Departamento de Química Orgánica . Facultad de Ciencias, Universidad de Alicante , 03080 Alicante , Spain.
Centro de Innovación en Química Avanzada (ORFEO-CINQA).
Org Lett. 2018 Jun 15;20(12):3522-3526. doi: 10.1021/acs.orglett.8b01292. Epub 2018 Jun 6.
The thermal 1,3-dipolar cycloaddition of unactivated azomethine ylides derived from allylamine and aromatic or heteroaromatic aldehydes with maleimides and 1,1- and 1,2-bis(phenylsulfonyl)ethylene affords endo-2,5- trans cycloadducts in moderate to good yields. DFT calculations provide evidence that the diastereoselectivity observed depends on the isomerization between S- and W-ylides according to Curtin-Hammett's principle. DFT calculations also explain the different diastereomeric ratio observed for 2-pyridyl and 2-thienyl derivatives in which the isomerization is not possible due to the competitiveness between isomerization barrier and the rate-limiting step (ylide formation barrier). This methodology is applied to the diastereoselective synthesis of a tricyclic thrombin inhibitor.
未活化的偕胺肟叶立德与马来酰亚胺和 1,1-和 1,2-双(苯磺酰)乙烯的热 1,3-偶极环加成反应，可从丙烯胺和芳基或杂芳基醛得到中等至良好收率的endo-2,5-反式环加成产物。DFT 计算提供的证据表明，观察到的非对映选择性取决于根据 Curtin-Hammett 原理 S-和 W-叶立德之间的互变异构。DFT 计算还解释了在 2-吡啶基和 2-噻吩基衍生物中观察到的不同非对映异构体比例，由于互变异构体的竞争以及限速步骤（叶立德形成势垒），在这些衍生物中，互变异构是不可能的。该方法应用于三环凝血酶抑制剂的非对映选择性合成。
