Directing Group-Promoted Inert C-O Bond Activation Using Versatile Boronic Acid as a Coupling Agent

Area of Science:

• Organic Chemistry
• Catalysis
• Sustainable Chemistry

Background:

• Aryl methyl ethers (methoxyarenes) are abundant but underutilized in C-C cross-coupling due to inert C-O bonds.
• Haloarenes are common coupling partners but pose toxicity and environmental concerns.
• Developing efficient methods for activating C-O bonds in methoxyarenes is crucial for sustainable synthesis.

Purpose of the Study:

• To develop an efficient catalytic cross-coupling strategy for methoxyarenes.
• To utilize directing groups for the activation of inert C-O bonds in aryl methyl ethers.
• To establish methoxyarenes as viable, less toxic alternatives to haloarenes in cross-coupling reactions.

Main Methods:

• A nickel-catalyzed (Ni(cod)2) cross-coupling reaction mediated by a carbene.
• Employing directing groups to facilitate C-O bond activation in methoxyarenes.
• Utilizing various organoboron reagents, including readily available arylboronic acids.

Main Results:

• Efficient catalytic cross-coupling of methoxyarenes with diverse organoboron reagents was achieved.
• The protocol demonstrated unprecedented C-C cross-coupling with economical arylboronic acids.
• The method successfully enabled chemo-selective C-O bond cleavage and synthesis of bifunctionalized biaryls.

Conclusions:

• Directing group-assisted nickel catalysis provides an efficient route for C-C cross-coupling of methoxyarenes.
• This strategy offers a sustainable and less toxic alternative to traditional haloarene coupling methods.
• The developed protocol expands the synthetic utility of aryl methyl ethers in organic synthesis.