Studies On Lewis Acid-Catalyzed Asymmetric Transformations Of Aziridines

This dissertation focuses on the catalytic asymmetric transformations of aziridines under Lewis acid catalysis,and has developed several reaction systems involving the asymmetric desymmetrization of meso-aziridines,asymmetric kinetic resolutions and dynamic kinetic asymmetric transformations of race-aziridines,as outlined below:1.The Lewis acid-catalyzed asymmetric desymmetrization of meso aziridines and kinetic resolution of racemic 2-aryl aziridines with aliphatic amines have been investigated.After establishing the optimum reaction conditions,the substrate scope and scalability of the reaction have been probed,and the corresponding chiral diamine products were obtained in 58–98% yields and with 60–95% ee.Preliminary mechanistic study revealed a negative nonlinear effect between the ees of the product and the diphosphine ligand,and a transition-state model has been proposed to rationalize the observed stereochemical results.Elaboration of some of the products to structures present in common chiral ligands and/or catalysts has also been performed.2.Based on the high reactivity of racemic aziridines bearing electron-rich 2-(hetero)aryl group,the Lewis acid-catalyzed dynamic kinetic asymmetric aminolysis of such racemic aziridines with amines has been developed.Under the optimized reaction conditions,the reaction proceeded well with aromatic and aliphatic,and primary and secondary amines to provde the diamine products in excellent regioselectivity and enantioselectivity(84–98% yields,80–93% ee),and could be readily scaled up on gram-scale.Starting from the product III-1ha,it takes only one step to synthesize a chiral piperazine compound in high yield and enantiopurity;chiral piperazines are a structural motif widely existing in many important drug molecules.3.The Lewis acid-catalyzed dynamic kinetic asymmetric transformations of racemic 2-(hetero)aryl-N-sulfonylaziridines with aldehydes has been developed.Under mild reaction conditions,of the reaction tolerated both(hetero)aryl aldehydes and ?,?-unsaturated aldehydes to provide chiral 1,3-oxazolidines(84-98% yields,10:1-> 20:1 dr,74-99% ee).The results of a series of control experiments suggest the reaction might have proceeded via a type I DyKAT process and a stereochemical model of this reaction has also been proposed.4.The Lewis acid-catalyzed dynamic kinetic asymmetric reaction between racemic 2-aryl-N-sulfonylaziridines and electron-rich arenes or hetero-arenes has been developed.Depending on the structures of the nucleophilic(hetero)arenes,either Friedel-Crafts-type or [3+2] annulation reaction may take place to provid a range of chiral nitrogen-containing products,which could be further elaborated other useful structures through simple synthetic manipulations.All the new compounds were fully characterized by NMR,high resolution mass spectrometry and high performance liquid chromatography,and the absolute configurations of representative compounds have been assigned based on x-ray crystallographic analyses.