Nucleophilic strategies to construct -CF₂- linkages using borazine-CF₂Ar reagents

Area of Science:

• Organic Chemistry
• Fluorine Chemistry
• Synthetic Methodology

Background:

• The incorporation of fluorine atoms into organic molecules can significantly alter their physicochemical and biological properties.
• Developing efficient methods for introducing difluoromethylene (-CF2-) groups is crucial for medicinal chemistry and materials science.

Purpose of the Study:

• To develop a new synthetic strategy for forming carbon-carbon bonds using a difluoromethylene-containing reagent.
• To demonstrate the versatility of this approach in constructing molecules with internal -CF2- linkages.

Main Methods:

• Utilized a Lewis acid-quenched CF2Ph- reagent for nucleophilic addition reactions.
• Employed S_NAr reactions and Palladium-catalysis for C(sp²)-C(sp³) coupling.
• Applied S_N2 reactions for C(sp³)-C(sp³) bond formation.

Main Results:

• Successfully achieved C-C bond formation via nucleophilic addition.
• Demonstrated the preparation of molecules containing internal -CF2- linkages.
• Showcased efficient C(sp²)-C(sp³) and C(sp³)-C(sp³) bond constructions.
• Confirmed tolerance of medicinally-relevant functional groups in S_N2 reactions.

Conclusions:

• The developed Lewis acid-quenched CF2Ph- reagent provides a powerful tool for synthesizing molecules with internal -CF2- groups.
• The methodology offers diverse and operationally simple routes for C-C bond formation, applicable to complex molecular architectures.