Aziridines : stereocontrol of ring-making and ring-breaking

(S)-3-Amino-2-(1-hydroxy-2,2-dimethylprop-1-yl)-quinazolin-4(3H)-one (Q*NH2) was prepared from (L)-tert-leucine and its 3-acetoxyamino derivative (Q*NHOAc) used to aziridinate a range of alkenes. In the presence of titanium (IV) tert-butoxide, Q*NHOAc was found to convert styrene, indene, butadiene and tert-butyl acrylate with complete diastereoselectivity into the corresponding N-Q* substituted aziridines in good yield; aziridination of methyl acrylate and -methylstyrene was also highly diastereoselective. In the absence of titanium (IV) tert-butoxide, aziridination proceeded with poor diastereoselectivity in every case.;The quinazolinone (Q*) ring has proved to be invaluable in directing or assisting the course of ring-opening of the N-(Q*) aziridines produced above. Thus Q* as a substituent on nitrogen was found to be sufficiently electron-withdrawing to activate the aziridine ring towards attack by nucleophiles in the absence of acid. The C-4 carbonyl oxygen of the quinazolinone (Q*) was found to participate in the aziridine ring-opening under some conditions with the result that retention of configuration was found in the alcohol product; evidence for this participation was obtained by exchange of the Q* carbonyl for a thione when the ring-opening was carried out in the presence of hydrogen sulphide. The two N-invertomers of the indene-derived aziridine were separately ring-opened by hydrogen chloride with very different stereochemistry, mediated by the Q* group. Finally, the sense of regioselectivity in the ring-opening of the methyl acrylate-derived aziridine can be changed by forming a lactone tether between the aziridine and Q* rings before ring-opening.