Molecular Iodine-Catalyzed Imine Activation for Three-Component ­Nucleophilic Addition Reactions

Abstract

β-Amino ketones and α-amino nitriles were synthesized from silyl enol ethers and trimethylsilyl cyanides, via a three-component nucleophilic addition reaction with aromatic aldehydes and amines; the reaction was found to be significantly accelerated by molecular iodine under neutral conditions.

molecular iodine - imine activation - three-component reaction - Mannich-type reaction - Strecker-type reaction

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Typical Procedure for β-Amino Ketone and α-Amino Nitrile Synthesis.
To a MeOH solution (10 mL) was added aldehyde (1.0 mmol), aniline (1.1 mmol) and nucleophile (1.2 mmol, silyl enol ether for β-amino ketone or trimethylsilyl cyanide for α-amino nitrile). Upon completion of the reaction (monitored by TLC), aq Na₂SO₃ (1 mL) and H₂O (100 mL) were added. The organic compounds were extracted with EtOAc (3 × 20 mL) from the aqueous solution and the combined extract was dried over Na₂SO₄. The solvent was evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel to afford pure product, characterized by ¹H NMR, ¹³C NMR and mass spectrometry.