Twisted Cycloalkynes and Remote Activation of "Click'' Reactivity
Twisted Cycloalkynes and Remote Activation of "Click'' Reactivity
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DOI：
10.1016/j.chempr.2017.07.011
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发表时间：
2017-10-12
期刊：
影响因子：
23.5
通讯作者：
Alabugin, Igor V.
中科院分区：
文献类型：
--
作者：
Harris, Trevor;Gomes, Gabriel dos Passos;Alabugin, Igor V.
“扭曲和弯曲”的环癸炔结构基序与休眠电子效应交织在一起，开启了一种控制“点击”反应性的概念上强大的方法。环癸炔的环内杂原子通过超共轭（直接）和共轭（远程）效应提供双重电子激活。这些效应因扭曲主干施加的几何约束而减弱，但过渡态 (TS) 中的结构重组消除了这些约束，并释放了远程电子效应用于选择性 TS 稳定的能力。克级合成和重结晶纯化使其成为对映体纯环炔的有效且实用的方法。实验动力学证实，这些扭曲的环癸炔比活化的环壬炔对叠氮化物更具反应性，并且接近环辛炔的反应性。此外，具有扭曲的多芳香族主链的环炔可以潜在地为“点击”化学工具箱添加轴向手性。
The "twisted and bent'' cyclodecyne structural motif, intertwined with dormant electronic effects, opens a conceptually powerful way to control "click'' reactivity. The endocyclic heteroatoms of cyclodecynes provide dual electronic activation via hyperconjugative (direct) and conjugative (remote) effects. These effects are weakened by the geometric constraints imposed by the twisted backbone, but structural reorganization in the transition state (TS) removes these constraints and unlocks the power of remote electronic effects for selective TS stabilization. Gram-scale synthesis and purification by recrystallization make this an efficient and practical approach to enantiopure cycloalkynes. Experimental kinetics confirm that these twisted cyclodecynes can be more reactive toward azides than activated cyclononynes and approach the reactivity of cyclooctynes. Furthermore, cycloalkynes with a twisted polyaromatic backbone can potentially add axial chirality to the "click'' chemistry toolbox.