Calvo-Losada Saturnino, Pino-González María Soledad, Quirante José Joaquín
Departamento de Química Física, Facultad de Ciencias, Universidad de Málaga , Campus de Teatinos, s/n. 29071 Málaga, Spain.
J Phys Chem B. 2015 Jan 29;119(4):1243-58. doi: 10.1021/jp5055414. Epub 2015 Jan 20.
The distinct role of the Cu(I) in the Huisgen dipolar cycloaddition of azides to alkynes (denoted as CuAAC) is disclosed by following the evolution of the topology of the Laplacian of the electronic charge density, ∇(2)ρ(r), and its gradient vector field, ∇∇(2)ρ(r), along the reaction coordinate with several density functionals (wB97XD, LCwPBE, M06-2X, M06-L, B3LYP) and the 6-311++G(d,p) basis set. Remarkably, in view of the topology of ∇(2)ρ(r) and ∇∇(2)ρ(r), the mechanism appears to be diverse (asynchronous concerted or stepwise) depending on the reaction conditions. Overall, the catalyst orchestrates first the formation of the external N-C and subsequently the internal one by following alternatively a pericyclic-like or a pseudopericyclic-like mechanism. The role of the catalyst is envisaged as transforming the type of the mechanism from pericyclic to pseudopericyclic, and thence eventually facilitating the process. The mononuclear process (CuAAC) is concerted (with L = CH3CN) with all the functionals tested (i.e., wB97XD, LCwPBE, M06-2X, M06-L), except for the B3LYP who rendered a stepwise mechanism. Nevertheless, with L = H2O and CH3OH attached to the copper, the process becomes asynchronous concerted. Interestingly, upon introduction of the second Cu (Cu2AAC) at our best theory level (i.e., LCwPBE/6-311++G(d,p)), all the processes considered turned out to be concerted except for the 1,4-Cu2AAC which is predicted to be stepwise, with an extremely low enthalpy for the ring-contraction process (0.18 kcal/mol). This fact is explicated by the stability of the intermediate, which is in turn rationalized by the hole within the valence shell of the carbon attached to the Cu and the position of the (3, -3)LP, of the internal N, toward it. Furthermore, due to the tiny energy difference between the stepwise dinuclear and concerted mononuclear mechanisms (0.39 kcal/mol), we argue that the concurrence of both processes (CuAAC and Cu2AAC) is feasible.
通过采用几种密度泛函（wB97XD、LCwPBE、M06 - 2X、M06 - L、B3LYP）和6 - 311++G(d,p)基组，沿着反应坐标追踪电子电荷密度的拉普拉斯算子∇(2)ρ(r)及其梯度向量场∇∇(2)ρ(r)的拓扑结构演化，揭示了Cu(I)在叠氮化物与炔烃的惠斯根偶极环加成反应（记为CuAAC）中的独特作用。值得注意的是，鉴于∇(2)ρ(r)和∇∇(2)ρ(r)的拓扑结构，根据反应条件，该反应机理似乎多种多样（异步协同或分步）。总体而言，催化剂首先通过交替遵循类周环或类假周环机理来协调外部N - C键的形成，随后是内部N - C键的形成。催化剂的作用被设想为改变反应机理的类型，从周环转变为假周环，从而最终促进反应过程。单核过程（CuAAC）在所有测试的泛函（即wB97XD、LCwPBE、M06 - 2X、M06 - L）下都是协同的（配体L = CH3CN），除了B3LYP泛函给出了分步机理。然而，当配体L = H2O和CH3OH连接到铜上时，反应过程变为异步协同。有趣的是，在我们最佳的理论水平（即LCwPBE/6 - 311++G(d,p)）引入第二个Cu（Cu2AAC）后，除了预测为分步的1,4 - Cu2AAC外，所有考虑的反应过程都是协同的，其环收缩过程的焓极低（0.18千卡/摩尔）。这一事实可以通过中间体的稳定性来解释，而中间体的稳定性又可以通过与Cu相连的碳的价壳层内的空穴以及内部N的(3, -3)孤对电子相对于它的位置来合理化。此外，由于分步双核和协同单核机理之间的能量差很小（0.39千卡/摩尔），我们认为这两种过程（CuAAC和Cu2AAC）同时发生是可行的。
