Synthesis, Structure, and Catalytic Reactivity of Pd(II) Complexes of Proline and Proline Homologs

Round 1

Reviewer 1 Report

Merola and co-workers report a number of new palladium(II) acetate with prolines derivatives as the chelating ligands. These structures were used as plausible catalysts for the oxidative coupling of an olefin derivative and phenylboronic acids.

In my opinion, this paper mainly presents and is mainly focused on the syntheses, structural and spectroscopic characterization of palladium proline complexes. However, and unfortunately, the authors only try one substrate for the catalytic reaction what is a really poor example.

 Moreover, if you apply the catalysts in just one example and the results are really poor, overall in ee, you cannot conclude anything. Therefore, the mechanism explanation is not well supported.

Please, if all catalysts are chiral, indicate the chirality in their structures (Figure 2 and Table 1). Otherwise, it is difficult to understands why you are using them in enantioselective reaction and even more, how you can obtain a bit of enantioselectivity.

The DFT-optimized geometry of the transmetallated intermediate does not provide any useful information. The calculations are really short.

Please, provide the HPLC at least for the best ee with a racemic separation

This article is not suitable for Catalysts, it is more appropriate for journals such as Polyhedron, J. Mol. Struct. or Chem. Cent. J.. Therefore, I do support the publication of this article in this journal. Morevover, the authors should consider reorganize the manuscript.

Author Response

If this had been a paper describing a new organic synthesis method, I would agree with this reviewer that the use of only one substrate would be deficient.  We demonstrated more than one substrate although not in depth.  We think that our findings here are significant even with the limited number of substrates.  First, even though ee's are not up to the standards that would make this a winning method, the finding of any enantioselectivity for such a simple system is significant.  In addition, the finding that this catalyst will continue to act on a product that is bulkier and bulkier is also a significant finding.  We looked for this multiple addition product with other Pd systems and did not observe it.  So, overall, we are confident (as other reviewers seem to feel) that this is a worthwhile contribution to the literature.

In the revision, the nature of the chirality of the ligands in figure 1 and table 1  is explicitly identified.. 

 I am not sure what the reviewer means that the DFT calculations are "short".  We do think there is some value to see this intermediate and it does show information on how enantioselectivity can be achieved.

I am also not sure what "moderate English changes required' refers to in his assessment.  I believe we used grammatical English with much attention paid to avoiding typographical errors, although I am sure we missed some and I went through the  manuscript in detail.

Reviewer 2 Report

In this paper, the authors describe the preparation of Pd(II) complexed with amino acids as chelate ligands. Several derivatives of proline were used in the complexation of palladium acetate. The complexes are well characterized by various methods and the authors were able to obtain crystal structures of all complexes. Although palladium complexed proline are already known (for example, Eur. J. Org. Chem, 2009, 98), however, this study include more derivatives and interesting application of the complexes in the oxidative coupling of phenylboronic acid and alkenes, including non-activated alkenes. The possibility to obtain chiral products in such reactions is very interesting, but the catalysts showed very poor enantioselectivity. Overall, this work is publishable in Catalysts.  

Author Response

We thank this reviewer for calling attention to the article that we missed in our studies - the title suggested they were looking at nano particles of palladium when the paper was actually saying that nanoparticles played no role when Pd proline complexes were examined.  This reviewer also made us look a little deeper into the literature with different keywords that might have caught this paper and we did find a few others relevant to the topic.  The suggested paper and a few others are now cited in our revision.

Reviewer 3 Report

The manuscript by Merola et al. reports the synthesis of several complexes of Pd(II) with proline and analogues. Application in oxidative catalysis is also described. The manuscript is potentially suitable for publication in the journal. The following changes should be made prior to the final acceptance:

1.     Introduction. Please, add a paragraph on the previous work on the synthesis of Pd(II)-amino acid complexes, and their application in catalysis. Such complexes are well-established in the literature. Relevant references should be added.

2.     Figure 6, 14, 26 and 27 should be removed from the manuscript and placed in the SI.

3.     The discussion on x-ray structures should be condensed on a single page and x-rays also combined in one or two figures to improve the clarity.

4.     Please, cite a relevant review involving a similar type of N-Pd(II)-coordination: Acc. Chem. Res. 2018, 51, 2589-2599.

5.     Table 2. Has lower temp been tested?

6.     Figures 30-32 should also be moved to the SI, or at least condensed. This is a general comment on the manuscript. The strength relies on the synthesis of Pd(II) complexes and x-ray structures, however, the manuscript should be significantly shortened to improve readability. 

Author Response

  We have added the requested paragraph on catalysis with Pd amino acid compounds.  In all honesty, there is very little catalysis with Pd amino acid compounds even though there is a general impression that there are a lot of studies in this area.  There are many more on amino-acid based ligands, or ligands derived from amino acids, but actually vey few with amino acids.  Several more references on Pd amino acid, especially proline containing, are included now in the revision.

2.  I may have an incorrect philosophy in regard to the inclusion of SI in completely online journals, so correct me if I am wrong, but I believe it is better to put everything in the main paper since there is no actual page printed and no cost to having it in the paper itself.  Whether in the paper or in the supplementary information, it takes the same amount of storage.  Nevertheless, I complied with this reviewer's suggestion to move some  figures into SI.

Round 2

Reviewer 1 Report

The same opinion.