D-D1 (involving methyl/hydrogen position exchange) and 1CS TS D1-E1 (involving 1,4-proton transfer and isomerization)—to generate 1CS 3 (Fig. 6a). An alternative pathway was also explored: computational studies reveal that the selectivity of the nitrene transfer reaction is governed by the controlled release of free nitrene 3 B'. This spin densities property of the nitrene facilitates the formation of N:···H−N non-covalent interactions between 3 B' and N-methyl aniline. Subsequently, a hydrogen atom transfer (HAT) process occurs between 3 B' and N-methyl aniline, yielding intermediate 3 E' via transition state 3 TS C'-D' with an energy barrier of 11.5 kcal/mol (Fig. 6b) (see Supplementary Fig. 9 for details of non-covalent interactions (NCI) map of 3 1a-1, 3 C', 3 TS C'-D' and 3 D').

In this study, we report a sulfilimine-mediated approach for selective intermolecular N-N coupling, leveraging photochemical nitrene-involved transformations. This method leverages the inherent properties of sulfilimines to achieve controlled nitrene-mediated reactivity under photochemical activation. The protocol exhibits broad functional group compatibility, facilitating the synthesis of diverse N-N-containing compounds under mild, metal-free conditions. As such, this work provides a complementary tool to the synthetic toolkit for constructing nitrogen-rich architectures, which are relevant to materials science and drug discovery. Mechanistic experiments combined with DFT calculations confirm that the protocol proceeds via dual-state nitrene-mediated N-H bond insertion.

Methods
General procedure for the photo-induced N-N coupling reaction
To a 25 mL Schlenk tube, sulfilimine (0.2 mmol), amine (0.4 mmol) and analytical grade CHCl3 (2 mL) were added under nitrogen atmosphere, then the light (50 W, 365 nm LEDs) was turned on and the reaction mixture was irradiated and stirred at room temperature. After the reaction was completed (monitored by TLC), solvent was removed under vacuum, and the residue was purified by column chromatography on silica gel with a gradient eluent of petroleum ether and ethyl acetate to give products.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "Li, Tang, Yu and coworkers present a construction of N-N bond via photoredox nitrene transfer of a bespoke sulfilimine.\nEven though sulfilimines have been exploited as a nitrene source (Ref. 36-38), the acceptors of nitrenes are primarily\nrestricted to unsaturated systems or intramolecular reaction mode. In the manuscript, the authors develop a novel\nintermolecular nitrene transfer reaction which allows the formation of hydrazine bearing N-N bond while overcoming the\ngeneration of urea via homodimerization of nitrenes. For the scope of nitrene acceptors (Figure 2), the chemoselectivity is\ngenerally modest to poor, but much improved chemoselectivity has been observed while the nitrene donors have been\ninvestigated (Figure 3). The synthetic utility of this transformation was showcased in natural products modification and\ndownstream derivatization. A combined experimental and computational study of mechanism was conducted to shed light\non the details of the reaction mechanism. In general, even though hydrazine derivatives have been prepared via nitrene\ntransfer of amines (Nat. Chem. 2021, 13, 378 (ref. 19); ACIE, 2025, doi.org/10.1002/anie.202509056; Org. Lett. 2023,25, 36,\n6671-6676; 2025,27.7,1626-1630) the novelty and significance of this work can warrant its acceptancy by Nat. Comm., but\nthe following issues should be addressed first:\n1. In the optimization part, control experiments should be provided, such as standard conditions without light, or under the\natmosphere of air instead of N2.\n2. The phororedox protocol is very sensitive to the setup, so the authors should provide the details of their setup, ideally with\na photo.\n3. Why the chemoselectivity indicated in Figure 2 or 3 cannot be accurately determined? It is weird to see something like “>\n3.5 : 1”.\n4. For the mechanism part, Figure 4g, since the reaction was performed in deuterium solvent, where is the source of\nhydrogen? In another word, what part of 1a-1 was deteriorate? This information is particularly important to support the\nmechanistic proposal by DFT, perhaps 31a-1?\n5. From the computational study (Figure 5A), the carbonyl group on nitrogen of 1a-1 is very important, in agreement of the\nprevious report (J. Am. Chem. Soc. 2023, 145, 6310). Did the authors try DBT sulfilimine bearing a non-coordinating group\non nitrogen, for example, phenyl? Is the chemistry still proceeding smoothly?\n6. Three very related papers (ACIE, 2025, doi.org/10.1002/anie.202509056; Org. Lett. 2023,25, 36, 6671-6676;\n2025,27.7,1626-1630) should be cited in the manuscript.", "reviewer_2": "The paper reports a photo-selective N–N bond formation protocol employing sulfilimines as nitrene precursors, providing\naccess to a range of hydrazide derivatives. This approach demonstrates commendable control over reaction selectivity\nthrough structural modification of the sulfilimine scaffold. The method shows broad functional-group tolerance. However,\nwhile the authors present their approach as highly novel, they appear to overstate the significance of their contribution,\nparticularly in comparison to existing N–N bond-forming methodologies (see references 17–20). These prior works already\nprovide powerful and versatile solutions for N–N bond construction, and this paper should more carefully contextualize the\ncurrent method within this established landscape. Furthermore, although the authors emphasize the use of structurally\nmodified sulfilimines, it should be noted that these species have already been employed in related C–N bond-forming\nreactions (e.g., Chem. Eur. J. 2020, 26, 8235; Nat. Chem. 2022, 14, 898–904). The authors are encouraged to acknowledge\nthis prior work more explicitly. Overall, the framing of the work does not convincingly demonstrate the level of originality or\nurgency. The discussion of N–N bond formation is limited to energy configuration data, which is unsatisfying. Additionally,\nthe selectivity with respect to urea byproducts appears rather poor. In its current form, the manuscript falls short of the\nstandards for Nature Communications.\nQuestions and concerns.\n-in Figure 2, it is unclear whether primary (aryl) amines participate in the reaction. If reactivity is restricted to secondary\namines, the mechanistic basis should be discussed.\n-In Page 8, evidence for intermolecular hydrogen bonding should be provided. In DFT studies, this could be supported by\nbond distances from optimized structures or NCI plots. Without such evidence, it is questionable for hydrogen bonding.\n-In Figure 4j: The Stern–Volmer plot appears cropped. The slope and linearity should be clearly displayed. Data related to\nStern–Volmer quenching studies and CV measurements are missing in SI and should be included.\n-In Figure 1b, the description of the N–N bond as weak and nonpolar is unclear with respect to hydrazides. To substantiate\nthis statement, bond dissociation energies of hydrazide N–N bonds should be provided.\n-In Figure 3, it would be informative to test sulfilimines with unencumbered, longer aliphatic chains to determine whether the\nreaction proceeds in the absence of steric protection.\n-Organic azides are known to undergo photodecomposition to triplet nitrenes (J. Am. Chem. Soc. 1965, 87, 1947; 87, 5491).\nThe authors should examine whether their protocol also operates with azides or other precursors. If so, the limitation posed\nby equivalent recovery of dibenzothiophene as waste should be acknowledged.\n-Sulfilimine 1a-1 exhibits a high triplet energy (61.6 kcal/mol, Fig. 5) yet delivers 32% yield under blue LED irradiation\nwithout catalyst (Table 1, entry 14). However, no absorbance is observed near this wavelength (Fig. 4i), and the UV–vis\nbaseline appears incorrectly measured. A clear rationale should be provided. UV–vis data for both 1a-16 and 1a-1 are\nnecessary.\n-The proposed HAT pathway via triplet nitrene should be further validated. In particular, sulfilimines containing cyclopropane\nsubstituents should be tested for ring-opened olefin products. Additionally, experiments with added triplet sensitizers under\nblue LEDs could help correlate yields with sensitizer triplet energies.\n-In Figure 5a, the nucleophilic attack step is incorrectly placed; the amine should add only after the nitrene state 1csB1.\n-In Figure 5a, for the 1CSE1 intermediate, evidence of its detection by crude NMR or LC–MS would strengthen the\nmechanistic proposal.\n-In ON/OFF light experiment, product yield continues to increase (~5%) in the dark phase (4–8 h). A plausible explanation or\nadditional controls are needed.\n- Many spectra are of poor quality. Impurities appear to have been obscured by decreasing peak intensities, which\ncompromises reproducibility. High-quality spectra from purified samples should be provided. Numerous typographical errors\nand solvent misannotations (e.g., Fig. S96) are present. The SI should be carefully proofread and corrected.", "reviewer_3": "This manuscript by Tang and Li et al. discloses an N–N bond formation via photoinduced generation of nitrenes from\nsulfilimine precursors. The acylnitrenes were produced under 365 nm LED irradiation from sulfilimines bearing a\ndibenzo[b,d]thiophene (DBT) moiety, which showed moderate to good selectivity for N–N formation with aromatic and\naliphatic amine coupling partners. The mechanism of this reaction was probed using experimental and computational\nmethods and shown to proceed at least partially through radical intermediates. I will focus my comments primarily on the\ncomputational investigations.\n- In Figure 5, the singlet (Fig 5a) and triplet (Fig 5b) pathways appear to be calculated at two completely different levels of\ntheory. This is very confusing and contradicts the computational methods section in the Supporting Information. The authors\nshould clarify what level of theory was actually used.\n- In addition, Figure 5’s caption also implies that the singlet pathway (Fig 5a) showes the free energies while the triplet\npathway (Fig 5b) shows the electronic energies. This again contradicts the figure itself, which shows G (Gibbs free energy)\non both Fig 5a and Fig 5b. What energies are these two diagrams actually showing? This is very important to clarify before\nany conclusions about the mechanism can be drawn.\n- Furthermore, if the mechanism in Fig 5a is indeed calculated at the B3LYP/def2-SVP level of theory (as stated in the\ncaption), that would imply that these energies are not calculated with a triple-zeta quality basis set or with the incorporation\nof dispersion effects. DFT energies should generally be calculated with triple-zeta basis sets and with at least empirical\ndispersion incorporated.\n- While the computational methods section in the Supporting Information states that empirical dispersion was included, it is\nnot clear how dispersion was included, as neither B3LYP nor BP86 includes dispersion. Please clarify how dispersion was\nactually included in the calculations.\n- In the SI, imaginary frequencies should be provided for transition states.", "reviewer_4": "Selective N-N bond construction remains a significant challenge in organic synthesis. Li, Tang, Yu, and their coworkers\nhave reported a robust and efficient method for synthesizing substituted hydrazines via a photochemical nitrene strategy.\nSpecifically, they employed a sulfilimine-based photoinduced approach to achieve controlled nitrene release and\nintermolecular N-N coupling under metal-free conditions. This method enables precise tuning of nitrene reactivity through\nstructural modification of sulfilimines, which effectively suppresses the side reactions associated with free nitrenes.\nThis transformation demonstrates broad functional group compatibility that overcomes the substrate limitations of conventional\nmetal-catalyzed and photochemical methods. Additionally, it addresses critical gaps in nitrene chemistry by integrating\nphotoactivation and controlled nitrene transfer, thereby expanding the synthetic toolkit for constructing nitrogen-rich\nmolecular scaffolds.\nBased on its scientific merit, I recommend this work for publication in Nature Communications pending the resolution of the\nfollowing minor revisions:\nManuscript corrections:\nwhether chlorine-containing additives contribute to improved yield and selectivity of the reaction.\nany side products were observed (e.g., products derived from nitrene insertion into the sulfur atom of DMSO) and\ndiscuss their formation.\nfor a broader range of amines (e.g., primary amines and diarylamines) to provide a more comprehensive assessment of\nsubstrate applicability.\nIt is recommended that the authors investigate and include additional types of sulfonyl nitrene precursors to validate the\ngenerality of the method.\nas reactants and tested with the sulfilimine nitrene precursor under standard reaction conditions to probe potential\nnitrene trapping pathways.\nSupporting Information Corrections:\nsupplemented with the manufacturer’s name and product model for reproducibility.\nassigned. These issues should be corrected.\npeaks are missing and should be added to ensure data completeness."}, "author_response": "Response to the comments from Reviewer #1.\nComment: Li, Tang, Yu and coworkers present a construction of N-N bond via\nphotoredox nitrene transfer of a bespoke sulfilimine. Even though sulfilimines have\nbeen exploited as a nitrene source (Ref. 36-38), the acceptors of nitrenes are primarily\nrestricted to unsaturated systems or intramolecular reaction mode. In the manuscript,\nthe authors develop a novel intermolecular nitrene transfer reaction which allows the\nformation of hydrazine bearing N-N bond while overcoming the generation of urea via\nhomodimerization of nitrenes. For the scope of nitrene acceptors (Figure 2), the\nchemoselectivity is generally modest to poor, but much improved chemoselectivity has\nbeen observed while the nitrene donors have been investigated (Figure 3). The\nsynthetic utility of this transformation was showcased in natural products\nmodification and downstream derivatization. A combined experimental and\ncomputational study of mechanism was conducted to shed light on the details of the\nreaction mechanism. In general, even though hydrazine derivatives have been\nprepared via nitrene transfer of amines (Nat. Chem. 2021, 13, 378 (ref. 19); ACIE, 2025,\ndoi.org/10.1002/anie.202509056; Org. Lett. 2023,25, 36, 6671-6676; 2025,27.7,1626-\n1630) the novelty and significance of this work can warrant its acceptancy by Nat.\nComm., but the following issues should be addressed first.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nyour constructive feedback. We deeply appreciate your recognition of the novelty of our\nmethodology and the robustness of the mechanistic studies. We also note the issues\nraised and will promptly address them in revisions. Specifically, we have provided\nsupplement additional control experiments/data as needed and response your\ncomment point-to-point listed below. We thank you again for your support in\nconsidering our work.\nComment: In the optimization part, control experiments should be provided, such as\nstandard conditions without light, or under the atmosphere of air instead of N .\nyour constructive feedback. We have tested standard conditions without light, no\ntarget product was obtained, target product was obtained in 31% yield (sel.=1.6 : 1)\nunder the atmosphere of air instead of N . These data were added to the optimization\n2\npart (Table 1, entry 17 and 18) of manuscript.\nComment: The photo-redox protocol is very sensitive to the setup, so the authors\nshould provide the details of their setup, ideally with a photo.\nResponse: Thank you for your valuable comment. We fully agree that the photoredox\nprotocol is sensitive to experimental setup, and we have supplemented the detailed\nsetup information as requested. We have taken clear photos of the complete\nexperimental setup, including the light source, reaction vessel, and temperature\ncontrol system. These photos were added as Supplementary Figure S1 in the revised\nSupporting Information. “The photochemical reactor consisted of a commercially\navailable LED light, the LED light utilized in this paper were purchased via the\nfollowing link: https://e.tb.cn/h.SwkpWCCj49D8q05?tk=ipUIfOw7qbs (Brand: New\nStar Source, 50 W, 365 nm)”\nComment: Why the chemoselectivity indicated in Figure 2 or 3 cannot be accurately\ndetermined? It is weird to see something like “> 3.5 : 1”.\nResponse: Thank you for your insightful comment regarding the presentation of\nchemoselectivity data. We apologize for the ambiguity caused by the expression \"> 3.5 :\n1\". This notation stemmed from our initial attempt to unify data presentation, but we\nfully acknowledge its lack of precision. In the revised manuscript, all chemoselectivity\nvalues in Figures 2 and 3 have been updated to accurately quantified ratios, reported\nto one decimal place (e.g., \"3.52 : 1\" is presented as \"3.5 : 1\"). These revisions ensure\nthe data is clear, rigorous, and readily interpretable, and we greatly appreciate your\nreminder to refine the data presentation.\nComment: For the mechanism part, Figure 4g, since the reaction was performed in\ndeuterium solvent, where is the source of hydrogen? In another word, what part of 1a-\n1 was deuterated? This information is particularly important to support the\nmechanistic proposal by DFT, perhaps 31a-1?\nResponse:Thank you for your critical question regarding the hydrogen source whether\nsubstrate 1a-1 was deuterated in Figure 4g. We believe that the hydrogen originates\nfrom the methyl group of substrate amine 1b. To verify this, we conducted control\nexperiments using N-methylaniline-d3 (2-D ) as the substrate, and the corresponding\n3\nproduct 3-D showed 22% deuteration ratio at the N-D position, thus we speculate\n3\nexcess of amine substrate(2a) was deuterated reasonably in eq1. These results\ncollectively support the mechanism involving hydrogen atom abstraction from the\nmethyl group of N-methylaniline by the generated nitrene. We supplement these\nexperimental details and corresponding data to the revised manuscript (figure 4g) and\ncorresponding part of Supporting Information.\nComment: From the computational study (Figure 5A), the carbonyl group on nitrogen\nof 1a-1 is very important, in agreement of the previous report (J. Am. Chem. Soc. 2023,\n145, 6310). Did the authors try DBT sulfilimine bearing a non-coordinating group\non nitrogen, for example, phenyl? Is the chemistry still proceeding smoothly?\nResponse:Thank you for your insightful question regarding the role of the carbonyl\ngroup and the potential of DBT sulfilimines with non-coordinating nitrogen\nsubstituents.\nConsistent with the previous report (J. Am. Chem. Soc. 2023, 145, 6310), the\ncarbonyl group on the nitrogen of 1a-1 is indeed crucial for stabilizing the nitrene\nintermediate and guiding selective N-N coupling through a significant bonding\ninteraction between a carbonyl oxygen lone pair and an empty orbital on the nitrene\nnitrogen. (Ref :J. Org. Chem. 2016, 81, 6320−632, J. Org. Chem. 2007, 72, 6848-6859.).\nWe have conducted control experiments using a DBT sulfilimine with a phenyl group\n(non-coordinating substituent) on nitrogen. Unfortunately, the reaction did not work.\nWe also conducted experiments using a DBT sulfilimine bearing a pyridine group (a\ncoordinating substituent) on the nitrogen atom, but this substrate was similarly\nineffective for the reaction under our established conditions. This result further\nconfirms the key role of the carbonyl group in modulating nitrene reactivity and\nensuring reaction efficiency.\nComment: Three very related papers (ACIE, 2025, doi.org/10.1002/anie.202509056;\nOrg. Lett. 2023,25, 36, 6671-6676; 2025,27.7,1626-1630) should be cited in the\nmanuscript.\nResponse: Thank you for your advice. We assessed the relevance of these papers to this\nmanuscript, and we added these papers to citation (ref 8, 14, 23).\nResponse to the comments from Reviewer #2.\nComment: The paper reports a photo-selective N–N bond formation protocol employing\nsulfilimines as nitrene precursors, providing access to a range of hydrazide derivatives.\nThis approach demonstrates commendable control over reaction selectivity through\nstructural modification of the sulfilimine scaffold. The method shows broad functional-\ngroup tolerance. However, while the authors present their approach as highly novel,\nthey appear to overstate the significance of their contribution, particularly in\ncomparison to existing N–N bond-forming methodologies (see references 17–20). These\nprior works already provide powerful and versatile solutions for N – N bond\nconstruction, and this paper should more carefully contextualize the current method\nwithin this established landscape.\nResponse: We would like to express our sincere gratitude for your meticulous review\nand valuable comments on our research. We highly appreciate your insightful point\nregarding the elaboration of the innovation of our work and its connection with existing\nN-N bond formation methodologies (as cited in Refs. 17-20). Your comments have\nprovided crucial guidance for us to more accurately position the value of our research\nand refine the presentation of our manuscript.\nFirst and foremost, we agree with your core opinion-the pioneering works such as those\nreported in Refs. 17-20 have developed highly influential strategies for N-N bond\nconstruction, laying a solid foundation for the advancement of this field. In the\nsubsequent revision, we have further strengthened the recognition and elaboration of\nthe contributions of these classic methodologies, avoiding overstatement of the\nsignificance of our work.\nMeanwhile, we hope to further clarify the limitations of existing methods that our\nresearch aims to address, as well as the unique value derived therefrom, by combining\nthe research background and core design. This will help to more clearly contextualize\nour work within the existing research landscape: Although significant progress has\nbeen made in existing N-N bond formation methods, there are still bottlenecks that\nurgently need to be broken through. As mentioned in the introduction, the transition-\nmetal-catalyzed nitrene transfer strategies reported in Refs. 17-20 (employing\ncatalysts such as Ag, Rh, Fe/Ir, and Ni) exhibit excellent performance in reactions\ninvolving sulfonyl/acetyl nitrenes. However, they generally face the issue of\ninsufficient amine compatibility, particularly limited applicability to aliphatic amines\ndue to strong coordination ability and weak nucleophilicity of aliphatic amines, which\ngreatly restricts their scope of application in the synthesis of complex molecules,\nalthough the inferior selectivity and yield of aliphatic amines were obtained on this\npaper. Meanwhile, the types of nitrene precursors are often limited (sulfonyl or acetyl\nnitrenes), and the protocol we proposed showcase high compatibility on different kinds\nof substitution. Additionally, the generation of nitrene species without metal-catalyst\nis often accompanied by gas evolution, making it difficult to precisely control the\nconcentration of nitrenes tend to induce side reactions and poor selectivity.\nEntry Reaction condition Nitrene precursor Amine\nRef. 20 [Tp*, BrAg] Ts- Tertiary alkyl J. Am. Chem. Soc. 139,\nChen and Chang et. FeCl4HO Dioxazolones Amines (aryl 385,(2021).\n2 2\nal. amine)\nRef 23 Cu(L)Cl (OH) Alkyl acyl- Secondary Angew. Chem. Int. Ed. 2025,\n2 2\nPaul and Mondal Dioxazolones Amines (aryl 64, e202509056\net. al. amine)\nRef. 24 Ni(Cp)(NHCi-Pr)(Cl), Acyl- Primary arylamine; J. Am. Chem. Soc.\nStoltz and Reisman Reduction agent Hydroxamate Secondary 145,15071 (2023).\net. al. alkyamines\nOur Work 365 nm LEDs Acyl- (Alkyl and Secondary\naryl); Sulfonyl- Amines (aryl amine\nSulfilimine and alkyl amine)\nThe photoinduced N-N bond formation strategy proposed in this study, which uses\nsulfilimines as nitrene precursors, is not intended to negate or replace existing\nmethods. Instead, it aims to achieve targeted breakthroughs in addressing the\nlimitations, thereby forming a complementary solution to metal-catalyzed systems.\nComment: Furthermore, although the authors emphasize the use of structurally\nmodified sulfilimines, it should be noted that these species have already been employed\nin related C–N bond-forming reactions (e.g., Chem. Eur. J. 2020, 26, 8235; Nat. Chem.\n2022, 14, 898–904). The authors are encouraged to acknowledge this prior work more\nexplicitly. Overall, the framing of the work does not convincingly demonstrate the level\nof originality or urgency. Additionally, the selectivity with respect to urea byproducts\nappears rather poor. In its current form, the manuscript falls short of the standards\nfor Nature Communications.\nResponse: Thank you for your insightful comment regarding the contextualization of\nour work with prior studies. We fully acknowledge that structurally modified\nsulfilimines have been utilized in C–N bond-forming reactions, as highlighted in key\nreferences (Chem. Eur. J. 2020, 26, 8235; Nat. Chem. 2022, 14, 898–904). We sincerely\napologize for not explicitly recognizing these pioneering contributions in the original\nmanuscript.\nIn the revised version, we have cited and discussed these works to clarify the distinct\nfocus of our study: while previous reports leveraged sulfilimines for C–N bond\nconstruction, our work represents the application of such precursors for intermolecular\nN–N bond formation via photoinduced nitrene transfer. This strategic shift pave the\npathway to selective N–N coupling under metal-catalyst free condition (vs. C–N bond\nformation) and overcomes limitations of existing free nitrene-mediated N–N bond\nmethodologies (e.g., poor aliphatic amine compatibility, uncontrollable nitrene\nreactivity).\nWe have refined the manuscript’s framing to emphasize this unique direction,\nhighlighting how our design of sulfilimines as photoactive nitrene precursors enables\na complementary reactivity profile. And, we revised the wording describing the\ninnovation of our work, avoiding absolute expressions, and emphasizing core\ncharacteristics such as \"complementarity\" and \"targeted breakthroughs\" to ensure\nthat the elaboration of the research significance is objective and accurate.\nComment: The discussion of N–N bond formation is limited to energy configuration\ndata, which is unsatisfying.\nResponse: Thank you for your constructive comment regarding the mechanistic\ndiscussion of N–N bond formation. We fully agree that the original focus solely on\nenergy configuration data is insufficient and greatly appreciate your reminder to\nstrengthen this section.\nIn the revised manuscript, we have significantly strengthened the mechanistic study\nby integrating multi-dimensional experimental evidence. First, nitrene-probe\nexperiments were conducted to verify the generation of nitrene intermediates during\nthe reaction, and electron paramagnetic resonance (EPR) spectroscopy was employed\nto confirm the formation of nitrogen-centered radicals, which indirectly supports the\ngeneration of triplet nitrenes via hydrogen atom transfer (HAT). NCI maps of\nrepresentative systems on triplet mechanism were also added to verify the hydrogen-\nbonding. More importantly, given the short-lived nature of singlet nitrenes, we\nsupplemented nanosecond transient absorption (ns-TA) spectroscopy data to validate\nthe ground-state singlet acylnitrene as the pivotal reactive intermediate responsible\nfor productive N–N bond formation.\nAs shown in the revised manuscript, we supplemented nanosecond transient\nabsorption (ns-TA) spectroscopy data (Fig. 5e-5f, Fig. S3, and Fig. S4) below:\nFig. 5| Mechanistic studies. (a) Light/dark on-off experiment; (b) UV-vis absorption\nspectra of 1-16, 2a, and 1-16 + 2a in CHCl ; (c) Cyclic voltammetry experiment; (d)\nVolmer plot for 1-16 + 2a (e) Transient absorption spectra of 1-16 in CHCl after 355\n3\nnm laser excitation; (f) Decay traces at 450 nm for triplet acylnitrene of 1-16 and 370\nnm for singlet acylnitrene of 1-16; (g) Decay traces at 450 nm for triplet acylnitrene of\n1-16, and triplet acylnitrene of 1-16 + 200 mM 2a; (h) Decay traces at 370 nm for singlet\nacylnitrene of 1-16 at different concentrations of 2a; (i) Stern-Volmer plots for singlet\nacylnitrene of 1-16 + 2a (orange) and singlet acylnitrene of 1-16 + 21a (purple).\nFig. S3 (a) Decay traces at 450 nm for triplet acylnitrene of 1-16 under air-saturated\nand N -saturated conditions; (b) Decay traces at 450 nm for triplet acylnitrene of 1-16,\n2\nand triplet acylnitrene of 1-16 + 500 mM MeOH; (c) Decay traces at 450 nm for triplet\nacylnitrene of 1-16, and triplet acylnitrene of 1-16 + 200 mM 21a; (d) Decay traces at\n370 nm for singlet acylnitrene of 1-16 under air-saturated and N -saturated conditions;\n2\n(e) Decay traces at 370 nm for singlet acylnitrene of 1-16, and singlet acylnitrene of 1-\n16 at different concentrations of MeOH; (f) Decay traces at 450 nm for singlet\nacylnitrene of 1-16 at different concentrations of 21a. Solvent: CHCl , except oxygen-\n3\nsensitivity kinetics in CH CN to avoid volatility issues during purging.\ntraces at 540 nm for triplet acylnitrene of 1-18 and 370 nm for singlet acylnitrene of 1-\n18; (c) Decay traces at 540 nm for triplet acylnitrene of 1-18, and triplet acylnitrene of\n1-18 + 200 mM 2a; (d) Decay traces at 540 nm for triplet acylnitrene of 1-18, and triplet\nacylnitrene of 1-18 + 200 mM 21a; (e) Decay traces at 370 nm for singlet acylnitrene of\n1-18 at different concentrations of 2a; (f) Decay traces at 370 nm for singlet acylnitrene\nof 1-18 at different concentrations of 21a. Solvent: CHCl\nreaction. If reactivity is restricted to secondary amines, the mechanistic basis should\nbe discussed.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nconstructive feedback. We appreciate your attention to the substrate scope regarding\nprimary (aryl) amines. To clarify, we have tested a series of primary aryl amines under\nthe standard reaction conditions, and they indeed show negligible reactivity (trace\namount) compared to secondary amines.\nThe restricted reactivity of primary aryl amines stems from two key mechanistic\nfactors: 1) Primary amines possess two N–H bonds, which the unstable property of\ncorresponding radical intermediate under standard condition leading to messy\nmixture and no product generated; 2) The lone pair of electrons on the nitrogen atom\nof primary amines is more nucleophilic, which promotes undesired side-product of\nnitrene intermediates (forming ureas) rather than the targeted N–N coupling.\nComment: In Page 8, evidence for intermolecular hydrogen bonding should be provided.\nIn DFT studies, this could be supported by bond distances from optimized structures\nor NCI plots. Without such evidence, it is questionable for hydrogen bonding.\nResponse: We thank the reviewer for this insightful comment. To firmly substantiate\nthe intermolecular hydrogen bonding, we have conducted the following analyses:\nFirstly, we quantified the interaction by measuring the critical H...Acceptor distance\nin the optimized structures. The obtained values (e.g., ~2.5/~1.9 Å for O...H/N...H) are\nmarkedly less than the sum of the relevant van der Waals radii (e.g., ~2.6-2.7 Å for\nO...H/N...H), fulfilling the primary geometric criterion for a hydrogen bond. These key\ndistances have been annotated onto the structures in Figure 5 in the revised\nmanuscript. Secondly, as recommended, we have performed an NCI analysis, the\nresults of which (provided in Figure S9 of the Supporting Information) clearly visualize\nthe attractive interaction. We believe this combined evidence from both geometric and\nelectronic structure analyses firmly substantiates our claim.\nFigure S9. NCI maps of representative systems (31a-1, 3C', 3TS\nC'-D'\n, 3D') highlighting\nnoncovalent interactions. The color indicates the sign(λ )ρ values, with blue\n2\nrepresenting prominent attractive interactions, red indicating prominent repulsive\ninteractions in the regions with steric effect, and green exhibiting very weak\ninteractions.\nComment: In Figure 4j: The Stern–Volmer plot appears cropped. The slope and\nlinearity should be clearly displayed. Data related to Stern–Volmer quenching studies\nand CV measurements are missing in SI and should be included.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nyour constructive feedback. We acknowledge the deficiencies in the presentation of the\nStern–Volmer plot and the missing experimental data in the Supporting Information\n(SI), and we apologize for these oversights.We have re-tested and re-plotted the Stern–\nVolmer data with a complete, uncropped axis range to clearly illustrate the linear\ncorrelation of the dataset. The revised figure now explicitly labels the linear fitting\nequation, the correlation coefficient (R² = 0.997), and the quenching constant (K\nsv\n=\n2.28 M-1) derived from the slope, ensuring full transparency of the plot’s linearity and\nquantitative parameters.The revised figure was added to the Figure 5d. of manuscript.\nWe have compiled all raw experimental data related to the Stern–Volmer quenching\nstudies in “Steady-state Spectral Measurement” section and cyclic voltammetry (CV)\nmeasurements into “Procedure for the CV experiment” section of the revised SI.\nIn the manuscript, the original Figure 4j was replaced by Figure 5d.\nIn the Supporting Information, we have added the corresponding section:\n“Steady-state Spectral Measurement. The UV-vis absorption spectra were measured using a UV-\nvis spectrometer (U-3010, Hitachi). Each measurement was collected from 300 to 700 at a scan\nspeed of 600 nm/min. The spectrum of a blank sample containing the pure solvent was used as the\nbackground, which was subtracted from the averaged spectra. Emission spectra were measured on\na fluorescence spectrometer (F4600, Hitachi). Quartz cuvettes of 1 × 1 cm were used for all\nabsorption and emission spectral measurements. Emission quenching experiments were conducted\nto investigate the interaction between the excited state of 1a-16 and the amine 2a. The emission\nspectra of 1a-16 (20 mM in CHCl ) were recorded upon excitation at 365 nm, monitoring the\n3\nemission range from 380 to 700 nm with a maximum peak at ca. 470 nm. Upon the incremental\naddition of 2a, a significant decrease in the luminescence intensity was observed. The quenching\nefficiency was analyzed using the Stern–Volmer equation:\nI /I = 1 + K [Q]\nwhere I and I are the luminescence intensities in the absence and presence of the quencher 2a,\n0\nrespectively, [Q] is the concentration of 2a, and K is the Stern–Volmer quenching constant. The\nSV\nplot of I /I versus [2a] exhibited a good linear relationship (R2 = 0.997), yielding a Stern–Volmer\n0\nconstant (K ) of 2.28 M-1. This result indicates an effective quenching process between the excited\nSV\nphotocatalyst and the substrate.”\n“Procedure for the CV experiment: Cyclic voltammograms were measured using a CHI 605E\npotentiostat equipped with electrochemical analysis software, using a conventional three electrode\ncell. The working electrode was a steady glassy carbon disk electrode. The auxiliary and reference\nelectrodes consisted of an Ag wire and Ag/AgCl (saturated aqueous KCl solution), respectively.\nThe concentration of 1a-1 is 0.1 mol L-1, the supporting electrolyte (tBu NBF ) was 0.3 mol L-1 in\n4 4\nCH CN (10 mL). The scan rate is 100 mV s-1.”\nunclear with respect to hydrazides. To substantiate this statement, bond dissociation\nenergies of hydrazide N–N bonds should be provided.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nconstructive feedback. To clarify and substantiate the description of hydrazide N–N\nbonds in Figure 1b, we have supplemented relevant bond dissociation energy (BDE)\ndata. As reported in cited references (e.g., J. Am. Chem. Soc. 2021, 143, 14464-14469.,\nAngew. Chem., Int. Ed. 2016, 55, 7534., J. Am. Chem. Soc. 2020, 142, 4390.), the BDE\nof hydrazide N–N bonds is approximately 56 kcal/mol. This value notably falls within\nthe range of weak covalent bonds. Additionally, the similar electronegativity of the two\nnitrogen atoms in hydrazides results in minimal charge separation, rendering the N–\nN bond predominantly nonpolar. We have updated this clarification in the caption of\nFigure 1b and the main text to enhance the rigor of our statement.\nComment: In Figure 3, it would be informative to test sulfilimines with unencumbered,\nlonger aliphatic chains to determine whether the reaction proceeds in the absence of\nsteric protection.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nconstructive feedback. To address your insightful suggestion, we have tested\nsulfilimines substituted with unencumbered, longer aliphatic chains (e.g., 18-alkyl\nsubstituent) under standard reaction conditions. Gratifyingly, the reaction proceeded\nsmoothly to afford the desired product in 69% yield. And CF -These results clearly\n3\ndemonstrate that steric protection is not a prerequisite for the reaction, validating the\nrobustness of our protocol with substrates bearing linear, less hindered aliphatic\nsubstituents. We have supplemented this data to Figure 3.\nComment: Organic azides are known to undergo photodecomposition to triplet nitrenes\n(J. Am. Chem. Soc. 1965, 87, 1947; 87, 5491). The authors should examine whether\ntheir protocol also operates with azides or other precursors. If so, the limitation posed\nby equivalent recovery of dibenzothiophene as waste should be acknowledged.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nyour constructive feedback. Organic azides are known to release N and then to\n2\ngenerate triplet nitrenes, when the organic azides reacted with the N-methyl aniline\nunder standard conditions, the side urea product 3’ were obtained in 53% yield, and\nN-N coupling product was obtained in 3% yield. Other nitrene precursors, such as 4-\nmethylbenzenesulfonyl azide, p-toluenesulfonyl iminoiodinane, were selected as\nnitrene precursor, however, no target product was obtained. And O-Benzoylated\nhydroxamate and dioxazolones were also fail substrates in this protocol, no N-N\ncoupling product was obtained.\nComment: Sulfilimine 1a-1 exhibits a high triplet energy (61.6 kcal/mol, Fig. 5) yet\ndelivers 32% yield under blue LED irradiation without catalyst (Table 1, entry 14).\nHowever, no absorbance is observed near this wavelength (Fig. 4i), and the UV–vis\nbaseline appears incorrectly measured. A clear rationale should be provided. UV–vis\ndata for both 1a-16 and 1a-1 are necessary.\nResponse:We sincerely thank the reviewer for identifying the critical issue regarding the UV–vis\ndata and the mechanistic rationale for the reactivity of sulfilimine 1a-1 under blue LED irradiation.\nWe apologize for the inaccurate baseline measurement and improper concentration of sulfilimine\nused in the original UV–vis experiment (Fig. 4i), which resulted in the absence of distinct\nabsorbance signals in the relevant wavelength range. To address this concern comprehensively, we\nhave reacquired the UV–vis absorption spectra of representative sulfilimines (including 1a-1 and\n1a-16) under optimized experimental conditions (see the revised figure provided below).\nKey enhancements in these new measurements are as follows: (1) rigorous baseline correction to\neliminate background interference; (2) adjustment of the sulfilimine concentration to 15 mM, far\ncloser to the actual reaction concentration (100 mM) than the overly low 0.28 mM employed in the\noriginal study. The revised UV–vis spectra reveal two key characteristics: (1) All tested sulfilimines\ndisplay a strong absorption band below 360 nm, where absorbance intensifies with decreasing\nwavelength; (2) A prominent absorption tail is observed in the range of ca. 360 - 500 nm (with some\n1a species extending this tail up to ca. 600 nm). These results establish a clear mechanistic rationale\nfor the reactivity of 1a-1 under 450 nm blue LED irradiation: while 1a-1 possesses a high excited-\nstate energy (61.6 kcal/mol), corresponding to a wavelength of ca. 464 nm, the absorption tail\nextending up to 500 nm facilitates efficient photon absorption at 450 nm. From a photon energy\nstandpoint, the 450 nm photons emitted by the blue LED possess adequate energy to match the\nexcited-state energy of 1a-1 (corresponding to ca. 464 nm), which further validates the feasibility\nof this excitation pathway. This low-energy absorption tail is precisely what enables 1a-1 to attain\na 32% yield under blue LED irradiation in the absence of a catalyst.\nThe revised UV–vis data, including spectra for 1a-1 and 1a-16, have been incorporated into the\nmain text and Supporting Information. Additionally, the key discussion points outlined above have\nbeen added as annotations beneath the corresponding figure to ensure clarity. We believe these\ncorrections and supplementary data fully address the reviewer’s concern and significantly\nstrengthen the reliability of our mechanistic reasoning.\nIn the main text, the original Fig. 4i is replaced with the following one as revised Fig.\n5b:\nFig. 5b UV-vis absorption spectra of 1-16, 2a, and 1-16 + 2a in CHCl\ncorresponding discussion:\nFig. S2 UV-vis absorption spectra in CHCl for (a) 1-16, 21a, and 1-16+21a; (b) 1a-1, 2a, and 1a-\n3\n1+2a; (c) 1a-1, 21a, and 1a-1+21a; (d) 1-8, 2a, and 1-8+2a; (e) 1-8, 21a, and 1-8+21a; (f) 1-\n17, 2a, and 1-17+2a; (g) 1-17, 21a, and 1-17+21a; (h) 1-18, 2a, and 1-18+2a; (i) 1-18, 21a, and\n1-18+21a.\nAs shown in Fig. 5b and Fig. S2, all tested sulfilimines display strong absorption below 360 nm,\nwhere absorbance intensifies with decreasing wavelength. Besides, an absorption tail is observed in\nthe range of ca. 360 - 500 nm (with some extending this tail up to ca. 600 nm). These results establish\na clear mechanistic rationale for the reactivity of 1a-1 under 450 nm blue LED irradiation: while\n1a-1 possesses a high excited-state energy (61.6 kcal/mol), corresponding to a wavelength of ca.\n464 nm, the absorption tail extending up to 500 nm facilitates efficient photon absorption at 450 nm.\nFrom a photon-energy standpoint, 450 nm photons emitted by blue LED possess adequate energy\nto match the excited-state energy of 1a-1 (corresponding to ca. 464 nm), which further validates the\nfeasibility of this excitation pathway. This low-energy absorption tail is precisely what enables 1a-\n1 to attain a 32% yield under blue LED irradiation in the absence of a catalyst. In contrast, the amine\npartner, displays negligible absorbance beyond 350 nm, thus ensuring that the observed transient\ndynamics originate exclusively from the photoactivated sulfilimine precursor.\nComment: The proposed HAT pathway via triplet nitrene should be further validated.\nIn particular, sulfilimines containing cyclopropane substituents should be tested for\nring-opened olefin products. Additionally, experiments with added triplet sensitizers\nunder blue LEDs could help correlate yields with sensitizer triplet energies.\nResponse: We would like to thank the reviewer for these constructive comments. We\nfully agree that additional experimental validation is essential to support the proposed\nHAT pathway via triplet nitrenes, and we have implemented your suggested\nexperiments:\nWe have tested two sulfilimine bearing cyclopropane substituent and subjected it to\nstandard reaction conditions, no ring-open product detected. Then, we use alkenyl\ncyclopropane derivative as triplet nitrene trapping agent, we successfully detected the\ncorresponding ring-opened olefin product via HRMS.\nAdditionally, Electron Paramagnetic Resonance Spectroscopy were carried out to\ncapture species with a single electro, and EPR studies confirmed the generation of\nnitrogen-centered radicals, which are key intermediates of triplet nitrene-mediated\nHAT process. These results directly confirm the generation of triplet nitrenes and their\ninvolvement in HAT.\nWe have supplemented these experimental details, including product\ncharacterization data and yield correlations, in the revised Supporting Information\nand discussed their implications for the HAT pathway in the mechanism section. These\nresults collectively provide robust validation of the proposed triplet nitrene-involved\nHAT process.\n1.0\n0.5\n0.0\n-0.5\n-1.0\n3450 3500\nytisnetnI\n2\nsimulation\nnormaliztion\n1\n0\n-1\n-2\n3400 3450 3500 3550\nMagnetic Field (G)\nytisnetnI\nMagnetic Field (G)\nWhat is more, we conducted reactions under blue LED irradiation with the addition of\ntriplet sensitizers. The reaction yield showed a negative correlation with the\nsensitizer’s triplet energy: yields were obtained in 38% yield (benzophenone) and 35%\nyield (xanthone) compared to the sensitizer-free control (32%). And we also used\nIr(ppy) and[Ru(bpz) ](PF ) as triplet sensitizer, and target product were obtained in\n3 3 6 2\n36% and 43% yield respectively. This trend supports that triplet energy transfer\npromotes triplet nitrene formation, further validating the HAT pathway. And due to\nthe triplet nitrene attribute to the N-N coupling partly, so the yields of product in these\ncondition increased slightly.\nComment: In Figure 5a, the nucleophilic attack step is incorrectly placed; the amine\nshould add only after the nitrene state 1csB1.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nconstructive feedback. We fully agree with your critical correction regarding the\nmechanistic step ordering in Figure 5a. We have revised Figure 6a to correct the step\nsequence, clearly illustrating the amine’s nucleophilic attack on the pre-formed nitrene\nintermediate (1csB1). The corresponding discussion in the mechanism section has also\nbeen updated to reinforce this accurate ordering. We greatly appreciate your\nmeticulous attention to detail, which has helped eliminate this critical error and\nenhance the precision of our mechanistic presentation.\nComment: In Figure 5a, for the 1CSE1 intermediate, evidence of its detection by crude\nNMR or LC–MS would strengthen the mechanistic proposal.\nResponse: Thank you sincerely for your insightful suggestion regarding the detection\nof the 1CSE1 intermediate via crude NMR or LC–MS, which is crucial for strengthening\nour mechanistic proposal. Following your advice, we have conducted targeted detection\nexperiments: crude 1H NMR analysis of the reaction mixture failed to identify the\ncharacteristic peaks of 1CSE1. We attribute this to the high structural similarity\nbetween 1CSE1 and the target product–their chemical shifts overlap significantly,\nmaking distinguishing signals in the complex crude system extremely challenging.\nAdditionally, crude LC–MS analysis also did not capture 1CSE1, as the intermediate\nundergoes rapid isomerization to the final product under the reaction conditions,\nresulting in a concentration too low to be detected.\nComment: In ON/OFF light experiment, product yield continues to increase (~5%) in\nthe dark phase (4–8 h). A plausible explanation or additional controls are needed.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nconstructive feedback. We appreciate your attention to the ON/OFF light experiment\nresults, where 3% yield increase was observed during the dark phase (4–8 h). A\nplausible explanation for this phenomenon is the persistence of long-lived active\nintermediates (e.g., radical species or some intermediates generated in light-on period)\nin the reaction system although at the moment of turning off the lights, the excited-\nstate substrates cease to be produced. These species remain reactive in the dark and\ncontinue to undergo N–N coupling with amines before being quenched or decomposed.\nTo validate this hypothesis, we have supplemented two control experiments: 1) A\n\"dark-only\" control (no light irradiation throughout 8 h) showed no change on yield,\nconfirming that light is essential for initiating the reaction; 2) A \"quenching\nexperiment\" where a radical scavenger (2,2,6,6-tetramethylpiperidine-1-oxyl, TEMPO)\nwas added at the start of the dark phase, which suppressed the 3% yield increase to\n<1%. This confirms that the dark-phase reaction is mediated by persistent radical\nintermediates generated during the light phase.\nComment: Many spectra are of poor quality. Impurities appear to have been obscured\nby decreasing peak intensities, which compromises reproducibility. High-quality\nspectra from purified samples should be provided. Numerous typographical errors\nand solvent misannotations (e.g., Fig. S96) are present. The SI should be carefully\nproofread and corrected.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nconstructive feedback. We fully acknowledge the critical issues regarding spectral\nquality, reproducibility, and errors in the Supporting Information (SI), and we\napologize for these oversights. To address these concerns comprehensively: Spectral\nquality improvement: We have re-purified all target compounds via column\nchromatography or recrystallization, and re-recorded high-quality ¹H NMR, ¹³C\nNMR,(with clear peak resolution, minimal noise, and no obscured impurities). These\nrevised spectra, along with detailed purification protocols, are included in the updated\nSI to ensure reproducibility. And we have conducted a rigorous, section-by-section\nproofread of the entire SI. All typographical errors, solvent misannotations (e.g.,\ncorrected Fig. S96), and formatting inconsistencies have been rectified.\nResponse to the comments from Reviewer #3.\nComment: This manuscript by Tang and Li et al. discloses an N–N bond formation via\nphotoinduced generation of nitrenes from sulfilimine precursors. The acylnitrenes\nwere produced under 365 nm LED irradiation from sulfilimines bearing a\ndibenzo[b,d]thiophene (DBT) moiety, which showed moderate to good selectivity for N–\nN formation with aromatic and aliphatic amine coupling partners. The mechanism of\nthis reaction was probed using experimental and computational methods and shown\nto proceed at least partially through radical intermediates. I will focus my comments\nprimarily on the computational investigations.\nResponse: We sincerely appreciate your detailed and insightful evaluation of our\nmanuscript, as well as your focus on the computational aspects of our work. We are\ngrateful for your recognition of our photoinduced sulfilimine-derived acylnitrene\nsystem for selective N-N bond formation with aromatic and aliphatic amines, and for\nyour constructive feedback on the computational investigations, which is crucial for\nstrengthening the mechanistic rigor of our study. We have carefully reviewed your\ncomments and will address each point thoroughly in the revised manuscript.\nComment: In Figure 5, the singlet (Fig 5a) and triplet (Fig 5b) pathways appear to be\ncalculated at two completely different levels of theory. This is very confusing and\ncontradicts the computational methods section in the Supporting Information. The\nauthors should clarify what level of theory was used.\nResponse: We would like to clarify that the geometry optimizations and frequency\ncalculations for all stationary points (including both the singlet and triplet pathways\nin Figure 5) were indeed performed at the same level of theory: B3LYP/def2-SVP in\nthe gas phase, as stated in the Computational Methods section. The relative energies\nreported in Figure 5 for both the singlet (Fig. 5a) and triplet (Fig. 5b) pathways are\nexclusively based on the single-point energies calculated at the BP86/def2-TZVPP level\nwith the SMD (chloroform) solvation model and including the D3 dispersion correction.\nTo clarify, the figure caption and the main text have been revised to explicitly state:\n\"DFT-calculated free energy profiles for the photo-induced N-N coupling reaction. a,\nSinglet pathway. b, Triplet pathway. The relative free energies (ΔG, in kcal/mol) are\ngiven relative to the separated reactants and were derived from BP86/def2-TZVPP\nsingle-point energies incorporating the SMD solvation model (chloroform) and D3\nempirical dispersion correction (GD3BJ), combined with thermochemical corrections\nobtained from B3LYP/def2-SVP frequency calculations.\" in the revised manuscript.\nComment: In addition, Figure 5’s caption also implies that the singlet pathway (Fig 5a)\nshows the free energies while the triplet pathway (Fig 5b) shows the electronic\nenergies. This again contradicts the figure itself, which shows G (Gibbs free energy)\non both Fig 5a and Fig 5b. What energies are these two diagrams actually showing?\nThis is very important to clarify before any conclusions about the mechanism can be\ndrawn.\nResponse: We are deeply grateful to the reviewer for this exceptionally meticulous\nobservation. Both Figure 5a and Figure 5b display the relative Gibbs free energies. To\nclarify, we have completely rewritten the caption for Figure 5 to remove any ambiguous\nor incorrect statements. Please see the Answer to Question 1.\nComment: Furthermore, if the mechanism in Fig 5a is indeed calculated at the\nB3LYP/def2-SVP level of theory (as stated in the caption), that would imply that these\nenergies are not calculated with a triple-zeta quality basis set or with the incorporation\nof dispersion effects. DFT energies should generally be calculated with triple-zeta basis\nsets and with at least empirical dispersion incorporated.\nResponse: We thank the reviewer for raising this critical point regarding the level of\ntheory. The reviewer's concern stems from an incomplete and potentially misleading\ndescription in the original Figure 5 caption. We sincerely apologize for this lack of\nclarity. We would like to clarify that the energy values reported in the figures and used\nfor all mechanistic discussions are NOT solely from the B3LYP/def2-SVP level.\nThe reported relative Gibbs free energies are, in fact, a composite of higher-level\ncalculations, as detailed in our Computational Methods section:\na)The electronic energy is obtained from single-point calculations at the BP86/def2-\nTZVPP level of theory, which utilizes a triple-zeta quality basis set. This calculation\nincorporates the SMD solvation model (chloroform) and the D3 empirical dispersion\ncorrection.\nb)The thermal corrections to the Gibbs free energy (at 298.15 K and 1 atm) are taken\nfrom the gas-phase frequency calculations at the B3LYP/def2-SVP level.\nc)The final reported energy is the sum of (a) and (b).\nTherefore, our energy benchmark does meet the standard advocated by the reviewer,\nas it is based on a triple-zeta basis set and includes both solvation and dispersion\neffects.\nCorrection Made:\nWe have thoroughly revised the caption for Figure 5 to explicitly state this composite\napproach. The new caption clearly indicates that the relative free energies are derived\nfrom \"BP86/def2-TZVPP single-point energies with SMD (chloroform) and D3\ndispersion correction, combined with thermochemical corrections from B3LYP/def2-\nSVP frequency calculations.\"\nComment: While the computational methods section in the Supporting Information\nstates that empirical dispersion was included, it is not clear how dispersion was\nincluded, as neither B3LYP nor BP86 includes dispersion. Please clarify how\ndispersion was actually included in the calculations.\nResponse: We thank the reviewer for this precise technical question regarding the\nimplementation of dispersion corrections. For the single-point energy calculations at\nthe BP86/def2-TZVPP level with the SMD model,\nthe empirical dispersion correction was explicitly incorporated using the DFT-D3\nmethod with Becke-Johnson (BJ) damping, as developed by Grimme et al. (reference 8\nin the SI).\nCorrection Made:\nWe have revised the Computational Methods section in the revised Supporting\nInformation to make this explicit. The text now reads:\n\"... Single-point energy calculations were performed at the BP86/def2-TZVPP level\nusing the SMD solvation model with chloroform as the solvent and including the D3\nempirical dispersion correction with BJ damping (GD3BJ)8.\"\nComment: In the SI, imaginary frequencies should be provided for transition states.\nResponse: We thank the reviewer for this valuable suggestion. As requested, we have\nnow included the imaginary frequencies for all reported transition states in the revised\nSupporting Information.\nResponse to the comments from Reviewer #4.\nSelective N-N bond construction remains a significant challenge in organic synthesis.\nLi, Tang, Yu, and their coworkers have reported a robust and efficient method for\nsynthesizing substituted hydrazines via a photochemical nitrene strategy. Specifically,\nthey employed a sulfilimine-based photoinduced approach to achieve controlled\nnitrene release and intermolecular N-N coupling under metal-free conditions. This\nmethod enables precise tuning of nitrene reactivity through structural modification of\nsulfilimines, which effectively suppresses the side reactions associated with free\nnitrenes. This transformation demonstrates broad functional group compatibility that\novercomes the substrate limitations of conventional metal-catalyzed and\nphotochemical methods. Additionally, it addresses critical gaps in nitrene chemistry\nby integrating photoactivation and controlled nitrene transfer, thereby expanding the\nsynthetic toolkit for constructing nitrogen-rich molecular scaffolds.\nResponse:We sincerely appreciate your thoughtful and insightful summary of our\nwork on photochemical nitrene-mediated N-N bond construction. We are particularly\nencouraged by your recognition of the method’s value in addressing long-standing\nchallenges in N-N bond synthesis, such as substrate limitations of conventional\nstrategies and the precise regulation of nitrene reactivity. We thank you for your\nrigorous and positive evaluation, which serves as valuable encouragement for our\ncontinued investigations in nitrene chemistry and N-N bond construction. We have\ncarefully reviewed your comments and will address each point thoroughly in the\nrevised manuscript.\nBased on its scientific merit, I recommend this work for publication in Nature\nCommunications pending the resolution of the following minor revisions:\nManuscript corrections:\nComment: In the condition table (Entries 1–6), chlorinated solvents are listed prior to\nother solvents. The authors should clarify whether chlorine-containing additives\ncontribute to improved yield and selectivity of the reaction.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nconstructive feedback. We appreciate your insightful question regarding whether\nchlorinated species contribute to the reaction’s yield and selectivity, given the\nprioritization of chlorinated solvents in Entries 1–6 of the condition table. To clarify\nthis point, we have conducted supplementary experiments by adding common\nchlorinated additives (including NCS, NaCl, and TBACl) under our standard reaction\nconditions. The results showed that the target product yields were only 32%, 40%, and\n72%, respectively—values comparable to those obtained in the absence of additional\nchlorinated additives. These data confirm that exogenous chlorinated additives do not\nexert a promotional effect on either the yield or selectivity of the N–N coupling reaction.\nComment: In the condition table (Entries 10–12), only trace amounts of the target\nproduct are obtained. The authors should specify if any side products were observed\n(e.g., products derived from nitrene insertion into the sulfur atom of DMSO) and\ndiscuss their formation.\nResponse: Thank you sincerely for your thorough evaluation of our manuscript and\nyour constructive feedback. DMSO CH CN and DMF these polar solvents would\n3\naccelerate the N-S bond of dissociation, and byproduct 4-methylbenzamide was\ngenerated.\nComment: For the amine substrate scope: Even if certain amine types are incompatible,\nthe authors should discuss and present data for a broader range of amines (e.g.,\nprimary amines) to provide a more comprehensive assessment of substrate\napplicability.\nResponse: Thank you for your suggestion of substrate description. We have assessed\nthe primary amine (aryl amine and aliphatic amine), but the primary amines were not\ncompatible to this method. We also added some of these failed examples in Figure 2.\nH2N H2N H2N\nH2N\nPh H2N\nMe OMe CN\nfailed substrates\nComment: The substrate scope of sulfonyl nitrene precursors is also critical, yet only\nfour examples are reported in the manuscript. It is recommended that the authors\ninvestigate and include additional types of sulfonyl nitrene precursors to validate the\ngenerality of the method.\nResponse: Thank you for your suggestion of substrate description. We have added some\nmore sulfonyl nitrene precursors to validate the generality of the method. All these\nadditional examples of sulfonyl nitrene precursors were added in figure 3b.\nComment: Further mechanistic studies are needed to clarify the reaction mechanism.\nFor instance, internal alkenes should be added as reactants and tested with the\nsulfilimine nitrene precursor under standard reaction conditions to probe potential\nnitrene trapping pathways.\nResponse: Thank you sincerely for your insightful suggestion on strengthening our\nmechanistic investigations. We fully agree that nitrene trapping experiments with\ninternal alkenes are crucial to delineate nitrene-mediated pathways, and we have\nsupplemented this work alongside other targeted mechanistic studies to\ncomprehensively clarify the reaction mechanism. First, in response to your specific\nrecommendation, we tested representative internal alkenes (e.g., cyclohexa-1,4-diene)\nas nitrene trapping agents under our standard reaction conditions. Second, SPh /PPh\n2 3\nwere added as nitrene-trapping agent under our standard reaction conditions, HR-MS\nanalysis confirmed the formation of corresponding adducts, which directly verifies the\ngeneration of free nitrene intermediates.\nIn addition to the alkene trapping studies, we have implemented two other\ncomplementary mechanistic tools as you noted: 1) Electron Paramagnetic Resonance\n(EPR) spectroscopy with a spin-trapping agent (DMPO) successfully captured the\nnitrogen-centered radical signal (Fig 4i), confirming radical intermediates derived\nfrom nitrene; 2) Time-resolved absorption (ns-TA) spectroscopy identified the transient\nabsorption band of the triplet nitrene intermediate, providing direct photophysical\nevidence for its existence and reactivity (Fig 5e-i). All these new data-including EPR\nspectra, and ns-TA data-have been compiled into the revised manuscript and\nSupporting Information and discussed in the mechanistic section.\nSupporting Information Corrections:\nComment: In the \"General Information\" section, the description of the \"commercially\navailable LED light (50 W, 365 nm)\" must be supplemented with the manufacturer’s\nname and product model for reproducibility.\nResponse: Thank you for your valuable comment. We fully agree that the photoredox\nprotocol is sensitive to experimental setup, and we will supplement the detailed setup\ninformation as requested. We have taken clear photos of the complete experimental\nsetup, including the light source, reaction vessel, and temperature control system.\nThese photos were added as Supplementary Figure S1 in the revised Supporting\nInformation.\nComment: In Figure S189 (¹H NMR spectrum of compound 53), some peaks are not\nlabeled, and the peak at 1.25 ppm is incorrectly assigned. These issues should be\ncorrected.\nResponse: Thank you for your careful review and valuable comments. We fully\nacknowledge the issues raised and have addressed them as follows: regarding Figure\nS189 (¹H NMR spectrum of compound 53), we have thoroughly revised the spectrum.\nAll previously unlabeled peaks have now been assigned with accurate chemical shifts,\nand the incorrect assignment of the peak at 1.25 ppm has been corrected. The revised\nspectrum ensures that each proton environment in compound 53 is clearly and\ncorrectly labeled for clarity.\nComment: Several ¹H NMR spectra exhibit non-standard formatting: In Figures S223,\nS219, and S215, the integral values for key peaks are missing and should be added to\nensure data completeness.\nResponse: We agree that complete integral values are essential for NMR data\nintegrity. For Figures S223, S219, and S215, we have recalculated and added the\nintegral values for all key peaks, ensuring that the relative proton counts are\naccurately reflected. This supplementation will enhance the reproducibility and\nreliability of the data. All revised figures have been updated in the supplementary\ninformation, and we have all the other NMR spectra to avoid similar issues."}, {"round": 2, "reviewer_comments": {"reviewer_1": "I have reviewed the revised version of the manuscript and the authors’ responses to the previous round of review\ncomments.The authors have addressed all the points raised in the previous review meticulously. Given the satisfactory\nrevisions of all previously raised issues, I am pleased to recommend the manuscript to be accepted by Nature\nCommunications in its current form.", "reviewer_2": "The authors addressed the issues and questions and the revised version can be acceptable.", "reviewer_3": "The authors have satisfactorily addressed my concerns and I recommend the manuscript for publication."}, "author_response": ""}]

Decision letter