School of Chemistry, University of Melbourne, VIC 3010, Australia.
J Am Chem Soc. 2012 Feb 1;134(4):2434-41. doi: 10.1021/ja211568k. Epub 2012 Jan 17.
Quantum mechanical calculations have been used to study the intramolecular additions of hydroxylamines to alkenes and alkynes ("reverse Cope eliminations"). In intermolecular reverse Cope eliminations, alkynes are more reactive than alkenes. However, competition experiments have shown that tethering the hydroxylamine to the alkene or alkyne can reverse the reactivity order from that normally observed. The exact outcome depends on the length of the tether. In agreement with experiment, a range of density functional theory methods and CBS-QB3 calculations predict that the activation energies for intramolecular reverse Cope eliminations follow the order 6-exo-dig < 5-exo-trig < 5-exo-dig ≈ 7-exo-dig. The order of the barriers for the 5-, 6-, and 7-exo-dig reactions of alkynes arises mainly from differences in tether strain in the transition states (TSs), but is also influenced by the TS interaction between the hydroxylamine and alkyne. Cyclization onto an alkene in the 5-exo-trig fashion incurs slightly less tether strain than a 6-exo-dig alkyne cyclization, but its activation energy is higher because the hydroxylamine fragment must distort more before the TS is reached. If the alkene terminus is substituted with two methyl groups, the barrier becomes so much higher that it is also disfavored compared to the 5- and 7-exo-dig cyclizations.
量子力学计算已被用于研究羟胺与烯烃和炔烃的分子内加成反应（“反向 Cope 消除”）。在分子间反向 Cope 消除中，炔烃比烯烃更具反应性。然而，竞争实验表明，将羟胺连接到烯烃或炔烃上可以使反应性顺序与通常观察到的顺序相反。确切的结果取决于连接体的长度。一系列密度泛函理论方法和 CBS-QB3 计算与实验结果一致，预测分子内反向 Cope 消除的活化能遵循 6-endo-dig < 5-exo-trig < 5-exo-dig ≈ 7-exo-dig 的顺序。炔烃的 5-、6-和 7-exo-dig 反应的势垒顺序主要源于过渡态（TS）中连接体应变的差异，但也受到羟胺和炔烃之间 TS 相互作用的影响。以 5-exo-trig 方式环化到烯烃上比 6-exo-dig 炔烃环化产生的连接体应变略小，但由于在达到 TS 之前羟胺片段必须更多地扭曲，其活化能更高。如果烯烃末端用两个甲基取代，则由于势垒变得高得多，与 5-和 7-exo-dig 环化相比也变得不利。
