title: Ruthenium-catalyzed cycloadditions of 1-haloalkynes with nitrile oxides and organic azides: synthesis of 4-haloisoxazoles and 5-halotriazoles.
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.
authors: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-7562.
authors: James S
authors: JS
authors: Oakdale
authors: Rakesh K
authors: RK
authors: Sit
authors: Valery V
authors: VV
authors: Fokin
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D061565:Cycloaddition Reaction; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D014230:Triazoles / Q000138:chemical synthesis*
chemical_list: D000480:Alkynes; D001386:Azides; D009570:Nitriles; D010087:Oxides; D014230:Triazoles; D012428:Ruthenium
keywords: alkynes; cycloadditions; halides; regioselectivity; ruthenium