Rhodium-Catalyzed Alkylation of Aromatic Ketones with Allylic Alcohols and α,β-Unsaturated Ketones
Round 1
Reviewer 1 Report
The work presented by Fan and Xian-Ying Shi and collaborators is an interesting contribution and I consider that it can appear in an important journal such as Catalysts. Overall, the paper is well prepared, well organized, the language is not inappropriate and the spectra are well presented. I consider that the paper can be published after addressing the following suggestions:
- The authors demonstrated in Figure 1 the need for the use of copper salt for the reaction to occur. In the opposite way in Figure 2 the use of copper salt was not necessary. What is the reason for this change in reaction conditions?
- What function does HFIP play in this reaction. Obviously the effect of HFIP here is beyond a simple solvent.
- Why was RhCp* chosen by the authors? Other rhodium species are efficient in the present reaction. The choice of the pre-catalyst should be better contextualized.
- Scheme 1 should be improved For example, Scheme 1A could describe which catalysts, oxidants, research groups are involved. In short, more information should be inserted in Scheme 1.
- The authors describe the mechanism of the reaction and Cu species are present in the mechanism, but the authors do not elaborate the discussion about the necessity of the presence or absence of the copper salt. In mechanistic terms, the authors should discuss in detail the mechanistic differences with the presence and absence of copper species and also the peculiarities related to the different solvents used in the reaction, HFIP and TFE.
- Important references on CH activation could be cited: Chemical Communications 58 (2022) 3101-3121; Important references on CH activation reactions via weak O-coordination could be cited: Chemical Communications 54 (2018) 12840-12843;
No Comments
Author Response
Comments 1: The work presented by Fan and Xian-Ying Shi and collaborators is an interesting contribution and I consider that it can appear in an important journal such as Catalysts. Overall, the paper is well prepared, well organized, the language is not inappropriate and the spectra are well presented. I consider that the paper can be published after addressing the following suggestions.
Response: Thank you very much for your positive comments on our work.
Comments 2: - The authors demonstrated in Figure 1 the need for the use of copper salt for the reaction to occur. In the opposite way in Figure 2 the use of copper salt was not necessary. What is the reason for this change in reaction conditions?
Response: Although the final products are the same employing allylic alcohols and α,β-unsaturated ketones as substrates, the mechanism is different. Using allylic alcohols as substrate, the reaction undergoes the addition of C–H bond to double bond in allylic alcohol and β-hydride elimination, which need the oxidant to finish the catalytic cycle. As for α,β-unsaturated ketones, the reaction undergoes the addition of C–H bond to double bond in α,β-unsaturated ketones and protonation, in which protonation does not require oxidant.
Comments 3: - What function does HFIP play in this reaction. Obviously the effect of HFIP here is beyond a simple solvent.
Response: TFE and HFIP may play an important role in the stabilization of intermediate bearing electron-deficient metal center via coordination (Chem. Rev. 2022, 122, 12544-12747; Chem. Sci. 2021, 12, 3857-3870), which we have added in the revised manuscript, and the corresponding references were also cited as [46,47] (Lines 67-71, page 2).
Comments 4: - Why was RhCp* chosen by the authors? Other rhodium species are efficient in the present reaction. The choice of the pre-catalyst should be better contextualized.
Response: Thanks for your question. In fact, we examined the several rhodium and ruthenium catalysts, such as [Cp*Rh(CH3CN)3](SbF6)2, [RhCl2(1,5-COD)]2, [Rh(C2H4)Cl]2, Rh(PPh3)3Cl, [RuCl2(1,5-COD)]2 and [RuCl2(p-cymene)]2, the unsatisfactory results were obtained, which we have added in the revised manuscript and supporting information (Lines 73-74, page 2 and Table S1 in Supporting Information).
Comments 5: - Scheme 1 should be improved For example, Scheme 1A could describe which catalysts, oxidants, research groups are involved. In short, more information should be inserted in Scheme 1.
Response: Thanks, we have revised scheme 1 according your suggestions.
Comments 6: - The authors describe the mechanism of the reaction and Cu species are present in the mechanism, but the authors do not elaborate the discussion about the necessity of the presence or absence of the copper salt. In mechanistic terms, the authors should discuss in detail the mechanistic differences with the presence and absence of copper species and also the peculiarities related to the different solvents used in the reaction, HFIP and TFE.
Response: Thanks for your kind suggestions. We have revised the discussion about mechanism. In the revised manuscript, the role of copper species was described (Lines 62-65, page 6). The desired products can be detected both in TFE and HFIP utilizing α,β-unsaturated ketones as coupling partner, and HFIP afforded a slight higher yield.
Comments 7: - Important references on CH activation could be cited: Chemical Communications 58 (2022) 3101-3121; Important references on CH activation reactions via weak O-coordination could be cited: Chemical Communications 54 (2018) 12840-12843;
Response: Thanks for your information. These two references were cited as [2] and [3] in the revised manuscript.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The article entitled “Rhodium-Catalyzed Alkylation of Aromatic Ketones with Allylic Alcohols and α,β-Unsaturated Ketones” describes the rhodium catalyzed alkylation of aromatic rings characterized by the presence of a ketone as a directing group. The last feature represents the novelty of the work.
In my opinion the article is publishable on Catalyst after minor revisions.
· My concerns are mainly about the proposed mechanism. Authors should find ways to implement a mechanistic cycle in which it is better understood what is formed in each step. For example, in the transition from D' to A, which product is obtained beyond the catalyst? or from D to Cp*Rh what happened to the OAc?
· Acetophenone and propiophenone are present only in the text (pag 3, lines 110/111). It would be better if they were represented into figure 1 with a yield of 0%.
· Scheme in table 2. The reaction temperature is 120°C but some experiments were made at 100°C.
Pag 2 line 55. “Pan and Zhao successively [38,39]” Please correct because Zhao is not among the authors of references 38 and 39.
Author Response
Comments 1: The article entitled “Rhodium-Catalyzed Alkylation of Aromatic Ketones with Allylic Alcohols and α,β-Unsaturated Ketones” describes the rhodium catalyzed alkylation of aromatic rings characterized by the presence of a ketone as a directing group. The last feature represents the novelty of the work. In my opinion the article is publishable on Catalyst after minor revisions.
Response: Thank you very much for your positive comments on our work.
Comments 2: My concerns are mainly about the proposed mechanism. Authors should find ways to implement a mechanistic cycle in which it is better understood what is formed in each step. For example, in the transition from D' to A, which product is obtained beyond the catalyst? or from D to Cp*Rh what happened to the OAc?
Response: Thanks, we have revised the mechanism.
Comments 2: Acetophenone and propiophenone are present only in the text (pag 3, lines 110/111). It would be better if they were represented into figure 1 with a yield of 0%.
Response: Thanks for your suggestions, we have added these two products in Figure 1 in the revised manuscript.
Comments 3: Scheme in table 2. The reaction temperature is 120°C but some experiments were made at 100°C.
Response: Thanks and sorry for this. The temperature in equation (Table 1) was corrected.
Comments 4: Page 2 line 55. “Pan and Zhao successively [38,39]” Please correct because Zhao is not among the authors of references 38 and 39.
Response: Thanks for your careful reading our manuscript and sorry for these two mistakes, we have corrected these in the revised manuscript (Lines 55-56, page 2).
Author Response File: Author Response.pdf
Reviewer 3 Report
The authors have provided a synthetic methodology to couple aromatic ketones with allylic alcohols and unsaturated ketones, to afford ortho substituted ketones via C-H activation promoted by a rhodium(III) complex. The procedure has been extended successfully to various substrates and the products are well characterized. The subject and work are suitable for publication in Catalysts, provided that the authors address the following matters. Language corrections are needed, some of which are indicated in this review.
Line 143 – 148. Even if most experiments were performed using 0.1 mmol of substrate, the reaction at 1 or 2mmol scale cannot really be considered as a significant scale up, as 1 mmol scale for this kind of substrate and products can still be regarded as small-scale conditions.
Lines 152-158 and Scheme 3. The deuterium isotope effect experiments should be better explained. In line 153 please express in the text the positions of H/D exchange on the benzene ring. Only the ortho positions are involved in the exchange?
In the experiment of Scheme 3b, it appears that H/D exchange involves other positions as well. Please clarify and change text accordingly. As it is, it seems that the ring undergoes substitution at various positions.
Also, explain in the text how the kinetic isotopic effect was calculated.
Line 18: aromatic ketoneS…
Line 30:….which makes such addition reaction more powerful…..(erase “to be”)
Line 45: ….. intermediates due to that AS they can….
Line 46: However, due to the weakly coordinating ability of ketone carbonyl, the application…
Line 55: successively or succesfully?
Line 74: …..rise………were detected (not was)
Line 96:….were established
Line 98: . 2.2-Dimethyl….same in line 100, use capital letter after dot.
Line 103: erase the comma in the middle of the sentence
Line 104:…..secondary alkyl….
Line 111: erase the comma in the middle of the sentence
Line 116:..to moderate to…
Line 146: …was performed…
In Tables, ND? Express acronym
Author Response
Response to comments from Referee 3
Comments 1: The authors have provided a synthetic methodology to couple aromatic ketones with allylic alcohols and unsaturated ketones, to afford ortho substituted ketones via C-H activation promoted by a rhodium(III) complex. The procedure has been extended successfully to various substrates and the products are well characterized. The subject and work are suitable for publication in Catalysts, provided that the authors address the following matters. Language corrections are needed, some of which are indicated in this review.
Response: Thank you very much for your positive comments on our work.
Comments 2: Line 143 – 148. Even if most experiments were performed using 0.1 mmol of substrate, the reaction at 1 or 2mmol scale cannot really be considered as a significant scale up, as 1 mmol scale for this kind of substrate and products can still be regarded as small-scale conditions.
Response: Thanks, we have deleted this scheme and related discussion.
Comments 3: Lines 152-158 and Scheme 3. The deuterium isotope effect experiments should be better explained. In line 153 please express in the text the positions of H/D exchange on the benzene ring. Only the ortho positions are involved in the exchange?
Response: Thanks for your suggestion. the deuterium isotope effect experiments should be better explained. Due to the reversible cyclorhodation process via C−H bond cleavage, the H/D exchange occurred, which we have discussed in the revised manuscript (Lines 147-148, page 6). Yes, only the ortho positions of carbonyl are involved in the deuteration.
Comments 4: In the experiment of Scheme 3b, it appears that H/D exchange involves other positions as well. Please clarify and change text accordingly. As it is, it seems that the ring undergoes substitution at various positions.
Response: Thanks. The unclear scheme caused a misunderstanding. We revised the Scheme 3b, which displayed clearly that 2,2-dimethyl-1-phenylpropan-1-one and 2,2-dimethyl-1-phenylpropan-1-one-D5 reacted with alcohols separately (page 5). According to the 1H NMR spectra of isolated product using 2,2-dimethyl-1-phenylpropan-1-one-D5 as substrate, the ortho position of carbonyl did not be deuterated.
Comments 5: Also, explain in the text how the kinetic isotopic effect was calculated.
Response: Thanks for your suggestion. The calculation of kinetic isotopic effect was added in the supporting Information (part 2.2).
Comments 6: Comments on the Quality of English Language. Line 18: aromatic ketoneS…Line 30:which makes such addition reaction more powerful… (erase “to be”). Line 45: ….. intermediates due to that AS they can…..Line 46: However, due to the weakly coordinating ability of ketone carbonyl, the application…Line 55: successively or succesfully? Line 74: rise… were detected (not was). Line 96:….were established. Line 98: 2.2-Dimethyl….same in line 100, use capital letter after dot. Line 103: erase the comma in the middle of the sentence. Line 104:…..secondary alkyl….Line 111: erase the comma in the middle of the sentence. Line 116:..to moderate to…. Line 146: …was performed…In Tables, ND? Express acronym
Response: Thanks for your careful reading our manuscript, we have revised manuscript according to the above suggestions.
Author Response File: Author Response.pdf
Reviewer 4 Report
The manuscript by Fan and Shi describes the C-H alpha activation of an aryl ketone in the presence of an allylic alcohol (or unsaturated ketone). This paper is a spin-off from papers by the same group on related C-H activations starting from aldehydes or carboxylic acids.
The SI appears of good quality.
Minor points to be corrected:
- Table 1: change 3a' to 3a
- Figure 2: 4a=3a; 4b=3b etc.. One molecule, one number!?!
- in the mechanism ( Scheme 4 ), D' (formation and fate) is not discussed in the main text.
Related Ru-Catalyzed reactions have been reported (EJOC 2021-2411); this paper should be discussed and cited.
Overall, the publication is interesting, concisely written and pleasant to read
Publication is recommended after discussion of the above-mentioned points.
Author Response
Comments 1: The manuscript by Fan and Shi describes the C-H alpha activation of an aryl ketone in the presence of an allylic alcohol (or unsaturated ketone). This paper is a spin-off from papers by the same group on related C-H activations starting from aldehydes or carboxylic acids. The SI appears of good quality.
Response: Thank you very much for your positive comments on our work.
Comments 2: Minor points to be corrected: - Table 1: change 3a' to 3. - Figure 2: 4a=3a; 4b=3b etc.. One molecule, one number!?! - in the mechanism ( Scheme 4 ), D' (formation and fate) is not discussed in the main text.
Response: Thanks for your careful reading our manuscript, we have revised manuscript according to your suggestions.
Comments 3: Related Ru-Catalyzed reactions have been reported (EJOC 2021-2411); this paper should be discussed and cited.
Response: Thanks for your information. This reference was cited as [5] in the revised manuscript.
Author Response File: Author Response.pdf
