Staudinger reaction

The Staudinger reaction or Staudinger reduction is a chemical reaction in which the combination of an azide with a phosphine or phosphite produces an iminophosphorane intermediate. Combined with the hydrolysis of the aza-ylide to produce a phosphine oxide and an amine, this reaction is a mild method of reducing an azide to an amine. Triphenylphosphine is commonly used as the reducing agent, yielding triphenylphosphine oxide as the side product in addition to the amine.

The reaction was invented by and named after Hermann Staudinger.

An example of a Staudinger reduction is the organic synthesis of this pinwheel compound :



Reaction mechanism
The reaction mechanism centers around the formation of an iminophosphorane through nucleophilic addition of the phosphine at the terminal nitrogen atom of the azide and expulsion of nitrogen:



This intermediate is then hydrolyzed in the second step to the amine and triphenylphosphine oxide.

Staudinger ligation
Developed by Saxon and Bertozzi in 2000, the Staudinger ligation is a modification of the classical Staudinger reaction in which an electrophilic trap (usually a methyl ester) is appropriately placed on the triaryl phosphine. In the Staudinger ligation, the aza-ylide intermediate rearranges, in aqueous media, to produce an amide linkage and the phosphine oxide, and is so named the Staudinger ligation because it ligates the two molecules together, whereas in the classical Staudinger reaction, the two products are not covalently linked after hydrolysis.

The general schematic for the Staudinger ligation is shown below.

Applications
The Staudinger ligation has seen many applications in the field of chemical biology.

In one application this reaction is used to create a bond between a nucleoside and a fluorescent marker :