Design?Synthesis Of Spiro-Pyrrolidine Catalyst And Its Application To Asymmetric Catalysis And Synthetic Study Of Tenuipesine A

Semipinacol rearrangement reaction shows a greater advantage in construction of quaternary carbon center.Based on previous works in our group,1)compound 1-4.19containing aza-spiro-quaternary carbon was synthesized using semipinacol rearrangement reaction,with it a type of spiro-pyrrolidine catalyst was devolped and related catalytic asymmetric reaction was carried out using spiro-pyrrolidine catalyst;2)synthetic study of tenuipesine A,which contains a polysubstituted pyran unit with more quaternary centers,was carried out using bromination/semipinacol reaction as a key step.In particular,there are two parts in this dissertation:Part I:The secondary amine catalysts,a type of privileged catalyst,have been demonstrated with excellent-stereoselectivity,high-efficiency and versatility in the organocatalysis;Therefore,designing new secondary amine catalysts and applying them in the important and unexplored asymmeric chemical transformations become a hot topic in organic chemistry.In this part,a novel spiro-pyrrolidine catalyst has been developed according to our previous works on total synthesis of natural products containing spiro-amino unit via Semipinacol rearangement and the acknowledge of chiral spiro-backbone ligand.With them in hand,a challenging catalytic asymmetric Michael reaction for construction of all-carbon quarternary center in acyclic system has been accomplished using?,?-disubstituted?,?-unsaturated aldehydes and CH₃NO₂ in up to 99%ee and 87%yield,and this synthetic method has been successfully applied to a concise 2-step total synthesis of(-)-coerulescine.At the same time,a catalytic asymmetric double-Michael reaction to construct adjacent all-carbon quarternary centers is being tried,only an unexpected Michael/aldol product is obtained.In addition,a catalytic asymmetric aza-Michael/Michael/aldol/dehydrogenation reaction for construction of hydrophenanthridine core are also being tried and total synthesis of(-)-murrayazoline using this key reaction is on going in our laboratory.Part II:It's a prolonged challenge for construction of natural products containing polysubstituted pyran unit with more quaternary centers in organic synthesis.In this part,tenuipesine A is chosen as a target,construction of adjacent all-carbon quarternary carbon centers and polysubstituted pyran unit have been realized respectively using tandem Mitsunobu/3,3-rearrangement reaction and bromination/semipinacol rearrangement reaction efficiently.