Synthesis And Catalytic Performace On Asymmetric Darzens Reaction And Biginelli Reaction Of Novel Chiral Catalysts Derives From Quinine Alkaloids

The discovery and development of catalytic asymmetric reaction is one of themost important achievements of the chemical industry and the whole field of naturalsciences in20th century. So far, it is no doubt that it would be the best to using themost important enzyme in nature to complete the asymmetric synthesis reaction. It isa challenge for scientists to develop an effective chemical catalyst system likeenzymec, but what is worth noting is that in this process, some of the chiral organiccatalyst obtained a breakthrough in the development of the organic chemist in recentyears. The alkaloid derivatives like quinine is a small molecule catalytic system ofconcern in many small organic molecules chiral catalyst, As this alkaloid derivativesare provided with the multi-chiral centers, a rigid configuration, lipophilic andhydrophilic groups, the special electronic effects as well as the complexity of themolecular skeleton, they have large potential to be a good catalytic in the asymmetricsynthesis reaction and would injecte new vitality for industrial-scale catalyticasymmetric synthesis.In the field of catalytic asymmetric synthesis, building new effective ligand isthe core in the sustainable development of asymmetric catalysis research. We use theliterature data in hand to analyse the skeleton features of quinine derivatives as well asits catalytic application. This thesis mainly includes the following aspects:1.Using quinine alkali as the raw materials to synthetize11N-substitutedquaternary ammonium salt, the spatial steric effect and electronegativity factors in thestructure of catalyst as the starting point, to applied mainly to the asymmetricphase-transfer catalysis,2-chloroacetophenone and benzaldehyde’s Darzenscondensation reaction, examine its asymmetric catalytic performance, and to furtheranalyse the effect which the structure of the series of quaternary ammonium salts,different solvents, different alkali catalyst have aroused for the asymmetric induction.Under optimized conditions, the type of catalyst have moderate catalytic activity(chemical yield49%) and enantioselectivity (up to46%ee value) when Darzens occer.This set of experimental data provides a clear idea for our future design and synthesisof chiral phase transfer catalyst of this type.2. Transform the9-hydroxyl groups in the quinine alkaloid to the amino on thereaction after several steps, and on this basis, design and synthetizes amides and ureasalkali, all together10quinine derivative chiral catalyst of secondary amines, mainlyapply to the catalytic asymmetric Biginelli reaction. The experiments showed that inthe presence of the metal Lewis cocatalyst, chloride lanthanum, and in the optimumreaction conditions, raw material benzaldehyde, ethyl acetoacetate and urine (orthiourea) occured a chemical reaction, the Biginelli reaction, produced the R-configuration two hydrogen pyridine-2-ketone. In this process,the ligand9-aminoquinine catalytic showed the best catalytic performance, in which the chemical yieldup to80%and the optical yields up to76%ee.The research results showed that these two kinds of quinine alkaloidsderivatives chiral catalysts can not only catalyze asymmetric Darzens reaction andBiginelli reaction independently, but obtain a medium catalytic activity, whichvalidated the connection between the structure and activity of the chiral catalystpreliminarily.These two types of catalysts have easily-getting raw materials, simpleand convenient synthesis, low cost and low consumption, all these made the catalyticproduct of important practical value. This subject provived theoretical guidance forchiral quinine base derivative catalysts that catalyze asymmetric Darzens reaction and Biginelli reaction.