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

研究了协同催化的新概念，探讨了Lewis酸和甜菜碱的分子内协同作用。甜菜碱中的裸芳基氧化物作为Brønsted碱使原亲核试剂去质子化。这样在催化剂中生成的芳香醇将通过氢键激活并在空间上控制亲电试剂。它也可以作为质子源来实现细胞的转换。甜菜碱中的偶氮部分也可以作为氢键供体，但也可以允许静电相互作用。我们最近在一项研究中提出了多功能协同催化的概念，在1,4-酮酯加成到硝基烯烃中形成罕见的非对映体。在最初的后续研究中，我们发现这个概念是广泛适用的。另一方面，根据反应类型的不同，可以有明显的机械差异。本研究的主要目标是：(1)建立Lewis酸/甜菜碱协同催化各种吸引立体选择转化的概念；(2)如果可能的话，发展立体发散的不对称过程；(3)特别是通过力学研究了解更多关于多功能作用模式的信息。除了开发高效的合成方法和直接获取增值的手性合成构件，我们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建立一个深刻的基础。

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.