Design And Synthesis Of Chiral Carbohydrate-derived Prolinamides And Their Application In Asymmetric Aldol Reaction

Organocatalyst, as characterized by its environmental benignity, cheapness, easy availability, efficiency and low toxicity, has becoming the third kind of important catalyst besides of metal catalyst and enzyme catalyst. To develop efficient organocatalyst and apply them in asymmetric synthesis has grown into a hot researchD-glucose, as the object of the study, is modified and protected to fuse the proline field.moiety to the glucose scaffold in order to synthesize the novel sugar-based prolinamide. The effect of spatial configuration is afforded by the sugar-ring structure. The latter as well linked different groups, so that it adjusts the solubility and steric bulk of the catalyst to control its catalytic property. The main content of the paper is divided into the following two chapters.1. Starting with D-glucose, pivaloyl protection, azido substitution and catalytic hydrogenation was used to synthesize the2,3,4,6-tetrapivaloyl glucosamine, which condensated with carbobenzoxyl protected L-proline, deprotected of carbobenzoxyl, hydrolyzed to remove the protecting pivaloyl to afford two difunctional prolinamide organocatalysts. We applied the catalysts to the asymmetric aldol reaction of cyclic ketones and substituted benzaldehydes, and suggested probable catalytic mechanism. The catalytic reaction showed excellent catalytic activity of the catalysts, with the yield up to99%, enantiomeric excess up to97%, diastereomeric ratio up to97:3.2.N-acetyl-D-Glucosamine, as raw material, was protected of its1-and4,6-hydroxyl in order to give the precursor4,6-O-benzylidene-methyl/benzyl-N-glucosamine. With that in hand, in one side, it was fused by condensation with carbobenzoxyl protected proline, thus afforded the organocatalyst prolineglycosyl ester after the deprotection of N-acetyl of the glucosamine. In another side, further hydrolysis of the precursor generated4,6-O-benzylidene-methyl/benzyl-glucosamine, which condensated with fluorenyl methoxy carbonyl(fmoc) protected L-proline, removed the Fmoc protecting group to produce the other organocatalyst. The mentioned three organocatalysts were applied to catalyze the asymmetric aldol reaction of acetone and substituted benzaldehydes, and demonstrated good activity with the yield up to88%, enantiomeric excess up to83%. Also, the probable catalytic reaction mechanism was proposed.As stated above, two series of carbohydrate derived multifunctional organocatalyst were designed, synthesized and applied in catalytic reactions. All the catalysts showed good catalytic activity. The work provided practical basis to research in future of saccharide organocatalysts.