The Methodology Research of Cycloaddition and Rearrangement Reaction Based on Oxonium Intermediate

Author:Zhang Jian Tao

Supervisor:zhu shi fa


Degree Year:2019





In the field of organic synthesis,oxonium ions are often used as important reaction intermediates in the construction of oxygen-containing heterocyclic skeletons.In this process,the oxonium intermediate is closely related to the cycloaddition reaction and the rearrangement reaction.In recent years,reports on cycloaddition reactions have emerged in an endless stream.During such reactions,multiple carbon-carbon bonds can be formed in a single step,often with a high degree of regioselectivity and stereoselectivity to synthesize small and medium-sized carbocyclic skeletons.Rearrangement reaction is one of the important approaches to synthesize complex natural products and other target molecules.The molecular skeleton is rearranged to form new compounds with the break of old bonds and the formation of new bonds.Based on the above basis,we would like to describe the achievements about the transition-metal catalyzed cycloaddition and rearrangement reactions based on oxonium intermediates,which generate in situ from enynals and enyne-ethers,and a series of compounds with polycyclic skeleton are synthesized.This dissertation is divided into five parts as follow:(1)Zinc-catalyzed tandem Diels-Alder reactions of enynals with alkenes:Generation and trapping of cyclic o-quinodimethanes(o-QDMs).The benzoisopyran salt formed from the enynal,which was activated by ZnCl2,underwent[4+2]cyclization reaction with alkene,giving a highly active species,ortho-benzoquinone(o-QDMs).o-QDMs tended to undergo another[4+2]cyclization with the electron-poor alkene if an electron-poor alkene was added to the system,resulting in a three-component propeller-like system;Without the addition of an electron-poor alkene,there would be a bridged system in which two molecules of the same alkene were involved.DFT calculations were performed to understand the reaction mechanism.(2)Cascade one-pot synthesis of indanone-fused cyclopentanes from the reaction of donor-acceptor cyclopropanes and enynals.A cascade reaction of donor-acceptor cyclopropanes with enynals to construct indanone-fused cyclopentanes via a sequential hydrolysis/Knoevenagel condensation/[3+2]cycloaddition is reported.This method features mild reaction conditions and broad substrate scope.Moreover,the products could be further converted into compounds with different functional groups through the well-known transformations.(3)Catalytic[1,3]O-to-C rearrangement:Rapid access to bridged bicyclic systems.5-exo-dig and 6-endo-dig cyclization could be selectively carried out by the difference of the substrate by the activation of catalyst.When the enyne-ethers tethered with terminal alkyne or electron-deficient alkyne were used as the substrates,they tended to undergo 5-exo-dig/[1,3]O-to-C rearrangement process;giving the bicyclo-[4.2.1]-products;When the enyne-ethers tethered with ynamide side chain were utilized as substrates,they tended to undergo 6-endo-dig/[1,3]O-to-C rearrangement process;giving the bicyclo-[3.2.2]-products.For both systems,a vinyl oxonium intermediate was proposed as the precursor for the[1,3]O-to-C rearrangement.This catalytic system can also be extended to[3,3]-rearrangement when a vinyl group was introduced.(4)Rapid access to oxa-bridged bicyclic skeletons through gold-catalyzed tandem rearrangement reaction.A gold(I)-catalyzed reaction of enyne-ethers to rapidly construct oxa-bridged compounds via a tandem 1,2-acyloxy migration/intramolecular oxonium formation/1,2-rearrangement process was reported.The reaction was shown to be robust with a wide range of substitution patterns tolerated to provide the corresponding oxygen-containing bridged products in good to excellent yields.Besides,various benzaldehydes with a long chain were also synthesized with regard to the vinyltethered substrates,which would be the products arising from intramolecular nucleophilic attack/oxonium formation/3,3-rearrangement/intermolecular nucleophilic attack/retro-aldol process.(5)Construction of polycyclic bridged indene derivatives by a tandem 1,3-rearrangement/intramolecular Friedel-Crafts cyclization of propargyl acetates.An efficient Lewis-catalyzed method for the synthesis of polycyclic bridged indene derivatives from propargyl acetates has been developed using 1,3-rearrangement/intramolecular Friedel-Crafts reaction.The acyloxy group of the propargyl acetates substrate was removed by the activation of Lewis acid,and the resulting allene cation was attacked by the intramolecular nucleophile to obtain the oxonium intermediate,which underwent the[1,3]-rearrangement to form another oxonium intermediate,this intermediate could be captured by an aryl group and initiate Friedel-Crafts reaction to construct oxygen bridged polycyclic compound.On the other hand,after the introduction of the vinyl group,the oxonium intermediate produced by 3,3-rearrangement could not be consumed by the Friedel-Crafts reaction of the phenyl group,but the Prins type reaction was further generated,furnishing the carbon cation,which was comsumed by the halogen introduced from the catalyst.Finally,the cyclopentane-fused oxo-bridge polycyclic compound was formed.