Palladium-catalyzed benzo[d]isoxazole synthesis by C-H activation/[4+1] annulation

We report a palladium-catalyzed intermolecular [4 + 1] annulation pathway for N-phenoxyacetamides with aldehydes to form 1,2-benzisoxazoles. By activating the C-H bonds ortho to phenol-derived O-N bonds, the method enables the simultaneous construction of C-C and CN bonds in 1,2-benzisoxazoles with the O-N bonds intact. The method has been successfully applied to the synthesis of active pharmaceutical intermediates, such as risperidone. © 2014 The Royal Society of Chemistry.