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

Abstract

Base-promoted cyclocondensation of hindered nitrile oxides and cyclic diketones affords highly functionalized, sterically-encumbered isoxazole products in good yield. The mild reaction conditions (NEt 3, 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.