Chemistry Department, Istanbul Technical University, Faculty of Science and Letters, Ayazaga Campus, Maslak, Istanbul, Turkey.
J Mol Graph Model. 2012 Apr;34:101-7. doi: 10.1016/j.jmgm.2011.12.012. Epub 2012 Jan 8.
In this study, the mechanism of CuAAC reaction and the structure of copper acetylides have been investigated with quantum mechanical methods, namely B3LYP/6-311+G(d,p). A series of possible copper-acetylide species which contain up to four copper atoms and solvent molecules as ligand has been evaluated and a four-copper containing copper-acetylide, M1A, was proposed more likely to form based on its thermodynamic stability. The reaction has been modeled with a representative simple alkyne and a simple azide to concentrate solely on the electronic effects of the mechanism. Later, the devised mechanism has been applied to a real system, namely to the reaction of 2-azido-1,1,1-trifluoroethane and ethynylbenzene in the presence of copper. The copper catalyst transforms the concerted uncatalyzed reaction to a stepwise process and lowers the activation barrier. The pre-reactive complexation of the negatively charged secondary nitrogen of azide and the positively charged copper of copper-acetylide brings the azide and the alkyne to a suitable geometry for cycloaddition to take place. The calculated activation barrier difference between the catalyzed and the uncatalyzed reactions is consistent with faster and the regioselective synthesis of triazole product.
在这项研究中，我们使用量子力学方法（B3LYP/6-311+G(d,p)）研究了铜催化的叠氮-炔环加成（CuAAC）反应的机理和铜炔化物的结构。我们评估了一系列可能包含多达四个铜原子和溶剂分子作为配体的铜炔化物物种，并基于其热力学稳定性，提出了更有可能形成的四核铜炔化物 M1A。我们使用一个代表性的简单炔烃和一个简单的叠氮化物来模拟反应，以集中研究反应机理的电子效应。随后，我们将设计的反应机理应用于一个实际体系，即 2-叠氮-1,1,1-三氟乙烷和苯乙炔在铜存在下的反应。铜催化剂将协同无催化反应转化为逐步反应，并降低了活化能垒。叠氮化物的带负电荷的仲氮和铜炔化物的带正电荷的铜之间的预反应配位使叠氮化物和炔烃处于适合环加成发生的合适几何形状。催化和非催化反应之间的计算得到的活化能垒差异与更快和区域选择性的三唑产物的合成一致。
