Axially Chiral Guanidines as Efficient Bronsted Base Catalysts for Enantioselective Transformations

Abstract

Asymmetric transformations catalyzed by small chiral organic molecules, the so-called enantioselective organocatalysis, have been developed as an efficient protocol for obtaining optically active products in modern organic synthesis. In organocatalytic transformations, the activation of reactants through hydrogen bonding interactions has proven to be a brilliant strategy to provide a chiral environment for the transient assembly of reactants and organocatalysts. In this context, we were interested in the characteristic properties of guanidines, namely, their strong basic character and their ability to act as recognition elements through two parallel hydrogen bonds, which can be manipulated to enable their use as enantioselective organocatalysts. Thus, guanidines are expected to capture nucleophilic components through hydrogen bonding interactions without forming loose ion pairs, after deprotonation from pro-nucleophiles. In addition, the N-H proton would function as a Bronsted acidic site and hence could convey the acid/base dual function even to monofunctional guanidine catalysts. From these basic ideas, we aimed to develop novel axially chiral guanidines as enantioselective Bronsted base catalysts. In this account article, we present our recent achievements in the development of enantioselective transformations using these axially chiral guanidine catalysts.