Aza-Wittig reaction
The Aza-Wittig reaction or is a chemical reaction of a carbonyl group with an aza-ylide, also known as an iminophosphorane. Aza-Wittig reactions are most commonly used to convert aldehydes and ketones to imines, which may be further reduced to yield secondary amines.[1] Aza-ylides can be obtained via the reaction of a trialkylphosphine and an organic azide with the loss of dinitrogen, with triphenylphosphine being the most commonly used. For substrates with both an azide and a carbonyl group, intramolecular coupling can be achieved.[2]
Reaction mechanism[edit]
The mechanism of the aza-Wittig reaction is analogous to that of the Wittig reaction, with the Wittig reagent replaced by an iminophosphorane.[1]
The formation of the iminophosphorane from the azide begins with the attack of triphenylphosphine on the terminal nitrogen atom. The intermediate loses nitrogen via a four-membered ring transition state.[1]
Scope and limitations[edit]
Besides preparing imines from aldehydes and ketones, the aza-Wittig-reaction can also convert carbon dioxide to isocyanates, carbon disulfide to organic thiocyanates, and isocyanates to carbodiimides.[1][3]
There exists solid-supported modifications of the reaction.[4][1][5]
Similar to the Wittig reaction, the reaction suffers from issues with triphenylphosphine oxide by-product removal. Such an issue is mitigated via catalytic aza-Wittig-reactions, some of which entail elements other than phosphorus, like arsenic and tellurium[5][6].
History[edit]
The reagent for the aza-Wittig reaction, iminophosphorane, was discovered in 1919 by Hermann Staudinger. The reaction itself was discovered thirty years later.[3]
Examples[edit]
An example of the aza-Wittig-reaction being utilized in organic synthesis is the synthesis of (–)-benzomalvin A. Two intramolecular aza-Wittig-reactions were used to construct the seven-membered ring and the six-membered ring in the molecule's skeleton.[1]
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See also[edit]
References[edit]
- ^ a b c d e f Kurti 1 Czako 2, Laszlo 1 Barbara 2 (15 September 2005). Strategic Applications of Named Reactions in Organic Synthesis. Elsevier. pp. 24–25. ISBN 0-12-429785-4.
{{cite book}}: CS1 maint: numeric names: authors list (link) - ^ Wamhoff, Heinrich; Richardt, Gabriele; Stölben, Stephan (1995-01-01), Katritzky, Alan R. (ed.), Iminophosphoranes: Versatile Tools in Heterocyclic Synthesis, Advances in Heterocyclic Chemistry, vol. 64, Academic Press, pp. 159–249, doi:10.1016/s0065-2725(08)60172-5, ISBN 978-0-12-020764-0, retrieved 2024-05-24
- ^ a b "Aza-Wittig Reaction". Retrieved 2024-05-24.
- ^ Hemming, Karl; Bevan, Matthew J.; Loukou, Christina; Patel, Snahal D.; Renaudeau, Denis (2001-02-20). "ChemInform Abstract: A One-Pot Aza-Wittig Based Solution and Polymer-Supported Route to Amines". ChemInform. 32 (8). doi:10.1002/chin.200108116. ISSN 0931-7597.
- ^ a b Lao, Zhiqi; Toy, Patrick H (2016-11-30). "Catalytic Wittig and aza-Wittig reactions". Beilstein Journal of Organic Chemistry. 12: 2577–2587. doi:10.3762/bjoc.12.253. ISSN 1860-5397. PMC 5238588. PMID 28144327.
- ^ Li, Huaifeng; Lupp, Daniel; Das, Pradip K.; Yang, Li; Gonçalves, Théo P.; Huang, Mei-Hui; El Hajoui, Marwa; Liang, Lan-Chang; Huang, Kuo-Wei (2021-04-02). "Redox-Neutral Imination of Alcohol with Azide: A Sustainable Alternative to the Staudinger/Aza-Wittig Reaction". ACS Catalysis. 11 (7): 4071–4076. doi:10.1021/acscatal.1c00379. hdl:10754/668169. ISSN 2155-5435.
External links[edit]
- Wittig reaction in Organic Syntheses, Coll. Vol. 10, p. 703 (2004); Vol. 75, p. 153 (1998). (Article)
- Wittig reaction in Organic Syntheses, Coll. Vol. 5, p. 361 (1973); Vol. 45, p. 33 (1965). (Article)