Synthesis of 3-Fluoro 3-Substituted 2-Oxindoles by Deacylative Alkylation

Abstract

The fluorination of 3-acetyl-2-oxindole with N-fluorobenzenesulfonimide under Lewis acid catalysis using Mg(ClO4)2 (30 mol%) in EtOAc at r.t. giving the starting compound 3-acetyl-3-fluoro-2-oxindole in 89% yield. This compound is submitted to base-promoted deacylative alkylation (DaA) for the in situ generation of 3-fluoro-2-oxindole enolate under very mild reaction conditions using Triton B (1 equiv.) as base in THF at r.t. and alkyl halides and Michael acceptors as electrophilic reagents. The corresponding 3-alkylated 3-fluoro-2-oxindoles are obtained in good to very high yields. In addition, the palladium-catalyzed deacylative allylation is carried out with allylic alcohols using LiOtBu as base and 6 mol% of Pd(OAc)2 and dppp at r.t. in toluene, giving the resulting 3-allylated 3-fluoro-2-oxindoles in good yields.