The authors have developed a methodology for selective functionalization of cephalosporin at the C3 position using palladium catalysis. While several palladium-catalyzed couplings of cephalosporin with various partners (e.g., organotin, metal halides, sulfur, and nitrogen nucleophiles) have been explored previously (J. Org. Chem. 1990, 55, 23, 5833–5847; J. Org. Chem. 1989, 54, 20, 4962–4966), it appears that this methodology was already known. In my view, the authors have modified the coupling partner to a boronic acid. The article needs major revision as the following queries are required to be addressed.
1. The manuscript discusses palladium-catalyzed C3 functionalization of cephalosporin, but the authors should cite relevant literature on the topic, such as J. Org. Chem. 1990, 55, 23, 5833–5847.
2. The solvent optimization section needs further clarification. Did the authors extend the reaction time in dioxane? The 30% yield observed after 5 hours suggests the possibility of improving the yield with more time. It would be helpful for the authors to perform the reaction for 24 hours and provide further details. Additionally, while the yield is calculated by LC-MS for most reactions, it is not for the THF reaction, which creates confusion. The authors should address this inconsistency. Also, try CH3CN, and DMF.
3. In Table 1, the superscript "e" is misplaced and should be corrected.
4. The substrate scope should be expanded slightly. It would be beneficial to explore the effects of electron-withdrawing and electron-donating groups as well as heterocycle-fused phenylboronic acids.
5. The substrate scope table is somewhat difficult to read. For instance, in entry 2, "b'c" refers to the pinacol ester of phenylboronic acid. It would be easier for the readers if the structure of this compound were included. Simplifying the presentation would improve clarity.
6. On page 5, line 33, it is mentioned that “in the case of dioxolane 2d, the corresponding cephalosporin 3d was obtained with a good yield (Table 2, Entry 4).” However, the characterization data for compound 3d (in SI part) corresponds to the deprotected diol, not the compound 3d as described. The authors should clarify and ensure consistency.
7. The yield of compound 3e is listed as 86% in the manuscript, but as 76% in the SI file. The authors should confirm the correct yield.
8. The yield of compound 3f after TFA treatment is noted as 45% in the SI file, but 77% in the table. The authors should explain this discrepancy.
9. If possible, the authors should provide the NMR data for compound 4. The 1H NMR Spectra of compound 3b need to be cleaned.