Insight into the Mechanism of the CuAAC Reaction by Capturing the Crucial Au₄Cu₄–π-Alkyne Intermediate

Abstract

The classic Fokin mechanism of the CuAAC reaction of terminal alkynes using a variety of Cu(I) catalysts is well-known to include alkyne deprotonation involving a bimetallic σ,π-alkynyl intermediate. In this study, we have designed a CNT-supported atomically precise nanocluster Au₄Cu₄ (noted Au₄Cu₄/CNT) that heterogeneously catalyzes the CuAAC reaction of terminal alkynes <i>without alkyne deprotonation to a</i> σ,π<i>-alkynyl intermediate</i>. Therefore, three nanocluster-π-alkyne intermediates [Au₄Cu₄(π-CH≡C-p-C₆H₄R)], R = H, Cl, and CH₃, have been captured and characterized by MALDI-MS. This Au₄Cu₄/CNT system efficiently catalyzed the CuAAC reaction of terminal alkynes, and internal alkynes also undergo this reaction. DFT results further confirmed that HC≡CPh was activated by π-complexation with Au₄Cu₄, unlike the classic dehydrogenation mechanism involving the bimetallic σ,π-alkynyl intermediate. On the other hand, a Cu₁₁/CNT catalyst was shown to catalyze the reaction of terminal alkynes following the classic deprotonation mechanism, and both Au₁₁/CNT and Cu₁₁/CNT catalysts were inactive for the AAC reaction of internal alkynes under the same conditions, which shows the specificity of Au₄Cu₄ involving synergy between Cu and Au in this precise nanocluster. This will offer important guidance for subsequent catalyst design.