Copper-catalyzed Asymmetric Selective Addition Of Pyrrolidone Derivatives

There are many sources of chiral molecules,mainly including the following three aspects:(1)to isolate and extract from nature;(2)to split up the racemate;(3)asymmetric catalysis and synthesis.Since the 21st century,asymmetric catalysis has been developed vigorously,and more and more catalytic systems and reactions have been reported,providing a more favorable tool for the synthesis of chiral drugs.The work of this thesis is based on the catalytic system developed in our laboratory,realizing the selective asymmetric catalysis of 2,3-dioxopyrrolidine.(1)Enantioselective formal hetero Diels-Alder reaction and the synthesis of spiropyrrolidone derivatives.Based on our research on enatioselective formal hetero DA reaction,we developed copper-catalyzed asymmetric formal hetero DA reactions of Danishefsky's diene with 2,3-dioxopyrrolidines.Under mild conditions,we obtained a series of chiral spiral ring compounds with excellent yields(up to 99%)and enantioselectivities(up to 99%ee),and also extended the reaction to the gram scale.The mechanism study showed that the reaction pathway depended on the substrate diene and was related to the stability of silane.(2)Copper catalyzed diastereoselective and enantioselective 1,4-Michael addition reaction of 2,3-dioxopyrrolidines with nitroalkanes in aqueous media.Based on the asymmetric Michael addition reactions in aqueous media in our laboratory,we developed asymmetric Michael addition reactions of 2,3-dioxopyrrolidines with nitroalkanes catalyzed by proline-derived ligands with copper complex in the aqueous media.The effect of electron and steric hindrance on the reaction was not obvious.Different substrates could be converted to 1,4-nitro Michael addition products with high yields(up to 93%)and enantioselectivities(up to 96%ee),and almost only a pair of diastereomers was obtained.Meanwhile,the gram-scale reaction was realized,which showed the practicability of this method.(3)Copper catalyzed asymmetric Michael and cascade Hemiketalization/Retro-Henry reaction of 2,3-dioxopyrrolidines with ?-nitroketones in aqueous mediaDue to the low yield of the direct Michael addition reaction between nitromethane and 2,3-dioxopyrrolidine,we used the Michael addition-acyl transfer strategy between 2,3-dioxypyrrolidine and ?-nitroketone to solve the problem of the yield.However,all such reactions have been reported under the catalysis of small alkaline organocatalysts.So far,Lewis acid catalyzed rections of this kind have not been reported.Through a series of optimizations,we finally achieved this kind of tandem reaction.The target products were obtained with medium to good yields and enantioselectivities.Furthemore,the reaction was also extended to the gram scale,and the possible reaction mechanism was proposed by calculation.