Preparation Of Responsive Supported L-proline Catalyst For Asymmetric Aldol Reaction In Water

Asymmetric aldol reaction,one of the most efficient methods for the formation of carbon-carbon bonds,has been found widespreadly applications in recent years.L-proline chiral organocatalysts are widely used to catalysis asymmetric aldol reaction because of many advantages,such as simple structure,low cost and much more sources,etc.However,there are many problems during actual operation,such as the excessive dosage of catalysts,the use of organic solvents,and the difficult recovery and reuse of catalysts.Since the immobilization of L-proline could simplify the separation of the products and pacilitate catalyst recovery and reuse,the immobilization of L-proline and their applications in asymmetric reaction are caused high concern.The carriers include ionic liquids,organic polymers and inorganic nanoparticles.These carriers not only make it possible to catalyze asymmetric reaction in pure water,can also recycle and reuse L-proline according to the nature of the carriers.However,there are many problems on the existing supported L-proline catalysts.Accordingly,efforts are needed to design and synthesize novel kinds of L-proline catalyst that can be used as highly effective in water and reusable catalyst in direct asymmetric organic reactions.Based on the above background,this work prepared two kinds of supportedcatalystsincludingthermal andmagneticresponsive organic-inorganic hybrid microspheres supported L-proline organocatalysis?TMHMs?and temperature responsive core-shell microgels supported L-proline organocatalysis?MTCSMs?.These two kinds of supported catalysts were used as catalysts for the asymmetric aldol reaction in water.The catalytic performance?catalytic activity and asymmetric selectivity?and recyclability of TMHMs and MTCSMs were further studied.The detailed researches and conclusions are as follows:1.The preparation of TMHMs and study on of its performance.First,the thiol-terminatedpolymerspoly?N-isopropylacrylamide-co-boc-protected O-acrylic hydroxy-proline?-block-poly?oligo?ethylene oxide?acrylate?-SH?P?NIPAM-co-L-ProlA?-b-POEGA-SH?were prepared by combining reversible addition fragmentation chain transfer?RAFT?polymerization and reduction method.On the other hand,Fe₃O₄@SiO₂-MPS MNPs modified with vinyl groups were prepared by combined chemical coprecipitation method and sol-gelmethod.ThenTMHMswerepreparedbygrafting P?NIPAM-co-L-ProlA?-b-POEGA-SH to Fe₃O₄@SiO₂-MPS MNPs via thiol-ene click chemistry.The influence of the weight ratio between thiol-terminated polymers and the magnetic particles with vinyl groups Fe₃O₄@SiO₂-MPS on the L-proline catalyst loading of TMHMs was studied.The results show that TMHMs are thermo-responsive and superparamagnetic with spherical shapes.With the increase of thiol-terminated polymer content in the reaction system,L-proline loading of TMHMs increases firstly,then decreases,and then keeps unchanged.In other words,when the weight ratio between thiol-terminated polymers and Fe₃O₄@SiO₂-MPS magnetic particles is kept at 2:1,TMHMs have the highest L-proline catalyst loading.2.The preparation of MTCSMs and study on of its performance.MTCSMs were prepared by distillation precipitation copolymerization.The results show that MTCSMs have smooth surfaces,thermo-responsive and spherical shapes with a well-defined core-shell structure.The L-proline loading of the core-shell microgels is 0.46 mmol/g.3.TMHMs catalyst for asymmetric aldol reaction.First,four kinds of TMHMs with different L-proline loading were evaluated as chiral catalysts in aldol reaction between cyclohexanone and 4-nitrobenzaldehyde.The reactions were carried out with 5 mol%catalyst loading at different temperatures in pure water for 24 h.The results show that the catalytic activity and selectivity of TMHMs increases with the increasing temperature and L-proline loading.When the reaction temperature is 50?,TMHMs have the best catalytic performance with 94%conversion,81/19 anti/syn and 95%ee,higher than that showed in literature.TMHMs could be simply separated from reaction system by a magnetic field and reused for five times without significant loss of conversion and stereoselectivity.4.MTCSMs catalyst for asymmetric aldol reaction.First,MTCSMs were evaluated as chiral catalysts in aldol reaction between cyclohexanone and4-nitrobenzaldehyde.The reactions were carried out with 5 mol%catalyst loading at different temperatures in pure water for 24 h.The results show that the catalytic performance of TMHMs increases with the increasing temperature.When the reaction temperature is 50?,MTCSMs have the best catalytic performance with 90%conversion,78/22 anti/syn and 91%ee.MTCSMs could be simply separated from reaction system and reused for five times with no significant loss of stereoselectivity and a slight decrease of reaction conversion.