Direct asymmetric aldol reactions of glycine Schiff base with aldehydes catalyzed by chiral quaternary ammonium salts
Direct asymmetric aldol reactions of glycine Schiff base with aldehydes catalyzed by chiral quaternary ammonium salts
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DOI：
10.1002/1521-3773(20021202)41:23
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发表时间：
2002-01-01
影响因子：
16.6
通讯作者：
Maruoka, K
中科院分区：
文献类型：
--
作者：
Ooi, T;Taniguchi, M;Maruoka, K
作为天然存在的α-氨基酸以及许多复杂的生物活性环肽和酶抑制剂的组成部分，光学活性β-羟基-α-氨基酸是非常重要的手性单元，特别是从药学的角度来看。[1]此外，它们是有机合成中有用的手性构件[2]，例如它们转化为β内酰胺、[3]β-卤代-α-氨基酸、[4]和氮杂环丙烷。[5]相应地，许多不对称合成β-羟基-α氨基酸的方法已被阐述。在这方面，通过甘氨酸供体与醛受体的直接催化不对称Aldol反应来构建具有正确立体化学的一级结构被认为是一个理想的方案。然而，迄今为止，除了与甘氨酸依赖的醛缩酶的化学酶反应之外，几乎没有成功的例子，[10，11]。[9B，12]我们报道了在有机/水两相条件下，甘氨酸Schiff碱2[13]与醛的直接不对称Aldol反应。C2-对称手性季铵盐1[14]作为相转移催化剂(方案1)。该方法为合成光学活性β-羟基-α氨基酸提供了一种实用且环境友好的化学方法。首先，我们考察了前手性甘氨酸席夫碱2与3-苯丙醛在相转移条件下的直接不对称羟醛缩合反应。对催化剂结构和反应条件的全面优化表明，在手性季铵盐存在下，2与3-苯丙醛(2当量)在甲苯/氢氧化钠(1%)(v/v为1.25：1；2当量碱为2)中反应。
As naturally occurring α-amino acids as well as components of many complex biologically active cyclic peptides and enzyme inhibitors, optically active β-hydroxy-α-amino acids are extremely important chiral units, especially from the pharmaceutical viewpoint.[1] Furthermore, they are useful chiral building blocks in organic synthesis [2] as exemplified by their transformation into βlactams,[3] β-halo-α-amino acids,[4] and aziridines.[5] Accordingly, numerous methods for the asymmetric synthesis of β-hydroxy-αamino acids have been elaborated, most of which unfortunately involve multistep procedures and/or the inevitable use of a stoichiometric amount of chiral auxiliaries.[6±8] In this regard, the construction of their primary structure with the correct stereochemistry by the direct catalytic asymmetric aldol reaction of a glycine donor with aldehyde acceptors has been considered to be an ideal protocol.[9] However, there have been few successful examples to date,[10, 11] except for the chemoenzymatic process with glycine-dependent aldolases.[9b, 12] We report herein an efficient and direct asymmetric aldol reaction of glycine Schiff base 2 [13] with aldehydes under organic/aqueous biphasic conditions by using enantiomerically pure, C2-symmetric chiral quaternary ammonium salt 1 [14] as a phase-transfer catalyst (Scheme 1). This approach provides a practical and environmentally benign chemical process for the synthesis of optically active β-hydroxy-αamino acids.Initially, we examined the direct asymmetric aldol reaction of prochiral glycine Schiff base 2 and 3-phenylpropanal as a representative acceptor under phase-transfer conditions. Thorough optimization of the catalyst structure and reaction conditions revealed that treatment of 2 with 3-phenylpropanal (2 equiv) in toluene/aqueous NaOH (1%)(v/v 1.25: 1; 2 equiv of base for 2) in the presence of chiral quaternary ammonium