Application of a recyclable fluorous oxime in the convenient synthesis of 3-amino-1,2-benzisoxazoles and 4-amino-1H-2,3-benzoxazines

Abstract

A microwave-assisted, fluorous synthetic route to 3-amino-1,2-benzisoxazoles and 4-amino-1H-2,3-benzoxazines has been developed. The strategy comprises linking the respective 2-fluorobenzonitrile or 2-(bromomethyl)benzonitrile to a fluorous oxime tag to give an aryloxime intermediate which then undergoes cyclization with concomitant cleavage of the substrate-tag in acidic conditions to provide the desired product in good to moderate yields. In addition, the aryloxime intermediate could be subjected to further reactions to expand the compound library. The product could be easily separated using fluorous solid-phase extraction (F-SPE) and the fluorous ketone recovered could be converted back to the fluorous oxime and reused in the next run of the synthesis.