Download PDF
Synthesis 2009(9): 1485-1493  
DOI: 10.1055/s-0028-1087991
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Base-Catalysed One-Pot Three-Component Coupling Reaction Leading to Nitrosubstituted Pyrroles

Ian R. Baxendale, Christopher D. Buckle, Steven V. Ley*, Lucia Tamborini
Innovative Technology Centre for Advanced Chemical Synthesis, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
Fax: +44(1223)336442; e-Mail: svl1000@cam.ac.uk;
Further Information

Publication History

Received 22 December 2008
Publication Date:
06 March 2009 (online)

   Permissions and Reprints All articles of this category
Preview

Abstract

Tosyl isocyanide and ethyl chloroformate react with nitrostyrenes to afford nitro-substituted pyrroles in good yield when a catch-and-release protocol was employed as a purification strategy.

Key words

pyrroles - immobilized reagents - heterocycles - multi-component

    References

  • 1a Davies DT. Aromatic Heterocyclic Chemistry   OUP; Oxford: 1992. 
  • 1b Barton D. Ollis WD. Sammes PG. Comprehensive Organic Chemistry   Vol. 4:  Jackson AH. Pergamon Press; Oxford: 1979.  p.276 
    Search in Google Scholar
  • 1c Lesage S. Xu H. Durham L. Hydrol. Sci. J.  1993,  38:  343 
    Search in Google Scholar
  • 1d The Porphyrins   Dolphin D. Academic Press; New York: 1977. 
  • 1e Joh Y. Kotate Y. Macromolecules  1970,  3:  337 
    Search in Google Scholar
  • 1f Anez M. Uribe G. Mendoza L. Contreras R. Synthesis  1981,  214 
  • 2a Hui F. Peng P. Hamann MT. Hu J.-F. Chem. Rev.  2008,  108:  264 
    Search in Google Scholar
  • 2b Wang W. Namikoshi M. Heterocycles  2007,  74:  53 
    Search in Google Scholar
  • 2c Morris JC. Phillips AJ. Nat. Prod. Rep.  2008,  25:  95 
    Search in Google Scholar
  • 2d Hughes CC. Prieto-Davo A. Jensen PR. Fenical W. Org. Lett.  2008,  10:  629 
    Search in Google Scholar
  • 2e Donohoe TJ. Thomas RE. Chem. Rec.  2007,  7:  180 
    Search in Google Scholar
  • 2f Walsh CT. Garneau-Tsodikova S. Howard-Jones AR. Nat. Prod. Rep.  2006,  23:  517 
    Search in Google Scholar
  • 2g Gupton JT. In Topics in Heterocyclic Chemistry   Springer; Berlin/Heidelberg: 2006.  p.53-92  
  • 3a Nogami T. Shigehara Y. Matsuda N. Takahashi Y. Naganawa H. Nakamura H. Hamada M. Muraoka Y. Takita T. Iitaka T. Takeuchi T. J. Antibiot.  1990,  43:  1192 
    Search in Google Scholar
  • 3b Jacobi PA. Coults LD. Guo JS. Leung SI. J. Org. Chem.  2000,  65:  205 
    Search in Google Scholar
  • 3c Fürstner A. Angew. Chem. Int. Ed.  2003,  42:  3582 
    Search in Google Scholar
  • 3d Domingo VM. Aleman C. Brillas E. Julia L. J. Org. Chem.  2001,  66:  4058 
    Search in Google Scholar
  • 3e Hong F. Zaidi J. Pang Y.-P. Cusack B. Richelson E. J. Chem. Soc., Perkin Trans. 1  1997,  2997 
  • 3f Lea AP. McTavish D. Drugs  1997,  53:  828 
    Search in Google Scholar
  • 3g Higasio YS. Shoji T. Appl. Catal., A  2001,  221:  197 
    Search in Google Scholar
  • 3h Sigman DS. Chen CB. Annu. Rev. Biochem.  1990,  59:  207 
    Search in Google Scholar
  • 3i Skotheim TA. Handbook of Conducting Polymers   Marcel Dekker; New York: 1986. 
  • For a selection of the most generic methods see:
  • 4a De Kimpe N. Abbaspour TK. Stevens C. De Cooman P. Tetrahedron  1997,  53:  3693 ; and references cited therein
    Search in Google Scholar
  • 4b Crawley ML. Goljer I. Jenkins DJ. Mehlmann JF. Nogle L. Dooley R. Mahaney PE. Org. Lett.  2006,  8:  5837 
    Search in Google Scholar
  • 4c Martin R. Rivero MR. Buchwald SL. Angew. Chem. Int. Ed.  2006,  45:  7079 
    Search in Google Scholar
  • 4d Larionov OV. de Meijere A. Angew. Chem. Int. Ed.  2005,  117:  5809 
    Search in Google Scholar
  • 4e Gorin DJ. Davis NR. Toste FD. J. Am. Chem. Soc.  2005,  127:  11260 
    Search in Google Scholar
  • 4f Aydogan F. Demir AS. Tetrahedron  2005,  61:  3019 
    Search in Google Scholar
  • 4g Chien T.-C. Meade EA. Hinkley JM. Townsend LB. Org. Lett.  2004,  6:  2857 
    Search in Google Scholar
  • 4h Ramanathan B. Keith AJ. Armstrong D. Odom AL. Org. Lett.  2004,  6:  2957 
    Search in Google Scholar
  • 4i Trofimov BA. Zaitsev AB. Schmidt EY. Vasil’tsov AM. Mikhaleva AI. Ushakov IA. Vashchenko AV. Zorina NV. Tetrahedron Lett.  2004,  45:  3789 
    Search in Google Scholar
  • 4j Almerico AM. Montalbano A. Diana P. Barraja P. Lauria A. Cirrincione G. Dattolo G. ARKIVOC  2001,  (vi):  129 
    Search in Google Scholar
  • 4k Trofimov BA. Markova MV. Morozova LV. Mikhaleva AI. ARKIVOC  2001,  (ix):  24 
    Search in Google Scholar
  • 4l Trofimov BA. Tarasova OA. Mikhaleva AI. Kalinina NA. Sinegovskaya LM. Henkelmann J. Synthesis  2000,  1585 
  • 5a Van Leusen AM. Siderius H. Hoogenboom BE. van Leusen D. Tetrahedron Lett.  1972,  52:  5337 
    Search in Google Scholar
  • 5b ten Have R. Leusink FR. van Leusen AM. Synthesis  1996,  871 
  • 6a Barton DHR. Zard SZ. J. Chem. Soc., Chem. Commun.  1985,  1098 
  • 6b Barton DHR. Kervagoret J. Zard SZ. Tetrahedron  1990,  21:  7587 
    Search in Google Scholar
  • 6c Bergman J. Rehn S. Tetrahedron  2002,  58:  9179 
    Search in Google Scholar
  • 7a Cohen BJ. Kraus MA. Patchornik A. J. Am. Chem. Soc.  1977,  99:  4165 
    Search in Google Scholar
  • 7b Cainelli G. Contento M. Manescalchi F. Regnoli R. J. Chem. Soc., Perkin Trans. 1  1980,  2516 
  • 7c Cohen BJ. Kraus MA. Patchornik A. J. Am. Chem. Soc.  1981,  103:  7620 
    Search in Google Scholar
  • 7d Bergbreiter DE. Chem.-Tech.  1987,  17:  686 
    Search in Google Scholar
  • 7e Brown SD. Armstrong RW. J. Am. Chem. Soc.  1996,  118:  331 
    Search in Google Scholar
  • 7f Wentworth P. Janda KD. Chem. Commun.  1999,  1917 
  • For selected reviews and application articles see:
  • 8a Solinas A. Taddei M. Synthesis  2007,  2409 
  • 8b Bhattacharyya S. Mol. Diversity  2005,  9:  253 
    Search in Google Scholar
  • 8c Storer RI. Takemoto T. Jackson PS. Brown DS. Baxendale IR. Ley SV. Chem.-Eur. J.  2004,  10:  2529 
    Search in Google Scholar
  • 8d Kirschning A. Wittenberg R. In Merging Solid-Phase and Solution-Phase Synthesis - The ”Resin-Capture-Release" Hybrid Technique, Organic Synthesis Highlights V   Wiley-VCH; Weinheim: 2003.  p.265-279  
  • 8e Ley SV. Baxendale IR. Chem. Rec.  2002,  2:  377 
    Search in Google Scholar
  • 8f Ley SV. Baxendale IR. Brusotti G. Caldarelli M. Massi A. Nesi M. Farmaco  2002,  57:  321 
    Search in Google Scholar
  • 8g Ley SV. Baxendale IR. Nat. Rev. Drug Discovery  2002,  1:  573 
    Search in Google Scholar
  • 8h Ley SV. Baxendale IR. Bream RN. Jackson PS. Leach AG. Longbottom DA. Nesi M. Scott JS. Storer RI. Taylor SJ. J. Chem. Soc., Perkin Trans. 1  2000,  3815 
  • 8i Baxendale IR. Ley SV. Bioorg. Med. Chem. Lett.  2000,  10:  1983 
    Search in Google Scholar
  • 8j Kirschning A. Wittenberg R. Monenschein H. Chem.-Eur. J.  2000,  6:  4445 
    Search in Google Scholar
  • 8k Flynn DL. Devraj RV. Parlow JJ. Curr. Opin. Drug Discovery Dev.  1998,  1:  41 
    Search in Google Scholar
  • 8l Flynn DL. Crich JZ. Devraj RV. Hockerman SL. Parlow JJ. South MS. Woodard SS. J. Am. Chem. Soc.  1997,  119:  4874 
    Search in Google Scholar
  • 8m Kaldor SW. Siegel MG. Fritz JE. Dressmann BA. Hahn PJ. Tetrahedron Lett.  1996,  37:  7193 
    Search in Google Scholar
  • 8n Booth RJ. Hodges JC. J. Am. Chem. Soc.  1997,  119:  4882 
    Search in Google Scholar
  • 8o Kaldor SW. Fritz JE. Tang J. McKinney ER. Bioorg. Med. Chem. Lett.  1996,  6:  3041 
    Search in Google Scholar
  • 12 Fornicola RS. Oblinger E. Montgomery J. J. Org. Chem.  1998,  63:  3528 
    CrossrefSearch in Google Scholar
9

PS-BEMP refers to 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine on polystyrene 2% DVB, loading 2.2 mmol/g. Commercially available from Aldrich Cat No. 20026-XXG where XX is the quantity in grams.

10

PS-TBD refers to 1,5,7-triazabicyclo[4.4.0]dec-5-ene-polystyrene cross-linked with 2% DVB, loading 1.33 mmol/g. Commercially available from Biotage Cat. No. 800422.

11

Available from Varian Inc. named as Bond Elut silica packed cartridges.

13

Experiments to try and exclude the possibility of excess ethyl chloroformate being responsible for the secondary products following addition to the nitrostyrene were conducted using sub-stoichiometric quantities to quench the original TosMIC anion. These reactions gave comparable crude mixtures accompanied by the components from the standard Barton-Zard condensation. The possibility that the TosMIC could still act as a leaving group and consequently as an ethyl formate transfer agent can still not be excluded.

14

The reaction between the lithio enolate 4 and ethyl acrylate gave only a mixture of products from which only 7% of a rearrangement product (ethyl 5-tosylpyrrole-1H-3-carboxylate) could be isolated. ¹H NMR and X-ray analysis was used to confirm the structure.