Catalytic Asymmetric Construction Of Chiral Homoallylic Amines

Chiral homoallylamine derivatives are a class of representative and important structural units,which are important active fragments in many bioactive natural products and drug molecules.They are also effective precursor in biologically active nitrogen-containing heterocycles,?-amino acids as well as ?-lactams.Hence,the efficient synthesis of chiral homoallylamine is of great significance for asymmetric synthetic chemistry.In the early days,the traditional synthesis methods of chiral homoallylamine compounds were the addition of allyl reagents to carbon-nitrogen double bonds,induced by chiral substrates(including those containing chiral auxiliary groups)or controlled by chiral allyl reagents.The use of equivalent amounts of chiral reagents greatly restricted their wide application potential in organic synthesis.In recent years,the transition metal-catalyzed asymmetric allylation has become much more effective synthesis method,including the asymmetric addition of nucleophilic allylic reagents to carbon-nitrogen double bonds,or the reaction of electrophilic allylic reagents with nucleophilic reagents such as iminoesters,azlactones,and so on.Based on the research of the copper/iridium bimetal catalyzed allylation reaction in our group,this thesis studies the asymmetric allylation of arylidene diisopropyl aminomalonates and allylic carbonates catalyzed by monometallic iridium catalyzed allylation/2-aza-Cope rearrangement tandem reaction,a variety of chiral homoallylic amine compounds were obtained with high yields and high enantioselectivies.Using the imine synthesized from aldehydes and aminomalonates as nucleophiles,by introducing two electron-withdrawing groups in the ?-position of iminoesters,it can easily generate the more active nucleophilic carbanion under basic condition.The nucleophile can react with chiral allyl iridium complex to obtain ?-branched allylated products with excellent enantioselectivies,and then through a stereospecific 2-aza-Cope rearrangement to obtain linear allylated products.The chiral homoallylamine derivatives can be obtained with 100% chiral transfer efficiency.The reaction has good functional group suitability,excellent yields and excellent enantioselectivies(up to 96% ee).Compared with the previously reported dual-catalyst system of copper/iridium and phase-transfer catalyst/iridium co-activation,this catalytic system is implemented with the mono metal complex.The reaction system has the characteristic of simple operation and high reaction efficiency,which provides a more economical and practical method for the synthesis of chiral homoallylamine compounds.The reaction could be scaled up to the gram scale,and the branched allylated intermediates can be easily converted into enantioenriched tetrahydropyrrole derivatives containing two consecutive chiral centers.