Migratory Aryl Cross-Coupling.

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Cross-coupling reactions typically exhibit regiospecificity, dictated by the leaving group's position.
• Synthesizing different substitution patterns usually necessitates preparing new starting material isomers.

Purpose of the Study:

• To develop cross-coupling variants for accessing multiple structural isomers from identical coupling partners.
• To establish a method that bypasses the need for synthesizing distinct starting material isomers.

Main Methods:

• Utilizing a bulky palladium catalyst to promote reversible aryl halide transposition via transient metal aryne intermediates.
• Employing a gradual nucleophile addition strategy for dynamic kinetic resolution of isomeric intermediates.
• Investigating the reaction mechanism using computational and experimental data, including a Curtin-Hammett kinetic analysis.

Main Results:

• Demonstrated efficient and reversible transposition of aryl halides.
• Achieved high yields of unconventional product isomers through dynamic kinetic resolution.
• Showcased the method's compatibility with various oxygen- and nitrogen-centered nucleophiles and common functional groups.

Conclusions:

• Developed a novel migratory cross-coupling strategy offering access to diverse structural isomers.
• Established a general mechanistic framework for this approach, supported by kinetic analysis.
• The method provides a versatile alternative to traditional isomer synthesis in cross-coupling reactions.