Studies On The Activation And Carbon-Nitrogen Bond Cleavage Reactions Of Alkylamines

Aliphatic amines are present in many biologically relevant molecules,and usually serve as organic base and nitrogenphilic reagents in many organic reactions.However,there were a few reports on the carbon-nitrogen bond cleavage of a limited number of alkylamines served as carbon electrophiles.The research on new method for the selective construction of carbon-carbon or carbon-heteroatom bond though the cleavage of carbon-nitrogen bond remains a major challenge in organic synthsis.In this dissertation,we have developed many methods to active the alkyamines.In the cooperative combination of chiral a-amino acid,we have developed a new protocol for the use of allylic amines as allylating agents in the chiral a-amino acid/palladium-catalyzed asymmetric allylation of a-branched ?-ketoesters.We reported a modified Darzens-type reaction by in situ formation of unstrained ammonium ylides from tertiary amines and benzyne.In the presence of palladium,we have developed aromatic substitution reaction of benzylic ammonium salts through carbon-nitrogen bond cleavage.In the presence of palladium,we have developed a new method for obtaining allyl aromatic compounds using benzylic ammonium salts as coupling partners.This dissertation is divided into five chapers.Chapter 1:Reviews in activation and carbon-nitrogen bond cleavage reaction of alkylaminesThis chapeter gives an overview of activation and carbon-nitrogen bond cleavage reaction of alkylamines.Firstly,the attachment of an electron-withdrawing group such as sulfonyl and acyl group to the nitrogen atom of a carbon-nitrogen bond in alkylamines can significantly facilitate its cleavage.Secondly,the synthetic utility of transition-metal-catalyzed the cleavage of carbon-nitrogen bond activated by an acid provides another powerful method for the transformation of carbon-nitrogen bond.Thirdly,the carbon-nitrogen bond is activated in situ by electrophiles compound such as arynes,allenones,and alkynes to convert alkylamine into corresponding ammonium salt,which makes the removal of the amino group easier.Finally,N-alkylation reaction makes the alkylamine into the ammonium salt.Then the carbon-nitrogen bond is cleavaged by other reagent.By activating the amino group using different methods,the alkylamine can selectively cleave the carbon-nitrogen bond to form a plurality of carbon-carbon bond and carbon-heteroatom bond.Chapter 2:Asymmetric allylation of ?-branched ?-ketoesters with allylic amines.In this chapter,a new protocol has been developed for the use of allylic amines as allylating agents in the chiral a-amino acid/palladium-catalyzed asymmetric allylation of a-branched ?-ketoesters,providing highly enantioselective access to all-carbon quaternary stereocenters.The primary,secondary and tertiary amine all can be used as effective allylation reagent in this reaction.Notably,the formation of a primary amine,a secondary amine,or ammonia as a byproduct has little influence on the enantioselectivity for the catalytic asymmetric synthesis of structurally diverse ?,?-disubstituted ?-ketoesters.The reaction goes smoothly with the five-membered,six-membered,seven-membered ring,aza-six-membered ring or even the ring-opened ?-substituted ?-ketoester.Chapter 3:Benzyne-promoted Darzens-type reaction of tertiary aminesA range of tertiary amines having electron-withdrawing groups such as ester,carbonyl,carbamoyl,cyano,and 2-benzoxazolyl go nuclephile addition and proton exchange reaction with benzyne.The unstrained ammonium ylides from tertiary amines and benzyne react with carbonyl compounds,imines,and vinyl ketones to afford structurally diverse epoxides,aziridines,and cyclopropanes,respectively,in moderate to excellent yields with high trans-selectivity.Starting from the chiral benzylamine-derived tertiary amine,the epoxy three-membered ring product can be obtained with high stereoselectivity in 98%ee.Chapter 4:Palladium-catalyzed highly regioselective aromatic substitution of benzylic ammonium salts with amines.In all palladium-catalyzed reactions discussed thus far,attack of the nucleophilic moiety has occurred at the benzylic carbon of the ?-metal complex.However,functionalization at an arene carbon has been reported rarely.We have developed for the first time an aromatic substitution reaction of benzylic ammonium salts through palladium-catalyzed carbon-nitrogen bond cleavage.In the presence of palladium acetate,a range of primary and secondary amines participated in the aromatic substitution reaction of benzylic ammonium salts to afford sterically hindered aromatic amines in moderate to excellent yields with extremely high regioselectivity.A broad substrate scope for the benzylic ammonium such as(naphthalen-1-yl)methyl-,(anthracen-9-yl)methyl-,(phenanthren-1-yl)methyl-and dibenzylic ammonium triflates served as suitable substrates in the reaction.A plausible reaction mechanism was proposed according to the successful identification of ?-benzylpalladium complexes and?-vinyl allylic amines as key intermediates.This study paves the way for the use of benzylic ammonium salts in the aromatic substitution reactions.Chapter 5:Palladium-catalyzed highly regioselective aromatic substitution of benzylic ammonium salts with allylic reagents.In the presence of palladium,a range of benzylic ammonium salts react with allytrimethoxysilane,delivering a wide variety of allyl aromatic compounds in moderate to excellent yields with extremely high regioselectivity.A broad substrate scope for the benzylic ammonium such as(naphthalen-1-yl)methyl-,(anthracen-9-yl)methyl-,(phenanthren-1-yl)methyl-,even the 1-(thiophen-2-yl)-methanaminium triflates can served as suitable substrates in the reaction.Potassium allyl trifluoroborate and allyl tin reagent can also be coupled as good allylation reagents with benzylic ammonium salts.