Ru-Catalyzed One-Pot Synthesis of Heterocyclic Backbones

Round 1

Reviewer 1 Report

The manuscript titled as "Ru-Catalyzed One-Pot Synthesis of Heterocyclic Backbones" by Saeed Balalaie and co-workers highlighted the ruthenium-catalyzed organic transformations in a one-pot manner to achieve heterocyclic backbones, including indoles, benzofurans, indazoles, pyrans, pyrimidines, quinolines, and isoquinolines. This review is important for this field and well organized. Only one suggestion: heterocyclic backbones should be added as keywords.

Author Response

Dear Esteemed Reviewer,

I wish you and your family a happy new year that brings you happiness, health, peace, and luck.

 

Thank you for your revision about my submitted article entitled:

 “Ru-Catalyzed One-Pot Synthesis of Heterocyclic Backbones”

We are very grateful for your valuable comments in this revise, which helped us improve the manuscript significantly. We thank you for your interest in our work and for helpful comments that will dramatically improve the manuscript, and we have tried to do our best to respond to the points raised. As indicated below, we have checked all the general and specific comments provided by you and have made necessary changes accordingly to your indications.

You may kindly find step-by-step responses by your comments below.

 

The manuscript titled as "Ru-Catalyzed One-Pot Synthesis of Heterocyclic Backbones" by Saeed Balalaie and co-workers highlighted the ruthenium-catalyzed organic transformations in a one-pot manner to achieve heterocyclic backbones, including indoles, benzofurans, indazoles, pyrans, pyrimidines, quinolines, and isoquinolines. This review is important for this field and well organized. Only one suggestion: heterocyclic backbones should be added as keywords.

• Response:

Thanks for your positive sight on this manuscript. The keyword was added.

 

Sincerely yours,

Saeed Balalaie

Reviewer 2 Report

Ru-Catalyzed One-Pot Synthesis of Heterocyclic Backbones (review) describes the ruthenium complexes as remarkable catalysts for the C–H activation approaches and organic transformations. Specifically for the synthesis of heterocyclic backbones, including indoles, benzofurans, indazoles, pyrans, pyrimidines, quinolines, and isoquinolines. The manuscript is well written, a very complete work. Therefore I recommend that it be accepted for publication in Catalysts after minor revision.

oxa-Michael addition in the Scheme 7 it is ok, bu oxa-Michael addition in line 110, page 6 Scheme 8 it is not correct

In the Scheme 15, R' should be R

In the structure 49 page 11 N-R2 should be N-R1

In the Scheme 20, check the position of R1 in all structures

homogenize the position of R1 in the Scheme 23

homogenize the position of R2 in the Scheme 27

homogenize R or Ph in the Scheme 29

Author Response

Dear Esteemed Reviewer,

I wish you and your family a happy new year that brings you happiness, health, peace, and luck.

 

Thank you for your revision about my submitted article entitled:

 “Ru-Catalyzed One-Pot Synthesis of Heterocyclic Backbones”

We are very grateful for your valuable comments in this revise, which helped us improve the manuscript significantly. We thank you for your interest in our work and for helpful comments that will dramatically improve the manuscript, and we have tried to do our best to respond to the points raised. As indicated below, we have checked all the general and specific comments provided by you and have made necessary changes accordingly to your indications.

You may kindly find step-by-step responses by your comments below.

 

Comments and Suggestions for Authors

Ru-Catalyzed One-Pot Synthesis of Heterocyclic Backbones (review) describes the ruthenium complexes as remarkable catalysts for the C–H activation approaches and organic transformations. Specifically for the synthesis of heterocyclic backbones, including indoles, benzofurans, indazoles, pyrans, pyrimidines, quinolines, and isoquinolines. The manuscript is well written, a very complete work. Therefore, I recommend that it be accepted for publication in Catalysts after minor revision.

 

 

• Response:

Thanks for your positive sight on this manuscript, your time, and valuable comments which helped us improve this manuscript.

 

oxa-Michael addition in the Scheme 7 it is ok, bu oxa-Michael addition in line 110, page 6 Scheme 8 it is not correct

• Response:

Thanks for your precision. “oxa” in scheme 8 was deleted, and it was corrected to “aza-Michael addition/oxidation”. The corresponding text was also corrected.

 

In the Scheme 15, R' should be R

• Response:

It was corrected.

 

In the structure 49 page 11 N-R2 should be N-R1

• Response:

It was corrected.

 

In the Scheme 20, check the position of R1 in all structures

• Response:

It was checked and corrected.

 

homogenize the position of R1 in the Scheme 23

homogenize the position of R2 in the Scheme 27

homogenize R or Ph in the Scheme 29

• Response:

All them were homogenize.

In scheme 29, the position of Ph was homogenized and R was corrected to Ph.

 

Sincerely yours,

Saeed Balalaie

Reviewer 3 Report

In the present review article, Balalaie and co-workers have highlighted important contributions to the synthesis of heterocyclic backbones in a one-pot manner under ruthenium catalysis. Although prof. Ackermann has reviewed the employment of Ru(II)-complexes for the activation of strategic C-H bonds in the construction of some heterocyclic systems under the assistance of carboxylate, the considered literature is only up to 2013. In 2021, Bruneau and Gramage-Doria published a review comprising the ruthenium-catalysis in cascade/one-pot transformations in general with no special attention to the preparation of heterocycles. Since they have covered articles up to 2020, the submitted review from Balalaie and co-workers may fill a gap specifically considering the advances on Ru-catalyzed one-pot synthesis of heterocyclic scaffolds up to 2022 with emphasis of annulation reactions. Therefore, I would like to recommend the submitted review article for publication as long as the issues listed on the attachment are addressed by the authors.

Comments for author File: Comments.pdf

Author Response

Dear Esteemed Reviewer,

I wish you and your family a happy new year that brings you happiness, health, peace, and luck.

 

Thank you for your revision about my submitted article entitled:

 “Ru-Catalyzed One-Pot Synthesis of Heterocyclic Backbones”

We are very grateful for your valuable comments in this revise, which helped us improve the manuscript significantly. We thank you for your interest in our work and for helpful comments that will dramatically improve the manuscript, and we have tried to do our best to respond to the points raised. As indicated below, we have checked all the general and specific comments provided by you and have made necessary changes accordingly to your indications.

You may kindly find step-by-step responses by your comments below.

 

Comments and Suggestions for Authors

In the present review article, Balalaie and co-workers have highlighted important contributions to the synthesis of heterocyclic backbones in a one-pot manner under ruthenium catalysis. Although prof. Ackermann has reviewed the employment of Ru(II)-complexes for the activation of strategic C-H bonds in the construction of some heterocyclic systems under the assistance of carboxylate, the considered literature is only up to 2013. In 2021, Bruneau and Gramage-Doria published a review comprising the ruthenium-catalysis in cascade/one-pot transformations in general with no special attention to the preparation of heterocycles. Since they have covered articles up to 2020, the submitted review from Balalaie and co-workers may fill a gap specifically considering the advances on Ru-catalyzed one-pot synthesis of heterocyclic scaffolds up to 2022 with emphasis of annulation reactions. Therefore, I would like to recommend the submitted review article for publication as long as the issues listed on the attachment are addressed by the authors.

• Response:

Thanks for your positive sight on this manuscript, your time, and valuable comments which helped us improve this manuscript.

 

1. While describing and highlighting the work done by the considered different authors, please use past tense forms of the employed verbs (E.g., Page 5, Line 88-89. Please change “generates” to generated). A complete revision regarding this issue is needed. Additionally, with special attention to pages 2-7, please try to have a connection/link between paragraphs. A great way to do that is to use transition words in conjunction with “In/As of 20XX (specify the date), lead author and co-workers reported/disclosed/demonstrated/established/illustrated/achieved…”. An interesting review from Catalyst to have as a model is found here.

• Response:

All paragraphs were reviewed and rewritten to use the past tense.

Thank you for the review sample. Unfortunately, we only had five days to update this paper, and changing the text is a crucial task that requires further time. In future works, we will therefore consider your opinion on the "connection of paragraphs." We appreciate your attention to this publication and the effort you invested in reading this review, checking all the references, and comparing the data on schemes with those reported in the related papers. This is significant to us. Thank you incredibly.

 

2. Please represent Cu(OAc)₂.H₂O as Cu(OAc)₂^.H₂O for all the instances. The “dot” should be superscripted.

• Response:

The dots in all schemes involving Cu(OAc)₂.H₂O were edited. And the caption of these schemes were highlighted.

3. Suggestion: It is interesting to have all the intermediate species from the Ru-catalyzed processes properly numbered/identified.

• Response:

Thank you for your suggestion. Although numbering the intermediates would have been better, we only had five days to complete the task. Unfortunately, we were unable to make this comment because, as you are aware, numbering requires extra time because each time a number is added, all other numbers must also be changed.

4. Please revise the mechanism depicted in Scheme 1. According to the authors of the referenced work, Tadigoppula and Kumar, the carbamide should be considered instead of having an imidate-like group complexed to Ru for intermediate 3. Upon the acetate anion's aid with acetic acid release, intermediate 4 is obtained (please do not forget to show the -O-H group). Additionally, please include the participation of the copper catalyst for the last mechanistic step while reoxidizing the Ru species.

 

• Response:

We eliminated the intermediate 3 and substituted it with the complexed Ru intermediate. The oxidizing role of Cu(II) was added in the last step. And the text was rewritten according to the changes.

5. Page 2, Line 58. Please change “pyrazolone 7” to “pyrazolones 7”.

• Response:

It was corrected.

6. Page 4, Scheme 4. AgSbF6 is missing as the co-catalyst. Please include this information over or below the reaction arrow.

• Response:

It was added.

7. Page 4, Lines 79 and 80. The font size for “…xanthene products, respectively [28].” seems to differ from the rest of the paragraph. It should be adjusted.

• Response:

Thanks for your precision. It was corrected.

8. Page 4, Line 82. Please include a reference to figure 1 in the text.

• Response:

Figure 1 was cited in the text.

9. Page 4, Scheme 5. Since hydrogen gas and water are also products of the reaction, I would like to suggest their inclusion in the reaction scheme and a brief note in the text (Line 78) as “…to give the target product 13 plus hydrogen gas and water (Scheme 5)”.

• Response:

Thanks for your comment, H₂ and water was added to Scheme 5 and text was corrected.

10. Page 6, Scheme 8. It would be interesting to also include the “Reductive elimination saying” prior to the aza-Michael addition. Please replace “oxa-Michael” by “aza-Michael addition” in the scheme and on line 110 of the same page.

• Response:

Both “reductive elimination” and “aza-” were added to the scheme.

Since this reaction includes an oxidation process, “oxidation” was added after Michael addition. Also “aza” was also added to the text.

11. Page 7, Scheme 10. There is a typo for “ruthenium carben”. Please address this issue.

• Response:

It was corrected.

 

12. Page 7, line 138. Does the yield range of 41-80% reported in scheme 12 apply to reference 45 or 46? It has been noticed that both works comprise the synthesis of pyrrole and indole-fused isocoumarins from the same starting materials, but with different ruthenium catalysts ([RuCl(PySO3)(p-cym)] and [RuCl2(pcymene)]2, respectively). The second one gave the best results, and this scenario should be discussed in the review. Additionally, please highlight the importance of the performed DFT calculations by Yu et al. Were they useful to rationalize the observed regioselectivity?

• Response:

We appreciate your comment. Scheme 12 has been changed. Under the product yields, reference number 45 was inserted. The reaction conditions for reference 46 were then put beneath the reaction.

In the text, both the efficacy of [RuCl₂(pcymene)]₂ and the influence of solvent on the regioselectivity of this reaction are described.

We added the results obtained by DFT calculation: “They computed Gibbs free energy changes of the formed intermediates in different solvents, suggesting the more polar solvent, the more chemoselective product. This study also recommends the use of terminal alkynes, in the case of using unsymmetrical alkynes, to control the regioselectivity of this reaction.”

 

13. Page 8, Scheme 12. As a suggestion, it would become clearer to show 30 as depicted below. The numbering 30 and 5: is resulting in some confusion. You may also consider the dashing representation for 31.

• Response:

Thanks. The number 5 has been changed to 30.

 

14. Page 10, line 177. K2CO3 should be K₂CO₃.

• Response:

It had subscript numbers

 

15. Page 11, Scheme 17. Please number all structures.

• Response:

Thanks. Regarding the fact that we must explain all numbered structures in the text and that we have just discussed the application of this strategy to the synthesis of structure 47, we believe that it is not necessary to number all structures of scheme 17.

 

16. Page 11, Line 184. “Scheme 17. Synthesis of oxyavicine derivative.” Should be “Scheme 17. Synthesis of oxyavicine derivative 47.”

• Response:

Thanks. It was done.

 

17. Page 12, Scheme 19. According to reference 57, yields greater than 81% were obtained by its authors. Therefore, the yield range of 40-81% is not correct. Specifically for intermediate 52, the sulfur atom from sulfoximine is not protonated after the proto-demetalation step. Scheme 19 should be revised.

• Response:

We appreciate your consideration. The maximum yield has been adjusted to 85. We missed it previously. And the proton was removed from S.

 

18. Page 12, line 200. “amide 4” should be “amide 54”.

• Response:

Thanks for your precision. It was done.

 

19. Page 14, Line 216. “product 7” should be “product 63”. As a suggestion, try to rewrite the final sentence comprising lines 216 and 217 to better emphasize the photoluminescence properties of the obtained dimeric 2H-Pyrrolo[2,3-c]isoquinoline-2,5(3H)-diones and their importance.

• Response:

The product number has been updated.

The following explanation of the features of the products has been added to the text: “The products showed steady-state fluorescence emission with large Stokes shifts up to 5100 cm^-1. Moreover, cyclic voltammetry study displayed redox properties of products 63 due to reductive processes and enol-keto conversions.”

 

20. Page 15, Scheme 23. A double bond is missing for 63. Please revise its structure.

• Response:

It was corrected.

 

21. Page 16, Scheme 24. Instead of using “2” next to 65, please place it below its structure as “2.0 equiv” and include “1.0 equiv” for 64. Is the yield range for quinolines of type 69 not 72-86%? Please revise this information.

• Response:

The equivalents were added. This comment was also applied for Schemes 2, 3, and 15. The yields were corrected to 72-86.

 

22. Page 17, lines 242-243. “These heterocycles” is placed right after the isoquinoline paragraph, and it may be misleading. Suggestion = “As mentioned before in Schemes 6, 8, and 9, the reaction of nitrogenbased heterocycles with olefins under Ru-catalysis comprising electronegative groups, such as carboxylates, can afford five-membered fused heterocycles.”

• Response:

The equivalents were added. Thanks, the mentioned sentence was revised.

 

23. Page 18, Scheme 29 and Page 20, Scheme 32. Please show the release of methyl phenylsulfoxide in the presence of acetic acid, and keep the same representation for the aromatic moiety in all intermediates from the proposed mechanisms.

• Response:

In both schemes, the release of methyl phenylsulfoxide is now detectable.

Ar moieties for all species were displayed.

Regarding comment 21, the equivalents of 80 and diphenyl acetylene were added beneath them.

 

Sincerely yours,

Saeed Balalaie