Water in organocatalytic processes: Debunking the myths
Water in organocatalytic processes: Debunking the myths
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DOI：
10.1002/anie.200604952
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Wells, Andrew
中科院分区：
文献类型：
--
作者：
Blackmond, Donna G.;Armstrong, Alan;Wells, Andrew
在过去的几十年里，由于学术和工业上对各种液体和多相有机转化的高效、选择性催化剂的发现，催化路线在合成复杂有机分子方面的应用取得了巨大的增长。这些发展与制药和化工行业在一个经济竞争日益激烈和具有生态意识的市场中精简制造和废物处理成本的重大努力不谋而合。有机催化领域因其绿色化学优势和类似于未完善的酶催化而备受关注。最近，开发高效的水相有机催化过程的挑战已经提出。水是一种诱人的溶剂：生物过程在水中进行；一些有机反应被水加速，而另一些在这种介质中被抑制。氢键、极性、酸度、熵和疏水性都在水在其存在下对有机反应产生的最终影响中发挥重要作用。从工业角度来看，这些性质可以赋予水不同的行为，使其成为一种有趣的候选溶剂或助溶剂，甚至在考虑其潜在的环境效益之前。[1]我们在此为最近发表的关于在含水系统中进行的基于烯胺的有机催化这一特定问题的交换发表了贡献。[2]Janda和他的同事[2a]开始讨论时，对S选择的反应条件的机理含义发表了重要评论，他们指出，开发由小分子催化剂催化的反应的真正水溶液版本仍然是一个挑战。对此，Hayashi[2b]选择将重点放在他认为只是“术语混乱”的问题上，即我们是否应该说反应是在“水中”、“在水存在的情况下”还是“在大量过剩的水存在的情况下”进行的。事实上，这门学科现在似乎面临着以牺牲科学为代价，陷入语义学泥潭的危险。我们想谈谈我们认为在讨论中迄今被忽视的几个关键方面。我们提出了两个问题，直接挑战了我们对水基有机催化的假设：水基有机催化反应有多“绿色”，效率有多高。
The past several decades have witnessed a tremendous growth in the application of catalytic routes to the synthesis of complex organic molecules, driven by academic and industrial discoveries of efficient, selective catalysts for a wide variety of liquid-and multiphase organic transformations. These developments coincide with major efforts in the pharmaceutical and chemical industries toward streamlining the costs of manufacture and waste disposal in an evermore economically competitive and ecologically aware market. The area of organocatalysis has received much attention in light of a perception both of its green chemistry advantages and its analogy to eon-perfected enzyme catalysis. Most recently, the challenge of developing efficient aqueous-phase organocatalytic processes has been posed. Water is a beguiling solvent: biological processes are conducted in water; some organic reactions are accelerated by water, while others are inhibited in this medium. Hydrogen bonding, polarity, acidity, entropy, and hydrophobicity all have important roles to play in the ultimate influence that water exerts on organic reactions mediated in its presence. The varied behavior that these properties can impart makes water an interesting candidate as a solvent or cosolvent from an industrial perspective, even before its potential environmental benefits are considered.[1] We contribute herein to the recent exchange published on the specific issue of enamine-based organocatalysis carried out in systems containing water.[2] Janda and co-workers [2a] began the discussion with important comments about the mechanistic implications of one s choice of reaction conditions, and they noted that development of a truly aqueous version of a reaction catalyzed by a small-molecule catalyst remains a challenge. In response, Hayashi [2b] chose to focus on what he sees as simply “confusion over the terminology”, that is, whether we should say that a reaction is carried out “in water”,“in the presence of water”, or “in the presence of a large excess of water”. Indeed, the subject now seems in danger of being mired down in semantics at the expense of science. We would like to address several critical aspects that we feel have been neglected in the discussion to date. We pose two questions that directly challenge our assumptions about aqueous-based organocatalysis: how “green” and how efficient are aqueous-based organocatalytic reactions.