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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;
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Publication History

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

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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

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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.

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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.

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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).