Direct Sulfoxidation of Aromatic Methyl Thioethers with Aryl Halides by Copper-Catalyzed C(sp³)–H Bond Activation

Round 1

Reviewer 1 Report

Dear colleague

,

Thank you for your article.

Here is some remarks.

Line 16 :

Change « rylbenzysufoxide » in arylbenzysufoxide 

Line 39 :

Reference is not labelled correctly « field .¹¹ must be read field.[11]

Line 64-65 :

The text should be written  with the words at the right place.

Change 

« It was delight to find that the electron-wirthdrawing effect of the trifluoromethyl group «  very strong »,… »

By

It was delight to find that the very strong electron-wirthdrawing effect of the trifluoromethyl group,… 

Line 73 :

Change « chlorlbenzene » in chlorobenzene

Change « (entry 4) » in (entry 6) 

Line 73-74 :

The text is not consistant with the data showed in table 3, where we find a yield of 63% for the entry 3

Correct or delete this line.

Line 17 :

Reference [17] can not be found in the references

Line 94 :

The intermediate 14 is not present in the Scheme 5

Line 108 :

Change « 3000plus » with 3000 plus 

Yours,

Author Response

Reviewer 1

Comment 1: Line 16: Change “rylbenzysufoxide” in arylbenzysufoxide. The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 2: Line 39: Reference is not labelled correctly “field.11 must be read field.[11]” The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 3: Line 64-65: The text should be written with the words at the right place. Change “It was delight to find that the electron-wirthdrawing effect of the rifluoromethyl group «very strong»,…»By It was delight to find that the very strong electron-wirthdrawing effect of the trifluoromethyl group,….” The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 4: Line 73: Change “chlorlbenzene” in chlorobenzene Change “(entry 4)” in (entry 6). The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 5: Line 73-74: The text is not consistant with the data showed in table 3, where we find a yield of 63% for the entry 3 Correct or delete this line. The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 6: Line 17: Reference [17] can not be found in the references. The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 7: Line 94: The intermediate 14 is not present in the Scheme 5. The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 8: Line 108: Change “3000plus” with 3000 plus. The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Reviewer 2 Report

RunshengXu,and co-workers reported Copper-Catalyzed Direct Sulfoxidationof Aromatic Methyl Thioethers with Aryl Halides by  C(sp³)-H Bond Activation.

Comments:

1)    Title of the paper itself is confusing and it should be changed.

2)    Manuscript is not properly written and it is full of grammatical and typographical errors. Manuscript should be rewritten completely.

3)    There is no proper optimization of the reaction with the catalyst loading, absence of the catalyst etc. Author should present a thorough optimization. 

4)    Mechanism C=O should be replaced with S=O

5)    In the supporting information author last name is missing and procedures are very poorly written, should be written properly. 

6)    In HRMS, the difference in calculated and observed mass is 0.0003 in every compound, which is very difficult to get. 

Based on these comments I recommend not to publish this paper.

Author Response

Reviewer 2

Comment 1: Title of the paper itself is confusing and it should be changed.

The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 2: Manuscript is not properly written and it is full of grammatical and typographical errors. Manuscript should be rewritten completely.

The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 3: There is no proper optimization of the reaction with the catalyst loading, absence of the catalyst etc. Author should present a thorough optimization.

The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 4: Mechanism C=O should be replaced with S=O.

The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 5: In the supporting information author last name is missing and procedures are very poorly written, should be written properly.

The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 6: In HRMS, the difference in calculated and observed mass is 0.0003 in every compound, which is very difficult to get.

The authors’ answer: Thanks for the referee’s good comment. The HRMS Spectrums have been added in the supporting information.

Reviewer 3 Report

See attached.

Comments for author File: Comments.pdf

Author Response

Reviewer 3

Comment 1: While the reaction shows equally effective in chloroform and dioxane, the yield is significantly low in DMF. Do the authors have any rationales for this solvent effect?

The authors’ answer: Thanks for the referee’s good comment. We have also tried other solvent, for example entry 15 and 16. However, the corresponding products were not satisfied. The main reason is that the alkalinity and coordination of DMF were inappropriate.

Comment 2: The substrate scope is limited to thioanisole bearing alkyl/halide groups. Only two examples of thioanisole with functional group (‐OMe) are provided. Given that there is a huge amount of possible functional groups on benzene ring, please provide some more examples of standard functional groups in organic synthesis, such as hydroxyl, aniline, ester, carboxylic acid, amide… The orthosubstituted thioanisole should also be considered in order to probe for steric effect.

The authors’ answer: Thanks for the referee’s good comment. The other huge amounts of possible functional groups have been employed in the reaction. However, the yields which we obtained were very low. And the steric effect is been studying now.

Comment 3: To demonstrate its capability, a gram‐scale experiment should be provided.

The authors’ answer: Thanks for the referee’s good comment. As the obtained results, the reaction capability is almost same when a gram-scale experiment.

Table 2. Copper-catalyzed sulfoxidation of thioanisoles 1 with bromobenzenes 2.^a

^aReaction conditions were 1 (0.5 mmol), 2 (0.6 mmol), Cu(OAc)₂ (10 mol%), DBU (2 equiv), 1,4-dioxane (3 mL), 110 °C for 10 h. ^bIsolated yield. ^c Reaction conditions were 1 (0.1 mol), 2 (0.12 mmol), Cu(OAc)₂ (10 mol%), DBU (2 equiv), 1,4-dioxane (3 mL), 110 °C for 10 h.

Comment 4: Please provide these two controlled experiments to support the claim that thioanisole is oxidized in situ, followed by a copper catalyzed cross coupling. Thioanisole is not too air sensitive, so probably it is the copper that promotes the oxidation of thioanisole.

The authors’ answer: Thanks for the referee’s good comment. We have done the two controlled experiments as the referee quested. The results showed both the two reaction proceeded smoothly.

Comment 5: The proposed mechanism is hard to read and understand and written unintelligibly. Intermediates 9, 12 & 13 in the proposed mechanism are not clearly drawn and represented especially their oxidation states. One would presume 9 is Cu(I) and this going by “At the reaction beginning, the ligand coordination process of Cu(OAc)2 and DBU generated intermediate 9” is very confusing and does not explain if Cu(II) was reduced. If however the authors are claiming that an oxidative addition occurs with 9 as Cu(II), it will make the copper intermediates 12 and 13 at +4 oxidation state, which has never been reported. An intermediate 14 is mentioned but not in the scheme 5.

The authors’ answer: Thanks for the referee’s good comment. We think the ligand coordination process of Cu(OAc)₂ and DBU generated intermediate 9 is possible Cu(I). Copper salt catalytic cycle is always Cu(I)/Cu(III). And we are using the 1D/2D ESI- HRMS and DFT to investigate the possibility reaction mechanism just now. We promise that once have the results, we will report our results in time.

Comment 6: It is known that sulfoxide under basic conditions can act as a single electron transfer reagent (See Murphy, J.A. et al J. Am. Chem. Soc. 2016, 138, 7402−7410). It is possible that this reaction involves radical processes like these two mechanisms:

Please provide controlled experiment with radical scavengers in excess (such as TEMPO), as well as controlled experiment where the anisole sulfoxide is submitted to the same reaction conditions excluding the Cu(OAc)2.

The authors’ answer: Thanks for the referee’s good comment. We think the reaction mechanism have many possibility. As our results domestication, the proposed reaction mechanism in the manuscript was most probably. And we are using the 1D/2D ESI- HRMS and DFT to investigate the possibility reaction mechanism just now.

The application of electrospray ionization mass spectrometry (ESI-MS) provides the key intermediates with mass information. The density functional theory (DFT) can compute the reaction pathways with respect to different energy prolfiles for intermediate species and transition states. We promise that once have the results, we will report our results in time.

Comment 7: Please provide a rationale why CuBr gave no reaction in catalyst screening.

The authors’ answer: Thanks for the referee’s good comment. Up to now, we have no idea of why CuBr gave no reaction. However, the probably reason is that the catalytically and coordination ability were inappropriate.

Comment 8: The manuscript is filled with so many grammatical mistakes and needs to be polished.

The authors’ answer: hanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 9: The last reaction in the SI is a NiBr2‐catalyzed cross coupling between thiophenol and trideuteromethylbenzene, which is not discussed in the manuscript. What is the point of this reaction?

The authors’ answer: Thanks for the referee’s good comment. There have a mistake. The corrections have been added in the revised SI.

Comment 10: Please show all of NMR peaks in the processed 1H‐NMR. The authors should show both processed peaks on 13C‐NMR and 1H‐NMR. Futhermore, the authors overused the term “multiplet” as it appeared that many peaks coined “multiplet” by the author are analysable.

The authors’ answer: Thanks for the referee’s good comment. There have a mistake. The corrections have been added in the revised SI.

Author Response File: Author Response.docx

Reviewer 4 Report

The manuscript is dealing with an interesting development in preparative organic chemistry. Good yield C-H activation reactions are particularly important. The present Referee advices the Editor to publish the paper with some small changes.

These are:

(1) References at the end of sentences should be given BEFORE the point and not after. For example, in row 20 one finds: ...materials.[3]   This should be correctly written as  ...materials [3].

(2) In the text one finds reference [17], but in the Reference list there are only 16 references. The lacking reference should be added.

(3) To Reference 16 (dealing with CO2 activation) a broader review should be added, as:

Caglioti, L., Micskei, K., Tacconi, L., & al., Carbon dioxide: A C-1 source for chemical industry. Chem. Today 2009, 27 (2) 18-22.

Author Response

Reviewer 4

Comment 1: References at the end of sentences should be given BEFORE the point and not after. For example, in row 20 one finds: ...materials.[3]   This should be correctly written as  ...materials [3].

The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 2: In the text one finds reference [17], but in the Reference list there are only 16 references. The lacking reference should be added.

The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Comment 3: To Reference 16 (dealing with CO2 activation) a broader review should be added, as:

Caglioti, L., Micskei, K., Tacconi, L., & al., Carbon dioxide: A C-1 source for chemical industry. Chem. Today 2009, 27 (2) 18-22.

The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

Round 2

Reviewer 2 Report

Author have answered the queries and provided the sufficient supporting information. I still see typographical and grammatical errors, should be fixed before publication.

Author Response

Reviewer 2

Comment 1: Author have answered the queries and provided the sufficient supporting information. I still see typographical and grammatical errors should be fixed before publication.

The authors’ answer: We are very grateful for the referee’s valuable comment. This manuscript has been checked for correct use of grammar and common technical terms, and edited to a level suitable for reporting research in MDPI scholarly.

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors need to address the questions and not defend them as 'will be reported in due course'. Especially so we have a responsibility to readers about the accuracy of the science reported in peer-reviewed journals. Therefore the authors should review their manuscript accordingly and make improvements as such. From the previous to current manuscript iteration there seems to be only cosmetic changes or text edits.   

C3) The authors could include their new gram-scale experiments into the manuscript and I am not sure why this wasn't done since they already did the experiments?

C4) Is this written in the MS?

C5) Can the authors further elaborate on the proposed mechanism. Scheme 5 should be drawn again showing the oxidation state of the Cu.

C6) These experiments should be simple and should be done!

Author Response

Reviewer 3

Comment 1: The authors need to address the questions and not defend them as 'will be reported in due course'. Especially so we have a responsibility to readers about the accuracy of the science reported in peer-reviewed journals. Therefore the authors should review their manuscript accordingly and make improvements as such. From the previous to current manuscript iteration there seems to be only cosmetic changes or text edits.

The authors’ answer: We are very grateful for the referee’s valuable comment. This manuscript has been checked for correct use of grammar and common technical terms, and edited to a level suitable for reporting research in MDPI scholarly.

Comment 3: To demonstrate its capability, a gram‐scale experiment should be provided.

The authors’ answer: Thanks for the referee’s good comment. As the obtained results, the reaction capability is almost same when a gram-scale experiment.

Table 2. Copper-catalyzed sulfoxidation of thioanisoles 1 with bromobenzenes 2^a.

^a Unless otherwise noted, reaction conditions were 1 (0.5 mmol), 2 (0.6 mmol), Cu(OAc)₂ (10 mol%), DBU (2 equiv), 1,4-dioxane (3 mL), 110 °C for 10 h. ^b Isolated yield. ^c Reaction conditions were 1 (0.1 mol), 2 (0.12 mmol), Cu(OAc)₂ (10 mol%), DBU (2 equiv), 1,4-dioxane (3 mL), 110 °C for 10 h.

Table 3. Copper-catalyzed sulfoxidation of aromatic methyl thioethers 1 with aryl chlorides 4 ^a.

^a Unless otherwise noted, reaction conditions were 1 (0.5 mmol), 4 (0.6 mmol), Cu(OAc)₂ (10 mol%), DBU (2 equiv), 1,4-dioxane (3 mL), 110 °C for 10 h. ^b Isolated yield. ^c Reaction conditions were 1 (0.1 mol), 2 (0.12 mmol), Cu(OAc)₂ (10 mol%), DBU (2 equiv), 1,4-dioxane (3 mL), 110 °C for 10 h.

Comment 4: Please provide these two controlled experiments to support the claim that thioanisole is oxidized in situ, followed by a copper catalyzed cross coupling. Thioanisole is not too air sensitive, so probably it is the copper that promotes the oxidation of thioanisole.

The authors’ answer: Thanks for the referee’s good comment. The corrections have been added in the revised manuscript.

We also have done the two controlled experiments (Scheme 5). The results showed both the two reaction proceeded smoothly.

Scheme 5. The two controlled experiments.

Comment 5: The proposed mechanism is hard to read and understand and written unintelligibly. Intermediates 9, 12 & 13 in the proposed mechanism are not clearly drawn and represented especially their oxidation states. One would presume 9 is Cu(I) and this going by “At the reaction beginning, the ligand coordination process of Cu(OAc)2 and DBU generated intermediate 9” is very confusing and does not explain if Cu(II) was reduced. If however the authors are claiming that an oxidative addition occurs with 9 as Cu(II), it will make the copper intermediates 12 and 13 at +4 oxidation state, which has never been reported. An intermediate 14 is mentioned but not in the scheme 5.

The authors’ answer: Thanks for the referee’s good comment. We think the ligand coordination process of Cu(OAc)₂ and DBU generated intermediate 9 is possible Cu(I). Copper salt catalytic cycle is always Cu(I)/Cu(III). The corrections have been added in the revised manuscript.

Scheme 6. A possible mechanism for copper-catalyzed direct sulfoxidation.

Comment 6: It is known that sulfoxide under basic conditions can act as a single electron transfer reagent (See Murphy, J.A. et al J. Am. Chem. Soc. 2016, 138, 7402−7410). It is possible that this reaction involves radical processes like these two mechanisms:

Please provide controlled experiment with radical scavengers in excess (such as TEMPO), as well as controlled experiment where the anisole sulfoxide is submitted to the same reaction conditions excluding the Cu(OAc)2.

The authors’ answer: Thanks for the referee’s good comment. The controlled experiment with radical scavengers in excess TEMPO has been done. Furthermore, the corresponding product yield as well as controlled experiment. As our results domestihcation, the proposed reaction mechanism in the manuscript was most probably.

Reaction conditions were 1 (0.5 mmol), 2 (0.6 mmol), Cu(OAc)₂ (10 mol%), DBU (2 equiv), 1,4-dioxane (3 mL), 110 °C for 10 h.

Author Response File: Author Response.pdf

Round 3

Reviewer 3 Report

For scheme 6 I see that the structures are not drawn properly and the same scheme that was drawn in reply letter is different from the version they submitted. 

The rest are OK.

Author Response

Reviewer 3

Comment 1: For scheme 6 I see that the structures are not drawn properly and the same scheme that was drawn in reply letter is different from the version they submitted.

The authors’ answer: Thanks for the referee’s good comment. The revised manuscript has been resubmitted. We are very appreciated for your help in improving the level of the manuscript.

Author Response File: Author Response.docx