无痕施陶丁格连接反应机理的理论研究.PDFVIP

2009 年第67 卷 化 学 学 报 Vol. 67, 2009 第20 期, 2335～2342 ACTA CHIMICA SINICA No. 20, 2335～2342 ·研究论文· 无痕施陶丁格连接反应机理的理论研究 方葛敏 王 晨 石 景* 郭庆祥* ( 中国科学技术大学化学系 合肥 230026) 摘要 叠氮化合物和膦硫酯的无痕施陶丁格连接反应是一种有效生成酰胺键的方法. 通过密度泛函方法研究了无痕施 陶丁格连接的反应机理. 计算结果表明反应的决速步为反应的第一步, 即膦进攻叠氮的端基氮, 形成膦基叠氮化物的 过程. 膦亚胺中间体形成之后, 向不同方向转化(酰基迁移后水解或者直接水解) 的难易程度决定了最终产物的组成. 对 几种不同偶联试剂介导的无痕施陶丁格连接反应的计算结果, 都与实验数据相吻合. 关键词 无痕施陶丁格连接; 密度泛函; 酰基迁移; 水解 Theoretical Study on Reaction Mechanism of Traceless Staudinger Ligation Fang, Gemin Wang, Chen Shi, Jing* Guo, Qingxiang* (Department of Chemistry, University of Science and Technology of China, Hefei 230026) Abstract The traceless Staudinger ligation of azides and phosphines is an effective method to produce an amide bond. In this work, density functional theory (DFT) calculations were carried out to investigate the mechanism of the traceless Staudinger ligation, which suggested that its rate-limiting step was the attack of azide on phosphine leading to the formation of phosphazide. After the formation of iminophosphorane in- termediate, competition between acyl transfer followed by hydrolysis and direct hydrolysis determined dif- ferent product distributions. The traceless Staudinger ligations mediated by different coupling reagents were then computed. The results were consistent with the experiments. Keywords traceless Staudinger ligation; density functional theory; acyl transfer; hydrolysis 多肽片段的化学选择性连接是多肽和蛋白质合成 1919 年, Staudinger 和Meyer[4]发现有机叠氮化合物 领域中重要的策略. 当前最常用的