Polyethyleneimine-Supported Triphenylphosphine and Its Use as a Highly Loaded Bifunctional Polymeric Reagent in Chromatography-Free One-Pot Wittig Reactions

Abstract

A polyethyleneimine-supported triphenylphosphine reagent has been synthesized and used as a highly loaded bifunctional homogeneous reagent in a range of one-pot Wittig reactions that afforded high yields of the desired products after simple purification procedures. The approach also served efficiently in tandem reaction sequences involving a one-pot Wittig reaction followed by conjugate reduction of the newly formed alkene product in situ. In these transformations, the phosphine oxide groups generated in the Wittig reaction served as the catalyst for activating trichlorosilane in the subsequent reduction reaction.

Key words

conjugate reduction - polyethyleneimine - polymer supported reagents - triphenylphosphine - Wittig reactions

• References and Notes

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• 20 General Procedure for One-Pot Wittig Reactions: Polymer 8 (0.2 g, 0.4 mmol phosphine) was dissolved in CHCl₃ (1 mL) in a 10-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser, and 13 (0.3 mmol) and 16 (0.2 mmol) were added. The mixture was stirred at 65 °C until the reaction was determined to be complete by TLC or ¹H NMR analysis. The reaction mixture was then cooled to r.t. and poured into a mixture of Et₂O (10 mL) and hexane (30 mL) in a beaker. The flask was rinsed with additional Et₂O (10 mL), and the combined organic solution was allowed to stand for 10 min before it was filtered through a short pad of diatomaceous earth, using additional Et₂O (2 × 10 mL) for rinsing. The filtrate was concentrated under reduced pressure to afford the desired product in an essentially pure state based on ¹H NMR analysis. Ethyl Cinnamate (8Aa): ¹H NMR (400 MHz, CDCl₃): δ = 7.79 (d, J = 16.0 Hz, 1 H), 7.53–7.51 (m, 2 H), 7.38–7.37 (m, 3 H), 6.44 (d, J = 16.0 Hz, 1 H), 4.26 (q, J = 7.1 Hz, 2 H), 1.34 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 167.1, 144.7, 134.6, 130.3, 129.0, 128.2, 118.4, 60.6, 14.4. MS: m/z calcd for C₁₁H₁₂O₂: 176.1; found: 176.1.
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• 24 General Procedure for Tandem Wittig/Conjugate Reduction Reactions: The Wittig reaction was conducted as before,^[20] but when it was determined to be complete, the mixture was cooled to 0 °C in an ice-water bath, and HSiCl₃ (0.4 mmol) was added. The reaction mixture was stirred for 2 h at 0 °C and then warmed to room temperature. When the reaction was determined to be complete by TLC analysis, the excess HSiCl₃ and solvent were evaporated under reduced pressure. The resulting mixture was dissolved in CHCl₃ (20 mL) and then added to sat. aq Na₂CO₃ (20 mL). The mixture was stirred for 30 min, then the aqueous phase was separated and washed with CH₂Cl₂ (3 × 15 mL). The combined organic layer was dried over MgSO₄ and concentrated under reduced pressure to afford the desired product in an essentially pure state based on ¹H NMR analysis. 1-(4-Bromophenyl)-3-phenylpropan-1-one (21Ad): ¹H NMR (400 MHz, CDCl₃): δ = 7.82 (d, J = 8.6 Hz, 2 H), 7.59 (d, J = 8.6 Hz, 2 H), 7.30–7.21 (m, 5 H), 3.26 (t, J = 7.5 Hz, 2 H), 3.06 (t, J = 7.5 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 198.3, 141.1, 135.6, 132.0, 129.6, 128.7, 128.5, 128.3, 126.3, 40.5, 30.1. MS: m/z calcd for C₁₅H₁₃BrO: 288.0; found 288.2.