Structurally and stereochemically diverse tetrahydropyran synthesis through oxidative C-H bond activation.
Structurally and stereochemically diverse tetrahydropyran synthesis through oxidative C-H bond activation.
复制标题
DOI：
10.1002/anie.201000033
复制
发表时间：
2010-04-12
影响因子：
16.6
通讯作者：
Floreancig, Paul E.
中科院分区：
文献类型：
--
作者：
Liu, Lei;Floreancig, Paul E.
四氢吡喃是许多生物活性天然产物中的核心单元，[1]并且期望利用C-H键官能化作为C-C键形成的前奏来制备这些结构的方法。这种方法是步骤[2]和原子[3]经济的，因为底物制备和反应性中间体产生采用非反应性C-H键，而不是常规的离去基团。我们已经表明，杂环可以形成高水平的非对映体控制从苄醚和烯丙基醚通过DDQ介导的（2，3-二氯-5，6-二氰基-1，4-苯醌）oxocarbenium离子的形成，和随后的分子内亲核加成。[4]该方法与基于Prins的四氢吡喃制备方法高度互补，[5]并已通过其在天然产物合成中的应用得到验证。[6]这种方法的其他战略优势包括酸不稳定官能团对氧化条件的耐受性，[7]应用简单的醚化反应在链段偶联反应中形成稳定的键，以及获得通用的不饱和产物。我们已经表明，这种不饱和提供了一个途径，通过postcyclization操作的一系列结构和立体化学不同的四氢吡喃。含乙烯基硅烷和炔的产物在目标和多样性导向的合成中是有用的部分。乙烯基硅烷是功能和立体化学多样性结构的杰出前体，因为它们能够参与许多转化[8]，并且它们具有明确的[9]构象偏好。环化底物可以通过相应的甲硅烷基烯丙醇的醚化反应来制备。[10]这种方法通过在片段偶联之前引入甲硅烷基而使收敛性最大化，因此适用于高效的天然产物和其他靶向合成。为该研究制备的甲硅烷基化醚底物的类别描述于方案1中。
Tetrahydropyrans are core units within a multitude of biologically active natural products,[1] and methods to prepare these structures, which utilize C–H bond functionalization as a prelude to C–C bond-formation are desirable. This approach is both step [2] and atom [3] economical, because the substrate preparation and reactive intermediate generation employ unreactive C–H bonds, rather than conventional leaving groups. We have shown that heterocycles can be formed with high levels of diastereocontrol from benzylic and allylic ethers through the DDQ-mediated (2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone) oxocarbenium ion formation, and subsequent intramolecular nucleophilic addition.[4] This method is highly complementary to Prins-based methods in the preparation of tetrahydropyrans,[5] and has been validated through its application to natural product synthesis.[6] Additional strategic benefits of this approach include the tolerance of acid labile functional groups towards oxidative conditions,[7] the application of facile etherification reactions to form stable linkages in segment coupling reactions, and the access to versatile unsaturated products. We have shown that this unsaturation provides a route towards a range of structurally and stereochemically diverse tetrahydropyrans through postcyclization manipulations. Vinylsilane-and alkyne-containing products serve as useful moieties for application in target-and diversity-oriented synthesis.Vinylsilanes are outstanding precursors for functionally and stereochemically diverse structures because of their ability to engage in numerous transformations,[8] and their welldefined [9] conformational preferences. The cyclization substrates can be prepared by etherification reactions of the corresponding silylallylic alcohols.[10] This approach maximizes convergency by introducing the silyl group prior to the fragment coupling, and is therefore applicable in efficient natural product and other target-oriented syntheses. The class of silylated ether substrates that were prepared for this study are depicted in Scheme 1.
登录
查看更多内容
影响因子：
2.1
作者：
Jung HH;Floreancig PE
通讯作者：
Floreancig PE
影响因子：
1.8
作者：
HASAN, I;KISHI, Y
通讯作者：
KISHI, Y
影响因子：
5.2
作者：
Liu L;Floreancig PE
通讯作者：
Floreancig PE
影响因子：
1.8
作者：
Bhattacharjee, A;De Brabander, JK
通讯作者：
De Brabander, JK
影响因子：
15
作者：
Hubig, SM;Rathore, R;Kochi, JK
通讯作者：
Kochi, JK