Step-Economical Synthesis of Tetrahydroquinolines by Asymmetric Relay Catalytic Friedlander Condensation/Transfer Hydrogenation
Step-Economical Synthesis of Tetrahydroquinolines by Asymmetric Relay Catalytic Friedlander Condensation/Transfer Hydrogenation
复制标题
不对称接力催化弗里德兰德缩合/转移氢化一步经济合成四氢喹啉
DOI：
10.1002/anie.201106808
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Gong, Liu-Zhu
中科院分区：
文献类型：
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作者：
Ren, Lei;Lei, Tao;Gong, Liu-Zhu
手性1，2，3，4-四氢喹啉衍生物在天然生物碱和药物相关分子的制备中具有广泛的应用。[1]它们在合成中的重要性促进了不对称合成方法的发展。[2，3]这种结构基序的最常见途径是喹啉的不对称还原。[3]虽然它是直接的，但这种方法需要预先形成的喹啉衍生物，因此具有适度的步骤经济性。将容易获得的喹啉前体直接和对映选择性地转化为1，2，3，4-四氢喹啉将提供更优雅的方法，但这样的方法仍然非常罕见。本文介绍了一种新的接力催化反应，以易得的2-氨基苯甲醛和可烯醇化的羰基化合物为原料，合成高纯度的1，2，3，4-四氢喹啉。[4]构建药物化合物和复杂的天然产物已被公认为最终目标。最近，有机催化剂和金属配合物在接力和协同催化中的组合使用导致了新的对映选择性方案的创建。[5-14]更重要的是，不对称接力催化（ARC）已被证明能够发现前所未有的分步经济转化。[5]成功的接力催化依赖于金属配合物和有机催化剂的相容性，更重要的是依赖于它们之间的协同作用。迄今公开的二元有机/金属催化剂体系包括基于以下的过渡金属络合物的组合：
Chiral 1, 2, 3, 4-tetrahydroquinoline derivatives have found widespread application in the preparation of naturally occurring alkaloids and pharmaceutically relevant molecules.[1] Their great synthetic importance has stimulated a boom in the development of asymmetric synthetic methods.[2, 3] The most common access to this structural motif is the asymmetric reduction of quinolines.[3] Although it is straightforward, this approach requires preformed quinoline derivatives and thereby suffers from moderate step economy. The direct and enantioselective conversion of readily available precursors of quinolines into the 1, 2, 3, 4-tetrahydroquinolines would provide a more elegant approach, but such methods remain extremely rare. Herein we describe a new relay catalytic reaction to produce 1, 2, 3, 4-tetrahydroquinolines in high levels of enantiopurity by using easily accessible 2-aminobenzaldehydes and enolizable carbonyl-containing compounds as reagents.Step economy is a preeminent concept in contemporary organic synthesis.[4] It has been accepted as an ultimate goal to construct pharmaceutical compounds and complex natural products. Recently, the combined use of organocatalysts and metal complexes in relay and cooperative catalysis has led to the creation of new enantioselective protocols.[5–14] More significantly, asymmetric relay catalysis (ARC) has been proven to enable the discovery of unprecedented stepeconomical transformations.[5] Successful relay catalysis relies on the compatibility and more importantly, on the synergism of metal complexes and organocatalysts. The binary organo/metal catalyst systems disclosed so far include the combination of transition-metal complexes based on