Engineering and Performance of Ruthenium Complexes Immobilized on Mesoporous Siliceous Materials as Racemization Catalysts

Round 1

Reviewer 1 Report

The article by Kuźnik et al. deals with the development of a synthetic protocol suitable for chemo-enzymatic dynamic kinetic resolution (DKR) purposes, enabling the racemization of enantiomerically pure secondary 1-arylethanols (Ar = phenyl and 2-naphthyl) in the presence of an alkoxide base (tBuOK). The catalysts employed are two ruthenium-based complexes, which were immobilized (both covalently and non-covalently) on mesoporous silica particles (namely, MCF and SBA-15).

The study is well conceived and organized and does deserve publication in Catalysts after, however, some major revisions.

1. The number of secondary alcohols investigated is quite low; the authors should broaden it, to make the procedure they propose more general and reproducible.
2. The authors should clearly explain in the text (and in the caption to tables as well) how they calculated the percentage of conversion for the racemization reaction (i.e., the enantioselective technique used to check it). Furthermore, they’d better report their results in terms of enantiomeric excess (e.e.%) reached.
3. For the full characterization of their immobilized systems, beyond TGA and FT-IR, the authors are strongly encouraged to provide elemental analysis (i.e., carbon and nitrogen content) and the corresponding coverage data, to gain another comparative term for the two SBA and MCF systems. In fact, beyond the difference in the porosity, the two materials could differ in the catalyst loading achieved.
4. Page 3: the sentence “In a typical DKR of secondary alcohols the complexes cooperate in tandem with a lipase B from Candida Antarctica (CAL-B) leading to enantioselective acylation of the targeted alcohol [25]” is ambiguous, given the section where it has been reported (i.e., Results and Discussion). Since the authors did not resort to the use of any enzyme, they'd better not write it here (if they wish, they could move the sentence to the Introduction).
5. Table 7, please add, as a footnote to the table, the definition of S_BET, V_p, d_p and d_w descriptors.

Minor items

In the Title: please replace “immobilized in” by “immobilized on”

In the Abstract: please type, after “Dynamic kinetic resolution”, the corresponding acronym. Moreover, for a better impact and visibility of their study, the authors could introduce here all the techniques used for the characterization of their materials (by writing something like: “the synthesized materials were fully characterized by FT-IR, TGA and nitrogen adsorption/desorption isotherms at 77 K”).

Page 12, section 4.1: for the synthesis of MCF and SBA-15 materials, the authors refer to their own [30] and [34] publications, respectively, but the it seems to me that the references quoted are not by their research group. Please, check the reference numbers properly.

Author Response

Please, kindly find the attached file the Author's Reply to the Review Report (Reviewer 1).

Author Response File: Author Response.pdf

Reviewer 2 Report

This was a detailed paper describing a fairly comprehensive study of the solid-supporting of a racemisation catalyst and its subsequent testing. Such approaches to the heterogenisation of homogeneous catalysts are very popular ways in which to make the homogeneous reaction more practical e.g. in theory the catalyst can be filtered off and reused. In practice it is actually extremely difficult to achieve due to access limitations of the substrate to the catalyst and the problems of leaching of the catalyst from the support.

The results are interesting enough but in their present form they are not, in my view, acceptable for publication and significant improvement to the results and the presentation is required.

Figure 2 is confusing, there are three homogeneous complexes numbered 1-3 then another Ru(3) (non covalent supported) and Ru(2) (covalent supported).

There should be more information in the main text on how they were prepared. At least a sentance of explanation.

I don’t understand what the result in Table 1 is. Is the 'conversion' a measure of racemisation? The alcohol is not actually converted into another molecule. If it is racemisation then make this clear and maybe add the ee over time change graph to supporting information. Or is it a measure of the acylation with an enzyme (the preceding paragraph hints at this but there is no mention of an enzyme in the experimental part). The racemisation is no real surprise anyway as these complexes have been known to have this type of activity for almost 20 years now.

After preparing the two supported catalysts illustrated in Figure 2, how was it confirmed that the catalyst had been incorporated and what level? IR data is useful but does not give a measure of the level of loading. Was some material recovered unsupported that could give a clue for example if 1g of catalyst was used to support and 650 mg was recovered then that at least provides an estimate that about 350 mg might have been supported. Given that there are two stages of functionalisation, which can include an over-benzoylation of the silicas, then there really needs to be some sort of assessment of how much actual catalyst has been incorporated – could ICP of Ru be used?

I have my doubts about the study of the ncBn reagent. Can pi-stacking really hold a catalyst in a support? I am not aware of any strong precedents for this sort of supporting and would expect that it would be easily leached. From what I have read of the literature on supporting catalysts, covalent linkers seem essential, or in some cases electrostatic ones through charged complexes. The authors need to study the leaching and try to obtain some idea of how much catalyst comes off in each recycle attempt.

The last paragraph on page 4 is confusing, The authors say that supported compounds were made but were poor so the catalysts were prepared under different conditions (e.g. higher T for calcination) and then the synthesis is discussed. But how does this differ from the initial conditions use to prepare the supported catalysts? And another was made with twice as much CMBC. The expression of mmol of triethoxy silyl and CMBC per g of support is a little confusing – is this sufficient to overwhelm the sites on the support or is it well short of stoichiometric?

I found Table 2 the most confusing. In the first entry there in no MCF but the reaction still works – because it is pure catalyst? But this is known to work so the entry is essentially redundant. The other results are confusing, What does ‘pure ‘ mean? And in the other entries there are just pictures of the molecules used to modify the support. So please – in the footnotes, define what catalyst is used in each entry. Also in Table 2 I have the same comment on conversion. What does this mean? Racemisation? – if so then make this clear.

But really none of the results in Table 2 (or Table 3) are very meaningful for the purpose of the paper because it is not clear whether or not the reaction is being carried out in the silica or in the solution, i.e. by any complex that leaches. Table 4 is really the one that matters in a study of this type – and it tells us that the catalyst does not stay on the support or cannot remain active.

So whilst this is interesting work, it serves as an example of how challenging this work is. At present the paper does not have enough novel or urgent material to warrant acceptance. The authors need to get an idea of how much catalyst is actually supported, and how much leaches. Then the results will be much more meaningful.

Author Response

Please, kindly find the attached file the Author's Reply to the Review Report (Reviewer 2).

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The article by Kuźnik et al. has been revised according to the reviewer suggestions and the efforts of the authors have been very appreciated. Now the manuscript, as far as I am concerned, can be accepted for publication in Catalysts.

Just a clarification on S_BET definition in Table 7. Rather than simply writing “multilayer adsorption”, I would suggest defining SBET as follows: “specific surface area measured by the BET method”.

Reviewer 2 Report

I was originally referee 1 on this submission. The authors have gone to significant lengths to accommodate my suggestions and have made satisfactory changes to the paper to make it acceptable for publication.