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Tandem ? Acid/? Acid Metal Relay Catalysis:Synthesis Of Multisubstituted Heterocycles

Posted on:2018-02-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:B WangFull Text:PDF
GTID:1311330512989892Subject:Organic Chemistry
Abstract/Summary:PDF Full Text Request
How to improve the efficiency of chemical synthesis,and improve the utilization rate of atoms and achieve the "atom economy" and "step economy" of chemical reaction has always been the eternal topic of synthetic chemists.Tandem reaction model which has the benefits of atom and step economy,avoids the separation and purification of intermediates,constructs several new chemical bonds in one-pot with readily available starting materials.Therefore,tandem reaction has more potential in creating unprecedented chemical transformation.On basis of the advantage of tandem reaction,two parts of different tandem reaction were developed in this dissertation:1:efficient synthesis of heterocycles with ? acid/? acid tandem metal relay catalysis;2:study on the synthesis and application of nitrogen-bridgehead heterocycles by J Wang's tandem reaction.In Part 1,a bimetallic Au(I)/Yb(OTf)3 sequential catalyzed cascade reaction to access a series of nitrogen-containing spiro heterocycles was studied.The spiro heterocycles could serve as an important structural unit in many bioactive natural products,pharmaceuticals as well as agricultural chemicals.The alkynyl alcohols or amides were choosen to be substrate to undergo a ? acid catalyst gold-catalyzed 5-exo-dig intramolecular hydroxylation or hydroamination cyclization to afford the vinyl ethers or enamides intermediates.2,2-diester aziridines favored selectively C-C bond heterolytic cleavage in the presence of ? acid catalyst Yb(OTf)3 which could chelation coordinate with two carbonyl groups,generating active transient azomethine ylide intermediates.A diastereoselective[3 + 2]dipole cycloaddition reaction took place between the two active intermediates to form the expected spiro heterocycles.Asymmetric Au(?)/Lewis acid bimetallic relay catalysis was also explored,although the enantioselectivity was only moderate at present stage,it still provided theoretical possibility for achieving the asymmetric version.Then,the synthetic methodology toward oxazole derivatives with Zn(II)or Zn(?)/Sc(?)tandem relay catalysis was studied.As is well known,oxazole derivatives are privileged five-membered heterocycles with significant biological activities and pharmaceutical values,it's pregnant to develop a universal and simple synthetic process.The propargylic amides were choosen to be substrate to form the active oxazoline intermediate,an intramolecular 5-exo-dig nucleophilic cyclization was catalyzed by ? acid catalyst Zn(OTf)2 which could coordinate and activate the triple bond.Zn(OTf)2 could also act as a acid catalyst to activate allylic alcohols to form allylcarbenium ion intermediate.An allylic substitution reaction happened between the two active intermediates to afford allylic oxazoles.They could be oxidized to conjugated dienes in the presence of Yb(OTf)3 and DDQ,which proved to be good AIE luminogens and will potentially have more applications as the AIE active materials.Sc(OTf)3 could act as ? acid catalyst to activate aromatic aldehydes to form an electrophilic intermediate,then a carbonyl-ene reaction took place between it and oxazoline intermediate to produce oxazole alcohols.In Part 2,various 5-cyanopyrazolo[1,5-a]pyridine and 7-cyanoindolizine derivatives were synthesized by JWang's tandem reaction and extended the application scope of JWang's tandem reaction.Nitrogen-bridgehead heterocycles that contain the pyrazolo[1,5-a]pyridine and indolizine core unit widely spread in natural products,pharmaceuticals and photoelectric materials.1H-pyrazole-5-carboxides or 1H-pyrrole-2-carboxides were used as substrates to react with(E)-4-bromobut-2-enenitrile under weak base condition,the reaction underwent an intermolecular nucleophilic substitution,deprotonation,electron transfer,intermolecular nucleophilic addition and water elimination aromatization successively.2-and 2,4-substituted 5-cyanopyrazolo[1,5-a]pyridines or 2-and 2,3-substituted 7-cyanoindolizines were conveniently constructed under mild conditions.It provided a simple way to introduce a nitrile group in a conjugated ring which is a promising group in photoelectric field and redecorated potential.Moreover,part of 2,4-disubstituted pyrazolo[1,5-a]pyridines present intense blue fluorescence not only in dilute solution but also in solid state.Besides,the absolute fluorescence quantum yield of 2-(4-fluorophenyl)-4-phenylpyrazolo[1,5-a]pyridine-5-carbonitrile was 0.95,which can be used as promising blue emissive material.
Keywords/Search Tags:tandem reaction, relay catalysis, ? acid metal catalyst, ? acid metal catalyst, nitrogen heterocyclic
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