Modification of Amidic Resonance Through Heteroatom Substitution at Nitrogen: Anomeric Amides

Anomeric amides have two electronegative atoms, X and Y, on nitrogen. Their combined electron demand reduces amide resonance through introduction of 2s character into the nitrogen lone pair, resulting in a pyramidal conformation and longer N-C(O) bonds, for which there is structural, spectroscopic, and theoretical evidence. Resonance can be reduced to 50% that of typical values with strongly electronegative atoms. The compromised resonance renders such amides reactive at nitrogen at which both S _N 1 and S _N 2 processes occur. Both are driven by n _Y -σ* NX anomeric destabilization of N-X bonds. Despite weakened resonance, nucleophilic addition to the carbonyls is not observed. However, where X is a poor leaving group, anomeric destabilization leads to intramolecular rearrangements (HERON reactions) in which X migrates from nitrogen to the carbonyl, resulting in acyl substitution through cleavage of the amide bond and production of Y-stabilized nitrenes. Numerous examples of substitution reactions at nitrogen and HERON reactions are described.