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Synlett 2006(12): 1887-1890  
DOI: 10.1055/s-2006-947341
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel Liquid-Phase Synthesis of Baylis-Hillman Products Using PEG-Supported α-Phenylselenopropionate Ester

Shou-Ri Sheng*a, Qiong Wanga, Qiu-Ying Wanga, Lei Guoa, Xiao-Ling Liua, Xian Huanga,b
a Institutes of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330027, P. R. of China
b Department of Chemistry, Zhejiang University, Hangzhou, 310027, P. R. of China
Fax: +86(791)8120380; e-Mail: shengsr@jxnu.edu.cn;
Further Information

Publication History

Received 17 April 2006
Publication Date:
24 July 2006 (online)

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Abstract

Treatment of the lithio derivative of novel PEG-supported α-phenylselenopropionate ester with aldehydes and subsequent cleavage from the PEG support by oxidative elimination with 30% hydrogen peroxide efficiently afforded Baylis-Hillman products in good yields and high purities.

Key words

liquid-phase organic synthesis - PEG-supported α-selenopropanoate ester - Baylis-Hillman products

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PEG-Bound α-Phenylselenopropionate Ester 2: To a stirred solution of PEG (5.0 g, 2.5 mmol) in CH2Cl2 (20 mL) were added α-phenylselenopropanoic acid (1.72 g, 7.5 mol), DCC (2.06 g, 10 mol), and DMAP (0.305 g, 2.5 mol). After the mixture was stirred at r.t. for 24 h, the precipitate was removed by filtration, and the polymer was precipitated by addition of Et2O (200 mL) to the filtrate. To allow complete precipitation, the suspension was left at 0 °C for 30 min. The precipitate was collected and washed with Et2O (3 × 30 mL), and dried in vacuo to afford the PEG-bound ester 2 as a pale yellow solid. IR (KBr): 2886, 1728, 1644, 1455, 1350, 1252, 1146, 950, 849 cm-1. 1H NMR (CDCl3): δ = 7.61-7.59 (m, 2 H), 7.31-7.29 (m, 3 H), 4.18 (t, J = 4.98 Hz, 2 H, PEG-OCH2CH 2 OCO), 4.08 (q, J = 6.8 Hz, 1 H), 3.46-3.81 (m, PEG CH2), 1.54 (d, J = 6.8 Hz, 3 H).

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Liquid-Phase Synthesis of Target Molecules 5a-k; General Procedure. To a stirred solution of LDA [2.0 mmol; from i-Pr2NH (2.2 mmol) and n-BuLi (2.0 mmol)] in anhyd THF (10 mL) at -78 °C under a nitrogen atmosphere was added PEG-bound ester 2 (1.0 mmol). After stirring at -78 °C for 30 min, the neat aldehyde (2.0 mmol) in THF (5 mL) was added dropwise over ca. 15 min. After 20 min the reaction mixture was warmed to 0 °C and glacial AcOH (0.5 mL) and 30% aqueous H2O2 (1.0 mL, 11.6 mmol) were added. After 30 min, the ice bath was removed and the mixture was allowed to stir at r.t. for 1-2 h. After completion of the reaction, the reaction mixture was cooled and Et2O (100 mL) was added to allow the precipitation of resin 4, which was collected by filtration and washed with Et2O (3 × 30 mL). Resin 4 was stirred at r.t. for 8 h with 0.1 N NaOEt in EtOH (10 mL), then Et2O (40 mL) and H2O were added to the mixture, and the organic phase was separated. The organic extracts were dried over anhyd Na2SO4 and concentrated to afford BH crude products 5a-k, which were further purified by passing the crude product through a silica gel column (EtOAc-hexane, 1:9→1.5:8.5), if necessary. The products were characterized from their spectra (1H NMR and IR) and by comparison with authentic samples. 5a: IR (neat): 3468, 1720, 1630 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.43-7.41 (m, 2 H), 7.21-7.19 (m, 3 H), 6.31 (s, 1 H), 5.90 (s, 1 H), 5.51 (s, 1 H), 3.70 (s, 3 H), 2.83 (br s, 1 H). 5b: IR (neat): 3448, 1722, 1629 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.28 (d, J = 8.8 Hz, 2 H), 6.70 (d, J = 8.8 Hz, 2 H), 6.34 (s, 1 H), 6.30 (s, 1 H), 5.10 (s, 1 H), 3.78 (s, 3 H), 3.74 (s, 3 H), 2.85 (br s, 1 H). 5c: IR (neat): 3448, 1716, 1630 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.33 (d, J = 7.6 Hz, 2 H), 7.20 (d, J = 7.6 Hz, 2 H), 6.32 (s, 1 H), 5.80 (s, 1 H), 5.49 (s, 1 H), 3.74 (s, 3 H), 2.59 (br s, 1 H). 5d: IR (neat): 3445, 1718, 1631 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.65 (d, J = 7.8 Hz, 1 H), 7.39-7.26 (m, 3 H), 6.33 (s, 1 H), 5.81 (s, 1 H), 5.50 (s, 1 H), 3.75 (s, 3 H), 2.62 (br s, 1 H). 5e: IR (neat): 3446, 1718, 1626 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.30-7.36 (m, 2 H), 6.98-7.05 (m, 2 H), 6.32 (s, 1 H), 5.80 (s, 1 H), 5.53 (s, 1 H), 3.71 (s, 3 H), 2.57 (br s, 1 H). 5f: IR (neat): 3450, 1721, 1628 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.49 (s, 1 H), 7.24-7.36 (m, 2 H), 6.30 (s, 1 H), 5.90 (s, 1 H), 5.55 (s, 1 H), 3.76 (s, 3 H), 2.97 (br s, OH). 5g: IR (neat): 3473, 1689, 1630, 1520 cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.18 (d, J = 8.8 Hz, 2 H), 7.55 (d, J = 8.8 Hz, 2 H), 6.37 (s, 1 H), 5.86 (s, 1 H), 5.60 (s, 1 H), 3.73 (s, 3 H), 2.93 (br s, 1 H). 5h: IR (neat): 3498, 1715, 1620 cm-1. 1H NMR (400 MHz, CDCl3): δ = 6.24 (s, 1 H), 5.85 (s, 1 H), 4.41 (t, J = 6.5 Hz, 1 H), 3.78 (s, 3 H), 2.72 (br s, 1 H), 1.71-1.62 (m, 2 H), 1.39-1.25 (m, 2 H), 0.92 (t, J = 7.0 Hz, 3 H). 5i: IR (neat): 3440, 1721, 1633 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.35 (s, 1 H), 6.36 (s, 1 H), 6.24-6.35 (m, 2 H), 5.92 (s, 1 H), 5.57 (s, 1 H), 3.74 (s, 3 H), 2.87 (br s, 1 H). 5j: IR (neat): 3450, 1718, 1626 cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.35 (s, 1 H), 8.25 (d, J = 3.6 Hz, 1 H), 7.64 (d, J = 7.8 Hz, 1 H), 7.17 (dd, J = 4.8, 8.1 Hz, 1 H), 6.31 (s, 1 H), 5.98 (s, 1 H), 5.20 (s, 1 H), 5.17 (br s, 1 H), 3.60 (s, 3 H). 5k: IR (neat): 3445, 1718, 1634 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.91-7.30 (m, 7 H), 6.36 (s, 1 H), 6.31 (s, 1 H), 5.18-5.19 (m, 1 H), 3.75 (s, 3 H), 2.58 (br s, 1 H).

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Compound 6a: IR (neat): 3330, 1690, 1628 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.42-7.40 (m, 2 H), 7.22-7.19 (m, 3 H), 6.43 (s, 1 H), 6.02 (s, 1 H), 5.70 (s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 169.5, 140.6, 139.8, 128.7, 127.6, 127.2, 126.1, 69.2.

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Liquid-Phase Synthesis of Methyl ( E )-3-Phenyl-2-bromomethyl-2-propenoate ( 8a).
To a stirred solution of resin 4a (2.3 g, approximate loading 0.45 mmol/g) and Ph3P (2.7 g, 10 mmol) in anhyd CH2Cl2 (15 mL) at -50 °C under a nitrogen atmosphere was added NBS (1.79 g, 10 mmol) in CH2Cl2 (5 mL) dropwise. After warming to r.t. overnight, the resin 7a was precipitated by adding Et2O (100 mL) to the reaction mixture. The sus-pension was kept at 0 °C for a further 30 min to ensure complete precipitation and finally the polymer was filtered, washed with Et2O (3 × 30 mL), and dried in vacuo. The cleavage step for 8a was performed according to the above procedure. IR (neat): 1715, 1641, 1440, 1387, 1356 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.81 (s, 1 H), 7.46-7.44 (m, 2 H), 7.31-7.29 (m, 3 H), 4.23 (s, 2 H), 3.89 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 165.5, 146.2, 131.8, 129.7, 128.2, 127.4, 120.7, 52.1, 20.4.

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Compound 8b: IR (neat): 1715, 1641, 1440, 1387, 1356 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.78 (s, 1 H), 7.45-7.43 (m, 2 H), 7.30-7.27 (m, 3 H), 4.25 (s, 2 H), 3.88 (s, 3 H), 3.23 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 165.3, 145.9, 131.3, 129.3, 128.8, 127.1, 121.0, 57.1, 52.2, 20.7.