Acid–Base Jointly Promoted Copper(I)-Catalyzed Azide–Alkyne Cycloaddition

Abstract

In this novel acid-base jointly promoted CuAAC, the combination of CuI/DIPEA/HOAc was developed as a highly efficient catalytic system. The functions of DIPEA and HOAc have been assigned, and HOAc was recognized to accelerate the conversions of the C-Cu bond-containing intermediates and buffer the basicity of DIPEA. As a result, all drawbacks occurring in the popular catalytic system CuI/NR(3) were overcome easily.

Copper-catalyzed steroid reactions

“…As was expected, the reaction of these more sterically hindered azidosteroids proceeded more slowly and proved sensitive to the composition of a catalytic system. The use of CuSO4·5H2O and NaAsc in aqueous THF (method A) allowed them to obtain product 149c (R = Bu) via reaction of azidosteroid 145 with propargyl alcohol, but in the case of phenylacetylene conversion was only 48% after 14 h. Since copper carboxylates are known to accelerate the CuAAC reaction, 58 they applied presumably more active Cu(OAc)2·H2O as a catalyst. Triethylamine was added to increase the solubility of the catalyst in CH2Cl2 and facilitate the formation of copper acetylide.…”

1-[5-Methyl-1-(4-methylphenyl)-1H-1,2,3-triazol-4-yl]ethanone

“…The most common one involves cycloaddition of azides and alkynes in the presence of a catalyst (Rostovtsev et al, 2002;Himo et al, 2005;Boren et al, 2008;Quan et al, 2014;Banday & Hruby, 2014;Kolarovič et al, 2011;Shao et al, 2011;Liu & Reiser, 2011). A number of heterocycles containing the 1,2,3-triazole moiety show various medicinal applications (Bock et al, 2006(Bock et al, , 2007Agalave et al, 2011).…”

Exploiting the benefits of continuous-flow processing for the development of novel sustainable catalytic procedures

“…82,184,185 Additionally, it was recently shown that catalytic amounts of certain acids can further accelerate the formation of the triazole product through promotion of the conversion of C-Cu bond-containing intermediates by protonation. [186][187][188] Furthermore, utilization of acidic additives is beneficial as it prevents the formation of unwanted byproducts, such as diacetylenes, bis-triazoles, etc.…”

“…[186][187][188] Furthermore, utilization of acidic additives is beneficial as it prevents the formation of unwanted byproducts, such as diacetylenes, bis-triazoles, etc. 185 In contrast, byproduct formation is catalyzed by base. The joint application of a basic and an acidic additive is therefore highly advantageous: this buffer system improves reactivity in CuAAC, even at RT, but without the formation of byproducts.…”

“…Catalytic cycle of the base-acid jointly promoted CuAAC reaction. 185 As basic and acidic additives, DIEA and AcOH were selected, relying on literature data. 185 To investigate the effects of additives, pressure and flow rate was set to 100 bar and 0.5 mL min -1 , respectively, and heating was avoided (i.e.…”