Mechanistic and thermodynamic studies on directing group-assisted copper-catalyzed α-C(sp2)−H amination of aryl amines with alkylamines

• Published in: Journal of organometallic chemistry 2024-12, Vol.1022, p.123400, Article 123400
• Main Authors: Cui, Jinglei, Zheng, Wenrui, Jiao, Peilei, Jin, Hao
• Format: Article
• Language: English
• Subjects: Mechanistic; Reduction potential; SET; Thermodynamic; α-C(sp2)−H functionalization
• ISSN: 0022-328X
• DOI: 10.1016/j.jorganchem.2024.123400

•In the mechanism study, we calculated three possible paths of the model reaction.•The SET involved radical-cation mechanism is proved to be the most favorable.•In the thermodynamic study, the ered involved in the SET process was evaluated.•The many quantitative structure-activity relationships are analyzed. In mechanistic, three possible pathways of α-C(sp[2])−H functionalization amination of picolinamide with morpholine catalyzed by Cu(OAc)2/O2 in p-xylene were studied. Through theoretical calculations, it was found that the pathway involving the radical-cation intermediates produced by the subsequent single electron transfer (SET) was proved to be the most favorable. Then, we also discussed the solvation and substituent effects of three key steps, including N − H bond deprotonation, C − N bond formation rate-determining step and C − H bond deprotonation step, so as to fully understand the mechanism of directing group-assisted copper-catalyzed α-C − H functionalization of aniline and the screening of substrates and solvents. In thermodynamic, the SET process plays a crucial role in the entire catalytic cycle. Therefore, we further studied the reduction potential (Ered) values of Cu(II) radical-cation intermediates involved in the SET process, reflecting the occurrence trend of SET from the thermodynamic point of view, and studied the substituent effects and structure-activity relationships on Ered values of Cu(II) complexes derivatives formed by different Cu(Ⅱ) catalysts, different directing groups, different alkylamines and aromatic amines substrates. It is also found that there are many quantitative structure-activity relationships between Ered and the singly occupied molecular orbital (SOMO) energy, Hammett substituent constant σ+ and other structural parameters. [Display omitted]