Chiral Organotin Hydride Catalyzed Enantioselective Radical Cyclization of Aldehydes
Chiral Organotin Hydride Catalyzed Enantioselective Radical Cyclization of Aldehydes
复制标题
手性有机锡氢化物催化醛的对映选择性自由基环化
DOI：
10.1002/ajoc.201300138
复制
发表时间：
2013
影响因子：
2.7
通讯作者：
Keiji Maruoka
中科院分区：
文献类型：
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作者：
Seiji Shirakawa;Asuka Usui;S. B. Jennifer Kan;Keiji Maruoka
有机锡氢化物介导的自由基环化是有机合成中构建有用的碳环和杂环化合物的强大工具。 [1]通过使用手性助剂和路易斯酸作为手性模板实现这些反应的不对称版本已成为近年来引起极大科学兴趣的话题。 [2]在这种背景下，手性有机锡促进的对映选择性自由基环化的发展似乎非常有吸引力。尽管之前已经制备了几种手性有机锡氢化物并将其应用于对映选择性自由基还原，[3]但从未报道过使用这些试剂进行对映选择性环化。开发手性有机锡介导的对映选择性自由基环化的困难源于两个主要原因。首先，该反应通常需要化学计量的有机锡试剂，这使得仅使用催化量的珍贵手性有机锡来执行不对称变体具有挑战性。另一个原因是，在许多自由基环化反应中，从手性有机锡试剂到产物的有效手性转移很难实现，因为有机锡试剂往往只参与原子抽象以在底物中生成自由基，但不参与成键过程（Scheme 1a）。为了解决这些问题，我们一直对醛的对映选择性自由基环化的发展感兴趣，如方案1b所示。 [4]自由基反应通过 O-甲锡烷基羰基中间体进行，使得有机锡化合物的手性信息可以在环化步骤中转移到产物中（方案 1b）。此外，这种类型的自由基反应可以通过催化量的有机锡氢化物与作为化学计量还原剂的甲硅烷基氢化物结合来促进。 [5]在此，我们报告了第一个手性有机锡氢化物催化醛的对映选择性自由基环化以产生苯并二氢吡喃醇衍生物[6]作为生物学上有趣的化合物[7]的例子（方案2）。所需的手性有机锡氢化物(S)-1可以由已知的化合物(S)-5[8]制备(方案3)。因此，在水存在下用锡粉处理化合物(S)-5，得到二溴化锡。[3c, 9]随后用苯基溴化镁处理所得二溴化锡，得到稳定的合成中间体化合物(S)-6，通过硅胶柱色谱纯化。通过等摩尔量的溴处理，将化合物(S)-6中的一个苯基选择性地交换为溴基，所得一溴化锡用硼氢化钠还原，得到目标氢化锡(S)-1，为相对稳定的化合物，也通过硅胶柱色谱纯化。 [10]手性有机锡 com 的结构-[a] S. Shirakawa 博士、A. Usui 博士、SBJ Kan 博士、K. Maruoka 博士教授 合成有机化学实验室和有机催化化学特殊实验室 京都大学理学研究生院化学系，Sakyo，Kyoto 606-8502（日本） 传真：(+ 81) 75-753-4041
Organotin-hydride-mediated radical cyclizations are powerful tools in organic synthesis for the construction of useful carbocyclic and heterocyclic compounds.[1] The realization of the asymmetric version of these reactions by using chiral auxiliaries and Lewis acids as chiral templates has become a topic of great scientific interest in recent years.[2] In this context, the development of chiral organotin-promoted enantioselective radical cyclization appears to be very attractive. Although several chiral organotin hydrides have previously been prepared and applied to enantioselective radical reductions,[3] the enantioselective cyclization using these reagents has never been reported. The difficulty in developing chiral organotin-mediated enantioselective radical cyclization stems from two main reasons. First, the reaction generally requires a stoichiometric amount of the organotin reagent, which renders it challenging to execute the asymmetric variant by using only a catalytic amount of precious chiral organotin. Another reason is that efficient chirality transfer from the chiral organotin reagent to the product is difficult to implement in many radical cyclizations because the organotin reagent often only engages in atom abstraction to generate a radical in the substrate, but does not participate in the bond formation process (Scheme 1a). To solve these problems, we have been interested in the development of enantioselective radical cyclization of aldehydes, as shown in Scheme 1b.[4] The radical reaction proceeds via an O-stannyl ketyl intermediate, such that chiral information of the organotin compound can transfer to the product in the cyclization step (Scheme 1b). Furthermore, this type of radical reaction can be promoted by a catalytic amount of organotin hydride, in combination with silyl hydride as a stoichiometric reducing reagent.[5] Herein, we report the first example of chiral organotin-hydride-catalyzed enantioselective radical cyclization of aldehydes to produce chromanol derivatives [6] as biologically interesting compounds [7](Scheme 2). The requisite chiral organotin hydrides (S)-1 can be prepared from the known compounds (S)-5 [8](Scheme 3). Thus, treatment of compounds (S)-5 with tin powder in the presence of water gave tin dibromides.[3c, 9] The obtained tin dibromides were subsequently treated with phenylmagnesium bromide to give compounds (S)-6 as stable synthetic intermediates, which were purified by silica gel column chromatography. One of the phenyl groups in compounds (S)-6 was selectively exchanged for a bromo group by the treatment with an equimolar amount of bromine, and the resulting tin monobromides were reduced with sodium borohydride to afford target tin hydrides (S)-1 as relatively stable compounds, which were also purified by silica gel column chromatography.[10] The structure of chiral organotin com-[a] Dr. S. Shirakawa, A. Usui, Dr. SBJ Kan, Prof. Dr. K. Maruoka Laboratory of Synthetic Organic Chemistry and Special Laboratory of Organocatalytic Chemistry Department of Chemistry, Graduate School of Science Kyoto University, Sakyo, Kyoto 606-8502 (Japan) Fax:(+ 81) 75-753-4041