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Synthesis of 5-Iodo-1,2,3-triazoles from Organic Azides and Terminal Alkynes: Ligand Acceleration Effect, Substrate Scope, and Mechanistic Insights
Received: 26 March 2013
Accepted after revision: 06 June 2013
19 July 2013 (online)
An improved method has been developed for the preparation of 5-iodo-1,2,3-triazoles directly from organic azides and terminal alkynes by a reaction mediated by copper(I) and iodinating agents generated in situ. The major methodological advance of the current procedure is that it provides a high conversion and good iodo/proto selectivity with a broad range of substrates without using an excess of the alkyne, which was required in the previous method. The use of an accelerating ligand is essential to the success of reactions involving unreactive azides or alkynes. New mechanistic insights are provided, including the confirmation that a 1-iodoalkyne is formed as a key intermediate under the established conditions for the reaction.
Key wordsazides - alkynes - copper - catalysis - heterocycles - cyclizations - triazoles - halogenation - iodine
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- Supporting Information
- 1a Deng J, Wu Y.-M, Chen Q.-Y. Synthesis 2005; 2730
- 1b Spiteri C, Moses JE. Angew. Chem. Int. Ed. 2010; 49: 31
- 1c Carcenac Y, David-Quillot F, Abarbri M, Duchêne A, Thibonnet J. Synthesis 2013; 45: 633
- 2 Hein JE, Tripp JC, Krasnova LB, Sharpless KB, Fokin VV. Angew. Chem. Int. Ed. 2009; 48: 8018
- 3 Wu Y.-M, Deng J, Li Y, Chen Q.-Y. Synthesis 2005; 1314
- 4 Li L, Zhang G, Zhu A, Zhang L. J. Org. Chem. 2008; 73: 3630
- 5 Smith NW, Polenz BP, Johnson SB, Dzyuba SV. Tetrahedron Lett. 2010; 51: 550
- 6 Brotherton WS, Clark RJ, Zhu L. J. Org. Chem. 2012; 77: 6443
- 7a Yan R, El-Emir E, Rajkumar V, Robson M, Jathoul AP, Pedley RB, Årstad E. Angew. Chem. Int. Ed. 2011; 50: 6793
- 7b Yan R, Sander K, Galante E, Rajkumar V, Badar A, Robson M, El-Emir E, Lythgoe MF, Pedley RB, Årstad E. J. Am. Chem. Soc. 2013; 135: 703
- 8 Kuang G.-C, Michaels HA, Simmons JT, Clark RJ, Zhu L. J. Org. Chem. 2010; 75: 6540
- 9 Kuang G.-C, Guha PM, Brotherton WS, Simmons JT, Stankee LA, Nguyen BT, Clark RJ, Zhu L. J. Am. Chem. Soc. 2011; 133: 13984
10 Chan TR, Hilgraf R, Sharpless KB, Fokin VV. Org. Lett. 2004; 6: 2853
- 11 To the best of our knowledge, carboxyl-containing substrates have not previously been shown to participate in the formation of 5-iodo-1,2,3-triazoles.
- 12 Rodionov VO, Fokin VV, Finn MG. Angew. Chem. Int. Ed. 2005; 44: 2210
- 13 In a few cases the scale was doubled, as indicated in the experimental section.
- 14 A 10 mol% excess of the alkyne was used for convenience in monitoring the azide as the limiting reagent.
- 15 The following experiment showed that the oxidant is O2, not perchlorate or its derivatives. When 28−30% aq NH3 was added to a suspension of CuCl in EtOAc, the aqueous phase immediately turned deep blue, thereby precluding the involvement of perchlorate in the oxidation of copper(I). When CuCl was added to a stirred mixture of EtOAc and aq NH3 purged with argon for 10 min, the solution turned from clear to a pale light blue. The minimal blue coloration may have been the result of minor oxidation of copper(I) by the residual O2 in the solution. Two to three minutes after argon purging was terminated, the solution turned to deep blue, suggesting rapid aerobic oxidation of most, if not all, the copper(I) ions to form tetraammine copper(II) ions.
- 16 Pelletier G, Lie S, Mousseau JJ, Charette AB. Org. Lett. 2012; 14: 5464
- 17a Lespieau R. Bull. Soc. Chim. Fr. 1908; 3: 638
- 17b Passiniemi M, Koskinen AM. P. Org. Biomol. Chem. 2011; 9: 1774
- 18a Dolbier WR. Guide to Fluorine NMR for Organic Chemists. Wiley; Hoboken: 2009
- 18b Yeste SL, Powell ME, Bull SD, James TD. J. Org. Chem. 2009; 74: 427
- 19a Donnelly PS, Zanatta SD, Zammit SC, White JM, Williams SJ. Chem. Commun. 2008; 2459
- 19b Michaels HA, Zhu L. Chem. Asian J. 2011; 6: 2825