Synthesis Of Novel Chiral1,2,3-triazoies And Their Application In Catalytic Asymmetric Reactions

Due to the wide use of chiral compounds in the field of pharmaceutical andfunctional materials, synthesis of chiral small organic molecules has draw more andmore attention. Among these small organic molecules catalysts, N-O ligands havebeen widely used in asymmetric synthesis, which became a research focus in manydomestic and foreign chemical workers.1,2,3-triazole compounds are highly stablefive-membered aromatic heterocycles, and there are three nitrogen atoms which arelinked together, they are rich of coordination sites which provide these compoundsstrong coordinate ability. Such compounds are widely used in the fields of chemistry,materials and drugs, which has became a hot topic in recent years. The nitrogen oftriazole ring could coordinate a variety of transition metal to catalyze many reactions.Obviously,1,2,3-triazole compounds have the potential to become chiral a ligand,but unfortunately, reports of1,2,3-triazole chiral compounds are rare. In this thesiswe used commercially and available nitro-olefin to obtain C-chiral1,2,3-triazoleligands containing hydroxyl group. After the separation of these ligands, asymmetricreduction of prochiral ketones, successfully modification and transformation ofoptically pure ligands and applying in asymmetric reactions, we expanded theresearch scope of1,2,3-triazole compounds. And we obtained the followingInnovative results:(1) First, we designed two and β-hydroxy-1,2,3-triazole chiral ligands6a and8. After several steps reaction we synthesized nitroolefin compounds3a,3b.3a By1,3-dipolar cycloaddition reaction we synthesized1,2,3-triazole compound4a; then weoxidized olefine to ketone; finally, it was reduced to hydroxy-1,2,3-triazole chiralligands6a. Additionally, we synthesized1,2,3-triazole compound4b, via1,3-dipolar cycloaddition reaction epoxidized4b to6b, rearranged6b to7b, finally, reduced itto β-hydroxy-1,2,3-triazole chiral ligands8. The successful synthesis of chiralligands6a and8, to provide a chiral skeleton for further study.(2) Ligand6a was chemically resolved by (-)-quinine and we obtained99%eeafter twice recrystallization. We resolved ligand8a,8b by Enzyme kinetic resolutionwith lipase Novozym435. After discussing the effects of temperature, solvent,reaction time and substrate concentration, we got the optimal catalytic reactionconditions. And99%ee value of alcohol and99%ee value of ester were alsoobtained.(3) As a result of transformation and modification of chiral ligands (-)-8a,(+)-8b and the corresponding ethyl ester which obtained by enzymatic resolution, wegot eight kinds of new ligands. All of the ligands were applied to catalyzeddiethylzinc with various aromatic aldehydes asymmetric addition reactions. TheOptimal reaction conditions were obtained through the study of the kind of solventsand the dosage of catalyst. These ligands were shown a certain catalytic properties,wherein the ligand (-)-8a best. With20mol%of ligand (-)-8a, hexane and toluene1:1(V: V) as the mixed solvent, the reaction at room temperature for48h to give aproduct having the S configuration. The resulting catalytic products ee values underthe condition of up to99%.(4) Using Oxazaborolidine to reduce prochiral ketone7b. Under the conditionsof45℃, anhydrous tetrahydrofuran as solvent,10%of the amount of catalystcatalyzed reduction of prochiral ketones to give the cis-configuration of the product.It reached stereoselectity up to58%ee and55%yield. Under identical conditions wereduced prochiral ketones to give the trans-configuration of the optical purity of theproduct was72%ee,45%yield. At the same time we applied Noyori reductionmethod on prochiral ketones, with a ruthenium catalyst. In this study of rutheniumcatalyst prochiral ketone7b in asymmetric catalytic hydrogenation, we found thebest result of the reaction: at room temperature, ethyl acetate as solvent, the productwas obtained with trans configuration, and stereoselectity up to99%ee,17%yield.