Access to a Wide Range of Sultams by Cyclodialkylation of alpha-Substituted Methanesulfonanilides

Abstract

A wide range of five- and six-membered sultams bearing an a-ethoxycarbonyl-a-methyl substituent or an a-aryl group (17 examples) were synthesized by the cyclodialkylation of a-substituted methanesulfonanilides with a,?-dihaloalkanes in the presence of K2CO3 or under phase-transfer catalysis (PTC) conditions. Upon treatment with K2CO3 in N,N-dimethylformamide (DMF) or NaH in dimethyl sulfoxide (DMSO), N-(2,3-dibromopropyl)-a-toluenesulfonanilides furnished different 1,3-diaryl-2-thia-3-azabicyclo[3.1.0]hexane 2,2-dioxides in good to excellent yields (5188?%, 16 examples). The 4-methoxyphenyl (PMP) group was easily removed from the sultam nitrogen atom by treatment of the corresponding bicyclic sultams with cerium(IV) ammonium nitrate in acetonitrile (7184?% yield, 6 examples).