The Origins of Dramatic Differences in Five-Membered vs Six-Membered Chelation of Pd(II) on Efficiency of C(sp3)–H Bond Activation

• Published in: Journal of the American Chemical Society 2017-06, Vol.139 (25), p.8514-8521
• Main Authors: Yang, Yun-Fang, Chen, Gang, Hong, Xin, Yu, Jin-Quan, Houk, K. N
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.7b01801

The origin of the unique effectiveness of six-membered chelates on the β-methylene C­(sp3)–H activation reactions by Pd­(II) catalyst was explained with density functional theory. The Pd­(II) catalysts that involve five-membered chelates are inactive in this transformation. Computational studies suggest that the C­(sp3)–H bond activation is the rate-limiting step in both cases. The C­(sp3)–H bond activation with a five-membered chelate is unfavorable by 7.7 kcal/mol compared to the corresponding six-membered chelate with Pd­(II). Two factors cause the difference: (1) the dimeric Pd species with five-membered chelation square-planar structure is more stable than that with six-membered chelation by 2.0 kcal/mol; (2) steric repulsion between the ArF group of the substrate and the quinoline group of the acetyl-protected aminomethyl quinoline ligand destabilizes the five-membered chelate transition structure by 5.7 kcal/mol. The six-membered chelate of Pd­(II) with an acetyl-protected aminoethyl quinoline ligand orients the ligand away from the ArF group of the substrate and alleviates the steric repulsion.