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Synlett 2010(12): 1829-1832  
DOI: 10.1055/s-0030-1258111
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Amide Activation by Tf2O: Reduction of Amides to Amines by NaBH4 under Mild Conditions

Shao-Hua Xianga, Jian Xua, Hong-Qiu Yuana, Pei-Qiang Huang*a,b
a Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. of China
Fax: +86(592)2186400; e-Mail: pqhuang@xmu.edu.cn;
b The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. of China
Further Information

Publication History

Received 7 April 2010
Publication Date:
30 June 2010 (online)

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Abstract

An expeditious and practical method for the reduction of amides to amines is reported. The method is consisted of activation of amides with Tf2O followed by reduction with sodium borohydride in THF at room temperature. Various amides/lactams gave the corresponding amines in good to excellent yields, even with hindered amides and secondary amides. This method also presents other advantages such as TBDPS-group tolerance, short reaction time, simple workup and purification procedure.

Key words

reduction - amides - amines - amide activation - triflic anhydride

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14

All new compounds gave satisfactory analytical and spectral data. General Procedure for the Preparation of Amines from Amides
To a solution of an amide (1.0 mmol) in anhyd CH2Cl2 (10 mL) was added Tf2O (1.1 mmol) in an ice bath. After stirring for 30 min, NaBH4 (1.3 mmol) was added in one portion, and THF (5 mL) was added dropwise. After stirring for 60 min at r.t., the reaction was quenched with H2O (5 mL). The solution was brought to pH 10.5-11.0 by addition of a sat. aq Na2CO3 solution at 0 ˚C. The cooled aqueous solution was extracted with Et2O (5 × 15 mL). The combined organic layers were washed with brine (5 mL), dried over anhyd Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to give the corresponding amine (yields 69-93%). All new compound gave satisfactory spectral and analytical data (see Supporting Information).