Helical Chiral Pyridine N-Oxides: A New Family of Asymmetric Catalysts
Helical Chiral Pyridine N-Oxides: A New Family of Asymmetric Catalysts
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DOI：
10.1002/anie.200803338
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Captain, Burjor
中科院分区：
文献类型：
--
作者：
Takenaka, Norito;Sarangthem, Robindro Singh;Captain, Burjor
新催化剂结构的设计、合成和研究对化学合成产生了巨大的影响，并且仍然是不对称催化的核心挑战。[1]我们最近描述了2-氨基吡啶离子可能是一种有前途的过氧化氢载体[2]，用于设计新的不对称氢键供体催化剂。[3]在这方面，我们对1-氮杂[6]螺烯[4] 1作为手性基团[2]产生了兴趣，因为对类似的1，16-二氮杂[6]螺烯[5]的晶体结构的一级分析表明，其吡啶环在上下和左右区分方面都是不对称的。据我们所知，1和类似的螺旋手性吡啶[5-7]在不对称催化中的应用还没有研究过，尽管1自1975年以来就在文献中已知。[4d]在这种情况下，我们被提示开发一种有效的合成1-azahelicenes，这使得系统的结构变化，重要的催化剂结构，反应性和选择性之间的关系的阐明，并利用它们作为手性。鉴于螺旋手性吡啶如1的效用，我们想到相应的吡啶N-氧化物可能被证明是有效的不对称催化剂。[8]在本文中，我们描述了1-氮杂螺烯的可扩展合成和相应N-氧化物的结构表征，并且我们将这种新的化合物家族应用于内消旋环氧化物的催化对映选择性去对称化（参见表1）。本研究首次报道了氮杂螺烯在不对称催化中的应用。[9]An对1的结构的研究表明，氮原子附近的手性环境可以通过碳原子11-16处的结构修饰来调节。因此，我们设计了一种收敛的合成路线，其中苯并喹啉单元2和C11-C16单元3可以迅速地结合（方案1）。该策略将允许通过简单地用其容易获得的结构类似物如9和12（方案2）代替3而容易地获得必要的1-氮杂螺烯衍生物。钥匙的准备
The design, synthesis, and study of new catalyst structures have had an enormous impact on chemical synthesis, and continue to be a central challenge in asymmetric catalysis.[1] We recently described that a 2-aminopyridinium ion might be a promising catalaphore [2] for the design of new asymmetric hydrogen-bond donor catalysts.[3] In that connection, we became interested in 1-aza [6] helicene [4] 1 as a chiraphore [2] because a first-order analysis of the crystal structure of an analogous 1, 16-diaza [6] helicene [5] suggests that its pyridine ring is well-desymmetrized in terms of both top-from-bottom and left-from-right differentiations. To our knowledge, the application of 1 and analogous helical chiral pyridines [5–7] in asymmetric catalysis has not been studied, even though 1 has been known in the literature since 1975.[4d] In this context, we were prompted to develop an efficient synthesis of 1-azahelicenes, which allows systematic structural variation—important for the elucidation of the relationship between catalyst structure, reactivity, and selectivity—and to exploit them as chiraphores. In view of the utility of helical chiral pyridines such as 1, it occurred to us that the corresponding pyridine N-oxides might prove to be effective asymmetric catalysts.[8] Herein, we describe the scalable synthesis of 1-azahelicenes and the structural characterization of the corresponding N-oxides, and we apply this new family of compounds to the catalytic enantioselective desymmetrization of meso epoxides (see Table 1). This study provides the first report of the application of azahelicenes in asymmetric catalysis.[9]An examination of the structure of 1 suggests that the chiral environment in the vicinity of the nitrogen atom can be tuned by structural modification at cabon atoms 11–16. Therefore, we devised a convergent synthetic route to 1 in which benzoquinoline unit 2 and C11–C16 unit 3 could be expeditiously united (Scheme 1). This strategy would allow ready access to the necessary 1-azahelicene derivatives by simply replacing 3 with its readily available structural analogues, such as 9 and 12 (Scheme 2). Preparation of key