Department of Chemistry & Biochemistry, University of California, Santa Barbara, 93106, USA.
Institute of Organic Chemistry, University of Würzburg, 97074, Würzburg, Germany.
Chemistry. 2019 Nov 7;25(62):14237-14245. doi: 10.1002/chem.201903832. Epub 2019 Oct 15.
A stereoselective total synthesis of O,N-dimethylhamatine, an analogue of an axially chiral naphthylisoquinoline natural biaryl product from tropical Ancistrocladus lianas, is reported. The route features a late-stage atropo-diastereoselective biaryl bond formation. Generation of this especially challenging, sterically hindered tetra-ortho-substituted array was achieved by using Nolan's (IPr*NHC)PdCinCl pre-catalyst under mild Negishi coupling conditions. Discussion is offered regarding the selectivity obtained experimentally and predicted from DFT calculations on the key biaryl coupling step that leads to the desired M-diastereomer.
本文报道了一种对映选择性全合成 O,N-二甲基哈马汀的方法，O,N-二甲基哈马汀是一种来自热带 Ancistrocladus 藤本植物的轴手性萘基异喹啉天然联芳产物的类似物。该路线的特点是在后阶段进行对映选择性的联芳键形成。通过使用 Nolan 的（IPr*NHC）PdCinCl 预催化剂在温和的 Negishi 偶联条件下，生成了这种特别具有挑战性的、空间位阻四面体邻位取代的联芳基。文中讨论了实验获得的选择性以及通过对关键联芳偶联步骤的密度泛函理论（DFT）计算预测的选择性，该步骤导致所需的 M-非对映异构体的形成。
