Novel bisisoquinolines : synthesis, resolution and application in asymmetric Henry reaction
Yao, Qiong Ji
Date of Issue2012
School of Chemical and Biomedical Engineering
This research project presented in this thesis focuses on the synthesis of enantiopure novel 1,3-diposed and classical 1,2-diposed bisisoquinolines, and application of those bisisoquinolines as ligands for one powerful C-C bond formation reaction―Henry reaction. Condition for synthesis of the anticipated 1,3-disposed bisisoquinolines and its derivatives have been established. Racemic symmetric 1,3-disposed bisisoquinolines was prepared through classical double Bischler-Napieralski reaction followed by reduction with Sodium cyanoborohydride. Resolution of the racemic symmetric 1,3-disposed bisisoquinolines to afford individual enantiomers was solved via diastereomeric salt formation with (L)-(+)-citramalic acid. The absolute configuration of this novel 1,3-diamine 1,1’-methylene-bis(1,1’,2,2’,3,3’,4,4’-octahydroisoquinoline) was established by X-Ray crystallography. Mono-, di- and bridged N-alkyl derivatives based on racemic, (R,R)-parent compound were synthesized to explore this 1,3-diposed bisisoquinolines’ chemistry. Application of the enantiopure 1,3- and 1,2-diposed bisisoquinolines in catalysis of asymmetric henry reaction was examined, C1-1’,2’,3’,4’-terahydro-1,1’-bisisoquinoline’s copper(I) complex proved to be the most efficient catalyst for the enantioselective Henry reaction between aldehydes and nitromethane. β-nitroalcohol adducts were obtained in high yields and enatioselectivities. This catalyst system was simple in operation since no special precautions were taken to exclude moisture or air from the reaction flask. (R)-N-alkyl-C1-1’,2’,3’,4’-terahydro-1,1’-bisisoquinoline differing in the steric bulkiness were successfully afforded to be examined in the asymmetric Henry reaction. The ligand bearing the smallest substituent was proved to be the most effective one in the CuI-catalyzed addition of nitromethane, nitroethane and nitropropane to aldehydes. Excellent catalytic results were achieved in this thesis, represented a major contribution to the application of bisisoquinolines as ligands in asymmetric catalysis of Henry reaction.