Ruthenium-catalyzed cycloadditions of 1-haloalkynes with nitrile oxides and organic azides: synthesis of 4-haloisoxazoles and 5-halotriazoles

Chemistry. 2014 Aug 25;20(35):11101-10. doi: 10.1002/chem.201402559. Epub 2014 Jul 24.

Abstract

(Cyclopentadienyl)(cyclooctadiene) ruthenium(II) chloride [CpRuCl(cod)] catalyzes the reaction between nitrile oxides and electronically deficient 1-choro-, 1-bromo-, and 1-iodoalkynes leading to 4-haloisoxazoles. Organic azides are also suitable 1,3-dipoles, resulting in 5-halo-1,2,3-triazoles. These air-tolerant reactions can be performed at room temperature with 1.25 equivalents of the respective 1,3-dipole relative to the alkyne component. Reactive 1-haloalkynes include propiolic amides, esters, ketones, and phosphonates. Post-functionalization of the halogenated azole products can be accomplished by using palladium-catalyzed cross-coupling reactions and by manipulation of reactive amide groups. The lack of catalysis observed with [Cp*RuCl(cod)] (Cp* = pentamethylcyclopentadienyl) is attributed to steric demands of the Cp* (η(5)-C5Me5) ligand in comparison to the parent Cp (η(5)-C5H5). This hypothesis is supported by the poor reactivity of [(η(5)-C5Me4CF3)RuCl(cod)], which serves as a an isosteric mimic of Cp* and as an isoelectronic analogue of Cp.

Keywords: alkynes; cycloadditions; halides; regioselectivity; ruthenium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkynes / chemistry*
  • Azides / chemical synthesis
  • Azides / chemistry*
  • Catalysis
  • Cyclization
  • Cycloaddition Reaction
  • Molecular Structure
  • Nitriles / chemistry*
  • Oxides / chemistry*
  • Ruthenium / chemistry*
  • Triazoles / chemical synthesis*

Substances

  • Alkynes
  • Azides
  • Nitriles
  • Oxides
  • Triazoles
  • Ruthenium