Studies on alkene aziridination using N-acetoxyaminoquinazolin-4(3H)-ones
The work contained in this thesis re-examines the mechanism of formation of aziridines from lead tetra-acetate (LTA) oxidation of N-aminoquinazolones in the presence of alkenes. Hitherto, the intermediates involved in these aziridinations were thought to be the corresponding N-nitrenes. However, evidence presented in this thesis shows that these intermediates are the corresponding N-acetoxyaminoquinazolones. This conclusion was supported, inter alia, by the low temperature (-20C) 1H n.m.r. spectra of N-acetoxyaminoquinazolones, obtained by LTA oxidation of the corresponding N-aminoquinazolones at -20C. Solutions of N-acetoxyamino-2-ethylquinazolone were found to be stable at this temperature but brought about the aziridination of alkenes when allowed to warm to room temperature in the presence of the latter. An analogy is drawn between aziridination of alkenes using N-acetoxyaminoquinazolones and epoxidation of alkenes using peracids. Using N-acetoxyamino-2-ethylquinazolone, aziridination of geraniol is more regioselective and aziridination of cyclohex-2-en-1-ol is more facially selective than epoxidation of these alkenes using peracids. Aziridination of cyclohex-3-en-1-ol is also examined and in contrast to epoxidation using peracids, aziridination of this alkene is stereo- specific and gives only the syn-aziridine. As solutions of the N-acetoxyamino-2-ethylquinazolone are stable at -20C, it is now possible to bring about aziridination of LTA-labile alkenes: the addition of silyl ketene acetals to these solutions followed by warming to room temperature afforded the corresponding N-protected alpha-amino acid esters in excellent yields. The same methodology has been used to bring about aziridination of vinylstannanes and vinylsilanes. Desilylation of the derived silyl-substituted aziridines provides a new route to 2H-azirines and the presumed intermediate aziridinyl carbanions have been intercepted with benzaldehyde or protons as electrophiles. Aziridination of alkenes by oxidative (LTA or PhI(OAc)2) addition of N-aminoquinazolones in the presence of trifluoroacetic acid is also examined; the dramatic increases in yields in some cases are rationalised by protonated N-acetoxyaminoquinazolone intermediates.