Organocatalysis: A Brief Overview on Its Evolution and Applications

Round 1

Reviewer 1 Report

The review reports the use of small organic compounds as catalysts. They are presented as better catalysts than the alternative organometallic complexes or enzymes.

Some observations.

Let’s start from the Introduction. I do not agree that “a catalyst is a substance that can make the course of a reaction easier”; it always makes the course of a reaction easier. I do not agree that “it acts by reacting with one of the reactants and forming an intermediate that will follow for the formation of the product”; not all the catalysts react with the reactants and form an intermediate. Some do it, some do not.

What does the legend of Scheme 1 mean? (“Chinchona alkaloids getting by Bredig and Fiske”).

According to the formulas in Schemes 2 and 3 the attack to one of the ring carbonyl (which one? the pro-R or pro-S?) is on the Si face and not the Re face as the Authors state.

In the example reported in Scheme 6 the catalyst is achiral though the section is named “Chiral amines …”

Why the general statement “The α-alkylation of carbonyl compounds is a very useful methodology to create new stereocenters and C−C bonds” has been put in lines 104-105 though it applies to a lot of other examples mentioned before and after?

Schemes 7 and following. Which is the role of the additive? Advantages and disadvantages for the additive to be incorporated into the catalyst are not discussed.

Line 129. What does “95:5 ee” mean? (95% ee or 95:5 er?)

Line 151. Which is the “para-substituted phenol” the Authors refer to?

Line 188. Compound 66 is not an imidazolidinone.

Scheme 14. What is the role of 4-nitrobenzoic acid?

Lines 209-210. Compound 72 is not an α-imino γ-lactone, and compound 73 is not an α-arylidene pyrazolonone.

Line 211.  Compound 74 is not a squaramide and compound 75 is not the product.

Scheme 20. The Breslow intermediate and the homogenate equivalent are resonance structures. They are not two distinct intermediates in equilibrium.

Line 311. “… aldehydes (3 …” ?

Line 312. “… different ketones (114) …”? Compound 114 in Scheme 23 is acetone.

Line 315 and Scheme 23. In order to obtain compound 118, acetone must attack 113 on the Si face.

Line 398 and Scheme 30. Compound 150? Two different compounds named 151?

Scheme 33. The structure of b-CD is wrong!

Line 504. Is (S)-1-phenyl-ethylamine an acylating agent?

These are just some examples of errors and inaccuracies present in the text.

In conclusion, I found this review poorly organized and lacking any generalizations that may be useful to the reader. The review is a simple list of reactions without a true unifying element. No conclusion is drawn so that the review is useless for any reader. The text is full of errors. Moreover, the quality of English language is often poor and a lot of sentences are not well formulated.

So, the manuscript is unsuitable to be published.

Author Response

Reviewer: 1

Comments and Suggestions for Authors

The review reports the use of small organic compounds as catalysts. They are presented as better catalysts than the alternative organometallic complexes or enzymes.

Some observations.

Let’s start from the Introduction. I do not agree that “a catalyst is a substance that can make the course of a reaction easier”; it always makes the course of a reaction easier. I do not agree that “it acts by reacting with one of the reactants and forming an intermediate that will follow for the formation of the product”; not all the catalysts react with the reactants and form an intermediate. Some do it, some do not.

-What does the legend of Scheme 1 mean? (“Chinchona alkaloids getting by Bredig and Fiske”). DONE

-According to the formulas in Schemes 2 and 3 the attack to one of the ring carbonyl (which one? the pro-R or pro-S?) is on the Si face and not the Re face as the Authors state. DONE

-In the example reported in Scheme 6 the catalyst is achiral though the section is named “Chiral amines …” DONE

-Why the general statement “The α-alkylation of carbonyl compounds is a very useful methodology to create new stereocenters and C−C bonds” has been put in lines 104-105 though it applies to a lot of other examples mentioned before and after? DONE

-Schemes 7 and following. Which is the role of the additive? Advantages and disadvantages for the additive to be incorporated into the catalyst are not discussed. DONE

-Line 129. What does “95:5 ee” mean? (95% ee or 95:5 er?) DONE

-Line 151. Which is the “para-substituted phenol” the Authors refer to? DONE

-Line 188. Compound 66 is not an imidazolidinone. DONE

-Scheme 14. What is the role of 4-nitrobenzoic acid? DONE

-Lines 209-210. Compound 72 is not an α-imino γ-lactone, and compound 73 is not an α-arylidene pyrazolonone. DONE

-Line 211. Compound 74 is not a squaramide and compound 75 is not the product. DONE

-Scheme 20. The Breslow intermediate and the homogenate equivalent are resonance structures. They are not two distinct intermediates in equilibrium. DONE

-Line 311. “… aldehydes (3 …” ? DONE

-Line 312. “… different ketones (114) …”? Compound 114 in Scheme 23 is acetone. DONE

-Line 315 and Scheme 23. In order to obtain compound 118, acetone must attack 113 on the Si face. DONE

-Line 398 and Scheme 30. Compound 150? Two different compounds named 151? DONE

-Scheme 33. The structure of b-CD is wrong! DONE

-Line 504. Is (S)-1-phenyl-ethylamine an acylating agent? DONE

Reviewer 2 Report

The paper by Forezi et al., entitled Organocatalysis: brief Historic, applications and  evolution” constitutes an interesting partial revision on organocatalysis.  

 There are a few mistakes that must be corrected. For instance:

1.    Intermediate 95 in Scheme 19 is not an enamine, but really the Breslow intermediate formed in the addition of  carbene 92 to aldehyde 90.

2.    The formation of furoins summarized in Scheme 19 really constitutes a variation of benzoin condensation.

3.    Some of the epigraph are correct, and summarizes the most important advancements on organocatalysis. Nevertheless, some others, such as immobilized organocatalysts must be enlarged considering important contributions such as: ASC 2012, 354, 2905; OL 2013, 15 3498; Catal. Sci. Tech. 2016, 6, 4668; EJOC, 2013, 4490; Synthesis 2016, 1474; ACS Catal. 2014, 4, 2137; JOC 2017, 82, 8444. All these papers must be commented and referenced.

4.    The epigraph 9 must also be completed considering more recent contributions such as those to Melchiorre or Aleman.

Once the commented corrections and additions were introduced in the manuscript, the paper could be considered for acceptation.

Author Response

Reviewer: 2

Comments and Suggestions for Authors

The paper by Forezi et al., entitled Organocatalysis: brief Historic, applications and evolution” constitutes an interesting partial revision on organocatalysis.

There are a few mistakes that must be corrected. For instance:

1. Intermediate 95 in Scheme 19 is not an enamine, but really the Breslow intermediate formed in the addition of carbene 92 to aldehyde 90. DONE

2. The formation of furoins summarized in Scheme 19 really constitutes a variation of benzoin condensation. DONE

3. Some of the epigraph are correct, and summarizes the most important advancements on organocatalysis. Nevertheless, some others, such as immobilized organocatalysts must be enlarged considering important contributions such as: ASC 2012, 354, 2905; OL 2013, 15 3498; Catal. Sci. Tech. 2016, 6, 4668; EJOC, 2013, 4490; Synthesis 2016, 1474; ACS Catal. 2014, 4, 2137; JOC 2017, 82, 8444. All these papers must be commented and referenced. DONE

4. The epigraph 9 must also be completed considering more recent contributions such as those to Melchiorre or Aleman. DONE

-Once the commented corrections and additions were introduced in the manuscript, the paper could be considered for acceptation.

Reviewer 3 Report

In this review Oliveira et al. aimed to present a summary of some classic works and recent publications, explaining the advantages of organocatalysis.

My first concern is about the scientific relevance of publishing another paper regarding a topic which is already widely represented in literature, like organocatalysis in general, where even more specific topics (e.g. cinchona alkaloids catalysis, enamine catalysis, mechanism etc.) where already deeply analysed by books and reviews. However considering that “Catalysts” is an open access journal, I recognize that a review on organocatalysis could be of interest to increase general scientific knowledge.

For each paragraph based on molecules used as catalyst, I suggest to include as reference, besides the most recent literature, books which already covered the subject, as could be beneficial for readers.

English used needs a deep revision, starting from the title. “Historic” is an adjective. I suggest the aid of a native or fluent speaker.

Moving on to science, it is not possible to use specific cases to justify propaganda-like statements. It is simply not true that Organocatalysis is greener than other catalysis, but it is complementary. Statements reported from line 40 to line 50 are “potentially” true, depending on numerous factors. This is, of course, a general problem, which plague scientific community, the anxiety to oversell methods and ideas push scientists to use too enthusiastic tones at the expense of objectivity. Therefore I invite the authors to rephrase the introduction highlighting that organocatalysis is a valuable tool to solve determined problems and not the solution for everything.

I recommend publication of the article, after the modification suggested and deep revision of English language and style.

Author Response

Reviewer: 3

Comments and Suggestions for Authors

In this review Oliveira et al. aimed to present a summary of some classic works and recent publications, explaining the advantages of organocatalysis.

My first concern is about the scientific relevance of publishing another paper regarding a topic which is already widely represented in literature, like organocatalysis in general, where even more specific topics (e.g. cinchona alkaloids catalysis, enamine catalysis, mechanism etc.) where already deeply analysed by books and reviews. However considering that “Catalysts” is an open access journal, I recognize that a review on organocatalysis could be of interest to increase general scientific knowledge.

-English used needs a deep revision, starting from the title. “Historic” is an adjective. I suggest the aid of a native or fluent speaker. DONE

New title: Organocatalysis: a brief overview on its evolution and applications

-Moving on to science, it is not possible to use specific cases to justify propaganda-like statements. It is simply not true that Organocatalysis is greener than other catalysis, but it is complementary. Statements reported from line 40 to line 50 are “potentially” true, depending on numerous factors. This is, of course, a general problem, which plague scientific community, the anxiety to oversell methods and ideas push scientists to use too enthusiastic tones at the expense of objectivity. Therefore I invite the authors to rephrase the introduction highlighting that organocatalysis is a valuable tool to solve determined problems and not the solution for everything. DONE

-I recommend publication of the article, after the modification suggested and deep revision of English language and style. DONE

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

-According to the formulas in Schemes 2 and 3 the attack to one of the ring carbonyl (which one? the pro-R or pro-S?) is on the Si face and not the Re face as the Authors state. DONE NOT DONE. No answer is given to my question.

-Scheme 14. What is the role of 4-nitrobenzoic acid? DONE NOT DONE

-Line 211. Compound 74 is not a squaramide and compound 75 is not the product. DONE  NOT DONE

-Line 398 and Scheme 30. Compound 150? Two different compounds named 151? DONE NOT DONE. 151 still refers to two different compounds.

-Scheme 33. The structure of b-CD is wrong! DONE NOT DONE! The structure is still wrong!!! Have I to draw it? Look at the anomeric configuration!

Some other remarks:

- Line 68. Intermediate 11 is not an enamine.

- Line 95. "atested"?

- Line 100. "scalonated"?

Author Response

- According to the formulas in Schemes 2 and 3 the attack to one of the ring carbonyl (which one? the pro-R or pro-S?) is on the Si face and not the Re face as the Authors state. DONE NOT DONE. No answer is given to my question.

The scheme has been modified.

-Scheme 14. What is the role of 4-nitrobenzoic acid? DONE NOT DONE

4-nitrobenzoic acid is used as acidic additives

-Line 211. Compound 74 is not a squaramide and compound 75 is not the product. DONE NOT DONE

Corrected numbering: Squaramide (75) and product (74)

-Line 398 and Scheme 30. Compound 150? Two different compounds named 151? DONE NOT DONE. 151 still refers to two different compounds.

Corrected numbering (text and scheme 30): “Vitamin B1 can catalyze organic transformations, and in this case it was used to catalyze  the  three-component condensation between different aryl aldehydes (150), 1,3-cyclohexanediones (151a or 151b) or 4-hydroxy-coumarin (152), and malononitrile (153) or ethyl cyanoacetate (154) (Scheme 30).”

-Scheme 33. The structure of b-CD is wrong! DONE NOT DONE! The structure is still wrong!!! Have I to draw it? Look at the anomeric configuration!

CORRECTED.

Some other remarks:

- Line 68. Intermediate 11 is not an enamine.

CORRECTED. “The formed enamine 12 reacts with one of the ring carbonyls...”

- Line 95. "atested"?

MODIFIED

- Line 100. "scalonated"?

MODIFIED

Author Response File: Author Response.pdf

Reviewer 2 Report

The paper has improved after the corrections and additions. Now it could be accepted for publication

Author Response

Thanks for your considerations.

Kind regards,

Luana da S. M. Forezi

Author Response File: Author Response.pdf

Round 3

Reviewer 1 Report

The manuscript can be published