Expedient Mukaiyama-Type Mannich Reaction Catalyzed by Lithium Chloride
19 May 2008 (online)
The Mannich reaction of methylsilyl enol ether with arylaldimine proceeded in the presence of a catalytic amount of lithium chloride in dimethylformamide at room temperature. The reaction was mild enough to apply to aldimines having the AcO, TBDMSO, or MeS group. Microwave irradiation accelerated the reaction substantially to reduce reaction time.
Mannich reaction - aldimines - trimethylsilyl ketene acetal - microwave heating - lithium chloride
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References and Notes
Typical Experimental Procedure
To a stirred solution of N-p-toluenesulfonyl-p-chlorophenyl-aldimine (1, 118 mg, 0.4 mmol) and LiCl (3.4 mg, 0.08 mmol) in DMF (1.5 mL) was added trimethylsilyl ketene acetal 2 (130 µL, 0.6 mmol) at r.t. under nitrogen atmosphere. After stirring for 13 h, the reaction was quenched by adding H2O. The product was extracted with EtOAc twice and the combined organic layer was washed with H2O and brine, and then evaporated to dryness. Column chromatography of the residue (eluent, EtOAc-n-hexane, 1:2) afforded β-amino ester 3 (145 mg, 91%).