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Synlett 2010(19): 2956-2958  
DOI: 10.1055/s-0030-1259034
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Direct Preparation of Heteroaromatic Compounds from Alkenes

Timothy J. Donohoe*a, Mikhail A. Kabeshova,b, Akshat H. Rathia, Ian E. D. Smithb
a Department of Chemistry, University of Oxford, Chemistry Reasearch Laboratory, Mansfield Road, Oxford, OX1 3TA, UK
Fax: +44(1865)275674; e-Mail: timothy.donohoe@chem.ox.ac.uk;
b GlaxoSmithKline Research and Development Limited, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK
Fax: +44(1438)764502; e-Mail: ian.e.smith@gsk.com;
Further Information

Publication History

Received 11 October 2010
Publication Date:
10 November 2010 (online)

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Abstract

A series of aromatic heterocycles, thiazoles, imidazoles, and dimethoxyindoles, can be synthesised directly from alkenes via a ketoiodination-cyclisation protocol. The alkene starting materials are themselves easily accessible by many different and well-established approaches, and allow access to various aromatic hetero­cycles with excellent yields and regioselectivity.

Key words

heterocycles - alkenes - iodine - iodo ketones - oxidation

    References and Notes

  • 1a Alajarin M. Cabrera J. Pastor A. Sanchez-Anrada P. Bautista D. J. Org. Chem.  2006,  71:  5328 
    Google Scholar
  • 1b Schwarz G. Org. Synth., Coll. Vol. III  1955,  332 
    Google Scholar
  • 1c Hantzsch A. Ann. Chem.  1889,  250:  257 
    Google Scholar
  • 2 Ueno M. Nabana T. Togo H. J. Org. Chem.  2003,  68:  6424 
    CrossrefPubMedGoogle Scholar
  • 3 John ORS. Killeen NM. Knowles DA. Yau SC. Bagley MC. Tomkinson NCO. Org. Lett.  2007,  9:  4009 
    CrossrefPubMedGoogle Scholar
  • 4a Li B. Chiu CKF. Hank RF. Murry J. Roth J. Tobiassen H. Org. Process Res. Dev.  2002,  6:  682 
    Google Scholar
  • 4b Kempter G. Spindler J. Fiebig HJ. Sarodnick G. J. Prakt. Chem.  1971,  313:  977 
    Google Scholar
  • 5a Bischler A. Ber. Dtsch. Chem. Ges.  1892,  25:  2860 
    Google Scholar
  • 5b Pchalek K. Jones AW. Wekking MMT. Black DSC. Tetrahedron  2005,  61:  77 
    Google Scholar
  • 6 Jereb M. Stavber S. Zupan M. Tetrahedron  2003,  59:  5935 
    CrossrefGoogle Scholar
  • 7a Cort AD. J. Org. Chem.  1991,  56:  6708 
    Google Scholar
  • 7b De Dobbeleer C. Pospiil J. Marko IE. De Vleeschouwer F. De Proft F. Chem. Commun.  2009,  2142 
    Google Scholar
  • 8a Cardillo G. Shimizu M. J. Org. Chem.  1977,  42:  4268 
    Google Scholar
  • 8b Shamsuzzaman S. Anwar A. Suhail S. Synth. Commun.  1997,  27:  3997 
    Google Scholar
  • 9 Evans RD. Herman J. Synthesis  1986,  727 
    Article in Thieme ConnectGoogle Scholar
  • 10a Yadav JS. Reddy BVS. Singh AP. Basak AK. Tetrahedron Lett.  2008,  49:  5880 
    Google Scholar
  • 10b Moorthy JN. Senapati K. Singhal N. Tetrahedron Lett.  2009,  50:  2493 
    Google Scholar
  • 11 Basarab G, Hill P, and Zhou F. inventors; WO 2008152418, A1  20081218. See:
  • 13 Analytical Data for Crude 2-Iodo-1-phenyl-1-propanone ¹H NMR (400 MHz, CDCl3): δ = 2.04 (d, ³ J CH3,CH  = 7.0 Hz, 3 H, CH 3), 5.47 (q, ³ J CH3,CH  = 7.0 Hz, 1 H, CHI), 7.40-7.46 (m, 2 H, Ph), 7.50-7.56 (m, 1 H), 7.92-7.98 (m, 2 H, Ph) are in agreement with the literature: Cambie RC. Hayward RC. Lindsay BG. Phan ALT. Rutledge PS. Woodgate PD. J. Chem. Soc., Perkin Trans. 1  1976,  1961 
    CrossrefGoogle Scholar
  • 14a Cai L. Brouwer C. Sinclair K. Cuevas J. Pike VW. Synthesis  2006,  133 
    Google Scholar
  • 14b Hirano K. Urban S. Wang C. Glorius F. Org. Lett.  2009,  11:  1019 
    Google Scholar
  • 14c Bailey N. Bamford MJ. Brissy D. Brookfield J. Demont E. Elliott R. Garton N. Farre-Gutierrez I. Heyhow T. Hutley G. Neylor A. Panchal TA. Seow H.-X. Spalding D. Takle AK. Bioorg. Med. Chem. Lett.  2009,  19:  3602 
    Google Scholar
12

0.25 M solution, analysed by LCMS calibrated with nitrobenzene; see Supporting Information for details.

15

In the reaction of 2-chloro-1-phenylpropan-1-one with benzamidine in the presence of K2CO3 at r.t. in DMF, only traces of the corresponding imidazole were detected after
2 h.

16

To distinguish between two isomeric aminothiazoles: 5-propyl-4-(3-pyridinyl)-1,3-thiazol-2-amine and 4-propyl-5-(3-pyridinyl)-1,3-thiazol-2-amine.