Highly efficient asymmetric direct stoichiometric aldol reactions on/in water
Highly efficient asymmetric direct stoichiometric aldol reactions on/in water
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DOI：
10.1002/anie.200703606
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Armstrong, Daniel W.
中科院分区：
文献类型：
--
作者：
Huang, Junmin;Zhang, Xiaotong;Armstrong, Daniel W.
许多酶在温和的条件下在水中催化反应，具有高效率和良好的立体选择性。这种高效且环境友好的合成方法通常被认为是现代有机化学的目标。[1]虽然酶具有合成效用，但它们通常受到缺乏大规模相容性的限制。[2]非常需要开发一种能够模拟酶的作用并以优异的效率和立体选择性在水中进行有机反应的化学体系。水是一种安全、廉价和环保的溶剂，这使得它在学术实验室和工业中的使用都很有利。Breslow [3]在20世纪80年代初对水中Diels-Alder反应的开创性研究引发了人们对使用水作为有机合成介质的更广泛的兴趣，不仅因为这些反应消除了剧烈干燥溶剂和底物的必要性，而且还因为在水性反应中经常观察到独特的反应性和选择性。在过去的二十年里，人们在发展水基合成有机反应方面做出了相当大的努力。[4]到目前为止，只有相对有限数量的对映选择性有机反应可以有效地进行在这种溶剂中，相关的机制可能是不清楚的。[5]事实上，水中的不对称合成似乎仍然不是一个常规或优选的程序。对映选择性金属催化在过去的20年里彻底改变了不对称合成，并获得了2001年诺贝尔化学奖。[6]随后，List，Lerner和Barbas关于脯氨酸催化的直接不对称羟醛缩合反应的分子间适应性的开创性工作[7]将注意力集中在无金属有机小分子（有机催化剂）的催化不对称反应上。该合成方法因其绿色化学优势而备受关注。[8]脯氨酸被认为是一种有效和多功能的小分子“酶”[9]，催化广泛的有机转化。然而，与自然界中在水中发生的酶促反应不同，对映选择性有机催化过程通常在有机溶剂中进行。为
Many enzymes catalyze reactions in water under mild conditions with high efficiency and excellent stereoselectivity. This highly effective and environmentally benign synthetic methodology is often regarded as a goal in modern organic chemistry.[1] Although enzymes have synthetic utility, they are usually limited by their lack of large-scale compatibility.[2] It is highly desirable to develop a chemical system that can mimic the action of enzymes and effect organic reactions in water with excellent efficiency and stereoselectivity. Water can be a safe, inexpensive, and environmentally friendly solvent, which makes its use favorable both in academic laboratories and in industry. The pioneering studies of Diels–Alder reactions in water by Breslow [3] in the early 1980s triggered a more widespread interest in the use of water as a medium for organic synthesis, not only because these reactions eliminate the necessity of vigorously drying solvents and substrates, but also because of the unique reactivity and selectivity often observed in aqueous reactions. In the past two decades considerable effort has been made in developing water-based synthetic organic reactions.[4] Thus far, only a relatively limited number of enantioselective organic reactions can be carried out effectively in this solvent and the associated mechanisms can be unclear.[5] Indeed, it appears that asymmetric synthesis in water is still not a routine or preferred procedure.Enantioselective metal catalysis has revolutionized asymmetric synthesis over the past 20 years and was recognized by the 2001 Nobel Prize in Chemistry.[6] Subsequently, the seminal work by List, Lerner, and Barbas on the intermolecular adaptation of the proline-catalyzed direct asymmetric aldol reaction [7] has focused attention on the catalytic asymmetric reaction by metal-free small organic molecules (organocatalysts). This synthetic approach has received much attention in light of its green chemistry advantages.[8] Proline is regarded as an effective and versatile small-molecule “enzyme”[9] that catalyzes a wide range of organic transformations. However, unlike enzymatic reactions in nature that occur in water, enantioselective organocatalytic processes have typically been carried out in organic solvents. For