Iminium Ion Catalysis: Chemical and theoretical tools to understand the catalytic cycle

在合成化学中，无金属工艺被越来越多地用于开发新的、更清洁的、更有效的和选择性的转化。最近的兴趣主要集中在使用环仲胺催化亚胺离子和烯胺，这已经被证明是一个有效的平台，在广泛的反应范围内，提供了丰富的新方法来执行标准的合成方案，高产率和过量对映体。然而，尽管近年来取得了令人印象深刻的进展，但对这些反应的机理的详细了解仍然是令人费解的，催化剂设计基本上仍然是一种偶然事件。我们建议通过对涉及亚胺离子催化的各个步骤以及最终到整个催化循环的关键数量的一系列物理测量来解决这种根本的知识缺乏的问题。这些测量将得到我们小组已经在进行的反应机理的理论计算的补充。通过这种方式，我们将使用这类实际上简单且机械上令人着迷的转换来增强现有的备受瞩目的合成方法，并最终促进新的、更高效的催化剂的合理设计。

Metal free processes are increasingly used to develop novel, cleaner, more efficient and selective transformations in synthetic chemistry. Much recent interest has centred on iminium ion and enamine catalysis using cyclic secondary amines, which has been shown to be an effective platform a wide range of reactions, providing a wealth of new methods with which to perform standard synthetic protocols in high yield and enantiomeric excess. Despite impressive advances in recent years, however, a detailed understanding of the mechanisms for these reactions remains elusive and catalyst design remains essentially a hit-and-miss affair.We propose to address this fundamental lack of knowledge by carrying out a series of physical measurements of key quantities, such as rate constants and activation barriers, for individual steps involved in iminium ion catalysis, and ultimately to the entire catalytic cycle. Such measurements will be complemented by theoretical calculations of reaction mechanisms, already underway in our group. In this way, we will augment the existing high profile synthetic methodologies using this practically simple and mechanistically fascinating class of transformation, and ultimately facilitate rational design of new, more efficient catalysts.