Synthesis Of Novel Chiral Squaramides And Correlative Ligands And Their Applications In Catalytic Asymmetric Reactions

Asymmetric synthesis and catalysis is a hot field in mordern organic chemistry. In this paper, we synthesized a number of new bifunctional N-squaryl aminoalcohol ligands, mono- and bis- squaramidoacids. The asymmetric reduction of prochiral ketones catalyzed by these ligands were deeply studied, many good to excellent results were obtained. We also studied the asymmetric reduction catalyzed by 2-substituted thiazolidine carboxyl acid and asymmetric aldol reaction catalyzed by N-tosyl amino acids .Using natural ephedrine and L-proline as chiral sources, we first synthesized series of squaramidoalcohol ligands with alkoxy, amino and sulfur groups on C-3 position, respectively. Many novel mono- and bis- squaramidoacids with alkoxy, amino and sulfur groups on C-3 position of squaric cycle were also synthesized firstly. After optimizing the reaction conditions, these ligands were prepared conveniently with high yields. Crystal structures of three squaramidoalcohols and one squaramidoacid were confirmed by X-ray analysis.In the reduction of prochiral ketones catalyzed by N-squaryI prolinol, excellent enantioselectivities were obtained, the ee values were up to 99%. 3-mercapto-4-[(2'S)-2'-(diphenylhydroxy-methyl)pyrrolidino]-3-cyclobutene-1, 2-dione was used for asymmetric reduction of many aromatic ketones, the ee values were also good to excellent for most ketones, which indicated thatthis kind of ligands could be applied to many different substrates and to be catalysts with high efficiency and selectivity. For squaramidoacids, their enantioselectivities were much higher than relative A'-tosyl amino acids. In the case of asymmetric reduction of co-bromoacetophenone catalyzed by N-squaric proline, up to 96% ee was obtained. The bisquaramidoacids also showed good enantioselectivities in the reduction of diketones and up to 90% ee were obtained. We supposed the mechanism of these kinds of reactions, the hetero atoms on C-3 position might act as Lewis base in the asymmetric process.We also studies the asymmetric reduction of prochiral ketone catalyzed by several 2-subsitituted 4-thiazolidinecarboxylic acids. The ligands with aromatic substituents on C-2 position showed opposite enantioselectivity related to CBS catalyst derived from L-prolinols, this result was different from with literature. We supposed the transition state model to rationalise the asymmetric process.The asymmetric aldol reaction catalyzed A^-tosyl amino acids were studied, which indicated that tosyl D-phenylglycine was a good lignad for this kind of reaction. The ees were up to 81.7%. We proposed a transition state to explain the enantioselectivity. We also synthesized a new kind of N-losy\ pyrrolidine-amine, which may be good catalysts in the asymmetric C-C bond forming reactions.