Academic literature on the topic '5-a]pyridines'

The reduction of pyridines offers an attractive approach to piperidine synthesis, and now Toshimichi Ohmura and Michinori Suginome of Kyoto University have developed (J. Am. Chem. Soc. 2012, 134, 3699) a rhodium-catalyzed hydroboration of pyridines, including the reaction of 1 to produce 3. Timothy J. Donohoe at the University of Oxford has found (Org. Lett. 2011, 13, 2074) that pyridinium silanes 4 undergo intramolecular hydride transfer by treatment with TBAF to produce dihydropyridones (e.g., 5) with good diastereoselectivity. Enantioselective amination of allylic alcohols has proven challenging, but Ross A. Widenhoefer at Duke University has reported (Angew. Chem. Int. Ed. 2012, 51, 1405) that a chiral gold catalyst can effect such intramolecular cyclizations with good enantioselectivity, as in the synthesis of 7 from 6. Alternatively, Masato Kitamura at Nagoya University has developed (Org. Lett. 2012, 14, 608) a ruthenium catalyst that operates at as low as 0.05 mol% loading for the conversion of substrates such as 8 to 9. Efforts to replace transition metal catalysts with alkaline earth metal-based alternatives have been gaining increasing attention, and Kai C. Hultzsch at Rutgers University has found (Angew. Chem. Int. Ed. 2012, 51, 394) that the magnesium complex 12 is capable of catalyzing intramolecular hydroamination (e.g., 10 to 11) with high enantioselectivity. Meanwhile, a stereoselective Wacker-type oxidation of tert-butanesulfinamides such as 13 to produce pyrrolidine derivatives 14 has been disclosed (Org. Lett. 2012, 14, 1242) by Shannon S. Stahl at the University of Wisconsin at Madison. Though highly desirable, Heck reactions have rarely proven feasible with alkyl halides due to competitive β-hydride elimination of the alkyl palladium intermediates. Sherry R. Chemler at the State University of New York at Buffalo has demonstrated (J. Am. Chem. Soc. 2012, 134, 2020) a copper-catalyzed enantioselective amination Heck-type cascade (e.g., 15 and 16 to 17) that is thought to proceed via radical intermediates. David L. Van Vranken at the University of California at Irvine has reported (Org. Lett. 2012, 14, 3233) the carbenylative amination of N-tosylhydrazones, which proceeds through η3-allyl Pd intermediates constructed via carbene insertion. This chemistry was applied to the two-step synthesis of caulophyllumine B from vinyl iodide 18 and N-tosylhydrazone 19.

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.

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.

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.

Enantiomerically-pure natural amino acids can serve as starting materials for alkaloid synthesis. In his synthesis (J. Org. Chem. 2007, 72, 10114) of (-)-α-kainic acid 3, Kyung Woon Jung of the University of Southern California prepared the diazo sulfone 1 from (L)-glutamic acid. Rh-mediated intramolecular C-H insertion proceeded with the predicted high diastereoselectivity, to give the lactam 2, containing seven of the ten carbon atoms and two of the three stereogenic centers of (-)-α-kainic acid 3. The absolute configuration of the nitrogen ring system(s) can also be established by chiral catalysis. Dawei Ma of the Shanghai Institute of Organic Chemistry has developed (J. Am. Chem. Soc. 2007, 129, 9300) a chiral Cu catalyst that mediated the addition of alkynyl esters and ketones to the prochiral acylated pyridine 4 in high enantiomeric excess. The dihydro-pyridines (e.g. 5) so produced will be versatile starting materials both for alkaloid synthesis, as illustrated by the preparation of the Dendrobatid alkaloid 223AB 6, and for the production of pharmaceuticals. In his synthesis of the Dentrobatid alkaloid pumiliotoxin 251D 9, Timothy F. Jamison took (J. Org. Chem. 2007, 72, 7451) as his starting material another amino acid, proline. Ni-mediated cyclization of the epoxide 8 proceeded with high geometric and regiocontrol, to give 9. The chemistry to convert 7 into 8 with high diastereocontrol and without racemization is a substantial contribution that will have many other applications. In his synthesis (Organic Lett. 2007, 9, 2763) of spirotryprostatin B 12, Barry M. Trost of Stanford University also started with proline, which was readily elaborated to the oxindole 10. The question was, could the Pd-catalyzed decarboxylation of 10 be induced to provide specifically 11? Counting geometric isomers of the trisubstituted alkene, and allylic regioisomers, as well as diastereomers, there were sixteen possible products from this prenylation. Using chiral Pd control, the rearrangement proceeded with 14:1 regiocontrol, and 16:1 diasterocontrol. Oxidative cyclization of 11 then delivered spirotryprostatin B 12. The Cephalotaxus alkaloid (-)-drupacine 19 has five stereogenic centers, including four of the five positions on the cyclopentane ring.