Direct Preparation of Heteroaromatic

Compounds from Alkenes (original) (raw)

Synlett 2010(19): 2956-2958
DOI: 10.1055/s-0030-1259034

LETTER

© Georg Thieme Verlag Stuttgart ˙ New York

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)

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

Supporting Information for this article is available online:

• Supporting Information

References and Notes

• 1a Alajarin M. Cabrera J. Pastor A. Sanchez-Anrada P. Bautista D. J. Org. Chem. 2006, 71: 5328
• 1b Schwarz G. Org. Synth., Coll. Vol. III 1955, 332
• 1c Hantzsch A. Ann. Chem. 1889, 250: 257
• 2 Ueno M. Nabana T. Togo H. J. Org. Chem. 2003, 68: 6424
• 3 John ORS. Killeen NM. Knowles DA. Yau SC. Bagley MC. Tomkinson NCO. Org. Lett. 2007, 9: 4009
• 4a Li B. Chiu CKF. Hank RF. Murry J. Roth J. Tobiassen H. Org. Process Res. Dev. 2002, 6: 682
• 4b Kempter G. Spindler J. Fiebig HJ. Sarodnick G. J. Prakt. Chem. 1971, 313: 977
• 5a Bischler A. Ber. Dtsch. Chem. Ges. 1892, 25: 2860
• 5b Pchalek K. Jones AW. Wekking MMT. Black DSC. Tetrahedron 2005, 61: 77
• 6 Jereb M. Stavber S. Zupan M. Tetrahedron 2003, 59: 5935
• 7a Cort AD. J. Org. Chem. 1991, 56: 6708
• 7b De Dobbeleer C. Pospiil J. Marko IE. De Vleeschouwer F. De Proft F. Chem. Commun. 2009, 2142
• 8a Cardillo G. Shimizu M. J. Org. Chem. 1977, 42: 4268
• 8b Shamsuzzaman S. Anwar A. Suhail S. Synth. Commun. 1997, 27: 3997
• 9 Evans RD. Herman J. Synthesis 1986, 727
• 10a Yadav JS. Reddy BVS. Singh AP. Basak AK. Tetrahedron Lett. 2008, 49: 5880
• 10b Moorthy JN. Senapati K. Singhal N. Tetrahedron Lett. 2009, 50: 2493
• 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 C_H3_,C_H_ = 7.0 Hz, 3 H, C_H_ 3), 5.47 (q, ³ J C_H3_,C_H_ = 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
• 14a Cai L. Brouwer C. Sinclair K. Cuevas J. Pike VW. Synthesis 2006, 133
• 14b Hirano K. Urban S. Wang C. Glorius F. Org. Lett. 2009, 11: 1019
• 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 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.

• Supplementary Material