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

点击翻译按钮获取中文摘要

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.