Staudinger Reaction
Staudinger Reduction

Azides may be converted to amines by hydrogenation, but another possibility is the Staudinger Reaction, which is a very mild azide reduction. As there are a variety of methods for preparing azides readily, the Staudinger Reaction makes it possible to use ^-N₃ as an ^-NH₂ synthon.

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Mechanism of the Staudinger Reaction

Triphenylphosphine reacts with the azide to generate a phosphazide, which loses N₂ to form an iminophosphorane. Aqueous work up leads to the amine and the very stable phosphine oxide.

W. Q. Tian, Y. A. Wang, J. Org. Chem. 2004, 69, 4299. DOI
F. L. Lin, H. M. Hoyt, H. v. Halbeek, R. G. Bergman, C. R. Bertozzi, J. Am. Chem. Soc, 2005, 127, 2686. DOI

Recent Literature

Catalytic Staudinger Reduction at Room Temperature
D. C. Lenstra, J. J. Wolf, J. Mecinović, J. Org. Chem., 2019, 84, 6536-6545.

A One-Pot, Solid-Phase Synthesis of Secondary Amines from Reactive Alkyl Halides and an Alkyl Azide
S. Ayesa, B. Samuelsson, B. Classon, Synlett, 2008, 89-93.

ROMPgel-Supported Triphenylphosphine with Potential Application in Parallel Synthesis
E. Arstad, A. G. M. Barrett, B. T. Hopkins, J. Koebberling, Org. Lett., 2002, 1975-1977.

Catalytic Staudinger-Vilarrasa Reaction for the Direct Ligation of Carboxylic Acids and Azides
J. Burés, M. Martín, F. Urpí, J. Vilarrasa, J. Org. Chem., 2009, 74, 2203-2206.

High-Yielding Staudinger Ligation of a Phosphinothioester and Azide To Form a Peptide
B. L. Nilsson, L. L. Kiessling, R. T. Raines, Org. Lett., 2001, 3, 9-12.

Synthesis of Acyl Phosphoramidates Employing a Modified Staudinger Reaction
I. Currie, B. E. Sleebs, Org. Lett., 2021, 23, 464-468.

One-Pot Synthesis of Polysubstituted Imidazoles via Sequential Staudinger/aza-Wittig/Ag(I)-Catalyzed Cyclization/Isomerization
J. Xiong, X. Wei, Z.-M. Liu, M.-W. Ding, J. Org. Chem., 2017, 82, 13735-13739.

Synthesis of Polysubstituted Pyridines via a One-Pot Metal-Free Strategy
H. Wei, Y. Li, K. Xiao, B. Cheng, H. Wang, L. Hu, H. Zhai, Org. Lett., 2015, 17, 5974-5977.

A Tandem Approach to Isoquinolines from 2-Azido-3-arylacrylates and α-Diazocarbonyl Compounds
Y.-Y. Yang, W.-G. Shou, Z.-B. Chen, D. Hong, Y.-G. Wang, J. Org. Chem., 2008, 73, 3928-3930.

Three-Component, One-Pot Sequential Synthesis of 1,3-Disubstituted 5-Arylhydantoins
F. Olimpieri, A. Volonterio, M. Zanda, Synlett, 2008, 3016-3020.

Staudinger Condensation for the Preparation of Thiohydantoins
S. Gosling, C. El Amri, A. Tatibouët, Synthesis, 2014, 46, 1079-1084.

Enantioselective Synthesis of Quaternary Oxindoles: Desymmetrizing Staudinger-Aza-Wittig Reaction Enabled by a Bespoke HypPhos Oxide Catalyst
C. Xie, J. Kim, B. K. Mai, S. Cao, R. Ye, X.-Y. Wang, P. Liu, O. Kwon, J. Am. Chem. Soc., 2022, 144, 21318-21327.