Substituents on quinone methides strongly modulate formation and stability of their nucleophilic adducts

Emily Weinert, Ruggero Dondi, Stefano Colloredo-Melz, Kristen N. Frankenfield, Charles H. Mitchell, Mauro Freccero, Steven E. Rokita

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Abstract

Electronic perturbation of quinone methides (QM) greatly influences their stability and in turn alters the kinetics and product profile of QM reaction with deoxynucleosides. Consistent with the electron-deficient nature of this reactive intermediate, electron-donating substituents are stabilizing and electron-withdrawing substituents are destabilizing. For example, a dC N3-QM adduct is made stable over the course of observation (7 days) by the presence of an electron-withdrawing ester group that inhibits QM regeneration. Conversely, a related adduct with an electron-donating methyl group is very labile and regenerates its QM with a half-life of approximately 5 h. The generality of these effects is demonstrated with a series of alternative quinone methide precursors (QMP) containing a variety of substituents attached at different positions with respect to the exocyclic methylene. The rates of nucleophilic addition to substituted QMs measured by laser flash photolysis similarly span 5 orders of magnitude with electron-rich species reacting most slowly and electron-deficient species reacting most quickly. The reversibility of QM reaction can now be predictably adjusted for any desired application.

Original languageEnglish (US)
Pages (from-to)11940-11947
Number of pages8
JournalJournal of the American Chemical Society
Volume128
Issue number36
DOIs
StatePublished - Sep 13 2006

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All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Weinert, E., Dondi, R., Colloredo-Melz, S., Frankenfield, K. N., Mitchell, C. H., Freccero, M., & Rokita, S. E. (2006). Substituents on quinone methides strongly modulate formation and stability of their nucleophilic adducts. Journal of the American Chemical Society, 128(36), 11940-11947. https://doi.org/10.1021/ja062948k