Reaction of 3-(acetoxyamino)quinazolin-4(3H)-ones with enolic β-diketones: the N–N bond as a chiral axis in N-(3,4-dihydro-4-oxoquinazolin-3-yl)-N-acyl-α-aminoketones; reductive and base-catalysed cleavage of the N–N bond in N-acetyl-N-(3,4-dihydro-4-oxoquinazolin-3-yl)-α-amino acid esters
Following the method of Foucaud and coworkers, reaction of pentane-2,4-dione with 3-(acetoxyamino)quinazolin-4-one 8 gave the keto amide 9(15%). 3-Methylpentane-2,4-dione reacts with compound 8 to give a relatively stable enol 11(66%) which can be isolated in a crystalline form. Rotation around the N–N bonds in both compounds 9 and 11 is believed to be slow on the real time-scale and hence the N–N bonds can be considered as a chiral axes. As a result, protonation of the enol double bond in compound 11 and the creation of an additional chiral centre, gives rise to the separable keto amides 14 and 15; this protonation can be accomplished completely diastereoselectively. Lead tetraacetate acetoxylation of compound 11 to give compound 19 is also completely diastereoselective. Brief heating of the enol effects the elimination of the quinazolinone and the formation of the N-acetylimine 16via an 8-membered transition state. Base-catalysed elimination of the quinazolinone ring from compound 22 is surprisingly easy: reductive cleavage of this N–N bond in compound 22 is facile by comparison with the 3-(alkylamino)quinazolin-4-ones.