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Synlett 2006(14): 2339-2341  
DOI: 10.1055/s-2006-950410
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© Georg Thieme Verlag Stuttgart · New York

Convenient Access to 2-Arylpyrroles from 2-Lithio-N,N-dibenzylcyclopropylamine and Nitriles [1]

Chloé Tanguya,b, Philippe Bertusa, Jan Szymoniak*a, Oleg V. Larionovb, Armin de Meijere*b
a Réactions Sélectives et Applications, CNRS (UMR6519) and Université de Reims, 51687 Reims Cedex 2, France
Fax: +33(3)26913431; e-Mail: jan.szymoniak@univ-reims.fr;
b Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany
Fax: +49(551)399475; e-Mail: Armin.deMeijere@chemie.uni-goettingen.de;
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Publikationsverlauf

Received 8 May 2006
Publikationsdatum:
24. August 2006 (online)

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Abstract

N,N-Dibenzylaminocyclopropyl ketimines formed as ­intermediates upon treatment of 2-lithiated N,N-dibenzylcyclo­propylamines with nitriles, being donor-acceptor-substituted cyclopropanes, immediately underwent ring-enlarging rearrangement and 1,2-elimination of dibenzylamine to produce 2-substituted ­pyrroles in good yields (14 examples, 55-80%).

Key words

tin-lithium exchange - nitriles - 2-arylpyrroles - cyclopropylamines - donor-acceptor-substituted cyclopropanes

    References and Notes

  • For one of us (A.d.M.) this is to be counted as Part 133 in the series, ‘Cyclopropyl Building Blocks for Organic Synthesis’:
  • 1a For Part 132, see: Marradi M. Brandi A. Magull J. Schill H. de Meijere A. Eur. J. Org. Chem.  2006,  in press 
  • 1b Part 131: Bagutski V. Moszner N. Zeuner F. Fischer UK. Adv. Synth. Catal.  2006,  in press 
  • 2 Tanguy C. Bertus P. Szymoniak J. Larionov OV. de Meijere A. Synlett  2006,  in press  (e-First, DOI: 10.1055/s-2006-941600)
  • The well-known vinylcyclopropane-to-cyclopentene rearrangement is significantly accelerated by donor substit-uents like alkoxy and dialkylamino groups in the 2-position; compare with:
  • 3a McGaffin G. Grimm B. Heinecke U. Michaelsen H. de Meijere A. Walsh R. Eur. J. Org. Chem.  2001,  3559 ; and references cited therein
    Thieme Connect
  • 3b Voigt T. Winsel H. de Meijere A. Synlett  2002,  1362 
    Thieme Connect
  • The rearrangement of cyclopropylketimines, which is catalyzed by acids and known as the Cloke rearrangement, should also be accelerated by donor substituents:
  • 4a Cloke JB. J. Am. Chem. Soc.  1929,  51:  1174 
    CrossrefSuche in Google Scholar
  • 4b Review: Hudliky T. Becker DA. Fan RL. Kozhushkov SI. In Methods of Organic Chemistry, Houben-Weyl   Vol. E17c:  de Meijere A. Thieme; Stuttgart: 1997.  p.2538 
    CrossrefSuche in Google Scholar
  • 4c See also: Funke C. Es-Sayed M. de Meijere A. Org. Lett.  2000,  2:  4249 ; and references cited therein
    CrossrefSuche in Google Scholar
  • For reviews on vicinally donor-acceptor-substituted cyclopropanes see:
  • 5a von Angerer S. Carbocyclic Three- and Four-Membered Ring Compounds, In Methods of Organic Chemistry, Houben-Weyl   Vol. 17c:  de Meijere A. Thieme; Stuttgart: 1997.  p.2121 
    CrossrefSuche in Google Scholar
  • 5b Reissig H.-U. Zimmer R. Chem. Rev.  2003,  103:  1151 
    CrossrefSuche in Google Scholar
  • 5c Yu M. Pagenkopf BL. Tetrahedron  2005,  61:  321 
    CrossrefSuche in Google Scholar
  • 6a Shimada S. Hashimoto Y. Sudo A. Hasegawa M. Saigo K. J. Org. Chem.  1992,  57:  7126 
    CrossrefPubMedSuche in Google Scholar
  • 6b Graziano ML. Cimminiello G. J. Chem. Res., Miniprint  1989,  446 
    CrossrefPubMed
  • 6c Graziano ML. Chiosi S. J. Chem. Res., Synop.  1989,  44 
    CrossrefPubMed
  • 6d Yadav VK. Sriramurthy V. Angew. Chem. Int. Ed.  2004,  43:  2669 ; Angew. Chem. 2004, 116, 2723
    CrossrefPubMedSuche in Google Scholar
  • 7a Pohlhaus PD. Johnson JS. J. Am. Chem. Soc.  2005,  127:  16014 
    CrossrefSuche in Google Scholar
  • 7b Bernard AM. Frongia A. Piras PP. Secci F. Spiga M. Org. Lett.  2005,  7:  4565 
    CrossrefSuche in Google Scholar
  • 7c Wurz RP. Charette AB. Org. Lett.  2005,  7:  2313 
    CrossrefSuche in Google Scholar
  • 7d Yu M. Pagenkopf BL. J. Am. Chem. Soc.  2003,  125:  8122 
    CrossrefSuche in Google Scholar
  • 7e Yu M. Pagenkopf BL. Org. Lett.  2003,  5:  5099 
    CrossrefSuche in Google Scholar
  • 8 Wiedemann S. Rauch K. Savchenko A. Marek I. de Meijere A. Eur. J. Org. Chem.  2004,  631 
    Crossref
  • 9 The conversion of 3-oxoketimines into 2-hydroxy-5-arylpyrrolines has been reported, see: Chiu P.-K. Sammes MP. Tetrahedron  1988,  44:  3531 
    CrossrefSuche in Google Scholar
  • 10 Jones RCF. Howard KJ. Nichols JR. Snaith JS. J. Chem. Soc., Perkin Trans. 1  1998,  2061 
    Crossref
  • 13a Ohri RV. Radosevich AT. Hrovat KJ. Musich C. Huang D. Holman TR. Toste FD. Org. Lett.  2005,  7:  2501 
    CrossrefSuche in Google Scholar
  • 13b Pinna GA. Loriga G. Murineddu G. Grella G. Mura M. Vargiu L. Murgioni C. La Colla P. Chem. Pharm. Bull.  2001,  49:  1406 
    CrossrefSuche in Google Scholar
  • 13c Hunt DA. Pestic. Sci.  1996,  47:  201 
    CrossrefSuche in Google Scholar
  • 14a Gorin DJ. Davis NR. Toste FD. J. Am. Chem. Soc.  2005,  127:  11260 
    Thieme ConnectSuche in Google Scholar
  • 14b Rieth RD. Mankad NP. Calimano E. Sadighi JP. Org. Lett.  2004,  6:  3981 
    Thieme ConnectSuche in Google Scholar
  • 14c Knight LW. Huffman JW. Isherwood ML. Synlett  2003,  1993 
    Thieme Connect
  • 14d Quiclet-Sire B. Quintero L. Sanchez-Jimenez G. Zard SZ. Synlett  2003,  75 
    Thieme Connect
  • 14e Johnson CN. Stemp G. Anand N. Stephen SC. Gallagher T. Synlett  1998,  1025 
    Thieme Connect
  • 14f Katritzky AR. Li J. Gordeev MF. Synthesis  1994,  93 
    Thieme Connect
11

Typical Procedure. To a solution of trans-2-(tributylstan-nyl)-N,N-dibenzylcyclopropylamine (3, 526 mg, 1 mmol) in THF (3 mL) was added n-BuLi (1.2 mmol, 2 M in hexane) at -30 °C. After stirring for 30 min at -30 °C, the respective nitrile (1.2 mmol) was added. The mixture was warmed to 0 °C within 2 h. At this stage, the reaction was quenched with AcOH (2 M in THF, 0.5 mL), the mixture extracted with EtOAc, the extracts dried over MgSO4, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (PE-EtOAc, 9:1).

12

2-Phenyl-1 H -pyrrole ( 10a). 1H NMR (250 MHz, CDCl3): d = 6.24 (br s, 1 H), 6.46 (br s, 1 H), 6.79 (br s, 1 H), 7.13 (br s, 1H), 7.21-7.32 (m, 2 H), 7.35-7.41 (m, 2 H), 8.36 (br s, 1 H, NH). 13C NMR (63 MHz, CDCl3): d = 105.9, 110.1, 118.8, 123.8, 126.2, 128.9, 132.6, 132.8. HRMS (ESI): m/z calcd for C10H10N: 144.0813 (M + H)+; found: 144.0811.
2- m -Tolyl-1 H -pyrrole ( 10b). 1H NMR (250 MHz, CDCl3): d = 6.26 (br s, 1 H), 6.44 (br s, 1 H), 6.78 (br s, 1 H), 6.96 (br s, 1 H), 7.17-7.23 (m, 3 H), 8.35 (br s, 1 H, NH). 13C NMR (63 MHz, CDCl3): d = 21.5, 105.8, 110.0, 118.6, 120.9, 124.6, 127.0, 128.7, 132.2, 132.6, 138.4. HRMS (ESI): m/z calcd for C11H12N: 158.0970 (M + H)+; found: 158.0972.
2-(3-Methoxyphenyl)-1 H -pyrrole ( 10d). 1H NMR (250 MHz, CDCl3): d = 3.82 (s, 3 H), 6.28 (br s, 1 H), 6.51 (br s, 1 H), 6.73-6.77 (m, 1 H), 6.83 (br s, 1 H), 6.99-7.06 (m, 2 H), 7.22-7.29 (m, 1 H), 8.42 (br s, 1 H, NH). 13C NMR (63 MHz, CDCl3): d = 55.2, 106.1, 109.7, 110.0, 111.5, 116.4, 118.8, 129.9, 131.9, 134.1, 160.0. HRMS (ESI): m/z calcd for C11H12NO: 174.0919 (M + H)+; found: 174.0918.