Academic literature on the topic 'Pyrrolo (3,2-C) Pyridine(Methyl-1)'

Simultaneously, Aaran Aponick of the University of Florida (Organic Lett. 2009, 11, 4624) and Shuji Akai of the University of Shizuoka (Organic Lett. 2009, 11, 5002) reported the Au-mediate conversion of a propargylic diol such as 1 to the furan 2. Pyrroles can also be prepared using the same protocol. Jason K. Sello of Brown University developed (Organic Lett. 2009, 11, 2984) the direct aldol condensation of an acetoacetate 3 with the protected 1,3-dihydroxy acetone 4 to give 5, the methyl ester of a methylenomycin furan (MMF) bacterial-signaling molecule from Streptomyces coelicolor. Nobuharu Iwasawa of the Tokyo Institute of Technology demonstrated (Angew. Chem. Int. Ed. 2009, 48, 8318) that the imine 6 was sufficiently nucleophilic to react with the Rh vinylidene derived from the alkyne 7, leading to the pyrrole 8. Min Shi of the Shanghai Institute of Organic Chemistry extended (J. Org. Chem. 2009, 74, 5983) the reactivity of methylene cyclopropanes to the condensation of the aldehyde 9 with an acyl hydrazide, to give the pyrrole 11. Xue-Long Hou, also of the Shanghai Institute of Organic Chemistry, described (Tetrahedron Lett. 2009, 50, 6944) the Au-mediated reorganization of the alkynyl aziridine 12 to the pyrrole 13. Masahiro Yoshida of the University of Tokushima carried out (Tetrahedron Lett. 2009, 50, 6268) a similar rearrangement under oxidative conditions, giving the iodinated pyrrole 15. André M. Beauchemin of the University of Ottawa showed (Angew. Chem. Int. Ed. 2009, 48, 8325) that under acid catalysis, the oxime 16 cyclized to the pyridine 17. Shunsuke Chiba of Nanyang Technological University developed (J. Am. Chem. Soc. 2009, 131, 12570) the Mn(III)-mediated fusion of a cyclopropanol 18 with an alkenyl azide 19 to deliver the pyridine 20. Kazuaki Shimada of Iwate University found (Tetrahedron Lett. 2009, 50, 6651) that an isotellurazole such as 21, easily prepared from the corresponding alkyne, condensed with another alkyne 22, delivering the pyridine 23 with high regiocontrol. Christopher J. Moody of the University of Nottingham devised (Organic Lett. 2009, 11, 3686) a new route to the 1,2,4-triazine 24 from an α-diazoacetoacetate. He carried 24 on to the pyridine 26 by condensation with norbornadiene 25.

Troels Skrydstrup of Aarhus University devised (Angew. Chem. Int. Ed. 2012, 51, 4681) a gold-catalyzed protocol for the condensation of 1 with 2 to deliver the furan 3. Thomas A. Moss of AstraZeneca Mereside found (Tetrahedron Lett. 2012, 53, 3056) that readily-available α-chloroaldehydes such as 4 could be combined with 5 to make the furan 6. This same approach can be used to assemble pyrroles. Yong-Qiang Tu and Shao-Hua Wang of Lanzhou University developed (J. Org. Chem. 2012, 77, 4167) a Pd-cascade cyclization that transformed the ester 7 into the pyrrole 8. Cheol-Min Park of the Nanyang Technological University rearranged (Chem. Commun. 2012, 48, 3996; J. Am. Chem. Soc. 2012, 134, 4104) the oxime ether 10 to the pyrrole 11. Glenn C. Micalizio of Scripps/Florida established (J. Am. Chem. Soc. 2012, 134, 1352) a Ti-mediated coupling of 12 with an aromatic aldehyde to deliver the pyridine 13. Yoichiro Kuninobu, now at the University of Tokyo, and Kazuhiko Takai of Okayama University observed (Org. Lett. 2012, 14, 3182) high regioselectivity in the Re-mediated condensation of 14 with 15 to give the pyridine 16. Douglas M. Mans of GlaxoSmithKline, King of Prussia, cyclized (Org. Lett. 2012, 14, 1604) the amide 17 to the oxazole (not illustrated), leading, after intramolecular 4+2 cycloaddition, to the pyridine 18. Karl Hemming of the University of Huddersfield combined (Org. Lett. 2012, 14, 126) the cyclopropenone 20 with the imine 19 to construct the pyridine 21. Shu-Jiang Tu of Xuzhou University and Guigen Li of Texas Tech University condensed (Org. Lett. 2012, 14, 700) enamine 22 with the aldehyde hydrate 23 to give the pyrrole 24, which should be readily aromatized to the corresponding indole. Biaolin Yin of the South China University of Technology cyclized (Org. Lett. 2012, 14, 1098) the furan 25 to the indole 26. Richmond Sarpong of the University of California, Berkeley rearranged (J. Am. Chem. Soc. 2012, 134, 9946) the alkynyl cyclopropane 27 to an intermediate that was aromatized to the indole 28. Stefan France of Georgia Tech uncovered (Angew. Chem. Int. Ed. 2012, 51, 3198) an In catalyst that rearranged the cyclopropene 29 to the indole 30.

Alessandro Palmieri of the University of Camerino developed (Synlett 2010, 2468) the condensation of a nitro acrylate 1 with a 1,3-dicarbonyl partner 2 to give the furan 3. Chaozhong Li of the Shanghai Institute of Organic Chemistry showed (Tetrahedron Lett. 2010, 51, 3678) that an alkenyl halide 4 could be cyclized to the furan 5. Ayhan S. Demir of Middle East Technical University established (Chem. Commun. 2010, 46, 8032) that a Au catalyst could catalyze the addition of an amine 7 to a cyanoester 6 to give the pyrrole 8 . Bruce A. Arndtsen of McGill University effected (Org. Lett. 2010, 12, 4916) the net three-component coupling of an imine 9, an acid chloride 10, and an alkyne 11 to deliver the pyrrole 12. Bernard Delpech of CNRS Gif-sur-Yvette prepared (Org. Lett. 2010, 12, 4760) the pyridine 15 by combining the diene 13 with the incipient carbocation 14. Max Malacria, Vincent Gandon, and Corinne Aubert of UPMC Paris optimized (Synlett 2010, 2314) the internal Co-mediated cyclization of a nitrile alkyne 5 to the tetrasubstituted pyridine 17. Yoshiaki Nakao of Kyoto University and Tamejiro Hiyama, now at Chuo University, effected (J. Am. Chem. Soc. 2010, 132, 13666) selective substitution of a preformed pyridine 18 at the C-4 position by coupling with an alkene 19. We showed (J. Org. Chem. 2010, 75, 5737) that the anion from deprotonation of a pyridine 21 could be added in a conjugate sense to 22 to give 23. Other particularly useful strategies for further substitution of preformed pyridines have been described by Olafs Daugulis of the University of Houston (Org. Lett. 2010, 12, 4277), by Phil S. Baran of Scripps/La Jolla (J. Am. Chem. Soc. 2010, 132, 13194), and by Robert G. Bergmann of the University of California, Berkeley, and Jonathan A. Ellman of Yale University (J. Org. Chem. 2010, 75, 7863). K. C. Majumdar of the University of Kalyani developed (Tetrahedron Lett. 2010, 51, 3807) the oxidative Pd-catalyzed cylization of 24 to the indole 25. Nan Zheng of the University of Arkansas showed (Org. Lett. 2010, 12, 3736) that Fe could be used to catalyze the rearrangement of the azirine 26 to the indole 27.

Kyungsoo Oh of Chung-Ang University cyclized (Org. Lett. 2015, 17, 450) the chloro enone 1 with NBS to the furan 2. Hongwei Zhou of Zhejiang University acylated (Adv. Synth. Catal. 2015, 357, 389) the imine 3, leading to the furan 4. H. Surya Prakash Rao of Pondicherry University found (Synlett 2014, 26, 1059) that under Blaise conditions, exposure of 5 to three equivalents of 6 led to the pyrrole 7. Yoshiaki Nishibayashi of the University of Tokyo and Yoshihiro Miyake, now at Nagoya University, prepared (Chem. Commun. 2014, 50, 8900) the pyrrole 10 by adding the silane 9 to the enone 8. Barry M. Trost of Stanford University developed (Org. Lett. 2015, 17, 1433) the phosphine-mediated cyclization of 11 to an intermediate that on brief exposure to a Pd catalyst was converted to the pyridine 12. Nagatoshi Nishiwaki of the Kochi University of Technology added (Chem. Lett. 2015, 44, 776) the dinitrolactam 14 to the enone 13 to give the pyridine 15. Metin Balci of the Middle East Technical University assembled (Org. Lett. 2015, 17, 964) the tricyclic pyridine 18 by adding propargyl amine 17 to the aldehyde 16. Chada Raji Reddy of the Indian Institute of Chemical Technology cyclized (Org. Lett. 2015, 17, 896) the azido enyne 19 to the pyridine 20 by simple exposure to I2. Björn C. G. Söderberg of West Virginia University used (J. Org. Chem. 2015, 80, 4783) a Pd catalyst to simultaneously reduce and cyclize 21 to the indole 22. Ranjan Jana of the Indian Institute of Chemical Biology effected (Org. Lett. 2015, 17, 672) sequential ortho C–H activation and cyclization, adding 23 to 24 to give the 2-substituted indole 25. In a complementary approach, Debabrata Maiti of the Indian Institute of Technology Bombay added (Chem. Eur. J. 2015, 21, 8723) 27 to 26 to give the 3-substituted indole 28. In a Type 8 construction, Nobutaka Fujii and Hiroaki Ohno of Kyoto University employed (Chem. Eur. J. 2015, 21, 1463) a gold catalyst to add 30 to 29, leading to 31.

Masahiro Yoshida of the University of Tokushima described (Tetrahedron Lett. 2008, 49, 5021) the Pt-mediated rearrangement of alkynyl oxiranes such as 1 to the furan 2. Roman Dembinski of Oakland University reported (J. Org. Chem. 2008, 73, 5881) a related zinc-mediated rearrangement of propargyl ketones to furans. The cyclization of aryloxy ketones such as 3 to the benzofuran 4 developed (Tetrahedron Lett. 2008, 49, 6579) by Ikyon Kim of the Korea Research Institute of Chemical Technology is likely proceeding by a Friedel-Crafts mechanism. Sandro Cacchi and Giancarlo Fabrizi of Università degli Studi “La Sapienza”, Roma, observed (Organic Lett. 2008, 10, 2629) that base converted the enamine 5 to the pyrrole 6. Alternatively, oxidation of 5 with CuBr led to a pyridine. Zhuang-ping Zhuan of Xiamen University prepared (Adv. Synth. Cat. 2008, 350, 2778) pyrroles such as 9 by condensing an alkynyl carbinol 7 with a 1,3-dicarbonyl compound. Richard C. Larock of Iowa State University found (J. Org. Chem. 2008, 73, 6666) that combination of an alkynyl ketone 10 with 11 followed by oxidation with I-Cl led to the pyrazole 12. The “click” condensation of azides with alkynes, leading to the 1,4-disubstituted 1,2,3- triazole, has proven to be a powerful tool for combinatorial synthesis. Valery V. Fokin of Scripps/La Jolla and Zhenyang Lin and Guochen Jia of the Hong Kong University of Science and Technology have developed (J. Am. Chem. Soc. 2008, 130, 8923) a complementary approach, using Ru catalysts to prepare 1,5-disubstituted 1,2,3- triazoles. Remarkably, internal alkynes participate, and, as in the conversion of 13 to 15, propargylic alcohols direct the regioselectivity of the cycloaddition. A variety of methods have been put forward for functionalizing pyridines. Sukbok Chang of KAIST described (J. Am. Chem. Soc. 2008, 130, 9254) the direct oxidative homologation of a pyridine N -oxide 16 to give the unsaturated ester 18. Jonathan Clayden of the University of Manchester observed (Organic Lett. 2008, 10, 3567) that metalation of 19 gave an anion that rearranged to 20 with complete retention of enantiomeric excess. Shigeo Katsumura of Kwansei Gakuin University developed (Tetrahedron Lett. 2008, 49, 4349) an intriguing three-component coupling, combining 21, 22, and methanesulonamide 23 to give the pyridine 24.

Mei-Huey Lin of the National Changhua University of Education rearranged (J. Org. Chem. 2014, 79, 2751) the initial allene derived from 1 to the γ-chloroenone. Displacement with acetate followed by hydrolysis led to the furan 2. A. Stephen K. Hashmi of Ruprecht-Karls-Universität Heidelberg showed (Angew. Chem. Int. Ed. 2014, 53, 3715) that the Au-catalyzed conversion of the bis alkyne 3, mediated by 4, proceeded selectively to give 5. Tehshik P. Yoon of the University of Wisconsin used (Angew. Chem. Int. Ed. 2014, 53, 793) visible light with a Ru catalyst to rearrange the azide 6 to the pyrrole 7. Cheol-Min Park, now at UNIST, found (Chem. Sci. 2014, 5, 2347) that a Ni catalyst reorganized the methoxime 8 to the pyrrole 9. A Rh catalyst converted 8 to the corresponding pyridine (not illustrated). In the course of a synthesis of opioid ligands, Kenner C. Rice of the National Institute on Drug Abuse optimized (J. Org. Chem. 2014, 79, 5007) the preparation of the pyridine 11 from the alcohol 10. Vincent Tognetti and Cyrille Sabot of the University of Rouen heated (J. Org. Chem. 2014, 79, 1303) 12 and 13 under micro­wave irradiation to give the 3-hydroxy pyridine 14. Tomislav Rovis of Colorado State University prepared (J. Am. Chem. Soc. 2014, 136, 2735) the pyridine 17 by the Rh-catalyzed combination of 15 with 16. Fabien Gagosz of the Ecole Polytechnique rearranged (Angew. Chem. Int. Ed. 2014, 53, 4959) the azirine 18, readily available from the oxime of the β-keto ester, to the pyridine 19. Matthias Beller of the Universität Rostock used (Chem. Eur. J. 2014, 20, 1818) a Zn catalyst to mediate the opening of the epoxide 21 with the aniline 20. A Rh cata­lyst effected the oxidation and cyclization of the product amino alcohol to the indole 22. Sreenivas Katukojvala of the Indian Institute of Science Education & Research showed (Angew. Chem. Int. Ed. 2014, 53, 4076) that the diazo ketone 23 could be used to anneal a benzene ring onto the pyrrole 24, leading to the 2,7-disubstituted indole 25.

It has been known for some time that an acid chloride 1 can be added to an alkyne 2 to give the β-chloro enone. Yasushi Tsuji of Kyoto University found (J. Am. Chem. Soc. 2009, 131, 6668) that with an Ir catalyst, the condensation of 1 with 2 could be directed to the furan 3. Huanfeng Jiang of the South China University of Technology described (Organic Lett. 2009, 11, 1931) a complementary route to furans, Cu-mediated condensation of a propargyl alcohol 4 with the diester 5 to give 6. Bruce A. Arndtsen of McGill University developed (Organic Lett. 2009, 11, 1369) an approach to pyrroles such as 9, by condensation of an α,β-unsaturated α-cyano imine 7 with the acid chloride 8. Thomas J. J. Müller of Heinrich-Heine-Universität Düsseldorf observed (Organic Lett. 2009, 11, 2269) the condensation of an acid chloride 11 with a propargyl amine 10, leading to the iodo pyrrole 12. John A. Murphy of the University of Strathclyde uncovered (Tetrahedron Lett. 2009, 50, 3290) a new entry to the Fischer indole synthesis, by Petasis homologation of a hydrazide 13. Dali Yin of Peking Union Medical College took advantage (Organic Lett. 2009, 11, 637) of the easy sequential displacement of the fluorides of 15, leading, after acid-catalyzed cyclization, to the indole 17. Kang Zhao of Tianjin University extended (Organic Lett. 2009, 11, 2417; Organic Lett. 2009, 11, 2643) his studies of oxidation of an enamine 18 to the 2H -azirine, that on heating cyclized to the indole 19. Peter Wipf of the University of Pittsburgh established (Chem. Commun. 2009, 104) a microwave-promoted indole synthesis, illustrated by the intramolecular Diels-Alder cyclization of 20 to 21. A review delineating all nine types of indole syntheses will appear shortly in Angewandte Chemie . Fushun Liang and Qun Liu of Northeast Normal University demonstrated (J. Org. Chem. 2009, 74, 899) that the readily-prepared ketene thioacetal 22 condensed with NH3 to give the pyridine 23. Sundaresan Prabhakar and Ana M. Lobo of the New University of Lisbon observed (Tetrahedron Lett. 2009, 50, 3446) that the addition of the alkoxy propargyl amine to the alkyne 25 gave a Z alkene, that on warming rearranged to the pyridine 26.

Nabyl Merbouh and Robert Britton of Simon Fraser University developed (Eur. J. Org. Chem. 2013, 3219) a general route to a 2,5-disubstituted furan 3 by taking advantage of the ready α-chlorination of an aldehyde 1, followed by coupling with a ketone eno­late 2. Jérôme Waser of the Ecole Polytechnique Fédérale de Lausanne used (Angew. Chem. Int. Ed. 2013, 52, 6743) 5 to oxidize the allene 4 to the furan 6. Qian Zhang and Xihe Bi of Northeast Normal University used (Angew. Chem. Int. Ed. 2013, 52, 6953) Ag catalysis to prepare the pyrrole 9 by coupling the alkyne 7 with the isonitrile 8. Aiwen Lei of Wuhan University reported (Angew. Chem. Int. Ed. 2013, 52, 6958) similar results. Professor Lei also developed (Chem. Commun. 2013, 49, 5853) the Pd-catalyzed oxidation of the allyl imine 10 to the pyrrole 11. Kamal K. Kapoor of the University of Jammu reduced (Tetrahedron Lett. 2013, 54, 5699) the Michael adduct 12 to the pyrrole 13 with triethyl phosphite. Edgar Haak of the Otto-von-Guericke-Universität, Magdeburg condensed (Eur. J. Org. Chem. 2013, 7354) the alkynyl carbinol 14 with aniline to give the N-phenyl pyrrole 15. Jean Rodriguez and Thierry Constantieux of Aix-Marseille Université prepared (Eur. J. Org. Chem. 2013, 4131) the pyridine 18 by combining the ketone 16 and the unsaturated aldehyde 17 with NH4OAc. Teck-Peng Loh of the University of Sciences and Technology of China and Nanyang Technological University found (Angew. Chem. Int. Ed. 2013, 52, 8584) that TMEDA was an effective organocatalyst for the assembly of the pyridine 21 from 19 and 20. Andrew D. Smith of the University of St Andrews showed (Angew. Chem. Int. Ed. 2013, 52, 11642) that the pyridyl tosylate 24, avail­able by the combination of 22 and 23, readily coupled with both carbon and amine nucleophiles. In a related development, D. Tyler McQuade of Florida State University prepared (Org. Lett. 2013, 15, 5298) the 2-bromopyridine 26 from the alkylidene malononitrile 25. Two versatile approaches to substituted indoles were recently described. David F. Wiemer of the University of Iowa cyclized (J. Org. Chem. 2013, 78, 9291) the Stobbe product 27 to the 3-bromo indole 28.

Huanfeng Jiang of the South China University of Technology showed (J. Org. Chem. 2010, 75, 966) that an alkynoate 1 could be condensed with a 1,3-dicarbonyl compound 2 to give, under oxidizing conditions, the furan 3. Phil Ho Lee of Kangwon National University found (Tetrahedron Lett. 2010, 51, 1899) that the enyne 4 cyclized smoothly to the furan 5. Yahong Li of Suzhou University and Vladimir Gevorgyan of the University of Illinois, Chicago, demonstrated (J. Am. Chem. Soc. 2010, 132, 7645) that the cyclization of 6 proceeded with silyl migration, to give 7. François Bilodeau and Pat Forgione of Boehringer Ingelheim (Canada) optimized (J. Org. Chem. 2010, 75, 1550) the Pd-mediated decarboxylative coupling of a furoic acid 8 with 9 to give 10. This protocol also worked well with pyrrole carboxylic acids. In another transformation of a preformed pyrrole, Masatomo Iwao of Nagasaki University observed (Organic Lett. 2010, 12, 2734) that in the presence of LDA/diisopropylamine, the initially formed 2-anion from the deprotonation of 11 gave the 2-product 12 with more reactive electrophiles but the 5-product 13 with less reactive electrophiles. Umasish Jana of Jadavpur University developed (J. Org. Chem. 2010, 75, 1674) a route to more highly substituted pyrroles such as 17 using the remarkable four-component coupling of 14, 15, and 16 with nitromethane, the carbon of which was incorporated in the product. Laura L. Anderson, also of the University of Illinois, Chicago, designed (Organic Lett. 2010, 12, 2290) a clever approach to pyrroles, based on the Ir-catalyzed rearrangement of O-allyl oximes such as 18. Xiaofeng Tong of the East China University of Science and Technology reported (Chem. Commun. 2010, 312) the condensation of 20 with 21 to give the dihydropyridine 22. Base-mediated elimination of sulfinate could convert 22 into the pyridine. Jin-Quan Yu of Scripps/La Jolla found (Angew. Chem. Int. Ed. 2010, 49, 1275) that Pd-mediated activation of the nictotinamide 23 proceeded with high regioselectivity, leading to 25. Zhiping Li of Remnin University of China demonstrated (J. Org. Chem. 2010, 75, 4636) that the chloroenamine 26 cyclized to the indole 27 on exposure to NaI.

Xin-Yan Wu of East China University of Science and Technology and Jun Yang of the Shanghai Institute of Organic Chemistry added (Tetrahedron Lett. 2014, 55, 4071) the Grignard reagent 1 to propargyl alcohol 2 to give an intermediate that could be bory­lated, then coupled under Pd catalysis with an anhydride, leading to the furan 3. Fuwei Li of the Lanzhou Institute of Chemical Physics constructed (Org. Lett. 2014, 16, 5992) the furan 6 by oxidizing the keto ester 4 in the presence of the enamide 5. Yuanhong Liu of the Shanghai Institute of Organic Chemistry prepared (Angew. Chem. Int. Ed. 2014, 53, 11596) the pyrrole 9 by reducing the azadiene 7 with the Negishi reagent, then adding the nitrile 8. Yefeng Tang of Tsinghua University found (Tetrahedron Lett. 2014, 55, 6455) that the Rh carbene derived from 11 could be added to an enol silyl ether 10 to give the pyrrole 12. Pazhamalai Anbarasan of the Indian Institute of Technology Madras reported (J. Org. Chem. 2014, 79, 8428) related results. Zheng Huang of the Shanghai Institute of Organic Chemistry established (Angew. Chem. Int. Ed. 2014, 53, 1390) a connection between substituted piperidines and pyridines by dehydrogenating 13 to 15, with 14 as the acceptor. Joseph P. A. Harrity of the University of Sheffield conceived (Chem. Eur. J. 2014, 20, 12889) the cascade assembly of the pyridine 18 by cycloaddition of 16 with 17 followed by Pd-catalyzed coupling. Teck-Peng Loh of Nanyang Technological University converted (Org. Lett. 2014, 16, 3432) the keto ester 19 into the azirine, then eliminated it to form an aza­triene that cyclized to the pyridine 20. En route to a cholesteryl ester transfer protein inhibitor, Zhengxu S. Han of Boehringer Ingelheim combined (Org. Lett. 2014, 16, 4142) 21 with 22 to give an intermediate that could be oxidized to 23. Magnus Rueping of RWTH Aachen used (Angew. Chem. Int. Ed. 2014, 53, 13264) an Ir photoredox catalyst in conjunction with a Pd catalyst to cyclize the enamine 24 to the indole 25. Yingming Yao and Yingsheng Zhao of Soochow University effected (Angew. Chem. Int. Ed. 2014, 53, 9884) oxidative cyclization of 26 to 27.