3-Acetoxyaminoquinazolinones (QNHOAc) as aziridinating agents: ring-opening of N-(Q)-substituted aziridines

3-Acetoxyaminoquinazolin-4-(3H)-ones (QNHOAc) are nitrogen analogues of peroxy-acetic acid and are efficient aziridinating agents for a range of alkenes from silyl ketene acetals to α,β-unsaturated esters. The presence of a chiral substituent in the 2-position of the quinazolinone allows complete (reagent-controlled) diastereoselective aziridination of prochiral alkenes. Greatly improved yields of aziridines from otherwise less reactive alkenes are obtained by reaction with QNHOAc in the presence of trifluoroacetic acid and this additive also greatly increases the diastereoselectivity in aziridination of some α,β-unsaturated esters. The corresponding nitrenes (QN), formally derived from QNHOAc by removal of the elements of acetic acid, are also aziridinating agents for alkenes with a reactivity similar to, but identifiably different from that of QNHOAc. The availability of enantiopure Q-substituted aziridines has led to an examination of their ring-opening reactions with particular emphasis on the use of the Q group to control the regio- or stereo-chemistry of the latter. Electrophilic ring-opening with inversion or with predominant retention of configuration has been demonstrated. Nucleophilic ring-opening of these aziridines is successful, e.g. with cuprates. Reductive cleavage of the Q group in the ring-opened products using samarium diiodide proceeds in excellent yield to allow retrieval of chirons containing only the chiral centres created in the diastereoselective aziridination: the recovered 3-H- quinazolinones (QH) can be reconverted back to 3-aminoquinazolinones (QNH2) from which the QNHOAc are prepared in good yield, in situ, by acetoxylation using lead tetra-acetate. The Q group has also been used to direct the regioselectivity of ring-opening.