Powerful chiral phase-transfer catalysts for the asymmetric synthesis of α-alkyl- and α,α,-dialkyl-α-amino acids
Powerful chiral phase-transfer catalysts for the asymmetric synthesis of α-alkyl- and α,α,-dialkyl-α-amino acids
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DOI：
10.1002/anie.200462257
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Maruoka, K
中科院分区：
文献类型：
--
作者：
Kitamra, M;Shirakawa, S;Maruoka, K
相转移催化技术因具有操作简单、反应条件温和、环境友好、适合大规模反应等优点，在学术界和工业界被公认为是一种方便和实用的工具。[1，2]此外，发展有效的方法来制备天然和非天然的α-烷基和α，α-二烷基-α-氨基酸，特别是通过不对称相转移催化合成具有对映体纯度的氨基酸，由于它们具有很高的合成效率，因此变得非常重要。几种相转移催化剂已经被开发出来，从而以高产率获得具有良好的对映选择性的产品。[4]然而，尽管有大量的研究，真正有效的催化系统在非常低的催化剂装载量下具有高的对映选择性(例如，<；在不对称碳-碳键的形成中仍然很少见，在催化剂负载量方面的重大进展仍然是实用的不对称合成所需的。自从我们最近开发的手性螺型(R，R)-或(S，S)-3，4，5-三氟苯基-溴化钠1在α-氨基酸衍生物的不对称烷基化反应中表现出极高的对映选择性，[4d，e，m]我们的下一个目标是设计一种非常活性的催化剂。考虑到1的高度亲油性和界面层中金属烯烃的生成，[5]这种亲脂性1(Qx)必须移动到界面层以诱导与金属烯醇的简单交换反应(图式1)。基于这一假设，我们的策略是用柔性直链烷基取代1中的刚性联萘部分，以提供一种新的2型催化剂，由于二烷基铵部分的极性增加，大大加速了与2的烯醇交换。在此，我们报道了这种设计的手性季铵盐2是一种非常有效的手性相转移催化剂，用于保护甘氨酸和α烷基α氨基酸衍生物的高度实用的对映选择性烷基化反应。以市售的(S)-1，1‘-联萘-2，2’-二元酸(3)[6]为原料，经六步反应制得所需的催化剂(S)-2。因此，(S)-二元酸3与异溴化氢、催化丁四氮和KF·2H2O反应生成相应的二异丙酯4，产率为95%。4在四氢呋喃中与新合成的Mg(TMP)2(TMP=2，2，6，6-四甲基哌啶)反应，然后加溴，得到(S)-3，3‘-二溴-1，1’-联萘基-2，2‘-二羧酸酯5，收率91%。在Pd(OAc)2、PPh3和K2CO3的催化下，5与3，4，5-三氟苯基硼酸在N，N-二甲基甲酰胺(DMF)中发生偶联反应，合成了(S)-3，3‘-二(3，4，5-三氟苯基)-1，1’-联萘基-2，2‘-二羧酸酯(6)，产率为94%。减少了6个
Phase-transfer catalysis (PTC) has been recognized as a convenient and highly useful tool in academia and industry because it offers several advantages for practical organic synthesis, such as operational simplicity, mild reaction conditions in aqueous media, environmental benefits, and suitability for large-scale reactions.[1, 2] Also the development of efficient methods for the preparation of natural and nonnatural α-alkyl-and α, α-dialkyl-α-amino acids, especially in their enantiomerically pure forms by asymmetric PTC, has become very important because of their high synthetic utility.[3, 4] Accordingly, several phase-transfer catalysts have been developed that lead to products with excellent enantioselectivities in high yields.[4] However, despite numerous studies, truly efficient catalytic systems with high enantioselection at very low catalyst loading (eg,< 0.1 mol%) are still rare in asymmetric carbon–carbon bond formation, and major progress in terms of catalyst loading is still desirable for practical asymmetric synthesis. Since our recently developed, chiral spiro-type (R, R)-or (S, S)-3, 4, 5-trifluorophenyl-NAS bromide 1 shows exceedingly high enantioselectivity in asymmetric alkylation of α-amino acid derivatives,[4d, e, m] our next target was the design of a very active catalyst. Considering the highly lipophilic nature of 1 and the generation of a metal enolate in an interfacial layer,[5] such lipophilic 1 (QX) must move to the interfacial layer to induce a facile exchange reaction with a metal enolate (Scheme1). Based on this assumption, our strategy was to replace the rigid binaphthyl moiety in 1 by flexible straight-chain alkyl groups to furnish a new catalyst of type 2, which substantially accelerates the enolate exchange with 2 because of the increasing polarity of the dialkylammonium moiety. Herein, we report that such a designer chiral quaternary ammonium salt 2 behaves as a very powerful chiral phase-transfer catalyst for the highly practical, enantioselective alkylation of protected-glycine and αalkyl-α-amino acid derivatives. The requisite catalyst (S)-2 can be readily prepared from the commercially available (S)-1, 1’-binaphthyl-2, 2’-dicarboxylic acid (3)[6] in a six-step sequence as outlined in Scheme 2.[7]Thus,(S)-dicarboxylic acid 3 was transformed with iPrBr, catalytic Bu4N· HSO4, and KF· 2H2O to the corresponding diisopropyl ester 4 in 95% yield. Treatment of 4 with freshly prepared Mg (TMP) 2 (TMP= 2, 2, 6, 6-tetramethylpiperidide) in THF and subsequent additon of bromine gave rise to (S)-3, 3’-dibromo-1, 1’-binaphthyl-2, 2’-dicarboxylic ester 5 in 91% yield. Suzuki–Miyaura cross coupling of 5 with 3, 4, 5-trifluorophenylboronic acid in the presence of catalytic Pd (OAc) 2, PPh3, and K2CO3 in N, N-dimethylformamide (DMF) afforded(S)-3, 3’-bis (3, 4, 5-trifluorophenyl)-1, 1’-binaphthyl-2, 2’-dicarboxylic ester (6) in 94% yield. Reduction of 6 with