Site-Selective Cross-Coupling of Remote Chlorides Enabled by Electrostatically Directed Palladium Catalysis

Area of Science:

• Synthetic organic chemistry
• Catalysis
• Organometallic chemistry

Background:

• Controlling site-selectivity in reactions remote from existing functional groups is a significant challenge.
• Cross-coupling reactions are vital tools in synthetic chemistry but often lack precise site-control on complex substrates.

Purpose of the Study:

• To develop a strategy for achieving high site-selectivity in cross-coupling reactions on dichloroarenes with acidic functional groups.
• To repurpose a bifunctional phosphine ligand for directed catalysis.

Main Methods:

• Utilized a sulfonylated phosphine ligand with inherent bifunctionality.
• Employed three common cross-coupling reactions.
• Conducted mechanistic studies to elucidate the reaction pathway.

Main Results:

• Achieved high site-selectivity in cross-coupling reactions on dichloroarenes bearing acidic functional groups.
• Demonstrated successful application of three major cross-coupling processes.
• Identified electrostatic interactions between the sulfonate group and substrate cation as the directing force.

Conclusions:

• The study presents a novel strategy for site-selective cross-coupling using a bifunctional ligand.
• Electrostatic interactions can be effectively employed to direct catalysis, even with anionic ligands and substrates.
• This work offers an alternative design principle for noncovalent interactions in catalysis.