Making Amines from Azides
The Staudinger reaction, named after its discoverer Hermann Staudinger (1919), is a useful reaction that involves the reduction of an azide compound to an amine. If the azide is present on a stereogenic centre, the reaction occurs with retension of stereochemical configuration. The reliability and chemoselectivity of the reaction allows the azide group to effectively serve as an amine protecting group, that can be later unmasked when required.
Mechanism of the Staudinger Reaction
The reaction typically employs a phosphine compound, such as triphenylphosphine or trimethylphosphine, as a reducing agent. The reaction proceeds through the formation of an intermediate iminophosphorane, which then undergoes hydrolysis to yield the desired amine product.
Alternative Reactions of the Iminophosphorane Intermediate
Alternatively, the intermediate iminophosphorane can be intercepted by a carboxylic acid to form an amide (Staudinger-Vilarrasa reaction), or by a carbonyl compound to form an imine (aza-Wittig reaction).
Reaction Scope
The Staudinger reaction has found widespread use in organic synthesis due to its versatility and mild reaction conditions. The reaction is more chemoselective than the alternative conditions of LiAlH4 or H2-Pd/C, where substrates containing susceptible functional groups can be problematic.
The scope of the reaction allows azides to serve as a protecting groups for amines. Overall, the reaction is a valuable tool for the construction of complex organic molecules in both academic and industrial settings.
References
Staudinger, H.; Hauser, E. J. Helv. Chim. Acta. 1919, 2, 635–646.
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