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

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.

reduction - amides - amines - amide activation - triflic anhydride

References and Notes

<A NAME="RW05110ST-1A">1a</A> Ricci MA. Modern Amination Methods   Wiley; New York: 2000. 

<A NAME="RW05110ST-1B">1b</A> Encyclopedia of the Alkaloids   Glasby JS. Plenum Press; New York: 1975. 

<A NAME="RW05110ST-2A">2a</A> Handbook of Reagents for Organic Synthesis Oxidizing and Reducing Agents   Burke SD. Danheiser RL. Wiley and Sons; West Sussex: 1999. 

<A NAME="RW05110ST-2B">2b</A> Seyden-Penne J. Reductions by the Alumino and Borohydrides in Organic Synthesis   2nd ed.:  Wiley; New York: 1997. 

<A NAME="RW05110ST-3">3</A> Brown HC. Weissman PM. Yoon N.-M. J. Am. Chem. Soc.  1966,  88:  1458 

<A NAME="RW05110ST-4A">4a</A> Kornet MJ. Tan SI. J. Org. Chem.  1968,  33:  3637 

<A NAME="RW05110ST-4B">4b</A> Brown HC. Heydkamp WR. Breuer E. Murphy WS. J. Am. Chem. Soc.  1964,  86:  3566 

For reduction with other agents/systems, see:

<A NAME="RW05110ST-5A">5a</A> DIBAL-H: Winterfeldt E. Synthesis  1975,  617 

<A NAME="RW05110ST-5B">5b</A> NaBH₄-TFA and NaBH₄-TFAA: Gribble GW. Nataitis CF. Org. Prep. Proced. Int.  1985,  17:  317 

<A NAME="RW05110ST-5C">5c</A> NaBH₄-I₂: Mckennon MJ. Meyers AI. Drauz K. Schwarm M. J. Org. Chem.  1993,  58:  3568 

<A NAME="RW05110ST-5D">5d</A> 9-BBN: Collins CJ. Lanz M. Singaram B. Tetrahedron Lett.  1999,  40:  3673 

<A NAME="RW05110ST-5E">5e</A> LiH₃BNMe₂: Flaniken JM. Collins CJ. Lanz M. Singaram B. Org. Lett.  1999,  1:  799 

<A NAME="RW05110ST-6A">6a</A> Rajashekhar B. Kaiser ET. J. Org. Chem.  1985,  50:  5480 

<A NAME="RW05110ST-6B">6b</A> McWilliams JC. Clardy J. J. Am. Chem. Soc.  1994,  116:  8378 

<A NAME="RW05110ST-6C">6c</A> Huang P.-Q. Wei B.-G. Ruan Y.-P. Synlett  2003,  1663 

<A NAME="RW05110ST-6D">6d</A> Campbell AL. Pilipauqkas DR. Khanna IK. Rhodes RA. Tetrahedron Lett.  1987,  28:  2331 

<A NAME="RW05110ST-7">7</A> Akamatsu H. Kusumoto S. Fukase K. Tetrahedron Lett.  2002,  43:  8867 

<A NAME="RW05110ST-8A">8a</A> Brown HC. Heim P. J. Org. Chem.  1973,  38:  912 

<A NAME="RW05110ST-8B">8b</A> Brown HC. Choi Y.-M. Narasimhan S. J. Org. Chem.  1982,  47:  3153 

<A NAME="RW05110ST-8C">8c</A> Hercouet MB. Le Corre M. Synth. Commun.  1991,  21:  1579 

For selected examples, see:

<A NAME="RW05110ST-9A">9a</A> Motoyama Y. Mitsui K. Ishida T. Nagashima H. J. Am. Chem. Soc.  2005,  127:  13150 

<A NAME="RW05110ST-9B">9b</A> Ohta T. Kamiya M. Nobutomo M. Kusui K. Furukawa I. Bull. Chem. Soc. Jpn.  2005,  78:  1856 

<A NAME="RW05110ST-9C">9c</A> Fernandes AC. Romão CC. J. Mol. Catal. A: Chem.  2007,  272:  60 

<A NAME="RW05110ST-9D">9d</A> Núňez Magro AA. Eastham GR. Cole-Hamilton DJ. Chem. Commun.  2007,  3154 

<A NAME="RW05110ST-9E">9e</A> Zhou S.-L. Junge K. Addis D. Das S. Beller M. Angew. Chem. Int. Ed.  2009,  48:  9507 

<A NAME="RW05110ST-9F">9f</A> Sunada Y. Kawakami H. Imaoka T. Motoyama Y. Nagashima H. Angew. Chem. Int. Ed.  2009,  48:  9511 

<A NAME="RW05110ST-9G">9g</A> Hanada S. Tsutsumi E. Motoyama Y. Nagashima H. J. Am. Chem. Soc.  2009,  131:  15032 ; and references cited therein

For two mild Lewis acid catalyzed amide reduction methods, see:

<A NAME="RW05110ST-10A">10a</A> InBr₃, TES: Sakai N. Fujii K. Konakahara T. Tetrahedron Lett.  2008,  49:  6873 

<A NAME="RW05110ST-10B">10b</A> Zn(OAc)₂, silanes: Das S. Addis D. Zhou S.-L. Junge K. Beller M. J. Am. Chem. Soc.  2010,  132:  1770 

For other methods of amides activation, see:

<A NAME="RW05110ST-11A">11a</A> Et₃O⁺BF₄ ^-: Borch RF. Tetrahedron Lett.  1968,  1:  61 

<A NAME="RW05110ST-11B">11b</A> POCl₃/PCl₅: Atta-ur-Rahman AB. Ahmed S. Tetrahedron Lett.  1976,  3:  219 

<A NAME="RW05110ST-11C">11c</A> POCl₃: Kuehne ME. Shannon PJ. J. Org. Chem.  1977,  42:  2082 

<A NAME="RW05110ST-12">12</A> Barbe G. Charette AB. J. Am. Chem. Soc.  2008,  130:  18 

<A NAME="RW05110ST-13">13</A> Xiao K.-J. Luo J.-M. Ye K.-Y. Wang Y. Huang P.-Q. Angew. Chem. Int. Ed.  2010,  49:  3037 

<A NAME="RW05110ST-14">14</A>

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).

<A NAME="RW05110ST-15A">15a</A> Bisseret P. Bouix-Peter C. Jacques O. Henriot S. Eustache J. Org. Lett.  1999,  1:  1181 

<A NAME="RW05110ST-15B">15b</A> Hall DG. Laplante C. Manku S. Nagendran J. J. Org. Chem.  1999,  64:  698 

<A NAME="RW05110ST-16">16</A> Xiang S.-H. Yuan H.-Q. Huang P.-Q. Tetrahedron: Asymmetry  2009,  20:  2021 

<A NAME="RW05110ST-17A">17a</A> Courcambeck J. Bihel F. Michelis C. Quelever G. Kraus JL. J. Chem. Soc., Perkin Trans. 1  2001,  1421 

<A NAME="RW05110ST-17B">17b</A> Huang P.-Q. Deng J. Synlett  2004,  247