The catalytic asymmetric aziridination of imines and diazo compounds mediated by boroxinate catalysts derived from the VANOL and VAPOL ligands was investigated with chiral imines derived from α-methylbenzyl amine and various aldehydes. The matched case for cis-aziridines from ethyl α-diazo acetate involves the (R)-imine with the (S)-ligand whereas the matched case for trans-aziridines from N-phenyl-α-diazo acetamide involves the (R)-imines with the (R)-ligand for imines from benzaldehyde and butyraldehyde, and the (R)-imines with the (S)-ligand for imines derived from the bulkier aliphatic aldehydes, pivaldehyde and cyclohexane carboxaldehyde. Optically pure aziridines could be obtained in good yields and with high diastereoselectivity, which could be converted to α- or β-amino ester derivatives via hydrogenolysis. Extension of our protocol for di-substituted aziridine synthesis to tri-substituted aziridine proved to be challenging. However, it was realized by employing N-Boc imines and α-diazo carbonyl compounds in which the diazo carbon was disubstituted. The highly reactive α-diazo esters give only moderate yields, but the more slowly reacting α-diazo-N-acyloxazolidinones give much higher yields. The optimal ligand is VANOL that can provide a catalyst for the stereocomplimentary approaches to tri-substituted aziridines: trans-isomers via aziridination and cis-isomers via aziridination/alkylation. Having established a very efficient catalytic asymmetric synthesis of aziridines, the next logical step would be to develop its potential in organic synthesis. The ring expansion of aziridine-2-carboxylic acids has significant potential for the synthesis of hetereocycles and the type of heterocycles proved to be dependent on the structure of the aziridine-2-carboxylic acids. When there is alkyl group on the C2 position and an aromatic group on the C3 position, the reaction of aziridine-2-carboxylic acids with (COCl)2 provides N-carboxyanhydrides whereas morpholine-2,3,5-triones are formed if there is an aromatic group on the C3 position with a hydrogen on C2. Curiously, β-lactams are formed in a stereoselective manner when aziridine-2-carboxylic acids with an alkyl group present on the C3 position is treated with (COCl)2. Finally, it proved possible to convert the aziridine-2-carboxylic acids with an aromatic group on the C3 position to β-lactams with a Vilsmeier reagent.
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