| In recent years, organocatalysis has attracted the attention of chemists, in which metal-free small organic molecules is used as catalyst. It has became the research focus and successfully applied to many catalytic asymmetric reactions. Among them,the Br?nsted acid catalyst, especially the chiral phosphoric acid was the most intensively investigated one. Currently, studies were focused on chiral BINOL-phosphoric acid, in which the chemical modification of BINOL skeleton was complex and expensive, so the design and synthesis of novel chiral phosphoric acids was continued to be concerned by organic chemists. In this thesis, chiral1,1,4,4-tetrasubstituted butanetetraols were prepared via a “one-pot rection” of L-tartrate ester with Grignard reagents. Chiral phosphoric acids with TADDOL analogue skeleton were designed and synthesized based on highly region-selective derivatization. And the synthesized chiral phosphoric acids were applied to catalyze asymmetric Biginelli reaction.The thesis is devided into 3 chapters.In chapter 1, recent application of chiral phosphoric acid in asymmetric synthesis is reviewed, and overall research plan of the thesis is outlined.In chapter 2, three kinds of(2R,3R)-1,1,4,4-tetrasubstituted butanetetraols were prepared via “one-pot reaction” of Grignard reagent with L-tartrate ester, and two kinds of butanetetraols were synthesized for the first time. Based on highly region-seselective 2,3-cyclosulfitation reaction of(2R,3R)-1,1,4,4-tetraphenylbutanetetraol with thionyl chloride,4,5-bis-(diphenylhydroxymethyl)-1,3,2-dioxathiolane 2-oxide was synthesized, which was then reacted with PCl3 and sequently underwent oxidation with I2 and hydrolysis with alkaline liquid to affored seven-membered cyclic chiral phosphoric acid CPA1.4,5-bis-(diphenylchloromethyl)-1,3,2-dioxathiolane 2-oxide was obtained from the reaction of(2R,3R)-1,1,4,4-tetraphenylbutanetetraol with excess SOCl2, and methoxyl groups were introduced into the molecule via its reaction with methanol.(2R,3R)-1,4-dimethoxy-1,1,4,4-tetraphenyl-2,3-butanediol was synthesized after hydrolysis with alkaline liquid, then it was reacted with phosphorus trichloride and underwent oxidation with I2 to afford five-membered cyclic chiral phosphoric acid CPA2.In chapter 3, asymmetric Biginelli reaction catalyzed by(2R,3R)-1,1,4,4-tetrasubstituted butanetetraols,(2R,3R)-1,4-dimethoxy-1,1,4,4-tetraphenyl-2,3-butane-diol and the synthsized chiralphosphoric acids was examined. It was found that chiral all the synthesized tetraols and diol could promote the asymmetric Biginelli reaction via intermolecular hydrogen bonding interaction, but they showed very low catalytic activity to Biginelli reaction.While the designed and synthesized chiral phosphoric acids with TADDOL analogous skeleton showed excellent enantioselectivities of up to 99% ee. |
