Review Reports

Round 1

Reviewer 1 Report

The authors report an interesting catalyst design that gives access to a versatile new organo(pre)catalyst in a straightforward manner.

Overall the basic catalyst scaffold shown herein and the concept of generating the active catalyst in situ is not entirely new but given the ease of preparation and the high enantioselectivities that can be obtained I think that this report will be of interest to the synthesis and catalysis community and I thus recommend publication of this article in this journal.

Some minor points that I would however find worth being addressed are:

- In the introduction the authors should give a few more citations on previous literature where such an diaza-Cope rearrangement was already successfully used to generate such catalysts

- Experimentally I would find it interesting if the authors could try to generate the "real" catalyst upfront and use it in an independent reaction to check if the cleaved off aldehyde group has any effect.

- In the text accompanying Fig. 1 the authors write about compounds Ia-c but these are not indexed in Fig. 1

- Table 1: what is compound 3a'?

 

Author Response

Dear Reviewer 1,

The manuscript "Chiral Bis(8-quinolyl)ethane-derived diimine: structure elucidation and catalytic performance in asymmetric synthesis of (S)-Warfarin" submitted to Catalysts (ID: catalysts-2128122) has been revised by the authors according to your comments. We are grateful to you for careful evaluation of our paper and useful suggestions. The comments and made changes are summarized below. All changes are marked up in the revised manuscript using the “Track Changes” function.

Comment  from Reviewer 1: In the introduction the authors should give a few more citations on previous literature where such an diaza-Cope rearrangement was already successfully used to generate such catalysts

Response to the comment: The additional citations [19-21] on usage of the diaza-Cope rearrangement in asymmetric organocatalysis were added into the first paragraph of the Results and discussion section and into the List of references.

Comment from Reviewer 1: Experimentally I would find it interesting if the authors could try to generate the "real" catalyst upfront and use it in an independent reaction to check if the cleaved off aldehyde group has any effect.

Response to the comment: As stated in the introduction, mono-protected chiral 1,2-diphenylethane diamine (DPEN) derivatives were synthesized earlier. However, selective functionalization of just one of the two amino groups in DPEN required auxiliary protection/deprotection steps that complicate the synthesis of such compounds. Enantioselective preparation of mono-protected 1,2-bis(heteroaryl)diamines would be even more difficult and enantiomerically pure heterocyclic compounds of this type have not been prepared so far.

Comment from Reviewer 1: In the text accompanying Fig. 1 the authors write about compounds Ia-c but these are not indexed in Fig. 1

Response to the comment: Compounds Ia-c have been indexed in Fig. 1 of the revised manuscript.

Comment from Reviewer 1: Table 1: what is compound 3a'?

Response to the comment: Compound 3a’ is cyclic tautomeric form of Warfarin (3a). In the original manuscript it was shown only in Figure 4. For clarity, we have duplicated it in the scheme for Table 1 of the revised manuscript.

Taking into account that all reviewers’ comments are addressed in the revised manuscript, we kindly ask you to make final decision on the acceptance of our contribution for publication in Catalysts.

Sincerely yours,

Alexander Kucherenko

Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences

Leninsky prosp.47, 119991, Moscow, Russia

Tel: (+7) 499-137-1353,

Fax: (+7) 499-135-5328

mailto: alexkucherenko@yandex.ru

 

please see attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Line 37 - check word propection and correct accordingly

Line 71 - Grammar - Rephrase to say - According to the X-ray diffraction (XRD) study, the obtained crystals ...

Line 73 - Should XRS not be XRD?

Figure 3 caption - it is no X-ray diffraction picture but a crystal structure obtained from the XRD analysis

Line 90 - define HRMS 

line 95 - grammar - ... which push the organocatalyst ...

Author Response

Dear Reviewer 2,

The manuscript "Chiral Bis(8-quinolyl)ethane-derived diimine: structure elucidation and catalytic performance in asymmetric synthesis of (S)-Warfarin" submitted to Catalysts (ID: catalysts-2128122) has been revised by the authors according to your comments. We are grateful to you for careful evaluation of our paper and useful suggestions. The comments and made changes are summarized below. All changes are marked up in the revised manuscript using the “Track Changes” function.

Comments from Reviewer 2:

Line 37 - check word propection and correct accordingly

Line 71 - Grammar - Rephrase to say - According to the X-ray diffraction (XRD) study, the obtained crystals ...

Line 73 - Should XRS not be XRD?

Figure 3 caption - it is no X-ray diffraction picture but a crystal structure obtained from the XRD analysis

Line 90 - define HRMS 

line 95 - grammar - ... which push the organocatalyst ...

Response to the comments: All comments from Reviewer 2 are addressed in the revised manuscript.

Taking into account that all reviewers’ comments are addressed in the revised manuscript, we kindly ask you to make final decision on the acceptance of our contribution for publication in Catalysts.

Sincerely yours,

Alexander Kucherenko

Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences

Leninsky prosp.47, 119991, Moscow, Russia

Tel: (+7) 499-137-1353,

Fax: (+7) 499-135-5328

mailto: alexkucherenko@yandex.ru

Please see attachment

Author Response File: Author Response.pdf

Reviewer 3 Report

The paper of Kucherenko, Zlotin and co-workers is very well written, packing a large amount of information into a concisely-presented manuscript. In my opinion,

1.     The adducts 3a–e were formed as inseparable mixtures of linear and cyclic tautomers. However, from the HPLC spectra, it seems that these compounds could be separated. How to explain?

2.     How were the absolute configurations of these adducts of the asymmetric Michael reaction determined?

3.     In Supporting information (1. HRMS data for reaction mixture), the structure of salicylic aldehyde should be drawn out in the reversible chemical equilibrium.

4.     The catalytic mechanism should be proposed, if possible.

I recommend publication after minor modifications.

Author Response

Dear Reviewer 3,

The manuscript "Chiral Bis(8-quinolyl)ethane-derived diimine: structure elucidation and catalytic performance in asymmetric synthesis of (S)-Warfarin" submitted to Catalysts (ID: catalysts-2128122) has been revised by the authors according to your comments. We are grateful to you for careful evaluation of our paper and useful suggestions. The comments and made changes are summarized below. All changes are marked up in the revised manuscript using the “Track Changes” function.

 

Comment from Reviewer 3: The adducts 3a–e were formed as inseparable mixtures of linear and cyclic tautomers. However, from the HPLC spectra, it seems that these compounds could be separated. How to explain?

 

Response to the comment: According to NMR spectra compounds 3a–e exist in solution (CDCl₃ or DMSO-d₆) as dynamic equilibrium mixture of linear and cyclic tautomers. However the signals of the tautomers in the HPLC picture are overlapped due to fast interconversion process. Therefore, isolation of individual tautomers is impossible. To address the reviewer’s comment, we change the word “inseparable” for the phrase “dynamic equilibrium” in the paragraph above Figure 4 of the revised manuscript.

 

Comment from Reviewer 3: How were the absolute configurations of these adducts of the asymmetric Michael reaction determined?

 

Response to the comment: The phrase “The absolute S configuration of warfarin was established by the comparison of optical rotation angle with reported data [α]_D²⁵ = - 21.7^o (c 1, CH₂Cl₂) (lit.[15] for (R)-isomer : [α]_D²⁵ = +24.0 (c 1, CH₂Cl₂, 94% ee))” has been added as footnote “e” to Table 1. The phrase “The absolute S configuration was assigned to products 3b-e by analogy with Warfarin 3a” was added to the paragraph above Figure 4.

 

Comment from Reviewer 3: In Supporting information (1. HRMS data for reaction mixture), the structure of salicylic aldehyde should be drawn out in the reversible chemical equilibrium.

 

Response to the comment: The structure of salicylic aldehyde was added to the reversible chemical equilibrium at the HRMS data section in Supporting information.

 

Comment from Reviewer 3: The catalytic mechanism should be proposed, if possible.

 

Response to the comment: Plausible transition state for the catalytic reaction in the presence of primary amine catalyst III and corresponding description have been added to the revised manuscript.

 

Taking into account that all reviewers’ comments are addressed in the revised manuscript, we kindly ask you to make final decision on the acceptance of our contribution for publication in Catalysts.

Sincerely yours,

Alexander Kucherenko

Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences

Leninsky prosp.47, 119991, Moscow, Russia

Tel: (+7) 499-137-1353,

Fax: (+7) 499-135-5328

mailto: alexkucherenko@yandex.ru

Please see attachment

Author Response File: Author Response.pdf