| A cascade reaction is developed to form complex cyclopentanones using an asymmetric Michael/Benzoin sequence. This reaction employs simple aliphatic aldehydes and ketoesters in conjunction with a chiral amine catalyst and a chiral NHC catalyst. Further investigation reveals a surprising interplay between these two catalysts. This relationship is manifested in a pseudo-dynamic kinetic resolution, which is responsible for the high diastereoselectivity observed.;Subsequent work details the discovery of the aminomethylation of enals using NHC catalysis. This reaction utilizes an iminium source as well as cinnamaldehyde derivatives to form gamma-amino butyrate derivatives. Rendering this reaction asymmetric has proven a challenge, despite extensive effort to resolve these issues. In the course of these studies, an unexpected NHC-catalyzed Morita-Baylis-Hillman reaction was observed. Optimal conditions for this reaction were established, proving access to useful amino-enals.;In an effort to design suitable catalysts for the asymmetric aminomethylation reaction, a strategy for the late-stage manipulation of NHC catalysts was developed. Key to this strategy is the 'protection' of the triazolium salt by reduction to the triazoline. An aryl C-Br bond is then exploited for cross-coupling reactions, building a small library of new catalysts. The triazolium salt is then recovered by oxidation with a trityl salt. |
