Synlett 2007(19): 3073-3074  
DOI: 10.1055/s-2007-990855
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

1,1′-Carbonyldiimidazole (CDI)

Rohit K. Sharma*
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160 062, India
e-Mail: rohitksg@gmail.com;

Further Information

Publication History

Publication Date:
08 November 2007 (online)

Biographical Sketches

Rohit K. Sharma was born in Chandigarh, India in 1980. He obtained his B.Sc. (Honors) in chemistry in 2002 and M.Sc. (Honors) in chemistry in 2004 from Panjab University. After that, he joined the research group of Dr. Rahul Jain at the National Institute of Pharmaceutical Education & Research (NIPER) in 2004 and is currently working towards his Ph.D. His main interests lie in the development of synthetic methodologies, biological evaluation and mechanistic studies of antimicrobial peptides, peptoids, and unnatural amino acids.

Introduction

1,1′-Carbonyldiimidazole (CDI; Figure [1] , 1), a white crystalline solid with its melting point between 117 °C and 122 °C, has been widely exploited in organic chemistry for carrying out reactions involving transfer of a carbonyl group, [1-3] imidazole moiety, [4] and coupling between different functional groups under various conditions. [5-9]

Figure 1

Preparation

1,1′-Carbonyldiimidazole (CDI, 1) can be readily prepared by the reaction of four equivalents of imidazole 2 with phosgene (3) under anhydrous conditions (Scheme [1] ). The imidazole serves as both nucleophile and base in this conversion. Removal of the side product, imidazolium chloride, and solvent results in the crystalline product in ca. 90% yield.

Scheme 1

Abstracts

(A) 1,1′-Carbonyldiimidazole (CDI) has been efficiently employed in asymmetric synthesis of tetramic acid derivatives 6. In this reaction, CDI transfers a carbonyl group to α-diimines 4 in the presence of BF3·OEt2 to afford N-alkyl-4-alkylamino-5-methylene­-pyrrol-2-ones 5 in moderate yields. The total asymmetric synthesis of tetramic acid derivatives 6 involves four steps in which the key step is a carbonyl transfer from CDI to the α-ketodiimine. [1]
(B) Amidation reactions between different sterically hindered acid aldehydes and amines have been reported to be efficiently catalyzed by CDI. First, compound 7 is activated with CDI, then, addition of N,N-diethylethylenediamine (8) to the reaction mixture leads to the imine amide product 9. Remarkable rate enhancement was observed in the reaction due to catalysis by the released carbon dioxide. [5]
(C) The aqueous CDI-based synthetic method offers an easy and inexpensive way to prepare peptides and peptide thioesters. The synthesis involves reaction of amino acid 10 with CDI to give the amino acid carboxyanhydride intermediate 11 that condenses to both dipeptide 12 and dipeptide thioester 13 in the presence of added amino acid or thiol. Repeated aminoacylation steps on these dipeptide derivatives produce peptide and peptide thioester chains. [6-8]
(D) Cyanohydrins 14 on stepwise reaction with CDI and O-substituted hydroxylamines 15 give O-substituted 3-hydroxy-4-­iminooxazolidin-2-ones 16 in a high-yielding one-pot synthesis. [2] Then, sodium methoxide mediated conversion of 16 produces the corresponding O-substituted α-hydroxyamidoximes 17.
(E) Recently, the first amidation reaction of unprotected α-amino acids in water under neutral conditions with various aliphatic, aromatic, and heteroaromatic primary amines in the presence of CDI at ambient temperature was reported. [4] Zwitterionic amino acids 18 first react with CDI leading to the formation of the intermediate mixed anhydride, followed by nucleophilic attack of amines 19 facilitating the formation of amides 20 in moderate yields.
(F) In one of the steps in an enantiospecific pathway described by Davidson and Corey to synthesize an antitubercular tetracyclic oxazole marine natural product called pseudopteroxazole 21, cyclization of the phenol derivative 22 with CDI gave the cyclic carbamate 23 in 94% yield. [3]
(G) Cyclization of various γ-amino alcohols 24 to substituted azetidines 25 and other N-heterocycles has been conveniently carried out in quantitative yields by using 1,1′-carbonyldiimidazole. [9] CDI efficiently activates the hydroxyl groups avoiding the use of toxic reagents and tolerating a wide variety of functional groups.

    References

  • 1 Fustero S. Torre MG. Sanz-Cervera JF. Arellano CR. Piera J. Simn A. Org. Lett.  2002,  4:  3651 
  • 2 Kurz T. Widyan K. Org. Lett.  2004,  6:  4403 
  • 3 Davidson JP. Corey EJ. J. Am. Chem. Soc.  2003,  125:  13489 
  • 4 Sharma RK. Jain R. Synlett  2007,  603 
  • 5 Vaidyanathan R. Kalthod VG. Ngo DP. Manley JM. Lapekas SP. J. Org. Chem.  2004,  69:  2565 
  • 6 Weber AL. Orig. Life Evol. Biosph.  2005,  35:  421 
  • 7 Dawson PE. Muir TW. Clark-Lewis I. Kent SBH. Science  1994,  266:  776 
  • 8 Hackeng TM. Griffin JH. Dawson PE. Proc. Natl. Acad. Sci. U. S. A.  1999,  96:  10068 
  • 9 Figueiredo RM. Fröhlich R. Christmann M. J. Org. Chem.  2006,  71:  4147 

    References

  • 1 Fustero S. Torre MG. Sanz-Cervera JF. Arellano CR. Piera J. Simn A. Org. Lett.  2002,  4:  3651 
  • 2 Kurz T. Widyan K. Org. Lett.  2004,  6:  4403 
  • 3 Davidson JP. Corey EJ. J. Am. Chem. Soc.  2003,  125:  13489 
  • 4 Sharma RK. Jain R. Synlett  2007,  603 
  • 5 Vaidyanathan R. Kalthod VG. Ngo DP. Manley JM. Lapekas SP. J. Org. Chem.  2004,  69:  2565 
  • 6 Weber AL. Orig. Life Evol. Biosph.  2005,  35:  421 
  • 7 Dawson PE. Muir TW. Clark-Lewis I. Kent SBH. Science  1994,  266:  776 
  • 8 Hackeng TM. Griffin JH. Dawson PE. Proc. Natl. Acad. Sci. U. S. A.  1999,  96:  10068 
  • 9 Figueiredo RM. Fröhlich R. Christmann M. J. Org. Chem.  2006,  71:  4147 

Figure 1

Scheme 1