Structural studies of the low-valent titanium "solution": What goes on in the pinacol coupling reaction?
Structural studies of the low-valent titanium "solution": What goes on in the pinacol coupling reaction?
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DOI：
10.1021/ja001843t
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发表时间：
2001-01
影响因子：
15
通讯作者：
Yuko Hashimoto;Utako Mizuno;H. Matsuoka;T. Miyahara;M. Takakura;M. Yoshimoto;K. Oshima;K. Utimoto;S. Matsubara
中科院分区：
文献类型：
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作者：
Yuko Hashimoto;Utako Mizuno;H. Matsuoka;T. Miyahara;M. Takakura;M. Yoshimoto;K. Oshima;K. Utimoto;S. Matsubara
低价金属盐在有机合成中有着广泛的应用。[1]它们作为电子给体和刘易斯酸的潜力适用于以羰基化合物为底物的反应：即Grignard、Barbier、Reformatsky和频哪醇偶联反应。根据溶剂和配体的不同，低价金属盐可以作为均相溶液或非均相分散体使用。均匀溶液通常促进反应的效率，包括立体化学的控制。例如，在低价钛盐介导的频哪醇偶联反应中，2均相反应给出了更高的非对映选择性。3最近，我们报道了使用氯化钛（II）（TiCl 2）-手性胺的对映选择性频哪醇偶联反应（方案1）。4在该反应的过程中，将TiCl 2溶解在THF和胺的混合物中，并作为似乎是均匀的溶液用于反应。然而，仅仅从外观判断为均匀的溶液实际上不能被识别为均匀的。5为了控制反应途径，需要更详细的溶液信息。分析溶液中金属盐结构的方法是有限的。EXAFS（扩展X射线吸收精细结构）是一种常用的方法，主要显示原子之间的距离及其配位数。6如我们所愿，获得了关于金属盐的更多宏观信息。（例如，聚合情况和簇大小），我们尝试应用SAXS我们在方案1中使用的低价钛是氯化钛（II）（1），根据所报道的方法（方案2），通过用六甲基二硅烷处理氯化钛（IV）制备。7该方法得到氯化钛（II）和三甲基氯硅烷，因此在除去挥发性化合物后可以分离氯化钛（II）。在我们的反应（方案1）中，向氯化钛（II）（1）中加入THF（5.0 mL）和胺（4）（4.0 mmol），得到实现苯甲醛的频哪醇偶联的溶液，其ee为40%。
Low-valent metal salts have been widely used for organic syntheses. 1 Their potential as electron donor and Lewis acid is suitable for reactions using a carbonyl compound as a substrate: ie, Grignard, Barbier, Reformatsky, and pinacol coupling. The low-valent metal salts are used either as a homogeneous solution or heterogeneous dispersion depending on the solvent and ligand. The homogeneous solution often promotes the efficiency of the reaction, including control of the stereochemistry. For example, in the low-valent titanium salt-mediated pinacol coupling reactions, 2 the homogeneous reaction gave higher diastereoselectivity. 3 Recently, we reported an enantioselective pinacol coupling reaction using titanium (II) chloride (TiCl2)-chiral amine (Scheme 1). 4 In the procedure of this reaction, TiCl2 was dissolved into a mixture of THF and amine and used for the reaction as a solution that seemed to be homogeneous. However, a solution that is judged to be homogeneous merely from its appearance cannot in fact be identified as such. 5 To control the reaction pathway, more detailed information about the solution is necessary. Methods to analyze the structure of the metal salt in a solution are limited. EXAFS (Extended X-ray Absorption Fine Structure), which is a common method, shows mainly the distance between atoms and its coordination number. 6 As we wished obtain more macroscopic information regarding the metal salt (for example, the aggregation situation and cluster size), we tried to apply SAXS (Small-Angle X-ray Scattering) to the structural analysis of our titanium reagent solution.The low-valent titanium which we used in Scheme 1 was titanium (II) chloride (1), prepared by treatment of titanium (IV) chloride with hexamethyldisilane according to the reported procedure (Scheme 2). 7 The method affords titanium (II) chloride and chlorotrimethylsilane, so titanium (II) chloride could be isolated after the removal of volatile compounds. In our reaction (Scheme 1), an addition of THF (5.0 mL) and amine (4)(4.0 mmol) to titanium (II) chloride (1) gave a solution that realized the pinacol coupling of benzaldehyde in 40% ee. First, we measure SAXS of this THF solution containing TiCl2 (1) and amine 4.