Yang Yuhang, Cao Fei, Yao Linbin, Shi Tao, Tang Bencan, Kuninobu Yoichiro, Wang Zhen
School of Pharmacy, Lanzhou University, West Donggang Road No. 199, Lanzhou 730000, Gansu, China.
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, Gansu, China.
J Org Chem. 2020 Aug 7;85(15):9713-9726. doi: 10.1021/acs.joc.0c01038. Epub 2020 Jul 29.
Mechanistic studies on Cu-catalyzed/mediated sp C-H amidation and acetoxylation are investigated from experimental and computational aspects. The concerted metalation-deprotonation (CMD) mechanism rather than a radical-involved pathway is proved to occur in amidation and acetoxylation reactions, and this is the rare example of the CMD mechanism involved in the more challenging sp C-H activations. Theoretical calculations demonstrated that CMD is the rate-determining step either for methylic or benzylic positions in amidation and acetoxylation reactions, and intermolecular nucleophilic addition of acetate anions is more favorable than the ring opening of β-lactams and intramolecular acetoxylation. These mechanistic studies on the divergent and condition-dependent product formation are critical for developing Cu-promoted C-H functionalization via the CMD mechanism.
从实验和计算方面对铜催化/介导的sp C-H酰胺化和乙酰氧基化反应的机理进行了研究。结果表明，酰胺化和乙酰氧基化反应中发生的是协同金属化-去质子化（CMD）机理，而非涉及自由基的途径，这是在更具挑战性的sp C-H活化反应中涉及CMD机理的罕见例子。理论计算表明，CMD是酰胺化和乙酰氧基化反应中甲基或苄基位置的速率决定步骤，并且醋酸根阴离子的分子间亲核加成比β-内酰胺的开环和分子内乙酰氧基化更有利。这些关于不同的、依赖条件的产物形成的机理研究对于通过CMD机理开发铜促进的C-H官能化反应至关重要。
