SSPC, the SFI Research Centre for Pharmaceuticals, School of Chemistry, University College Cork, Cork, T12 K8AF, Ireland.
Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Org Biomol Chem. 2021 Apr 28;19(16):3656-3664. doi: 10.1039/d0ob02458a.
The first catalytic enantioselective aza-Cope rearrangement was reported in 2008 by Rueping et al. The reaction is catalyzed by a 1,1'-bi-2-naphthol-derived (BINOL-derived) phosphoric acid and achieved high yields and enantioselectivities (up to 97 : 3 er with 75% yield). This work utilizes Density Functional Theory to understand the mechanism of the reaction and explain the origins of the enantioselectivity. An extensive conformational search was carried out to explore the different activation modes by the catalyst and, the Transition State (TS) leading to the major product was found to be 1.3 kcal mol-1 lower in energy than the TS leading to the minor product. The origin of this stabilization was rationalized with NBO and NCI analysis: it was found that the major TS has a greater number of non-bonding interactions between the substrate and the catalyst, and shows stronger H-bond interactions between H atoms in the substrate and the O atoms in the phosphate group of the catalyst.
2008 年， Rueping 等人首次报道了首例催化对映选择性氮杂-Cope 重排反应。该反应由 1,1'-联萘酚衍生的（BINOL 衍生的）磷酸催化，产率和对映选择性高（最高可达 97:3er，产率为 75%）。这项工作利用密度泛函理论来理解反应的机理并解释对映选择性的起源。通过催化剂进行了广泛的构象搜索，以探索不同的活化模式，并且发现导致主要产物的过渡态（TS）的能量比导致次要产物的 TS 低 1.3 kcal mol-1。通过 NBO 和 NCI 分析对这种稳定化作用进行了合理化解释：发现主要的 TS 具有更多的非键相互作用，在底物和催化剂之间，并且在底物中的 H 原子和催化剂的磷酸基团中的 O 原子之间显示出更强的氢键相互作用。
