Synlett 2008(17): 2723-2724  
DOI: 10.1055/s-2008-1067133
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

DEAD/DIAD - More than Simple Mitsunobu Reagents

Arthur Eugen Kümmerle*
LASSBio, sala B-16, CCS, Universidade Federal do Rio de Janeiro, CEP 21944-970, Rio de Janeiro, Brazil
e-Mail: akummerle@hotmail.com;
Further Information

Publication History

Publication Date:
02 July 2008 (online)

Introduction

Diethyl azodicarboxylate (DEAD) and diisopropyl azodicarboxylate (DIAD) (Figure  [¹] ), are widely used reagents in organic synthesis.

Figure 1

These are important reagents in the Mitsunobu reaction, [¹] [²] which is a versatile and widely used method for the dehydrative coupling of an alcohol with clean stereogenic inversion and is perhaps the most favorable reaction to invert chiral centers of secondary alcohols. [¹] [²] This kind of reaction can also be applied in aminations, cyclodehydrations, deoxygenations, and in dehydrative alkyl­ations. [³]

Besides the direct association of DEAD/DIAD with the Mitsunobu reaction, [²] there are many other reactions in which these reagents can be applied. For example, DEAD/DIAD are efficient components in Diels-Alder reactions and in click chemistry, [4a] they function as dienophiles in some cycloadditions, [4b] and they can be used in the synthesis of functionalized β-amino alcohols from aldehydes and ketones. [4c] DEAD and DIAD are commercially available or can be prepared in the laboratory in a two-step synthesis from hydrazine, first by condensation with ethyl chloroformate followed by treatment of the resulting ethyl hydrazodicarboxylate with chlorine or fuming nitric acid (Scheme  [¹] ). [5]

Scheme 1

    References

  • 1a Mitsunobu O. Yamada M. Bull. Chem. Soc. Jpn.  1967,  40:  2380 
  • 1b Mitsunobu O. Eguchi M. Bull. Chem. Soc. Jpn.  1971,  41:  3427 
  • 1c Mitsunobu O. Wada M. Sano T. J. Am. Chem. Soc.  1972,  94:  679 
  • 1d Mitsunobu O. Synthesis  1981,  1 
  • 2 Nune SK. Synlett  2003,  1221 
  • 3 But TYS. Toy PH. Chem. Asian J.  2007,  2:  1340 
  • 4a Gassman PG. Mansfield KT. Org. Synth., Coll. Vol. 5  1973,  96 
  • 4b Ellis JM. King SB. Tetrahedron Lett.  2002,  43:  5833 
  • 4c Chowdari NS. Ramachary DB. Barbas CF. Org. Lett.  2003,  5:  1685 
  • 5a Rabjohn N. Org. Synth., Coll. Vol. 3  1955,  375 
  • 5b Kauer JC. Org. Synth., Coll. Vol. 4  1963,  411 
  • 6a Ludek OR. Meier C. Synlett  2006,  324 
  • 6b Ludek OR. Meier C. Synlett  2005,  3145 
  • 7 Bertolini F. Bussolo VD. Crotti P. Pineschi M. Synlett  2007,  3011 
  • 8 Kim HS. Jeong G. Hyoung CL. Kim JH. Park YT. Okamoto Y. Kajiwara S. Kurasawa Y. J. Heterocycl. Chem.  2000,  37:  1277 
  • 9 Shao L.-X. Shi M. Eur. J. Org. Chem.  2004,  426 
  • 10 Kroutil J. Trnka T. Čern M. Synthesis  2004,  446 
  • 11 Kuethe JT. Davies IW. Tetrahedron Lett.  2004,  45:  4009 
  • 12 Dolzhenko AV. Chui W.-K. J. Heterocycl. Chem.  2006,  43:  95 
  • 13 Morais GR. Falconer RA. Tetrahedron Lett.  2007,  48:  7637 
  • 14 Guo Z. Huang H. Fu Q. Hu W. Synlett  2006,  2486