The Synthesis Of Cinchonine Quaternary Ammonium Salts And The Catalysis Of Asymmetric Alkylation

The Asymmetric alkylation catalyzed by phase-transfer catalysts is one of the most important methods for establishing a C-C bond. This dissertation mainly focuses on the synthesis of cinchonine derivatived quaternary ammonium salts and the phase-transfer catalysis of the glycine imine ester asymmetric benzylation reaction.14 Substituted benzylbromides were synthesized by 4 different methods:benzaldehyde reduction-bromination, benzyl chloride halogen metathesis, benzylamine hydrolyzation-bromination, NBS bromination, yields 38%～97%. The benzaldehyde reduction-bromination was the best method for achieving substituted benzylbromide.We optimized the synthetic condition of cinchonine derivatived quaternary ammonium salts.11 catalysts bearing a free hydroxyl group and 5 catalysts with the chiral secondary alcohol protected were prepared by direct N-alkylation with corresponding substituted benzyl bromides under a reflux condition in 57%～88%yields. These quaternary ammonium salts identified by 1H-NMR,13C-NMR, HRMS, specific rotation and melting point.6 of them were novel compounds.16 catalysts were screened for alkylation of glycine imine ester using benzyl bromide. We found that the catalyst bearing an 4-Br benzyl group or the hydroxyl group protected by ether moiety could increase both the yield and e.e.. Cinchonine derived catalyst Cn-15 proved to be highly reactivity and selectivity, and up to 95%yield with 96%e. e..