A universal asymmetric catalytic aziridination system, and other forays in chiral catalysis

A universal asymmetric catalytic aziridination system is described. Contributions were made to the development of a robust, efficient and scalable cis-selective aziridination of imines and diazoacetates. By simply switching to diazoacetamides, the diastereoselectivity could be cleanly reversed, and the corresponding trans-aziridines could be accessed efficiently. Thus, employing the same imine and the same chiral catalyst, we can now independently access both cis- and trans- aziridines with excellent yields, diastereoselectivities and asymmetric inductions. The substrate scope is broad for both the cis- and trans- selective aziridination protocols, and includes imines prepared from both electron rich and electron deficient aromatic aldehydes, and also from 1°, 2° and 3° aliphatic aldehydes. The face selectivity of the addition to the imine was found to be independent of the diazo compounds. The (S)-VANOL or (S)-VAPOL catalyst will cause both diazoesters and diazoacetamides to add to the Si-face of the imine when cis-aziridines are formed, and both to add to the Re-face of the imine when trans-aziridines are formed.;The stereochemistry determining step of the universal aziridination reactions was studied using ONIOM(B3LYP/6-31G*:AM1) calculations in collaboration with Dr. Mathew Vetticatt. The origin of cis-selectivity in reactions of ethyldiazoacetate, and trans-selectivity in reactions of N-phenyldiazoacetamide, was understood on the basis of the difference in specific non-covalent interactions at the stereochemistry determining transition state. An H-bonding interaction between the amidic hydrogen and an oxygen atom of the chiral counterion was identified as the key interaction responsible for this reversal in diastereoselectivity. KIE experiments subsequently provided evidence for a rate limiting ring closure for the step-wise mechanism in the universal aziridination reaction.;Other forays in chiral catalysis were also made. New structurally distinct chiral Bronsted acids and ligands were prepared based on the framework of VAPOL and VANOL. Development of other catalytic asymmetric reactions was initiated, including the Darzens reaction, the transfer hydrogenation of quinolines, and the rhodium catalyzed aziridination of olefins, with varying degrees of success.