Synlett 2006(2): 327-328  
DOI: 10.1055/s-2006-926228
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

Cu(BF4)2 ·xH2O: A Versatile Catalyst

Raj Kumar Khunger*
Department of Medicinal Chemistry, National Institute of ­Pharmaceutical Education and Research (NIPER), SAS Nagar, Punjab 160062, India
e-Mail: khunger_raj@rediffmail.com;

Further Information

Publication History

Publication Date:
24 January 2006 (online)

Biographical Sketches

Raj Kumar was born in 1979. He received his B. Pharm. in 2001 from Maharshi Dayanand University, Rohtak, Haryana, India. He started to study chemistry in 2001 at the Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and ­Research (NIPER), Punjab, India, where he completed his M.S. (Pharm) thesis under the supervision of Prof. Asit K. Chakraborti, FRSC. After completion of his degree in 2003 he joined Discovery Research, Dr. Reddy’s Laboratories Ltd, ­Hyderabad, India as a research chemist. He then returned to NIPER and is currently working on his Ph.D. thesis, again under the ­guidance of Prof. Chakraborti. His primary research interests focus on the synthesis of small ­heterocyclic compounds of medicinal ­importance and the development of new methodologies.

Introduction

Copper(II) tetrafluoroborate hydrate Cu(BF4)2·xH2O [CAS: 314040-98-7] is a corrosive, moisture-sensitive, blue crystalline solid readily soluble in water and sparingly soluble in alcohols. Cu(BF4)2·xH2O is readily available and widely used as the starting material for homometallic, trinuclear heteroscorpionate [1] complexes applied in the studies of electronic and magnetic properties. It causes decomposition of 9-diazofluorene in acetonitrile solvent. [2] As it does not require special storage conditions and is safe and stable under normal environmental conditions, Cu(BF4)2·xH2O has emerged as one of most useful reagent in various transformations such as acylation reactions and 1,1-diacetate formations. In all the cases, this reagent has been found to be superior to other available Lewis acids such as triflates, tetrafluoroborates and perchlorates with regard to short reaction times, requirement of stoichio­metric amount of reagent, mild reactions conditions, solvent-free conditions and low cost. Further, the distinct advantage of the use of Cu(BF4)2.xH2O as a catalyst for thia-Michael addition reactions [3] with α,β-unsaturated ­carbonyl compounds is evidenced by the fact that the ­reaction of 3-methylcyclohexenone with thiophenol ­afforded the product in 45 minutes while the corresponding reaction did not proceed in the presence of an ionic ­liquid. [4]

Abstract

(A) Acylation reactions: Acetylation [5] of structurally diverse phenols, alcohols, thiols, and amines with stoichiometric amounts of Ac2O under solvent-free conditions at room temperature has been efficiently catalyzed by Cu(BF4)2·xH2O. Excellent chemoselectivity was observed during reaction with secondary and tertiary alcohols without any competitive dehydration and no rearrangement took place with allylic and propargylic substrates.

(B) Diacetate formation: A strong catalytic effect of Cu(BF4)2·xH2O has also been observed in the formation of aldehyde 1,1-diacetates [6] from aldehydes and acetic anhydride under solvent-free conditions at room temperature. The rate of reaction was found to be very fast and in most of the cases the reaction was completed in 1-20 minutes in excellent yields, which could make this method more attractive and industrially viable.

(C) Conjugate addition: Cu(BF4)2·xH2O has been found to be a new and highly efficient catalyst for Michael addition of thiols [3] to α,β-unsaturated carbonyl compounds under solvent-free conditions.

(D) Electrophilic ring opening: A ring opening of siloxycyclopropane, [7] via β-copper substituted ketone intermediate, is efficiently catalyzed by Cu(BF4)2·xH2O leading to the formation of a 1,6-diketone. The reaction takes place in 0.5-1 hour at 15 °C in Et2O.

(E) Epoxide ring opening by alcohols: A general, simple and efficient protocol [8] has been developed for ring opening of different epoxides by reaction with various alcohols under the catalytic influence of Cu(BF4)2·xH2O. The reactions were carried out at room temperature and offered the use of cheap and commercially available copper tetrafluoroborate.

(F) Epoxide ring opening by amines: Another mild, efficient and selective ring opening of epoxides [9] has been effected by amines leading to the synthesis of β-amino alcohols under the catalytic ­effect of Cu(BF4)2·xH2O. The mild reaction conditions, short ­reaction times, solvent-free conditions, and excellent regio-, dia­stereo-, and chemoselectivity are the important features of this method.

(G) Cyclization: Exposure of unsaturated malonates bearing pendant alcohols to Cu(BF4)2·xH2O [10] and Mn(OAc)3 gives rise to the formation of carbocycles linked to oxygen heterocycles. The use of copper(II) salts bearing poorly coordinating anions has a profound influence on the product distribution.

(H) Acetal formation: Dimethyl/diethyl acetal formation [11] in high yields from aldehydes and ketones by reaction with trimethyl/triethyl orthoformate at room temperature and in short reaction time has been successfully carried out in the presence of a catalytic amount of Cu(BF4)2·xH2O which can be recycled.

(I) 1,3-Dithiolane/dithiane formation: Recently, Cu(BF4)2·xH2O has emerged as an extremely efficient catalyst for 1,3-dithiolane/dithiane formation from aromatic, heteroaromatic and aliphatic aldehydes and cyclic saturated ketones under solvent-free conditions at room temperature. [12]

(J) Carbamate formation: N-tert-Butoxycarbonylation [13] of amines by reaction with di-tert-butyldicarbonate under solvent-free conditions and at room temperature was successfully carried out in the presence of a catalytic amount of Cu(BF4)2·xH2O in high yield.

    References

  • 1a Higgs TC. Spartalian K. O’Connor CJ. Matzanke BF. Carrano CJ. Inorg. Chem.  1998,  37:  2263 
  • 2 Ahmad I. Int. J. Chem. Kinet.  1984,  17:  763 
  • 3 Garg SK. Kumar R. Chakraborti AK. Tetrahedron Lett.  2005,  46:  1721 
  • 4 Ranu BC. Dey SS. Tetrahedron  2004,  60:  4183 
  • 5 Chakraborti AK. Shivani RG. Synthesis  2004,  111 
  • 6 Chakraborti AK. Thilagavathi R. Kumar R. Synthesis  2004,  831 
  • 7 Ryu I. Ando M. Ogawa A. Murai S. Sonoda N. J. Am. Chem. Soc.  1983,  105:  7192 
  • 8 Barluenga J. Vazquez-Villa H. Ballesteros A. Gonzalez JM. Org. Lett.   2002.  4:  p.2817 
  • 9 Kamal A. Ramu R. Azhar MA. Khanna GBR. Tetrahedron Lett.  2005,  46:  2675 
  • 10 Hulcoop DG. Sheldrake HM. Burton JW. Org. Biomol. Chem.  2004,  965 
  • 11 Kumar R. Chakraborti AK. Tetrahedron Lett.  2005,  46:  8319 
  • 12 Besra RC. Rudrawar S. Chakraborti AK. Tetrahedron Lett.  2005,  46:  6213 
  • 13 Chankeshwara SV. Chakraborti AK. Tetrahedron Lett.  2006,  47:  1087 

    References

  • 1a Higgs TC. Spartalian K. O’Connor CJ. Matzanke BF. Carrano CJ. Inorg. Chem.  1998,  37:  2263 
  • 2 Ahmad I. Int. J. Chem. Kinet.  1984,  17:  763 
  • 3 Garg SK. Kumar R. Chakraborti AK. Tetrahedron Lett.  2005,  46:  1721 
  • 4 Ranu BC. Dey SS. Tetrahedron  2004,  60:  4183 
  • 5 Chakraborti AK. Shivani RG. Synthesis  2004,  111 
  • 6 Chakraborti AK. Thilagavathi R. Kumar R. Synthesis  2004,  831 
  • 7 Ryu I. Ando M. Ogawa A. Murai S. Sonoda N. J. Am. Chem. Soc.  1983,  105:  7192 
  • 8 Barluenga J. Vazquez-Villa H. Ballesteros A. Gonzalez JM. Org. Lett.   2002.  4:  p.2817 
  • 9 Kamal A. Ramu R. Azhar MA. Khanna GBR. Tetrahedron Lett.  2005,  46:  2675 
  • 10 Hulcoop DG. Sheldrake HM. Burton JW. Org. Biomol. Chem.  2004,  965 
  • 11 Kumar R. Chakraborti AK. Tetrahedron Lett.  2005,  46:  8319 
  • 12 Besra RC. Rudrawar S. Chakraborti AK. Tetrahedron Lett.  2005,  46:  6213 
  • 13 Chankeshwara SV. Chakraborti AK. Tetrahedron Lett.  2006,  47:  1087