Department of Organic Chemistry, University of Valencia, Dr Moliner 50, E-46100 Burjassot, Valencia, Spain.
Org Biomol Chem. 2019 Jan 16;17(3):498-508. doi: 10.1039/c8ob02568a.
[3 + 2] cycloaddition (32CA) reactions of cyclohexyne, a cyclic strained acetylene, with methyl azide and methoxycarbonyl diazomethane have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d) computational level. These 32CA reactions, which take place through a one-step mechanism involving highly asynchronous transition state structures, proceed with relatively low activation enthalpies of 6.0 and 4.3 kcal mol-1, respectively, both reactions being strongly exothermic. The reactions are initiated by the creation of a pseudoradical center at one of the two acetylenic carbons of cyclohexyne with a very low energy cost, 1.0 kcal mol-1, which promotes the easy formation of the first C-N(C) single bond in the adjacent acetylenic carbon. This scenario is completely different from that of the 32CA reaction involving non-strained but-2-yne; thus, strain in cyclohexyne triggers a high reactivity as a consequence of its unusual electronic structure at the ground state. Finally, the experimental regioselectivity of the 32CA reactions involving 3-alkoxy-cyclohexyne derivatives is correctly explained within MEDT.
[3 + 2]环加成（32CA）反应的环己炔，环状应变乙炔，与甲基叠氮和甲氧羰基重氮甲烷已经研究了分子电子密度理论（MEDT）在 MPWB1K/6-311G（d）计算水平。这些 32CA 反应，通过涉及高度异步过渡态结构的一步机制发生，进行具有相对较低的活化焓分别为 6.0 和 4.3 kcal mol-1，这两个反应都是强烈的放热反应。反应是由在环己炔的两个炔碳原子之一创建伪自由基中心引发的，能量成本非常低，为 1.0 kcal mol-1，这促进了相邻炔碳原子中第一个 C-N（C）单键的容易形成。这种情况与不涉及应变的但-2-炔的 32CA 反应完全不同；因此，环己炔中的应变引发了高反应性，这是由于其在基态下的异常电子结构。最后，实验性的 3-烷氧基-环己炔衍生物的 32CA 反应的区域选择性在 MEDT 中得到了正确的解释。
