Transition-Metal Catalyzed Asymmetric Synthesis Of Chiral Benzorofuran-Fused Azepines And Enynes

Chiral compounds are widely existed in many drugs,natural products and other functional molecules.Therefore,the development of the asymmetric synthesis of chiral compounds is an important issue in the field of organic synthetic chemistry.Among numbers of structurally and functionally different chiral compounds,the chiral benzofuran-fuszed azepines and enynes are two important classes of chiral compounds.Based on the efficient and powerful transition-metal asymmetric catalysis,the thesis demonstrates the efficient synthetic methods for the important chiral benzofuran-fuszed azepines and two kinds of enynes.Herein,the thesis includes two parts.The 1^st Part:Given the importance of chiral benzofuran-fuszed azepines and the urgent need for the development of asymmetric[4+3]-cyclization of TMM,we employed the Pd-chiral phosphoramidite as chiral catalyst to promote the cyclization reaction of TMM with benzofuran-fused 1-azadienes.The reaction delivered the vicinal two stereocenters containing chiral benzofuran-fuszed azepines in up to 92%yield with up to 99%ee and high dr.The 2^nd Part:Given the importance of chiral 1,3-enynes and unconjugated1,5-enynes and rare synthetic methods for these compounds,the thesis demonstrates the transition-metal catalytic reactions,which are the Pd-catalyzed asymmetric nucleophilic reaction of conjugated vinyl-propargylc esters and Cu-catalyzed Doyle-Kirmse reaction of alkynyldiazoacetates with allylic sulfides.For the Pd-catalyzed asymmetric nucleophilic reaction of conjugated vinyl-propargylic esters,the coumarins linked a remote nucleophilic center were employed to react with allylpalladium intermediates.The reaction afforded the enantioenriched coumarin scaffold containing 1,3-enynes in up to 80%yield and 95%ee.Moreover,the reaction is the first remoted asymmetric catalytic reaction of non-terminal propargylic esters.For the Cu-catalyzed Doyle-Kirmse reaction of alkynyldiazoacetates with allylic sulfides,the preferred asymmetric catalysis of copper and chiral Box ligands is identified to give the 1,5-enynes bearing a sulfur-quaternary stereocenter in 80%yield and 72%ee.Despite the moderate stereoselectivity,the Doyle-Kirmse reaction of alkynyldiazoacetates with allylic sulfides is a highly efficient and new method for the synthesis of 1,5-enynes.Therefore,the substrate scopes are investigated and shown in the Cu-catalysis of Doyle-Kirmse,delivering a class of significant 1,5-enynes bearing a sulfur-quaternary stereocenter.In summary,the thesis provides the efficiently catalytic synthesis for chiral benzofuran-fuszed azepines,coumarin scaffold containing 1,3-enynes and 1,5-enynes bearing a sulfur-quaternary stereocenter.Moreover,they enrich the transition-metal catalyzed asymmetric[4+3]-cyclization of TMM with benzofuran-fused 1-azadienes,remote asymmetric nucleophilic reaction of conjugated vinyl-propargylic esters and Doyle-Kirmse reaction of alkynyldiazoacetates.