Metal-Free Synthesis of Benzisoxazolones Utilizing ortho-Ester and ortho-Cyano-Functionalized Diaryliodonium Salts...

Herein, we report the development of metal-free one/two-pot procedures for the synthesis of benzo[c]isoxazol-3(1H)-one (benzisoxazolone) heterocycles by designing diaryliodonium salts featuring ortho-ester or nitrile functional groups. These react smoothly with protected hydroxylamines under mild conditions to produce N-arylhydroxylamine intermediates, which readily cyclize to give benzisoxazolone derivatives under acidic conditions. This metal-free process maintains the weak N-O bond, tolerates a wide range of diaryliodonium salts and protected hydroxylamines with diverse functional/protecting groups, thereby overcoming the challenges associated with previous transformations. The protocol expands the reaction scope and broadens the chemical space of the fused isoxazolone backbones to include unprecedented five-membered heteroaryl-fused isoxazolones in high yields. This method is also applicable to gram-scale synthesis, and the resulting benzisoxazolones can be effectively derivatized at the N-position to afford valuable compounds.