Substituent-dependent negative hyperconjugation in 2-aryl-1,3-N,N-heterocycles. Fine-tuned anomeric effect?

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The epimerization reactions of conformationally inflexible 2-aryl-1,3-N,N-heterocycles were used as model systems to study the role of the nitrogen lone pair-C2 associated antibonding orbital hyperconjugative interactions in the experimentally observed substituent-dependent generalized anomeric effect. The measured reaction free enthalpies were found to correlate well with the sum of the hyperconjugative stabilization energies of all the vicinal donor - acceptor orbital overlaps around C2, obtained from ab initio NBO analysis, and both quantities correlated linearly with the Hammett-Brown substituent constant. The individual stereoelectronic interactions (nN-σ*C2-N, nN-σ*C2-Ar, nN-σ*C2-H) were also observed to exhibit a substituent dependence, despite their distance from the 2-aryl substituent and their nonperiplanar arrangement. The higher the electron-withdrawing effect of the 2-aryl substituent, the larger was the stabilization for nN-σ*C2-Ar, while the overlaps nN-σ*C2-N and nN-σ*C2-H changed in the opposite sense. The different polarization of the acceptor σ* orbitals, caused by the 2-aryl substituent, accounted for the observed propagation of the substituent effect. These results promote a detailed explanation of the useful tautomeric behavior of the 2-aryl-1,3-X,N-heterocycles, and reveal the nature of the connection between the anomeric effect and the Hammett-type linear free energy relationship.

Original languageEnglish
Pages (from-to)5705-5712
Number of pages8
JournalJournal of Organic Chemistry
Issue number14
Publication statusPublished - Jul 11 2003


ASJC Scopus subject areas

  • Organic Chemistry

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