Theoretical studies on the regioselectivity of iridium-catalyzed 1,3-dipolar azide-alkyne cycloaddition reactions

J Org Chem. 2014 Dec 19;79(24):11970-80. doi: 10.1021/jo5018348. Epub 2014 Sep 25.

Abstract

Iridium-catalyzed cycloaddition of thioalkynes and bromoalkynes with azides have been investigated with the aid of density functional theory (DFT) calculations at the M06 level of theory. Our investigation focused on the different regioselectivity observed for the reactions of the two classes of alkynes. The DFT results have shown that the mechanisms of cycloaddition reactions using thioalkynes and bromoalkynes as substrates are similar yet different. The reactions of thioalkynes occur via a metallabicyclic Ir-carbene intermediate formed through alkyne-azide oxidative coupling via attack of the azide terminal nitrogen toward the β alkyne carbon, whose carbene ligand is stabilized by an alkylthio/arylthio substituent. Reductive elimination from the intermediate leads to the formation of the experimentally observed 5-sulfenyltriazole. In the reactions of bromoalkynes RC≡CBr, the reaction mechanism involves the initial formation of a six-membered-ring metallacycle intermediate in the oxidative coupling step. The six-membered-ring intermediate then undergoes isomerization via migrating the terminal azide nitrogen from the β carbon to the α carbon to form a much less stable metallabicyclic Ir-carbene species from which reductive elimination gives 4-bromotriazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Azides / chemistry*
  • Catalysis
  • Cycloaddition Reaction
  • Iridium / chemistry*
  • Methane / analogs & derivatives
  • Methane / chemistry
  • Models, Molecular
  • Triazoles / chemistry

Substances

  • 4-bromotriazole
  • Alkynes
  • Azides
  • Triazoles
  • carbene
  • Iridium
  • Methane