Predicting Regioselectivity in Nucleophilic Aromatic Substitution
2012 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 77, no 7, 3262-3269 p.Article in journal (Refereed) Published
We have investigated practical and computationally efficient methods for the quantitative prediction of regioisomer distribution in kinetically controlled nucleophilic aromatic substitution reactions. One of the methods is based on calculating the relative stabilities of the isomeric sigma-complex intermediates using DFT. We show that predictions from this method can be used quantitatively both for anionic nucleophiles with F- as leaving group, as well as for neutral nucleophiles with HF as leaving group. The sigma-complex approach failed when the leaving group was Cl/HCl or Br/HBr, both for anionic and neutral nucleophiles, because of difficulties in finding relevant sigma-complex structures. An approach where we assumed a concerted substitution step and used such transition state structures gave quantitatively useful results. Our results are consistent with other theoretical works, where a stable sigma-complex has been identified in some cases, whereas others have been indicated to proceed via a concerted substitution step.
Place, publisher, year, edition, pages
2012. Vol. 77, no 7, 3262-3269 p.
IdentifiersURN: urn:nbn:se:kth:diva-93912DOI: 10.1021/jo202569nISI: 000302388000023ScopusID: 2-s2.0-84859611539OAI: oai:DiVA.org:kth-93912DiVA: diva2:525140
QC 201205072012-05-072012-05-032012-05-07Bibliographically approved