Nucleophilic Addition Reactions of Nitriles to Nitrones under Mild Silylation Conditions

Fumihiko Yoshimura; Taiki Abe; Keiji Tanino

doi:10.1055/s-0034-1378274

Synlett, Inhaltsverzeichnis

Synlett 2014; 25(13): 1863-1868
DOI: 10.1055/s-0034-1378274

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Nucleophilic Addition Reactions of Nitriles to Nitrones under Mild Silylation Conditions

Fumihiko Yoshimura*

^aDepartment of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan Fax: +81(11)7064920 eMail: fumi@sci.hokudai.ac.jp eMail: ktanino@sci.hokudai.ac.jp

,

Taiki Abe

^bGraduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan

,

Keiji Tanino*

^aDepartment of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan Fax: +81(11)7064920 eMail: fumi@sci.hokudai.ac.jp eMail: ktanino@sci.hokudai.ac.jp

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Abstract

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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

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Referenzen

References and Notes

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8 We could not detect N-silyl ketene imine 4 when monitoring the reaction by ¹H and ¹³C NMR spectroscopy. The isomerization of 3 did not proceed in the absence of either TMSOTf or Et₃N. Accordingly, very reactive intermediate 4 was immediately protonated by triethylamine salt of triflic acid generated in situ as a proton source, providing the isomerized product 3
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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%).

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