Unveiling the mechanism: an alkyne-protected Au₆Cu₆ catalyst for accelerated CuAAC reaction of internal alkynes

The classical Fokin mechanism for CuAAC catalysis, which involves a deprotonation step, is inherently restricted to terminal alkynes. Recently, a bimetallic Au₄Cu₄ cluster enabled π-activation of phenylacetylene (HC≡CPh) via Au-Cu synergy, overcoming this limitation. In this study, we designed and synthesized three types of carbon nanotube-supported atomically precise nanoclusters-Au₆Cu₆PA₁₂(PA=Phenylacetylene), Au₆Cu₆PET₁₂ (PET=phenethylsulfate), and Au₆Cu₆MBT₁₂(MBT=3-methylbenzenethiol) - as heterogeneous catalysts for the CuAAC reaction of internal alkynes without requiring alkyne deprotonation. Among these, the alkyne-protected Au₆Cu₆(PA)₁₂ exhibited exceptional performance, with a turnover number (TON) of 1,133.9 that surpasses all reported catalytic systems for this reaction. DFT calculations further confirmed a non-dehydrogenation mechanism. By comparing five possible reaction pathways, we elucidated the origin of the superior activity of Au₆Cu₆(PA)₁₂ over other systems, including the previously reported Au₄Cu₄ cluster. This work provides important insights for the rational design of efficient catalysts for internal alkyne cycloaddition reactions.