| Azide-alkyne Huisgen cycloaddition | |
|---|---|
| Named after | Rolf Huisgen |
| Reaction type | Ring forming reaction |
| Identifiers | |
| Organic Chemistry Portal | huisgen-1,3-dipolar-cycloaddition |
| RSC ontology ID | RXNO:0000269 |
The azide-alkyne Huisgen cycloaddition is a 1,3-dipolar cycloaddition between an azide and a terminal or internal alkyne to give a 1,2,3-triazole. Rolf Huisgen[1] was the first to understand the scope of this organic reaction. American chemist Karl Barry Sharpless has referred to copper-catalyzed version of this cycloaddition as "the cream of the crop" of click chemistry[2] and "the premier example of a click reaction".[3]
In the reaction above[4] azide 2 reacts neatly with alkyne 1 to afford the product triazole as a mixture of 1,4-adduct (3a) and 1,5-adduct (3b) at 98 °C in 18 hours.
The standard 1,3-cycloaddition between an azide 1,3-dipole and an alkene as dipolarophile has largely been ignored due to lack of reactivity as a result of electron-poor olefins and elimination side reactions. Some success has been found with non-metal-catalyzed cycloadditions, such as the reactions using dipolarophiles that are electron-poor olefins[5] or alkynes.
Although azides are not the most reactive 1,3-dipole available for reaction, they are preferred for their relative lack of side reactions and stability in typical synthetic conditions.
- ^ Huisgen, R. (1961). "Centenary Lecture - 1,3-Dipolar Cycloadditions". Proceedings of the Chemical Society of London: 357. doi:10.1039/PS9610000357.
- ^ H. C. Kolb; M. G. Finn; K. B. Sharpless (2001). "Click Chemistry: Diverse Chemical Function from a Few Good Reactions". Angewandte Chemie International Edition. 40 (11): 2004–2021. doi:10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5. PMID 11433435.
- ^ Kolb, H.C.; Sharpless, B.K. (2003). "The growing impact of click chemistry on drug discovery". Drug Discov Today. 8 (24): 1128–1137. doi:10.1016/S1359-6446(03)02933-7. PMID 14678739.
- ^ Development and Applications of Click Chemistry Gregory C. Patton November 8, 2004 http://www.scs.uiuc.edu Online[permanent dead link]
- ^ David Amantini; Francesco Fringuelli; Oriana Piermatti; Ferdinando Pizzo; Ennio Zunino & Luigi Vaccaro (2005). "Synthesis of 4-Aryl-1H-1,2,3-triazoles through TBAF-Catalyzed [3 + 2] Cycloaddition of 2-Aryl-1-nitroethenes with TMSN3 under Solvent-Free Conditions". The Journal of Organic Chemistry. 70 (16): 6526–6529. doi:10.1021/jo0507845. PMID 16050724.