Palladium-Catalyzed Asymmetric Alkylation Of Azlactone

The construction of a C-C bond via the asymmetric alkylation,accomplishing a quaternary stereocenter,is an important subject in enantioselective synthetic process.Many biologically active molecules in organisms are chiral,including the quaternary carbon center skeleton,so the development of a potential protocol for enantioselective synthesis of a quaternary stereocenter skeleton is highly valuable and desirable.The asymmetric alkylation of azlactone is one of the ways to synthesize a quaternary stereocenter skeleton.By the asymmetric alkylation of azlactone,we can realize the synthesis of a chiral quaternary stereocenter skeleton in one-step.However,at present,most of the terminal alkenes involved in the asymmetric alkylation of azlactone are branched ones.Therefore,it is highly necessary to explore the asymmetric alkylation of azlactone with cyclic alkenes in organic synthesis.In this thesis,the electron-deficient allylcyclopropane was used as the substrate and palladium was used as the catalyst.Through the comprehensive screening of the solvent,base,ligand structure,palladium at different valences and temperature,the optimized conditions for the basic reaction of the alkylation of lactone at C4 position are as follows:the ratio of azlactone and electron-deficient allylcyclopropane is 1:1.3,and the catalyst is a complex of Trost's ligand and Pd₂(dba)₃,acetonitrile.As the best solvent for the reaction,the reaction was carried out at-20oC for 12 h,the yield was up to 99%,and the ee value was up to 94%.In this paper,the generality of substrates was also investigated to synthesize quaternary carbon center heterocyclic skeletons with different substituents.The yield is mostly between 70%and 90%,and the ee value is mostly above90%.We carried out a gram-scale experiment and found that after the scale of the reaction was expanded,it was still able to reach a medium yield and a high ee value,thus demonstrating the potential utility of the reaction.Then the absolute configuration of the product was unambiguoously determined by X-ray ananlysis of 3w.For the asymmetric alkylation of azlactones,this paper provides a completely new idea that we can achieve allylcyclopropane through the ring opening process,followed by alkylation.The experiment proves that this subject is not only practical,but also has important value in chemical synthesis methodology.More importantly,the chiral quaternary carbon heterocyclic skeleton synthesized by us has potential value in natural product and drug synthesis.