Download PDF
Synlett 2008(16): 2532-2534  
DOI: 10.1055/s-2008-1078175
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient One-Pot Synthesis of ω-Hydroxy Ketones from Lactones

Shao-Bo Yang, Feng-Feng Gan, Guo-Ju Chen, Peng-Fei Xu*
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. of China
Fax: +86(931)8915557; e-Mail: xupf@lzu.edu.cn;
Further Information

Publication History

Received 22 April 2008
Publication Date:
10 September 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient and convenient one-pot strategy was developed for the synthesis of 1-hydroxydodecan-6-one, an important precursor for total synthesis of sphingofungin F. A series of ω-hydroxy ketones were prepared from readily available lactones using this one-pot reaction.

Key words

Weinreb ketone synthesis - one-pot reaction - ω-hydroxy ketones - lactones

    References and Notes

  • 1 Nahm S. Weinreb S. Tetrahedron Lett.  1981,  22:  3815 
    CrossrefGoogle Scholar
  • 2a Sibi MP. Org. Prep. Proced. Int.  1993,  25:  15 
    Google Scholar
  • 2b Mentzel M. Hoffmann HMR. J. Prakt. Chem.  1997,  339:  517 
    Google Scholar
  • 2c Singh J. Satyamurthi N. Aidhen IS. J. Prakt. Chem.  2000,  342:  340 
    Google Scholar
  • 3a Oishi T. Ando K. Inomiya K. Sato H. Iida M. Chida N. Org. Lett.  2002,  4:  151 
    Google Scholar
  • 3b Oishi T. Ando K. Chida N. Chem. Commun.  2001,  1932 
    Google Scholar
  • 4a Myriocin D. Payette DR. Tetrahedron Lett.  1980,  21:  3219 
    Google Scholar
  • 4b Oishi T. Ando K. Inomiya K. Sato H. Iida M. Chida N. Org. Lett.  2002,  4:  151 
    Google Scholar
  • 5a Trost BM. Lee CB. J. Am. Chem. Soc.  1998,  120:  6818 
    Google Scholar
  • 5b Trost BM. Lee CB. J. Am. Chem. Soc.  2001,  123:  12191 
    Google Scholar
  • 5c Lee K.-Y. Oh C.-Y. Ham W.-H. Org. Lett.  2002,  4:  4403 
    Google Scholar
  • 5d Nakamura T. Shiozaki M. Tetrahedron  2002,  58:  8779 
    Google Scholar
  • 5e Hayes CJ. Bradley DM. Thomson NM. J. Org. Chem.  2006,  71:  2661 
    Google Scholar
  • 6 Liu D.-G. Wang B. Lin G.-Q. J. Org. Chem.  2000,  65:  9114 
    CrossrefPubMedGoogle Scholar
  • 7 Wang M.-X. Liu Y. Gao H.-Y. Zhang Y. Yu C.-Y. Huang Z.-T. Fleet GWJ. J. Org. Chem.  2003,  68:  3281 
    CrossrefGoogle Scholar
  • 8 Taillier C. Bellosta V. Meyer C. Cossy J. Org. Lett.  2004,  6:  2145 
    CrossrefGoogle Scholar
  • 9a Williams JM. Jobson RB. Yasuda N. Marchesini G. Dolling U.-H. Grabowski EJJ. Tetrahedron Lett.  1995,  36:  5461 
    Google Scholar
  • 9b Nilsson T. Acta Chem. Scand.  1973,  27:  888 
    Google Scholar
  • 11a Suzuki T. Usui K. Miyake Y. Namikoshi M. Nakada M. Org. Lett.  2004,  6:  553 
    Google Scholar
  • 11b Kiewel K. Luo Z. Sulikowski GA. Org. Lett.  2005,  7:  5163 
    Google Scholar
  • 11c Beshore DC. Smith AB. J. Am. Chem. Soc.  2007,  129:  4148 
    Google Scholar
10

It is worth to note that when phenylmagnesium bromide was used, an unexpected small amount byproduct was obtained. Its structure was identified as 1,4-dihydroxy-1-phenyl-butane. The reaction detail is being studied.

12

General Procedure for the Synthesis of ω-Hydroxy Ketones from Lactones
A slurry of lactone (1.0 mmol), HN(OMe)Me˙HCl (116 mg, 1.2 mmol), and NaOMe (14 mg, 0.25 mmol) in THF (20 mL) was cooled with an ice-salt bath under nitrogen. A solution of Grignard reagent in THF (16 mL, 0.5 M, 8.0 mmol) was added slowly. After 2 h in an ice-salt bath the reaction mixture was allowed to warm to r.t. and stirred for 8 h. The reaction was quenched with 1 N HCl solution (10 mL). The mixture was stirred for another 2 h, and THF was evaporated. The residue was treated with H2O (20 mL) and then extracted with CH2Cl2. The organic extract was dried over MgSO4 and concentrated. The residue was purified by flash column chromatography on silica gel (EtOAc-PE) to give the desired hydroxy ketone.

13

Spectral Data for Compound 7 Mp 45-47 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 0.82-0.87 (m, 3 H, CH3), 1.24-1.37 (m, 8 H, 4 CH2), 1.50-1.59 (m, 6 H, 3 CH2), 1.94 (s, 1 H, OH), 2.37 (dd, J = 8.4, 15.9 Hz, 4 H, 2 CH2), 3.60 (t, J = 6.3 Hz, 2 H, CH2). ¹³C NMR (75 MHz, CDCl3): δ = 13.92, 22.38, 23.34, 23.76, 25.26, 28.81, 31.49, 32.31, 42.52, 42.78, 62.38, 211.67. MS (EI): m/z (%) = 200 (0.8) [M+], 183 (0.3), 141 (1.3).