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Synlett 2004(14): 2603-2605  
DOI: 10.1055/s-2004-834804
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Facile Solid-Phase Synthesis of Substituted 2(5H)-Furanones with Sulfone Traceless Linker

Shou-Ri Sheng*, Pei-Gang Huang, Wei Zhou, Hai-Rong Luo, Shu-Ying Lin, Xiao-Ling Liu
Institutes of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330027, P. R. China
Fax: +86(791)8517500; e-Mail: shengsr@163.com;
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Publication History

Received 28 August 2004
Publication Date:
20 October 2004 (online)

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Abstract

A novel solid-phase synthetic method for substituted 2(5H)-furanones with traceless sulfone linker strategy has been developed. The products were obtained in good yields and excellent purities.

Key words

solid-phase organic synthesis - traceless sulfone linker - substituted 2(5H)-furanone

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Preparation of Polymer-Supported Phenylmethylsulfone 2: Polystyrene/1% divinylbenzene lithium sulfinate (1, 1.0 g, 1.0 mmol), prepared according to literature, [4h] was swollen under nitrogen in THF-DMF (2:1, 10 mL). MeI (5.0 mmol) was added and the reaction mixture was shaken at 80 °C for 15 h. After which, the reaction mixture was cooled to r.t., quenched with H2O, and filtered. The resin was washed successively with THF-H2O (2:1, 3 × 10 mL), THF (2 × 5 mL), CH2Cl2 (2 × 5 mL) and Et2O (2 × 5 mL), and then dried under vacuum overnight to afford the pale yellow resin 2. FT-IR (single bead reflection): 1600, 1495, 1452, 1380, 1313, 1150 cm-1.

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General Procedure for the Solid-Phase Synthesis of Target Molecules ( 6): Under nitrogen n-BuLi (2.0 mmol, 1.65 M, 1.2 mL) was added to DMSO (4.0 mmol) in THF (10 mL) at 0 °C and stirred for 5 min. The resulting dimsyl anion solution was transferred to a suspension of polymer 2 (1.0 g, 1.0 mmol) in THF (8 mL) at r.t. After stirring for 30 min, epoxide (3.0 mmol) was added to this mixture and stirred for 2 h, the color of the breads turned light orange. The reaction was quenched with 10% HCl (aq) after 1 h and the resin was filtered, washed and dried to afford resin 3 as pale yellow beads. A solution of methyl chloroformate (2.0 mmol) in THF (2 mL) was added to a suspension of the obtained resin 3 in THF (8 mL) at 0 °C, and followed with pyridine (1.5 mmol, 0.2 mL). The mixture was stirred 0 °C for 1 h and the γ-phenylsulfonylalkyl methyl carbonate resin 4 was collected by filtration and washed successively with 3% HCl (3 × 10 mL), H2O (3 × 10 mL), THF (3 × 5 mL), and dried in a vacuum. Subsequently, the resin 4 was swollen in THF (10 mL) and treated with LDA (2.0 mmol) at -78 °C for 1 h under dry nitrogen, at 0 °C for 2 h, and then at r.t. for 1 h. The resin 5 was collected by filtration and washed successively with THF-H2O (1:1, 30 mL), H2O (3 × 10 mL), and THF (3 × 5 mL). After drying in a vacuum, the resin 5 was swollen in CH2Cl2 (10 mL) and treated with Et3N (5.0 mmol) at r.t. for 10 h. The residual resin was collected by filtration and washed with CH2Cl2 (2 × 3 mL). The organic extracts were washed with H2O, dried over anhyd MgSO4 and concentrated to afford crude product 6 with 90-95% purity (determined by HPLC), which was further purified by silica gel chromatographic column (petroleum ether-EtOAc = 20:1) affording the pure products for 1H NMR and MS analysis.