Aldol Reaction of Trimethylsilyl Enolate with Aldehyde Catalyzed by Pyridine N-Oxide as a Lewis Base Catalyst

Abstract

Aldol reaction of trimethylsilyl enolate with aldehydes proceeded in the presence of a catalytic amount of a Lewis base, pyridine N-oxide, and lithium chloride in DMF at room temperature. Not only aryl aldehydes but also alkyl aldehydes provided the aldol products in satisfactory yields. The reaction was mild enough to ­apply to aldehydes having HO, AcO, THPO, TBDMSO, MeS, ­pyridyl, or olefinic groups.

Key words

aldol reactions - organomolecular catalysis - pyridine N-oxide - trimethylsilyl ketene acetal - Lewis base

References

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16

Typical experimental procedure: To a stirred solution of pyridine N-oxide (3.8 mg, 0.04 mmol) and LiCl (3.4 mmol, 0.08 mmol) in DMF (1.5 mL) were added benzaldehyde 2 (R = Ph) (42 µL, 0.4 mmol) and trimethylsilyl ketene acetal 1 (105 µL, 0.52 mmol) at r.t. under a nitrogen atmosphere. After stirring for 5 h, the reaction was quenched by the addition of 1 N aq HCl. The product was extracted with EtOAc twice. The combined organic layer was washed with water, brine, and evaporated to dryness. The residue was purified by medium-pressure LC (EtOAc-hexane, 1:2) to afford aldol product 3 (R = Ph) (92 mg, 81%) as a solid.

17

All new compounds have satisfactory analytical data including ¹H NMR, ¹³C NMR and IR spectra and HRMS.