Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
J Org Chem. 2021 Apr 16;86(8):5584-5615. doi: 10.1021/acs.joc.1c00085. Epub 2021 Mar 26.
Cobalt-catalyzed Mukaiyama-type cyclization of γ-hydroxy olefins is known as an atom- and step-economical means for stereoselective synthesis of 2,5--substituted tetrahydrofuran derivatives. In this study, we investigated the synthesis of a series of 2,5-substituted tetrahydrofuran derivatives by means of a cobalt-catalyzed Hartung-Mukaiyama cyclization. The stereochemical consequence of the reaction was found to be largely dependent on the substitution pattern and relative configuration of γ-hydroxy olefins. 2,5--Substituted tetrahydrofuran derivatives could be obtained diastereoselectively from appropriately substituted γ-hydroxy olefins. Additionally, relatively bulky olefin substituents and unprotected hydroxy groups at non-interfering positions (e.g., α and δ) were well tolerated in the reaction. Finally, the synthetic versatility of the Hartung-Mukaiyama cyclization was demonstrated through a stereocontrolled synthesis of the tetrahydrofuran moiety of amphidinolide N, a potent cytotoxic macrolide of marine origin. This study expands the capacity of Mukaiyama-type cyclization in that it can be used in convergent assembly of complex tetrahydrofuran motifs from internal olefins.
钴催化的 Mukaiyama 型环化反应是一种原子经济性和步骤经济性的方法，可用于立体选择性合成 2,5-取代的四氢呋喃衍生物。在这项研究中，我们通过钴催化的 Hartung-Mukaiyama 环化反应研究了一系列 2,5-取代的四氢呋喃衍生物的合成。反应的立体化学结果在很大程度上取决于 γ-羟基烯烃的取代模式和相对构型。通过适当取代的 γ-羟基烯烃可以立体选择性地获得 2,5-取代的四氢呋喃衍生物。此外，相对较大的烯烃取代基和非干扰位置（例如，α 和 δ）上未保护的羟基在反应中得到很好的容忍。最后，通过对具有海洋来源的强效细胞毒性大环内酯 Amphidinolide N 的四氢呋喃部分进行立体控制合成，展示了 Hartung-Mukaiyama 环化的合成多功能性。这项研究扩展了 Mukaiyama 型环化反应的能力，使其能够用于从内部烯烃进行复杂四氢呋喃结构单元的收敛组装。
