Synlett 2007(5): 0826-0827  
DOI: 10.1055/s-2007-967961
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

Al-NiCl2·6H2O: A Mild and Efficient System for Selective Reduction of Functional Groups in Organic Synthesis

B. Rama Raju*
Department of Chemistry, Indian Institute of Technology ­Guwahati, Guwahati 781039, India
e-Mail: bachu@iitg.ernet.in;

Further Information

Publication History

Publication Date:
08 March 2007 (online)

Biographical Sketches

B. Rama Raju was born at Pathara, Orissa in India. He received his B.Sc. in Chemistry (Hons) from Khallikote (Autonomous) College, India. He completed his M.Sc. at Berhampur University, Orissa, in 2001. Currently he is pursuing his Ph.D. under the tutelage of Dr. Anil K. Saikia, Department of Chemistry, Indian Institute of ­Technology, Guwahati, India. His research interests include the development of new synthetic methodologies, incorporation of ­fluorine in organic molecules and their applications, and the syn­thesis of biologically active molecules.

Introduction

The most common broad-spectrum reducing agents are metal hydrides like LiAlH4, NaBH4, DIBAL-H, and 9-BBN. Apart from this, some hydrogenation catalysts have been investigated in order to find conditions under which a given group will be reduced chemoselectively. [1] Metal-metal-salt binary systems such as Al-NiCl2·6H2O·THF, [2] Al-SbCl3 or Zn-SbCl3, [3] Fe-NiCl2·6H2O·THF, [4] or Sm-NiCl2·6H2O·THF [5] have long been used as reducing agents for many functional groups.

Reagents based on aluminum find wide application in ­organic synthesis. [6] The Al-NiCl2·6H2O system is a highlight in current organic chemistry due to its selectivity, mild reaction conditions, easy handling, low cost, and convenient isolation process.

Abstracts

(A) Chemoselective reduction of α-enones:
α,β-Unsaturated carbonyl compounds give saturated ketones upon treatment with Al-NiCl2·6H2O. Aromatic aldehydes and ketones are smoothly reduced to the corresponding alcohols. Isolated ­double bonds, esters, aliphatic aldehydes, and ketones remain unaffected by this reagent. [7]

(B) Reduction of nitroarenes to amines:
Sarmah et al. showed that aromatic nitro compounds are reduced to the corresponding amines efficiently under neutral and mild conditions. Short reaction times and a simple work-up procedure make this a versatile reagent. [8]

(C) Conversion of oxiranes into alcohols:
Ring opening of the oxiranes takes place from the less hindered side of the epoxides, thereby giving the highest-substituted alcohols. An exception is the case of styrene oxide, where 1-phenyl­ethanol is the major product. α,β-Epoxy ketones remain unaffected under these reaction conditions. [2]

(D) Addition to electron-deficient alkenes:
The Al-NiCl2·6H2O redox couple promotes the addition of per(poly)fluoroalkyl iodides to per(poly)fluoroalkyl-substituted ethenes, giving the corresponding addition-elimination products in moderate yields. [9]

(E) Conversion of nitroolefins into carbonyl compounds:
Saturated ketones can be obtained from nitroolefins in mild reaction conditions with Al-NiCl2·6H2O. [10]

(F) Synthesis towards pyrrolo[2,1-c][1,4]benzodiazepines (PBD):
Employing Al-NiCl2·6H2O, many heterocyclic compounds like PBDs and dilactams can be synthesized via solid-phase reductive cyclization of nitro and azido compounds. [11]

(G) Facile reduction of sulfoxides to sulfides:
Sulfoxides can be reduced to the corresponding sulfides within short periods of time in high yields. Interestingly, ketones are not reduced under these reaction conditions. [12]

    References

  • 1 March J. Advanced Organic Chemistry   4th ed.:  John Wiley & Sons; New York: 1992.  p.1206  ;and references cited therein
  • 2 Sarmah BK. Barua NC. Tetrahedron  1991,  47:  8587 
  • 3 Wang WB. Shi LL. Huang YZ. Tetrahedron Lett.  1990,  31:  1185 
  • 4 Barua M. Boruah A. Prajapati D. Sandhu JS. Tetrahedron Lett.  1996,  37:  4559 
  • 5 Wu H. Chen R. Zhang Y. Synth. Commun.  2002,  32:  189 
  • 6 Chen JG. Beebe TP. Crowell JE. Yates JT. J. Am. Chem. Soc.  1987,  109:  1726 
  • 7 Hazarika MJ. Barua NC. Tetrahedron Lett.  1989,  30:  6567 
  • 8 Sarmah P. Barua NC. Tetrahedron Lett  1990,  31:  4065 
  • 9 Hu QS. Hu CM. J. Fluorine Chem.  1996,  76:  117 
  • 10 Bezbarua MS. Bez G. Barua NC. Chem. Lett.  1999,  325 
  • 11 Kamal A. Reddy KL. Devaiah V. Reddy GSK. Tetrahedron Lett.  2003,  44:  4741 
  • 12 Raju BR. Devi G. Nongpluh YS. Saikia AK. Synlett  2005,  358 

    References

  • 1 March J. Advanced Organic Chemistry   4th ed.:  John Wiley & Sons; New York: 1992.  p.1206  ;and references cited therein
  • 2 Sarmah BK. Barua NC. Tetrahedron  1991,  47:  8587 
  • 3 Wang WB. Shi LL. Huang YZ. Tetrahedron Lett.  1990,  31:  1185 
  • 4 Barua M. Boruah A. Prajapati D. Sandhu JS. Tetrahedron Lett.  1996,  37:  4559 
  • 5 Wu H. Chen R. Zhang Y. Synth. Commun.  2002,  32:  189 
  • 6 Chen JG. Beebe TP. Crowell JE. Yates JT. J. Am. Chem. Soc.  1987,  109:  1726 
  • 7 Hazarika MJ. Barua NC. Tetrahedron Lett.  1989,  30:  6567 
  • 8 Sarmah P. Barua NC. Tetrahedron Lett  1990,  31:  4065 
  • 9 Hu QS. Hu CM. J. Fluorine Chem.  1996,  76:  117 
  • 10 Bezbarua MS. Bez G. Barua NC. Chem. Lett.  1999,  325 
  • 11 Kamal A. Reddy KL. Devaiah V. Reddy GSK. Tetrahedron Lett.  2003,  44:  4741 
  • 12 Raju BR. Devi G. Nongpluh YS. Saikia AK. Synlett  2005,  358