Tetrachloromethane as an editable all-carbon quaternary source

Domain: chemistry
Published: 2026-01-07
Editorial outcome: minor_revision

Abstract
Despite the widespread presence of all-carbon quaternary centers in natural products and bioactive compounds, a concise construction strategy remains very challenging. Herein, we introduce a highly controllable sequential dechlorination strategy of tetrachloromethane by means of relay catalysis with different photocatalysts of eosin Y, 1,2,3,5-tetrakis(carbazol-9-yl)−4,6-dicyanobenzene and Au (µ-dcpm) Cl . Four C-Cl bonds in CCl can undergo sequential, highly selective cleavage by combination of outer-sphere and inner-sphere crossover single electron transfer mechanism, enabling radical-addition reactions with a wide range of terminal alkenes to construct all-carbon quaternary centers in four steps with 17-38% yields. Furthermore, using 1,1-disubstituted styrene as the substrates, cyclopropanes bearing with challenging vicinal all-carbon quaternary centers are also successfully constructed from CCl in two-pots three steps with moderate yields of 10-50%. This work suggests the possibility of tetrachloromethane as an editable C1 synthon to facilitate the construction of all-carbon quaternary centers.

Introduction
The properties of organic molecules are intrinsically linked to their structures. C(sp3)-hybridized atoms, particularly all-carbon quaternary centers, serve as an important scaffold in pharmaceuticals, functionalized materials, and natural products (Fig. 1a)1–5, providing a promising platform to escape flatland6. Consequently, the development of practical synthetic methodologies to construct quaternary carbon centers has gained increasing momentum in recent years7–10. While significant progress11–17 has been achieved, the assembly of a general method for all-carbon quaternary centers, especially those with four distinct carbon substituents, still represents the state-of-the-art in organic synthesis. Very recently, atomic carbon strategy has been proven to be a valuable strategy which can facilitate the formation of four covalent bonds using a C1 synthon (Fig. 1b)18–21. For example, in 2023, Tobisu22 reported a N-heterocyclic carbenes facilitated atomic carbon transfer reaction, which could construct γ-lactams from acrylamides. In 2025, Hansmann23 reported a C(sp3)-atom transfer reaction to construct highly strained spiro[2.2]pentanes structures in a three steps manner.

Considering the highly functionalized C1 synthon needed in most atomic carbon strategies, as well as with our continuing interest in photocatalytic activation of C-Cl bonds24–38, we questioned if the commercially available carbon tetrachloride, one of the functionalized C1 sources, would serve as an editable carbon center by photocatalyst-controlled relay dechlorinative functionalization. Generally, both carbon tetrachloride and alkyl carbon trichloride have a moderate reduction potential (E =−1.6 ~ −2.0V versus saturated calomel electrode (SCE))39 and could be actively involved in radical C(sp³)–C(sp³) bond formation by using a redox-matched photocatalyst40. However, the gem-dichloroalkanes and tertiary alkyl chlorides (E = ~−2.8V versus SCE)41 in such an outer-sphere single electron transfer mechanism are limited by the inherent redox potentials of the photocatalysts.

A pioneering but in non-catalytic approach was described by Wang and co-workers in 202242,43, who successfully used Lewis base–boryl radicals as promoters and selectively alkylated the three C–Cl bonds of activated trichloromethyl groups. Despite this impressive advance, significant challenges remain in the development of a new catalytic strategy to realize selective relay activation of four C–Cl bonds in CCl , accessing all-carbon quaternary carbon centers. As part of our ongoing efforts, we sought to combine different kinds of commercially available photocatalysts bearing different redox potential44 with dinuclear gold-complex developed in our group45–53, which would precisely control the dechlorination selectivity through outer-sphere and inner-sphere crossover single electron transfer (SET) mechanism (Fig. 1c).

Herein, we report a photocatalytic relay strategy that enables construct all-carbon quaternary centers from carbon tetrachloride (Fig. 1d). Four C−Cl bonds in CCl have been selectively and sequentially activated by eosin Y, 1,2,3,5-tetrakis(carbazol-9-yl)−4,6-dicyanobenzene (4CzlPN), and Au (μ-dcpm) Cl , generating corresponding alkyl radical intermediates, which can subsequently add to alkenes to introduce four different alkyl substituted quaternary carbon center compounds in moderate yields. Interestingly, cyclopropanes bearing with challenging vicinal all-carbon quaternary centers have been successfully constructed for CCl with relay dechlorinative strategy.

Results
We initiated our investigations by reacting CCl with 4-methoxystyrene using various photocatalysts under visible light irradiation (λ =460nm). After a preliminary screening, it was found that the organic dye eosin Y (1/2E=−1.01V vs. SCE)44 could successfully activate only one C–Cl bond of CCl (E =−1.51V vs. SCE, Fig. 2a) in acetonitrile, yielding the desired trichloroalkane (4) in 81% yield without over dechlorination. Additional experiments demonstrated that γ-terpinene, acting as an H-donor, and N,N’-dimethyl-1,3-propanediamine, serving as a base, are crucial for a productive outcome. During the optimization process, it is interesting to find that employing photoredox catalyst 4CzIPN (1/2E=−1.21V vs. SCE)44, enables the second dechlorination process of trichloroalkane (4) (E =−1.75V vs. SCE), yielding the gem-dichloroalkanes as byproduct. This finding suggests that continuous dechlorinative process can be controlled via relay photocatalysis. Inspired by this, we successfully obtained the desired two different alkyl-substituted gem-dichloroalkane (5) with an overall yield of 69% in a one-pot process (Fig. 2b). Light irradiation, triethanolamine, and the photocatalyst 4CzIPN were essential for the success of the transformation.

It is notable that commonly used strong reducing photocatalysts, such as fac-Ir(ppy) , remain challenging to activate the unactivated C-Cl bonds in gem-dichloroalkanes and tertiary alkyl chlorides (E = ~−2.8V vs. SCE)54. In light of our recent work on light-mediated inner-sphere SET mechanisms29,30,32,35,55, we examined the reaction of gem-dichloroalkanes (5) with alkenes in the presence of Au (µ-dcpm) Cl in MeCN under blue light irradiation (λ =460nm) (Fig. 2c). The reactions successfully produced the expected tertiary alkyl chlorides (6-8) in 65-75% yields using Hantzsch ester as the reductant and 1,1,3,3-tetramethylguanidine (TMG) as the base additive (conditions C).

Significantly, as shown in Fig. 3, we successfully obtained the product 9 that bears four different alkyl substituents on a quaternary carbon center, from tertiary alkyl chlorides (6) in 62% yield (conditions D) by changing the light wavelength from 460nm to 390nm, replacing Hantzsch ester with γ-terpinene, and TMG with 1,4-diazabicyclo[2.2.2]octane (DABCO). This would imply that the activation of both C-Cl bonds in gem-dichloroalkanes would be tuned by different wavelength LEDs and additives. Different from our previous work29,32, unactivated monochlorinated alkanes, which typically require harsh reductive reaction conditions56, can react smoothly in this process, further demonstrating the advances of inner-sphere SET mechanism of Au (µ-dcpm) Cl photocatalyst. With these standard conditions, we next turned our attention to explore the generality of dechlorinative alkylation reaction with tertiary alkyl chlorides. It is found that they underwent this transformation readily to, result in the formation of the corresponding all-carbon quaternary center products (9-16) in 40-68% yields. Substrates containing ether, ester, amide (9-11), chlorine (12), fluorine (13) and trifluoromethyl (16) groups all successfully yielded the desired products in moderate yields. Additionally, the bulky substituents, such as 2-naphthyl (14), were successfully incorporated under standard reaction conditions.

Compounds containing vicinal all-carbon quaternary centers are commonly found in secondary metabolites and are known to exhibit significant biological and pharmacological activities57–59. With the successful implementation of photocatalyzed sequential dechlorination of CCl to generate an editable all-carbon quaternary center, we employed CCl to construct vicinal all-carbon quaternary centers through the homolysis of another C–Cl bond (Fig. 4). Intriguingly, we found that the 1,1-disubstituted styrenes could undergo gold-catalyzed cyclopropanation smoothly with gem-dichloroalkanes60,61, furnishing the desired highly substituted cyclopropanes in 23–64% yields from gem-dichloroalkanes. It is important to point out that the resulting unsymmetrical gem-dichloroalkanes in this protocol are challenging to prepare by classical synthetic methods owing to the unavailability of corresponding starting materials62. This strategy allows for facile construction of structurally diverse cyclopropanes in moderate yields. The 1-vinylnaphthalene and 2-vinylnaphthalene were also applicable in the reaction, producing the products in 50–53% yields (31, 33). To our delight, unactivated olefins such as 4-phenyl-1-butene and allylbenzene tolerated the reaction conditions well (35, 37). Electron-deficient olefins besides ethyl acrylate were also studied and it was found that they could participate in this transformation to afford the products (41, 43, 47) in moderate yields. Substrates containing nitrile group seem to lead to a decrease in the reaction efficiency, and only 23% yield in the cycloaddition reaction (45) was obtained. Styrene with electron-withdrawing substituents such as methyl 4-vinylbenzoate could also replace ethyl acrylate, giving rise to the desired products (50, 52, 53) in moderate yields. Moreover, derivatives of 1,1-diphenylethylene could be used, affording the desired product (48) in moderate yield. It is important to find that the neutral terminal olefins and styrene with electron-donating groups behaved well in the first dechlorinative alkylation reaction, while the election-deficient olefins behaved well in the second step. Overall, the above cases successfully demonstrate the proof-of-concept for concise construction of challenging cyclopropanes bearing with vicinal all-carbon quaternary centers from CCl , with an overall yield ranging from 10 to –50% in two-pots three-step procedure.

To verify if the relay radical dechlorination is involved in this strategy, electron paramagnetic resonance (EPR) experiments were carried out (Fig. 5). Two equivalents of N-tert-butyl-α-phenylnitrone (PBN) were added into each model reaction. Interestingly, in all four independent reactions, we detected signal of alkyl radicals, which would suggest the alkyl radicals were involved in all reactions. In the first and second dechlorinative alkylation process, for eosin Y and 4CzIPN, oxidative quenching of the photoexcited photocatalyst via outer-sphere SET process can readily occur with alkyl chloride owing to the matched redox potential, followed by the cleavage of C-Cl bond to generate corresponding alkyl radicals. In addition, a signal of H-radical in the first step was observed, which may originate from terpene within the system63 (see Supplementary Fig. 5 for details). For the third and fourth reaction steps, the reactions became more difficult due to the reduced number of electron-negative chlorine atoms directly bonded to the central carbon atom. The use of dinuclear gold catalyst will lead to an inner-sphere SET mechanism to break the unactivated C-Cl bonds and furnish the corresponding alkyl radicals64. It is interesting to disclose that the use of different wavelength LEDs together with additives would tune the C-Cl cleavage sequence in gem-dichloroalkanes. The selectivity of first two steps is probably controlled by outer-sphere SET mechanism with different reductive potentials while the last two steps may be tuned by inner-sphere SET mechanism.

Methods
General procedure A. In a 10mL transparent glass bottle equipped with a stirrer, eosin Y (2mol%) is added, then the tube is moved into glovebox. Alkenes 1 (0.1mmol), CCl (5 equiv.) MePDA (2.5 equiv.), γ-terpinene (3 equiv.), MeCN (1mL) are added successively under nitrogen atmosphere. The bottle is sealed and putted under blue LEDs (λ =460nm) irradiation with vigorous stirring. Upon reaction completion judged by TLC, the reaction mixture is concentrated under reduced pressure and directly used for subsequent procedure.

General procedure B. The crude product obtained from General procedure A is added 4CzIPN (2mol%), then this tube is moved into glovebox. Alkene 2 (0.4mmol), TEOA (0.2mmol) and DCM (1mL) are added successively under nitrogen atmosphere. The bottle is sealed and putted under blue LEDs (λ =460nm) irradiation with vigorous stirring. Upon reaction completion judged by TLC, the reaction mixture is concentrated under reduced pressure and purified by flash column chromatography on silica gel (eluent = PE/EA).

In a 10mL transparent glass bottle equipped with a stirrer, Au (μ-dcpm) Cl (2mol%), Hantzsch ester (2 equiv.) and gem-dichloroalkanes (0.1mmol) are added successively. Then the tube is moved into glovebox. Alkene 3 (2 equiv.), TMG (2 equiv.), MeCN (1mL) are added successively under nitrogen atmosphere. The bottle is sealed and putted under blue LEDs (λ =460nm) irradiation with vigorous stirring. Upon reaction completion judged by TLC, the reaction mixture is concentrated under reduced pressure and purified by flash column chromatography on silica gel (eluent = PE/EA).

In a 10mL transparent glass bottle equipped with a stirrer, Au (μ-dcpm) Cl (2mol%), monochlorinated alkanes (0.1mmol) and DABCO (2.5 equiv.) is added. Then the tube is moved into glovebox. Alkene 4 (5 equiv.), γ-terpinene (4 equiv.), LiF (2 equiv.), DMAc: 1,4-dioxane = 2:1 mix solvent (1mL) are added successively under nitrogen atmosphere. The bottle is sealed and putted under 390nm LEDs irradiation with vigorous stirring. Upon reaction completion judged by TLC, the reaction mixture is concentrated under reduced pressure and purified by flash column chromatography on silica gel (eluent = PE/EA).

In a 10mL transparent glass bottle equipped with a stirrer, Au (μ-dcpm) Cl (2mol%), Hantzsch ester (1.2 equiv.) and gem-dichloroalkanes (0.1mmol) is added successively. Then the tube is moved into glovebox. Alkene 5 (2 equiv.), BTMG (2 equiv.), MeCN (1mL) are added successively under nitrogen atmosphere. The bottle is sealed and putted under blue LEDs (λ =460nm) irradiation with vigorous stirring. Upon reaction completion judged by TLC, the reaction mixture is concentrated under reduced pressure and purified by flash column chromatography on silica gel (eluent = PE/EA).

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "The construction of all-carbon quaternary centers compounds represents the state-of-the-art in organic synthesis, especially from readily available chemical stocks. It is very important yet desirable to develop an efficient method to achieve this challenging task. The current methods mainly focus on the introduction of one carbon-containing functional group into the tertiary carbon centers. The use of an editable C1 source to construct all-carbon quaternary centers is appealing for chemical community.\nIn this manuscript, Xie and coworkers have developed an interesting synthetic method for the concise construction of all-carbon quaternary centers from commercially available CCl4 by photocatalysis. By using different kinds of photocatalysts, sequential C-Cl activation of CCl4 can be realized for the successful generation of corresponding alkyl radical, allowing for radical addition to different electron-withdrawing alkenes. Compared with Tobisu (Science 2023) and Hansmann (Science 2025) work as well as Wang’s non-catalytic method from activated trichloroalkanes (JACS, 2022), this reviewer thinks that this work has enough novelty and originality for the publication in Nature Communications.\nThe key point is the application of PC1 Eosin Y, PC2 4CzIPN and PC3 bisgold-complex for relay C-Cl bond activation, avoiding over-dechlorination side reactions. The authors have carefully conducted the CV of CCl4, RCCl3, R2CCl2 and R3CCl. It would be very interesting for the others to realize cascade C-Cl bond activation through redox-potential matched manner. Furthermore, different from the author’s previous reports (Nat. Catal. 2022, 5, 1098–1109, Nat. Commun. 2024, 15, 3721), PC3 can selectively activate unactivated tertiary C-Cl bond for the generation of tertiary alkyl radical, significantly expanding the substrate scope of this catalytic system. This reviewer enjoys seeing the compounds such as 6 and 11, even only with moderate yields but four different alkyl partners have been sequentially introduced into one C1 center. It would be useful to construct structurally complex natural products in future. In addition, synthetically challenging cyclopropanes bearing vicinal all-carbon quaternary centers have been successfully constructed directly from CCl4 in two pots. With this method, a wide range of functionalized gem-dichloroalkanes, which are difficult to prepare by classical methods, can be easily constructed from CCl4, providing a nice addition to previous reports. The authors have performed mechanistic EPR experiments to support the radical relay C-Cl activation process.\nThe manuscript text and figures, as well as the Supplementary Information, are well organized. This reviewer would like to strongly recommend its acceptance in Nature Communications after minor revisions based on its originality and importance.\n1. Several references about C-Cl bond activation by photocatalysis are suggested to cite: J. Am. Chem. Soc., 2014, 10.1021/jacs.4c10915; Chem. Sci., 2025, 10.1039/D5SC00190K; Org. Lett., 2024, 10.1021/acs.orglett.4c04367; Nat. Chem. 2024, 10.1038/s41557-023-01385-w.\n2. For the EPR experiments, I would like to suggest the authors define the four figures as a, b, c and d. For the first EPR result, is there hydrogen radical in the reaction system? How can they be formed? The authors should give some suitable comments on this matter. Indeed, I would suggest the authors remove terpinene from standard conditions A and perform the EPR experiments again.\n3. The detailed reaction conditions are better to show in the caption in Figure 3 and Figure 4.\n4. Ref. 35, Steven P. Nolan, Thomas Scattolin, Xinyuan Ma should be as Nolan, S. P., Scattolin, T., and Ma, X. Please carefully check all the references. The styles should be kept in the same one.\n5. In Figure 4, the structure of PC3 can be removed, as this catalyst has been shown in previous figures.\n6. In every step, I would suggest the authors clearly illustrate the wavelength of LEDs in conditions or in the equations.", "reviewer_2": "In this work, Tang and Xie and co-workers report a sequential photocatalytic dechlorination of CCl₄, enabling the construction of all-carbon quaternary centers and cyclopropane derivatives through relay catalysis with multiple photocatalysts. The authors demonstrate that selective activation of each C–Cl bond can be achieved by combining outer-sphere and inner-sphere SET processes, employing Eosin Y, 4CzIPN, and a dinuclear gold complex.\nWhile the experiments are executed with care and the mechanistic rationale is sound, the conceptual framework largely builds upon previously established photocatalytic dechlorination strategies. In particular, the sequence of dechlorination steps and the underlying radical relay design appear to extend, rather than fundamentally transform, the methodologies reported in references 24-29 and 32. I have no doubt that the concept will be of value for the community, but in my opinion the novelty here resides more in the integration of known catalytic systems (or very related conditions) than in the development of a distinct reactivity paradigm.\nOverall, the manuscript represents a competent and well-documented piece of work, but its impact and originality may not meet the broad scope of Nature Communications. The study would be more appropriately suited for a synthesis-focused journal, where the systematic optimization would be better appreciated.\nAdditional comments:\n- Figure 2a: when measuring reduction potentials, how can one make sure that they refer to the population of the sigma* orbital of the C-Cl and not to the injection of an electron in the aromatic rings? Is this based on literature?\n- I recommend the author to better show the trace of H-radical capture in Figure 5.", "reviewer_3": "I am uncertain whether the authors are employing British English conventions; however, I am not familiar with the term \"decholo-\" and can only recognize the established term \"dichlorination.\" This terminology should be clarified or corrected to align with standard chemical nomenclature.\nThe manuscript would benefit from additional refinement to ensure that all statements—particularly those in the abstract—are grounded firmly in the experimental data rather than presenting speculative or conjectural suggestions. The abstract should reflect conclusions that are directly supported by the results obtained.\nThe research presents an interesting approach utilizing carbon tetrachloride as the primary synthon for generating quaternary carbon centers through a mechanistic pathway that involves both outer-sphere and inner-sphere crossover single-electron transfer (SET) processes. This mechanism facilitates radical-addition reactions with a diverse array of terminal alkenes, enabling the consecutive construction of increasingly complex molecular architectures. While the scope of reactivity is somewhat constrained—primarily limited to aromatic alkene substrates—the methodology demonstrates practical utility and synthetic value. Although the underlying concept may not represent a groundbreaking departure from existing approaches, it nonetheless offers a meaningful application that contributes to advancing the field of synthetic organic chemistry.\nThe study is executed with an appropriate level of scientific rigor and experimental thoroughness. THe claims and data set were collected and presented properly. Given its solid execution and practical implications, this work deserves broader visibility within the synthetic chemistry community, making it well-suited for publication as a communication in this journal."}, "author_response": "Point-by-point response to the reviewers\nMany thanks for the three reviewers’ insightful, helpful and useful suggestions and\ncomments, which are very helpful for us to improve the quality of our manuscript.\nAccording to the reviewers’ suggestions, we have tried our best to address all the points\nraised by three reviewers.\nReviewer #1 (Remarks to the Author):\n[...]\nThank you very much for your positive comments.\n1. Several references about C-Cl bond activation by photocatalysis are suggested to cite:\nJ. Am. Chem. Soc., 2014, 10.1021/jacs.4c10915; Chem. Sci., 2025,\n10.1039/D5SC00190K; Org. Lett., 2024, 10.1021/acs.orglett.4c04367; Nat. Chem. 2024,\n10.1038/s41557-023-01385-w.\nOur answer: Thank you very much. According to your suggestion, we have added the\nreferences in the revised manuscript as follows:\n(31) Tian, Y., Li, X.-T., Liu, J.-R., Cheng, J., Gao, A., Yang, N.-Y., Li, Z., Guo, K.-X., Zhang,\nW., Wen, H.-T., Li, Z.-L., Gu, Q.-S., Hong, X. & Liu, X.-Y. A general copper-catalysed\nenantioconvergent C(sp3)–S cross-coupling via biomimetic radical homolytic substitution.\nNat. Chem.16, 466–475 (2024).\n(33) Fang, C.-Z., Zhang, B.-B., Tu, Y.-L., Liu, Q., Wang, Z.-X. & Chen, X.-Y. Radical\nreplacement process for ligated boryl radical-mediated activation of unactivated alkyl\nchlorides for C(sp3)–C(sp3) bond formation. J. Am. Chem. Soc.146, 26574–26584 (2024).\n(34) Gong, D., Gao, C., Zhang, Y., Yao, F., Li, Q., Li, Y., Zhao, L. & Kong, D. Photocatalytic\nhydrodichloromethylation of unactivated alkenes with chloroform. Org. Lett. 26,\n11230–11235 (2024).\n(36) Liang, R.-B., Miao, T.-T., Li, X.-R., Huang, J.-B., Ni, S.-F., Li, S., Tong, Q.-X. & Zhong,\nJ.-J. Modular assembly of amines and diborons with photocatalysis enabled halogen atom\ntransfer of organohalides for C(sp3)–C(sp3) bond formation. Chem. Sci. 16, 3580–3587\n(2025).\n2. For the EPR experiments, I would like to suggest the authors define the four figures as\na, b, c and d. For the first EPR result, is there hydrogen radical in the reaction system?\nHow can they be formed? The authors should give some suitable comments on this\nmatter. Indeed, I would suggest the authors remove terpinene from standard conditions A\nand perform the EPR experiments again.\nOur answer: Thank you for your helpful suggestion. We repeated the EPR experiments\nfor Step 1 in the absence of terpinene. The results indicated that we successfully trapped\nthe alkyl radical, and no hydrogen radical signal was detected. Thus, we have revised the\nmanuscript figure.\nThe vision of EPR experiment performed in Standard condition A was also applied in\nSupplementary Information.\n“We also found a signal of H-radical in the first step, which may originate from\nterpinene within the system63 (see Supplementary Information for details).”\nBased on our experiments and literature (Science 377, 1323–1328 (2022).), we\nthought the hydrogen radical may generate from the pyrolysis of γ-terpinene.\nThank you again for your sincere suggestion.\n3. The detailed reaction conditions are better to show in the caption in Figure 3 and Figure\n4.\nOur answer: Thank you for your suggestion. We have added respond reaction conditions\nin the caption.\n“Scope of alkane with four alkyl substituents quaternary centers. Conditions D: PC 3\n(2 mol%), monochlorinated alkanes (0.1 mmol), alkene 4 (0.5 mmol), DABCO (0.25\nmmol), γ-terpinene (0.4 mmol), LiF (0.2 mmol), DMAc: 1,4-dioxane (v/v = 2 : 1, 1 mL),\nLEDs (λ = 390 nm), 24 h.”\nmax\n“Figure 4. Scope of cyclopropanes bearing with vicinal all-carbon quaternary\ncenters. Conditions E: PC 3 (2 mol%), gem-dichloroalkanes (0.1 mmol), alkene 5 (0.2\nmmol), Hantzsch ester (1.2 mmol), BTMG (0.2 mmol), MeCN (1 mL), LEDs (λ = 460\nmax\nnm), 24 h. The first step yield is for the synthesis of gem-dichloroalkanes and the second\nstep yield is for the target products.”\n4. Ref. 35, Steven P. Nolan, Thomas Scattolin, Xinyuan Ma should be as Nolan, S. P.,\nScattolin, T., and Ma, X. Please carefully check all the references. The styles should be\nkept in the same one.\nOur answer: Thank you very much. We have rechecked formation of the references and\namended the issues identified.\n5. In Figure 4, the structure of PC3 can be removed, as this catalyst has been shown in\nprevious figures.\nOur answer: Thank you for your suggestion. We have revised the manuscript as follows:\n6. In every step, I would suggest the authors clearly illustrate the wavelength of LEDs in\nconditions or in the equations.\nOur answer: Thank you very much for your suggestion. We have revised the manuscript\nas follows:\nFigure 3\nFigure 4\nReviewer #2 (Remarks to the Author):\n[...]\nOur answer: Thank you very much. The activation of inert C-Cl bonds under mild\nconditions has long been considered as important and challengeable task in organic\nchemistry (Nat. Catal.3, 40–47 (2019).). According to your suggestion, we added detailed\ndescription of our work in the abstract: “…to construct all-carbon quaternary centers in\nfour steps with 17-38% yields.” and “…are also successfully constructed for CCl in\n4\ntwo-pots three steps with moderate yields of 10-50%.”\nAdditional comments:\n- Figure 2a: when measuring reduction potentials, how can one make sure that they refer\nto the population of the sigma* orbital of the C-Cl and not to the injection of an electron in\nthe aromatic rings? Is this based on literature?\nOur answer: Thanks for the kind comments. We have reviewed some literature about\ndirect reduction of compounds with both C-Cl bonds and aromatic rings. Unfortunately, we\ndid not find detail data for substances very similar to our compounds. However, according\nto literature reports (Angew. Chem. Int. Ed. Engl.23, 84-85(1984)), the reduction potential\nof benzene is up to -3.42 V (VS. SCE), which is much negative than the reduction\npotential of alkyl chlorides (-2.8 V (VS. SCE)). Thus, we thought the reduction peak in CV\ncurve in our manuscript is more likely reflect to the directly reduction of C-Cl bonds.\n- I recommend the author to better show the trace of H-radical capture in Figure 5.\nOur answer: Thank you very much for your suggestion. We repeated the EPR\nexperiments under the Standard conditions in the absence of terpinene, and we detected\nthe formation of alkyl radical. The result showed the H-radical may came from the\nterpinene. The figure of EPR studies was modified to showed the alkyl radical more\nclearly and the H-radical captured was moved to Supplementary Information.\nReviewer #3 (Remarks to the Author):\n[...]\nOur answer: Thank you very much. We have rechecked all the spell of “dechlorination”,\nwhich means remove a chlorine atom from compounds (Zhou, Q., Zhang, G., Lan, Y.,\nLong, T., Du, L., Bian, T., Zhou, L. & Zhang, Z. Multicomponent synthesis of\nisoquinuclidines via Pd-catalyzed selective dechlorination. Org. Lett., 27, 10670−10675\n(2025).), and corrected the spelling errors in the text.\nThe manuscript would benefit from additional refinement to ensure that all\nstatements—particularly those in the abstract—are grounded firmly in the experimental\ndata rather than presenting speculative or conjectural suggestions. The abstract should\nreflect conclusions that are directly supported by the results obtained.\nOur answer: Thank you very much for your suggestion. We have made minor\nmodifications to the description of our result, such as compound structure and yields. The\ntext is:\n“…enabling radical-addition reactions with a wide range of terminal alkenes to construct\nall-carbon quaternary centers in four steps with 17-38% yields. Furthermore, using\n1,1-disubstituted styrene as the substrates, cyclopropanes bearing with challenging\nvicinal all-carbon quaternary centers are also successfully constructed for CCl in\n4\ntwo-pots three steps with moderate yields of 10-50%.”\n[...]\nThank you very much for your positive comments."}, {"round": 2, "reviewer_comments": {"reviewer_1": "I am satisfied with the revisions and agree to accept the manuscript.", "reviewer_2": "In the revised version of the manuscript, the authors addressed my minor concerns, however my main criticism was not addressed: this manuscript combines established methodologies to tackle a synthetic challenge. Albeit the approach is interesting, I do not believe the incremental advancement reaches the threshold of conceptual novelty typically expected for a high-impact journal such as Nature Communications.", "reviewer_3": "Revision#1\nThe authors have effectively positioned their work within the broader context of the field, highlighting both the persistent challenges in quaternary center formation and the innovative approaches being developed to overcome these limitations.\nThis work represents a meaningful advancement to the synthetic toolbox available for constructing quaternary carbon centers. The methodology presented:\nOffers a practical and efficient approach to accessing these sterically congested frameworks. Demonstrates good substrate scope and functional group tolerance to some extent. The authors have made appropriate changes to improve the quality of the presentation which was not well explained. The work has clear potential for application in complex molecule synthesis, including natural products and pharmaceutical targets"}, "author_response": "Point-by-point response to the reviewers\nMany thanks for the three reviewers’ insightful, helpful and useful suggestions and\ncomments, which are very helpful for us to improve the quality of our manuscript.\nREVIEWERS' COMMENTS\nReviewer #1 (Remarks to the Author):\nI am satisfied with the revisions and agree to accept the manuscript.\nOur answer: Thank you very much for your positive comments.\nReviewer #2 (Remarks to the Author):\nIn the revised version of the manuscript, the authors addressed my minor\nconcerns, however my main criticism was not addressed: this manuscript\ncombines established methodologies to tackle a synthetic challenge. Albeit the\napproach is interesting, I do not believe the incremental advancement reaches\nthe threshold of conceptual novelty typically expected for a high-impact journal\nsuch as Nature Communications.\nOur answer: Thank you very much for your comments. As emphasized in the\nrevised Introduction and Discussion, our approach addresses a long-standing\nlimitation in quaternary center construction by enabling efficient formation\nunder conditions that are orthogonal to many existing strategies.\nReviewer #3 (Remarks to the Author):\nRevision#1\nThe authors have effectively positioned their work within the broader context of\nthe field, highlighting both the persistent challenges in quaternary center\nformation and the innovative approaches being developed to overcome these\nlimitations.\nThis work represents a meaningful advancement to the synthetic toolbox\navailable for constructing quaternary carbon centers. The methodology\npresented:\nOffers a practical and efficient approach to accessing these sterically congested\nframeworks. Demonstrates good substrate scope and functional group\ntolerance to some extent. The authors have made appropriate changes to\nimprove the quality of the presentation which was not well explained. The work\nhas clear potential for application in complex molecule synthesis, including\nnatural products and pharmaceutical targets\nOur answer: Thank you very much for your positive comments."}]

Decision letter