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Synlett 2011(19): 2789-2794  
DOI: 10.1055/s-0031-1289556
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Rhodium(III)-Catalyzed Synthesis of Pyridines from α,β-Unsaturated Ketoximes and Internal Alkynes

Pei Chui Tooa, Toshiharu Nojib, Ying Jie Lima, Xingwei Li*c, Shunsuke Chiba*a
a Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371 Singapore, Singapore
Fax: +6567911961; e-Mail: shunsuke@ntu.edu.sg;
b Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan
c Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P. R. of China
e-Mail: xwli@dicp.ac.cn;
Further Information

Publication History

Received 1 September 2011
Publication Date:
25 October 2011 (online)

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Abstract

A method for the synthesis of highly substituted pyri­dines from α,β-unsaturated oximes and internal alkynes has been developed using [Cp*RhCl2]2-CsOPiv as the catalyst system. The present transformation is carried out by a redox-neutral sequence of vinylic C-H rhodation, alkyne insertion, and C-N bond formation of the putative vinyl rhodium intermediate with the oxime nitrogen, where the N-O bond of oxime derivatives could work as an internal oxidant to maintain the catalytic cycle.

Key words

pyridines - oximes - alkynes - rhodium - C-H activation

    References and Notes

  • 1a Progress in Heterocyclic Chemistry   Vol. 20:  Gribble GW. Joule JA. Elsevier; Oxford: 2008. and other volumes in this series
  • 1b Comprehensive Heterocyclic Chemistry III   Katritzky AR. Ramsden CA. Scriven EFV. Taylor RJK. Pergamon; Oxford: 2008. 
  • 1c Comprehensive Heterocyclic Chemistry II   Katritzky AR. Rees CA. Scriven EFV. Taylor RJK. Pergamon; Oxford: 2008. 
  • 1d Comprehensive Heterocyclic Chemistry II   Katritzky AR. Rees CW. Scriven EFV. McKillop A. Pergamon; Oxford: 1996. and references therein
  • 1e Eicher T. Hauptmann S. The Chemistry of Heterocycles   Wiley-VCH; Weinheim: 2003. 
  • For recent reviews on synthesis of pyridines, see:
  • 2a Hill MD. Chem. Eur. J.  2010,  16:  12052 
    Search in Google Scholar
  • 2b Bagley MC. Glover C. Merritt EA. Synlett  2007,  2459 
  • 2c Heller B. Hapke M. Chem. Soc. Rev.  2007,  36:  1085 
    Search in Google Scholar
  • 2d Ciufolini MA. Chan BK. Heterocycles  2007,  74:  101 
    Search in Google Scholar
  • 2e Henry GD. Tetrahedron  2004,  60:  6043 
    Search in Google Scholar
  • 2f Varela JA. Saa C. Chem. Rev.  2003,  103:  3787 
    Search in Google Scholar
  • For recent selected reports on synthesis of pyridines, see:
  • 3a Wang YF. Toh KK. Ng PJE. Chiba S. J. Am. Chem. Soc.  2011,  133:  6411 
    Search in Google Scholar
  • 3b Nakamura I. Zhang D. Terada M. J. Am. Chem. Soc.  2010,  132:  7884 
    Search in Google Scholar
  • 3c Chiba S. Xu Y.-J. Wang Y.-F. J. Am. Chem. Soc.  2009,  131:  12886 
    Search in Google Scholar
  • 3d Wang YF. Chiba S. J. Am. Chem. Soc.  2009,  131:  12570 
    Search in Google Scholar
  • 3e Manning JR. Davies HML. J. Am. Chem. Soc.  2008,  130:  8602 
    Search in Google Scholar
  • 3f Manning JR. Davies HML. J. Am. Chem. Soc.  2008,  130:  8602 
    Search in Google Scholar
  • 3g Liu S. Liebeskind LS. J. Am. Chem. Soc.  2008,  130:  6918 
    Search in Google Scholar
  • 3h Barluenga J. Fernández-Rodríguez MA. García-García P. Aguilar E. J. Am. Chem. Soc.  2008,  130:  2764 
    Search in Google Scholar
  • 3i Parthasarathy K. Jeganmohan M. Cheng C.-H. Org. Lett.  2008,  10:  325 
    Search in Google Scholar
  • 3j Movassaghi M. Hill MD. Ahmad OK. J. Am. Chem. Soc.  2007,  129:  10096 
    Search in Google Scholar
  • 3k Dash J. Lechel T. Reissig H.-U. Org. Lett.  2007,  9:  5541 
    Search in Google Scholar
  • 3l Trost BM. Gutierrez AC. Org. Lett.  2007,  9:  1473 
    Search in Google Scholar
  • 3m Yamamoto Y. Kinpara K. Ogawa R. Nishiyama H. Itoh K. Chem. Eur. J.  2006,  12:  5618 
    Search in Google Scholar
  • 3n Movassaghi M. Hill MD. J. Am. Chem. Soc.  2006,  128:  4592 
    Search in Google Scholar
  • 3o Tanaka R. Yuza A. Watai Y. Suzuki D. Takayama Y. Sato F. Urabe H. J. Am. Chem. Soc.  2005,  127:  7774 
    Search in Google Scholar
  • 3p McCormick MM. Duong HA. Zuo G. Louie J. J. Am. Chem. Soc.  2005,  127:  5030 
    Search in Google Scholar
  • For recent reviews, see:
  • 4a Wencel-Delord J. Dröge T. Liu F. Glorius F. Chem. Soc. Rev.  2011,  40:  4740 
    Search in Google Scholar
  • 4b Ackermann L. Chem. Rev.  2011,  111:  1315 
    Search in Google Scholar
  • 4c Satoh T. Miura M. Chem. Eur. J.  2010,  16:  11212 
    Search in Google Scholar
  • 4d Colby DA. Bergman RG. Ellman JA. Chem. Rev.  2010,  110:  624 
    Search in Google Scholar
  • 4e Lyons TW. Sanford MS. Chem. Rev.  2010,  110:  1147 
    Search in Google Scholar
  • 4f Sun C.-L. Li B.-J. Shi Z.-J. Chem. Commun.  2010,  46:  677 
    Search in Google Scholar
  • 4g Ackermann L. Vicente R. Kapdi AR. Angew. Chem. Int. Ed.  2009,  48:  9792 
    Search in Google Scholar
  • 4h Chen X. Engle KM. Wang D.-H. Yu J.-Q. Angew. Chem. Int. Ed.  2009,  48:  5094 
    Search in Google Scholar
  • 4i Kulkarni AA. Daugulis O. Synthesis  2009,  4087 
  • 4j Kakiuchi F. Kochi T. Synthesis  2008,  3013 
  • 4k Park YJ. Park J.-W. Jun C.-H. Acc. Chem. Res.  2008,  41:  222 
    Search in Google Scholar
  • 4l Kakiuchi F. Chatani N. Adv. Synth. Catal.  2003,  345:  1077 
    Search in Google Scholar
  • 4m Ritleng V. Sirlin C. Pfeffer M. Chem. Rev.  2002,  102:  1731 
    Search in Google Scholar
  • 4n Kakiuchi F. Murai S. Acc. Chem. Res.  2002,  35:  826 
    Search in Google Scholar
  • 4o Dyker G. Angew. Chem. Int. Ed.  1999,  38:  1698 
    Search in Google Scholar
  • For selected reports on the ortho-metallation and carbon-carbon bond-formation sequence of aldimine and ketimine derivatives, see:
  • 5a Gao K. Lee P.-S. Fujita T. Yoshikai N. J. Am. Chem. Soc.  2010,  132:  12249 
    Search in Google Scholar
  • 5b Yoshikai N. Matsumoto A. Norinder J. Nakamura E. Angew. Chem. Int. Ed.  2009,  48:  2925 
    Search in Google Scholar
  • 5c Kuninobu Y. Nishina Y. Matsuki T. Takai K. J. Am. Chem. Soc.  2008,  130:  14062 
    Search in Google Scholar
  • 5d Kuninobu Y. Kikuchi K. Tokunaga Y. Nishina Y. Takai K. Tetrahedron  2008,  64:  5974 
    Search in Google Scholar
  • 5e Kuninobu Y. Nishina Y. Nakagawa C. Takai K. J. Am. Chem. Soc.  2006,  128:  12376 
    Search in Google Scholar
  • 5f Kuninobu Y. Tokunaga Y. Kawata A. Takai K. J. Am. Chem. Soc.  2006,  128:  202 
    Search in Google Scholar
  • 5g Kuninobu Y. Kawata A. Takai K. J. Am. Chem. Soc.  2005,  127:  13498 
    Search in Google Scholar
  • 5h Thalji RK. Ahrendt KA. Bergman RG. Ellman JA. J. Org. Chem.  2005,  70:  6775 
    Search in Google Scholar
  • 5i Ueura K. Satoh T. Miura M. Org. Lett.  2005,  7:  2229 
    Search in Google Scholar
  • 5j Lim S.-G. Ahn J.-A. Jun C.-H. Org. Lett.  2004,  6:  4687 
    Search in Google Scholar
  • 5k Thalji RK. Ahrendt KA. Bergman RG. Ellman JA. J. Am. Chem. Soc.  2001,  123:  9692 
    Search in Google Scholar
  • 5l Jun C.-H. Hong J.-B. Kim Y.-H. Chung K.-Y. Angew. Chem. Int. Ed.  2000,  39:  3440 
    Search in Google Scholar
  • 5m Kakiuchi F. Sato T. Tsujimoto T. Yamauchi M. Chatani N. Murai S. Chem. Lett.  1998,  1053 
  • 5n Fukuyama T. Chatani N. Kakiuchi F. Murai S. J. Org. Chem.  1997,  62:  5647 
    Search in Google Scholar
  • 5o Kakiuchi F. Yamauchi M. Chatani N. Murai S. Chem. Lett.  1996,  111 
  • 6 For a review, see: Patureau FW. Glorius F. Angew. Chem. Int. Ed.  2011,  50:  1977 
    Search in Google Scholar
  • For a report on rhodium(III)-catalyzed redox-neutral synthesis of azaheterocycles from benzhydroxamic acid derivatives and oxime derivatives with alkynes, see:
  • 7a Guimond N. Gorelsky SI. Fagnou K. J. Am. Chem. Soc.  2011,  133:  6449 
    Search in Google Scholar
  • 7b Rakshit S. Grohmann C. Besset T. Glorius F. J. Am. Chem. Soc.  2011,  133:  2350 
    Search in Google Scholar
  • 7c Too PC. Chua SH. Wong SH. Chiba S. J. Org. Chem.  2011,  76:  6159 
    Search in Google Scholar
  • 7d Hyster TK. Rovis T. Chem. Sci.  2011,  2:  1606 
    Search in Google Scholar
  • 7e Zhang X. Chen D. Zhao M. Zhao J. Jia A. Li X. Adv. Synth. Catal.  2011,  353:  719 
    Search in Google Scholar
  • 7f Too PC. Wang Y.-F. Chiba S. Org. Lett.  2010,  12:  5688 
    Search in Google Scholar
  • 7g Guimond N. Gouliaras C. Fagnou K. J. Am. Chem. Soc.  2010,  132:  6908 
    Search in Google Scholar
  • For pioneering studies on the reactivity of Cp*Rh(OAc)n for directing-group-assisted C-H bond fission, see:
  • 8a Davies DL. Al-Duaij O. Fawcett J. Giardiello M. Hilton ST. Russell DR. Dalton Trans.  2003,  4132 
  • For investigation of the reactivity of the rhodacycles as well as reaction mechanism of the cyclometallation, see:
  • 8b Li L. Brennessel WW. Jones WD. Organometallics  2009,  28:  3492 
    Search in Google Scholar
  • 8c Han Y.-F. Li H. Hu P. Jin G.-X. Organometallics  2011,  30:  905 
    Search in Google Scholar
  • For selected reports on rhodium(III)-catalyzed oxidative C-H bond functionalization-C-N bond formation with alkynes, see:
  • 9a Stuart DR. Alsabeh P. Kuhn M. Fagnou K. J. Am. Chem. Soc.  2010,  132:  18326 
    Search in Google Scholar
  • 9b Chen J. Song G. Pan C.-L. Li X. Org. Lett.  2010,  12:  5426 
    Search in Google Scholar
  • 9c Su Y. Zhao M. Han K. Song G. Li X. Org. Lett.  2010,  12:  5462 
    Search in Google Scholar
  • 9d Hyster TK. Rovis T. J. Am. Chem. Soc.  2010,  132:  10565 
    Search in Google Scholar
  • 9e Rakshit S. Patureau FW. Glorius F. J. Am. Chem. Soc.  2010,  132:  9585 
    Search in Google Scholar
  • 9f Morimoto K. Hirano K. Satoh T. Miura M. Org. Lett.  2010,  12:  2068 
    Search in Google Scholar
  • 9g Mochida S. Umeda N. Hirano K. Satoh T. Miura M. Chem. Lett.  2010,  39:  744 
    Search in Google Scholar
  • 9h Guimond N. Fagnou K. J. Am. Chem. Soc.  2009,  131:  12050 
    Search in Google Scholar
  • 9i Fukutani T. Umeda N. Hirano K. Satoh T. Miura M. Chem. Commun.  2009,  5141 
  • 9j Stuart DR. Bertrand-Laperle M. Burgess KMN. Fagnou K. J. Am. Chem. Soc.  2008,  130:  16474 
    Search in Google Scholar
  • For synthesis of pyridine derivatives by utilization of 6π-electrocyclization of azatrienes generated by ortho-vinylation, see:
  • 10a Parthasarathy K. Cheng C.-H. J. Org. Chem.  2009,  74:  9359 
    Search in Google Scholar
  • 10b Colby DA. Bergman RG. Ellman JA. J. Am. Chem. Soc.  2008,  130:  3645 
    Search in Google Scholar
  • 10c Yotphan S. Bergman RG. Ellman JA. J. Am. Chem. Soc.  2008,  130:  2452 
    Search in Google Scholar
  • 10d Parthasarathy K. Jeganmohan M. Cheng C.-H. Org. Lett.  2008,  10:  325 
    Search in Google Scholar
  • 10e Lim S.-G. Lee JH. Moon CW. Hong J.-B. Jun C.-H. Org. Lett.  2003,  5:  2759 
    Search in Google Scholar
  • 11 Umeda N. Tsurugi H. Satoh T. Miura M. Angew. Chem. Int. Ed.  2008,  47:  4019 
    Search in Google Scholar
  • 13 Although E/Z isomerization of the N-O bond of oxime 1k might be possible in the present reaction conditions, we are not certain whether the Z-isomer of 1k was converted into pyridine via its isomerization to E-isomer during this reaction. For isomerization of the oxime N-O bonds, see: Johnson JE. Silk NM. Nalley EA. Arfan M. J. Org. Chem.  1981,  46:  546 
    Search in Google Scholar
12

The formation of 4aa could result in generation of rhodium(I) species, which should be re-oxidized to rhodium(III) by air (O2) to maintain the catalytic turnover.

14

General Procedure (Table 1, Entry 6)
To a MeOH solution (2.5 mL) of (2E,3E)-4-phenylbut-3-
en-2-one oxime (1a, 80.5 mg, 0.50 mmol) and diphenyl-acetylene (2a, 106.9 mg, 0.60 mmol) were added [Cp*RhCl2]2 (7.7 mg, 0.0125 mmol) and CsOPiv (35.1 mg, 0.15 mmol), and the reaction mixture was stirred at 60 ˚C under air for 7 h. After cooled to r.t., the solvent was removed in vacuo, and the resulting crude material was subjected to flash column chromatography (hexane-EtOAc = 90:10) to afford 6-methyl-2,3,4-triphenylpyridine (3aa, 126.4 mg, 0.393 mmol) in 79% yield.