Nucleophilic Addition Reactions of Nitriles to Nitrones under Mild Silylation Conditions

Abstract

In the presence of triethylsilyl trifluoromethanesulfonate and triethylamine, aliphatic nitriles undergo addition reactions with aldonitrones under non-basic, mild conditions, providing O-tri­ethylsilyl ethers of β-N-hydroxyamino nitriles with high yield. The reaction appears to proceed through formation of an N-silyl ketene imine in situ followed by a Mannich-type reaction.

Key words

nucleophilic addition - nitriles - nitrones - amines - ­hydroxylamine

• References and Notes


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• 19 General Procedure (Table 1, entry 6): To a mixture of nitrone 10 (0.4 mmol), nitrile 13 (0.4 mmol), and Et₃N (0.8 mmol) in DCE (2 mL), was added TESOTf (0.8 mmol) at –30 °C, and the reaction mixture was stirred at this temperature for 30 min. Sat. aq sodium bicarbonate (1 mL) was added to the mixture, and the product was extracted with EtOAc. The combined organic layers were dried over MgSO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂; hexane–Et₂O, 15:1) afforded O-TES β-hydroxyamino nitrile 14c (0.377 mmol, 94%).