利用串联反应合成异喹啉及吲哚类化合物
|
摘要
多样性导向合成是化学合成思维上的一个突破,是化学生物学、组合化学和药物化学相互交叉和渗透的产物,串联反应作为多样性导向合成的重要方法之一,具有操作简单、资源利用率高和原子经济性等特点,它可以大大节省操作步骤,同时构建结构多样的化合物库。与此同时,异喹啉和吲哚骨架是许多天然产物的核心结构单元,广泛存在于天然产物和药物分子中,通常具有广泛的生物活性。基于此,本论文主要研究了通过串联反应来合成含异喹啉和吲哚骨架等含氮杂环化合物的方法。
本论文共分为五个部分。
第一章,简单介绍了多样性导向合成的发展以及在构建类天然产物化合物库方面的应用。
第二章,发展了邻炔基苯甲醛腙与丁炔二酸二甲酯或端基炔之间的串联反应。研究发现邻炔基苯甲醛腙与丁炔二酸二甲酯在三氟甲磺酸银的催化下或者在溴的亲电环化下,产物为含异喹啉结构的叶立德化合物,而在碘的亲电环化下,产物含H-吡唑并[1,5-a]异喹啉类化合物;邻炔基苯甲醛腙与端基炔烃在AgOTf的催化下或者在亲电环化下反应产物均为含H-吡唑并[1,5-a]异喹啉骨架的化合物；研究还发现得到的带有卤素的此类化合物还可以通过钯催化的偶联反应来实现其骨架的多官能团化。
第三章,实现了N-杂环卡宾和三氟甲磺酸银共同催化下的2-炔基苯甲醛腙与α,β-不饱和醛以及甲醇的三组分反应,得到了一系列1,2-二氢异喹啉衍生物;基于此结果,随后又发展了2-炔基苯甲醛、对甲苯磺酰肼与α,β-不饱和醛酮以及醇类的四组分反应,合成了H-吡唑并[1,5-a]异喹啉类的化合物；与此同时,我们还发展了亲电试剂存在下的三组分反应合成了带卤素的H-吡唑并[1,5-a]异喹啉类化合物,并通过后续的钯催化的偶联反应实现了其骨架的官能团化。初步的生物活性测试结果表明,部分化合物对于CDC25B、TC-PTP以及PTPIB表现出了较好的抑制活性。
第四章,发展了2-炔基苯甲醛肟与异腈在三氟甲磺酸银和三氟甲磺酸铋的共同催化下,经串联重排反应一锅法合成了1-甲酰氨基异喹啉类化合物；研究发现该反应也可以在溴或碘的亲电环化作用下,经三氟甲磺酸铋催化得到相应的带卤素的1-甲酰氨基异喹啉。
第五章,发展了一例一价铜催化的三组分反应来合成多取代吲哚衍生物。该反应对底物官能团的兼容性良好,能在温和的条件下一步构建多取代的吲哚骨化合物。初步的生物活性测试结果表明,部分化合物对于HCT-116具有一定的抑制活性。
Diversity-oriented synthesis (DOS) is a breakthrough in the thought of chemical synthesis, which is overlapped and penetrated by chemical biology, combinatorial chemistry and medicinal chemistry. Among the strategies utilized in diversity-oriented synthesis, tandem reaction is highly characterized by simple operation, outstanding resource utilization and atom economy; which can greatly reduce the operation procedures as well as build up the structural diversity of compounds. Meanwhile, it is well-known that the isoquinoline and indole skeletons are found in many natural products and pharmaceuticals that exhibit remarkable biological activities. This thesis is mainly focused on the tandem reactions for the generation of isoquinoline and indole derivatives.
The dissertation is divided into five parts.
Chapter one introduces the development of diversity oriented synthesis briefly.
In chapter two, tandem reactions of N'-(2-alkynyl-benzylidene)hydrazides with dimethyl acetylenedicarboxylate (DMAD) or terminal alkynes are described. The unexpected isoquinoline-based azomethine ylides were obtained when the reaction of N'-(2-alkynylbenzylidene)hydrazide with DMAD was catalyzed by AgOTf or in the presence of bromine, while the fused 1,2-dihydroisoquinolines were afforded when iodine was employed in the above tandem reactions. Additionally, N'-(2-alkynylbenzylidene)hydrazide reacted with terminal alkynes catalyzed by AgOTf or in the presence of electrophile leading to H-pyrazolo[5,1-a]isoquinoline in good yields. The halide-containing products could be further elaborated by palladium-catalyzed cross-coupling reactions.
In chapter three, a three-component reaction of N'-(2-alkynylbenzylidene)-hydrazide,α,β-unsaturated aldehyde, and MeOH co-catalydzed by AgOTf and N-heterocyclic carbene (NHC) is presented, which produces 2-amino-1,2-dihydroiso-quinolines with high efficiency. Subsequently, based on the above results, a multicomponent reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, alcohol, and a,β-unsaturated aldehyde or ketone catalyzed by AgOTf or in the presence of an electrophile is discovered. Preliminary biological assays showed that some of these compounds display promising activities as CDC25B inhibitor, TC-PTP inhibitor, and PTP1B inhibitor.
In chapter four, an efficient tandem reaction of 2-alkynylbenzaldoximes with isocyanides co-catalyzed by AgOTf and Bi(OTf)3 is illustrated, which affords the unexpected N-(isoquinolin-1-yl)formamide in good to excellent yields. The iodo-or bromo-containing products can be obtained as well by variation of the reaction conditions, which may undergo further elaboration via known palladium chemistry.
The last chapter describes a Copper(Ⅰ)-catalyzed three-component reaction of 2-ethynylaniline, sulfonyl azide, and nitroolefin. The reaction generates functionalized indoles in good yields and proceeds smoothly under mild conditions. Furthermore, some hits as HCT-116 inhibitor are found from the preliminary biological screening.
本论文共分为五个部分。
第一章,简单介绍了多样性导向合成的发展以及在构建类天然产物化合物库方面的应用。
第二章,发展了邻炔基苯甲醛腙与丁炔二酸二甲酯或端基炔之间的串联反应。研究发现邻炔基苯甲醛腙与丁炔二酸二甲酯在三氟甲磺酸银的催化下或者在溴的亲电环化下,产物为含异喹啉结构的叶立德化合物,而在碘的亲电环化下,产物含H-吡唑并[1,5-a]异喹啉类化合物;邻炔基苯甲醛腙与端基炔烃在AgOTf的催化下或者在亲电环化下反应产物均为含H-吡唑并[1,5-a]异喹啉骨架的化合物；研究还发现得到的带有卤素的此类化合物还可以通过钯催化的偶联反应来实现其骨架的多官能团化。
第三章,实现了N-杂环卡宾和三氟甲磺酸银共同催化下的2-炔基苯甲醛腙与α,β-不饱和醛以及甲醇的三组分反应,得到了一系列1,2-二氢异喹啉衍生物;基于此结果,随后又发展了2-炔基苯甲醛、对甲苯磺酰肼与α,β-不饱和醛酮以及醇类的四组分反应,合成了H-吡唑并[1,5-a]异喹啉类的化合物；与此同时,我们还发展了亲电试剂存在下的三组分反应合成了带卤素的H-吡唑并[1,5-a]异喹啉类化合物,并通过后续的钯催化的偶联反应实现了其骨架的官能团化。初步的生物活性测试结果表明,部分化合物对于CDC25B、TC-PTP以及PTPIB表现出了较好的抑制活性。
第四章,发展了2-炔基苯甲醛肟与异腈在三氟甲磺酸银和三氟甲磺酸铋的共同催化下,经串联重排反应一锅法合成了1-甲酰氨基异喹啉类化合物；研究发现该反应也可以在溴或碘的亲电环化作用下,经三氟甲磺酸铋催化得到相应的带卤素的1-甲酰氨基异喹啉。
第五章,发展了一例一价铜催化的三组分反应来合成多取代吲哚衍生物。该反应对底物官能团的兼容性良好,能在温和的条件下一步构建多取代的吲哚骨化合物。初步的生物活性测试结果表明,部分化合物对于HCT-116具有一定的抑制活性。
Diversity-oriented synthesis (DOS) is a breakthrough in the thought of chemical synthesis, which is overlapped and penetrated by chemical biology, combinatorial chemistry and medicinal chemistry. Among the strategies utilized in diversity-oriented synthesis, tandem reaction is highly characterized by simple operation, outstanding resource utilization and atom economy; which can greatly reduce the operation procedures as well as build up the structural diversity of compounds. Meanwhile, it is well-known that the isoquinoline and indole skeletons are found in many natural products and pharmaceuticals that exhibit remarkable biological activities. This thesis is mainly focused on the tandem reactions for the generation of isoquinoline and indole derivatives.
The dissertation is divided into five parts.
Chapter one introduces the development of diversity oriented synthesis briefly.
In chapter two, tandem reactions of N'-(2-alkynyl-benzylidene)hydrazides with dimethyl acetylenedicarboxylate (DMAD) or terminal alkynes are described. The unexpected isoquinoline-based azomethine ylides were obtained when the reaction of N'-(2-alkynylbenzylidene)hydrazide with DMAD was catalyzed by AgOTf or in the presence of bromine, while the fused 1,2-dihydroisoquinolines were afforded when iodine was employed in the above tandem reactions. Additionally, N'-(2-alkynylbenzylidene)hydrazide reacted with terminal alkynes catalyzed by AgOTf or in the presence of electrophile leading to H-pyrazolo[5,1-a]isoquinoline in good yields. The halide-containing products could be further elaborated by palladium-catalyzed cross-coupling reactions.
In chapter three, a three-component reaction of N'-(2-alkynylbenzylidene)-hydrazide,α,β-unsaturated aldehyde, and MeOH co-catalydzed by AgOTf and N-heterocyclic carbene (NHC) is presented, which produces 2-amino-1,2-dihydroiso-quinolines with high efficiency. Subsequently, based on the above results, a multicomponent reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, alcohol, and a,β-unsaturated aldehyde or ketone catalyzed by AgOTf or in the presence of an electrophile is discovered. Preliminary biological assays showed that some of these compounds display promising activities as CDC25B inhibitor, TC-PTP inhibitor, and PTP1B inhibitor.
In chapter four, an efficient tandem reaction of 2-alkynylbenzaldoximes with isocyanides co-catalyzed by AgOTf and Bi(OTf)3 is illustrated, which affords the unexpected N-(isoquinolin-1-yl)formamide in good to excellent yields. The iodo-or bromo-containing products can be obtained as well by variation of the reaction conditions, which may undergo further elaboration via known palladium chemistry.
The last chapter describes a Copper(Ⅰ)-catalyzed three-component reaction of 2-ethynylaniline, sulfonyl azide, and nitroolefin. The reaction generates functionalized indoles in good yields and proceeds smoothly under mild conditions. Furthermore, some hits as HCT-116 inhibitor are found from the preliminary biological screening.
引文
[1]Schmitz,R.Pharm.Hist.1985,27,61.
[2]Yang,Z.Progress in Chemistry 2009,21,47.
[3]Nicolaou,K.C.；Sorensen,E.Classic,in Total SYNthesis.Weinheim:VCH Verlagsgellschaft mbH,1996.
[4]Nicolaou,K.；Edmonds,D.；Li,A.；Tria,G Angew.Chem.Int.Ed.2007,46,3942.
[5]Veitch,G.;Beckmann,E.；Burke,B.；Boye r,A.;Ayats,C.；Ley,S.Angew.Chem. Int.Ed.2007,46,7629.
[6](a)Corey,E.J.；Cheng,X.The Logical of Chemical Synthesis.John Wiley & Sons: New York,1995.(b)Corey,E.J.Angew.Chem.Int.Ed.1991,30,455；(c)Corey, E.J.；Wipke,W.T.Science 1969,166,178.
[7]For selected examples on DOS,see:(a)Woo,S.；Squires,N.；Fallis,A.Org.Lett. 1999,1,573.(b)Pelish,H.；Westwood,W.Feng,Y.;Kirchhausen,T.;Shair,M.J. Am.Chem.Soc.2001,123,6740.(c)Kwon,O.;Park,S.；Schreiber,S.L.J.Am. Chem.Soc.2002,124,13402.
[8]Tempest,P.；Armstrong,R.J.Am.Chem.Soc.1997,119,7607.
[9]Fergus,S.;Bender,A.；Spring,D.R.Curr.Opin.Chem.Biol.2005,9,304.
[10]Spring,D.R.Or.Biomol.Chem.2003,1,3867.
[11]Galloway,W.；Bender,A.；Welch,M.;Spring,D.R.Chem.Commum.2009, 2446.
[12]王治永,复旦大学博士学位论文2009.
[13]Corey,E.J.；Cheng,X.-M.The Logic of Chemica1 Synthesis.Wiley,New York, 1989.
[14]Tan,D.；Foley,M.；Stockwell,B.；Shair,M.；Schreiber,S.L.J.Am.Chem.Soc, 1999,121,9073；
[15](a)Li,C.；Liang,S.；Zhang,X.；Xie,Z.；Chen,J.；Wu,Y；Yang,Z.Org.Lett., 2005,7,3709.(b)Li,C.;Wang,C.；Liang,B.;zhang,X.；Deng,L.；Liang,S.； Chen,J.；Wu,Y；Yang,Z.J.Org.Chem.2006,71,6892.
[16]Lee,D.;Sello,J.；Schreiber,S.L.Org.Lett.2000,2,709.
[17](a)Nicolaou,K.；Pfefferkom,J.；Roecker,A.；Cao,G.;Barluenga,S.；Mitchell, H.J.Am.Chem.Soc.2000,122,9939.(b)Nicolaou,K.；Pfefferkom,J.；Mitchell, H.；Roecker,A.；Barluenga,S.；Cao,G.；Affleck,R.；Lillig,J.J.Am.Chem.Soc. 2000,122,9954.(c)Nicolaou,K.；Pfefferkorn,J.；Barluenga,S.；Mitchell,H.； Roecker,A.；Cao,G.J.Am.Chem.Soc.2000,122,9968.
[18]Nicolaou,K.;Pfefferkorn,J.;Schuler,F.;Roecker,A.；Cao,G.;Casida,J.Chem. Biol.2000.7,979.
[19]Nicolaou,K.;Roecker,A.；Barluenga,S.;Pfefferkom,J.;Cao,G.Chembiochem, 2001,2,460.
[20]Tan,D.;Foley,M.；Shair,M.；Schreiber,S.L.J.Am.Chem.Soc.1998,120. 8565.
[21]刘钢,李裕林,南发俊,化学进展,2006,18,734.
[22](a)Sternson,S.M.；Louca,J.B.；Wong,J.C.；Schreiber,S.L.J.Am.Chem.Soc. 2001,123,1740.(b)Wong,J.C.；Sternson,S.M.；Louca,J.B.；Hong,R.； Schreiber,S.L.Chem.Biol.2004,11,1279.
[23]Meseguer,B.；Alonso-Diaz,D.；Griebenow,N.;Herget,T.；Waldmann,H. Angew.Chem.,Int.Ed.1999,38,2902.
[24]Stavenger,R.;Schreiber,S.Angew.Chem.Int.Ed.2001,40,3417.
[25]Clardy,J.；Walsh,C.Nature 2004,432,829.
[26]Comer,E.；Rohan,E.；Porco,D.Org Lett.2007,9,2123.
[27]Jason,K.；Sello,P.；Lee,A.;Schreiber,S.Org.Lett.2003,5,4125.
[28]Dandapani,S.;Marcaurelle,L.Curr.Opin.In Chem.Bio.2010,14,362.
[29]Maclean,D.；Baldwin,J.；Ivanov,V.Comb.Chem.2000,2,562.
[30]Biggs-Houck,J.；Younai,A.；Shaw,J.Curr.Opin.In Chem.Bio.2010,14,371.
[1](a)Chrzanowska,M.:Rozwadowska,M D.Chem.Rev.2004,104.3341.(b) Rozwadowska,M.D.Heterocycles 1994,39,903.
[2](a)Bailly,C.;Curr.Med.Chem.Anti-Cancer Agents 2004,4,363.(b)E.Marco, E.；Laine,W.;Tardy,C.;Lansiaux,A.;Iwao,M.；Ishibashi,F.；Bailly,C.；Gago,F. J.Med Chem.,2005,48,3796.(c)Kluza,J.；Gallego,M.;Loyens,A.；Beauvillain, J.；Fernandez,S.;Cuevas,C.；Marchetti,P；Bailly,C.Cancer Res.2006,66,3177.
[3]Su,S.；J.A.Porco,Jr. J.Am.Chem.Soc.2007,129,7744 and references cited therein.
[4](a)Lober,S.；Hubner,H.；Gmeiner,P.Bioorg.Med. Chem.Lett.2002,12,2377.(b) Hasen,J.；Weis,J.；Suzdak,P；Eskesen,K.Bioorg.Med. Chem.Lett.1994,4, 695.
[5](a)Johns,B.A.；Gudmundsson,K.S.；Turner,E.M.；Allen,S.H.；Samano,V A.； Ray,J.A.；Freeman,G A.；Boyd,F. L.,Jr.;Sexton,C.J.;Selleseth,D.W.;Creech, K.L.；Moniri,K.R.Bioorg. Med Chem.2005,13,2397.(b)Akahane,A.； Katayama,H.；Mitsunaga,T.J.Med. Chem.1999,42,779.
[6](a)Meyers,A.；Kung,D.,J.Am.Chem.Soc.1999,121,10828.(b)Kiselyov,A.； Armstrong R.Tetrahedron Lett.1997,38,6163.
[7](a)Yoshinori,T.；Yuichi,I.；Tomoko,M.；Chizuko,K.；Akira,H.J.Heterocyclic Chem.1990,27,263；(b)Yoshinori,T.；Yuichi,I.；Akira,H. Heterocycles.1988, 27,2345.
[8]Potts,K.；Youzwak,H.；Zurawel,S,Jr.J.Org.Chem.1980,45,90.
[9]Harju,K.；Kylanlahti,I.；Paananen,T.；Polamo,M.;Nielsen,J.；Yli-Kauhaluoma,J. J.Comb.Chem.2006,8344.
[10]Kobayashi,M.；Tanabe,M.;Kondo,K.；Aoyama,T.Tetrahedron Lett. 2006,47, 1469.
[11]Kobayashi,M.;Kondo,K.；Aoyama,T.Tetrahedron Lett.2007,48,7019.
[12]Mousseau,J.；Fortier,A.；Charette,A.Org.Lett.2010,12,516.
[13](a)Ridchard N.B.；Anthony G.C.；Patrick,M.；Desmond,C.；Burke,Luke A._B. J.Chem.Soc.Perkin Trans.1,2001,1391.(b)Richard N.B.；Anthony G.C. William J.C.；Luke A.B.J.Chem.Soc.Perkin Trans.2,2002,1807.
[14]Wender,P. A.Chem.Rev.1996,96,1.
[15](a)Tamura,Y；Miki,Y；Nishikawa,Y；Ikeda,M.J.Heterocyclic Chem.1976, 13,317.(b)Tamura,Y；Miki,Y；Hayashi,H.；Sumida,Y；Ikeda,M.J. Heterocyclic Chem.1977,6,281.
[16]Lemi,T.；Gulec,Ahmet,G.Dyes and Pigments,1990,14,307.
[17]Elender,K.；N6th,H.；Weber,A.；Sauer,J.Thtrahedron 2000,56,5443.
[18](a)Ding,Q.；Wu,J.Adv.Synth.Catal.2008,350,1850.(b)Ding,Q.；Wang,Z.; Wu,J.J.Org.Chem.2009,74,921.(c)Ding,Q.；Wang,Z.;Wu,J.Tetrahedron Lett.2009,50.198.
[19](a)Coskun,N.；Tuncman,S.Tetrahedron 2006,62,1345.(b)Najera,C. Sansano,J.Curr.Org.Chem.2003,7,1105.
[20]For reviews,see:(a)Larock,R.C.in;Acetylene Chemistry,(Eds.;F.Diederich, P.J.Stang,R.R.Tykwinski,wiley-VCH,Weinheim,2005,pp 51.(b)Alonso,F.； Beletskaya,I.M.Yus,M.Chem.Rev.2004,104,3079.(c)Zeni,G.；Larock,R.C. Chem.Rev.2006,106,4644.
[21]For selected examples,see:(a)Bi,H.;Guo,L.;Duan,X.；Gou,F.;Huang,S.； Liu,X.;；Liang,Y.Org.Lett.2007,9,397.(b)A.Sniady,A.；Wheeler,K.； Dembinski,R Org.Lett.2005,7,1769.(c)Liu,Y.；Song,F.；Cong,L.J.Org. Chem.2005,70,6999.(d)Peng,A.；Ding,Y.Org.Lett.2004,6,1119.
[22]Ding,Q.；Chen,Z.；Yu,X.;Peng,Y.;Wu,J.Tetrahedron Lett.2009,50,340.
[23]Weibel,J.；Blanc,A.；Pale,P.Chem.Rev.2008,108,3149.
[24](a)Pyyko,P.Angew.Chem.Int.Ed.2004,43,4412.(b)Gorin,D.J.；Toste,D. Nature 2007,446,395.
[25]Halbes-Letinois,U.；Pale,P.；Berger,S.J.Org.Chem.2005,70,9185.
[26]Halbes-Letinois,U.；Weibel,J.；Pale,P.Chem.Soc.Rev.2007,36,759.
[27]Kinugasa,M.；Hashimoto,S.,Chem.Soc.,Chem.Commun.1972,466.
[28]Miura,M,;Enna,M.；Okuro,K.；Nomura,M.J.Org.Chem.1995,60,4999.
[29]Stanley,L.;Sibi,M.Chem.Rev.2008,108,2887.
[30]Mahbub,A.；Rebekah E.B.；Tom,C.；Richard J.D.；Karen M.D.；Mara,F. Bioorg.Med.Chem.Lett.2007,17,3463.
[31](a)Shintani,R.；Fu,G.C.J.Am.Chem.Soc.2003,125,10778.(b)Suarez,A.； Downey,C.W.；Fu,G.C.J.Am.Chem.Soc.2005,127,11244.
[32]For selected examples,see:(a)Ding,Q.；Wu,J.Org.Lett.2007,9,4959.(b)Gao, K.；Wu,J.J.Org.Chem.2007,72,8611.(c)Ding,Q.；Ye,Y；Fan,R；Wu,J.J. Org.Chem.2007,72,5439.
[33]Chen,Z.；Yang,X.；Wu,J.Chem.Commun.2009,23,3469.
[1]Tidwell,T.Acc.Chem.Res.1990,23,273.
[2]For recent reviews on NHC-catalyzed reactions,see:(a)Enders,D.；Niemeier,O.; Henseler,A.Chem.Rev.2007,107.5606 and references therein.(b)Enders,D.; Balensiefer,T.Ac.Chem.Res.2004,37,534.(c)Nair,V.;Vellalath,S.；Babu,B. CheM.Soc.Rev.2008,37,2691.
[3]For selected examples,see:(a)Sohn,S.；Rosen,E.；Bode,J.J.Am.Chem.Soc. 2004,126,14370.(b)He,M.；Bode,J.Org.Lett.2005,7,3131.(c)Nair,V.； Vellalath,S.；Poonoth,M.；Suresh,E.J.Am.Chem.Soc.2006,128,8736.(d) Zhao,H.；Foss,F.,Jr.；Breslow,R.J.Am.Chem.Soc.2008,130,12590.(e)Biju, A.;Wurz,N.；Glorius,F.J.Am.Chem.Soc.2010,132,5970.
[4]Zeitle r,K.Angew.Chem.,Int.Ed.2005,44,7506.
[5]Sohn,S.；Rosen,E.；Bode,J.J.Am.Chem.Soc.2004,,26,14370.(b)Burstein,C.； Glorius,F.Angew.Chem.,Int.Ed.2004,43,6205.(c)Burstein,C.；Tschan,S.； Xie,X.；Glorius,F.Synthesis 2006,2418.
[6](a)He,M.；Bode,J.Org.Lett.2005,7,3131.(b)Rommel,M.；Fukuzumi,T.;Bode, J.J.Am.Chem.Soc.2008,130,17266.
[7]He,M.;Struble,J.;Bode,J.J.Am.Chem.Soc.2006,128,8418.
[8]Chiang,P.；Kaeobamrung,J.;Bode,J.J.Am.Chem.Soc.2007,129,3520.
[9](a)He,M.；Bode,J.J.Am.Chem.Soc.2008,130,418.(b)Kaeobamrung,J.；Bode, J.Org.Lett.2009,11,677.
[10](a)Sohn,S.S.；Bode,J.Org.Lett.2005,7,3873.(b)Chan,A.；Scheidt,K.Org. Lett.2005,7,905.
[11](a)Bode,J.；Sohn,S.J.Am.Chem.Soc.2007,129,13798.(b)Vora,H.；Rovis,T. J.Am.Chem.Soc.2007,129,13796.
[12]Seayad,J.；Patra,P.；Zhang,Y.；Ying,J.Org.Lett.2008,10,953.
[13]Bamberger,E.Chem.Ber.1894,1347.
[14]Nai.r,V.；Babu,B.；Vellalath,S.；Varghese,V.Org.Lett.2009,11,2507.
[15]Nair,V.；Sinu,C.；Babu,B.;Varghese,V.；Jose,A.；Suresh,E.Org.Lett.2009, 11,5570.
[16]Li,G.；Dai,L.；You,S.Org.Lett.2009,11,1623.
[17]Chan,A.；Scheidt,K.J.Am.Chem.Soc.2007,129,5334.
[18]Phillips,E.；Reynolds,T.；Scheidt,K.J.Am.Chem.Soc.2008,130,2416.
[19](a)Shao,Z.;Zhang,H.Chem.Soc.Rev.2009,38,2745.(b)Park,Y.;Park,J.;Jun, C.Acc.Chem.Res.2008,41,222.
[20]Yang,T.；Ferrali,A.；Campbell,L.；Dixon,D.Chem.Communn.2008,2923.
[21]Binder,J.;Crone,B.；Haug,T.;Menz,H.；Kirsch,S.Org.Lett.2008,10.1025.
[22]Xu,X.；Zhou,J.;Yang,L.;Hu,W.Chem.Commun.2008,6564.
[23]Ding,Q.；Wu,J.Org.Lett.2007,9,4959.
[24](a)Hintermann,L.Beilstein,Org.Chem.2007,3.22.(b)http://bjoc.beilstein-journals.org/content/3/1/22.
[25]Chen,Z.；Yu,X.;Wu,J.Chem.Commun.2010,46,6356.
[26](a)Phillips,E.；Riedrich,M.；Scheidt,K.J.Am.Chem.Soc.2010,132,13179.(b) Yue,Y.；Yu,X.；Pu,L.Chem.-Eur.J.2009,15,5104.
[27]Yu,X.；Ye,S.；Wu,J.Adv.Synth.Catal.2010,352,2050.
[28]成静,付强,伍钢,中华肿瘤防治杂志,2007,14,872.
[29]For selected examples,see:(a)Frangioni,J.;Beahm,P；Shifrin,V；Jost,C.;Neel, B.Cell 1992,68,545.(b)Woodford-Thomas,T.;Rhodes,J.；Dixon,J.J.Cell Biol. 1992,117,401.(c)Haj,F.;Verveer,P；Squire,A.;Neel,B.；Bastiaens,P Science 2002,295,1708.
[30]For reviews,see:(a)Miyaura,N.Top.Curr.Chem.2002,2,9,11.(b)Suzuki,A. J.Organomet.Chem.1999,576,147.(c)Littke,A.；Fu,G.Angew.Chem.Int.Ed. 2002,41,4176.(d)De Meijere,A.;Diederich,F.Metal-Catalyzed Cross-Coupling Reactions,2nd ed,John Wiley & Sons,Weinheim,Germany,2004.
[1]Lieke,W.Justus Liebigs Ann.Chem.1859,112,316.
[2]For reviiews on isocyanides,see:(a)Lentz,D.Angew.Chem.1994,106,1377; Angew.Chem.Int.Ed.1994,33,1315.(b)Domling,A.Chem.Rev.2006,106,17. (c)Alexander,L.；Armin,de M.Angw.Chem.Int.Ed.2010,49,9094.
[3](a)Malatesta,L.；Bonati,F.Isocyanide Complexes of Metals,Wiley-Interscience, New York,N.Y.1969.(b)Horrocks,W.;Mann,R.Spectrochim.Acta.1963,19, 1375.(c)Malatesta,L.Progr.Inorg.Chem.1959,1,283.
[4](a)H.Eckert,H.；Forster,B.Angew.Chem.Int.Ed.1987,26,1221.(b)Obrecht, R.；Herrmann,R.；Ugi,I.Synthesis 1985,400.(c)Giesemann,G；von Hinrichs, E.;Ugi,I.J.Chem.Res(S),1982,79.
[5]Domling,A.；Ugi,I.Angew.Chem.Int.Ed.2000,39,3168.
[6](a)Passerini,M.Gazz.Chim.Ital.1921,51,126.(b)Baker,R.；Stanonis,D.J.Am. Chem.Soc.1951,73,699.
[7](a)Ugi,I.；Meyr,R.；Fetzer,U.；Steinbruckner,C.Angew.Chem.1959,71,386.(b) Ugi,I.；Steinbruckner,C.Angew.Chem.1960,72,267.
[8](a)Chatani,N.；Mamoru,O.；Tobisu,M.；Ishii,Y.；Murai,S.J.Am.Chem.Soc. 2003,125,7812.(b)Oshita,M.；Tobisu,M.；Yamashita,K.；Chatani,N.J.Am. Chem.Soc.2005,127,761.(c)Oshita,M.；Tobisu,M.；Yamashita,K.；Chatani, N.J.Am.Chem.Soc.2005,127,2363.
[9](a)Bez,G.;Zhao,C.Org.Lett.2003,5,4991.(b)Yoshioka,S.；Oshita,M.； Tobisu,M.；Chatani,N.Org.Lett.2005,7,3697.(c)Tobisu,M.；Kitajima,A.； Yoshioka,S.；Hyodo,I.；Oshita,M.；Chatani,N.J.Am.Chem.Soc.2007,129, 11431.
[10]Tobisu,M.；Ito,S.；Kitajima,A.；Chatani,N.Org.Lett.2008,10,5223.
[11](a)Tobisu,M.；Yamaguchi,S.；Chatani,N.Org.Lett.2007,9,3351.(b)Tobisu, M.；Imoto,S.；Ito,S.；Chatani,N.J.Org.Chem.2010,75,4835.
[12](a)Campeau,L.；Rousseaux,S.；Fagnou,K,J.Am.Chem.Soc.2005,127,18020. (b)Schipper,D.；El-Salfiti,M.；Whipp,C.；Fagnou,K.Tetrahedron 2009,4977.
[13]Campeau,L.；Schipper,D.；Fagnou,K.J.Am.Chem.Soc.2008,130,3266.
[14]Kanyiva,K.；Nakao,Y.；Hiyama,T.Angew.Chem.Int.Ed.2007,46,8872.
[15]Cho,S.；Hwang,S.；Chang,S.J.Am.Chem.Soc.2008,130,9254.
[16]Xi,P.；Yang,F.；Qin,S.；Zhao,D.；Lan,J.；Gao,G.;Hu,C.；You,J.Am.Chem. Soc.2010,132,1822.
[17]Kang,Y.;Sun,X.；Tang,Y.Angew.Int.Ed.2007,46,3918.
[18](a)Sims,J.;Houk,N.J.Am.Chem.Soc.1973,95,5798.(b)Jensen,K.； Roberson,M.；J6rgensen,K.J.Org.Chem.2000,65,9080.
[19](a)Yeom,H.;Lee,J.;Shin,S.Angew.Chem.Int.Ed.2008,47.7040.(b)Yeom, H.；Lee,Y.；Jeong,J.；So,E.；Hwang,S.；Lee,J.；Lee,S.；Shin,S.Angew.Chem. Int.Ed.2010,49,1611.
[20](a)Ding,Q.；Wu,J.Adv.Synth.Catal.2008,350.1850.(b)Ding,Q.;Wang,Z.; Wu,J.J.Org.Chem.2009,74,921.
[2l]Janza,B.;Studer,A.Org.Lett.2006,8,1875.
[22]Ding,Q.；Wang,Z.；Wu,J.Tetrahedron Lett.2009,50,198.
[23](a)Ajamian,A.,Gleason,J.Angew.Chem.Int.Ed.2004,43,3754.(b)Lee,J.； Na,Y；Han,H.；Chang,S.Chem.Soc.Rev.2004,33,302.(c)Wasilke,J.；Brey, O.;Baker,R.；Bazan,G Chem.Rev.2005,105,1001.(d)Enders,D.;Grondal, C.；Huttl,M.Angew.Chem.Int.Ed.2007,46,1570.(e)Chapman,C.；Frost,C. Synthesis 2007,1.(f)Walji,A.;MacMillan,D.Synlett.2007,1477.
[24](a)Ding,Q.；Wu,J.Org.Lett.2007,9,4959.(b)Gao,K.；Wu,J.J.Org.Chem. 2007,72,8611.(c)Ding,Q.;Yu,X.；Wu,J.Tetrahedron Lett.2008,49,2752.(d) Ding,Q.；Wang,Z.；Wu,J.Tetrahedron Lett.2009,50,198.
[1](a)Rostovtsev,V:Green,L.;Fokin,V；Sharpless,K.Angew.Chem.Int.Ed.2002, 41.2596.(b)Tomoe,C.；Christensen,C.；Meldal,M.J.Org.Chen.2002,67, 3057.(c)Bae,I.；Han,H.；Chang,S,J.Am.Chem.Soc.2005,127,2038.(d)Cho, S.;Yoo,E.;Bae,I.；Chang,S.J.Am..Chem.Soc.2005,127.16046.
[2]For recent reviews on ketenimine,see:(a)Lu,P；Wang,Y.Synlett 2010,165.(b) Yoo,E.；Chang,S.Curr. Org.Chem.2009,13,1766.
[3](a)Singer,L.；Davi's,G.J.Am.Chem.Soc.1967,89,598.(b)Lsvmnce,A.;Singer, L.；Bartlett,P.Tetrahedron Lett.1964,28,1887.
[4](a)Al ajarin,M.;Bonillo,B.;Ortin,M.；Sanchez-Andrada,P.;Vidal,A.Org.Lett. 2006,8,5645.(b)Alajarin,M.；Bonillo,B.；Sanchez-Andrada,P；Vidal,A.； Bautista,D.J.Org.Chem.2007,72,5863.(c)Alajarin,M.；Ortin,M.；Sanchez-Andrada,P；Vidal,A.J.Org.Chem.2006,71,8126.
[5](a)Bae,I.；Han,H.；Chang,S.J.Am.Chem.Soc.2005,127,2038.(b)Cho,S.； Chang,S.Angew.Chem.,Int.Ed.2008,47,2836.
[6]Yoo,E.;Bae,J.;Cho,S.；Han,H.;Chang,S.Org.Lett.2006,8,1347.
[7](a)Cho S.H.；Yoo E.J.；Bae I.；Chang S.J.Am.Chem.Soc.2005,127,16046.(b) ChO,S.；Chang,S.Angew.Chem.,Int.Ed.2007,46,1897.
[8]Kim,S.；Jung,D.；Chang,S.J.Org.Chem.2007,72,9769.
[9]Yoo.E.;Ahlquist,M.;Bae,J.；Sharpless,K.；Fokin,V；Chang,S.J.Org.Chem. 2008,73,5520.
[10]Mandal,S.；Gauniyal,H.；Pramanik,K.；Mukhopadhyay,B.J.Org.Chem.2007, 72,9753.
[11]C ui,S.；Lin,X.；Wang,Y Org.Lett.2006,8,4517.
[12]Cui,S.；Wang,J.；Wang,Y Tetrahedron 2008,64,487.
[13]Cui,S.；Wang,J.;Wang,Y Org.Lett.2007,9,5023.
[14]Han,Y；Xie,Y；Zhao,L.;Fan,M.；Liang,Y.Synthesis 2008,87.
[15]Shen,Y；Cui,S.；Wang,J.；Chen,X.；Lu,P；Wang,Y.Adv.Synth.Catal.2010, 352,1139.
[16]Shang,S.；Ju,K.;He,X.；Hu,J.；Yu,S.；Zhang,M.；Liao,K.；Wang,L.;zhang,P J.Org.Chem.2010,75,5743.
[17]Whiting,M.；Fokin,V.Angew.Chem.Int.Ed.2006,45,3157.
[18]Xu,X.;Cheng,D.；Li,J.；Guo,H.；Yan,J.Org.Lett.2007,9,1585.
[19]Lu,W.;Song,W；Hong,D.；Lu,P.;Wang,Y.Adv.Synth.Catal.2009,351,1768.
[20]Shang,S.;He,X.;Hu,J.;Wu,J.；Zhang,M.;Yu,S.;Zhang,Q.Adv.Synth.Catal. 2009,351,2709.
[21]Cui,S.;Wang,J.；Wang,Y.Org.Lett.2008,10,1267.
[22]Yao,W；Pan,L.；Zhang,Y；Wang,G；Wang,X.;Ma,C.Angew.Chem.,Int. Ed. 2010,49,9210.
[23]Yoo,E.;Park,S.；Lee,S.；Chang,S.Org.Lett.2009,11,1155.
[24](a)Song W.;Lu W.;Wang J.；Lu P；Wang Y.J.Org.Chem.2010,75,3481.(b) Husmann R.；Na Y S.；Bolm C.；Chang S.Chem.Commun.2010,46,5494.
[25](a)Baylis,A.；Hillman,M.German patent 2155113,1972；Chern.Abstr.1972,77,34174q.(b)张爱民,王伟,林国强,有机化学,2001,2,134.
[26]Song,W；Lei,M.；Shen,Y；Cai,S.；Lu,W；Lu,P；Wang,Y.Adv.Synth.Catal. 2010,352,2432.
[27](a)Saxton,J.E.Nat.Prod.Rep.1997,14,559.(b)Toyota,M.；Ihara,N.Nat. Prod.Rep.1998,15,327 and references therein.(c)Joule,J.A.Product Class 13: Indole and Its Derivatives,Thieme,Stuttgart,2001.(d)Kawasaki,T.；Higuchi,K. Nat.Prod.Rep.2005,22,761.(e)Humphrey,G R.；Kuethe,J.T.Chem.Rev. 2006,106,2875.
[28](a)Kobayashi,J.；Suzuki,H.；Shimbo,K.；Takeya,K.；Morita,H.J.Org.Chem. 2001,66,6626.(b)Morita,H.;Shimbo,K.；Shigemori,H.；Kobayashi,J.Bioorg. Med Chem.Lett.2000,10,469.For synthesis of Celogentin C,see:Ma,B.； Banerjee,B.；Litivinov,D.N.;He,L.；Castle,S.L.J.Am.Chem.Soc.2010,132, 1159 and references cited therein.
[29](a)Sundberg,R.J.In Comprehensive Heterocyclic Chemistry, Katritzky,A.R., Rees,C.W.,Pergamon:Oxford,1984;Vol.4,p 313.(b)Cacchi S.；Fabrizi G Chem.Rev.2005,105,2873.
[30](a)Fischer,E.；Jourdan,F.Ber.Dtsch.Chem.Ges.1883,16,2241.(b)Fischer,E.； Hess,O.Ber.Dtsch.Chem.Ges.1884,17,559.(c)Robinson,B.The Fischer Indole Synthesis; John Wiley and Sons:Chichester,1982.(d)Hughes,D.L.Org. Prep.Proced Int.1993,25.
[31](a)Stevens,C.；Van Meenen,E.；Eeckhout,Y.；Vanderhoydonck,B.；Hooghe,W. Chem.Commun 2005,38,4827.(b)Batail,N.；Bendj eriou,A.；Dj akovitch,L. Dufaud,V.Applid Catalysis A: General,2010,388,179.(c)Jeught,S.;Vos N, D.；Masschelein,K.；Ghiviriga,I.;Stevens C.Eur.Org.Chem.2010,5444.
[32](a)Larock,R.；Babu,S.Tetrahedron Lett. 1987,28,1037.(b)Larock,R.;Yum, E.J.Am.Chem.Soc.1991,113,6689.(c)Larock,R.;Yum,E.;Refvik,M.J.Org. Chem.1998,63.76523.(d)Huang,G.;Larock,R.J.Org.Chem.2003,68,7342.(e) Jia,Y.；Zhu,J.J.Org. Chem.2006,71.7826.(f)Zhao,J.；Larock,R.J.Org. Chem.2006,71,5340.(g)Zeni,G.;Larock R.Chem.Rev.2006,106,4644.(h) Patil,S.；Buolamwini,J.Curr.Org.Synth.2006,3,477.
[33]Yoo,E.;Chang,S.Org.Lett.2008,10,1163.
[34]Yurtsever. M.；Yurtsever,E.Polymer.2002,43.6019.
[35](a)Dong,X.;Teng,H.；Tong,M.；Huang,H.；Tao,H.；Wang,C.Chem.Commun. 2010,46,6840.(b)Cao,C.；Ye,M.；Sun,X.；Tang,Y.Org.Lett.2006,8,2901.(c) Noland,W；Chn.stensen,G.;Sauer,G；Dutton,G,J.Am.Chem.Soc. 1955,77, 456.
[36](a)Wang,Q.;Chan,T.;Hilgraf,R.；Fokin,V；Sharpless,K.；Finn,M.J.Am. Chem.Soc.2003,125,3192.(b)Krasinski,A.；Radic,Z.；Manetsch,R.；Raushel, J.；Taylor,P；Sharpless,K.；Kolb,H.J.Am.Chem.Soc.2005,127,6686.(c)Orski, S.；Poloukhtine,A.；Arumugam,S.；Mao,L.;Popik,V；Locklin,J.J.Am.Chem. Soc.2010,132,1024.
[2]Yang,Z.Progress in Chemistry 2009,21,47.
[3]Nicolaou,K.C.；Sorensen,E.Classic,in Total SYNthesis.Weinheim:VCH Verlagsgellschaft mbH,1996.
[4]Nicolaou,K.；Edmonds,D.；Li,A.；Tria,G Angew.Chem.Int.Ed.2007,46,3942.
[5]Veitch,G.;Beckmann,E.；Burke,B.；Boye r,A.;Ayats,C.；Ley,S.Angew.Chem. Int.Ed.2007,46,7629.
[6](a)Corey,E.J.；Cheng,X.The Logical of Chemical Synthesis.John Wiley & Sons: New York,1995.(b)Corey,E.J.Angew.Chem.Int.Ed.1991,30,455；(c)Corey, E.J.；Wipke,W.T.Science 1969,166,178.
[7]For selected examples on DOS,see:(a)Woo,S.；Squires,N.；Fallis,A.Org.Lett. 1999,1,573.(b)Pelish,H.；Westwood,W.Feng,Y.;Kirchhausen,T.;Shair,M.J. Am.Chem.Soc.2001,123,6740.(c)Kwon,O.;Park,S.；Schreiber,S.L.J.Am. Chem.Soc.2002,124,13402.
[8]Tempest,P.；Armstrong,R.J.Am.Chem.Soc.1997,119,7607.
[9]Fergus,S.;Bender,A.；Spring,D.R.Curr.Opin.Chem.Biol.2005,9,304.
[10]Spring,D.R.Or.Biomol.Chem.2003,1,3867.
[11]Galloway,W.；Bender,A.；Welch,M.;Spring,D.R.Chem.Commum.2009, 2446.
[12]王治永,复旦大学博士学位论文2009.
[13]Corey,E.J.；Cheng,X.-M.The Logic of Chemica1 Synthesis.Wiley,New York, 1989.
[14]Tan,D.；Foley,M.；Stockwell,B.；Shair,M.；Schreiber,S.L.J.Am.Chem.Soc, 1999,121,9073；
[15](a)Li,C.；Liang,S.；Zhang,X.；Xie,Z.；Chen,J.；Wu,Y；Yang,Z.Org.Lett., 2005,7,3709.(b)Li,C.;Wang,C.；Liang,B.;zhang,X.；Deng,L.；Liang,S.； Chen,J.；Wu,Y；Yang,Z.J.Org.Chem.2006,71,6892.
[16]Lee,D.;Sello,J.；Schreiber,S.L.Org.Lett.2000,2,709.
[17](a)Nicolaou,K.；Pfefferkom,J.；Roecker,A.；Cao,G.;Barluenga,S.；Mitchell, H.J.Am.Chem.Soc.2000,122,9939.(b)Nicolaou,K.；Pfefferkom,J.；Mitchell, H.；Roecker,A.；Barluenga,S.；Cao,G.；Affleck,R.；Lillig,J.J.Am.Chem.Soc. 2000,122,9954.(c)Nicolaou,K.；Pfefferkorn,J.；Barluenga,S.；Mitchell,H.； Roecker,A.；Cao,G.J.Am.Chem.Soc.2000,122,9968.
[18]Nicolaou,K.;Pfefferkorn,J.;Schuler,F.;Roecker,A.；Cao,G.;Casida,J.Chem. Biol.2000.7,979.
[19]Nicolaou,K.;Roecker,A.；Barluenga,S.;Pfefferkom,J.;Cao,G.Chembiochem, 2001,2,460.
[20]Tan,D.;Foley,M.；Shair,M.；Schreiber,S.L.J.Am.Chem.Soc.1998,120. 8565.
[21]刘钢,李裕林,南发俊,化学进展,2006,18,734.
[22](a)Sternson,S.M.；Louca,J.B.；Wong,J.C.；Schreiber,S.L.J.Am.Chem.Soc. 2001,123,1740.(b)Wong,J.C.；Sternson,S.M.；Louca,J.B.；Hong,R.； Schreiber,S.L.Chem.Biol.2004,11,1279.
[23]Meseguer,B.；Alonso-Diaz,D.；Griebenow,N.;Herget,T.；Waldmann,H. Angew.Chem.,Int.Ed.1999,38,2902.
[24]Stavenger,R.;Schreiber,S.Angew.Chem.Int.Ed.2001,40,3417.
[25]Clardy,J.；Walsh,C.Nature 2004,432,829.
[26]Comer,E.；Rohan,E.；Porco,D.Org Lett.2007,9,2123.
[27]Jason,K.；Sello,P.；Lee,A.;Schreiber,S.Org.Lett.2003,5,4125.
[28]Dandapani,S.;Marcaurelle,L.Curr.Opin.In Chem.Bio.2010,14,362.
[29]Maclean,D.；Baldwin,J.；Ivanov,V.Comb.Chem.2000,2,562.
[30]Biggs-Houck,J.；Younai,A.；Shaw,J.Curr.Opin.In Chem.Bio.2010,14,371.
[1](a)Chrzanowska,M.:Rozwadowska,M D.Chem.Rev.2004,104.3341.(b) Rozwadowska,M.D.Heterocycles 1994,39,903.
[2](a)Bailly,C.;Curr.Med.Chem.Anti-Cancer Agents 2004,4,363.(b)E.Marco, E.；Laine,W.;Tardy,C.;Lansiaux,A.;Iwao,M.；Ishibashi,F.；Bailly,C.；Gago,F. J.Med Chem.,2005,48,3796.(c)Kluza,J.；Gallego,M.;Loyens,A.；Beauvillain, J.；Fernandez,S.;Cuevas,C.；Marchetti,P；Bailly,C.Cancer Res.2006,66,3177.
[3]Su,S.；J.A.Porco,Jr. J.Am.Chem.Soc.2007,129,7744 and references cited therein.
[4](a)Lober,S.；Hubner,H.；Gmeiner,P.Bioorg.Med. Chem.Lett.2002,12,2377.(b) Hasen,J.；Weis,J.；Suzdak,P；Eskesen,K.Bioorg.Med. Chem.Lett.1994,4, 695.
[5](a)Johns,B.A.；Gudmundsson,K.S.；Turner,E.M.；Allen,S.H.；Samano,V A.； Ray,J.A.；Freeman,G A.；Boyd,F. L.,Jr.;Sexton,C.J.;Selleseth,D.W.;Creech, K.L.；Moniri,K.R.Bioorg. Med Chem.2005,13,2397.(b)Akahane,A.； Katayama,H.；Mitsunaga,T.J.Med. Chem.1999,42,779.
[6](a)Meyers,A.；Kung,D.,J.Am.Chem.Soc.1999,121,10828.(b)Kiselyov,A.； Armstrong R.Tetrahedron Lett.1997,38,6163.
[7](a)Yoshinori,T.；Yuichi,I.；Tomoko,M.；Chizuko,K.；Akira,H.J.Heterocyclic Chem.1990,27,263；(b)Yoshinori,T.；Yuichi,I.；Akira,H. Heterocycles.1988, 27,2345.
[8]Potts,K.；Youzwak,H.；Zurawel,S,Jr.J.Org.Chem.1980,45,90.
[9]Harju,K.；Kylanlahti,I.；Paananen,T.；Polamo,M.;Nielsen,J.；Yli-Kauhaluoma,J. J.Comb.Chem.2006,8344.
[10]Kobayashi,M.；Tanabe,M.;Kondo,K.；Aoyama,T.Tetrahedron Lett. 2006,47, 1469.
[11]Kobayashi,M.;Kondo,K.；Aoyama,T.Tetrahedron Lett.2007,48,7019.
[12]Mousseau,J.；Fortier,A.；Charette,A.Org.Lett.2010,12,516.
[13](a)Ridchard N.B.；Anthony G.C.；Patrick,M.；Desmond,C.；Burke,Luke A._B. J.Chem.Soc.Perkin Trans.1,2001,1391.(b)Richard N.B.；Anthony G.C. William J.C.；Luke A.B.J.Chem.Soc.Perkin Trans.2,2002,1807.
[14]Wender,P. A.Chem.Rev.1996,96,1.
[15](a)Tamura,Y；Miki,Y；Nishikawa,Y；Ikeda,M.J.Heterocyclic Chem.1976, 13,317.(b)Tamura,Y；Miki,Y；Hayashi,H.；Sumida,Y；Ikeda,M.J. Heterocyclic Chem.1977,6,281.
[16]Lemi,T.；Gulec,Ahmet,G.Dyes and Pigments,1990,14,307.
[17]Elender,K.；N6th,H.；Weber,A.；Sauer,J.Thtrahedron 2000,56,5443.
[18](a)Ding,Q.；Wu,J.Adv.Synth.Catal.2008,350,1850.(b)Ding,Q.；Wang,Z.; Wu,J.J.Org.Chem.2009,74,921.(c)Ding,Q.；Wang,Z.;Wu,J.Tetrahedron Lett.2009,50.198.
[19](a)Coskun,N.；Tuncman,S.Tetrahedron 2006,62,1345.(b)Najera,C. Sansano,J.Curr.Org.Chem.2003,7,1105.
[20]For reviews,see:(a)Larock,R.C.in;Acetylene Chemistry,(Eds.;F.Diederich, P.J.Stang,R.R.Tykwinski,wiley-VCH,Weinheim,2005,pp 51.(b)Alonso,F.； Beletskaya,I.M.Yus,M.Chem.Rev.2004,104,3079.(c)Zeni,G.；Larock,R.C. Chem.Rev.2006,106,4644.
[21]For selected examples,see:(a)Bi,H.;Guo,L.;Duan,X.；Gou,F.;Huang,S.； Liu,X.;；Liang,Y.Org.Lett.2007,9,397.(b)A.Sniady,A.；Wheeler,K.； Dembinski,R Org.Lett.2005,7,1769.(c)Liu,Y.；Song,F.；Cong,L.J.Org. Chem.2005,70,6999.(d)Peng,A.；Ding,Y.Org.Lett.2004,6,1119.
[22]Ding,Q.；Chen,Z.；Yu,X.;Peng,Y.;Wu,J.Tetrahedron Lett.2009,50,340.
[23]Weibel,J.；Blanc,A.；Pale,P.Chem.Rev.2008,108,3149.
[24](a)Pyyko,P.Angew.Chem.Int.Ed.2004,43,4412.(b)Gorin,D.J.；Toste,D. Nature 2007,446,395.
[25]Halbes-Letinois,U.；Pale,P.；Berger,S.J.Org.Chem.2005,70,9185.
[26]Halbes-Letinois,U.；Weibel,J.；Pale,P.Chem.Soc.Rev.2007,36,759.
[27]Kinugasa,M.；Hashimoto,S.,Chem.Soc.,Chem.Commun.1972,466.
[28]Miura,M,;Enna,M.；Okuro,K.；Nomura,M.J.Org.Chem.1995,60,4999.
[29]Stanley,L.;Sibi,M.Chem.Rev.2008,108,2887.
[30]Mahbub,A.；Rebekah E.B.；Tom,C.；Richard J.D.；Karen M.D.；Mara,F. Bioorg.Med.Chem.Lett.2007,17,3463.
[31](a)Shintani,R.；Fu,G.C.J.Am.Chem.Soc.2003,125,10778.(b)Suarez,A.； Downey,C.W.；Fu,G.C.J.Am.Chem.Soc.2005,127,11244.
[32]For selected examples,see:(a)Ding,Q.；Wu,J.Org.Lett.2007,9,4959.(b)Gao, K.；Wu,J.J.Org.Chem.2007,72,8611.(c)Ding,Q.；Ye,Y；Fan,R；Wu,J.J. Org.Chem.2007,72,5439.
[33]Chen,Z.；Yang,X.；Wu,J.Chem.Commun.2009,23,3469.
[1]Tidwell,T.Acc.Chem.Res.1990,23,273.
[2]For recent reviews on NHC-catalyzed reactions,see:(a)Enders,D.；Niemeier,O.; Henseler,A.Chem.Rev.2007,107.5606 and references therein.(b)Enders,D.; Balensiefer,T.Ac.Chem.Res.2004,37,534.(c)Nair,V.;Vellalath,S.；Babu,B. CheM.Soc.Rev.2008,37,2691.
[3]For selected examples,see:(a)Sohn,S.；Rosen,E.；Bode,J.J.Am.Chem.Soc. 2004,126,14370.(b)He,M.；Bode,J.Org.Lett.2005,7,3131.(c)Nair,V.； Vellalath,S.；Poonoth,M.；Suresh,E.J.Am.Chem.Soc.2006,128,8736.(d) Zhao,H.；Foss,F.,Jr.；Breslow,R.J.Am.Chem.Soc.2008,130,12590.(e)Biju, A.;Wurz,N.；Glorius,F.J.Am.Chem.Soc.2010,132,5970.
[4]Zeitle r,K.Angew.Chem.,Int.Ed.2005,44,7506.
[5]Sohn,S.；Rosen,E.；Bode,J.J.Am.Chem.Soc.2004,,26,14370.(b)Burstein,C.； Glorius,F.Angew.Chem.,Int.Ed.2004,43,6205.(c)Burstein,C.；Tschan,S.； Xie,X.；Glorius,F.Synthesis 2006,2418.
[6](a)He,M.；Bode,J.Org.Lett.2005,7,3131.(b)Rommel,M.；Fukuzumi,T.;Bode, J.J.Am.Chem.Soc.2008,130,17266.
[7]He,M.;Struble,J.;Bode,J.J.Am.Chem.Soc.2006,128,8418.
[8]Chiang,P.；Kaeobamrung,J.;Bode,J.J.Am.Chem.Soc.2007,129,3520.
[9](a)He,M.；Bode,J.J.Am.Chem.Soc.2008,130,418.(b)Kaeobamrung,J.；Bode, J.Org.Lett.2009,11,677.
[10](a)Sohn,S.S.；Bode,J.Org.Lett.2005,7,3873.(b)Chan,A.；Scheidt,K.Org. Lett.2005,7,905.
[11](a)Bode,J.；Sohn,S.J.Am.Chem.Soc.2007,129,13798.(b)Vora,H.；Rovis,T. J.Am.Chem.Soc.2007,129,13796.
[12]Seayad,J.；Patra,P.；Zhang,Y.；Ying,J.Org.Lett.2008,10,953.
[13]Bamberger,E.Chem.Ber.1894,1347.
[14]Nai.r,V.；Babu,B.；Vellalath,S.；Varghese,V.Org.Lett.2009,11,2507.
[15]Nair,V.；Sinu,C.；Babu,B.;Varghese,V.；Jose,A.；Suresh,E.Org.Lett.2009, 11,5570.
[16]Li,G.；Dai,L.；You,S.Org.Lett.2009,11,1623.
[17]Chan,A.；Scheidt,K.J.Am.Chem.Soc.2007,129,5334.
[18]Phillips,E.；Reynolds,T.；Scheidt,K.J.Am.Chem.Soc.2008,130,2416.
[19](a)Shao,Z.;Zhang,H.Chem.Soc.Rev.2009,38,2745.(b)Park,Y.;Park,J.;Jun, C.Acc.Chem.Res.2008,41,222.
[20]Yang,T.；Ferrali,A.；Campbell,L.；Dixon,D.Chem.Communn.2008,2923.
[21]Binder,J.;Crone,B.；Haug,T.;Menz,H.；Kirsch,S.Org.Lett.2008,10.1025.
[22]Xu,X.；Zhou,J.;Yang,L.;Hu,W.Chem.Commun.2008,6564.
[23]Ding,Q.；Wu,J.Org.Lett.2007,9,4959.
[24](a)Hintermann,L.Beilstein,Org.Chem.2007,3.22.(b)http://bjoc.beilstein-journals.org/content/3/1/22.
[25]Chen,Z.；Yu,X.;Wu,J.Chem.Commun.2010,46,6356.
[26](a)Phillips,E.；Riedrich,M.；Scheidt,K.J.Am.Chem.Soc.2010,132,13179.(b) Yue,Y.；Yu,X.；Pu,L.Chem.-Eur.J.2009,15,5104.
[27]Yu,X.；Ye,S.；Wu,J.Adv.Synth.Catal.2010,352,2050.
[28]成静,付强,伍钢,中华肿瘤防治杂志,2007,14,872.
[29]For selected examples,see:(a)Frangioni,J.;Beahm,P；Shifrin,V；Jost,C.;Neel, B.Cell 1992,68,545.(b)Woodford-Thomas,T.;Rhodes,J.；Dixon,J.J.Cell Biol. 1992,117,401.(c)Haj,F.;Verveer,P；Squire,A.;Neel,B.；Bastiaens,P Science 2002,295,1708.
[30]For reviews,see:(a)Miyaura,N.Top.Curr.Chem.2002,2,9,11.(b)Suzuki,A. J.Organomet.Chem.1999,576,147.(c)Littke,A.；Fu,G.Angew.Chem.Int.Ed. 2002,41,4176.(d)De Meijere,A.;Diederich,F.Metal-Catalyzed Cross-Coupling Reactions,2nd ed,John Wiley & Sons,Weinheim,Germany,2004.
[1]Lieke,W.Justus Liebigs Ann.Chem.1859,112,316.
[2]For reviiews on isocyanides,see:(a)Lentz,D.Angew.Chem.1994,106,1377; Angew.Chem.Int.Ed.1994,33,1315.(b)Domling,A.Chem.Rev.2006,106,17. (c)Alexander,L.；Armin,de M.Angw.Chem.Int.Ed.2010,49,9094.
[3](a)Malatesta,L.；Bonati,F.Isocyanide Complexes of Metals,Wiley-Interscience, New York,N.Y.1969.(b)Horrocks,W.;Mann,R.Spectrochim.Acta.1963,19, 1375.(c)Malatesta,L.Progr.Inorg.Chem.1959,1,283.
[4](a)H.Eckert,H.；Forster,B.Angew.Chem.Int.Ed.1987,26,1221.(b)Obrecht, R.；Herrmann,R.；Ugi,I.Synthesis 1985,400.(c)Giesemann,G；von Hinrichs, E.;Ugi,I.J.Chem.Res(S),1982,79.
[5]Domling,A.；Ugi,I.Angew.Chem.Int.Ed.2000,39,3168.
[6](a)Passerini,M.Gazz.Chim.Ital.1921,51,126.(b)Baker,R.；Stanonis,D.J.Am. Chem.Soc.1951,73,699.
[7](a)Ugi,I.；Meyr,R.；Fetzer,U.；Steinbruckner,C.Angew.Chem.1959,71,386.(b) Ugi,I.；Steinbruckner,C.Angew.Chem.1960,72,267.
[8](a)Chatani,N.；Mamoru,O.；Tobisu,M.；Ishii,Y.；Murai,S.J.Am.Chem.Soc. 2003,125,7812.(b)Oshita,M.；Tobisu,M.；Yamashita,K.；Chatani,N.J.Am. Chem.Soc.2005,127,761.(c)Oshita,M.；Tobisu,M.；Yamashita,K.；Chatani, N.J.Am.Chem.Soc.2005,127,2363.
[9](a)Bez,G.;Zhao,C.Org.Lett.2003,5,4991.(b)Yoshioka,S.；Oshita,M.； Tobisu,M.；Chatani,N.Org.Lett.2005,7,3697.(c)Tobisu,M.；Kitajima,A.； Yoshioka,S.；Hyodo,I.；Oshita,M.；Chatani,N.J.Am.Chem.Soc.2007,129, 11431.
[10]Tobisu,M.；Ito,S.；Kitajima,A.；Chatani,N.Org.Lett.2008,10,5223.
[11](a)Tobisu,M.；Yamaguchi,S.；Chatani,N.Org.Lett.2007,9,3351.(b)Tobisu, M.；Imoto,S.；Ito,S.；Chatani,N.J.Org.Chem.2010,75,4835.
[12](a)Campeau,L.；Rousseaux,S.；Fagnou,K,J.Am.Chem.Soc.2005,127,18020. (b)Schipper,D.；El-Salfiti,M.；Whipp,C.；Fagnou,K.Tetrahedron 2009,4977.
[13]Campeau,L.；Schipper,D.；Fagnou,K.J.Am.Chem.Soc.2008,130,3266.
[14]Kanyiva,K.；Nakao,Y.；Hiyama,T.Angew.Chem.Int.Ed.2007,46,8872.
[15]Cho,S.；Hwang,S.；Chang,S.J.Am.Chem.Soc.2008,130,9254.
[16]Xi,P.；Yang,F.；Qin,S.；Zhao,D.；Lan,J.；Gao,G.;Hu,C.；You,J.Am.Chem. Soc.2010,132,1822.
[17]Kang,Y.;Sun,X.；Tang,Y.Angew.Int.Ed.2007,46,3918.
[18](a)Sims,J.;Houk,N.J.Am.Chem.Soc.1973,95,5798.(b)Jensen,K.； Roberson,M.；J6rgensen,K.J.Org.Chem.2000,65,9080.
[19](a)Yeom,H.;Lee,J.;Shin,S.Angew.Chem.Int.Ed.2008,47.7040.(b)Yeom, H.；Lee,Y.；Jeong,J.；So,E.；Hwang,S.；Lee,J.；Lee,S.；Shin,S.Angew.Chem. Int.Ed.2010,49,1611.
[20](a)Ding,Q.；Wu,J.Adv.Synth.Catal.2008,350.1850.(b)Ding,Q.;Wang,Z.; Wu,J.J.Org.Chem.2009,74,921.
[2l]Janza,B.;Studer,A.Org.Lett.2006,8,1875.
[22]Ding,Q.；Wang,Z.；Wu,J.Tetrahedron Lett.2009,50,198.
[23](a)Ajamian,A.,Gleason,J.Angew.Chem.Int.Ed.2004,43,3754.(b)Lee,J.； Na,Y；Han,H.；Chang,S.Chem.Soc.Rev.2004,33,302.(c)Wasilke,J.；Brey, O.;Baker,R.；Bazan,G Chem.Rev.2005,105,1001.(d)Enders,D.;Grondal, C.；Huttl,M.Angew.Chem.Int.Ed.2007,46,1570.(e)Chapman,C.；Frost,C. Synthesis 2007,1.(f)Walji,A.;MacMillan,D.Synlett.2007,1477.
[24](a)Ding,Q.；Wu,J.Org.Lett.2007,9,4959.(b)Gao,K.；Wu,J.J.Org.Chem. 2007,72,8611.(c)Ding,Q.;Yu,X.；Wu,J.Tetrahedron Lett.2008,49,2752.(d) Ding,Q.；Wang,Z.；Wu,J.Tetrahedron Lett.2009,50,198.
[1](a)Rostovtsev,V:Green,L.;Fokin,V；Sharpless,K.Angew.Chem.Int.Ed.2002, 41.2596.(b)Tomoe,C.；Christensen,C.；Meldal,M.J.Org.Chen.2002,67, 3057.(c)Bae,I.；Han,H.；Chang,S,J.Am.Chem.Soc.2005,127,2038.(d)Cho, S.;Yoo,E.;Bae,I.；Chang,S.J.Am..Chem.Soc.2005,127.16046.
[2]For recent reviews on ketenimine,see:(a)Lu,P；Wang,Y.Synlett 2010,165.(b) Yoo,E.；Chang,S.Curr. Org.Chem.2009,13,1766.
[3](a)Singer,L.；Davi's,G.J.Am.Chem.Soc.1967,89,598.(b)Lsvmnce,A.;Singer, L.；Bartlett,P.Tetrahedron Lett.1964,28,1887.
[4](a)Al ajarin,M.;Bonillo,B.;Ortin,M.；Sanchez-Andrada,P.;Vidal,A.Org.Lett. 2006,8,5645.(b)Alajarin,M.；Bonillo,B.；Sanchez-Andrada,P；Vidal,A.； Bautista,D.J.Org.Chem.2007,72,5863.(c)Alajarin,M.；Ortin,M.；Sanchez-Andrada,P；Vidal,A.J.Org.Chem.2006,71,8126.
[5](a)Bae,I.；Han,H.；Chang,S.J.Am.Chem.Soc.2005,127,2038.(b)Cho,S.； Chang,S.Angew.Chem.,Int.Ed.2008,47,2836.
[6]Yoo,E.;Bae,J.;Cho,S.；Han,H.;Chang,S.Org.Lett.2006,8,1347.
[7](a)Cho S.H.；Yoo E.J.；Bae I.；Chang S.J.Am.Chem.Soc.2005,127,16046.(b) ChO,S.；Chang,S.Angew.Chem.,Int.Ed.2007,46,1897.
[8]Kim,S.；Jung,D.；Chang,S.J.Org.Chem.2007,72,9769.
[9]Yoo.E.;Ahlquist,M.;Bae,J.；Sharpless,K.；Fokin,V；Chang,S.J.Org.Chem. 2008,73,5520.
[10]Mandal,S.；Gauniyal,H.；Pramanik,K.；Mukhopadhyay,B.J.Org.Chem.2007, 72,9753.
[11]C ui,S.；Lin,X.；Wang,Y Org.Lett.2006,8,4517.
[12]Cui,S.；Wang,J.；Wang,Y Tetrahedron 2008,64,487.
[13]Cui,S.；Wang,J.;Wang,Y Org.Lett.2007,9,5023.
[14]Han,Y；Xie,Y；Zhao,L.;Fan,M.；Liang,Y.Synthesis 2008,87.
[15]Shen,Y；Cui,S.；Wang,J.；Chen,X.；Lu,P；Wang,Y.Adv.Synth.Catal.2010, 352,1139.
[16]Shang,S.；Ju,K.;He,X.；Hu,J.；Yu,S.；Zhang,M.；Liao,K.；Wang,L.;zhang,P J.Org.Chem.2010,75,5743.
[17]Whiting,M.；Fokin,V.Angew.Chem.Int.Ed.2006,45,3157.
[18]Xu,X.;Cheng,D.；Li,J.；Guo,H.；Yan,J.Org.Lett.2007,9,1585.
[19]Lu,W.;Song,W；Hong,D.；Lu,P.;Wang,Y.Adv.Synth.Catal.2009,351,1768.
[20]Shang,S.;He,X.;Hu,J.;Wu,J.；Zhang,M.;Yu,S.;Zhang,Q.Adv.Synth.Catal. 2009,351,2709.
[21]Cui,S.;Wang,J.；Wang,Y.Org.Lett.2008,10,1267.
[22]Yao,W；Pan,L.；Zhang,Y；Wang,G；Wang,X.;Ma,C.Angew.Chem.,Int. Ed. 2010,49,9210.
[23]Yoo,E.;Park,S.；Lee,S.；Chang,S.Org.Lett.2009,11,1155.
[24](a)Song W.;Lu W.;Wang J.；Lu P；Wang Y.J.Org.Chem.2010,75,3481.(b) Husmann R.；Na Y S.；Bolm C.；Chang S.Chem.Commun.2010,46,5494.
[25](a)Baylis,A.；Hillman,M.German patent 2155113,1972；Chern.Abstr.1972,77,34174q.(b)张爱民,王伟,林国强,有机化学,2001,2,134.
[26]Song,W；Lei,M.；Shen,Y；Cai,S.；Lu,W；Lu,P；Wang,Y.Adv.Synth.Catal. 2010,352,2432.
[27](a)Saxton,J.E.Nat.Prod.Rep.1997,14,559.(b)Toyota,M.；Ihara,N.Nat. Prod.Rep.1998,15,327 and references therein.(c)Joule,J.A.Product Class 13: Indole and Its Derivatives,Thieme,Stuttgart,2001.(d)Kawasaki,T.；Higuchi,K. Nat.Prod.Rep.2005,22,761.(e)Humphrey,G R.；Kuethe,J.T.Chem.Rev. 2006,106,2875.
[28](a)Kobayashi,J.；Suzuki,H.；Shimbo,K.；Takeya,K.；Morita,H.J.Org.Chem. 2001,66,6626.(b)Morita,H.;Shimbo,K.；Shigemori,H.；Kobayashi,J.Bioorg. Med Chem.Lett.2000,10,469.For synthesis of Celogentin C,see:Ma,B.； Banerjee,B.；Litivinov,D.N.;He,L.；Castle,S.L.J.Am.Chem.Soc.2010,132, 1159 and references cited therein.
[29](a)Sundberg,R.J.In Comprehensive Heterocyclic Chemistry, Katritzky,A.R., Rees,C.W.,Pergamon:Oxford,1984;Vol.4,p 313.(b)Cacchi S.；Fabrizi G Chem.Rev.2005,105,2873.
[30](a)Fischer,E.；Jourdan,F.Ber.Dtsch.Chem.Ges.1883,16,2241.(b)Fischer,E.； Hess,O.Ber.Dtsch.Chem.Ges.1884,17,559.(c)Robinson,B.The Fischer Indole Synthesis; John Wiley and Sons:Chichester,1982.(d)Hughes,D.L.Org. Prep.Proced Int.1993,25.
[31](a)Stevens,C.；Van Meenen,E.；Eeckhout,Y.；Vanderhoydonck,B.；Hooghe,W. Chem.Commun 2005,38,4827.(b)Batail,N.；Bendj eriou,A.；Dj akovitch,L. Dufaud,V.Applid Catalysis A: General,2010,388,179.(c)Jeught,S.;Vos N, D.；Masschelein,K.；Ghiviriga,I.;Stevens C.Eur.Org.Chem.2010,5444.
[32](a)Larock,R.；Babu,S.Tetrahedron Lett. 1987,28,1037.(b)Larock,R.;Yum, E.J.Am.Chem.Soc.1991,113,6689.(c)Larock,R.;Yum,E.;Refvik,M.J.Org. Chem.1998,63.76523.(d)Huang,G.;Larock,R.J.Org.Chem.2003,68,7342.(e) Jia,Y.；Zhu,J.J.Org. Chem.2006,71.7826.(f)Zhao,J.；Larock,R.J.Org. Chem.2006,71,5340.(g)Zeni,G.;Larock R.Chem.Rev.2006,106,4644.(h) Patil,S.；Buolamwini,J.Curr.Org.Synth.2006,3,477.
[33]Yoo,E.;Chang,S.Org.Lett.2008,10,1163.
[34]Yurtsever. M.；Yurtsever,E.Polymer.2002,43.6019.
[35](a)Dong,X.;Teng,H.；Tong,M.；Huang,H.；Tao,H.；Wang,C.Chem.Commun. 2010,46,6840.(b)Cao,C.；Ye,M.；Sun,X.；Tang,Y.Org.Lett.2006,8,2901.(c) Noland,W；Chn.stensen,G.;Sauer,G；Dutton,G,J.Am.Chem.Soc. 1955,77, 456.
[36](a)Wang,Q.;Chan,T.;Hilgraf,R.；Fokin,V；Sharpless,K.；Finn,M.J.Am. Chem.Soc.2003,125,3192.(b)Krasinski,A.；Radic,Z.；Manetsch,R.；Raushel, J.；Taylor,P；Sharpless,K.；Kolb,H.J.Am.Chem.Soc.2005,127,6686.(c)Orski, S.；Poloukhtine,A.；Arumugam,S.；Mao,L.;Popik,V；Locklin,J.J.Am.Chem. Soc.2010,132,1024.