Orthogonal Discrimination among Functional Groups in Ullmann-Type C-O and C-N Couplings

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Copper-catalyzed arylation is crucial for forming C-C and C-heteroatom bonds.
• Ligand selection significantly impacts catalytic efficiency in Ullmann-type couplings.
• Achieving orthogonal selectivity among different functional groups remains a synthetic challenge.

Purpose of the Study:

• To develop a toolkit of copper-based catalysts for chemoselective arylation.
• To achieve orthogonal arylation of amides in the presence of amines and phenols.
• To explore the influence of ligands on selectivity and reaction conditions.

Main Methods:

• Utilized copper-based catalysts with various ligands for arylation reactions.
• Employed aryl iodides and bromides as electrophiles.
• Conducted competitive reactions with amides, amines, and phenol derivatives.
• Performed radical clock experiments to investigate reaction mechanisms.

Main Results:

• Demonstrated chemoselective arylation of amides, orthogonal to amines and phenols.
• Showcased the ability to control selectivity using different ligands under mild conditions.
• Confirmed selectivity trends with electronically biased iodobenzene and bromobenzene electrophiles.
• Ruled out radical-based mechanisms through radical clock experiments.

Conclusions:

• Developed a versatile toolkit of copper catalysts for selective arylation.
• Achieved high chemoselectivity in competitive arylation reactions, enabling orthogonal functionalization.
• Mild reaction conditions and ligand control offer practical advantages for synthetic strategies.