Synthesis Of Chiral Bis-N-squaramidoacids And Thiazolidine Ligands And Their Applications In Catalytic Asymmetric Reductions

Asymmetric synthesis and catalysis is a hot field in morden organic chemistry. Exploration of high effective and enantioselective synthesis is a highlight in moden synthesis chemistry. In this paper, we designed two routes to synthesize a series of bis-squaramidoacid ligands bridged by 1,2-diphenylethylenediamine. Then we applied these chrial ligands to asymmetric borane reduction of w-bromoacetophenone and diketones. In the reduction of 1, 6-diphenyl-1, 6-hexanedione catalyzed by the bis-squaryl proline, good enantioselectivities were obtained, the ee values were up to 90%.We also studied the asymmetric borane reduction of prochiral ketone catalyzed by a series of thiazolidine ligands. In the reduction of w-bromoacetophenone, the thiazolidinecarboxylic acid and thiazolidine methanol ligand without substituent on C-2 position showed excellent enantioselectivities, the ee values were up to 99% and 94% respectively. The thiazolidine ligands with aromatic substituents on C-2 position provided relatively poor enantioselectivity. We also found that these two kinds of ligands afforded the alcohol product with opposite configuration, and the thiazolidine ligands with aromatic substituents on C-2 position showed opposite enantioselectivity related to CBS catalyst derived fromL-prolinols. We investigated the asymmetric reduction process and supposed a mechanism of the reaction.The C-2 substituted thiazolidinecarboxylic acids have two chiral centers, and the configuration on C-2 position may affect the enantioselectivity of the reduction. We synthesized (2S, 4R) and (2R, 4R)-2-phenyl-3- (tert-butoxycarbonyl) thiazolidine-4-carboxylic acids and their corresponding alcohol ligands. Crystal structure of (2R, 4R)-2 -phenyl- 3 - (tert-butoxycarbonyl) thiazolidine- 4 -carboxylic acid was confirmed by X-ray analysis.