Expression of Reaction Selectivity and the Substituent Effect in Ullmann, Suzuki, Hiyama, and Allylic Arylation Reactions Caused by Reducing Catalyst Loading

Round 1

Reviewer 1 Report

Dear Editor, Dera Authors,

Ohtaka and coworkers reported an interesting study about the selectivity and the substituent effect in Ullmann, Suzuki, Hiyama, and allylic arylation.

The work is well conducted, and different reaction parameters and substrates were evaluated. The manuscript is well written, and the experimental section is complete.

The results reported well support the conclusions and represent new work that makes a significant impact in the field. In my opinion the present manuscript is suitable for publication in Catalysts after minor revision.

Best Regards

·      Insert number for each structure reported in the manuscript and refered to it during discussion in the text.

·      Please report in the scheme 3 the results about “when the reaction of 4-bromophenyl trifluoromethanesulfonate with 4-methylphenylboronic acid was performed using 2.0 mol% of Pd(OAc)2 and PCy3 (1.2 90 equiv relative to Pd) in THF at 50 °C for 24 h, 4’-methylbiphenyl-4-yl triflate and 4,4’’-dimethyl-1,1’:4’,1’’-terphenyl were obtained in 91% and 4% yields, respectively, whereas at 60 °C, the yields were 75% and 25%, respectively.”

·      Page 4 line 130: “4-Methoxy-4’-(trifluoromethyl)biphenyl was obtained in 29% yield by the reaction of 4-benzotrifluoride with 4-methoxyphenylboronic”. Is it 4-benzotrifluoride or 4-bromo-benzotrifluoride?

Author Response

Thank you very much for reviewing the manuscript.

We revised the manuscript according to your suggestions.

1. The number was inserted for each product, and Tables and Schemes were revised.
2. Scheme 3 was revised.
3. “4-benzotrifluoride” was revised to “4-bromobenzotrifluoride”.

Reviewer 2 Report

This paper proposes an extensive, fundamental study of the effect of Pd catalysts concentrations on the fate of different important coupling reactions. The authors do show that reducing catalyst's concentration allows to evidence subtle differences between the reactivity of different substrates.

The results are in line with the already known specificities regarding the rate-determining steps of the studied reactions. The proposed approach could probably not generalised to the understanding of difficult cases, where high Pd loadings are necessary.

From this point of view, this paper doesn't bring new conclusions. However, the proposed methodology is interesting, and the results constitute an intersting and handy summary of Pd catalysis. It is thus an interesting starting point for those interested in Pd-based catalysis.

The paper lacks a conclusion to summarise the results. This is to be added i the revised version of the manuscript.

Minor English corrections needed.

Author Response

Thank you for reviewing the manuscript, and we revised the manuscript according to your suggestion.

The conclusion was revised as follows:

In summary, the expression of several selectivity in various catalytic reactions was confirmed by reducing the catalyst concentration. In the reaction catalyzed by in situ-generated Pd nanoparticles, the catalytic reaction on the Pd surface and in the solution phase can be controlled by changing the catalyst loading. A slight difference in the reaction rate was confirmed by the decrease in catalyst concentration. Moreover, the substituent effect was confirmed using the Pd catalyst at the mol ppm level, and the rate-determining step in the catalytic reaction could be predicted. That is, this study indicates that the control of the reaction selectivity or the confirmation of reaction mechanism is achieved simply by reducing the catalyst concentration. Therefore, reducing the catalyst concentration is crucial not only in terms of environmental aspects and industrial applications, but also for synthetic chemistry [41,42]. The investigation in other catalytic reactions is now in progress to extend the versatility of this concept.