A highly enantioselective amino acid-catalyzed route to functionalized α-amino acids
A highly enantioselective amino acid-catalyzed route to functionalized α-amino acids
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DOI：
10.1021/ja017270h
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发表时间：
2002-03-06
影响因子：
15
通讯作者：
Barbas, CF
中科院分区：
文献类型：
--
作者：
Córdova, A;Notz, W;Barbas, CF
提供对映体纯α-氨基酸的合成方法的发展已经引起了一代又一代化学家的兴趣，并成为激烈研究的主题。本报告描述了一种基于催化不对称合成的功能化α-氨基酸的一般方法。脯氨酸可催化n - pmp保护的α-亚氨基乙基乙醛酸酯与多种未修饰酮的曼尼基型反应，以高收率获得功能化α-氨基酸，具有优异的区域、非映对和对映选择性。7个样品中有6个产品ee值≥99%。在涉及酮体的反应中，可以形成非对映异构体产物，在完全立体控制下，碳-碳键形成时同时产生两个相邻的立体中心。值得注意的是，该方法利用现成且相当便宜的起始材料，不需要任何底物预活化或金属离子辅助，并且可以在操作简单的反应条件下以克为单位进行。产品中存在的酮功能为多功能修改提供了一个特别有吸引力的场所。这项研究补充并扩展了我们的不对称合成的生物有机方法到一个通用的合成类。鉴于我们已经证明了多种旋光性氨基酸可以用脯氨酸催化合成，其中反氨基酸生成其他氨基酸，我们的结果可能会激发基于这一途径合成旋光性氨基酸的益生元的想法。
The development of syntheses providing enantiomerically pure α-amino acids has intrigued generations of chemists and been the subject of intense research. This report describes a general approach to functionalized α-amino acids based on catalytic asymmetric synthesis. Proline catalyzed Mannich-type reactions ofN-PMP-protected α-imino ethyl glyoxylate with a variety of unmodified ketones to provide functionalized α-amino acids in high yields with excellent regio-, diastereo-, and enantioselectivities. Study of seven examples yielded six with product ee values of ≥99%. In reactions involving ketone donors where diastereoisomeric products could be formed, two adjacent stereogenic centers were created simultaneously upon carbon−carbon bond formation with completesyn-stereocontrol. Significantly, this methodology utilizes readily available and rather inexpensive starting materials, does not require any preactivation of substrates or metal ion assistance, and can be carried out on a gram scale under operationally simple reaction conditions. The keto-functionality present in the products provides a particularly attractive site for versatile modifications. This study compliments and extends our bioorganic approach to asymmetric synthesis to a versatile synthon class. Given that we have shown that a variety of optically active amino acids can be synthesized with proline catalysis, where anl-amino acid begets otherl-amino acids, our results may stimulate thoughts concerning prebiotic syntheses of optically active amino acids based on this route.