[3+2] Cycloaddition Reactions And Preliminary Study On Synthesis Of Spirotryprostatin Alkaloids

This dissertation is mainly about research on the synthesis of different chiral diamine-derived multifunctional amidophosphane ligands,exploring amidophosphane ligands in combination with metal ions to cooperatively catalyze asymmetric[3+2]cycloaddition,and expanding its application in the synthesis of spirotryprostatin alkaloids with physiological activity.1.Synthesis of different chiral diamine-derived amidophosphane ligands:First,nine kinds of 1,2-diphenylethylenediamine-derived multifunctional amidophosphane ligands 1a-1i were synthesized by three-step reaction including amide condensation,tert-butoxycarbonyl（Boc）removal,and condenssation with 2-（diphenylphosphino）benzoic acid by using different substituted chiral 1,2-diphenylethylenediamine andα-amino acids as raw materials.Subsequently,eight kinds of cinchona alkaloid-derived multifunctional amidophosphane ligands 1j-1q were also synthesized in the same manner.2.Studying on the asymmetric[3+2]cycloaddition reactions:First,we explored the 1,3-dipolar cycloaddition reaction of azomethine ylides and diethyl maleate catalyzed by different substituted chiral1,2-diphenylethylenediamines andα-amino acids-derived multifunctional amidophosphane ligands 1a-1i in combination with silver carbonate.By optimizing the conditions,we found that the optimal reaction condition is secondary amine-derived amidophosphane ligand 1g（4 mol%）/Ag₂CO₃（2mol%）/toluene at room temperature.Then,substrate expansion experiments were carried out under optimal reaction conditions,with better yields（65%-99%）and higher enantioselectivities（76%->99.9%）.In addition,by using the 1g/Ag₂CO₃/toluene catalytic system to catalyze the"three-component one-pot"synthesis of pyrrolidine derivatives,the same high yields（89%-99%）and good enantioselectivities（92%-96%）were also obtained.Next,we explore alkaloids-derived multifunctional amidophosphane ligands 1j-1q in combination with different silver salt Lewis acids to synergistic catalyze the 1,3-dipolar cycloaddition reactions of azomethine ylides and methyl acrylate.These results show high yields（72%-97%）and enantioselectivities（57%-95%）were also obtained under mild conditions by exploiting amidophosphane ligand 1q in combination with silver oxide to catalyze such kind of reactions.3.Synthesis of spirotryprostatin alkaloids:we attempted to synthesize spirotryprostatin alkaloids by asymmetric[3+2]cycloaddition reaction.Pyrrolidine derivatives with a quaternary center at the 4-position were obtained by exploiting amidophosphane ligand 1q in combination with silver oxide to cooperatively catalyze[3+2]cycloaddition ofα-substituted terminal double bond esters and azomethine ylides with70%-85%yields and 85%-90%enantioselectivities.It will establish a good foundation for the subsequent synthesis of spirotryprostatin alkaloids.