Metal-Mediated Entry to Functionalized 3-Substituted 3-Hydroxyindolin-2-ones via Regiocontrolled Carbonylallylation, Bromoallylation, 1,3-Butadien-2-ylation, Propargylation, or Allenylation Reactions of Isatins in Aqueous Media

Reactions of 2,3-indolinediones (isatins) with stabilized organometallic reagents were investigated in aqueous media. Isatins and a variety of stabilized organic halides undergo coupling under Barbier-type conditions in the presence of different metals (indium, tin, zinc) and additives (ammonium chloride, hydrobromic acid, bismuth(III) chloride, hafnium(IV) chloride). The regiochemistry of the processes (carbonylallylation, bromoallylation, 1,3-butadien-2-ylation, propargylation, or allenylation reactions) were generally excellent. On this basis, simple and fast protocols for the synthesis of the potentially bioactive 3-substituted 3-hydroxyoxindole moiety were developed.