Acylation of amines with 3-[n-(2-acetoxypropanoyl)‎-nacyl] aminoquinazolin-4(3h)‎-ones: mechanism and origin of the enantioselection

Abstract EN

In the title compounds (DAQs), the N-N bond is a chiral axis.

When used in enantiopure form, these DAQs are highly enantioselective acylation agents for racemic amines (kinetic resolution).

X-Ray crystal structures on three sets of DAQs (eight in all) have previously confirmed the presence of the N-N chiral axis and have shown that in each case the conformation of the imide moiety is exo / endo.

The relative rates of reaction with amines of DAQs within each set have been correlated with their X-ray crystal structures with the following assumptions; (i) that attack on the exo-oriented imide carbonyl (exo ≡cis to the Q group) from the diastereoface cis to the Q-carbonyl is greatly preferred, (ii) that attack on this carbonyl group is irreversible and rate-determining and (iii) that the torsion angle f1 between the two C-O bonds O=C-C-OAc) in the exo-2-acetoxypropanoyl group is maintained in solution.