Bis-NHC–Ag/Pd(OAc)2 Catalytic System Catalyzed Transfer Hydrogenation Reaction
Round 1
Reviewer 1 Report
In this manuscript, Dong-Sheng Lee and co-workers report a procedure for the semi-hydrogenation of alkynes through transfer hydrogenation using formic acid as the hydrogen source. The ligand is a bis-NHC and the catalytic system is formed in situ by mixing the corresponding [Ag(bis-NHC)]2 complex with Pd(OAc)2. The reported results are about the same as the ones obtained with previous systems. My biggest concern rests on the actual nature of the catalytic species, as no evidence is given in the manuscript concerning this point. The authors claim that the bis-NHC ligand is bidentate and chelating on Pd but I really doubt of this assertion. Indeed, with such a linker, the mode of coordination (chelating vs bridging) depends on the conditions of complexation. Moreover, chelation would prevent reductive elimination between NHC and hydride only if it forced the imidazolyl ring to be planar to the coordination plane, and here the linker is too flexible. Therefore, the authors should provide more evidence to support their statement. In addition, the possibility of a catalysis by metal nanoparticles, which is known to be operative with Pd-NHC complexes (Ananikov, Chem. Sci. 2020, 11, 6957 for example). Instead of figure 2, it would have been more instructive to have a kinetic curve for the conversion. A scheme over the tables would be beneficial for a better understanding. For example, to which compounds do 11 and 12 refer? NMR spectra of the products of catalysis should be added in the SI to prove the purity of the compounds. Finally, the references in the introduction should be updated.
Author Response
Q1. The authors claim that the bis-NHC ligand is bidentate and chelating on Pd but I really doubt of this assertion. Indeed, with such a linker, the mode of coordination (chelating vs bridging) depends on the conditions of complexation. Moreover, chelation would prevent reductive elimination between NHC and hydride only if it forced the imidazolyl ring to be planar to the coordination plane, and here the linker is too flexible. Therefore, the authors should provide more evidence to support their statement.
Response Q1: Reported in our previous article (RSC Adv. 2018, 8, 26407–26415), the bis-NHC–Pd complex, confirmed by X-ray structural determination, was prepared by the reaction of bis-NHC–Ag complex and PdCl2(CH3CN)2. Therefore, we propose the formation of bis-NHC–Pd complex in this study based on our previous results
Q2. Instead of figure 2, it would have been more instructive to have a kinetic curve for the conversion.
Response Q2: Because the NMR spectra were taken without quantitative calibration it will be difficult to transform the spectra into a kinetic curve we decided to remove figure 2 and related statements from our manuscript. (see revised manuscript: Catalysts_Text_2)
Q3. A scheme over the tables would be beneficial for a better understanding. For example, to which compounds do 11 and 12 refer?
Response Q3: The schemes were inserted into Table 3, Table 4, and Table 5, respectively. (see revised manuscript: Catalysts_Text_2)
Q4. NMR spectra of the products of catalysis should be added in the SI to prove the purity of the compounds.
Response Q4: The 1H and 13C NMR spectra of the products of catalysis have been added. (see revised supporting information: SI_catalysts_2)
Q5. Finally, the references in the introduction should be updated.
Response Q5: The references have been updated. (see revised manuscript: Catalysts_Text_2)
Reviewer 2 Report
After a deep reading of the manuscript, I have the following suggestions and comments that are compiled in the attached document.
Comments for author File: 
Comments.pdf
Author Response
Q1. Table 1. The control reaction of the trans-cinnamyl alcohol (entry 6) is performed in absence of bis-NHC–Ag complex (line 67). Can the authors confirm if this reaction is done in the absence or in presence of the Palladium precursor or only is absent the bis-NHC–Ag complex?
Response Q1: In Table 1. The control reaction of the trans-cinnamyl alcohol (entry 6) is performed in absence of bis-NHC–Ag complex, but in presence of Palladium precursor (Pd(OAc)2).
Q2. Table 2: replace the Ac– by the corresponding functional group in the nitroacetophenone and in the reduced product.
Response Q2: The Ac– has been replaced by the corresponding functional group. (see revised manuscript: Catalysts_Text_2)
Q3. Line 97: The authors describe quantitative hydrogenation of the alcohol 7a. Are the authors referring this data to the conversion or to the isolated yield? Because they describe the isolated yield at about 92%. Please correctly indicate in the manuscript.
Response Q3: “Quantitatively” means the conversion. It was replaced by “in 92% yield”. (see revised manuscript: Catalysts_Text_2)
Q4. Table 3; indicate in the legend of the table that the reactions are referred to the substrate 1,2-diphenylacetylene 3a.
Response Q4: “3a” is inserted after 1,2-diphenylacetylene in Line 78. (see revised manuscript: Catalysts_Text_2)
Q5. Line 105. The authors comment the absence of the over-reduced product (9a) of the substrate 3a, but the authors did not name this product and the neither propose the structure.
Response Q5: The scheme was inserted into Table 3. The over-reduced product (9a) is an alkane. (see revised manuscript: Catalysts_Text_2)
Q6. Line 108. Insert “8a” after cis-stilbene.
Response Q6: “8a” is inserted after cis-stilbene. (see revised manuscript: Catalysts_Text_2)
Q7. Line 121-123. Indicate that these results are referred to 3a. Now the sentence is confusing.
Response Q7: The sentence was revised to “For 1,2-diphenylacetylene 3a as the substrate, the use of DMF/H2O (5/5) solvent system at 80 oC (condition A) produced 100% a conversion yield confirmed by GC with a Z/E ratio of 93/7 (entry 1).” (see revised manuscript: Catalysts_Text_2)
Q8. Table 4 and Table 5. Insert a general reaction scheme before each table with the general structure of the possible reaction products 9, 11, and 12.
Response Q8: The schemes were inserted into Table 4 and Table 5, respectively. (see revised manuscript: Catalysts_Text_2)
Q9. Table 4: Did the authors check the reactions of 3b and 3d under the A reaction conditions?
Response Q9: The transfer hydrogenation reactions of 3b and 3d were not carried out under the A reaction conditions, an analog 3d, ethyl 3-phenylpropiolate, was carried out under condition A. Poor conversion (33%) and Z/E ratio of 85/15 were obtained and hence this result was nor reported in this manuscript.
Q10. Table 4: Have the authors tested the TH of bis-alkyl internal alkynes?
Response Q10: Although the TH of bis-alkyl internal alkynes was not tested, we believed that the results should be similar to those of the TH of bis-aromatic internal alkynes.
Q11. Table 4: Have the authors any idea why the substrates with alkyl substituents in the alkyne group react faster than others with the aromatic alkynes (2 h instead of 24 h)? Which is the influence of the aromatic groups?
Response Q11: In Table 4, the substrate with alkyl substituents in the alkynes, such as 3c, was proceeded the TH reaction within 24 h under condition A with 47% conversion. However, the substrate with aryl substituents in the alkynes, such as 3a, was carried out the TH reaction within 24 h under condition A with 100% conversion. It seems that the rate of 3a is faster than that of 3c. The other substrate with aryl substituents in the alkynes, 3b, was proceeded the TH reaction within 2 h under condition B with 100% conversion, while 3c was carried out the TH reaction within 24 h under condition B with 100% conversion. The rate of 3b is faster than that of 3c. It might be the reason that the aryl group, phenyl or pyridinyl, coordinate with metal.
Q12. Table 4 and Table 5: have the authors check the chemoselectivity of the reaction of internal and terminal alkynes with ketones or aldehydes, 4-Phenyl-3-butyn-2-one or 4-(Phenylethynyl)acetophenone
Response Q12: 4-Phenyl-3-butyn-2-one and 3-Phenylpropiolaldehyde have been used in the transfer hydrogenation to result in complicated mixture and therefore were not reported in the manuscript.
Q13. Table 4 and Table 5: The authors only tested p-substituted aromatic terminal alkynes in the TH reactions, did the authors any reaction with o- or m-substituted substrates? The position of the substituents can have any influence in the effectiveness of the reaction?
Response Q13: It will be interesting to examine the TH reaction on o- and m-substituted substrates, however, due to limited manpower we plan to carry out the study in due process.
Q14. Line 136: Legend Table 4: Delete the reaction time 24h as general time for all reactions in the legend because, as is descrived in the table 4, each substrate needs a different reaction time to completely react.
Response Q14: The reaction time “24 h” in the legend of Table 4 was deleted. (see revised manuscript: Catalysts_Text_2)
Q15. In the experimental procedures of the TH the authors write that the reaction takes place in presence of K3PO4 but in the legends of the tables and in the manuscript the authors did not mention it. Which is the role of the potassium phosphate in these transfer hydrogenations? Or, it is an erratum? In the experimental procedure the amount of NEt3 is missing.
Response Q15: “K3PO4·H2O” in the experimental procedure of the TH reaction is an erratum. It was replaced by “NEt3”. (see revised manuscript: Catalysts_Text_2)
Reviewer 3 Report
The present authors did a nice job on this work. It would be nice to include the following items in the manuscript/supporting file.
-Please also include structures for compounds 9, 11 and 12.
-Also, provide few key NMRs spectra (1H and 13C) for the products synthesized from this method in supporting file.
Author Response
Q1. Please also include structures for compounds 9, 11 and 12.
Response Q3: The schemes were inserted into Table 3, Table 4, and Table 5, respectively. (see revised manuscript: Catalysts_Text_2)
Q2. Also, provide few key NMRs spectra (1H and 13C) for the products synthesized from this method in supporting file.
Response Q2: The 1H and 13C NMR spectra of the products have been added. (see revised supporting information: SI_catalysts_2)
Round 2
Reviewer 1 Report
In this revised version, Dong-Sheng Lee and co-workers responded to my comments only in part. I will answer following their responses.
R2: I agree that without secured quantification means, the integration of the 1H NMR spectra and the establishment of a kinetic curve would be risky, and the removal of Figure 2 is a wise decision.
R3 and R4: Ok
R5: I think I was not enough precise, when requiring that the references in the introduction should be updated: The general references concerning the organometallic chemistry of NHCs are very old and much more recent references exist and should be preferred. More annoying is the addition of Ananikov’s reference as reference 1 without any discussion of the implications that it definitely has on the discussion and the treatment of the data in the present work. Moreover, this reference cannot illustrate the first sentence, as the latter relates to general reviews on the organometallic chemistry of NHCs.
R1: This is the most problematic point in my opinion. In this revised version, the authors still claim the chelating nature of the bis-NHC ligand, and give one of their previous reference as a proof (RSC Adv. 2018, 8, 26407). I had already checked this reference during the first round of refereeing and I am still staying on my position: this previous paper does NOT provide any proof that the bis-NHC ligand is chelating. Please remind that a chelating ligand binds ONE metal center. In this case, the bis-NHC is a bridging ligand between two Pd centers and in any case is chelating. Thus I reformulate my request in clearer words: Without an experimental evidence that the bis-NHC is really chelating on one Pd center, the authors should revise completely their hypothesis and discussion, and should fairly consider the possibility that the actual active species in this transfer hydrogenation catalysis are Pd nanoparticles either supported by the bis-NHC ligand or without any NHC ligand. Some hints: what is the aspect of the catalytic mixture (still colored, grey, with precipitate …), a mercury-drop test would provide a good start, kinetic profile of the catalytic reaction …
In this revised version, Dong-Sheng Lee and co-workers responded to my comments only in part. I will answer following their responses.
R2: I agree that without secured quantification means, the integration of the 1H NMR spectra and the establishment of a kinetic curve would be risky, and the removal of Figure 2 is a wise decision.
R3 and R4: Ok
R5: I think I was not enough precise, when requiring that the references in the introduction should be updated: The general references concerning the organometallic chemistry of NHCs are very old and much more recent references exist and should be preferred. More annoying is the addition of Ananikov’s reference as reference 1 without any discussion of the implications that it definitely has on the discussion and the treatment of the data in the present work. Moreover, this reference cannot illustrate the first sentence, as the latter relates to general reviews on the organometallic chemistry of NHCs.
R1: This is the most problematic point in my opinion. In this revised version, the authors still claim the chelating nature of the bis-NHC ligand, and give one of their previous reference as a proof (RSC Adv. 2018, 8, 26407). I had already checked this reference during the first round of refereeing and I am still staying on my position: this previous paper does NOT provide any proof that the bis-NHC ligand is chelating. Please remind that a chelating ligand binds ONE metal center. In this case, the bis-NHC is a bridging ligand between two Pd centers and in any case is chelating. Thus I reformulate my request in clearer words: Without an experimental evidence that the bis-NHC is really chelating on one Pd center, the authors should revise completely their hypothesis and discussion, and should fairly consider the possibility that the actual active species in this transfer hydrogenation catalysis are Pd nanoparticles either supported by the bis-NHC ligand or without any NHC ligand. Some hints: what is the aspect of the catalytic mixture (still colored, grey, with precipitate …), a mercury-drop test would provide a good start, kinetic profile of the catalytic reaction …
Author Response
- This is the most problematic point in my opinion. In this revised version, the authors still claim the chelating nature of the bis-NHC ligand, and give one of their previous reference as a proof (RSC Adv. 2018, 8, 26407). I had already checked this reference during the first round of refereeing and I am still staying on my position: this previous paper does NOT provide any proof that the bis-NHC ligand is chelating. Please remind that a chelating ligand binds ONE metal center. In this case, the bis-NHC is a bridging ligand between two Pd centers and in any case is chelating. Thus I reformulate my request in clearer words: Without an experimental evidence that the bis-NHC is really chelating on one Pd center, the authors should revise completely their hypothesis and discussion, and should fairly consider the possibility that the actual active species in this transfer hydrogenation catalysis are Pd nanoparticles either supported by the bis-NHC ligand or without any NHC ligand. Some hints: what is the aspect of the catalytic mixture (still colored, grey, with precipitate …), a mercury-drop test would provide a good start, kinetic profile of the catalytic reaction …
R1: We decided to remove the description of related to “chelate” due to no direct experimental evidence and lack of manpower to study the mechanism for the time being. At the same time, we do not rule out the possibility that the actual active species in this transfer hydrogenation catalysis are Pd nanoparticles. Therefore, the manuscript has been revised. (see revised manuscript: Catalyst_Text_3)
5: I think I was not enough precise, when requiring that the references in the introduction should be updated: The general references concerning the organometallic chemistry of NHCs are very old and much more recent references exist and should be preferred. More annoying is the addition of Ananikov’s reference as reference 1 without any discussion of the implications that it definitely has on the discussion and the treatment of the data in the present work. Moreover, this reference cannot illustrate the first sentence, as the latter relates to general reviews on the organometallic chemistry of NHCs.
R5: The references have been updated. (see revised manuscript: Catalysts_Text_3)
Round 3
Reviewer 1 Report
There is no major problem in this manuscript anymore, even if I still think that a more careful study should have been carried out to raise the significance of the work. This manuscript might be suitable for publication in Catalysts.
