New developments in enantioselective Brønsted acid catalysis: chiral ion pair catalysis and beyond.

Abstract

The design of catalytic reactions that proceed with high enantioselectivity is an important goal in organic synthesis. Increased interest in this research area has resulted in substantial progress, particularly in the field of metal catalyzed transformations. In recent years small organic molecules have been used as organocatalysts for a variety of enantioselective reactions. Among these, secondary amine catalysts are the most widely applied and can be used in the activation of the nucleophilic component through enamine formation (enamine catalysis), or by formation of an iminum intermediate to activate the electrophile (iminium catalysis). Additionally, chiral diols and thioureas, as well as carbene- and DMAP-derivatives (hydrogen bonding-, nucleophilic catalysis), have been shown to be versatile catalysts for enantioselective transformations. An alternative to these strategies is the activation of an electrophile or nucleophile by use of a chiral Brønsted acid. Compared to amino-, carbene-, pyridine- and hydrogen-bonding catalyzed transformations, enantioselective Brønsted acid catalysis has only recently emerged as important and promising area of research. In the course of our research program we were able to contribute significantly to the field of enantioselective Brønsted acid catalysis over the last 2 years, and could demonstrate for the first time that in various enantioselective transformations chiral Brønsted acid catalysts can give better or at least comparable results to metal-catalyzed processes. In this chapter we will highlight some of our most recent results and will, additionally, describe how we initially entered the field of asymmetric Brønsted acid catalysis by starting of from a biomimetic approach using nature as a role model.