Solid-Phase Synthesis of Isoxazoles Using Vinyl Ethers as Chameleon Catches

Regioselective 1,3-dipolar cycloadditions of supported vinyl ethers R1C(CH2)O-CH2-polymer, prepared by the Tebbe olefination of R1CO2-CH2-polymer, with ethyl cyanoformate N-oxide gave supported isoxazoline derivatives. Release from the support under mild acidic conditions gave the isoxazoles ethyl 5-R1-isoxazole-3-carboxylates. Alternatively, further on-resin functionalization of the R1 substituent using Suzuki coupling reactions and release from the support under acidic conditions gave more structurally diverse isoxazoles.