Catalytic asymmetric aziridination: Preparation of ligand, exploration of mechanism and discovery of new methodology

The large scale preparation of racemic VANOL ligand by oxidative coupling and the improved resolution of VANOL were examined in the first part of this thesis. A highly efficient and enantioselective deracemization process of the vaulted and linear biaryl ligands was developed for the preparation of optically pure S-VAPOL and S-VANOL ligands.; The mechanism of the chiral ligand-borate catalyzed asymmetric aziridination reaction of N-benzhydryl aldimines and ethyl diazoacetate as well as the origin of the enantioselectivity was studied in detail. It was proposed that the active catalyst was generated from one molecule of the chiral ligand and one equivalent of triphenyl borate. Modeling suggested that the coordination of the N-benzhydryl imine with the chiral borate Lewis acid catalyst involves two CH-pi (face-edge) interactions between the catalyst and the substrate.; In the second part of this thesis, aldimines with various symmetrically and/or asymmetrically substituted N-protecting groups were designed and prepared to examine this proposal, and the effects of electronics and sterics of these imines on the reaction outcome were studied. These mechanistic studies eventually led to the discovery of the aziridination methodology with the N-BUDAM and N-MEDAM imines, which exhibit significantly improved stereoselectivity and reactivity over the unsubstituted benzhydryl imines. The study on the alpha-alkylbenzyl imines suggested possible applications of the observed match/mismatched pair, whereas the studies of the relative reaction rates of various substrates suggested possible non-bonding interactions between the substrate and catalyst, provided insights into the mechanism of the aziridination reaction.; The exploration of the structures of the catalysts derived from the chiral ligand and triphenyl borate led to the discovery of two active borate species. The identification of the actual active aziridination catalyst species, along with the studies of match/mismatched relationships with chiral benzhydryl imines suggested that the aziridination reaction involves a bis-borate catalyst species which is different from the original proposal.