Nucleophilic Reactions Using Alkali Metal Fluorides Activated by Crown Ethers and Derivatives

Round 1

Reviewer 1 Report

 

This is an interesting and compact review on the use of crown ethers for promoting organic reactions, mainly nucleophilic substitution. Some examples of Michael and epoxidation reactions are also described. The emphasis is on the role of ion pairs, an important concept that opens many possibilities of crown ether design for tailor-made reactions. The manuscript describes the initial applications of crown ether in nucleophilic substitution reactions and the idea that crown ether would induce the formation of free ions. Then, the authors show how this initial misconception was proven to be wrong via both experimental and theoretical studies. In the sequence, the authors discuss how this new paradigm of ion pair has led to the design of new derivatives of crown ethers having both cation and anion interaction, including calixarenes, hydro-crowns and thiourea-crown-ether. The review also discusses some unimolecular processes and the use of asymmetric crown ethers to induce the formation of chiral products. This manuscript is a good initial reference for the newcomers to the field and also should inspire more research on this area. I think that the manuscript deserves publication, with minor corrections indicated below. No additional review is needed.

Some minor corrections:

On page 4, line 118, “was lowered 14.0 kcal/mol” should be “was lowered from 24 to 14 kcal/mol”.

Page 6, line 201, appears “[…]”. It should cite the Figure.

 

Page 7, line 215, there is an extra “within 12 hrs”.

Author Response

Rev. 1

 

On page 4, line 118, “was lowered 14.0 kcal/mol” should be “was lowered from 24 to 14 kcal/mol”.

Corrected.

Page 6, line 201, appears “[…]”. It should cite the Figure.

“[…]” is deleted.

Page 7, line 215, there is an extra “within 12 hrs”.

“within 12 hrs” is deleted.

Reviewer 2 Report

The authors review the recent progress in nucleophilic reactions using metal salts and facilitated by crown ethers and derivatives. The authors selected an excellent topic but the execution is poor and massive work needs to be done before it can be publish.

1. The scope of the review needs to be clearly stated. What is the period that is reviewed? What 'recent' means? If the review is based on mechanism, then organise the review based on different mechanisms.

2. The organisation is messy. Chapter 1 and 3 is based on compounds. Chapter 2 is based in mechanism and Chapter 4 is based on combination of catalysts and Chapter 5 is based in asymmetric reactions. The authors are just confused.

3. It is clear that the authors took many diagrams directly from other journals. This is not acceptable. It has either be re-drawn or permission received from all other journals that diagrams are taken. We suggest to re-drawn all diagrams.

4. Other issues:

1.     Figure 14a missing label

2.     Figure 14b: Form the energy diagram, SIP_2 should be the main mechanism instead of CIP. The author fail to note the Curtin-Henderson principle, which is essential for the explanation of energy diagram.

3.     In part 4, the synergistic effect is discussed in a rash manner.

4.     In part 5, none of the asymmetric fluorination is presented, which is not related to the topic of this review. More examples of crown ether catalyzed asymmetric synthesis could be found in ref1.

5.     Tables, schemes, and Figures are not in the same format.

Author Response

Rev. 2

 

The authors review the recent progress in nucleophilic reactions using metal salts and facilitated by crown ethers and derivatives. The authors selected an excellent topic but the execution is poor and massive work needs to be done before it can be published.

1.The scope of the review needs to be clearly stated. What is the period that is reviewed? What 'recent' means? If the review is based on mechanism, then organise the review based on different mechanisms.

The 'recent' in the Abstract is revised to 'in the past decades '. The mechanism discussed in this Review is entirely the CIP mechanism except that for Michael reactions. Since the latter is only a minor part, it does not seem to be necessary to organize the text based on different mechanisms. However, we follow the comments by the Reviewer next.

2. The organisation is messy. Chapter 1 and 3 is based on compounds. Chapter 2 is based in mechanism and Chapter 4 is based on combination of catalysts and Chapter 5 is based in asymmetric reactions. The authors are just confused.

Indeed, it looks messy. We reorganized the text by placing the Section “Mechanistic features for crown ether - facilitated S_N2 reactions” after “Synergetic effects of crown ether/alcohol and /ammonium combination”. Figure & Reference numbers are all rearranged.

3. It is clear that the authors took many diagrams directly from other journals. This is not acceptable. It has either be re-drawn or permission received from all other journals that diagrams are taken. We suggest to re-drawn all diagrams.

We revised the Figures completely, so that no copyright problems may arise at all.

4. Other issues:
5. Figure 14a missing label: corrected

 

2. Figure 14b: Form the energy diagram, SIP_2 should be the main mechanism instead of CIP. The author fail to note the Curtin-Henderson principle, which is essential for the explanation of energy diagram.

 

We thank the Reviewer for pointing this out. Indeed, the difference in the Gibbs free energies of TSs via CIP_2 and SIP_2 are so similar that they are considered to contribute to the fluorination nearly equally. We revise the paragraph from:

 

The Gibbs free energies of activation G^‡ for alternative reaction paths relative to the free reactants were the pivotal parameters determining the relative contributions of the CIP vs. SIP routes. We found that the CIP mechanism via the lowest G^‡ via the the TSs (TS_CIP_1) and (TS_CIP_2) (R_K-O = 2.555, 2.553 Å) predominate the S_N2 cyanation.

 

To:

 

The Gibbs free energies of the TSs for two reaction pathways via (TS_CIP_2) and (TS_SIP_2) are very similar (the difference is only 0.2 kcal/mol), thus they may be considered to contribute almost equally to the cyanation reaction.  

 

3. In part 4, the synergistic effect is discussed in a rash manner.

This part is an important ingredient in our present Review, but unfortunately, not many examples were published yet. The mechanism is not well-known, thus no discussion can be given at this point. Mechanistic study is in progress in our lab.

 

We add the following paragraph to supplement our discussion for the synergistic effects:

 

This line of works looks promising, which in line with the intramolecular combined use of BINOL and chiral OligoEGs for asymmetric S_N2 reactions described below.

 

We also discussed the works by Maruoka and co-workers by adding a paragraph:

 

Maruoka and co-workers’ [60] observation of dramatic rate increase of alkylation by using crown ether/achiral quaternary ammonium salt combinations as PTCs is another excellent example along this line of work. This scheme looks promising, which in line with the intramolecular combined use of BINOL and chiral OligoEGs for asymmetric S_N2 reactions described below,

 

4. In part 5, none of the asymmetric fluorination is presented, which

h is not related to the topic of this review. More examples of crown ether catalyzed asymmetric synthesis could be found in ref1.

We are aware of many more examples of crown ether catalyzed asymmetric synthesis, but we cannot hope to be exhaustive in this brief Review, since our focus is mainly on mechanism. For example, there exists recent progress in transition-metal assisted of crown ether catalyzed asymmetric synthesis. We added a short sentence for readers’ guide to the latter topic:

 

There also exist many examples for crown ether catalyzed asymmetric synthesis, for example, transition-metal assisted of crown ether catalyzed asymmetric synthetic methods. However, since we cannot hope to be exhaustive in this brief Review, we only cite a nice recent Review [63] for this topic.

 

5. Tables, schemes, and Figures are not in the same format: We revised the Tables, schemes, and Figures.

Reviewer 3 Report

The authors presented a review article which covers the nucleophilic reactions using alkali metal fluorides activated by Crown Ethers and their derivatives. However, since the introduction, they extended their discussion examining in general the phase transfer catalyzed reaction promoted by crown ethers whose mechanism is characterized by a contact ion pair. The topic covered is interesting and, to the best of my knowledge, poorly addressed sistematically so far. Considered this, it may be of considerable interest for the readers of Catalysts. It should be noted, however, that the general setting and the shape might be improved, and the topics must be better analyzed, also reporting some previous works, here totally neglected, as those reported below. Some aspects, as numbering, originality of the artworks, full and correct citations, are absolutely key factors for this article to be published. Below is a list of important improvements to be made.

 

 

Numbering of molecules is pretty random. Progressiveness is not fulfilled or numbering is repeated, or even worse, it matches the numbering in the original document from which the picture has been copy-pasted. Figures and schemes must be original, and not a pasted copy of other articles (e.g. figure 15 from ref 59, figure 16 from ref 60, figure 18 from ref 60, and so on).

 

Line 24, “ammoniums and pyridiums”, is it pyridinium?

 

Lines 38-42, “the suggestion was made that metal salts MX (M = K, Cs) may react as contact ion-pairs (CIPs) [13–20], in which the counter-cation and the nucleophile are in close contact (RMX < 3 Å) and that crown ethers do not ‘separate’ the ion pairs to large distances, but rather act as Lewis base (through the O atoms) on the counter-cation in CIP”: the following articles (Chem. Eur. J. 2019, 25, 7131, J. Org. Chem. 2017, 82, 6629, both of them including a DFT study, and also J. Org. Chem. 1998, 63, 5356) must be cited since a inherent detailed study of the crown-metal cation-nucleophilic anion contact ion pair and its effect on reactivity and stereoselectivity is widely addressed therein, strongly supporting the concept highlighted in this review. The knowledge of such works, at least in the reference list, is essential for the readers. I also encourage the authors to include a discussion of this works in the review (other Michael reactions are discussed elsewhere).

 

Lines 62-63, please change “Pirisi and coworkers [26,27] studied anion-promoted nucleophilic substitutions”, with, “Landini, Montanari and coworkers” (the corresponding authors). Please correct also in line 142.

 

Line 201, […] something is missing here.

 

Section 4, as a notable example of synergistic crown ether-ammonium salt, the article (Angew. Chem., Int. Ed., 2005, 44, 625) should be cited.

 

Figure 15, caption: results and figures are from reference 59, and not 46

 

Lines 263-265, “Vast amount of studies of asymmetric reactions promoted by crown ethers and de-263 rivatives have been reported in the last decades, thus a comprehensive review for the development in these exciting field would be impossible”: a quite comprehensive review of the application of crown ethers in enantioselective PTC processes, actually, has been published quite recently, and I believe it must be cited (Synthesis 2018, 50, 4777).

 

Chapter 5: as I told before, the use of crown ethers as chiral phase-transfer catalysis has been reviewed elsewhere. Most cases involve a base promoted catalysis leading to the formation of a contact ion pair acting as the nucleophile. Therefore, is not clear the basis adopted by the authors to make a selection, limiting their overview to so few cases. In my opinion, it would makes much more sense to list the examples not reported in the previous reviews (e.g. in Synthesis 2018, 50, 4777), because more recent or involving truncated crown ethers (e.g. Voyer’s and Song’s works).

 

Figure 18, in the caption, the authors cite a review, ref 56, but in my opinion it should be better to cite the original work (Nat. Commun. 2017, 8, 14877). The same should be done in the text.

 

In conclusion, my opinion is that the publication of the present article review in Catalysts should not be published in the present form. It could be re-considered provided that the major revisions here suggested are made.

Author Response

Rev. 3

Numbering of molecules is pretty random. Progressiveness is not fulfilled or numbering is repeated, or even worse, it matches the numbering in the original document from which the picture has been copy-pasted. Figures and schemes must be original, and not a pasted copy of other articles (e.g. figure 15 from ref 59, figure 16 from ref 60, figure 18 from ref 60, and so on).

We revised the Figures completely, so that no copyright problems may arise at all. We also revised the numbering of the compounds in the Figures.

Line 24, “ammoniums and pyridiums”, is it pyridinium?

“pyridiums” is corrected to “pyridium s”

Lines 38-42, “the suggestion was made that metal salts MX (M = K, Cs) may react as contact ion-pairs (CIPs) [13–20], in which the counter-cation and the nucleophile are in close contact (RMX < 3 Å) and that crown ethers do not ‘separate’ the ion pairs to large distances, but rather act as Lewis base (through the O atoms) on the counter-cation in CIP”: the following articles (Chem. Eur. J. 2019, 25, 7131, J. Org. Chem. 2017, 82, 6629, both of them including a DFT study, and also J. Org. Chem. 1998, 63, 5356) must be cited since a inherent detailed study of the crown-metal cation-nucleophilic anion contact ion pair and its effect on reactivity and stereoselectivity is widely addressed therein, strongly supporting the concept highlighted in this review. The knowledge of such works, at least in the reference list, is essential for the readers. I also encourage the authors to include a discussion of this works in the review (other Michael reactions are discussed elsewhere).

 The two papers are cited as Ref. [66] and [67]. A paragraph is added to discuss these two works:

Sala, Izzo and co-workers’ work on the arylogous Michael addition [66] and the fluoride-promoted vinylogous Mukaiyama–Michael reaction [67] are also to be noted as primary examples in which the crown ether/CIP metal salt was proposed to work for excellent diastereoselective reactions.

Lines 62-63, please change “Pirisi and coworkers [26,27] studied anion-promoted nucleophilic substitutions”, with, “Landini, Montanari and coworkers” (the corresponding authors). Please correct also in line 142.

Corrected

Line 201, […] something is missing here.

 […] is deleted.

Section 4, as a notable example of synergistic crown ether-ammonium salt, the article (Angew. Chem., Int. Ed., 2005, 44, 625) should be cited.

 It is cited as Ref. [60]. We also added a paragraph:

Maruoka and co-workers’ [60] observation of dramatic rate increase of alkylation by using crown ether/achiral quaternary ammonium salt combinations as PTCs is another excellent example along this line of work.

Figure 15, caption: results and figures are from reference 59, and not 46

Corrected

Lines 263-265, “Vast amount of studies of asymmetric reactions promoted by crown ethers and de-263 rivatives have been reported in the last decades, thus a comprehensive review for the development in these exciting field would be impossible”: a quite comprehensive review of the application of crown ethers in enantioselective PTC processes, actually, has been published quite recently, and I believe it must be cited (Synthesis 2018, 50, 4777).

 It is cited as Ref. [62].

Chapter 5: as I told before, the use of crown ethers as chiral phase-transfer catalysis has been reviewed elsewhere. Most cases involve a base promoted catalysis leading to the formation of a contact ion pair acting as the nucleophile. Therefore, is not clear the basis adopted by the authors to make a selection, limiting their overview to so few cases. In my opinion, it would makes much more sense to list the examples not reported in the previous reviews (e.g. in Synthesis 2018, 50, 4777), because more recent or involving truncated crown ethers (e.g. Voyer’s and Song’s works).

It is always tricky to determine which works would be included because of the lomitation of the length and the desire to be comprehensive. We indeed discussed Voyer’s and Song’s works in more detail, thus it seems to be apprpriate.

Figure 18, in the caption, the authors cite a review, ref 56, but in my opinion it should be better to cite the original work (Nat. Commun. 2017, 8, 14877). The same should be done in the text.

We cited the paper as Ref. [65]. The citations in Figure 18 and in the text are corrected.

Round 2

Reviewer 2 Report

1. 'in the past decades' is meaningless. I do not believe that this is the first review on crown ethers. In the introduction, it is not clear what other reviews on crown ethers has been written and how this review is different from the other reviews. I do not think the other reviews are cited as well.

2. the various chapters make better sense now.

3. the title is inaccurate. this is just a general review. the second half from colon onwards should be removed.

4. the authors can write an excellent review just by organizing it around different mechanisms. 

5. Please confirm that diagrams have received copyright approval from other journals if they are not drawn by the authors.

Author Response

Rev. 2

-'in the past decades' is meaningless. I do not believe that this is the first review on crown ethers. In the introduction, it is not clear what other reviews on crown ethers has been written and how this review is different from the other reviews. I do not think the other reviews are cited as well.

We revise the Abstract

From: We review the progress in the past decades in nucleophilic reactions using metal salts facilitated by crown ethers and derivatives. Studies on reaction systems using kinetic measurements and quantum chemical methods are presented. First, we focus on the reaction mechanism. The experimental verification of the contact ion-pair (CIP) form of the metal salt CsF complexed with [18-Crown-6] by H-NMR spectroscopy is described. The possibility of the CIP mechanism in S_N2 reactions facilitated by crown ethers and the use of chiral crown ethers and derivatives for enantioselective processes are discussed.

To: We review the crown ether - facilitated nucleophilic reactions using metal salts, presenting the studies using kinetic measurements and quantum chemical methods. We focus on the mechanistic features, specifically on the contact ion-pair (CIP) mechanism of metal salts for nucleophilic processes promoted by crown ethers and derivatives, Experimental verification of the CIP form of the metal salt CsF complexed with [18-Crown-6] by H-NMR spectroscopy is described. The use of chiral crown ethers and derivatives for enantioselective nucleophilic processes are also discussed.

-the various chapters make better sense now.

-the title is inaccurate. this is just a general review. the second half from colon onwards should be removed.

We revised the Title to: Nucleophilic Reactions Using Alkali Metal Fluorides Activated by Crown Ethers and Derivatives

-the authors can write an excellent review just by organizing it around different mechanisms. 

The mechanisms of crown ether – facilitated nucleophilic reactions using metal salts have not been clearly elucidated so far, except some theoretical predictions for the CIP mechanism discussed in this Review. For others (for example, for the use of crown ether/ammonium salt combination), we explicitly remarked that the mechanism was not clear yet, although we suspect that they would also involve the CIP nucleophiles. Thus, the mechanisms discussed here may be classified into two: the CIP-suspect’ (Section 3) and CIP (Section 4, 5) processes. We plan to present direct experimental evidences for the mechanism, which is in progress in our labs.

-Please confirm that diagrams have received copyright approval from other journals if they are not drawn by the authors.

We completely revised the diagrams, so that copyright approval is not needed at all.

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors have submitted a completely revised version of their manuscript largely addressing the issues raised in my previous comments. I sincerely appreciate their effort, and now the the article looks to be overall improved. There are some minor changes to be made, and after that the manuscript could be accepted for publication in Catalysts.

·         A careful spell checking of the entire manuscript should be made. For example (incorrect form -> correct form):

line 24: pyridiums -> pyridiniums

line 44: technique -> techniques

line 46: crow -> crown

line 47: this this -> in this

line 280: Sala -> Della Sala

·         In line 65, it still reads “Pirisi, Montanari and coworkers (the same in line 242). It should be changed to “Landini, Montanari and coworkers”, as the authors state they did. Landini is one of the corresponding authors in one of the two publications, whereas Pirisi is not.

·         In line 267 the authors write “Crown-ether-facilitated processes involving transition-metal catalysts have been well reviewed elsewhere [62,63]; therefore, they are not included here”. Actually this is correct, in part, just for review 63 (that discusses applications in supramolecular catalysis, but mostly using transition metal additives), not for 62, that only discusses applications in PTC, and therefore has nothing to do with transition metal catalysis. I would say something like that: “Crown-ether-facilitated processes involving asymmetric phase-transfer [62] or supramolecular [63] catalysis have been well reviewed elsewhere; therefore, they are not included here”.

·         Journal abbreviations need to be checked: e.g. ref 24: European J. Org. Chem. -> Eur. J. Org. Chem.; ref 28: Angew. Chemie Int. Ed. English -> Angew. Chem. Int. Ed.; ref. 38 and 39: Angew. Chemie -> Angew. Chem., but it is better to report the international edition in english of these articles for consistency (p. 4559 and p. 7683 respectively); ref 62: Synth. -> Synthesis

 

In my opinion, after the above mentioned corrections, the manuscript deserves to be accepted for publications in Catalysts.

 

Author Response

Rev. 3

line 24: pyridiums -> pyridiniums Corrected

line 44: technique -> techniques Corrected

line 46: crow -> crown Corrected

line 47: this this -> in this Corrected

line 280: Sala -> Della Sala Corrected

• In line 65, it still reads “Pirisi, Montanari and coworkers (the same in line 242). It should be changed to “Landini, Montanari and coworkers”, as the authors state they did. Landini is one of the corresponding authors in one of the two publications, whereas Pirisi is not. Corrected
• In line 267 the authors write “Crown-ether-facilitated processes involving transition-metal catalysts have been well reviewed elsewhere [62,63]; therefore, they are not included here”. Actually this is correct, in part, just for review 63 (that discusses applications in supramolecular catalysis, but mostly using transition metal additives), not for 62, that only discusses applications in PTC, and therefore has nothing to do with transition metal catalysis. I would say something like that: “Crown-ether-facilitated processes involving asymmetric phase-transfer [62] or supramolecular [63] catalysis have been well reviewed elsewhere; therefore, they are not included here”. Corrected
• Journal abbreviations need to be checked: e.g. ref 24: European J. Org. Chem. -> Eur. J. Org. Chem.; ref 28: Angew. Chemie Int. Ed. English -> Angew. Chem. Int. Ed.; ref. 38 and 39: Angew. Chemie -> Angew. Chem.,but it is better to report the international edition in english of these articles for consistency (p. 4559 and p. 7683 respectively); ref 62: Synth. -> Synthesis Corrected

Author Response File: Author Response.pdf