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Synthesis 2011(1): 109-118  
DOI: 10.1055/s-0030-1258326
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

β-Alkoxy-γ-amino Aldehydes by Internal Redox Ring Cleavages of Carbohydrate-Derived Enantiopure 1,2-Oxazines and Preparation of Heterocycles with Aminopolyol Side Chain

Ahmed Al-Harrasia,b, Léa Bouchéa, Reinhold Zimmera, Hans-Ulrich Reissig*a
a Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Fax: +49(30)83855367; e-Mail: hans.reissig@chemie.fu-berlin.de;
b University of Nizwa, College of Arts and Sciences, Department of Biological Sciences and Chemistry, P.O Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Sultanate of Oman
Further Information

Publication History

Received 7 September 2010
Publication Date:
15 November 2010 (online)

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Abstract

N-Methylation of syn- or anti-configured 3,6-dihydro-2H-1,2-oxazines and subsequent treatment with triethylamine smoothly provided enantiopure α,β-unsaturated β-alkoxy-γ-amino aldehydes bearing different protected diol, triol, or tetrol side chains in good to excellent yields. The N-O bond cleavage occurs under mild conditions and involves an internal redox process. The method is also applicable to tetrahydro-2H-1,2-oxazines, which either lead to 4-amino ketose or aldose derivatives (d-sorbose or d-idose configuration). The equivalency of the generated β-alkoxyenal moiety with 1,3-dicarbonyl compounds could be demonstrated by condensation reactions with hydrazine or 2-aminoimidazole derivatives providing a series of new pyrazole or imidazo[1,2-a]pyrimidine derivatives with stereodefined and protected aminopolyol side chains.

Key words

carbohydrates - 1,2-oxazines - alkylation - aldehydes - pyrazoles - imidazo[1,2-a]pyrimidines

    References

  • 1a Schade W. Reissig H.-U. Synlett  1999,  632 
  • 1b Pulz R. Cicchi S. Brandi A. Reissig H.-U. Eur. J. Org. Chem.  2003,  1153 
  • 1c Helms M. Schade W. Pulz R. Watanabe T. Al-Harrasi A. Fišera L. Hlobilová I. Zahn G. Reissig H.-U. Eur. J. Org. Chem.  2005,  1003 
  • For alternative approaches to synthetically very versatile 1,2-oxazines, see:
  • 1d Reissig H.-U. Homann K. Hiller F. Zimmer R. Synthesis  2007,  2681 
  • 1e Zimmer R. Collas M. Czerwonka R. Hain U. Reissig H.-U. Synthesis  2008,  237 
  • 1f Zimmer R. Schmidt E. Andrä M. Duhs M.-A. Linder I. Reissig H.-U. Beilstein J. Org. Chem.  2009,  5:  No. 44 ; and references cited therein
    Search in Google Scholar
  • Recent reviews:
  • 2a Brasholz M. Reissig H.-U. Zimmer R. Acc. Chem. Res.  2009,  42:  45 
    Search in Google Scholar
  • 2b Pfrengle F. Reissig H.-U. Chem. Soc. Rev.  2010,  39:  549 
    Search in Google Scholar
  • 2c Lechel T. Reissig H.-U. Pure Appl. Chem.  2010,  85:  1835 
    Search in Google Scholar
  • For selected recent applications developed by our group, see:
  • 2d Yekta S. Prisyazhnyuk V. Reissig H.-U. Synlett  2007,  2069 
  • 2e Pfrengle F. Al-Harrasi A. Brüdgam I. Reissig H.-U. Eur. J. Org. Chem.  2009,  282 
  • 2f Bressel B. Reissig H.-U. Org. Lett.  2009,  11:  527 
    Search in Google Scholar
  • 2g Pfrengle F. Lentz D. Reissig H.-U. Angew. Chem. Int. Ed.  2009,  48:  3165 ; Angew. Chem. 2009, 121, 3211
    Search in Google Scholar
  • 2h Al-Harrasi A. Pfrengle F. Prisyazhnyuk V. Yekta S. Koóš P. Reissig H.-U. Chem. Eur. J.  2009,  15:  11632 
    Search in Google Scholar
  • 2i Dekaris V. Reissig H.-U. Synlett  2010,  42 
  • 2j Dekaris V. Bressel B. Reissig H.-U. Synlett  2010,  47 
  • 2k Al-Harrasi A. Fischer S. Zimmer R. Reissig H.-U. Synthesis  2010,  304 
  • 3a Bressel B. Egart B. Al-Harrasi A. Pulz R. Reissig H.-U. Brüdgam I. Eur. J. Org. Chem.  2008,  467 
  • 3b Pulz R. Al-Harrasi A. Reissig H.-U. Org. Lett.  2002,  4:  2353 
    Search in Google Scholar
  • 3c Pulz R. Watanabe T. Schade W. Reissig H.-U. Synlett  2000,  983 
  • 4 Preliminary report: Al-Harrasi A. Reissig H.-U. Synlett  2005,  1152 
    Thieme Connect
  • 5a Murahashi S.-I. Kodera Y. Hosomi T. Tetrahedron Lett.  1988,  29:  5949 
    Search in Google Scholar
  • 5b For fragmentations of 5,6-dihydro-4H-1,2-oxazines by N-alkylation followed by base treatment, see also: Lidor R. Shatzmiller S. J. Am. Chem. Soc.  1981,  103:  5916 
    Search in Google Scholar
  • 6 Dugovič B. Wiesenganger T. Fišera L. Hametner C. Prónayová N. Heterocycles  2005,  65:  591 
    CrossrefSearch in Google Scholar
  • 7a Meske MJ. J. Prakt. Chem.  1997,  339:  426 
    Search in Google Scholar
  • 7b Bayón P. de March P. Figueredo M. Font J. Tetrahedron  1998,  54:  15691 
    Search in Google Scholar
  • 7c Machetti F. Cordero FM. De Sarlo F. Brandi A. Tetrahedron  2001,  57:  4995 
    Search in Google Scholar
  • 7d Chevrier C. Defoin A. Synthesis  2003,  1221 
  • 7e Dugovič B. Fišera L. Reissig H.-U. Eur. J. Org. Chem.  2008,  277 
  • 8 The 6-phenyl-substituted 1,2-oxazine derivative 4 was prepared from 1-methoxy-3-phenylprop-2-yne in a deprotonation-protonation-deprotonation-addition sequence with d-glyceraldehyde nitrone, analogously to the procedure described in: Chowdhury MA. Reissig H.-U. Synlett  2006,  2383 
    Thieme Connect
  • 9a Tchissambou L. Benechie M. Khuong-Huu F. Tetrahedron  1982,  38:  2687 
    Search in Google Scholar
  • 9b Nilsson BM. Ringdahl B. Hacksell U. J. Med. Chem.  1990,  33:  580 
    Search in Google Scholar
  • 9c Bergman R. Gericke R. J. Med. Chem.  1990,  33:  492 
    Search in Google Scholar
  • 9d Braña MF. Garranzo M. de Pascual-Teresa B. Pérez-Castells J. Torres MR. Tetrahedron  2002,  58:  4825 
    Search in Google Scholar
  • 11 Review: Schweizer F. Angew. Chem. Int. Ed.  2002,  41:  230 ; Angew. Chem. 2002, 114, 240
    CrossrefSearch in Google Scholar
  • 12 Elguero J. In Comprehensive Heterocyclic Chemistry II   Vol. 3:  Katritzky AR. Rees CW. Scriven EVC. Pergamon; Oxford: 1996.  p.1-75  
    Search in Google Scholar
  • 13 Lee K. Kim J. Kim J. Tetrahedron Lett.  2003,  44:  6737 ; and references cited therein
    CrossrefSearch in Google Scholar
  • Reviews:
  • 14a Tully WR. Gardner CR. Westwood R. Drug Dev. Res.  1991,  22:  299 
    Search in Google Scholar
  • 14b Hajos G. Riedl Z. In Science of Synthesis   Vol. 12:  Neier R. Thieme; Stuttgart: 2002.  p.613 
    Search in Google Scholar
  • Some selected publications:
  • 14c Künstlinger M. Breitmaier E. Synthesis  1983,  161 
  • 14d Drescher M. Öhler E. Zbiral E. Synthesis  1991,  362 
  • 14e Li W. Nelson DP. Jensen MS. Hoerrner RS. Javadi GJ. Cai D. Larsen RD. Org. Lett.  2003,  5:  4835 
    Search in Google Scholar
  • 14f Aggarwal R. Sumran G. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  2006,  45:  2690 ; and references cited therein
    Search in Google Scholar
  • 15 For related reaction conditions, see: Sosnicki J. Monatsh. Chem.  2000,  131:  475 
    CrossrefSearch in Google Scholar
  • For related reactions of 2-aminobenzimidazole with carbohydrate derivatives, see:
  • 16a Bari A. Feist H. Michalik D. Michalik M. Peseke K. Synthesis  2004,  2863 
  • 16b Bari A. Feist H. Michalik M. Peseke K. Molecules  2005,  10:  837 
    Search in Google Scholar
  • 16c Bari A. Milicevic S. Feist H. Michalik D. Michalik M. Peseke K. Synthesis  2005,  2758 
  • 17 Skattebøl L. J. Org. Chem.  1966,  31:  1554 
    CrossrefSearch in Google Scholar
  • 18 Al-Harrasi A. Reissig H.-U. Angew. Chem. Int. Ed.  2005,  44:  6227 ; Angew. Chem. 2005, 117, 6383
    CrossrefSearch in Google Scholar
10

Compound 16 was prepared by Grignard reaction of the corresponding 4-oxo-1,2-oxazine of 16 with MeMgBr: Hyrosová, E.; Reissig, H.-U., unpublished results.