Throwing Light on -O–O- Bond: Organic Peroxides in Visible-Light Photocatalysis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The review by Terent’ev and coworkers over the application and synthesis of peroxides through visible light photocatalysis will be a useful addition to the literature.  For example, I recently surveyed this general area of the literature and realize after seeing this manuscript that I had overlooked some key examples. The work is clearly laid out. The approach, for the most part based upon a paper-by-paper description, is clear but runs the risk of losing an overall perspective. the authors attempt to accommodate this with a mechanistic overview within the introduction.

The manuscript is well written and generally easy to follow.  Below, I have included some mior corrections and suggestions. 

Recent work of relevance: A recently published J. Org. Chem. paper that probably came after this review was put together seems very relevant to the topic.  The work compares the visible light photoredox cleavage of a variety of peroxides using three photoredox sensitizers offering very different reducing potentials and compares the results with reduction by Fe(II), Cu(I), and  an electrochemically forced photocatalyst.  Schuster, et al.  J. Org. Chem. 2025 90 (30), 10580-10587; DOI: 10.1021/acs.joc.5c00349

Introduction section: 

Might be useful to note within the text that one of main points of mechanistic difference is whether the peroxide is cleaved by the excited state of the photocatalyst or by a ground state radical anion generated by reaction of the excited photocatalyst with a sacrificial substrate.  

In one or more places in the review, the authors summarize papers  that claim visible light photoactivation of peroxides. It might be useful if the introduction might address at least briefly that a number of classes of peroxides undergo homolysis in the presence of UV light but there have been relatively few examples of activation at 400 nm and beyond; several will be presented here.  (As you will see, I have questions about whether several of these are actually sensitized by another reaction component).

I really like the layout of each reaction with the photocatalyst presented in an accompanying box; I would request that the box include the formula or name of the photocatalyst (which will make it easier when readers are referencing back to this.   My suggestion is that the each discrete photocatalysts be presented once graphically upon first usage and then after that rely on the formula.

Remaining suggestions and corrections organized by page number or section:

Scheme 4 and accompany text:  Given that the formula uses an abbreviation for the thioanthrone, the text should parenthetically use the same formula unless the boxed graphic is going to include:  Thioanthrone (TXT).  Note that I would not consider this a visible light photolysis (365 nm).

Scheme 5 may be mechanistically complex to the reader and no mechanism is discussed graphically or in the text.  If this is really photoredox cleavage of the peroxide with the catalyst recycled through oxidative decarboxylation of the substrate acid, it would be useful for that to be mentioned (the authors do a nice job of this for the mesityl acridinium system in the text associated with Scheme 10).

Scheme 6:  The bisquinoline is probably important enough to show the complex with Cu(I).  It might be useful to describe why photocatalysis is required given that Cu(I)•bisquinoline (presumably, much like Cu(I)•phenanthroline) is certainly capable of activating a diacyl peroxide without photolysis.

Page 7, line 175:  oxidized (not reduced).

Scheme 8:  Label Ir(ppy)3 in graphic box; also, this is Ir+3 as shown.

Text associated with Scheme 10:  Something that might be useful to note with the TiO2/TBHP system is that it is capable of generating sufficient flux  tBuOO• to not only initiate HAT reactions but also to trap intermediate carbon radicals to form dialkyl peroxides.

Scheme 12 and associated text:  Provide name of sensitizer (and then abbreviation, TPPT);  as mentioned before, helpful to put name or abbreviation in graphic box with PC.

Scheme 14 and associated text:  Is the recycling of the catalyst through oxidation of the hydroperoxide (to the radical) or oxidation of the intermediate carbon radical to a cation (to permit trapping by peroxide)? (Something like this is covered well in Scheme 31 and the associated text).

Scheme 15 and associated text: Label PC in graphic box and mention name in text that accompanies graphic. 

Scheme 16 and associated text:  No need for a full graphic but it would be helpful if text mentioned some idea of mechanism.  Is phosphorous-centered radical necessary for addition to alkene derived via oxidation of need a full scheme but useful to mention if this is driven by formation of P• arises by PC oxidation of H-phosphine oxide or via HAT from an oxy radical intermediate.  Also, is new C-O bond derived from trapping of an intermediate carbon by persistent peroxyl radical or by oxidation of carbon radical to cation and then trapping by TBHP.

Scheme 20 and associated text:  I was unaware that blue light was capable of activating TBHP; any chance this is the vinyl arene/heteroarenes or some derived impurities.

Scheme 22:  A full mechanistic scheme may not be necessary but it would be helpful to the reader to give an idea of some key intermediates.

Scheme 23 and associated text:  The efficiency for hetero- vs homocoupling is remarkable. Do the authors mention a basis for this?

Scheme 26 and associated text: If this is the first example of a reaction using a Ni(I) intermediate to capture an intermediate radical for subsequent C-C bond formation, might be helpful to briefly discuss this or show the key intermediates.

Scheme 51 and associated text:  The observation of reaction in the absence of any formal photocatalyst, suggesting that the substrate itself can serve as a photoredox catalyst, makes this transformation synthetically appealing,

Page 39, line 712:  biphasic dichloroethane/water system

Scheme 56 and associated text:  It would be helpful if the authors could speculate on the selectivity for these reactions stopping at the aldehyde stage (vs. further oxidation).

Scheme 62 and associated text:  Unclear what is meant by halogen-catalyzed?  No free halogen is shown in the reagent list. 

Scheme 63 and associated text:  suggest slight modification to say “…an intermediate, presumably an acyl hypoiodite,…”

Scheme 64 and associated text:  perhaps speculate on the role of the peroxide (for example, to oxidize Pd(II) to Pd(IV)?

Scheme 65 and associated text:  The compound/intermediate numbering is out of alignment between the scheme and the text. Also, could say “reacts with the protonated form of 170a to generate radical cation C…

Scheme 68 and associated text: Given the mechanism described, what is the purpose of the peroxide?

Scheme 69 and associated text: Clarify that DTBP generates secondary radicals via HAT from substrate.

Scheme 71:  Seems unlikely that visible light achieves homolysis of DTBP. 

 

 

 

  

Author Response

1. Recent work of relevance: A recently published J. Org. Chem. paper that probably came after this review was put together seems very relevant to the topic. The work compares the visible light photoredox cleavage of a variety of peroxides using three photoredox sensitizers offering very different reducing potentials and compares the results with reduction by Fe(II), Cu(I), and an electrochemically forced photocatalyst.  Schuster, et al.  Org. Chem. 2025 90 (30), 10580-10587; DOI: 10.1021/acs.joc.5c00349

Response: We are grateful for your suggestion. The corresponding article was cited and discussed in introduction.

 

2. Introduction section:

Might be useful to note within the text that one of main points of mechanistic difference is whether the peroxide is cleaved by the excited state of the photocatalyst or by a ground state radical anion generated by reaction of the excited photocatalyst with a sacrificial substrate.

Response: Thank you for helping to make the review more accessible. The scheme describing these two reaction pathways (Scheme 2) and the corresponding discussion have been moved to the introduction section and generalized.

 

3. In one or more places in the review, the authors summarize papers that claim visible light photoactivation of peroxides. It might be useful if the introduction might address at least briefly that a number of classes of peroxides undergo homolysis in the presence of UV light but there have been relatively few examples of activation at 400 nm and beyond; several will be presented here. (As you will see, I have questions about whether several of these are actually sensitized by another reaction component).

Response: Thank you for your valuable comment. The fact that various peroxides undergo homolysis under the influence of UV radiation is mentioned in the discussion of Scheme 1 in the introductory section. Also, several examples of such UV-driven homolysis are added to the "timeline of key discoveries" figure. The introduction section was updated to mention that the review describes papers postulating visible light-driven homolysis of peroxides. Such examples certainly deserve further investigation to exclude all alternative reaction routes.

 

4. I really like the layout of each reaction with the photocatalyst presented in an accompanying box; I would request that the box include the formula or name of the photocatalyst (which will make it easier when readers are referencing back to this. My suggestion is that the each discrete photocatalysts be presented once graphically upon first usage and then after that rely on the formula.

Response: The abbreviations for photocatalysts have been included in the boxes with their chemical formulas. From our point of view, introducing a structural formula for photocatalysts helps to improve the readability of the review. For example, several photocatalysts are mentioned repeatedly throughout all sections, which significantly complicates the search for the meanings of abbreviations.

 

Remaining suggestions and corrections organized by page number or section:

5. Scheme 4 and accompany text: Given that the formula uses an abbreviation for the thioanthrone, the text should parenthetically use the same formula unless the boxed graphic is going to include: Thioanthrone (TXT). Note that I would not consider this a visible light photolysis (365 nm).

Response: An abbreviation for the thioxanthone was added in the text. We agree that 365 nm is long-wave UV light. We kindly request that this article be retained for a comprehensive understanding of the subject.

 

6. Scheme 5 may be mechanistically complex to the reader and no mechanism is discussed graphically or in the text. If this is really photoredox cleavage of the peroxide with the catalyst recycled through oxidative decarboxylation of the substrate acid, it would be useful for that to be mentioned (the authors do a nice job of this for the mesityl acridinium system in the text associated with Scheme 10).

Response: To our disappointment, the authors didn’t investigate the mechanism of transformation in their study (new Scheme 6). We can propose that the process indeed initiates with the reduction of the peroxide by the excited form of the photocatalyst, followed by deprotonation of the substrate by the resulting benzoate anion. The formed anion is then oxidized by the oxidized form of the photocatalyst, generating an unstable O-centered radical that undergoes decarboxylation to afford a C-centered radical. Recombination of this radical with the aforementioned benzoyloxy radical yields the product.

 

7. Scheme 6: The bisquinoline is probably important enough to show the complex with Cu(I). It might be useful to describe why photocatalysis is required given that Cu(I)•bisquinoline (presumably, much like Cu(I)•phenanthroline) is certainly capable of activating a diacyl peroxide without photolysis.

Response: Thank you for your insightful comment. Indeed, the peroxide is reduced by copper(I) in the initial stage of the process, which doesn’t require light (new Scheme 7). The authors demonstrated that visible light initiates an LMCT process in the copper(II) carboxylate complex, leading to regeneration of copper(I) and the formation of the benzoyloxy radical. The discussion was added to the text.

 

8. Page 7, line 175: oxidized (not reduced).

Response: The mistake has been corrected.

 

9. Scheme 8: Label Ir(ppy)3 in graphic box; also, this is Ir+3 as shown.

Response: The scheme has been corrected.

 

10. Text associated with Scheme 10: Something that might be useful to note with the TiO2/TBHP system is that it is capable of generating sufficient flux tBuOO• to not only initiate HAT reactions but also to trap intermediate carbon radicals to form dialkyl peroxides.

Response: We acknowledge your suggestion. The recombination of these radicals was depicted in the scheme and discussed in the text.

 

11. Scheme 12 and associated text: Provide name of sensitizer (and then abbreviation, TPPT); as mentioned before, helpful to put name or abbreviation in graphic box with PC.

Response: Corrections were made.

 

12. Scheme 14 and associated text: Is the recycling of the catalyst through oxidation of the hydroperoxide (to the radical) or oxidation of the intermediate carbon radical to a cation (to permit trapping by peroxide)? (Something like this is covered well in Scheme 31 and the associated text).

Response: In this study authors postulated that recycling of the catalyst was through photoinduced ligand to metal charge transfer (LMCT) process.

 

13. Scheme 15 and associated text: Label PC in graphic box and mention name in text that accompanies graphic.

Response: Name of the photocatalyst was added to the text.

 

14. Scheme 16 and associated text: No need for a full graphic but it would be helpful if text mentioned some idea of mechanism. Is phosphorous-centered radical necessary for addition to alkene derived via oxidation of need a full scheme but useful to mention if this is driven by formation of P• arises by PC oxidation of H-phosphine oxide or via HAT from an oxy radical intermediate. Also, is new C-O bond derived from trapping of an intermediate carbon by persistent peroxyl radical or by oxidation of carbon radical to cation and then trapping by TBHP.

Response: The discussion of the mechanism has been added (new Scheme 17).

 

15. Scheme 20 and associated text: I was unaware that blue light was capable of activating TBHP; any chance this is the vinyl arene/heteroarenes or some derived impurities.

Response: Authors suggested that under blue LED TBHP undergoes O-O bond cleavage to form ^tBuO·, ^tBuOO^tBu and H₂O₂. Unfortunately, all literature data mentioned in the discussion mechanism part didn’t include any information about generation of alkoxy radicals from ^tBuOOH under 450-465 nm without photocatalysts of metals.

 

16. Scheme 22: A full mechanistic scheme may not be necessary but it would be helpful to the reader to give an idea of some key intermediates.

Response: Key intermediates have been included in the scheme (new Scheme 23).

 

17. Scheme 23 and associated text: The efficiency for hetero- vs homocoupling is remarkable. Do the authors mention a basis for this?

Response: In the SI, authors described the influence of the base used on the yield of homocoupling product 7a. The use of CF₃CO₂Na results in the formation of the heterocoupling product 3a, with traces of the heterocoupling product 3a observed. However, the utilization NaOAc or Na₂CO₃ led to the formation of homocoupling product 7a in 38% and 30% yield, respectively. Authors assumed that strong base increases the concentration of α-carbon radical leading to homocoupling product 7a formation.

 

18. Scheme 26 and associated text: If this is the first example of a reaction using a Ni(I) intermediate to capture an intermediate radical for subsequent C-C bond formation, might be helpful to briefly discuss this or show the key intermediates.

Response: The mechanism has been added to the scheme.

 

19. Scheme 51 and associated text: The observation of reaction in the absence of any formal photocatalyst, suggesting that the substrate itself can serve as a photoredox catalyst, makes this transformation synthetically appealing.

Response: The authors proposed that the reaction proceeds via the formation of a heteroarene-^tBuOOH complex. Under visible light (blue LED) this complex facilitates homolytic cleavage of ^tBuOOH leading to the ^tBuO∙ radical and ∙OH radical. ^tBuO∙ radical or ∙OH radical undergoes HAT from aldehyde to give the acyl radical and ^tBuOH or H₂O. The discussion was updated (new Scheme 52).

 

20. Page 39, line 712: biphasic dichloroethane/water system

Response: Corrections were made to the text.

 

21. Scheme 56 and associated text: It would be helpful if the authors could speculate on the selectivity for these reactions stopping at the aldehyde stage (vs. further oxidation).

Response: Likely, overoxidation did not occur due to the absence of oxidants: TBHP was consumed in aldehyde formation (the authors proposed that 1 equiv. of TBHP is required for aldehyde formation; we hypothesize that TBHP is additionally cleaved in the presence of the catalyst), and an argon atmosphere excluded oxygen.

 

22. Scheme 62 and associated text: Unclear what is meant by halogen-catalyzed? No free halogen is shown in the reagent list.

Response: The mistake has been corrected.

 

23. Scheme 63 and associated text: suggest slight modification to say “…an intermediate, presumably an acyl hypoiodite,…”

Response: Changes have been made.

 

24. Scheme 64 and associated text: perhaps speculate on the role of the peroxide (for example, to oxidize Pd(II) to Pd(IV)?

Response: Indeed, the function of the peroxide is to oxidize the Pd(II) complex to a Pd(IV).

 

25. Scheme 65 and associated text: The compound/intermediate numbering is out of alignment between the scheme and the text. Also, could say “reacts with the protonated form of 170a to generate radical cation C…

Response: Changes have been made.

 

26. Scheme 68 and associated text: Given the mechanism described, what is the purpose of the peroxide?

Response: The discussion of the mechanism (new Scheme 69) was revised.

 

27. Scheme 69 and associated text: Clarify that DTBP generates secondary radicals via HAT from substrate.

Response: Changes have been made.

 

28. Scheme 71: Seems unlikely that visible light achieves homolysis of DTBP.

Response: Based on experimental and literature data authors proposed that DTBP can undergo O-O cleavage under blue LED light to produce ^tBuO∙ radicals.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

In this manuscript, the author systematically reviews recent advances in the application of organic peroxides in visible-light photocatalysis. Several representative reaction systems are presented, illustrating the photocatalytic behavior of different organic peroxides. Visible-light photocatalysis offers a novel approach for the activation of organic peroxides, particularly through single-electron transfer via photoexcited catalysts, opening new dimensions in radical chemistry. The overall writing is generally satisfactory; however, prior to acceptance, the following major revisions should be addressed:

1. In the introduction, the author did not specify which key catalysts or reaction system breakthroughs drove the rapid development of this field during the 2000s-2010s. It is recommended to add 1-2 representative examples and briefly explain how they advanced new applications of organic peroxides.
2. While the reaction mechanisms are discussed in multiple sections, some of the schematic diagrams lack clarity in arrows and labeling of intermediates. It is suggested to uniformly use color coding for key intermediates and include brief descriptions in the figure captions to outline the electron- or energy-transfer pathways at each step, thereby improving readability and logical flow.
3. Although the article cites a substantial number of references, it lacks a comparative analysis of the strengths and weaknesses of different catalytic systems, such as metal-based versus organic photocatalysts. It is recommended to add concise summaries at the end of relevant sections, comparing the efficiency, selectivity, and substrate scope of various peroxides under different photocatalytic systems, so as to highlight emerging trends and remaining challenges in the field.
4. The current conclusion section primarily recaps existing progress without explicitly addressing the limitations of current research and future opportunities. It is recommended to add a paragraph discussing directions such as: "Energy transfer pathways in the photocatalysis of organic peroxides remain underexplored" and "How to further enhance the regioselectivity of C–H bond functionalization," thereby improving the article's insight and academic value.
5. The author should further incorporate recent studies to enhance the timeliness of the review, such as (e.g., Angew. Chem. Int. Ed. 2026, e21882; Org. Lett. 2025, 27, 7466; Org. Lett. 2025, 27, 7001).

 

Author Response

1. In the introduction, the author did not specify which key catalysts or reaction system breakthroughs drove the rapid development of this field during the 2000s-2010s. It is recommended to add 1-2 representative examples and briefly explain how they advanced new applications of organic peroxides.

Response: Thank you for your insightful comment. We added the historical time-line and the corresponding discussion in Introduction. The historical shortcut is now represented by a timeline-scheme showing key discoveries in photochemistry involving organic peroxides.

 

2. While the reaction mechanisms are discussed in multiple sections, some of the schematic diagrams lack clarity in arrows and labeling of intermediates. It is suggested to uniformly use color coding for key intermediates and include brief descriptions in the figure captions to outline the electron- or energy-transfer pathways at each step, thereby improving readability and logical flow.

Response: Thank you for your comment. Key intermediates are indicated by letters in the schemes and mentioned in the text. Intermediates formed from peroxides are highlighted in a single color.

 

3. Although the article cites a substantial number of references, it lacks a comparative analysis of the strengths and weaknesses of different catalytic systems, such as metal-based versus organic photocatalysts. It is recommended to add concise summaries at the end of relevant sections, comparing the efficiency, selectivity, and substrate scope of various peroxides under different photocatalytic systems, so as to highlight emerging trends and remaining challenges in the field.

Response: We appreciate your suggestion. Summaries was added to the end of sections 2 and 3.

 

4. The current conclusion section primarily recaps existing progress without explicitly addressing the limitations of current research and future opportunities. It is recommended to add a paragraph discussing directions such as: "Energy transfer pathways in the photocatalysis of organic peroxides remain underexplored" and "How to further enhance the regioselectivity of C–H bond functionalization," thereby improving the article's insight and academic value.

Response: The conclusion was revised according to the Reviewer’s comment.

 

5. The author should further incorporate recent studies to enhance the timeliness of the review, such as (e.g., Angew. Chem. Int. Ed. 2026, e21882; Org. Lett. 2025, 27, 7466; Org. Lett. 2025, 27, 7001).

Response: We are grateful for your suggestion. The corresponding articles were cited and discussed.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The review submitted to Chemistry has as main subject organic peroxides in photocatalysis, Alexander Terentev being the main author. The review is very elaborate, has 72 schemes, 105 references and 56 pages. The review has a great scientific impact and emphasizes the advancements of visible-light in some mediated reactions utilizing the large potential of organic peroxides for constructing different chemical bonds and therefore new molecules. This is an actual subject in organic chemistry with applications in many fields of science. The quality of the writing and drawing is quite high.

The Introduction part has 45 references and deals with details about peroxides, compounds characterized by a weak O–O bond, which is primarily responsible for their reactivity. These compounds have been widely utilized in various industrial processes, such as oxidants (including bleaching agents), antiseptics, radical initiators in polymerization, and reagents in rubber vulcanization. Numerous synthetic methods have been developed to produce organic peroxides from major classes of organic compounds, including alkenes, dienes, halogenated derivatives, carbonyl compounds, carboxylic acids, and their derivatives. For the synthesis usually are used available reagents, such as peroxides, ozone, molecular oxygen, hydrogen peroxide, and so on.

The second chapter demonstrates that peroxide are a source of oxygen-functional groups, that can be used in two ways, as oxidative or reductive quenching; as well, hydroperoxides can be employed. What is important in this review is the authors expertise previously demonstarted, for example their is available a method for activating titania under visible light, with the potential already demonstrated in the selective C–H peroxidation of barbituric acids and so on. Nowadays most photocatalytic system are primarily used for pollutants removal by oxidation. In this way, the authors expands the scope of the system used.

The third part of the review describes the use of peroxides as a source of carbon-functionality; the science behind all examples is well presented and genuine. A lot of examples are compiled and detailed.

The fourth part has as main topic peroxides as oxidants. In a similar way as previously, a good number of careful presented reactions are contained in this subchapter. 

The conclusion part is well developed and summarize the data embedded in this review. It focuses on processes spanning the use of peroxides as oxidants for photocatalyst regeneration to complex radical reactions in which peroxide–substrate redox transformations enable intermolecular C–C and C–O bond formation, very important types of reactions in organic synthetic chemistry (and not only).

As mentioned before, the paper ends with 105 references in a correct format. Based on all these, I recommend this work to be published as it is.

 

Author Response

We thank the reviewer for highly evaluating our review article.