Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto, 615-8510, Japan.
Nat Commun. 2017 Nov 9;8(1):1397. doi: 10.1038/s41467-017-01099-x.
Enantioselective approaches to synthesize six-membered oxacycles with multiple stereogenic centres are in high demand to enable the discovery of new therapeutic agents. Here we present a concise organocatalytic cycloetherification for the highly enantio- and diastereoselective synthesis of tetrahydropyrans involving simultaneous construction of two chiral centres, one of which is fully substituted. This method involves dynamic kinetic resolution of reversibly generated chiral cyanohydrins. A chiral bifunctional organocatalyst selectively recognizes a specific chair-like conformation of the intermediate, in which the small steric effect of the linear cyano group as well as its anomeric effect play important roles in controlling stereoselectivity. The products offer additional utility as synthetic intermediates because the cyano group can be further transformed into a variety of important functional groups. This strategy provides a platform to design efficient approaches to obtain a wide range of optically active tetrahydropyrans, which are otherwise synthetically challenging materials.
手性方法合成具有多个手性中心的六元氧杂环是发现新治疗剂的重要需求。在这里，我们提出了一种简洁的有机催化环醚化反应，用于高度对映选择性和非对映选择性地合成涉及同时构建两个手性中心的四氢吡喃，其中一个是完全取代的。该方法涉及可动态动力学拆分的可逆生成的手性氰醇。手性双功能有机催化剂选择性地识别中间体的特定椅式构象，其中线性氰基的小空间位阻以及其端基效应在控制立体选择性方面发挥重要作用。产物作为合成中间体具有额外的用途，因为氰基可以进一步转化为各种重要的官能团。该策略提供了一个设计高效方法获得广泛的光学活性四氢吡喃的平台，否则这些四氢吡喃是具有挑战性的合成材料。
