Design And Synthesis Of Chiral Thiourea Organocatalysts And Research And Discussion Of Reactions

In recent years, more and more scholars come to study on asymmetric organic reaction catalyzed by small organic molecule catalysts containing thiourea group(s). Rely on the structures containing N-H groups is apt to form dual Intermolecular hydrogen bonds with multiple substrates to achieve good catalytic activity and control of chiral.studies on and applications of asymmetric organic reaction catalyzed by thiourea catalysts have been regarded as one of the most remarkable fields in catalytic asymmetric reactions .Since 1998 the Jacobsen research team's pioneering work, had many applies with the amino acid skeleton connected urea/thiourea chiral catalyst in many kinds of asymmetrical reaction and has realized the very good Stereoselectivity. With the development of small organic molecule catalysts, Chemists began to simulate the structure and characteristics of enzymes which have multi- activation center and these activation centers compose suitable spatial structure and urge catalytic reaction to become more efficient. Receives the enzyme the structure inspiration, in 2003, Takemoto research team's proposed for the first time the single molecular double activation concept, and designed and synthesized bifunctional thiourea-tertiary amine catalyst, introduced other activating group during introduction thiourea groups and introduction another activation in another end (chiral amine) to form double functionalization double activation catalyst, enhances reaction activity and stereo selective greatly. Hereafter a series of includes each kind of chiral skeleton's bifunctional thiourea catalyst to report one after another by each research team that and obtained the widespread application in a series of asymmetrical catalytic reaction.The paper divided into three parts, the paper first part summarized the research development which was asymmetrical catalyzes, particularly thiourea catalyst and bifunctional thiourea catalyst, in was asymmetrical catalyzes the research development. The second part is the catalyst design and the synthesis. Third part of catalytic reaction discussion use synthesis catalyst (Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅴ,Ⅵ) attempts some common substrates the asymmetrical Michael addition reaction.The paper first part summarized the research development of asymmetrical catalyzes. Include: study the importance of asymmetric synthesis,Asymmetric synthesis asymmetric catalysis is the ultimate goal,Separate Of Asymmetric catalysis and advantage of small organic molecules catalysis,Develop of asymmetric organic catalytic,the Mechanism of small Organic molecule catalytic,classification of Organic small molecule catalyst and typical catalyst small organic molecules,Typical small organic molecules catalyst a number of reactions. Second part was chiral thiourea organic small molecule catalyst research and application.Third, dual-function thiourea catalyst of organic catalytic asymmetric organic reactions is reviewed. Include: thiourea - tertiary type of organic bifunctional thiourea catalyst thiourea - Base Bifunctional Cinchona Thiourea-based organic catalyst, thiourea - primary amine bifunctional catalysts of the organic thiourea, thiourea - Chung bifunctional organic amine thiourea catalyst for disulfide of thiourea-based bifunctional thiourea organic catalyst, organic bifunctional thiourea catalyst for catalytic asymmetric Friedel-Crafts alkylation reaction of organic bifunctional thiourea catalyst for asymmetric Henry Reaction (Nitro aldol reaction), dual function of the organic thiourea other asymmetric catalytic reactionsThe second part is the catalyst design and the synthesis. The design synthesized L-(+)- tartaric acid which by the small advantage, easy to result in is a raw material, after the esterification, ring closing reaction , grignard reaction , Chloro-Substituted, azide substitution,reduction and so on 7 step reactions has obtained (Ⅰ,Ⅱ,Ⅲ) three new by TADDAMIN ((4S,5S) - 2,2- dimethyl–α,α,α',α'- four benzyl - 1,3- dioxolane - 4,5- dimethylamine) are skeleton's chiral primary amine - thiourea catalysts. Take ((4R,5S) - 5- (amidogen - diphenyl - methyl) - 2,2- dimethyl -α,α, - diphenyl - 1,3- dioxolane - 4- methyl alcohol) as skeleton's thiourea catalyst (Ⅳ). And take (R,R)-1,2- diaminocyclohexane (DACH) as Chiral skeleton one end bonding with the proline by amide linkage, other end forms the thiourea the catalyst (Ⅵ) .Simultaneously also synthesized one kind already the thiourea - tertiary amine catalyst which reported (Ⅴ).The third part of catalytic reaction discussion, has attempted them in the catalyzedβ-Nitrostyrene and diethyl malonate,β-Nitrostyrene and Ketone Michael addition reaction, Cinnamate and nitromethane Michael addition reaction, Chalcone and nitromethane Michael addition reaction, Chalcone and p-Methoxyaniline aza-Michael addition reaction. But the catalyst does not have catalytic effect through the catalyst structure's analysis, we speculated that catalysts has not catalytic effect possibly is because take TADDAMIN as skeleton's catalysts and the diaminocyclohexane (DACH) skeleton's catalysts, compares among the TADDAMIN skeleton chiral carbon and the amine group also some carbon atom, the cause chiral center and the primary amine group and the thiourea groups space length is too big, when activates the substrate the two lack some kind of synergism. Need to try a new reaction system. And studies the catalyst the structure, the solvent effect, the temperature, the catalyst amount used and the reaction substrate type to the stereoselective influence, selects the suitable catalyst and the optimized reaction condition.Catalyst (Ⅵ) catalyzes 4-Nnitrobenzaldhyde and acetone aldol reaction. CatalystⅥcatalyzed 4-Nnitrobenzaldhyde and acetone aldol reaction has the catalytic activity possibly is because the catalyst includes the proline groups and bases. Compare CatalystⅥcatalyzed 4-Nnitrobenzaldhyde and acetone aldol reaction with L-Proline catalyzes 4-Nnitrobenzaldhyde and acetone aldol reaction the merit is the catalystⅥSoluble relative L-Proline has the improvement, the shortcoming is yield only then 22%, but literature [15] report L-Proline (30 mol%) catalyzes yield reach 68%, but also needs to continue to choose the appropriate system.