Glover, S.A.; Rosser, A.A. Heteroatom Substitution at Amide Nitrogen—Resonance Reduction and HERON Reactions of Anomeric Amides. Molecules2018, 23, 2834.
Glover, S.A.; Rosser, A.A. Heteroatom Substitution at Amide Nitrogen—Resonance Reduction and HERON Reactions of Anomeric Amides. Molecules 2018, 23, 2834.
This review describes how resonance in amides is greatly affected upon substitution at nitrogen by two electronegative atoms. Nitrogen becomes strongly pyramidal and resonance stabilisation, evaluated computationally, can be reduced to as little as 50% that of N,N-dimethylacetamide. However, this occurs without significant twisting about the amide bond, which is borne out both experimentally and theoretically. In certain configurations, reduced resonance and pronounced anomeric effects between heteroatom substituents are instrumental in driving the HERON (Heteroatom Rearrangement On Nitrogen)† reaction, in which the more electronegative atom migrates from nitrogen to the carbonyl carbon in concert with heterolysis of the amide bond, to generate acyl derivatives and heteroatom-substituted nitrenes. In other cases the anomeric effect facilitates SN1 and SN2 reactivity at the amide nitrogen.
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.