Catalytic Asymmetric Synthesis of Chiral Cyclic Ethers

手性环醚是生物活性化合物中最重要的结构单元之一。在迄今报道的许多关键构筑单元中，a-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广泛的官能团。特别是，重点是创建催化对映体选择性方案。基于[CpRu(CHSCN)3]PF6与吡啶-2-羧酸衍生物或相应的阳离子CpRu(IV)-St-烯丙基羧酸络合物结合的催化体系可以将醇和烯丙醇的1：1混合物转化为烯丙基醚，我们开发了一种新的手性配体，S-methyl-6-(2-R-naphthalen-l-yl)-pyridine-2-carboxylic酸(R-nAPH-吡甲酸)。该配体通过C(6)-C(1‘)键具有空间柔性的轴向手性，并通过C(2’)上的R取代基来调节萘环的电子和空间性质。作为配体结构-反应活性和选择性关系研究的结果，氯-naph-PyCOOH或其烯丙基酯与CpRu络合物的结合实现了具有良好的反应活性和选择性的环化反应，得到了各种a-烯基取代的环醚，如四氢呋喃、四氢-2H-吡喃、香豆素和色满，对映体比高达99：1。

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.