Arylamine-Catalyzed Enamlne Formation: Cooperative Catalysis with Arylamines and Acids

摘要

The explosive growth of organocatalysis has had a huge impact on asymmetric catalysis in the past decade. Transition-metal catalysis, on the other hand, has been established for a long time as one of the most powerful methods in organic synthesis. Aminocatalysis is a major field in organocatalysis. The combination of organocatalysis with the more traditional metal Lewis acid catalysis has emerged, aiming to achieve organic transformations that cannot be accomplished by organocatalysis or metal catalysis independently. Although it promises huge potential, this research area has grown only slowly. The major challenge lies in the incompatibility of the catalysts, in particular, the combination of enamine catalysis with harder metal Lewis acid is very difficult. The circumvention of this problem would represent an important breakthrough, given the huge number of substrates that can be activated by the large variety of metal Lewis acids. Herein, we present the solution to this longstanding problem by using arylamines as the catalysts in enamine catalysis. Very importantly, we demonstrate that arylamines can serve as efficient amine catalysts in direct asymmetric aldol reactions. Furthermore, we have developed a highly chemo- and enantioselective three-component aza-Diels-Alder reaction by combining arylamines with metal Lewis acids.