Synthesis of Isoxazole and 1,2,3-Triazole Isoindole Derivatives via Silver- and Copper-Catalyzed 1,3-Dipolar Cycloaddition Reactions.

The CuI- or Ag₂CO₃-catalyzed [3+2] cycloaddition of propargyl-substituted dihydroisoindolin- 1-one (3) with arylnitrile oxides 1a–d (Ar = Ph, p-MeC₆H₄, p-MeOC₆H₄, p-ClC₆H₄) produces in good yields novel 3,5-disubstituted isoxazoles 4 of the ethyl-2-benzyl-3-oxo-1-((3-arylisoxazol-5yl)methyl)- 2,3-dihydro-1H-isoindole-1-carboxylate type. With aryl azides 2a–d (Ar = Ph, p-MeC₆H₄, p-OMeC₆H₄, p-ClC₆H₄), a series of 1,4-disubstituted 1,2,3-triazoles 6 (ethyl-2-benzyl-3-oxo-1-((1-aryl-1H-1,2,3- triazol-4-yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylates) was obtained. The reactions proceed in a regioselective manner affording exclusively racemic adducts 4 and 6. Compared to the uncatalyzed cycloaddition, the yields are significantly improved in the presence of CuI as catalyst, without alteration of the selectivity. The regio- and stereochemistry of the cycloadducts has been corroborated by an X-ray diffraction study of 4a, and in the case of 6a by XH-correlation and HMBC spectra. [ABSTRACT FROM AUTHOR]