A Theoretical Study on Pd-catalyzed, Friedel-Crafts Intermolecular Acylation: Does Generated In Situ Aroyl Triflate Act as A Reactive Electrophile to Functionalize C–H Bond of Arenes?

Round 1

Reviewer 1 Report

The manuscript “A Theoretical Study on Pd-catalyzed Friedel-Crafts Intermolecular Acylation: Does Generated In Situ Aroyl Triflate Act as a Reactive Electrophile to Functionalize C-H Bond of Arenes?” by Guo, Li et al. deals with the computational investigation of the feasibility of Friedel-Crafts Acylation process for the formation of aromatic ketones catalysed by Pd complexes. In particular, the authors make some predictions on the feasibility of the process catalysed by the Pd(CO)3 complex and three different possible reaction pathways have been investigated. According to the present reviewer, although the authors have been carried out carefully the calculations, the manuscript lacks of the analysis of the electronic underpinnings, which rule the obtainment of the main reaction intermediates and a comparison with the same process catalysed by the Pd(PR3)3. Without these aspects, the manuscript is only a series of numbers and energetics without any solid chemical meaning. In addition, according to the present reviewer, some hints should be provided about the energy barriers associated to the formation of the AgI starting from AgAr with the exchange of the ligands with the palladium complex. The authors can performed a relaxed scan for the approaching of the AgAr and the final formation of the Ag-I bonding. For the aforementioned reasons, according to the present reviewer at this level the manuscript has to be largely improve before reconsideration for the publication on Catalysts.

Author Response

Please see our responses to referee 1 in the file of cover letter!

Author Response File: Author Response.pdf

Reviewer 2 Report

The authors are reporting a careful computational study on the Pd–catalyzed Friedel–Crafts acylation reaction of arenes to ketones. The computational study is very complete and details provided are sufficient to allow others to reproduce the work. I am suggesting below some minor changes that in my view will improve the quality of the manuscript.

i) The color code for spheres in the ball & stick representations in Figures 1-4, 6 and 7 must be added to the figure captions.

ii) Correct inconsistencies in which plural nouns are followed by singular verbs and vice-versa.

iii) Several calculated systems present aromatic rings and the quality of the calculations may suffer from deficiencies in the handling of dispersion interactions by the standard density functional theory approaches used in their work. Maybe the authors are interested in inserting the reference RSC Adv., 2013, 3, 13085-13100 (DOI: 10.1039/C3RA40713F), where it is reviewed that the "M06 functionals are able to approximate model dispersion effects at short-range", that "M06 functionals ... were suggested ... for systems containing transition metal elements" and also that the "M06 family of functionals seems to be a good choice for handling molecular systems where weak intermolecular interactions exist.", for supporting the quality of the calculations reported in the manuscript.

Author Response

Please see our responses to referee 2 in the file of cover letter!

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The authors have introduced all the modifications suggested by the reviewer although Figure 1 of the response is not so clear and also some modifications are needed for the Ag-I scan. Regarding Figure1, I do not understand why in the first step the substitution must occur together with the oxidative addition. Maybe, it is more easy for the readers if the two contributions are splitted, firstly the oxidative addition, which is easy with two phosphine ligands, and later the PR3/CO substitution. Also for the scan of the Ag---I distance, it is better to make some calculations starting from longer Ag---I distances, such as 3.6 A°, in order to be sure about the absence of any energy barrier. Some references,such as JACS 2014, 136, 14654, must be also added for the aryl-I activation. After these modifications, the article is suitable for publication.

Author Response

Please see our responses in cover letter.

Author Response File: Author Response.pdf