Ortho-Ortho Selective Oxidative Coupling of Phenols by Hydroxo Multicopper(II) Clusters

Area of Science:

• Organic Chemistry
• Catalysis
• Supramolecular Chemistry

Background:

• Oxidative coupling of phenols is a crucial reaction in organic synthesis.
• Achieving site selectivity, especially ortho-ortho coupling, with diverse phenol substrates remains challenging.
• Existing methods often require harsh conditions or are limited in substrate scope.

Purpose of the Study:

• To develop a highly ortho-ortho selective aerobic oxidative coupling method for a wide range of phenols.
• To utilize a readily available hydroxo multicopper cluster catalyst for this transformation.
• To elucidate the mechanism behind the observed unprecedented site selectivity.

Main Methods:

• Aerobic oxidative coupling reaction using a specific hydroxo multicopper cluster, [Cu(tmeda)(μ-OH)]2(ClO4)2.
• Reaction performed in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) solvent.
• Mechanistic investigations using Density Functional Theory (DFT) calculations, high-resolution mass spectrometry, and Infrared photodissociation (IRPD) spectroscopy.

Main Results:

• Achieved unprecedented ortho-ortho selectivity in the aerobic oxidative coupling of various phenols, including unsubstituted and substituted ones.
• Demonstrated the efficacy of the [Cu(tmeda)(μ-OH)]2(ClO4)2 complex under mild conditions.
• Provided mechanistic insights into the selectivity, attributing it to the dicopper complex's ability to position phenolate ligands for ortho-attack.

Conclusions:

• The developed method offers a simple, efficient, and highly selective route for phenol oxidative coupling.
• The study expands the utility of multicopper clusters in catalysis.
• The findings provide a deeper understanding of selectivity control in oxidative coupling reactions.