Molecular orbital studies of novel N to C migrations in N,N-bisheteroatom-substituted amides—HERON rearrangements

Abstract

Bisheteroatom-substituted amides (R–CO–NXY) can undergo a novel rearrangement of the more electronegative atom from nitrogen to the carbonyl carbon producing acyl derivatives (R–CO–X) and substituted nitrenes (N–Y). Such reactions have been observed chemically. AM1 molecular orbital calculations on N-substituted acetamides support the concerted nature of this process and predict that amino substituents (Y = NR₂) promote the rearrangement of similarly or more electronegative nitrogen substituents (X = NR₂, Cl, OR). Migration appears to be driven by an anomeric effect involving interaction between the lone pair on Y and the X–N σ* orbital. Favourable transiton states display a significant increase in N–Y double bond character, negative charge on the migrating substituent and little RCO–N heterolysis. 6–31G*ab initio calculations on migration of the hydroxy group in N-amino-N-hydroxyformamide largely accord with the AM1 findings for this model compound.