ROTf-induced annulation of heteroatom reagents and unsaturated substrates leading to cyclic compounds

The development of metal-free organic reactions is one of the hotspots in the synthesis of cyclic compounds. ROTf (alkyl trifluoromethanesulfonates), due to their good electrophilicity, are powerful alkylating reagents at heteroatoms such as nitrogen, oxygen, sulfur and phosphorus to induce an electrophilic centre for carbon–carbon or carbon–heteroatom bond formation. Inspired by this chemistry, a variety of research concentrating on heterocycles synthesis has been carried out. In this review, we mainly summarize the ROTf-induced annulation of heteroatom reagents such as nitriles, carbodiimides, azobenzenes, isothiocyanates, aldehydes, isocyanates and phosphaalkene with themselves or alkynes to afford cyclic compounds.

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REVIEWER(S) REPORTS:
Associate Editor Comments to Author: RSC Associate Editor: 1 Comments to the Author: It is clear from the referee reports that the authors' presentation in this invited review has missed the mark. I agree with the referees that the language should be improved. However, I do disagree with the manner in which some of the criticisms were presented (particularly Referee 1). Nevertheless, the overall criticisms are valid.
As this was an invited review I would welcome a resubmission of a substantially revised manuscript that takes into account the criticisms raised by all three referees. Also, I strongly suggest modifying the text in such a way that it is more than just a list of what has been done. Are there obvious deficiencies in the literature that could be addressed by future researchers? Are there cases where these methods are dramatically better than alternatives? Where will we see the next advances in this area?
Reviewers' Comments to Author: Reviewer: 1 Comments to the Author(s) This review is basically a list of cyclization reactions brought about by treating various heteroatom-substituted compounds with MeOSO3CF3 in the presence of compounds containing triple or double bonds.
The quality of the English is poor and I am sending as an attachment a scan of a partially corrected copy.
My overall impression is that the presentation lacks much intellectual content--it is simply a list illustrated by exemplary equations. I think the work is more appropriate for a journal that specializes in heterocycles; the readers of such journals would have the motivation to examine the document. As far as I can make out from the on-line information about the journal the present type of review is outside the scope of the Royal Society Open Science Journal.

Reviewer: 2
Comments to the Author(s) The manuscript is a brief review of the triflate (ROTf)-induced reactions of heteroatom reagents and unsaturated substrates to afford cyclic compounds. In general, it is poorly written and the standard of English is disappointing. There is no original science in the paper, since it is a review -was it an invited review? The literature coverage is not sufficiently comprehensive to be a full review. Taking all these factors into account, I cannot recommend acceptance.

Reviewer: 3
Comments to the Author(s) This review manuscript from Zou et al. gives an overview of the use of alkyltriflates for activation of cationic pathways to promote a number of cascade processes. This mini-review covers a number of transformations, which usually result in the formation of cyclic products, discussing aspects of the substrate scope, giving examples and highlighting probable mechanistic pathways.
Unfortunately, the manuscript is lacking somewhat in the introductory content; the background and prior art is not discussed in any great detail and the topic of the review is not surmised particularly well. There are also numerous errors in the schemes as well as the text. The work discussed within the review itself, albeit interesting, is also very niche. There are only a few examples presented and only 11 papers cited, the vast majority of which are from the authors own group. Hence, I do not find this work of sufficient value for publication in Royal Society Open Science.

Is the language acceptable? Yes
Is it clear how to access all supporting data? Not Applicable

Do you have any ethical concerns with this paper? No
Have you any concerns about statistical analyses in this paper? No

Recommendation?
Accept with minor revision (please list in comments)

Comments to the Author(s)
This resubmitted manuscript is significantly improved from it's previous form and the authors have addressed the majority of the issues risen by the reviewers on the initial submission. I do think that the document is somewhat lacking in the conclusions section, it would be better to see more of a comparative summary which highlights the benefits of these methodologies over the current state-of-the-art. Why is this approach better? What unique reactivities are there? Does the methodology provide access to unique architectures? Where will these methodologies lead in the future?
As this is an invited review I am inclined to accept this minireview with the caveat that the authors expand somewhat upon their closing remarks.

Are the interpretations and conclusions justified by the results? Yes
Is the language acceptable? Yes

Do you have any ethical concerns with this paper? No
Have you any concerns about statistical analyses in this paper? No

Recommendation?
Accept as is

Comments to the Author(s)
This review manuscript entitled "ROTf-induced annulation of heteroatom reagents and unsaturated substrates leading to cyclic compounds" by Xi and coworkers gives an overview of the use of alkyltriflates for the synthesis of various cyclic compounds. Three reviewers have put forward some suggestions about the original manuscript. The authors have corrected the whole manuscript carefully. This reviewer recommend acceptance of this revised review as it.

09-Oct-2018
Dear Professor Xi: Title: ROTf-induced annulation of heteroatom reagents and unsaturated substrates leading to cyclic compounds Manuscript ID: RSOS-181389 Thank you for submitting the above manuscript to Royal Society Open Science. On behalf of the Editors and the Royal Society of Chemistry, I am pleased to inform you that your manuscript will be accepted for publication in Royal Society Open Science subject to minor revision in accordance with the referee suggestions. Please find the reviewers' comments at the end of this email.
The reviewers and handling editors have recommended publication, but also suggest some minor revisions to your manuscript. Therefore, I invite you to respond to the comments and revise your manuscript.
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Once again, thank you for submitting your manuscript to Royal Society Open Science. The chemistry content of Royal Society Open Science is published in collaboration with the Royal Society of Chemistry. I look forward to receiving your revision. If you have any questions at all, please do not hesitate to get in touch. ************************************* RSC Associate Editor Comments to the Author: I agree with the reviewers that the revised manuscript is much improved over the previous version. At the same time, I agree with the suggestion that the conclusion and outlook could be expanded and improved upon. ************************************** Reviewer comments to Author: Reviewer: 3 Comments to the Author(s) This resubmitted manuscript is significantly improved from it's previous form and the authors have addressed the majority of the issues risen by the reviewers on the initial submission. I do think that the document is somewhat lacking in the conclusions section, it would be better to see more of a comparative summary which highlights the benefits of these methodologies over the current state-of-the-art. Why is this approach better? What unique reactivities are there? Does the methodology provide access to unique architectures? Where will these methodologies lead in the future?
As this is an invited review I am inclined to accept this minireview with the caveat that the authors expand somewhat upon their closing remarks.

Reviewer: 4
Comments to the Author(s) This review manuscript entitled "ROTf-induced annulation of heteroatom reagents and unsaturated substrates leading to cyclic compounds" by Xi and coworkers gives an overview of the use of alkyltriflates for the synthesis of various cyclic compounds. Three reviewers have put forward some suggestions about the original manuscript. The authors have corrected the whole manuscript carefully. This reviewer recommend acceptance of this revised review as it.
Author's Response to Decision Letter for (RSOS-181389.R0) Decision letter (RSOS-181389.R1) 16-Oct-2018 Dear Professor Xi: Title: ROTf-induced annulation of heteroatom reagents and unsaturated substrates leading to cyclic compounds Manuscript ID: RSOS-181389.R1 It is a pleasure to accept your manuscript in its current form for publication in Royal Society Open Science. The chemistry content of Royal Society Open Science is published in collaboration with the Royal Society of Chemistry.
The comments of the reviewer(s) who reviewed your manuscript are included at the end of this email. It is clear from the referee reports that the authors' presentation in this invited review has missed the mark. I agree with the referees that the language should be improved. However, I do disagree with the manner in which some of the criticisms were presented (particularly Referee 1). Nevertheless, the overall criticisms are valid.
As this was an invited review I would welcome a resubmission of a substantially revised manuscript that takes into account the criticisms raised by all three referees. Also, I strongly suggest modifying the text in such a way that it is more than just a list of what has been done. Are there obvious deficiencies in the literature that could be addressed by future researchers? Are there cases where these methods are dramatically better than alternatives? Where will we see the next advances in this area? Answer: 1. We reorganized the manuscript and addressed ROTf-induced annulation as metal-free methods for synthesis of heterocycles.
In addition, a variety of relative literatures has been discussed and reaction pathways have been described.

Respond to the Reviewer 1
Comments to the Author(s) This review is basically a list of cyclization reactions brought about by treating various heteroatom-substituted compounds with MeOSO3CF3 in the presence of compounds containing triple or double bonds.
The quality of the English is poor and I am sending as an attachment a scan of a partially corrected copy.
My overall impression is that the presentation lacks much intellectual content--it is simply a list illustrated by exemplary equations. I think the work is more appropriate for a journal that specializes in heterocycles; the readers of such journals would have the motivation to examine the document. As far as I can make out from the on-line information about the journal the present type of review is outside the scope of the Royal Society Open Science Journal.

Respond to the Reviewer 2
Comments to the Author(s) The manuscript is a brief review of the triflate (ROTf)-induced reactions of heteroatom reagents and unsaturated substrates to afford cyclic compounds. In general, it is poorly written and the standard of English is disappointing.
There is no original science in the paper, since it is a review -was it an invited review?
The literature coverage is not sufficiently comprehensive to be a full review. Taking all these factors into account, I cannot recommend acceptance.

Answer:
1. We reorganized the manuscript and the English proof reading was carefully done with the assistance of a native English speaker. 3. We carefully checked the literature and more references were added appropriately.

Respond to the Reviewer 3
Comments to the Author(s) This review manuscript from Zou et al. gives an overview of the use of alkyltriflates for activation of cationic pathways to promote a number of cascade processes. This mini-review covers a number of transformations, which usually result in the formation of cyclic products, discussing aspects of the substrate scope, giving examples and highlighting probable mechanistic pathways. Unfortunately, the manuscript is lacking somewhat in the introductory content; the background and prior art is not discussed in any great detail and the topic of the review is not surmised particularly well. There are also numerous errors in the schemes as well as the text. The work discussed within the review itself, albeit interesting, is also very niche. There are only a few examples presented and only 11 papers cited, the vast majority of which are from the authors own group. Hence, I do not find this work of sufficient value for publication in Royal Society Open Science.

As questioned by Reviewer 3, we have made correction for
Schemes and the text.
3. We carefully checked the literature and more references were added appropriately in the revised manuscript.

Summary
The development of metal-free organic reactions is one of the hotspots in the synthesis of cyclic compounds. ROTf (alkyl trifluoromethanesulfonates), due to their good electrophilicity are powerful alkylating reagents at heteroatom such as nitrogen, oxygen, sulfur, and phosphorus to induce an electrophilic center for carbon-carbon or carbon-heteroatom bond formation. Inspired by this chemistry, a variety of researches concentrating on heterocycles synthesis has been carried out.
In this review, we mainly summarize the ROTf-induced annulation of heteroatom reagents such as nitriles, carbodiimides, azobenzenes, isothiocyanates, aldehydes, isocyanates, and phosphaalkene with themselves or alkynes to afford cyclic compounds. ROTf (alkyl trifluoromethanesulfonates) are powerful alkylating reagents, which are frequently utilized in alkylation of nucleophiles [3].

ROTf-induced annulation of nitrogen-
containing substrates with unsaturated compounds 3.1 ROTf-induced annulation of nitriles Nitriles as unsaturated heteroatom reagents could react with ROTf to form N-alkylated nitriliums, which were well investigated by Booth [9] in 1980. However, electrophilicity of N-alkylated nitriliums has rarely been utilized in further reactions until recently. In 2014, our group [22] reported MeOTf-induced carboannulation of arylnitriles and aromatic alkynes to construct indenones 1 (Scheme 2). Triflate 3 was isolated one heterocycle. Although transition-metal-catalyzed annulation of benzimide or arylcarbonyl and arylnitrile with alkynes to formation of indenones has been reported [23], this reaction reveals a simple reaction process for the synthesis of indenones under metal-free.

R. Soc. open sci.
Arylnitriles and alkynes could be induced by MeOTf to afford indenones via intermediate I-5. We envisioned the utilization of alkylnitriles, which lack an aryl group for the ring closure, might lead to a different way for ring formation. To our delight, reaction of alkylnitriles, alkynes, and MeOTf indeed afforded tetrasubstituted NHpyrroles 4 with high regioselectivity. The structure includes one carbon from ROTf to join the pyrroles [24] (Scheme 3). It is noteworthy that the cyclized pyrrole captures another nitrilium leading to substituted 2acyl-NH-pyrroles after hydrolysis. When EtOTf was utilized instead of MeOTf, the product 5 was obtained. This reaction provides a practical and convenient method for the synthesis of multiply substituted 2acylpyrroles from readily available starting materials in a one-pot reaction.  Furthermore, unsymmetrical alkynes such as terminal alkynes, (bromoethynyl) benzenes, even alkynes containing ester group could be applied in this reaction. In addition, alkyltriflates bearing C-C triple bond gave polycyclic quinolines 11d via sequent cyclization process.
Great effort has been paid in transformation of thioalkoxyl group such as oxidation, reduction, and cross-coupling reaction, which make this method more powerful in organic synthesis [27]. This reaction represents a concise, metal-free, and one-pot method for synthesis of functionalized quinolines.

ROTf-induced annulation of alkylisothiocyanates
Substitution of arylisothiocyanates with alkylisothiocyanates that lack an aryl group for the ring closure, might lead to a new reaction mode. To our delight, the reaction proceeded well to afford indenone 12 after hydrolysis [28]. A range of arylalkynes could be employed in this reaction. The representative results are summarized in Scheme 9. A plausible mechanism is also described in Scheme  More recently, Li and co-workers [29] reported MeOTf-induced intramolecular cyclization of isothiocyanates to afford 1-(methylthio)-3,4-dihydroisoquinolines 13 (Scheme 10). The reaction may process by a tandem electrophilic activation and intramolecular Friedel-Crafts reaction.

ROTf-induced annulation of phosphorus-containing substrates
In 2006, Gates and co-workers [34]  heterocycles, which may be used as a propagating species in the cationic polymerization of phosphaalkenes.

Conclusion and future outlook
ROTf has been a powerful reagent in organic synthesis featuring efficient, metal-free, and easy of handing. A range of heteroatom-