Catalytic enantioselective cyanosilylation of ketones
Catalytic enantioselective cyanosilylation of ketones
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DOI：
10.1021/ja001643h
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发表时间：
2000-08-02
影响因子：
15
通讯作者：
Shibasaki, M
中科院分区：
文献类型：
--
作者：
Hamashima, Y;Kanai, M;Shibasaki, M
目前对羰基化合物如醛、亚胺和酮亚胺催化不对称加成氰化物进行了深入的研究。然而，目前还没有实际的酮类不对称氰硅化反应的报道。例如，在芳基甲基酮的情况下，使用化学催化剂的最佳结果是72% ee。然而，该催化剂不能用于乙基酮（~ 30% ee）和脂肪族酮。鉴于氰醇作为手性季r -羟基羰基衍生物前体的重要性，开发一种具有广泛用途的酮类的高效催化不对称氰硅化反应是人们期待已久的。在这里，我们描述了这一类中的第一个条目，我们认为它对合成各种季氰醇是有用的，由一种新型钛催化剂催化1。在我们从双功能催化的概念开发新的不对称催化剂7的研究过程中，我们发现Lewis酸(Al)-Lewis碱（氧化膦）催化剂3可以促进苯乙酮的氰硅化反应，但对映体过量（20%）很低。为了提高对映体选择性，基于以下考虑，我们计划在C3羟基上引入邻苯二酚部分。醚氧在C3上的配位应该能形成像1这样的络合物。因此，邻苯二酚的苯基应固定在屏蔽r侧的位置
The catalytic asymmetric addition of cyanide to carbonyl compounds1 such as aldehydes, 2 imines3 and ketoimines4 is currently intensively studied. However, no practical asymmetric cyanosilylation of ketones has been reported so far. For example, 5 the best result using chemical catalyst is 72% ee in the case of aryl methyl ketones. However, this catalyst could not be applied to ethyl ketones (∼ 30% ee) and aliphatic ketones. 6 In view of the importance of the cyanohydrins as precursors of chiral quaternary R-hydroxy carbonyl derivatives, development of an efficient catalytic asymmetric cyanosilylation of ketones with broad generality is long awaited. Herein, we describe the first entry in this category that we believe is useful for synthesizing a variety of quaternary cyanohydrins, catalyzed by a novel titanium catalyst 1.During the course of our studies to develop a new asymmetric catalyst from the concept of bifunctional catalysis, 7 we have found that the Lewis acid (Al)-Lewis base (phosphine oxide) catalyst 3 can promote the cyanosilylation of acetophenone, however, with low enantiomeric excess (20%). 8 To improve the enantioselectivity, we planned to introduce a catechol moiety at the C3 hydroxyl group on the basis of the following consideration. The coordination of the ether oxygen at C3 should make it possible to form a complex such as 1. As a result, the phenyl group of the catechol should be fixed at the position shielding the R-side (anti