钯催化的分子内Wacker-Type反应制备1,2-二氢喹啉衍生物
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摘要
1,2-二氢喹啉骨架结构在合成中间体和药物分子中具有广泛的应用。以邻位有端位烯烃取代的苯胺化合物为底物,应用过渡金属钯催化的Wacker-type反应及烯烃的异构化过程合成了一系列1,2-二氢喹啉衍生物。对苯环上不同位置或不同基团取代的底物,反应都可以顺利进行,而且对大部分底物都可以高产率得到相应的1,2-二氢喹啉产物。
1,2-Dihydroquinolines,as the important structural motifs,have been broadly applied in synthetic intermediates and pharmaceuticals. Many synthetic methods for the preparation of 1,2-dihydroquinolines have been reported over the past few years.Recently,following the rapid development of organometallic chemistry,the metal-catalyzed functionalization of alkenes has gradually become the research focus of organic synthesis methodology,and the method was also applied in the synthesis of 1,2-dihydroquinolines.In this work,a method involving the Pd-catalyzed Wacker-type reaction and isomerization of alkene was developed to prepare a series of 1,2-dihydroquinoline derivatives.In the exploration and optimization of the reaction conditions,N,N-dimethylacetamide(DMA)was found to be the best solvent and palladium acetate(Pd(OAc)2)was the best catalyst for our reactions.Then different additives(such as ligand,bases,acids and salts)were added to further optimize the reactions.The results show that pyridine or some ionic salts can inhibit the side reactions effectively,and 1,2-dihydroquinolines were prepared selectively.Among the ionic salts,sodium bromide(NaBr)was the best additive,therefore the amount of NaBr and reaction temperature were also optimized followed by the determination of the final standard conditions.Using NaBr at 40 ℃,the product was obtained in 94% yield for the standard substrate.The reactions proceeded smoothly for different substrates at the optimized standard conditions for both substrates bearing substituent groups at different positions on the benzene ring and substrates bearing different substituent groups.The yields were moderate for 3-substituted substrates,which may be due to the steric effect.For other substrates,the corresponding 1,2-dihydroquinolines can be obtained in high yields.The reaction mechanism was also proposed that an aryl-fused six-membered ring was formed firstly and then alkene was isomerized to obtain the 1,2-dihydroquinolines in the presence of palladiumhydrogen species.The released Pd was oxidized to Pd(Ⅱ)in the presence of benzoquinone(BQ)and oxygen to continue to the next catalytic cycle.
1,2-Dihydroquinolines,as the important structural motifs,have been broadly applied in synthetic intermediates and pharmaceuticals. Many synthetic methods for the preparation of 1,2-dihydroquinolines have been reported over the past few years.Recently,following the rapid development of organometallic chemistry,the metal-catalyzed functionalization of alkenes has gradually become the research focus of organic synthesis methodology,and the method was also applied in the synthesis of 1,2-dihydroquinolines.In this work,a method involving the Pd-catalyzed Wacker-type reaction and isomerization of alkene was developed to prepare a series of 1,2-dihydroquinoline derivatives.In the exploration and optimization of the reaction conditions,N,N-dimethylacetamide(DMA)was found to be the best solvent and palladium acetate(Pd(OAc)2)was the best catalyst for our reactions.Then different additives(such as ligand,bases,acids and salts)were added to further optimize the reactions.The results show that pyridine or some ionic salts can inhibit the side reactions effectively,and 1,2-dihydroquinolines were prepared selectively.Among the ionic salts,sodium bromide(NaBr)was the best additive,therefore the amount of NaBr and reaction temperature were also optimized followed by the determination of the final standard conditions.Using NaBr at 40 ℃,the product was obtained in 94% yield for the standard substrate.The reactions proceeded smoothly for different substrates at the optimized standard conditions for both substrates bearing substituent groups at different positions on the benzene ring and substrates bearing different substituent groups.The yields were moderate for 3-substituted substrates,which may be due to the steric effect.For other substrates,the corresponding 1,2-dihydroquinolines can be obtained in high yields.The reaction mechanism was also proposed that an aryl-fused six-membered ring was formed firstly and then alkene was isomerized to obtain the 1,2-dihydroquinolines in the presence of palladiumhydrogen species.The released Pd was oxidized to Pd(Ⅱ)in the presence of benzoquinone(BQ)and oxygen to continue to the next catalytic cycle.
引文
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[6] RANU B C,HAJRA A,DEY S S,et al.Efficient microwave-assisted synthesis of quinolines and dihydroquinolines under solvent-free conditions[J].Tetrahedron,2003,59(6):813-819.
[7] HU X Y,ZHANG J C, WEI W,et al.Brnsted acid(HNO3)-catalyzed tandem reaction ofα-ketoesters and arylamines:Efficient synthesis of 1,2-dihydroquinoline derivatives[J].Tetrahedron Letters,2011,52(22):2903-2905.
[8] GUSAROVA N K,VOLKOV P A,IVANOVA N I,et al.One-pot regio-and stereoselective synthesis of tertiary phosphine chalcogenides with(E)-N-ethenyl-1,2-dihydroquinoline functionalities[J].Tetrahedron Letters,2016,57(33):3776-3780.
[9] LYU S W,ZHU Y Z,MA X G,et al.What happens when the terminal aromatization is blocked?Construction of1,2-dihydroquinoline derivatives by sp3 C—H bond oxidation of N-arylalaninates[J].Advanced Synthesis&Catalysis,2016,358(7):1004-1010.
[10] THEERALADANON C, ARISAWA M, NISHIDA A,et al.A novel synthesis of substituted quinolines using ringclosing metathesis(RCM):Its application to the synthesis of key intermediates for anti-malarial agents[J].Tetrahedron,2004,60(13):3017-3035.
[11] WILLIAMSON N M,WARD A D.The preparation and some chemistry of 2,2-dimethyl-1,2-dihydroquino lones[J].Tetrahedron,2005,61(1):155-165.
[12] LUO Y M,LI Z G,LI C J.A silver-catalyzed domino route toward 1,2-dihydro quinoline derivatives from simple anilines and alkynes[J].Organic Letters,2005,7(13):2675-2678.
[13] YI C S,YUN S Y,GUZEI L A.Catalytic synthesis of tricyclic quinoline derivatives from the regioselective hydroamination and C—H bond activation reaction of benzocyclic amines and alkynes[J].Journal of the American Chemical Society,2005,127(16):5782-5783.
[14] YI C S,YUN S Y.Scope and mechanistic study of the ruthenium-catalyzed ortho-C—H bond activation and cyclization reactions of arylamines with terminal alkynes[J].Journal of the American Chemical Society,2005,127(48):17000-17006.
[15] LIU X Y,DING P,HUANG J S,et al.Synthesis of substituted 1,2-dihydroquinolines and quinolines from aromatic amines and alkynes by gold(I)-catalyzed tandem hydroamination hydroarylation under microwave-assisted conditions[J].Organic Letters,2007,9(14):2645-2648.
[16] XIA G Q,HAN X L,LU X Y.Palladium(Ⅱ)-catalyzed cyclization reaction of 2-(alk-2’-ynyloxy)benzonitriles or2-(alk-2’-ynylamino)benzonitriles:Afacilewayto2H-chromene and 1,2-dihydroquinoline derivatives[J].Advanced Synthesis&Catalysis,2012,354(14),2701-2705.
[17]罗倩,谢永新,陈朝阳,等.亲电碘环化反应合成双碘代苯并吡喃衍生物和双碘代1,2-二氢喹啉衍生物[J].有机化学,2014,34(12):2537-2542.
[18]刘冬,郭婷婷,王伟平,等.喹啉并吡咯烷和二氢喹啉并吡咯烷衍生物的合成及Kv2.1抑制活性评价[J].药学学报,2016,51(5):762-769.
[19]王道林,石晓策,董哲,等.分子内Povarov反应合成香豆素并[4,3-b]喹啉类化合物[J].化学研究与应用,2016,28(5):700-706.
[20] QIU Y F,SONG X R,LI M,et al.BF3·OEt2-AgSCF3mediated trifluoromethylthiolation/cascade cyclization of propynols:Synthesis of 4-((trifluoromethyl)thio)-2H-chromene and 4-((trifluoromethyl)thio)-1,2-dihydroquinoline derivatives[J].Organic Letters,2016,18(7):1514-1517.
[21] GIORGI P D,MIEDZIAK P J,EDWARDS J K,et al.Bicatalytic multistep reactions en route to the one-pot total synthesis of complex molecules:Easy access to chromene and 1,2-dihydroquinoline derivatives from simple substrates[J].ChemCatChem,2017,9(1):70-75.
[22] STAHL S S.Palladium oxidase catalysis:Selective oxidation of organic chemicals by direct dioxygen-coupled turnover[J].Angewandte Chemie International Edition,2004,43(26):3400-3420.
[23] SIGMAN M S,SCHULTZ M J.The renaissance of palladium(Ⅱ)-catalyzed oxidation chemistry[J].Organic&Biomolecular Chemistry,2004,2(18):2551-2554.
[24] BECCALLI E M,BROGGINI G,MARTINELLI M,et al.C—C,C—O,C—N bond formation on sp2 carbon by Pd(Ⅱ)-catalyzed reactions involving oxidant agents[J].Chemical Reviews,2007,107(11):5318-5365.
[25] MCDONALD R I,LIU G S,Stahl S S.Palladium(Ⅱ)-catalyzed alkene functionalization via nucleopalladation:Stereochemical pathways and enantioselective catalytic applications[J].Chemical Reviews,2011,111(4):2981-3019.
[26] ZHANG Y J,WANG F J,ZHANG W B.Chelation-induced axially chiral palladium complex system with tetraoxazoline ligands for highly enantioselective Wacker-type cyclization[J].The Journal of Organic Chemistry,2007,72(24):9208-9213.
[27] JIANG F,WU Z X,ZHANG W B.Pd-catalyzed asymmetric aza-Wacker-type cyclization reaction of olefinic tosylamides[J].Tetrahedron Letters,2010,51(23):5124-5126.
[28] HEGEDUS L S,ALLEN G F,BOZELL J J,et al.Palladium-assisted intramolecular amination of olefins.Synthesis of nitrogen heterocycles[J].Journal of the American Chemical Society,1978,100(18):5800-5807.
[29] LAROCK R C,HIGHTOWER T R,HASVOLD L A,et al.Palladium(Ⅱ)-catalyzed cyclization of olefinic tosylamides[J].Journal of Organic Chemistry,1996,61(11):3584-3585.
[30] KOU X Z,LI Y,WU L,et al.Palladium-catalyzed aerobic aminooxygenation of alkenes for preparation of isoindolinones[J].Organic Letters,2015,17(22):5566-5569.
[31] YANG G Q,SHEN C R,ZHANG W B.An asymmetric aerobic aza-Wacker-type cyclization:synthesis of isoindolinones bearing tetrasubstituted carbon stereocenters[J]. Angewandte Chemie International Edition,2012,51(36):9141-9145.
[32] LIU Q C,WEN K,ZHANG Z F,et al.Pd(Ⅱ)-catalyzed asymmetric Wacker-type cyclization for the preparation of2-vinylchroman derivatives with biphenyl tetraoxazoline ligands[J].Tetrahedron,2012,68(26):5209-5215.
[33] XU C R,WU Z X,CHEN J Z,et al.Palladium(Ⅱ)-catalyzed aerobic intramolecular allylic C-H activation for the synthesis of indolines[J].Tetrahedron,2017,73(14):1904-1910.
[2] YAMADA N,KADOWAKI S,TAKAHASHI K,et al.MY-1250,a major metabolite of the anti-allergic drug repirinast,induces phosphorylation of a 78-kDa protein in rat mast cells[J].Biochemical Pharmacology,1992,44(6):1211-1213.
[3] NESTEROVA I N,ALEKSEEVA L M,GOLOVIRA S M,et al.Synthesis and pharmacological activity of derivatives of5-(dimethylamino)pyrano[3,2-c]quinolin-2-ones[J].Zhurnal Prikladnoi Khimii,1995,29(2):31-34.
[4] PAL S,DURGADAS S,NALLAPATI S B,et al.Novel1-alkynyl substituted 1,2-dihydro quinoline derivatives from nimesulide(and their 2-oxo analogues):A new strategy to identify inhibitors of PDE4B[J]. Bioorganic Medicinal Chemistry Letters,2011,21(21):6573-6576.
[5] ARDUINI A,BIGI F,CASIRAGHI G,et al.Synthesis of2,4-diphenyl-2-methyl-1,2-dihydro quinolines from anilines and phenylacetylene[J].Synthesis,1981,12(12):975-977.
[6] RANU B C,HAJRA A,DEY S S,et al.Efficient microwave-assisted synthesis of quinolines and dihydroquinolines under solvent-free conditions[J].Tetrahedron,2003,59(6):813-819.
[7] HU X Y,ZHANG J C, WEI W,et al.Brnsted acid(HNO3)-catalyzed tandem reaction ofα-ketoesters and arylamines:Efficient synthesis of 1,2-dihydroquinoline derivatives[J].Tetrahedron Letters,2011,52(22):2903-2905.
[8] GUSAROVA N K,VOLKOV P A,IVANOVA N I,et al.One-pot regio-and stereoselective synthesis of tertiary phosphine chalcogenides with(E)-N-ethenyl-1,2-dihydroquinoline functionalities[J].Tetrahedron Letters,2016,57(33):3776-3780.
[9] LYU S W,ZHU Y Z,MA X G,et al.What happens when the terminal aromatization is blocked?Construction of1,2-dihydroquinoline derivatives by sp3 C—H bond oxidation of N-arylalaninates[J].Advanced Synthesis&Catalysis,2016,358(7):1004-1010.
[10] THEERALADANON C, ARISAWA M, NISHIDA A,et al.A novel synthesis of substituted quinolines using ringclosing metathesis(RCM):Its application to the synthesis of key intermediates for anti-malarial agents[J].Tetrahedron,2004,60(13):3017-3035.
[11] WILLIAMSON N M,WARD A D.The preparation and some chemistry of 2,2-dimethyl-1,2-dihydroquino lones[J].Tetrahedron,2005,61(1):155-165.
[12] LUO Y M,LI Z G,LI C J.A silver-catalyzed domino route toward 1,2-dihydro quinoline derivatives from simple anilines and alkynes[J].Organic Letters,2005,7(13):2675-2678.
[13] YI C S,YUN S Y,GUZEI L A.Catalytic synthesis of tricyclic quinoline derivatives from the regioselective hydroamination and C—H bond activation reaction of benzocyclic amines and alkynes[J].Journal of the American Chemical Society,2005,127(16):5782-5783.
[14] YI C S,YUN S Y.Scope and mechanistic study of the ruthenium-catalyzed ortho-C—H bond activation and cyclization reactions of arylamines with terminal alkynes[J].Journal of the American Chemical Society,2005,127(48):17000-17006.
[15] LIU X Y,DING P,HUANG J S,et al.Synthesis of substituted 1,2-dihydroquinolines and quinolines from aromatic amines and alkynes by gold(I)-catalyzed tandem hydroamination hydroarylation under microwave-assisted conditions[J].Organic Letters,2007,9(14):2645-2648.
[16] XIA G Q,HAN X L,LU X Y.Palladium(Ⅱ)-catalyzed cyclization reaction of 2-(alk-2’-ynyloxy)benzonitriles or2-(alk-2’-ynylamino)benzonitriles:Afacilewayto2H-chromene and 1,2-dihydroquinoline derivatives[J].Advanced Synthesis&Catalysis,2012,354(14),2701-2705.
[17]罗倩,谢永新,陈朝阳,等.亲电碘环化反应合成双碘代苯并吡喃衍生物和双碘代1,2-二氢喹啉衍生物[J].有机化学,2014,34(12):2537-2542.
[18]刘冬,郭婷婷,王伟平,等.喹啉并吡咯烷和二氢喹啉并吡咯烷衍生物的合成及Kv2.1抑制活性评价[J].药学学报,2016,51(5):762-769.
[19]王道林,石晓策,董哲,等.分子内Povarov反应合成香豆素并[4,3-b]喹啉类化合物[J].化学研究与应用,2016,28(5):700-706.
[20] QIU Y F,SONG X R,LI M,et al.BF3·OEt2-AgSCF3mediated trifluoromethylthiolation/cascade cyclization of propynols:Synthesis of 4-((trifluoromethyl)thio)-2H-chromene and 4-((trifluoromethyl)thio)-1,2-dihydroquinoline derivatives[J].Organic Letters,2016,18(7):1514-1517.
[21] GIORGI P D,MIEDZIAK P J,EDWARDS J K,et al.Bicatalytic multistep reactions en route to the one-pot total synthesis of complex molecules:Easy access to chromene and 1,2-dihydroquinoline derivatives from simple substrates[J].ChemCatChem,2017,9(1):70-75.
[22] STAHL S S.Palladium oxidase catalysis:Selective oxidation of organic chemicals by direct dioxygen-coupled turnover[J].Angewandte Chemie International Edition,2004,43(26):3400-3420.
[23] SIGMAN M S,SCHULTZ M J.The renaissance of palladium(Ⅱ)-catalyzed oxidation chemistry[J].Organic&Biomolecular Chemistry,2004,2(18):2551-2554.
[24] BECCALLI E M,BROGGINI G,MARTINELLI M,et al.C—C,C—O,C—N bond formation on sp2 carbon by Pd(Ⅱ)-catalyzed reactions involving oxidant agents[J].Chemical Reviews,2007,107(11):5318-5365.
[25] MCDONALD R I,LIU G S,Stahl S S.Palladium(Ⅱ)-catalyzed alkene functionalization via nucleopalladation:Stereochemical pathways and enantioselective catalytic applications[J].Chemical Reviews,2011,111(4):2981-3019.
[26] ZHANG Y J,WANG F J,ZHANG W B.Chelation-induced axially chiral palladium complex system with tetraoxazoline ligands for highly enantioselective Wacker-type cyclization[J].The Journal of Organic Chemistry,2007,72(24):9208-9213.
[27] JIANG F,WU Z X,ZHANG W B.Pd-catalyzed asymmetric aza-Wacker-type cyclization reaction of olefinic tosylamides[J].Tetrahedron Letters,2010,51(23):5124-5126.
[28] HEGEDUS L S,ALLEN G F,BOZELL J J,et al.Palladium-assisted intramolecular amination of olefins.Synthesis of nitrogen heterocycles[J].Journal of the American Chemical Society,1978,100(18):5800-5807.
[29] LAROCK R C,HIGHTOWER T R,HASVOLD L A,et al.Palladium(Ⅱ)-catalyzed cyclization of olefinic tosylamides[J].Journal of Organic Chemistry,1996,61(11):3584-3585.
[30] KOU X Z,LI Y,WU L,et al.Palladium-catalyzed aerobic aminooxygenation of alkenes for preparation of isoindolinones[J].Organic Letters,2015,17(22):5566-5569.
[31] YANG G Q,SHEN C R,ZHANG W B.An asymmetric aerobic aza-Wacker-type cyclization:synthesis of isoindolinones bearing tetrasubstituted carbon stereocenters[J]. Angewandte Chemie International Edition,2012,51(36):9141-9145.
[32] LIU Q C,WEN K,ZHANG Z F,et al.Pd(Ⅱ)-catalyzed asymmetric Wacker-type cyclization for the preparation of2-vinylchroman derivatives with biphenyl tetraoxazoline ligands[J].Tetrahedron,2012,68(26):5209-5215.
[33] XU C R,WU Z X,CHEN J Z,et al.Palladium(Ⅱ)-catalyzed aerobic intramolecular allylic C-H activation for the synthesis of indolines[J].Tetrahedron,2017,73(14):1904-1910.