Discovery and Evolution of Base-Free Neutral Phase-Transfer Reaction System

Although quaternary onium salts-catalyzed phase-transfer reactions are generally believed to require base additives, we discovered even without any base additives conjugate additions of 3-substituted oxindoles to nitroolefins proceeded smoothly in the presence of lipophilic quaternary ammonium bromide under water-organic biphasic conditions. The mechanism of this novel base-free neutral phase-transfer reaction system was investigated, and the assumed catalytic cycle was presented together with interesting effects of water and lipophilicity of the phase-transfer catalyst. The base-free neutral phase-transfer reaction system could be applied to highly enantioselective conjugate addition and aldol reactions under the influence of chiral bifunctional ammonium bromides as key catalysts. The efficient approach for the design of chiral quaternary phosphonium bromides as chiral phase-transfer catalysts was also introduced. A catalyst library with various structures has readily been constructed by the use of commercially available chiral phosphines as catalyst precursors. The optimized catalyst has successfully been applied to highly enantioselective conjugate additions and sulfenylation under base-free neutral phase-transfer conditions with low catalyst loading.