Amine-promoted cyclocondensation of highly substituted aromatic nitrile oxides with diketones

Base-promoted cyclocondensation of hindered nitrile oxides and cyclic diketones affords highly functionalized, sterically-encumbered isoxazole products in good yield. The mild reaction conditions (NEt3, EtOH) are tolerant to a wide variety of functionality and permit the preparation of precursors to complex polycycles typically inaccessible via direct, intermolecular carbon-carbon bond forming reactions. The ability to effect the cyclocondensation reaction with a catalytic amount of amine points to the intermediacy of an ammonium enolate as a key reactive species. A convenient, single step preparation of crystalline, stable nitrile oxides from the corresponding oximes enhances the advantages of this methodology for the preparation of functionalized polycycles. (C) 2003 Elsevier Science Ltd. All rights reserved.