Ruthenium-Catalyzed Cycloaddition of 1-Haloalkynes with Nitrile Oxides and Organic Azides; Synthesis of 4-Halo Isoxazoles and 5-Halo Triazoles

摘要

(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 equiv 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 using palladium-catalyzed cross-coupling reactions as well as via manipulation of reactive amide groups. The lack of catalysis observed with Cp*RuCl(cod) is attributed to steric demands of the Cp* (η⁵-C5Me5) ligand in comparison to the parent Cp (η⁵-C5H5). This hypothesis is supported by the poor reactivity of (η⁵-C5Me4CF3)RuCl(cod), which serves as a an isosteric mimic of Cp* and as an isoelectronic analog of Cp.