Synthesis 2008(6): 990-994  
DOI: 10.1055/s-2007-990933
PSP
© Georg Thieme Verlag Stuttgart · New York

Highly Substituted Imidazole Derivatives from a New Four-Component Synthesis Employing Methoxyallene

Maciej Gwiazda, Hans-Ulrich Reissig*
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany
Fax: +49(30)83855367; e-Mail: [email protected];
Further Information

Publication History

Received 14 August 2007
Publication Date:
28 November 2007 (online)

Abstract

A novel four-component reaction of alkoxyallenes with imines, iodine, and nitriles provided highly substituted imidazole derivatives in high overall yields. The simple three step protocol, exemplified by the reaction of methoxyallene (1) with imine 2, acetonitrile, and iodine leading to iodoethenyl imidazole 6 is presented with full experimental detail. Imidazole 6 could be further functionalized by palladium-catalyzed couplings yet offering an entry into diversity-oriented synthesis.

    References

  • Reviews:
  • 1a Zimmer R. Synthesis  1993,  165 
  • 1b Zimmer R. Khan FA. J. Prakt. Chem.  1996,  338:  92 
  • 1c Reissig H.-U. Hormuth S. Schade W. Okala Amombo MG. Watanabe T. Pulz R. Hausherr A. Zimmer R. J. Heterocycl. Chem.  2000,  37:  597 
  • 1d Reissig H.-U. Schade W. Okala Amombo MG. Pulz R. Hausherr A. Pure Appl. Chem.  2002,  74:  175 
  • 1e Zimmer R. Reissig H.-U. In Modern Allene Chemistry   Vol. 2:  Krause N. Hashmi ASK. Wiley-VCH; Weinheim: 2004.  p.847 
  • 2a Hoff S. Brandsma L. Arens JF. Recl. Trav. Chim. Pays-Bas  1969,  88:  609 
  • 2b Gange D. Magnus P. J. Am. Chem. Soc.  1978,  100:  7746 
  • 2c Hormuth S. Reissig H.-U. J. Org. Chem.  1994,  59:  67 
  • 2d Flögel O. Reissig H.-U. Eur. J. Org. Chem.  2004,  2797 
  • 2e Brasholz M. Reissig H.-U. Synlett  2007,  1294 
  • 3a Al-Harrasi A. Reissig H.-U. Angew. Chem. Int. Ed.  2005,  44:  6227 ; Angew. Chem. 2005, 117, 6383
  • 3b Sörgel S. Azap C. Reissig H.-U. Org. Lett.  2006,  8:  4875 
  • 3c Brasholz M. Reissig H.-U. Angew. Chem. Int. Ed.  2007,  47:  1634 ; Angew. Chem. 2007, 119, 1659
  • 4a Okala Amombo MG. Hausherr A. Reissig H.-U. Synlett  1999,  1871 
  • 4b Pulz R. Watanabe T. Schade W. Synlett  2000,  983 
  • 4c Breuil-Desvergnes V. Goré J. Tetrahedron  2001,  57:  1939 
  • 4d Breuil-Desvergnes V. Goré J. Tetrahedron  2001,  57:  1951 
  • 4e Pulz R. Al-Harrasi A. Reissig H.-U. Org. Lett.  2002,  4:  2353 
  • 4f Flögel O. Okala Amombo MG. Reissig H.-U. Zahn G. Brüdgam I. Hartl H. Chem. Eur. J.  2003,  9:  1405 
  • 4g Flögel O. Reissig H.-U. Synlett  2004,  895 
  • 4h Kaden S. Brockmann M. Reissig H.-U. Helv. Chim. Acta  2005,  88:  1826 
  • 4i Kaden S. Reissig H.-U. Brüdgam I. Hartl H. Synthesis  2006,  1351 
  • 4j Chowdhury MA. Reissig H.-U. Synlett  2006,  2383 
  • 4k Kaden S. Reissig H.-U. Org. Lett.  2006,  8:  4763 
  • 5a Flögel O. Dash J. Brüdgam I. Hartl H. Reissig H.-U. Chem. Eur. J.  2004,  10:  4283 
  • 5b Flögel O, and Reissig H.-U. inventors; German Patent DE  10336497.  2005
  • 6a Schade W. Reissig H.-U. Synlett  1999,  632 
  • 6b Pulz R. Cicchi S. Brandi A. Reissig H.-U. Eur. J. Org. Chem.  2003,  1153 
  • 6c Helms M. Schade W. Pulz R. Watanabe T. Al-Harrasi A. Fisera L. Hlobilová I. Zahn G. Reissig H.-U. Eur. J. Org. Chem.  2005,  1003 
  • For an alternative approach to synthetically very versatile 1,2-oxazine derivatives, see:
  • 6d Zimmer R. Reissig H.-U. Angew. Chem., Int. Ed. Engl.  1988,  27:  1518 ; Angew. Chem. 1988, 100, 1576
  • 6e Hippeli C. Zimmer R. Reissig H.-U. Liebigs Ann. Chem.  1990,  469 
  • 6f Hippeli C. Reissig H.-U. Liebigs Ann. Chem.  1990,  475 
  • 6g Reissig H.-U. Hippeli C. Arnold T. Chem. Ber.  1990,  123:  2403 
  • 7 For a review on Nazarov cyclizations of alkoxyallene derived compounds, see: Tius MA. Eur. J. Org. Chem.  2005,  2193 
  • 8 Gwiazda M. Reissig H.-U. Synlett  2006,  1683 ; see also: Snieckus, V.; Zhao, Y. Synfacts 2006, 1110
  • Accounts on multicomponent reactions:
  • 9a Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 ; Angew. Chem. 2000, 112, 3300
  • 9b Zhu J. Eur. J. Org. Chem.  2003,  1133 
  • 9c Zhu J. Bienaymé H. In Multicomponent Reactions   Wiley-VCH; Weinheim: 2005. 
  • 9d Doemling A. Chem. Rev.  2006,  106:  17 
  • 10 For a review on the Ritter reaction, see: Krimen LI. Cota DJ. Org. React.  1969,  17:  213 
  • 11a Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  4467 
  • 11b Sonogashira K. J. Organomet. Chem.  2002,  653:  46 
  • 11c For a recent review, see: Chinchilla R. Nájera C. Chem. Rev.  2007,  107:  874 
  • 12 Buettelmann B, Ceccarelli SM, Jaeschke G, Klczewski S, Porter RHP, and Vieri E. inventors; WO Patent WO  2005118568.  2005
  • Selected original publications:
  • 13a Lambardino JG. Wiesman EH. J. Med. Chem.  1974,  17:  1182 
  • 13b Tsuji S. Rinehart KL. J. Org. Chem.  1988,  53:  5446 
  • 13c Sakemi S. Sun HH. J. Org. Chem.  1991,  56:  4304 
  • 13d Lee JC. Laydon JT. McDonnel PC. Gallagher TF. Kumar S. Green D. McNulty D. Blumenthal MJ. Heys JR. Landvatter SW. Strickler JE. Mclaughlin MM. Siemens IR. Fisher SM. Livi GP. White JR. Adams JL. Young PR. Nature  1994,  372:  739 
  • 13e Boehm JC. Smietana JM. Sorenson ME. Garigipati RS. Gallagher TF. Sheldrake PL. Bradbeer J. Badger AM. Laydon JT. Lee JC. Hillegass LM. Griswold DE. Breton JJ. Chabot-Fletcher MC. Adams JL. J. Med. Chem.  1996,  39:  3929 
  • 13f McLay IM. Halley F. Souness JE. McKenna J. Benning V. Birrell M. Burton B. Belvisi M. Collis A. Constan A. Foster M. Hele D. Jayyosi Z. Kelley M. Maslen C. Miller G. Ouldelhkim M.-L. Page K. Phipps S. Pollock K. Porter B. Ratcliffe AJ. Redford EJ. Webber S. Slater B. Thybaud V. Wilsher N. Bioorg. Med. Chem.  2001,  9:  537 
  • 13g Williams DR. Lee M.-R. Song Y.-A. Ko S.-K. Kim G.-H. Shin I. J. Am. Chem. Soc.  2007,  129:  9258 
  • 14a Schilling K, and Dietz E. inventors; Hoechst AG, German Patent DE 1  188229.  1961; Chem. Abstr. 1961, 61, 25911
  • 14b Langhals H. Jaschke H. Ring U. Unold P. Angew. Chem. Int. Ed.  1999,  38:  201 ; Angew. Chem. 1999, 111, 143
  • Reviews:
  • 16a Grimmett MR. In Comprehensive Heterocyclic Chemistry   Vol. 5:  Katritzky AR. Rees CW. Pergamon Press; London: 1984.  p.374 
  • 16b Grimmet MR. In Comprehensive Heterocyclic Chemistry II   Vol. 3:  Katritzky AR. Rees CW. Scriven EFV. Pergamon Press; Oxford: 1996.  p.77 
  • 16c Grimmett MR. In Science of Synthesis   Vol. 12:  Neier R. Thieme Verlag; Stuttgart: 2002.  p.325 
  • 16d Kamijo S. Yamamoto Y. Chem. Asian J.  2007,  2:  568 
  • Selected new synthetic methods:
  • 16e Sisko J. J. Org. Chem.  1998,  63:  4529 
  • 16f See also: Fresneda PM. Molina P. Sanz MA. Synlett  2001,  218 
  • 16g See also: Zhong YL. Lee J. Reamer RA. Askin D. Org. Lett.  2004,  6:  929 
  • 16h See also: Langhammer I. Erker T. Heterocycles  2005,  65:  1975 
  • 16i See also: Bellina F. Cauteruccio S. Mannina L. Rossi R. Viel S. Eur. J. Org. Chem.  2006,  693 
  • 17 For an interesting approach to highly substituted imidazoles which employs a dilithiated allene derivative and nitriles, see: Langer P. Döring M. Seyferth D. Görls H. Eur. J. Org. Chem.  2003,  1948 
15

Several of the imidazole derivatives of type 6 are highly fluorescent: Gwiazda, M.; Reissig, H.-U., unpublished results.