Download PDF
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)

   Permissions and Reprints All articles of this category
Preview

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

    References and Notes

  • 1a Ricci MA. Modern Amination Methods   Wiley; New York: 2000. 
  • 1b Encyclopedia of the Alkaloids   Glasby JS. Plenum Press; New York: 1975. 
  • 2a Handbook of Reagents for Organic Synthesis Oxidizing and Reducing Agents   Burke SD. Danheiser RL. Wiley and Sons; West Sussex: 1999. 
  • 2b Seyden-Penne J. Reductions by the Alumino and Borohydrides in Organic Synthesis   2nd ed.:  Wiley; New York: 1997. 
    Search in Google Scholar
  • 3 Brown HC. Weissman PM. Yoon N.-M. J. Am. Chem. Soc.  1966,  88:  1458 
    CrossrefSearch in Google Scholar
  • 4a Kornet MJ. Tan SI. J. Org. Chem.  1968,  33:  3637 
    Search in Google Scholar
  • 4b Brown HC. Heydkamp WR. Breuer E. Murphy WS. J. Am. Chem. Soc.  1964,  86:  3566 
    Search in Google Scholar
  • For reduction with other agents/systems, see:
  • 5a DIBAL-H: Winterfeldt E. Synthesis  1975,  617 
  • 5b NaBH4-TFA and NaBH4-TFAA: Gribble GW. Nataitis CF. Org. Prep. Proced. Int.  1985,  17:  317 
    Search in Google Scholar
  • 5c NaBH4-I2: Mckennon MJ. Meyers AI. Drauz K. Schwarm M. J. Org. Chem.  1993,  58:  3568 
    Search in Google Scholar
  • 5d 9-BBN: Collins CJ. Lanz M. Singaram B. Tetrahedron Lett.  1999,  40:  3673 
    Search in Google Scholar
  • 5e LiH3BNMe2: Flaniken JM. Collins CJ. Lanz M. Singaram B. Org. Lett.  1999,  1:  799 
    Search in Google Scholar
  • 6a Rajashekhar B. Kaiser ET. J. Org. Chem.  1985,  50:  5480 
    Search in Google Scholar
  • 6b McWilliams JC. Clardy J. J. Am. Chem. Soc.  1994,  116:  8378 
    Search in Google Scholar
  • 6c Huang P.-Q. Wei B.-G. Ruan Y.-P. Synlett  2003,  1663 
  • 6d Campbell AL. Pilipauqkas DR. Khanna IK. Rhodes RA. Tetrahedron Lett.  1987,  28:  2331 
    Search in Google Scholar
  • 7 Akamatsu H. Kusumoto S. Fukase K. Tetrahedron Lett.  2002,  43:  8867 
    CrossrefSearch in Google Scholar
  • 8a Brown HC. Heim P. J. Org. Chem.  1973,  38:  912 
    Search in Google Scholar
  • 8b Brown HC. Choi Y.-M. Narasimhan S. J. Org. Chem.  1982,  47:  3153 
    Search in Google Scholar
  • 8c Hercouet MB. Le Corre M. Synth. Commun.  1991,  21:  1579 
    Search in Google Scholar
  • For selected examples, see:
  • 9a Motoyama Y. Mitsui K. Ishida T. Nagashima H. J. Am. Chem. Soc.  2005,  127:  13150 
    Search in Google Scholar
  • 9b Ohta T. Kamiya M. Nobutomo M. Kusui K. Furukawa I. Bull. Chem. Soc. Jpn.  2005,  78:  1856 
    Search in Google Scholar
  • 9c Fernandes AC. Romão CC. J. Mol. Catal. A: Chem.  2007,  272:  60 
    Search in Google Scholar
  • 9d Núňez Magro AA. Eastham GR. Cole-Hamilton DJ. Chem. Commun.  2007,  3154 
  • 9e Zhou S.-L. Junge K. Addis D. Das S. Beller M. Angew. Chem. Int. Ed.  2009,  48:  9507 
    Search in Google Scholar
  • 9f Sunada Y. Kawakami H. Imaoka T. Motoyama Y. Nagashima H. Angew. Chem. Int. Ed.  2009,  48:  9511 
    Search in Google Scholar
  • 9g Hanada S. Tsutsumi E. Motoyama Y. Nagashima H. J. Am. Chem. Soc.  2009,  131:  15032 ; and references cited therein
    Search in Google Scholar
  • For two mild Lewis acid catalyzed amide reduction methods, see:
  • 10a InBr3, TES: Sakai N. Fujii K. Konakahara T. Tetrahedron Lett.  2008,  49:  6873 
    Search in Google Scholar
  • 10b Zn(OAc)2, silanes: Das S. Addis D. Zhou S.-L. Junge K. Beller M. J. Am. Chem. Soc.  2010,  132:  1770 
    Search in Google Scholar
  • For other methods of amides activation, see:
  • 11a Et3O+BF4 -: Borch RF. Tetrahedron Lett.  1968,  1:  61 
    Search in Google Scholar
  • 11b POCl3/PCl5: Atta-ur-Rahman AB. Ahmed S. Tetrahedron Lett.  1976,  3:  219 
    Search in Google Scholar
  • 11c POCl3: Kuehne ME. Shannon PJ. J. Org. Chem.  1977,  42:  2082 
    Search in Google Scholar
  • 12 Barbe G. Charette AB. J. Am. Chem. Soc.  2008,  130:  18 
    CrossrefSearch in Google Scholar
  • 13 Xiao K.-J. Luo J.-M. Ye K.-Y. Wang Y. Huang P.-Q. Angew. Chem. Int. Ed.  2010,  49:  3037 
    CrossrefSearch in Google Scholar
  • 15a Bisseret P. Bouix-Peter C. Jacques O. Henriot S. Eustache J. Org. Lett.  1999,  1:  1181 
    Search in Google Scholar
  • 15b Hall DG. Laplante C. Manku S. Nagendran J. J. Org. Chem.  1999,  64:  698 
    Search in Google Scholar
  • 16 Xiang S.-H. Yuan H.-Q. Huang P.-Q. Tetrahedron: Asymmetry  2009,  20:  2021 
    CrossrefSearch in Google Scholar
  • 17a Courcambeck J. Bihel F. Michelis C. Quelever G. Kraus JL. J. Chem. Soc., Perkin Trans. 1  2001,  1421 
  • 17b Huang P.-Q. Deng J. Synlett  2004,  247 
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).