Aminocyclopropenium as a New Class of Hydrogen Bonding Catalyst in Friedel–Crafts Alkylation
Round 1
Reviewer 1 Report
In this manuscript, the authors synthesized a H-bond donor catalyst, named tris(phenylamino)cyclopropenium chloride (TPAC•Cl), which was used in a Friedel-Crafts alkylation reaction of 1H-indoles with β-nitrostyrenes. In this reaction, a series of 3-alkylsubstituted 1H-indoles were obtained with moderate to good yields. Furthermore, some control experiments were conducted using NMR techniques to validate the H-bond interactions of TPAC•Cl with the substrates. Therefore, before accepting this work for publication in Catalysts, some points should be considered.
The amount of catalyst used throughout the reactions was not mentioned. In my opinion, the authors should first consider evaluating the catalytic amount of TPAC•Cl. Then, some different solvents and temperature must be tested to improve the optimization of reaction conditions.
The number of examples illustrating the versatility of this method is narrow. To better demonstrate steric and electronic effects on substrates, results of reactions using strong electron withdrawing and bulky groups directly bonded to the benzene ring of the nitrostyrene must also be demonstrated. Furthermore, the authors suggest that the chloride ion acts cooperatively by interacting with the N-H of indoles. Did the authors perform experiments using N-protected indoles? Examples using N-metil, N-phenyl, N-tosyl, and/or N-acyl indoles would add to the discussion regarding electron demanding on indole nucleus.
Materials and Methods / SI should be reviewed. For example, are CHCl3 or DMSO protic solvents? What solvents were used for NMR analysis? How did the authors conduct the HRMS analysis? In my opinion, experimental procedures should be written using molar ratio instead of just “g” or “mL” of reagents.
The NMR spectra and X-ray diffraction analysis of the compound TPAC•Cl were published previously (DOI: 10.1039/C8PY00338F), apparently by the same group. I suggest checking the “Instructions for authors”.
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
This manuscript reports on the use of tris(phenylamino)cyclopropenium chloride as organocatalyst for performing the Friedel-Crafts‒type alkylation of indoles with nitroalkenes.
The manuscript is not suitable for publication in Catalysts for the following reasons:
- The novelty of the results is low. There are many other related methods for performing the same reaction, and it is unclear what improvement is achieved here with respect to the state-of-the-art
- The substrate scope is narrow (Table 1, entries 2 and 8-14), and only in a very limited number of examples the product yield is satisfactory (Table 1, entries 2, 8, 9, 14), while in the other cases (Table 1, entries 10-13) the yields range is 33-57%
- The manuscript has been poorly written, and would need extensive revision for the correct use of idiomatic English
After revision, the manuscript could be transferred to a more specialized journal, such as Molbank.
The manuscript has been poorly written, and would need extensive revision for the correct use of idiomatic English
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Reviewer 3 Report
The paper reports on the synthesis of 2-tri(phenylamino)cyclopropenium chloride (TPAC-Cl) an its use as an achiral hydrogen-bond catalyst for the Friedel-Crafts alkylation of indoles with beta-nitrostyrenes. This compound is isolated in good yields, and must be stored under Ar. At rt in DCM solution, the FC of indole with nitrostyrene takes place in 78% yield after 24 h. Similar yields (55-88%) are obtained for other (up to 7) substituted derivatives. Electron-withdrawing substituents in the indole, as expected, diminish the reactivity. Products are well characterized by NMR and HRMS.
The authors however do not indicate the amount of catalyst used, in % mol., they only indicate the mass. This should be corrected.
The results should be compared, ass to the yields, with previous studies for instance with thiourea or guanidinium catalysts. Most of them are chiral however and have been used in enantioselective FC reactions. For instance, Ricci's catalyst (2005) performs the benchmark reaction at -24ºC (72 h) in the same 78% yield. The authors should perform this reaction in their conditions with Schreiner's thiourea and report the result.
A drawback of the TPAC-Cl catalyst is that it is not easy to envision a chiral analogue.
The results are of moderate interest but after minor modification they can be published in Catalysts.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The authors have appropriately revised the manuscript that reads better now, acceptance is recommended.
Author Response
Thank you for your approval and your insightful comments, which are very important in guiding our work. We sincerely accept your criticism and will improve the research design in the next work to better present the research results.
Thank you for your time and consideration.
Reviewer 2 Report
I stick to my decision. The novelty and the substrate scope of the reaction are not sufficient for publication in Catalysts. I suggest transferring of the revised manuscript to Molbank
Dear Editors
I stick to my decision. The novelty and the substrate scope of the reaction are not sufficient for publication in Catalysts. I suggest transferring of the revised
Author Response
Thank you for your insightful comments, which are very important in guiding our work. We sincerely accept your criticism and will try to improve our research design in our next work to better present the research results.
Thank you for your time and consideration.
