A Catalytic Asymmetric Suzuki Coupling for the Synthesis of Axially Chiral Biaryl Compounds
A Catalytic Asymmetric Suzuki Coupling for the Synthesis of Axially Chiral Biaryl Compounds
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DOI：
10.1021/ja005622z
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发表时间：
2000-11
影响因子：
15
通讯作者：
Jingjun Yin and;S. Buchwald
中科院分区：
文献类型：
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作者：
Jingjun Yin and;S. Buchwald
轴向手性双芳基是天然产物中常见的结构基序，是许多最有效的手性配体的核心。这类化合物的不对称合成已经被许多有用的方法所影响，尽管大多使用化学计量手性助剂或手性起始材料。Hayashi3的开创性工作表明，通过ni或pd2催化的不对称熊田偶联，利用手性膦配体，可以高对映选择性地合成轴向手性双芳基。4,5 Nicolaou最近报道了一种不对称铃木偶联形成手性双芳基，其非对映选择性由所使用的手性配体控制。Uemura2c和Nelson也报道了手性芳基卤化物-铬π配合物的非对映选择性铃木偶联。芳基卤化物或芳基三氟酸酯与芳基硼酸的铃木偶联是合成联芳基化合物的有力方法。要得到构型稳定的手性双芳基，通常至少需要三个邻位取代基。这样的要求对耦合效率提出了严格的要求，而耦合效率通常是非常敏感的。我们已经报道了使用基于联苯骨架的体积大、富电子的膦配体进行铃木交叉偶联的有效和通用方案(1)（图1）。特别是，使用基于这些配体的催化剂体系，可以将立体受阻底物组合成具有三个邻位取代基的产物。10在这里，我们报道了2型双萘基配体可以用于催化不对称铃木偶联，形成高度对映体富集的双芳基。据我们所知，这是催化对映选择性交偶联过程的第一个例子，该过程允许制备功能化的双芳基。为了建立一个有效的不对称铃木偶联方案，我们首先在溴化物3a与邻甲基硼酸（反应a）以及2-硝基溴苯（反应4b）与2-苯基-1-萘基硼酸（反应B）之间的反应中测试了一些基于二萘基的膦配体2（表1）。
Axially chiral biaryls are common structure motifs in natural products and are the core for many of the most effective chiral ligands. 1 The asymmetric synthesis of this class of compound has been effected by a number of useful methods, albeit mostly using stoichiometric chiral auxiliaries or chiral starting materials. 2 Pioneering work by Hayashi3 has shown that axially chiral biaryls can be synthesized in high enantioselectivity by Ni-or Pdcatalyzed asymmetric Kumada couplings using chiral phosphine ligands. 4, 5 Nicolaou recently reported an asymmetric Suzuki coupling to form chiral biaryls, whose diastereoselectiVity was controlled by the chiral ligand used. 6 Diastereoselective Suzuki couplings of chiral aryl halide-chromium π-complexes were also reported by Uemura2c and Nelson. 2d Suzuki coupling of aryl halides or aryl triflates and aryl boronic acids is a powerful method for the synthesis of biaryl compounds. 7 To obtain configurationally stable chiral biaryls, at least three ortho substituents are usually necessary. 8 Such a requirement places stringent demands on the coupling efficiency, which generally is quite sterically sensitive. We have reported efficient and general protocols for Suzuki cross-couplings using bulky, electron-rich phosphine ligands that are based on a biphenyl backbone (1)(Figure 1). 9 In particular, the combination of sterically hindered substrates to give products with three ortho substituents can be accomplished using a catalyst system based on these ligands. 10 Here we report that binaphthyl ligands of type2 can be used for the catalytic asymmetric Suzuki coupling to form highly enantiomerically enriched biaryls. 11 To our knowledge, this is the first example of a catalytic enantioselective crosscoupling procedure that allows for the preparation of functionalized biaryls.To establish an efficient protocol for asymmetric Suzuki coupling, we first tested a number of binaphthyl-based phosphine ligands 2 in the reaction between bromide 3a and o-tolylboronic acid (reaction A) and in that between 2-nitrobromobenzene (4b) and 2-phenyl-1-naphthylboronic acid (5)(reaction B)(Table 1).