Development of anion-binding approaches to asymmetric catalysis

The dual catalytic approach in asymmetric catalysis has gained considerable attention in recent times. Many otherwise inefficient and unattainable chemical processes can be accomplished by this approach. Outlined within this dissertation are recent efforts in improving the overall efficiency of this process as well as expanding this method involving nucleophilic/anion-binding catalysis to the kinetic resolution of allylic amines and 1,2-diamines. An efficient catalytic system has been identified through targeted structural modifications of both the achiral nucleophilic catalyst and the chiral anion-binding co-catalyst. This has resulted in increased selectivities while simultaneously allowing for significantly reduced catalyst loadings. Based on the mechanistic insight into the anion binding approach for the kinetic resolution of amines, we established that there was a 1:1 catalyst to benzoate anion binding ratio. Cooperative approaches in which Brønsted acids act in concert with other Brønsted acids or (thio) urea co-catalysts have gained significance. This study describes the synthesis of a new class of chiral conjugate-base-stabilized Brønsted acid catalysts and a new concept for cooperative hydrogen bonding/ Brønsted acid catalysis. These chiral Brønsted acids contain a carboxylic acid group which is connected via an appropriate linker to an anion receptor moiety such as a thiourea. Substrate protonation by the catalyst results in the association of the conjugate base with the anion recognition site, resulting in the formation of a rigid catalyst/substrate ion pair. We were able to successfully apply this concept to the catalytic enantioselective Povarov and Pictet-Spengler reactions.Ph. D.Includes bibliographical referencesby Nisha Mitta