权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Catalytic Asymmetric Synthesis of Chiral Cyclic Ethers

手性环醚的催化不对称合成

基本信息

批准号：
22750088
负责人：
TANAKA Shinji
金额：
$ 2.66万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2011
项目状态：
已结题

项目摘要

Chiral cyclic ethers constitute one of the most important structural units in biologically active compounds. Among many key building blocks reported so far, a-alkenyl-substituted cyclic ethers are widely recognized as the most useful because the alkenyl moiety can be transformed to a wide range of functionalities. In particular, the focal point is the creation of catalytic enantioselective protocols. Here, we focused on a new type of protocol, in which non-activated or non-protected ow-hydroxy allyl alcohols dehydratively cyclize to the corresponding cyclic ethers.Based on the information that a catalytic system combined[CpRu(CHsCN) 3] PF6 with a pyridine-2-carboxylic acid derivative or the corresponding cationic CpRu(IV)-st-allyl carboxylato complex which can convert a 1 : 1 mixture of alcohols and allyl alcohols to allyl ethers with the liberation of water, we developed a new chiral ligand, s-methyl-6-(2-R-naphthalen-l-yl)-pyridine-2-carboxylic acid(R-Naph-PyCOOH). The ligand is characterized by the sterically flexible axial chirality through C(6)-C(1') bond and the adjustability of electronic and steric properties of the naphthalene ring by the R substituent at C(2'). As the result of an investigation of ligand structure-reactivity and selectivity relationships, the combination of Cl-Naph-PyCOOH or its allyl ester with a CpRu complex achieves the cyclization with excellent reactivity and selectivity, giving various a-alkenyl-substituted cyclic ethers, such as tetrahydrofuran, tetrahydro-2H-pyran, coumaran, and chromane, with up to> 99 : 1 enantiomer ratio.

手性环醚构成生物活性化合物中最重要的结构单元之一。在迄今为止报道的许多关键结构单元中，α-烯基取代的环醚被广泛认为是最有用的，因为烯基部分可以转化为多种官能团。特别是，重点是催化对映选择性方案的创建。在这里，我们重点关注一种新型的方案，其中非活化或非保护的低羟基烯丙醇脱水环化为相应的环醚。基于将[CpRu(CHsCN) 3] PF6与吡啶-2-羧酸衍生物或相应的阳离子CpRu(IV)-st-烯丙基结合的催化体系的信息羧基络合物可以将醇和烯丙醇的1:1混合物转化为烯丙基醚并释放水，我们开发了一种新的手性配体，s-甲基-6-(2-R-萘-1-基)-吡啶-2-羧酸(R-Naph-PyCOOH)。该配体的特点是通过C(6)-C(1')键实现空间柔性轴向手性，并通过C(2')处的R取代基调节萘环的电子和空间性质。通过对配体结构-反应性和选择性关系的研究，Cl-Naph-PyCOOH或其烯丙酯与CpRu配合物的结合实现了具有优异反应性和选择性的环化，得到各种α-烯基取代的环醚，例如四氢呋喃、四氢-2H-吡喃、香豆喃和苯并二氢吡喃，其环化率高达> 99 : 1 对映体比例。