Thiamine-inspired novel organocatalytic reactions with heterazolium precatalysts

随着有机目标分子复杂性的不断增加，新合成方法的不断发展和已知转化的不断改进可以被视为化学研究的永恒目标。在这种情况下，有机催化方法在不对称合成领域中越来越重要;特别是因为这些方法既易于处理，又不含金属的反应条件，而且还具有催化转化的新作用模式，例如聚合反应性。在本项目的范围内，N-杂环卡宾（NHC）催化反应的改进将尝试在协同，多学科的方法。在酶和有机催化的界面上，我们的目标是以双向的方式转移来自这两个领域的见解，以改进和开发新方法。在此前提下，本项目的目标是模拟二磷酸硫胺素（ThDP）依赖性酶的活性。具体而言，我们将研究催化bondcracking反应的基础上，他们的酶的原型和另外，应用洞察到立体分化的酶活性位点内的分子的w-功能化的合成，以提高立体诱导卡宾催化。该项目的另一个目标是将基于合成的知识应用于酶催化，这将在合作项目中实现，包括使用替代底物和实施ThDP依赖性酶的新型辅酶类似物。

With respect to the continuously increasing complexity of organic target molecules the ongoing development of new synthetic methods and improvement of known transformations can be seen as a perpetual goal of chemical research. In this context, organocatalytic processes are gaining importance in the field of asymmetric synthesis; in particular as these methods otter both easy to- handle, metal-free reaction conditions and, moreover, new modes of actions for catalytic transformations, such as umpolung reactivity. Within the scope of this project the improvement of N-heterocyclic carbene (NHC)-catalyzed reactions will be attempted in a synergistic, multidisciplinary approach. At the interface of enzyme and organic catalysis we aim to transfer insights from both fields in a bidirectional way to allow for improvement and development of new methods. With this prerequisite it is the objective of this project to mimic the activity of thiamine diphosphate (ThDP)-dependent enzymes. Specifically, we will investigate catalytic bondcleaving reactions for the synthesis of w-functionalized molecules based on their enzymatic archetypes and additionally, apply insights into the Stereodifferentiation within the enzymes active sites to improve stereoinduction in carbene catalysis. A further goal of this project is the application of synthetic based knowledge to enzyme catalysis, which will be realized in cooperative projects including the employment of alternative substrates and the implementation of novel coenzyme analogues for ThDP-dependent enzymes.