Study On Copper-Catalyzed 1,3-Aminative Functionalization Of Arylcyclopropanes

Cyclopropane has a high ring strain(about 27.5 kcal/mol),which can release the strain through cyclopropane ring opening under specific reaction conditions.Two functional groups are introduced at the 1-and 3-positions of the carbon chain structure,thus improving the structure complexity and the diversity of functional groups of the product.Therefore,cyclopropane ring-opening 1,3-bifunctional groups becomes an important synthetic method for complex 1,3-bifunctionalized chain compounds.So far,D-A cyclopropane ring opening functionalization is widely studied because the C-C bond between push-pull electron substituents is polarized by the two substituents which makes the ring opening functionalization reaction easily occur.However,there are a few reports on ring-opening 1,3-bifunctionalization non-D-A cyclopropane with relatively weak activity.Arylcyclopropane can be oxidized to form cyclopropane radical cationic intermediate by single electron oxidation,and then the ring-opening functionalization reaction is initiated by nucleophile attack.Nevertheless,there are very limited examples of non-D-A cyclopropane ring-opening 1,3-bifunctionalization involving multicomponent.The asymmetric catalyzed ring-opening difunctionalization of non-D-A cyclopropane still faces great challenges.In this thesis,single-electron oxidation of arylcyclopropanes is used to afford key arylcyclopropane radical cation intermediate,thereby realizing a series of ring-opening 1,3-bifunctionalization reactions,including: 1)copper-catalyzed asymmetric ring-opening 1,3-aminocyanation of arylcyclopropanes;2)copper-catalyzed ring-opening 1,3-aminolaction of arylcyclopropanes;3)copper-catalyzed four-component cascade reaction with arylcyclopropanes.1.Copper-catalyzed asymmetric ring-opening 1,3-aminocyanation of arylcyclopropanesWe have developed the first example of copper-catalyzed highly enantioseletive ring-opening reaction of arylcyclopropanes,whcih uses N-fluorobenzenesulfonimide(NFSI)as the oxidant and nitrogen source,trimethylsilyl cyanide(TMSCN)as cyanide source.Through this reaction ?-amino nitriles were synthesized with high yields and enantioselectivity under mild reaction conditions.In this asymmetric reaction,two types of functional groups were introduced to the strained arylcyclopropanes via a novel radical cation pathway,which provides a new strategy for asymmetric ring-opening 1,3-bifunctioanlization of cyclopropanes.2.Copper-catalyzed 1,3-aminolaction of arylcyclopropanesA class of arylcyclopropanes with an ester group at side chain was designed and synthesized as substrates.With copper as catalyst,the 1,3-aminolaction reaction of these arylcyclopropane was realized,furnishing a series of amino lactone compounds.Mechanism studies indicated the reaction firstly underwent single-electron oxidation/nucleophilic ring opening of arylcyclopropane,and then generated a benzylic radical,which was further oxidazed to form benzyl cation,and subsequently intramolecular nucleophilicly trapped by the oxygen atom to form an oxonium intermediate.The fianl demethyl-cation gives the ring-opening amino lactone products.In addition,we explored the asymmetric ring-opening 1,3-aminolaction reaction of arylcyclopropane.This reaction uses arylcyclopropanes with carboxyl group at side chain as substrates.Amino lactone compounds are synthesized with good yield in moerdate enantioselectivity under the combined photoredox and copper catalysis.This study provides a potential possibility for the further development and application of asymmetric ring-opening 1,3-amino oxygenation of arylcyclopropanes.3.Copper-catalyzed four-component 1,3-aminoimidization of arylcyclopropanesWe use readily available arylcyclopropanes,nitrile and carboxylic acid as substrates,NFSI as oxidant and nitrogen source to realize four-component ring-opening1,3-aminoimidization of arylcyclopropanes.A series of ?-aminoimide compounds were successful synthesized by this reaction.This reaction has the advantages of simple and efficient,step economy,high regioselectivity and broad functional group compatibility.Reaction mechanism studies showed the free radical cation intermediates generated by single-electron oxidation of arylcyclopropane,then the nucleophilic ring opening to produce benzylic radical,and then single-electron oxidation to form benzyl carbocation,which then underwent Ritter reaction with nitriles and 1,3-acyl transfer reaction with carboxylic acids to afford the important ?-aminoimides.This method provides a novel idea for the synthesis of ?-substituted unsymmetric imides.