The Staudinger reaction - a method for the synthesis of phosphazenes (iminophosphoranes) by the interaction of azides and phosphines (or phosphites ), was discovered in 1919 by German Staudinger [1] [2] :
- R 3 P + R'N 3 R 3 P = NR '+ N 2
Phosphazenes formed in the reaction are then introduced into further transformations. So, the hydrolysis of phosphazenes, leading to the formation of an amine and phosphine oxide, is used as a method for the gentle reduction of azides to amines (Staudinger reduction):
The interaction of phosphazenes with carbonyl compounds is used as a method for the synthesis of imines (Staudinger imination):
- ,
when isocyanates are used as the carbonyl component, such imination leads to the formation of carbodiimides :
- R 3 P = NR 1 + R 2 N = C = O R 2 N = C = NR 1 + R 3 PO
Reaction Mechanism
The reaction is based on the nucleophilic addition of phosphine to the terminal nitrogen atom of the azide group to form phosphazide. After the formation of a cyclic intermediate and cleavage of molecular nitrogen, iminophosphorane is formed, which can also be represented in the aza-ylide form with charge separation.
Modifications
In 2000, a group of K. Bertozzi proposed a modification of the Staudinger reaction [3] , in which an electrophilic trap was used - a carboxylic acid methyl ester that captures the aza-ylide intermediate with the formation of amide and phosphine oxide. In contrast to the usual Staudinger reaction, in this case both products are covalently linked, therefore, such a modification was called “ Staudinger ligation ” and was widely used in chemical biology and bioconjugation [4] .
Notes
- ↑ Staudinger H., Meyer J. Über neue organische Phosphorverbindungen III. Phosphinmethylenderivate und Phosphinimine. (German) // Helv. Chem. Acta. - 1919. - Bd. 2 , H. 1 . - S. 635–646 . - DOI : 10.1002 / hlca.19190020164 .
- ↑ Gololobov Yu. G., Zhmurova IN, Kasukhin LF Sixty years of staudinger reaction (English) // Tetrahedron. - 1981. - Vol. 37 , iss. 3 . - P. 437-472 . - DOI : 10.1016 / S0040-4020 (01) 92417-2 .
- ↑ Saxon E., Bertozzi CR Cell Surface Engineering by a Modified Staudinger Reaction (Eng.) // Science. - 2000. - Vol. 287 , iss. 5460 . - P. 2007-2010 . - DOI : 10.1126 / science.287.5460.2007 .
- ↑ Schilling CI, Jung N., Biskup M., Schepers U., Stefan Brase S. Bioconjugation via azide – Staudinger ligation: an overview (English) // Chem. Soc. Rev. - 2011. - Vol. 40 . - P. 4840–4871 . - DOI : 10.1039 / c0cs00123f .