Diastereoselective aziridination of alkenes using 3-acetoxyamino-2-(1-hydroxyalkyl)quinazolin-4(3H )-ones in the presence of titanium(IV) tert-butoxide

Abstract

3-Amino-2-[(S )-1-hydroxy-2,2-dimethylpropyl]quinazolin-4(3H )-one 9 (Q²NH) was prepared in four steps from (S )-tert-leucine in 43% yield without the need for chromatography. The corresponding 3-acetoxyaminoquinazolinone 10 (Q²NHOAc), prepared in dichloromethane solution by reaction of 9 with lead tetraacetate, reacts with alkenes in the presence of titanium(IV) tert-butoxide to give the corresponding aziridines diastereoselectively. With styrene and butadiene the corresponding aziridines 12a (65%) and 15a (85%) are obtained completely diastereoselectively. Indene gave the expected endo-N-invertomer of aziridine 16a as the kinetically-formed product (86%) also completely diastereoselectively: equilibration to give a 8∶1 ratio of exo∶endoN-invertomers occurs above 0  °C. From an X-ray structure determination of aziridine 12a, the sense of diastereoselectivity in its formation is in agreement with the transition state model 14. Aziridinations of methyl acrylate and of tert-butyl acrylate give respectively 23a (65%) and 24a (53%), highly diastereoselectively (dr ⩾ 20:1) and with the same sense of diastereoselectivity as identified by an X-ray crystal structure determination on 24a and chemical correlation of esters 23a and 24a via the acid 25.

Aziridinations of α-methylstyrene and methyl methacrylate are less completely diastereoselective; isoprene reacts completely diastereoselectively at its unsubstituted double bond but with little diastereoselectivity at its methyl-substituted double bond and the regioselectivity of aziridination on the two double bonds is 1.4:1 respectively by comparison to 1∶4.7 in the absence of titanium(IV) tert-butoxide.

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