Microwave-Assisted Tandem Nucleophilic Substitution-Wittig Reaction of α-Hypervalent Iodine Functionalized Phosphonium Ylide

Abstract

Under microwave irradiation conditions the tandem nucleophilic substitution-Wittig reaction of α-hypervalent iodine functionalized phosphonium ylide can occur readily to afford α-heteroatom substituted-α,β-unsaturated enoates in good yields stereoselectively.

Keywords

microwave irradiation conditions - α-hypervalent iodine functionalized phosphonium ylide - umpolung ylides - tandem reaction

References

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9

Typical procedure for the synthesis of α-bromo-substituted phosphonium ylide 3 under microwave irradiation conditions:
To a solution of α-hypervalent iodine functionalized phosphonium ylide in DMF was added Bu₄NBr, and the mixture was irradiated in a modified domestic microwave oven (National, power max. 750 W) for 3 min. The reaction mixture was poured into ice-cold water and extracted with benzene (4 × 20 mL), the organic layer was dried with Na₂SO₄. The solvent was evaporated to obtain a solid. Crystallization of this solid from acetone-hexane gave the pure α-bromosubstituted phosphonium ylide 3. mp155-156 °C (lit. [13] Mp 157-158 °C)

10

General procedure for the synthesis of product under microwave irradiation conditions:
To a solution of α-hypervalent iodine functionalized phosphonium ylide (2.0 mmol) and aldehyde (2.0 mmol) in anhydrous DMF was added the anions of nuleophiles (2.5 mmol), and the mixture was irradiated in a modified domestic microwave oven for a few minutes. The reaction mixture was poured into ice-cold water and extracted with ethyl acetate (3 × 20 mL), the organic layer was dried with Na₂SO₄. Removal of the solvent followed by column chromatography (ethyl acetate/hexane) of the crude product yielded (Z)-α-heteroatom-α,β-unsaturated enoates.
General procedure under conventional conditions: Under N₂, to a solution of α-hypervalent iodine functional-ized phosphonium ylide (2.0 mmol) (2.5 mmol) and aldehyde (2.0 mmol) in anhydrous DMF was added the anions of nuleophiles, the mixture was reacted under room temperature for 8-32 hours. After completion of the reaction, the following procedure was the same as above. [14]

11

The ratio of Z/E was determined by the ¹H NMR spectra. It was reported that the signal of vinyl and the methyl proton in ester of Z-type α-heteroatom substituted-α,-unsaturated enoates were in lower field than that of the corresponding E compounds. For example, ¹H NMR spectrum shows that the chemical shifts of vinyl and the methyl in ester proton of
Z-type ethyl 2-bromo-3-(4-methoxyphenyl)-2-propenoate are 7.80 ppm and 1.35 ppm, respectively. While the corresponding chemical shifts of the E-type ethyl 2-bromo-3-(4-methoxyphenyl)-2- propenoate compound are 7.07 ppm and 1.23 ppm, respectively. [12] The result is in accordance with our research.