Polyfunctional Lewis Acid/Betaine Catalysts as New Bioinspired Tool for Asymmetric Synthesis

研究了刘易斯酸与甜菜碱分子内协同作用的协同催化新概念。甜菜碱中的水裸芳氧基作为布朗斯台德碱使亲核体去质子化。催化剂中由此产生的芳香醇将通过氢键活化并空间控制亲电体。它也作为质子源，使营业额。甜菜碱内的唑鎓部分也应该充当H-键供体，但也可以允许静电相互作用。我们最近在文献中提出了多功能协同催化的概念，研究了在酮酯与硝基烯烃的1，4-加成中形成罕见的非对映异构体。在最初的后续研究中，我们发现这一概念是广泛适用的。另一方面，基于反应类型，可能存在明显的机理差异。本文的主要目标是：（1）建立刘易斯酸/甜菜碱协同催化的概念，（2）在可能的情况下发展立体分散的不对称过程，（3）特别是通过机理研究了解更多的多功能作用模式。除了开发高效的合成方法和直接获得增值的手性合成结构单元外，我们还希望通过基于知识的方法为类似催化过程的可预测性和适用性奠定坚实的基础。

A novel concept of synergistic catalysis is investigated exploring theintramolecular cooperation between a Lewis acid and a betaine. Aquasi naked aryloxide within the betaine acts as a Brønsted base todeprotonate a pronucleophile. The thus generated aromatic alcoholwithin the catalyst shall then activate and spatially control anelectrophile via a H-bond. It also serves as a proton source to enableturnover. An azolium moiety within the betaine shall also act a H-bonddonor, but could also allow for electrostatic interactions. We haverecently presented this concept of polyfunctional cooperative catalysisin literature in a study to form the otherwise rare diastereomers in 1,4-additions of ketoesters to nitroolefins. In initial follow-up studies wefound that this concept is broadly applicable. On the other hand –based on the reaction type– there can be distinct mechanisticdifferences. In the present proposal the primary goals are (1) toestablish the concept of cooperative Lewis acid / betaine catalysis invarious attractive stereoselective transformations, (2) if possible todevelop stereodivergent asymmetric processes, and (3) in particularto learn more about the polyfunctional mode of action by mechanisticstudies. Next to the development of efficient synthetic methods and astraightforward access to value-added chiral synthetic building blocks,we would like to create –via a knowledge based approach– aprofound basis for predictability and applicability in similar catalyticprocesses.