Asymmetric Synthesis Of Functionalized Chiral Propargylic Alcohols And Application In Total Synthesis Of Insect Pheromone

Chiral propargylic alcohols present in many bioactive natural products.These building blocks are also important pharmaceutical intermediates.The asymmetric alkynylation of carbonyls is proved to be one of the most powerful procedures for organic synthetic chemistry,where the formation of one carbon-carbon bond and one chiral center of propargylic alcohol can be achieved in one step,and has attracted organic chemists' most attentions.Plenty of works have been reported in recent years.This thesis mainly focuses on overcoming the substrates limition of the present catalytic systems,low catalytic efficiency,and application in total synthesis.1.Conveniently synthesized sulfonamide alcohol titanium complex has been used to catalyze the asymmetric addtition of methyl propiolate to various aromatic and aliphatic aldehydes with high enantioselectivity.With 1,2-dimethoxyethane(DME)as an additive,the reaction proceeded under mild condition to gave the highly functionalizedγ-hydroxy-α,β-acetylenic esters,and highly toxic reagent was avoided.Compared with other catalytic systems,the sulfonyl oxygen atoms of the sulfonamide alcohol played an important role in the catalytic addition as an Lewis base.2.Different supported chiral ligands have been used to catalyze the asymmetric alkynylation.the asymmetric addition of phenylacetylene to aromatic aldehydes can be effectively catalyzed by linear polystyrene supported sulfonamide alcohol-Titanium complex.Additive TEA can highly accelerate the turnover frequency of the catalyst.The efficiency of this catalytic system is much higher than that of its mono-analogue or any other homogeneous catalytic systems. The easily recoverble linear PS-supported ligand has been reused six times without loss of catalytic activity.In combination of the former studies,it is found that different type of Lewis base exhibit different influences.3.For the first time,we introduced the average enantioselective turnover frequency(E-TOF)in the asymmetric phenylacetylene addition to aromatic aldehydes to evaluate the positive efficiency for different catalytic systems in principle which taking enantioselectivity,yield, catalyst loading,as well as reaction time into account.The E-TOF will also be feasible and practical to assist chemists in screening the optimal reaction condition or evaluating the overall efficiency of different catalytic systems for a specific asymmetric reaction.4.For the first time,we explored chiralγ-hydroxy-α,β-acetylenic esters,which were prepared via asymmetric alkynylation,as key intermediates to the synthesis of chiralγ-butyrolactones. This convergent and enantioselective approach to chiralγ-butyrolactones is practical and easily handled with protecting group free.Under this strategy,enantioselective total synthesis of two important insect sex pheromones,(4S,5Z)-1(Anomala Osakana Pheromone)and(4R, 9Z)-2(Janus integer Pheromone),were successfully achieved with high ee of 84%and yields over 87%in short steps(6-8)from very sample starting materials.