PDF herunterladen
Synlett 2012(3): 381-384  
DOI: 10.1055/s-0031-1290310
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Reductive Ring Cleavage of Nonconjugated Δ²-Isoxazolines to β-Hydroxy Ketones with Aluminum and Copper(II) Chloride

Ieva Karpaviciene, Ringaile Lapinskaite, Algirdas Brukstus, Inga Cikotiene*
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, 03225 Vilnius, Lithuania
Fax: +370(5)2330987; e-Mail: inga.cikotiene@chf.vu.lt;
Weitere Informationen

Publikationsverlauf

Received 6 October 2011
Publikationsdatum:
19. Januar 2012 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

A facile, economic, and efficient protocol for the reduction of nonconjugated Δ²-isoxazolines to the corresponding β-hydroxy ketones using Al/CuCl2 as the reducing agent has been developed. The method is both rapid and complete requiring less than ten minutes to attain total ring cleavage. This is the first example of using an in situ prepared Al/Cu couple in organic synthesis.

Key words

reduction - isoxazolines - β-hydroxyketones - aluminum/copper couple

    References and Notes

  • 1a 1,3-Dipolar Cycloaddition Chemistry   Vol. 1 and 2:  Padwa A. Wiley; New York: 1984. 
    Google Scholar
  • 1b Torssell KBG. Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis   VCH; Weinheim: 1988. 
    Google Scholar
  • 1c Werner A. Buss H. Ber. Dtsch. Chem. Ges.  1894,  27:  2193 
    Google Scholar
  • 1d Minakata S. Okumura S. Nagamachi T. Takeda Y. Org. Lett.  2011,  13:  2966 
    Google Scholar
  • 1e Kim JN. Chung KH. Ryu EK. Heterocycles  1991,  32:  477 
    Google Scholar
  • 2a Wityak J. Sielecki TM. Pinto DJ. Emmett G. Sze JY. Liu J. Tobin AE. Wang S. Jiang B. Ma P. Mousa SA. Olson RE. Wexler RR. J. Med. Chem.  1997,  40:  50 
    Google Scholar
  • 2b Groutas WC. Venkataraman R. Chong LS. Yoder JE. Epp JB. Stanga MA. Kim EH. Bioorg. Med. Chem.  1995,  3:  125 
    Google Scholar
  • 3 Curran DP. J. Am. Chem. Soc.  1982,  104:  4024 
    Google Scholar
  • 4a McGarvey GJ. Mathys JA. Wilson KJ. J. Org. Chem.  1996,  61:  5704 
    Google Scholar
  • 4b Bartoli G. Bosco M. Marcantoni E. Massaccesi M. Rinaldi S. Sambri L. Eur. J. Org. Chem.  2001,  4679 
    Google Scholar
  • 4c Sinha SC. Barbas CF. Lerner RA. Proc. Natl. Acad. Sci. U.S.A.  1998,  95:  14603 
    Google Scholar
  • 4d Paterson I. Florence GJ. Gerlach K. Scott JP. Sereinig N. J. Am. Chem. Soc.  2001,  123:  9535 
    Google Scholar
  • 4e Colle S. Taillefumier C. Chapleur Y. Liebl R. Schmidt A. Bioorg. Med. Chem.  1999,  7:  1049 
    Google Scholar
  • 4f Muri D. Lohse-Fraefel N. Carreira EM. Angew. Chem. Int. Ed.  2005,  44:  4036 
    Google Scholar
  • 5a Poutiainen PK. Venäläinen TA. Peräkylä M. Matilainen JM. Väisänen S. Honkakoski P. Laatikainen R. Pulkkinen JT. Bioorg. Med. Chem.  2010,  18:  3437 
    Google Scholar
  • 5b León LG. Carballo RM. Vega-Hernández MC. Miranda PO. Martín VS. Padrón JI. Padrón JM. ChemMedChem  2008,  3:  1740 
    Google Scholar
  • 5c Pulkkinen JT. Honkakoski P. Perakyla M. Berczi I. Laatikainen R.
    J. Med. Chem.  2008,  51:  3562 
    Google Scholar
  • 6a Romanski J. Nowak P. Jurczak J. Chapuis C. Tetrahedron: Asymmetry  2011,  22:  787 
    Google Scholar
  • 6b Curran DP. Scanga SA. Fenk CJ. J. Org. Chem.  1984,  49:  3474 
    Google Scholar
  • 6c Casnati G. Quilico A. Ricca A. Finzi PV. Tetrahedron Lett.  1966,  233 
    Google Scholar
  • 6d Bull JA. Balskus EP. Horan AJ. Langner M. Ley SV. Chem. Eur. J.  2007,  13:  5515 
    Google Scholar
  • 7a Nitta M. Kobayashi T. J. Chem. Soc., Chem. Commun.  1982,  877 
    Google Scholar
  • 7b Baraldi PG. Barco A. Benetti S. Manfredini S. Simoni D. Synthesis  1987,  276 
    Google Scholar
  • 7c Paek S.-M. Yun H. Kim N.-J. Jung J.-W. Chang D.-J. Lee S. Yoo J. Park H.-J. Suh Y.-G. J. Org. Chem.  2009,  74:  554 
    Google Scholar
  • 8a Natale NR. Tetrahedron Lett.  1982,  23:  5009 
    Google Scholar
  • 8b Bode JW. Carreira EM. Org. Lett.  2001,  3:  1587 
    Google Scholar
  • 8c Bode JW. Carreira EM. J. Am. Chem. Soc.  2001,  123:  3611 
    Google Scholar
  • 9 Jiang D. Chen Y. J. Org. Chem.  2008,  73:  9181 
    Google Scholar
  • 10 Curran DP. J. Am. Chem. Soc.  1983,  105:  5826 
    Google Scholar
  • 11 Churykau H. Zinovich VG. Kulinkovich OG. Synlett  2004,  1949 
    Google Scholar
  • 12a Baraldi PG. Barco A. Benetti S. Pollini GP. Simoni D. Synthesis  1987,  857 
    Google Scholar
  • 12b Kozikowski AP. Acc. Chem. Res.  1984,  17:  410 
    Google Scholar
  • 12c Ignatovich ZhV. Chernikhova TV. Skupskaya RV. Bondar NF. Koroleva EV. Lakhvich FA. Chem. Heterocycl. Compd.  1999,  248 
    Google Scholar
  • 13a Li CJ. Chan T.-H. Organic Reactions in Aqueous Media   Wiley; New York: 1997. 
    Google Scholar
  • 13b Grieco PA. Organic Synthesis in Water   Kluwer Academic; Dordrecht: 1997. 
    Google Scholar
  • 14a Heinrichs B. Delhez P. Schoebrechts J. Pirard J. J. Catal.  1997,  172:  322 
    Google Scholar
  • 14b Lambert S. Heinrichs B. Brasseur A. Rulmont A. Pirard JP. Appl. Catal. A  2004,  270:  201 
    Google Scholar
  • 14c Ghauch A. Tuqan A. Chemosphere  2008,  73:  751 
    Google Scholar
  • 14d Lien HL. Zhang WX. J. Environ. Eng. (Reston, VA,U.S.)  2002,  131:  4 
    Google Scholar
  • 14e Lien HL. Zhang WX. Chemosphere  2002,  49:  371 ; and references cited therein
    Google Scholar
15

Typical Procedure for the Reductive Cleavage of 3,5-Disubstituted 4,5-Dihydroisoxazoles 1 To the mixture of the corresponding 3,5-disubstituted 4,5-dihydroisoxazole (1, 1 mmol) and Al dust (0.81 g, 30 mmol) in MeOH (5 mL) a solution of CuCl2×2H2O (1.75 g, 10 mmol) in H2O (5 mL) was added dropwise under vigorous stirring. After the evolution of hydrogen and full consumption of the starting material (observed by TLC, approximately after 5-10 min), the mixture was diluted with H2O (30 mL), and the product was extracted with CHCl3 (2 ×30 mL). The organic layer was dried over Na2SO4, evaporated under the reduced pressure, and the residue purified by column chromatography to give 2.
Analytical Data for 5-Hydroxy-7-tridecanone (2a)
Yield: 84%; colorless oil. IR (KBr): νmax = 3410 (OH), 1706 (C=O) cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 0.88 (3 H, t, J = 7.5 Hz, CH3), 0.91 (3 H, t, J = 7.5 Hz, CH3), 1.28-1.60 (14 H, m, 7 CH2), 2.43 [2 H, t, J = 7.5 Hz, C(8)H2], 2.48-2.54 [1 H, m, C(6)H], 2.57-2.64 [1 H, m, C(6)H], 3.03 (1 H, br s, OH), 3.99-4.07 [1 H, m, C(5)H] ppm. ¹³C NMR (75 Hz, CDCl3): δ = 13.8 (CH3), 13.9 (CH3), 22.4, 22.6, 23.5, 27.6, 28.7, 31.5, 36.1 (C-4), 43.6 (C-8), 48.9 (C-6), 67.5 (C-5), 212.6 (C-7) ppm. Anal. Calcd for C13H26O2: C, 72.84; H, 12.23. Found: C, 73.00; H, 12.19.
Compounds 1-4 were also fully characterized by IR, ¹H NMR, ¹³C NMR spectroscopic and microanalytical data, and data for known compounds are in agreement with published data.