Catalytic enantioselective cross-Mannich reaction of aldehydes
Catalytic enantioselective cross-Mannich reaction of aldehydes
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DOI：
10.1002/anie.200502630
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Marques, MMB
中科院分区：
文献类型：
--
作者：
Marques, MMB
曼尼希反应是合成含氮化合物最有用的反应之一，也是构建CÀC键的有效方法具有光学活性、含氮分子（蛋白质、核酸、生物活性化合物）的各种天然产物和药物引起了合成化学家和制药工业的极大关注，这刺激了不对称曼尼希反应的发展。[1,2]曼尼希反应和醛醇反应都是高度原子经济性的，解决了立体控制问题，因此经常被用作现代有机合成的关键步骤。控制曼尼希反应的三个组分（羰基供体、胺和醛受体）是主要的挑战之一，因为可能会发生相应的醛醇反应等副反应，从而降低收率。最近取得了令人印象深刻的成就，特别是在不对称催化方面，关于这种反应的多功能性。催化直接和间接对映选择性方法已经发展起来。直接曼尼希反应需要未修饰的酮体、胺和醛，而间接曼尼希反应使用预形成的烯酸酯等价物和/或亚胺。在过去的几年中，已经报道了许多催化不对称曼尼希方法Kobayashi， Sodeoka和Lectka研究小组已经报道了优秀的间接催化方法，包括在金属催化剂的存在下将烯醇化物加成到亚胺上，他们分别使用了手性锆/binol，钯(ii)/binap和铜(i)/binap配合物（binol= 1,1 ' -联萘酚，binap= 2,2 ' -双（二苯基磷酰）-1-1 ' -联萘酚）最近，Kobayashi及其同事以水为溶剂，开发了一种高效的对映和非对映选择性的肼酯与硅烯醇酯的曼尼奇型催化反应（方案1）。应该注意的是，这种方法提供了立体特异性地从(E)或(Z)烯醇化物中获得正合物或反合物的途径。这些方法的缺点是预成形的烯醇化物不稳定。因此，基于未修饰酮体的直接方法将提高曼尼希反应的效率。Trost和Terrell以及Shibasaki等人报道了直接和高度对映选择性催化的不对称Mannich反应，他们分别使用双核锌催化剂和锌与（S， S）连接的二醇结合作为催化剂A， b-的新方法
The Mannich reaction is one of the most useful reactions for the synthesis of nitrogen-containing compounds as well as an effective method for the construction of CÀC bonds.[1] A wide variety of natural products and drugs possessing optically active, nitrogen-containing molecules (proteins, nucleic acids, biologically active compounds) have attracted considerable attention from synthetic chemists and the pharmaceutical industry, which has stimulated the development of asymmetric Mannich reactions.[1, 2] Mannich and aldol reactions are both highly atom economic and address the problem of stereocontrol, and are therefore often used as key steps in modern organic synthesis. Control over the three components of the Mannich reaction (carbonyl donor, amine, and aldehyde acceptor) constitutes one of the main challenges, since side reactions such as the corresponding aldol reaction might occur, thus lowering the yield. Impressive achievements have recently been made, in particular in asymmetric catalysis, with regard to the versatility of this reaction. Catalytic direct and indirect enantioselective methodologies have been developed. While the direct Mannich reaction requires unmodified ketone donors, amines, and aldehydes, the indirect Mannich reaction uses preformed enolate equivalents and/or imines. Many catalytic asymmetric Mannich methods have been reported over the last few years.[3] Excellent indirect catalytic methods, which involve the addition of enolates to imines in the presence of metal catalysts, have been reported by the Kobayashi, Sodeoka, and Lectka research groups, who used chiral zirconium/binol, palladium (ii)/binap, and copper (i)/binap complexes, respectively (binol= 1, 1’-binaphthol, binap= 2, 2’-bis (diphenylphosphanyl)-1-1’-binaphthyl).[4] Recently, Kobayashi and co-workers developed an efficient catalytic, enantio-and diastereoselective Mannich-type reaction of a hydrazono ester with silicon enolates using water as the solvent (Scheme 1). It should be noted that this method provides access to either the syn or anti adducts stereospecifically from (E) or (Z)-enolates.[5]Most of these methods have the disadvantage that the preformed enolates are unstable. Thus, a direct methodology based on unmodified ketone donors would enhance the efficiency of the Mannich reaction. Direct and highly enantioselective catalytic asymmetric Mannich reactions were reported by Trost and Terrell as well as by Shibasaki and co-workers, who used a dinuclear zinc catalyst and zinc combined with (S, S)-linked-binol as the catalyst, respectively.[6] A new approach to a, b-