Synthetic methodology for 3,4-disubstituted isoxazole derivatives from the reductive cleavages of 4,5-dihydro-7H-pyrano[3,4-c]isoxazoles 1 or 4H,6H-furo[3,4-C]isoxazoles 5 is described. Pyrano[3,4-c]isoxazole 1, upon treatment with TMSCL/NaI in acetonitrile, undergoes selective C-O bond cleavage to furnish a 3,4-disubstituted isoxazole (2, 3, 4) in high yield without damaging the isoxazole ring. Likewise, the treatment of furo[3,4-c]isoxazoles 5 with TMSCl/Nal in acetonitrile results in the formation of a reduced iodide 7 and a hydroxy iodide 8.