Reagent-controlled switching of 5-exo to 6-endo cyclizations in epoxide openings
Reagent-controlled switching of 5-exo to 6-endo cyclizations in epoxide openings
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DOI：
10.1002/anie.200503143
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Tanaka, T
中科院分区：
文献类型：
--
作者：
Morimoto, Y;Nishikawa, Y;Tanaka, T
四氢呋喃（THF）和四氢吡喃（THP）环是广泛存在于许多具有生物活性的天然产物和功能分子中的结构单元。因此，构建四氢呋喃和四氢呋喃醚环的合成方法的发展引起了合成有机化学家的广泛关注。在这些可能性中，双聚环氧醇的分子内环化从区域选择性的角度来看是有趣的，并且它是合成四氢呋喃和四氢呋喃环醚的最实用和有效的方法之一。一般来说，5-外端tet环化比6-内端tet环化更受欢迎，因为这是一个主要的立体电子效应，被称为Baldwin规则然而，环化的确切模式取决于所采用的底物（方案1）。因此，为了观察与Baldwin规则相反的6-末端区域选择性，特别是在过去的二十年中，已经设计了各种各样的方法。然而，它们几乎都涉及对环氧化物底物的精细修饰，例如，通过在环氧化物或磺酰[4]或三甲基硅基（TMS）[5]取代基上引入π轨道[3]来激活C6位置。迄今为止只有两种例外，即抗体催化[6]和La (OTf) 3催化的环化，[7]克服了通常对5-外外tet环形成的偏好，而不需要对底物进行修饰，尽管在后一种情况下，底物仅限于不寻常的甲氧基甲基取代环氧化物1 （R5= CH2OMe；方案1）。在这里，我们报告了非酶
Tetrahydrofuran (THF) and tetrahydropyran (THP) rings are ubiquitous structural units that are extensively encountered in a number of biologically active natural products and functional molecules. Therefore, the development of synthetic methods for constructing THF and THP ether rings has attracted much attention from synthetic organic chemists.[1]Among the possibilities, the intramolecular cyclization of bishomoepoxy alcohols is intriguing from the point of view of regioselectivity as well as it being one of the most practical and effective methods for the synthesis of both THF and THP cyclic ethers. In general, 5-exo-tet cyclizations are preferred to the 6-endo-tet variant because of a dominant stereoelectronic effect, which is known as Baldwin s rule.[2] However, the exact mode of cyclization depends on the substrates employed (Scheme 1). Thus, to observe 6-endo regioselectivity in opposition to Baldwin s rule a wide variety of methods have been devised, particularly over the last two decades. However, they almost all involve elaborate modifications of the epoxide substrate, for example, by the introduction of a π orbital [3] adjacent to the epoxide or sulfonyl [4] or trimethylsilyl (TMS)[5] substituents on the epoxide to activate the C6 position. There have hitherto been only two exceptions, namely, antibody catalysis [6] and La (OTf) 3-catalyzed cyclizations,[7] which overcome the normal preference for 5-exo-tet ring formation without the need for modification of the substrate, although in the latter case the substrates are limited to unusual methoxymethyl-substituted epoxides 1 (R5= CH2OMe; Scheme 1). Herein, we report the non-enzymatic