Synthesis of 1,4,5-trisubstituted-1,2,3-triazoles by copper-catalyzed cycloaddition-coupling of azides and terminal alkynes

[(NHC)2Cu]X Complexes as Efficient Catalysts for Azide–Alkyne Click Chemistry at Low Catalyst Loadings

“…Thanks to its mild conditions and high efficiency, this reaction has found a myriad of applications in biology and material science. [4] Less attention has been focused on the development of novel copper(I)-based well-defined systems [5,6,7] and to the amount of copper used. [8] This last point is extremely important for future industrial applications and it might be one of the last challenges to overcome for this transformation.…”

Copper-Catalysed Multicomponent Click Synthesis of 5-Alkynyl 1,2,3-Triazoles under Ambient Conditions

“…8b A more direct strategy to access this type of compounds was reported by Porco's group, in which, organic azides and terminal alkynes reacted in a catalytic system comprised of Cu(MeCN) 4 PF 6 , N,N,N′-trimethylethylenediamine as ligand, Hünig's base, molecular oxygen, and 4-methylmorpholine N-oxide as co-oxidant in dichloromethane. 9 As noted by the authors, the Glaser coupling and cycloaddition towards the nonalkynylated 1,4-disubstituted triazoles were competing reactions which accounted for the low yields attained in many cases. Soon after, Chen et al presented the 1,3-dipolar cycloaddition-coupling reaction of terminal alkynes, phenylboronic acids, and sodium azide catalysed by CuI (10 mol%) and CuSO 4 ·5H 2 O (20 mol%) in 1,4-dioxane-water.…”

Well-defined copper(i) complexes for Click azide–alkyne cycloaddition reactions: one Click beyond

“…Hydroxylamines were reported inactive in this reaction in 2006, 63 however, histidine derivatives such as 34 accelerate CuAAC in a similar rate than wellestablished DIPEA or NEt 3 (Scheme 7). 64 Neither imidazole, nor N-methylimidazole displayed any activating properties in these reactions, proving the importance of the aminoacid moiety.…”