Preparation of Polystyrene-Supported α-Seleno Acetate and Application to Solid-Phase Synthesis of β-Keto Esters

Abstract

A novel polystyrene-supported α-seleno acetate has been developed. This novel resin was treated with LDA to produce a ­selenium-stabilized carbanion, which reacted with aldehydes, followed by selenoxide syn-elimination to give β-keto esters.

solid-phase synthesis - α-seleno acetate - selenoxide syn-elimination - β-keto esters - polymer reagent

References and Notes

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Preparation of Polystyrene-Supported α-Seleno Acetate. Under a nitrogen atmosphere, resin 1 (2 g; elemental analysis Br, 1.71 mmol/g) was swelled in THF (20 mL) overnight. The mixture added NaBH₄ (10 mmol) stirred at r.t. for 0.5 h and added 2 mL DMF. After 15 h, ethyl bromoacetate (15 mmol) was added and the resulting mixture stirred at r.t. for 12 h. The resin 3 was collected on a filter and washed alternately with THF (2 × 15 mL), H₂O (4 × 20 mL), EtOH (2 × 15 mL), MeOH (15 mL), THF (2 × 15 mL), CH₂Cl₂ (2 × 15 mL), and dried under vacuum. Resin 3 (1.64 mmol/g): IR (KBr): 3058, 3024, 2922, 1730, 1600, 1587, 1568, 1492, 1452, 1365, 1258, 1104, 1028, 758, 698, 540 cm^-1.

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Determined by acid-base titration to be 1.64 mmol/g (COOH). For analytical purposes, the resin of α-seleno acetic acid was prepared by reaction of resin 3 (1 g) with LiOH (1.5 mol/L, 3 mL) in THF (15 mL). After stirred at 35 °C overnight, the resin was washed successively with H₂O, 10% HCl, H₂O, THF and CH₂Cl₂. IR (KBr): 3058, 3024, 2922, 1700, 1600, 1588, 1568, 1492, 1452, 1285, 1106, 758, 698, 541 cm^-1.

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<A NAME="RW04806ST-10">10</A>

Typical Procedure for the Synthesis of β-Keto Ester. Under a nitrogen atmosphere, the resin 3 (0.5 g) was suspended in THF (15 mL) at -78 °C and LDA (1 mmol) was added with stirring. The mixture was stirred 0.5 h at
-78 °C, then benzaldehyde (1.5 mmol) was added. After stirring at -78 °C for 0.5 h, the mixture was warmed to r.t. in 2 h. Then, the mixture was filtered. The resin 4d was collected by filtration and washed with THF (2 × 10 mL), MeOH (2 × 10 mL), CHCl₃ (2 × 10 mL) and THF (2 × 10 mL). The washed resin 4d was suspended in THF (15 mL). To the mixture was added 30% H₂O₂ (2 mL) and followed by stirring for 2 h at r.t. The mixture was filtered and the resin was washed with CHCl₃ (3 × 15 mL). The filtrate was washed with H₂O (2 × 30 mL), dried over MgSO₄, and evaporated to dryness under vacuum to afford 130 mg (82%) of almost pure ethyl benzoylacetate.