Synthesis of Benzo[a]carbazoles from 2‐Arylindoles via a Sequential Propargylation, Propargyl‐Allenyl Isomerization, and 6π‐Electrocyclization

An efficient two-step synthetic approach of benzo[a]carbazoles from 2-arylindoles has been developed. The first step is a propargylation of 2-arylindoles at the 3-position catalyzed by montmorillonite K-10 in benzene. The second step is 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-catalyzed sequential propargyl-allenyl isomerization and a concomitant 6π-electrocyclization process involving two aromatic π-bonds.

[1]  Jae Nyoung Kim,et al.  Synthesis of 1H-benzo[g]indazole derivatives: propargyl–allenyl isomerization and 6π-electrocyclization involving two aromatic π-bonds , 2014 .

[2]  A. Dhakshinamoorthy,et al.  K10 montmorillonite clays as environmentally benign catalysts for organic reactions , 2014 .

[3]  B. Trofimov,et al.  Alkynylation of Aldehydes and Ketones Using the Bu4NOH/H2O/DMSO Catalytic Composition: A Wide‐Scope Methodology , 2014 .

[4]  D. Ess,et al.  Rapid synthesis of fused N-heterocycles by transition-metal-free electrophilic amination of arene C-H bonds. , 2014, Angewandte Chemie.

[5]  G. Kraus,et al.  First inverse electron-demand Diels-Alder methodology of 3-chloroindoles and methyl coumalate to carbazoles. , 2014, Organic letters.

[6]  Hongwei Zhou,et al.  Propargyl–Allenyl Isomerizations and Electrocyclizations for the Functionalization of Phosphonium Salts: One‐Pot Synthesis of Polysubstituted Vinylbenzenes and Naphthalenes , 2013 .

[7]  T. Choshi,et al.  Total Synthesis of the Neuronal Cell‐Protecting Carbazole Alkaloids Carbazomadurin A and (S)‐(+)‐Carbazomadurin B , 2013 .

[8]  S. Rapposelli,et al.  Discovery of novel N-substituted carbazoles as neuroprotective agents with potent anti-oxidative activity. , 2013, European journal of medicinal chemistry.

[9]  Xingwei Li,et al.  Rhodium(III)-catalyzed coupling of arenes with 7-oxa/azabenzonorbornadienes by C-H activation. , 2013, Angewandte Chemie.

[10]  H. Hendrickson,et al.  Amberlite IR-120H as an efficient and versatile solid phase catalyst for nucleophilic substitution of propargylic alcohols , 2013 .

[11]  C. Tsukano,et al.  Synthesis of 3-acyl-2-arylindole via palladium-catalyzed isocyanide insertion and oxypalladation of alkyne. , 2013, Organic letters.

[12]  Jae Nyoung Kim,et al.  Controlled synthesis of 1-vinylnaphthalenes versus (E)-α-(1,3-enyn-4-yl)-α,β-unsaturated esters from Morita–Baylis–Hillman bromides: a sequential alkynylation and competitive 6π-electrocyclization versus conjugative transposition of a triple bond , 2013 .

[13]  Jae Nyoung Kim,et al.  An efficient synthesis of o-terphenyls from Morita–Baylis–Hillman adducts of cinnamaldehydes: a consecutive bromination, Wittig reaction, 6π-electrocyclization, and an aerobic oxidation process , 2013 .

[14]  A. Palmieri,et al.  A Photochemical Route to Benzo[a]carbazoles via Domino Elimination/Electrocyclization of 2-Aryl-3-(1-tosylalkyl)indoles , 2013 .

[15]  K. Laali,et al.  Condensation of propargylic alcohols with N-methylcarbazole and carbazole in [bmim]PF6 ionic liquid; synthesis of novel dipropargylic carbazoles using TfOH or Bi(NO3)3·5H2O as catalyst , 2013 .

[16]  Sanghee Kim,et al.  Expedient synthesis of phenanthrenes via In(III)-catalyzed 6-exo-dig cycloisomerization. , 2013, Organic letters.

[17]  H. Fu,et al.  Copper-catalyzed synthesis of benzocarbazoles via α-C-arylation of ketones. , 2012, Chemical communications.

[18]  Antonia Iazzetti,et al.  Dibenzo[a,c]carbazoles from 2-(2-bromoaryl)-3-arylindoles via a palladium-catalyzed intramolecular C-H functionalization/C-C bond formation process. , 2012, Organic & biomolecular chemistry.

[19]  Jae Nyoung Kim,et al.  Copper-catalyzed tandem alkynylation, propargyl–allenyl isomerization, 6π-electrocyclization of Morita–Baylis–Hillman adducts to naphthalenes , 2012 .

[20]  Hongwei Zhou,et al.  Synthesis of polyfunctionalized quinolines via the sequence of propargyl-allenyl isomerization and aza-electrocyclization. , 2012, The Journal of organic chemistry.

[21]  Xue-Yuan Liu,et al.  Palladium(II)-catalyzed tandem cyclization/C-H functionalization of alkynes for the synthesis of functionalized indoles. , 2012, The Journal of organic chemistry.

[22]  Mukut Gohain,et al.  An Al(OTf)3-catalyzed environmentally benign process for the propargylation of indoles , 2012 .

[23]  A. Frontier,et al.  Cycloaromatization protocol for synthesis of polysubstituted phenol derivatives: method development and mechanistic studies. , 2012, The Journal of organic chemistry.

[24]  C. Tsukano,et al.  Palladium-catalyzed cascade process consisting of isocyanide insertion and benzylic C(sp3)-H activation: concise synthesis of indole derivatives. , 2012, Organic letters.

[25]  Hongwei Zhou,et al.  Applications of the in situ Propargyl-Allenyl Isomerization in Organic Synthesis , 2012 .

[26]  K. Laali,et al.  Condensation of propargylic alcohols with indoles and carbazole in [bmim][PF6]/Bi(NO3)3·5H2O: a simple high yielding propargylation method with recycling and reuse of the ionic liquid , 2012 .

[27]  Samuel R. Mendes,et al.  Propargylation of aromatic compounds using Ce(OTf)3 as catalyst , 2012 .

[28]  E. Kianmehr,et al.  A Direct Palladium‐Catalyzed Route for the Synthesis of Benzo[a]carbazoles through Sequential C–C Bond Formation and C–H Bond Functionalization , 2012 .

[29]  Xian Huang,et al.  Palladium-catalyzed sequential reaction viaSonogashira coupling, isomerization, Claisen rearrangement and [4 + 2] cycloaddition sequence for the rapid synthesis of tricyclo[3.2.1.02,7]oct-3-ene derivatives , 2012 .

[30]  Yi Chen,et al.  Design, synthesis and biological evaluation of substituted 11H-benzo[a]carbazole-5-carboxamides as novel antitumor agents. , 2011, European journal of medicinal chemistry.

[31]  P. Agarwal,et al.  One-pot Zn/CuI/TFA-catalyzed domino three-component-carbocyclization reaction involving biphenyl-2-carbaldehydes/alkynes/piperidine: allenes-mediated construction of phenanthrenes. , 2011, The Journal of organic chemistry.

[32]  Shyh‐Chyun Yang,et al.  Iodine-mediated cascade cyclization of enediynes to iodinated benzo[a]carbazoles. , 2011, The Journal of organic chemistry.

[33]  T. Choshi,et al.  Synthetic studies on nitrogen-containing fused-heterocyclic compounds based on thermal electrocyclic reactions of 6π-electron and aza 6π-electron systems , 2011 .

[34]  Hongwei Zhou,et al.  Heteroatom as a promotor: synthesis of polyfunctionalized benzenes and naphthalenes. , 2011, The Journal of organic chemistry.

[35]  N. Fujii,et al.  Direct synthesis of fused indoles by gold-catalyzed cascade cyclization of diynes. , 2011, The Journal of organic chemistry.

[36]  T. Choshi,et al.  Total synthesis of bioactive indolo〔3,2-j〕phenanthridine alkaloid, calothrixin B , 2010 .

[37]  Hongwei Zhou,et al.  Sulfur-assisted propargyl–allenyl isomerizations and intramolecular cyclization for the synthesis of tricyclic thiophene derivatives , 2010 .

[38]  Shyh‐Chyun Yang,et al.  Synthetic development and mechanistic study on Pd(II)-catalyzed cyclization of enediynes to benzo[a]carbazoles. , 2010, Organic letters.

[39]  Xian Huang,et al.  Facile synthesis of tetrahydro-1H-isoindolones via a sequential three-component copper-catalyzed coupling/propargyl-allenyl isomerization/[4 + 2] cyclization reaction. , 2010, Organic letters.

[40]  Hongwei Zhou,et al.  Sulfur-assisted propargyl-allenyl isomerizations and electrocyclizations for the convenient and efficient synthesis of polyfunctionalized benzenes and naphthalenes. , 2010, Organic letters.

[41]  T. Choshi,et al.  A novel total synthesis of the bioactive poly-substituted carbazole alkaloid carbazomadurin A , 2010 .

[42]  A. S. Dudnik,et al.  Computation-guided development of Au-catalyzed cycloisomerizations proceeding via 1,2-Si or 1,2-H migrations: regiodivergent synthesis of silylfurans. , 2010, Journal of the American Chemical Society.

[43]  Guang-liang Zhang,et al.  Montmorillonite K10: Catalyst for Friedel–Crafts Alkylation of Indoles and Pyrrole with Nitroalkenes Under Solventless Conditions , 2010 .

[44]  José A. Souto,et al.  Competing thermal electrocyclic ring-closure reactions of (2Z)-hexa-2,4,5-trienals and their Schiff bases. Structural, kinetic, and computational studies. , 2010, The Journal of organic chemistry.

[45]  Hongwei Zhou,et al.  Ga(OTf)3-promoted sequential reactions via sulfur-assisted propargyl-allenyl isomerizations and intramolecular [4 + 2] cycloaddition for the synthesis of 1,3-dihydrobenzo[c]thiophenes. , 2010, The Journal of organic chemistry.

[46]  Ruwei Shen,et al.  Palladium-Catalyzed Sequential Reactions via Allene Intermediates for the Rapid Synthesis of Fused Polycyclic Pyrrole Derivatives , 2009 .

[47]  Ruwei Shen,et al.  Facile Synthesis of Polycyclic Fluorene Derivatives via a Palladium‐Catalyzed Coupling, Propargyl‐Allenyl Isomerization and Schmittel Cyclization Sequence , 2009 .

[48]  N. Jiao,et al.  A palladium-catalyzed oxidative cycloaromatization of biaryls with alkynes using molecular oxygen as the oxidant. , 2009, Angewandte Chemie.

[49]  M. David-Cordonnier,et al.  Photochemical electrocyclisation of 3-vinylindoles to pyrido[2,3-a]-, pyrido[4,3-a]- and thieno[2,3-a]-carbazoles: design, synthesis, DNA binding and antitumor cell cytotoxicity. , 2009, European journal of medicinal chemistry.

[50]  Alberto Martínez,et al.  Synthesis of 3-Allenylindoles and 3-Dienylindoles by Brønsted Acid Catalyzed Allenylation of 2-Arylindoles with Tertiary Propargylic Alcohols , 2009 .

[51]  Ruwei Shen,et al.  Unexpected Pd-catalyzed coupling, propargyl-allenyl isomerization and alder-ene reaction: facile synthesis of some not readily available 2,3-dihydrofuran derivatives. , 2009, The Journal of organic chemistry.

[52]  T. Choshi,et al.  Progress Towards the Total Synthesis of the Bioactive Calothrixins A and B , 2009 .

[53]  Haiyang Sun,et al.  Synthesis of Fischer indole derivatives using carboxyl-functionalized ionic liquid as an efficient and recyclable catalyst , 2009 .

[54]  M. Kaneko,et al.  Indium-catalyzed annulation of 2-aryl- and 2-heteroarylindoles with propargyl ethers: concise synthesis and photophysical properties of diverse aryl- and heteroaryl-annulated[a]carbazoles. , 2008, Journal of the American Chemical Society.

[55]  J. Lao,et al.  Discovery and biological evaluation of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor. , 2008, Bioorganic & medicinal chemistry letters.

[56]  J. Yadav,et al.  PMA-silica gel catalyzed propargylation of aromatic compounds with arylpropargyl alcohols under solvent-free conditions , 2008 .

[57]  A. S. Dudnik,et al.  Metal-catalyzed 1,2-shift of diverse migrating groups in allenyl systems as a new paradigm toward densely functionalized heterocycles. , 2008, Journal of the American Chemical Society.

[58]  J. Yadav,et al.  Iodine-catalyzed C- and O-nucleophilic substitution reactions of aryl-propargyl methanols , 2007 .

[59]  J. Yadav,et al.  Indium(III) bromide catalyzed rapid propargylation of heteroaromatic systems by α-aryl-substituted propargyl alcohols , 2007 .

[60]  U. Jana,et al.  An FeCl3-catalyzed highly C3-selective Friedel–Crafts alkylation of indoles with alcohols , 2007 .

[61]  M. Prudhomme,et al.  Synthesis and biological activities of new checkpoint kinase 1 inhibitors structurally related to granulatimide. , 2007, Journal of medicinal chemistry.

[62]  V. Gevorgyan,et al.  Mechanistically diverse copper-, silver-, and gold-catalyzed acyloxy and phosphatyloxy migrations: efficient synthesis of heterocycles via cascade migration/cycloisomerization approach. , 2007, Journal of the American Chemical Society.

[63]  I. Columbus,et al.  Efficient and facile Ar-Si bond cleavage by montmorillonite KSF: synthetic and mechanistic aspects of solvent-free protodesilylation studied by solution and solid-state MAS NMR. , 2007, The Journal of organic chemistry.

[64]  J. Yadav,et al.  Sc(OTf)3-catalyzed alkylation of indoles with propargyl alcohols: an expeditious synthesis of 3-substituted indoles , 2007 .

[65]  Yan‐Chao Wu,et al.  InCl3-Catalyzed Propargylation of Indoles and Phenols with Propargylic Acetates: Application to the Syntheses of Benzofurans and Naphthofurans , 2007 .

[66]  K. Kaneda.  Cation-Exchanged Montmorillonites as Solid Acid Catalysts for Organic Synthesis , 2007 .

[67]  Yi Wang,et al.  Base-catalyzed cyclization of monofluorodienynes: a new route to substituted fluorobenzene derivatives , 2006 .

[68]  Yi Wang,et al.  Site-specific preparation of 2-carboalkoxy-4-substituted naphthalenes and 9-alkylphenanthrenes and evidence for an allene intermediate in the novel base-catalyzed cyclization of 2-alkynylbiphenyls. , 2006, Organic letters.

[69]  Yi Wang,et al.  A simple, two-step, site-specific preparation of fluorinated naphthalene and phenanthrene derivatives from fluorobromo-substituted alkenes. , 2006, The Journal of organic chemistry.

[70]  T. Choshi,et al.  A biomimetic synthesis of the indolo[3,2-j]phenanthridine alkaloid, calothrixin B , 2006 .

[71]  A. Palmieri,et al.  Solventless clay-promoted Friedel-Crafts reaction of indoles with alpha-amido sulfones: unexpected synthesis of 3-(1-arylsulfonylalkyl) indoles. , 2006, Organic letters.

[72]  Yi Wang,et al.  Site-specific preparation of 3-fluoro-1-substituted-naphthalenes via a novel base-catalyzed cyclization reaction from (E)-monofluoroenynes. , 2006, Organic letters.

[73]  Mohammed Abid,et al.  Synthesis of N-heteroaryl(trifluoromethyl)hydroxyalkanoic acid esters by highly efficient solid acid-catalyzed hydroxyalkylation of indoles and pyrroles with activated trifluoromethyl ketones , 2005 .

[74]  A. Dhakshinamoorthy,et al.  Facile clay-induced Fischer indole synthesis: A new approach to synthesis of 1,2,3,4-tetrahydrocarbazole and indoles , 2005 .

[75]  M. Kaneko,et al.  Easy access to aryl- and heteroaryl-annulated[a]carbazoles by the indium-catalyzed reaction of 2-arylindoles with propargyl ethers. , 2005, Angewandte Chemie.

[76]  InomataKatsuhiko,et al.  “Syn-Effect” in the Desilylation Reaction of γ-Silylated Allylic and Vinylic Sulfones , 2003 .

[77]  Oljan Repic,et al.  Dual nucleophilic catalysis with DABCO for the N-methylation of indoles. , 2003, The Journal of organic chemistry.

[78]  H. Knölker,et al.  Isolation and synthesis of biologically active carbazole alkaloids. , 2002, Chemical reviews.

[79]  B. Jiang,et al.  Alkynylation of carbonyl compounds with terminal acetylenes promoted by ZnCl2 and Et3N: simple, mild and efficient preparation of propargylic alcohols , 2002 .

[80]  Y. Harigaya,et al.  Dry reaction of indoles with carbonyl compounds on montmorillonite K10 clay: a mild, expedient synthesis of diindolylalkanes and vibrindole A , 2002 .

[81]  T. Choshi,et al.  Novel syntheses of murrayaquinone A and furostifoline through 4-oxygenated carbazoles by allene-mediated electrocyclic reactions starting from 2-chloroindole-3-carbaldehyde. , 2001, Chemical & pharmaceutical bulletin.

[82]  G. Kirsch.  Heterocyclic Analogues of Carbazole Alkaloids , 2001 .

[83]  M. Lakouraj,et al.  Desilylation-acetylation of Trimethylsilyl Ethers with Acetic Anhydride Catalysed by Montmorillonite K-10† , 2000 .

[84]  T. Choshi,et al.  New Syntheses of Murrayaquinone A and Furostifoline , 1998 .

[85]  U. Pindur,et al.  1,6-π-Electrocyclization of 3-Vinyl-Functionalized N,N-Dimethyl-2,2′-Bisindolyl: Some analysis of the educt transformation process , 1998 .

[86]  T. Pilati,et al.  Synthesis of [a]annulated carbazoles from indol-2,3-dione , 1993 .

[87]  H. Furukawa,et al.  New carbazole alkaloids from Murraya euchrestifolia Hayata. , 1990 .