Combined Metal-Metal and Metal-Ligand Cooperativity in Dicopper-Catalyzed
Azide-Alkyne Cycloaddition Reactions
#MMPMID41384035
van Beek CB
; Choi H
; Hilberts MLA
; Lammertink MM
; Park B
; Lutz M
; Baik MH
; Broere DLJ
Organometallics
2025[Dec]; 44
(23
): 2786-2795
PMID41384035
show ga
The mechanism of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction
has been under investigation for over two decades. While catalytically relevant
dicopper intermediates have been proposed and a few suspected intermediates have
been isolated, the mechanism remains poorly understood. In this work, we describe
the synthesis and characterization of neutral dicopper complexes bearing the
proton-responsive dinucleating (iPr ) PNNP "expanded pincer" ligand, which are
demonstrated to be relevant intermediates in the CuAAC reaction. The acetylide
complex [Cu(2)( (iPr ) PNNP*)-(?-C?C-p-F-C(6)H(4))] (2) reacts with
1-azido-4-fluorobenzene at ambient temperature to form the dicopper complex
[Cu(2)( (iPr ) PNNP*)-(?-(1,4-bis-(p-fluorophenyl)-1,2,3-triazolide)] (3),
featuring a symmetrically bridging 1,4-substituted 1,2,3-triazolide ligand.
Mechanistic studies were performed using both isotopic labeling experiments and
density functional theory (DFT) calculations for the subsequent protodemetalation
step. These studies show that the release of the triazole product proceeds via a
stepwise metal-ligand cooperative (MLC) pathway, which is favored over the direct
alkyne-to-triazolide proton transfer as it requires less structural
reorganization of the dicopper platform. This demonstrates how cooperativity
between the copper centers and metal-ligand cooperativity can offer an
alternative mechanistic pathway, bypassing the conventional rate-limiting
alkyne-to-triazolide proton transfer in the CuAAC reaction.
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