Reductive Claisen-Type Condensation Promoted by the Combination of Phosphine and Lewis Acid

Abstract

The Ph₃P/TiCl₄ combination was found to be an effective promoter for the Claisen-type condensation of α-bromothioesters. Both in the case of self-condensation and crossed-type reactions, corresponding β-ketothioesters were obtained in good yields.

Key words

Claisen condensation - Lewis acids - titanium tetra­chloride - thioesters - phosphines

References

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7

Typical Procedure for the Self-Claisen Condensation: Under an argon atmosphere, to a solution of S-phenyl-2-bromopropanethioate (2a, 95.0 mg, 0.39 mmol) and TiCl₄ (5 mol/L, 0.12 mL, 0.6 mmol) in DCE (3 mL) was added a solution of Ph₃P (151.6 mg, 0.58 mmol) in CH₂Cl₂ (1 mL). The reaction mixture was stirred for 1 h and quenched with water (3 mL) and ethylene glycol (2 mL). The mixture was extracted with CH₂Cl₂ (3 × 10 mL), washed with brine (10 mL), and dried over MgSO₄. The organic layer was filtered and evaporated under reduced pressure. The crude product was purified by preparative TLC (SiO₂, CH₂Cl₂-hexane = 1:1) to give S-phenyl-2-methyl-3-oxopentanethioate (3a, 32.6 mg, 76%).