Synthesis Of Bifunctional Phase-Transfer Catalysts Derived From Cinchona Alkaloids And Their Application To Aza-Henry Reaction

The asymmetric aza-Henry reaction catalyzed by organocatalysts has only developed dramatically in recent years.It is well-known that the catalytic asymmetric aza-Henry reaction is one of the strongest methods for constructing carbon-carbon bonds.In this context,developing novel asymmetric catalysts to realize this important chemical transformation and obtain valuable chiral products is desirable.For this purpose,we designed and prepared two kinds of novel quinine-derived bifunctional phase-transfer catalysts and applied them in asymmetric aza-Henry reactions.The main reseach work contains three parts as following:1.We prepared a kind of novel Cinchona-derived quaternary ammonium salt catalyst bearing multiple H-bonding donors and applied them to the asymmetric nitro-Mannich reaction of aminosulfones withα-arylnitromethanes.Through the screening catalysts,we found that the quaternary ammonium salt moiety of the catalyst is a bulky N-3,5-di-tert-butylbenzyl moiety gives the best result.After a series of screenings and optimizations（such as base,solvent,temperature and catalyst loading）,the optimal reaction conditions were identified as follows:catalyst（5 mol%）,LiOH（5 equiv.）,CHCl₃ used as solvent,the reaction temperature of-40°C and 12 h.A variety ofα-aryl nitromethanes and amidosulfones were investigated,and corresponding products were obtained in excellent yields（up to 99%）with excellent diastereo-and enantioselectivities（up to 99%ee and 99:1 dr）.Using this optimal asymmetric catalytic protocol,enantiopure unsymmetric and meso-symmetric1,2-diarylethylenediamines could be synthesized.2.Asymmetric aza-Henry reaction of ofβ,γ-unsaturated nitroalkenes with amidosulfones has been developed by using bifunctional chiral phase-transfer catalysts.Through the screening of the catalysts,we found that the catalyst containing the L-phenylglycinol moiety and bulky N-3,5-di-tert-butylbenzyl moiety gave the best results.Subsequently,the optimal reaction conditions were determined by screening for base,solvent,substrate,and temperature.Accordingly,we chose catalyst（5 mol%）,dichloromethane solvent,and the reaction temperature of-40°C as the optimal reaction conditions.The strategy has a broad substrate scope,and corresponding products were obtained in high to excellent yields（up to 99%）with high to excellent diastereo-and enantioselectivities（up to 99%ee and 99:1 dr）.Mechanism control experiments and theoretical calculations prove that the catalytic system is a bifunctional synergistic catalyst.The optically active products were readily transformed into 2,3-diamino alkenes.3.A series of novel thiourea based phase transfer catalysts derived from cinchona alkaloids were prepared.Under the catalysis of this kind of chiral catalysts,we have developed the first asymmetric aza-Henry reaction of arylα-ketoester-derived N-Ts ketimines.The optimal reaction conditions were catalyst（10 mol%）in the presence LiOH·H₂O（5 equiv）in m-xylene at-10°C for 3 h.The products bearing quaternary chiral centers were obtained in high to excellent yields（up to 99%yield）with good to high enantioselectivities（up to 99%ee）.In addition,we proposed a possible transition state model.Using this asymmetric catalytic protocol,usefulα,β-diamino esters could be synthesized.