Fluorine Effects on Group Migration via a Rhodium(V) Nitrenoid Intermediate

Area of Science:

• Organic Chemistry
• Organometallic Chemistry
• Fluorine Chemistry

Background:

• Hydroarylation reactions are crucial for constructing complex organic molecules.
• Developing efficient methods for synthesizing fluorinated compounds remains a significant challenge in organic chemistry.
• Rhodium(III)-catalyzed C-H activation offers a powerful strategy for C-C bond formation.

Purpose of the Study:

• To develop a novel rhodium(III)-catalyzed protocol for the hydroarylation of α,α-difluoromethylene alkynes.
• To synthesize difluorinated 2-alkenyl aniline derivatives with high yields and regioselectivity.
• To investigate the mechanistic aspects and the role of fluorine in the reaction manifold.

Main Methods:

• Utilized rhodium(III) catalysis for sequential C-H activation and aryl migration.
• Employed α,α-difluoromethylene alkynes and N-pivaloxyl aryl amides as substrates.
• Optimized reaction conditions to achieve high yields and selectivity.

Main Results:

• Successfully achieved the hydroarylation of a wide range of α,α-difluoromethylene alkynes with N-pivaloxyl aryl amides.
• Obtained difluorinated 2-alkenyl aniline derivatives in high yields and excellent regioselectivity.
• Identified unique fluorine effects influencing the reaction pathway.

Conclusions:

• Established an unprecedented rhodium(III)-catalyzed synthetic route to difluorinated 2-alkenyl anilines.
• Demonstrated the broad applicability of the developed protocol for diverse substrates.
• Highlighted the significance of fluorine's electronic properties in enabling this novel transformation.