Synthesis of Pentacycloundecane (PCUD) Based Spiro-Pyrano-Cage Framework via Ring-Closing Metathesis

Round 1

Reviewer 1 Report

This paper describes the synthesis of spiro-pyrano-cage molecules. The synthetic process was designed based on the combination of Diels-Alder reaction and [2+2] cycloaddition, Grignald reaction, and olefin metathesis. The developed method provided the products with very interesting cage structure. This reviewer thinks the present manuscript can be published in this journal after the following revisions.

The authors have mentioned that compound 17 is the target compound of this synthetic work. The reason for targeting this compound should be stated. It is unclear in the context of the current munuscript.

There is a typographical error in the structure of 14. In addition, I think authors should add a discussion of the reactivity of the allylation reaction in 14.

Author Response

Point-by-point response letter

We sincerely thank the reviewers for their valuable comments and suggestions. All the points raised by them are valuable for the betterment of the manuscript. We have addressed all the comments of the reviewers and revised the manuscript and supporting information accordingly. All the changes are highlighted in track change mode in the revised manuscript and supporting information. Herein, we write the point-by-point responses for all the comments (the comments are in blue and the responses are in black text).

Reviewer-1

This paper describes the synthesis of spiro-pyrano-cage molecules. The synthetic process was designed based on the combination of Diels-Alder reaction and [2+2] cycloaddition, Grignald reaction, and olefin metathesis. The developed method provided the products with very interesting cage structure. This reviewer thinks the present manuscript can be published in this journal after the following revisions.

We thank the reviewer for summerizing our work. The following comments have been addressed in the revised version.

1. The authors have mentioned that compound 17 is the target compound of this synthetic work. The reason for targeting this compound should be stated. It is unclear in the context of the current manuscript.

Response: We thank the reviewer for the valuable comment. We are interested in metathesis to expand the chemical space of the cage compounds. This is one of our major themes in cage molecules.

2. There is a typographical error in the structure of 14. In addition, I think authors should add a discussion of the reactivity of the allylation reaction in 14.

Response: We are indebted to the reviewer for raising this comment and for pointing out the mistake. The typographical error has been rechecked and corrected accordingly in the revised manuscript. The reactivity of the allylation reaction of 14 is because of the proximity of the carbonyls group in 13. We also got transannular product 15. In another instance like 16 we observed hydrogen bonding and therefore mono O-allylation was observed.

Reviewer-2

General Comments. The authors have presented a succinct but interesting paper on the synthesis of a pentacycloundecane (PCUD) based spiro-pyrano-cage framework. The article is generally well-written and sufficient evidence of product identity and purity has been provided. Recommendations to improve the manuscript are provided below.

We thank the reviewer for finding our work interesting. The following comments have been addressed in the revised version.

Editorial Comments.

17. Page 1, Line 17. As worded: “They are considered as a promising candidates…” Delete the word “a”.
18. Page 2, Line 45. As worded: “…we conceived ring-closing metathesis (RCM) approach…” Reword: “…we conceived a ring-closing metathesis (RCM) approach…”
19. Page 2, Line 52. As worded: “…hexacyclic dione 13 [21-22] was began with the preparation of…” Change the word “began” to “was begun”.
20. Page 3, Line 69. As worded: “…systems containing hetero atom via metathesis…” Change the word “atom” to “atoms”.
21. Page 3, Line 74. Misspelling. Change “triaallylated“ to “triallylated”.

Response: We are indebted to the reviewer for raising these comments and for pointing out the mistakes. All the Editorial Comment (a-e) has been rechecked and corrected accordingly in the revised manuscript.

Content Comments.

1. References listed include both historical and recent work in the subject area. They are satisfactory to give context to the accomplished synthesis work in the assembly of PCUD based caged compounds.

Response: We thank the reviewer for their valuable comment.

1. The authors have provided proton, carbon, DEPT-135 spectra for compounds prepared. A discussion of the assignment of protons and carbons in the final product (cage spiro-pyran 18) would be a great addition to the paper and would benefit the reader in supporting the final structure’s regio- and stereochemistry.

Response: We thank the reviewer for the valuable comment. A discussion of the assignment of protons and carbons in the final product (cage spiro-pyran 18) has been added accordingly in the revised manuscript.

Reviewer 2 Report

Review of Molbank-2150532

1. General Comments. The authors have presented a succinct but interesting paper on the synthesis of a pentacycloundecane (PCUD) based spiro-pyrano-cage framework. The article is generally well-written and sufficient evidence of product identity and purity has been provided. Recommendations to improve the manuscript are provided below.

2. Editorial Comments.

a.  Page 1, Line 17. As worded: “They are considered as a promising candidates…” Delete the word “a”.

b.  Page 2, Line 45. As worded: “…we conceived ring-closing metathesis (RCM) approach…” Reword: “…we conceived a ring-closing metathesis (RCM) approach…”

c. Page 2, Line 52. As worded: “…hexacyclic dione 13 [21-22] was began with the preparation of…” Change the word “began” to “was begun”.

d. Page 3, Line 69. As worded: “…systems containing hetero atom via metathesis…” Change the word “atom” to “atoms”.

e. Page 3, Line 74. Misspelling. Change “triaallylated“ to “triallylated”.

Content Comments.

a. References listed include both historical and recent work in the subject area. They are satisfactory to give context to the accomplished synthesis work in the assembly of PCUD based caged compounds.

b. The authors have provided proton, carbon, DEPT-135 spectra for compounds prepared. A discussion of the assignment of protons and carbons in the final product (cage spiro-pyran 18) would be a great addition to the paper and would benefit the reader in supporting the final structure’s regio- and stereochemistry.

Author Response

Point-by-point response letter

We sincerely thank the reviewers for their valuable comments and suggestions. All the points raised by them are valuable for the betterment of the manuscript. We have addressed all the comments of the reviewers and revised the manuscript and supporting information accordingly. All the changes are highlighted in track change mode in the revised manuscript and supporting information. Herein, we write the point-by-point responses for all the comments (the comments are in blue and the responses are in black text).

Reviewer-1

This paper describes the synthesis of spiro-pyrano-cage molecules. The synthetic process was designed based on the combination of Diels-Alder reaction and [2+2] cycloaddition, Grignald reaction, and olefin metathesis. The developed method provided the products with very interesting cage structure. This reviewer thinks the present manuscript can be published in this journal after the following revisions.

We thank the reviewer for summerizing our work. The following comments have been addressed in the revised version.

1. The authors have mentioned that compound 17 is the target compound of this synthetic work. The reason for targeting this compound should be stated. It is unclear in the context of the current manuscript.

Response: We thank the reviewer for the valuable comment. We are interested in metathesis to expand the chemical space of the cage compounds. This is one of our major themes in cage molecules.

2. There is a typographical error in the structure of 14. In addition, I think authors should add a discussion of the reactivity of the allylation reaction in 14.

Response: We are indebted to the reviewer for raising this comment and for pointing out the mistake. The typographical error has been rechecked and corrected accordingly in the revised manuscript. The reactivity of the allylation reaction of 14 is because of the proximity of the carbonyls group in 13. We also got transannular product 15. In another instance like 16 we observed hydrogen bonding and therefore mono O-allylation was observed.

Reviewer-2

General Comments. The authors have presented a succinct but interesting paper on the synthesis of a pentacycloundecane (PCUD) based spiro-pyrano-cage framework. The article is generally well-written and sufficient evidence of product identity and purity has been provided. Recommendations to improve the manuscript are provided below.

We thank the reviewer for finding our work interesting. The following comments have been addressed in the revised version.

Editorial Comments.

17. Page 1, Line 17. As worded: “They are considered as a promising candidates…” Delete the word “a”.
18. Page 2, Line 45. As worded: “…we conceived ring-closing metathesis (RCM) approach…” Reword: “…we conceived a ring-closing metathesis (RCM) approach…”
19. Page 2, Line 52. As worded: “…hexacyclic dione 13 [21-22] was began with the preparation of…” Change the word “began” to “was begun”.
20. Page 3, Line 69. As worded: “…systems containing hetero atom via metathesis…” Change the word “atom” to “atoms”.
21. Page 3, Line 74. Misspelling. Change “triaallylated“ to “triallylated”.

Response: We are indebted to the reviewer for raising these comments and for pointing out the mistakes. All the Editorial Comment (a-e) has been rechecked and corrected accordingly in the revised manuscript.

Content Comments.

1. References listed include both historical and recent work in the subject area. They are satisfactory to give context to the accomplished synthesis work in the assembly of PCUD based caged compounds.

Response: We thank the reviewer for their valuable comment.

1. The authors have provided proton, carbon, DEPT-135 spectra for compounds prepared. A discussion of the assignment of protons and carbons in the final product (cage spiro-pyran 18) would be a great addition to the paper and would benefit the reader in supporting the final structure’s regio- and stereochemistry.

Response: We thank the reviewer for the valuable comment. A discussion of the assignment of protons and carbons in the final product (cage spiro-pyran 18) has been added accordingly in the revised manuscript.