Combined Metal-Metal and Metal-Ligand Cooperativity in Dicopper-Catalyzed Azide-Alkyne Cycloaddition Reactions

Area of Science:

• Organometallic Chemistry
• Catalysis
• Reaction Mechanisms

Background:

• The mechanism of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is not fully understood despite extensive research.
• Dicopper intermediates are proposed but rarely isolated, hindering mechanistic elucidation.

Purpose of the Study:

• To synthesize and characterize neutral dicopper complexes as potential intermediates in the CuAAC reaction.
• To investigate the mechanism of triazole product release from these dicopper complexes.

Main Methods:

• Synthesis and characterization of novel dicopper complexes using an "expanded pincer" ligand.
• Reaction of an acetylide complex with an azide to form a triazolide complex.
• Mechanistic studies involving isotopic labeling and density functional theory (DFT) calculations.

Main Results:

• Neutral dicopper complexes bearing a proton-responsive dinucleating "expanded pincer" ligand were successfully synthesized.
• A dicopper acetylide complex reacted with an azide to yield a dicopper triazolide complex.
• Isotopic labeling and DFT calculations revealed a stepwise metal-ligand cooperative (MLC) pathway for triazole product release.

Conclusions:

• The synthesized dicopper complexes are relevant intermediates in the CuAAC reaction.
• The release of the triazole product occurs via an MLC pathway, which is favored over direct proton transfer.
• Metal-ligand cooperativity offers an alternative mechanistic route in CuAAC, bypassing the conventional rate-limiting step.