Abstract
The experimental rate law for the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was found to vary in complex ways with concentration, the presence of chloride ion, and the presence of accelerating ligands. Several examples of discontinuous ("threshold behavior") kinetics were observed, along with a decidedly nonlinear correlation of electronic substituent parameter with the rate of CuAAC reaction with p-substituted arylazides. The previously observed tendency of the CuAAC reaction to provide ditriazoles from a conformationally constrained 1,3-diazide was found to be affected by a class of polybenzimidazole ligands introduced in the accompanying article. Various lines of evidence suggest that the standard tris(triazolylmethyl)amine ligand binds less strongly to Cu(I) than its benzimidazole analogues. On the basis of these observations, it is proposed that (a) a central nitrogen donor provides electron density at Cu(I) that assists the cycloaddition reaction, (b) the three-armed motif bearing relatively weakly coordinating heterocyclic ligands serves to bind the metal with sufficient strength while providing access to necessary coordination site(s), (c) at least two active catalysts or mechanisms are operative under the conditions studied, and (d) pendant acid or ester arms in the proper position can assist the reaction by speeding the protiolysis step that cleaves the Cu-C bond of a Cu·triazolyl intermediate.
| Original language | English |
|---|---|
| Pages (from-to) | 12705-12712 |
| Number of pages | 8 |
| Journal | Journal of the American Chemical Society |
| Volume | 129 |
| Issue number | 42 |
| DOIs | |
| Publication status | Published - 24 Oct 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Chemistry(all)
Cite this
Ligand-accelerated Cu-catalyzed azide-alkyne cycloaddition : A mechanistic report. / Rodionov, Valentin O.; Presolski, Stanislav I.; Díaz, David Díaz; Fokin, Valery V.; Finn, M. G.
In: Journal of the American Chemical Society, Vol. 129, No. 42, 24.10.2007, p. 12705-12712.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ligand-accelerated Cu-catalyzed azide-alkyne cycloaddition
T2 - A mechanistic report
AU - Rodionov, Valentin O.
AU - Presolski, Stanislav I.
AU - Díaz, David Díaz
AU - Fokin, Valery V.
AU - Finn, M. G.
PY - 2007/10/24
Y1 - 2007/10/24
N2 - The experimental rate law for the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was found to vary in complex ways with concentration, the presence of chloride ion, and the presence of accelerating ligands. Several examples of discontinuous ("threshold behavior") kinetics were observed, along with a decidedly nonlinear correlation of electronic substituent parameter with the rate of CuAAC reaction with p-substituted arylazides. The previously observed tendency of the CuAAC reaction to provide ditriazoles from a conformationally constrained 1,3-diazide was found to be affected by a class of polybenzimidazole ligands introduced in the accompanying article. Various lines of evidence suggest that the standard tris(triazolylmethyl)amine ligand binds less strongly to Cu(I) than its benzimidazole analogues. On the basis of these observations, it is proposed that (a) a central nitrogen donor provides electron density at Cu(I) that assists the cycloaddition reaction, (b) the three-armed motif bearing relatively weakly coordinating heterocyclic ligands serves to bind the metal with sufficient strength while providing access to necessary coordination site(s), (c) at least two active catalysts or mechanisms are operative under the conditions studied, and (d) pendant acid or ester arms in the proper position can assist the reaction by speeding the protiolysis step that cleaves the Cu-C bond of a Cu·triazolyl intermediate.
AB - The experimental rate law for the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was found to vary in complex ways with concentration, the presence of chloride ion, and the presence of accelerating ligands. Several examples of discontinuous ("threshold behavior") kinetics were observed, along with a decidedly nonlinear correlation of electronic substituent parameter with the rate of CuAAC reaction with p-substituted arylazides. The previously observed tendency of the CuAAC reaction to provide ditriazoles from a conformationally constrained 1,3-diazide was found to be affected by a class of polybenzimidazole ligands introduced in the accompanying article. Various lines of evidence suggest that the standard tris(triazolylmethyl)amine ligand binds less strongly to Cu(I) than its benzimidazole analogues. On the basis of these observations, it is proposed that (a) a central nitrogen donor provides electron density at Cu(I) that assists the cycloaddition reaction, (b) the three-armed motif bearing relatively weakly coordinating heterocyclic ligands serves to bind the metal with sufficient strength while providing access to necessary coordination site(s), (c) at least two active catalysts or mechanisms are operative under the conditions studied, and (d) pendant acid or ester arms in the proper position can assist the reaction by speeding the protiolysis step that cleaves the Cu-C bond of a Cu·triazolyl intermediate.
UR - http://www.scopus.com/inward/record.url?scp=35548939058&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35548939058&partnerID=8YFLogxK
U2 - 10.1021/ja072679d
DO - 10.1021/ja072679d
M3 - Article
C2 - 17914817
AN - SCOPUS:35548939058
VL - 129
SP - 12705
EP - 12712
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 42
ER -