[3+2] Cycloaddition Reaction And Synthesis Of Ibophyllidine Alkaloids

In this thesis,the synthesis of two different types of chiral phosphine-secondary amine?tertiary amine?-amide ligands was first studied,and then a variety of chiral ligands were synthesized with metal salts to form metal complexes to catalyze Asymmetric[3+2]cycloaddition reaction,and finally use the appropriate chiral pyrrolidine derivatives to design synthetic routes and explore the synthesis of ibophyllidine alkaloids.1. Synthesis of chiral phosphine-secondary amine?tertiary amine?-amide ligands:Firstly,poly-substituted o-phenylenediamine and 2-?aminomethyl?aniline and Boc protected chiral amino acids were used as starting materials for amide condensation reaction and Removal of the tert-butoxycarbonyl?Boc?reaction yielded a free primary amine intermediate,which was then synthesized with 5-diphenylphosphonic acid through another amide condensation reaction to synthesize 5 chiral phosphine-secondary amines?tertiary amine?-Amide ligand compounds 1 a-1e;the chiral phosphines derived from hydrogenated cinkenitin primary amine and hydrogenated cinconyl primary amine were synthesized by the same synthetic method through the improvement of the synthesis method,using a new dehydration condensation reagent-Tertiary amine-amide ligand compounds 1f and 1g.2. Study on asymmetric[3+2]cycloaddition reaction:First,the asymmetric[3+2]cycloaddition reaction model of azomethine ylide and diethyl maleate was established,using synthetic chiral phosphine-Secondary amine?tertiary amine?-amide ligand compounds 1a-1e form metal complexes with metal salts to catalyze the reaction Butylamino-terminated 2-aminobenzylamine and L-tert-leucine-derived precatalyst 1e?4 mol%?/Ag₂O?2 mol%?,toluene was used as the reaction solvent at room temperature,and then the substrate expansion experiment was carried out,all reactions can obtain pyrrolidine derivatives exhibiting excellent enantioselectivity?80%-94%?with good yields?58%-90%?.Subsequently,on the basis of summarizing the previous research of the research group,the chiral phosphine-tertiary amine-amide ligand compound 1f/1g derived from hydrogenated octinidine primary amine and hydrogenated cinconimide primary amine and silver oxide at-5?co-catalyzed the 1,3-dipolar cycloaddition reaction of azomethine ylide derived from tert-butyl glycine and methyl acrylate in toluene,through the analysis of experimental results,the chiral ligand 1f/1g catalyzed reaction.The configuration of the chiral pyrrolidine product is completely opposite.The configuration of the target compound obtained by the chiral ligand 1g is exactly the same as the configuration required by our subsequent synthesis studies of alkaloids?70%-90%?to obtain pyrrolidine derivatives exhibiting excellent enantioselectivity?90%-99%?.3. Study on the synthesis of ibophyllidine alkaloids:use synthetic pyrrolidine derivatives as precursor compounds to try the synthesis of ibophyllidine alkaloids.One of the difficulties in the synthesis is the construction of multiple quaternary carbon chiral centers in the structure.At present,the form synthesis of ibophyllidine alkaloids is completed only through the precursor compounds.Through the exploration of the synthetic routes of different precursor compounds,the most suitable precursor compounds are identified and the synthetic transformation of key sites is achieved.Through our synthesis Strategy,hoping to accelerate the follow-up research on the synthesis of ibophyllidine alkaloids.