Isomerisation of (E)-O-acyl isoamides to N-acyl amides. Mechanism of an intramolecular [1,3] acyl group migration via a four-membered transition state

Abstract

The (Z)-O-acyl isoamides (7)(which do not themselves thermally rearrange) may be photoisomerised to the (E)isomers (8) which undergo a ready thermal rearrangement to the more stable N-acyl isomers (9). The mechanism of this rearrangement was investigated using solvent effects (a linear free energy correlation with dielectric constant was observed but with an overall low sensitivity to solvent) and substituent effects in the migrating aroyl group (8; R2= Ar)(ρ+ 0.65) and the aryl group attached to carbon (ρ–0.49) and to nitrogen (ρ–0.91). The mechanisms discussed include a sigmatropic π2s+σ2a pathway, but that favoured is rate-determining nucleophilic attack by the nitrogen lone pair on the carbonyl carbon with an early transition state. Intermolecular acylation of water by (7) and (8)(which is acid and base catalysed) and of piperidine were examined as analogues of the intramolecular process. In general, the rates of intermolecular reactions of the (Z)-and (E)-O-acyl isoamide isomers (7) and (8) are similar to one another and show the same sensitivity to substituent effects.