Ruthenium catalyzed azide—alkyne

C. Ruthenium catalyzed azide-alkyne cycloaddition (RuAAC)... 

Johansson, J. R. P. Lincoln B. Norden and N. Kann (2011). "Sequential One-Pot Ruthenium-Catalyzed Azide-Alkyne Cycloaddition from Primary Alkyl Halides and Sodium Azide." Jourrml cf Organic Chemistry, Vol.76, No.7, (Apr 1, 2011), pp. 2355-2359, ISSN152(T6904... 

The Ruthenium-Catalyzed Azide-Alkyne Cycloaddition (RuAAC) complements the well-established CuAAC reaction, as the formation of 1,5-substituted triazoles (instead of 1,4-substituted 1,2,3-triazoles) can be achieved with high regioselectivity. In contrast to the CuAAC reaction, triazoles that are synthesized via RuAAC reaction can be formed from terminal as well as internal alkynes. This offers the possibility of the formation of fully-substituted triazoles. 

Ruthenium-Catalyzed Azide-Alkyne Cycloaddition (RuAAC) Click Reactions... 

The regioselective formation of 1,4- and 1,5-disubstituted 1,2,3-triazoles can be accomplished by CuAAC reactions and ruthenium-catalyzed azide-alkyne [3+2] cycloaddition (RuAAC) reactions, respectively [69, 70]. Fokin and coworkers demonstrated that ruthenium complexes such as Cp RuCl(PPh3)2... 

Triazole derivatives could be synthesized from different starting substrates. Various triazoles 155 were synthesized from nonactivated terminal alkynes 152, allyl methyl carbonate 153 and trimethylsilyl azide 154 in a [3 + 2] cycloaddition with the use of the Pd(0)-Cu(I) bimetallic catalyst <03JA7786>. The allyl group of 155 was efficiently deprotected by ruthenium-catalyzed isomerization followed by ozonolysis to give 4-substituted triazoles 156. a-Aminoacetophenones 157 were reacted with hydrazines in acetic acid to give an efficient... 

Other metal-mediated reactions of azide reagents to terminal alkynes have also been reported. Indium(ll) triflate catalyzed tandem azidation/l,3-dipolar cycloaddition of various (o,(o-dialkoxyalkynes 134 with trimethylsilyl azide yielded fused 1,2,3-triazoles 135 <05TL8639>. A new ruthenium-catalyzed process for the regioselective synthesis of 1,5-disubstituted-1,2,3-triazoles has been developed <05JA15998>. 

The ruthenium-catalyzed cycloaddition of azides to alkynes to form 1,5-disubstituted triazoles is complimentary to the copper catalyzed route. The Cu(I)-catalyzed reaction is limited to terminal alkynes, and the Ru(II)-catalyzed reaction is active with internal alkynes. 

Bottom-line comments. Copper-catalyzed click chemistry is experimentally too easy and works too well in most cases not to be strongly considered as a means of stitching together just about any terminal alkyne and azide. The regiospecificity for 1,4-disubstituted heteroaromatic triazoles is complemented by the corresponding ruthenium-catalyzed cycloadditions to afford 1,5-adducts. And with options for heterogeneous processes, microwave-assisted thermal rate enhancements, and solvent-free conditions, click chemistry has become, and rightfully so, a tremendously powerful tool in synthesis. 

Functionahzed indoles were prepared in high yield through a ruthenium-catalyzed reaction between aryl azides and terminal alkynes (Scheme 3.63) [69]. The results of this reaction were in stark contrast to the normal reactivity of organoazides with alkynes that generated triazoles. The change in the direction of the reaction was proposed to be due to the presence of powerful electron-withdrawing groups on the aryl azide. 

While this copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition selectively produces 1,4-disubstituted 1,2,3-triazoles, Forkin and Jia et al. have disclosed a complementary ruthenium-catalyzed process for preparing 1,5- and 1,4,5-substituted 1,2,3-triazoles from terminal and internal alkynes, respectively (Scheme 16.6) [10]. 

Under ruthenium-catalyzed ortho-C-H activation and intramolecular C-N bond formation, the condensation of iminophosphoranes (in situ generated from acyl azides and triphenylphosphine) with internal alkynes afforded a variety of isoquinolinone derivatives (Eq. (7.43)) [53]. The regioselective insertion of unsymmetrical alkynes led to an (aryl)C-N bond formation. Thiophene and indole-based acyl azides were also compatible for this transformation. A domino reaction sequence via coordination of ruthenium with Af-atom of iminophosphoranes, ort/zo-cyclometalation, alkyne insertion, protonation, and reductive elimination was proposed for the catalytic cycle. Based on and NMR experiments, the involvement of benzamide during the reaction process was ruled out. 

To date, there is only one investigation concerning metals beyond ruthenium and copper that may catalyze triazole formation through an AAC reaction. Matyjaszewski et al. reported on the addition of palladium, platinum and nickel to azides and alkynes in comparison to the same model system without any catalyst. The rate-accelerating effect of the metals could only be detected in the case of the addition of PtCl2 and PdCb in... 

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