Palladium-Catalyzed Asymmetric[3+2] Cycloaddition Reaction Of Vinyl Cyclopropanes With Electron-Deficient 1,3-Dienes

The transition metal-catalyzed asymmetric[3+2]cycloaddition reaction of vinyl three-membered ring compounds and electron-deficient olefins is an important method to construct chiral multi-substituted five-membered ring compounds.Literature methods mainly focus on the cycloaddition reaction of vinyl three-membered ring compounds with simple electron-deficient olefins,while the cycloaddition reaction using electron-deficient 1,3-dienes as the substrates is rarely reported.In this thesis,the palladium-catalyzed asymmetric[3+2]cycloaddition reaction of vinyl cyclopropanes and electron-deficient 1,3-dienes is realized.The cycloaddition reaction regioselectively occurs at the terminal double bond far away from the electron withdrawing group of electron-deficient 1,3-dienes.The cycloaddition reaction has the advantages of simplicity and efficiency,ready availability of substrates,and high regio-,diastereo-and enantio-selectivities.The thesis is mainly divided into the following three parts:In the first part,the research progresses on the cycloaddition reactions of vinyl three-membered ring compounds with electron-deficient alkenes,electron-deficient alkynes,aldehydes,imines and other unsaturate compounds were introduced under the palladium catalysis.In the second part,a series of electron-deficient 1,3-diene compounds were synthesized based on the literature methods.Specifically,（E）-2-（alkoxycarbonyl）-2,4-pentadienoates were obtained by the condensation reaction ofα,β-unsaturated aldehydes and malonate diesters.In the third part,palladium-catalyzed asymmetric[3+2]cycloaddition reaction of vinyl cyclopropane with electron-deficient 1,3-dienes was explored.By adjusting the steric hindrance ofγ-substituents of（E）-2-（alkoxycarbonyl）-2,4-pentadienoates,the[3+2]cycloadditon regioselectively occurred at the terminal double bond of allylidene malonate diesters.By optimizing the reaction conditions,the[3+2]cycloaddition reaction was performed by using Pd₂（dba）₃ as the palladium source,（R）-SEGPHOS as the chiral ligand,and tetrahydrofuran as the solvent at room temperature.Trisubstituted cyclopentanes with three consecutive chiral centers were obtained in 25-68%yield with 64-93%enantioselectivity.The chiral trisubstituted cyclopentanes,bearing two different types of double bonds and two ester groups,were easily converted into other synthetic building blocks,which shows the promising potentiality of this protocol in organic synthesis.The factors affecting the regioselectivity of the cycloaddition were studied,and the possible reaction mechanism was proposed.