3-Acetoxyaminoquinazolin-4(3H)-ones as aziridinating agents for alkenes : stereochemistry and mechanism

• Main Author: Ulukanli, Sabri
• Published: University of Leicester 1999
• Subjects: 547
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.696614

Yields of aziridines from aziridinations of some alkenes using 3-acetoxyaminoquinoazolinones are greatly increased in the presence of hexamethyldisilazane (HMDS). It is concluded that the enhanced yields in these aziridinations are the result of scavenging of acetic acid which is produced in acetoxylation of N-aminoquinazolinones by lead tetra-acetate, as well as in the aziridination step, thus prolonging the lifetime aziridinating agent (QNHOAc). The effect of trifluoroacetic acid (TFA) on the competitive reactions of 5-H and 5-Me 3-acetoxyaminoquinazolinones with methyl and tert-butyl acrylate is interpreted as supporting a change in transition state geometry from one where (Q)C=O/(ester)C=O overlap is replaced by (Q)C=N+H/(ester)C=O overlap (Q=quinazolinone). Aziridination of methyl- and tert-butyl acrylate using 2-trifluoromethyl-substituted 5-H and 5-Me 3-acetoxyaminoquinazolinones takes place through the transition state involving (Q)C=N(ester)C=O overlap even in the absence of TFA. Aziridination of a range of -substituted-styrenes using enantiopure 3-acetoxyaminoquinazolinones has been carried out. diastereoselectivity for -methylstyrene, -chloromethylstyrene, -dichloromethylstyrene increases from 5:1 to 10:1 to 20:1 respectively. This increase is rationalised using Frontier Orbital Theory. The absence of two of the four possible diastereoisomers from the aziridination of a racemic ester-substituted allylic alcohol with a racemic 3-acetoxyaminoquinazolinone was confirmed by independent synthesis of the absent diastereoisomers. Diastereoselectivity in this reaction is attributed to the effects of hydrogen bonding in the transition state between the -hydroxy in the alkene and the N-acetoxyamino group in the quinazolinone and this conclusion is supported by modelling studies. Aziridination of the analogous phenyl-substituted allylic alcohol with the same racemic 3-acetoxyaminoquinazolinone has also been investigated.