Recyclable Trifluoromethylation Reagents from Fluoroform

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Fluorine Chemistry

Background:

• Trifluoromethylation is a crucial transformation in medicinal chemistry and materials science.
• Existing methods for generating trifluoromethyl anions often require harsh conditions or specialized reagents.
• Development of efficient and sustainable methods for trifluoromethyl group introduction is highly desirable.

Purpose of the Study:

• To develop a rational strategy for preparing trifluoromethyl (CF3-) transfer reagents.
• To achieve CF3- transfer at ambient temperature from fluoroform (HCF3).
• To enable the synthesis of diverse trifluoromethylation reagents with catalyst recycling.

Main Methods:

• Synthesis of a reactive CF3- adduct using alkali metal hydride, fluoroform (HCF3), and borazine Lewis acids.
• Demonstration of nucleophilic CF3- transfer to various substrates without additional chemical activation.
• Quantification of borazine Lewis acid regeneration after CF3 transfer.

Main Results:

• A highly reactive CF3- adduct was synthesized in quantitative yield at room temperature.
• The synthesized reagents efficiently transferred CF3- to substrates, forming valuable trifluoromethylated compounds.
• The borazine Lewis acid was quantitatively regenerated, enabling complete recycling.

Conclusions:

• A novel and efficient strategy for preparing CF3- transfer reagents from HCF3 at ambient temperature has been established.
• This method provides a sustainable route for synthesizing nucleophilic, radical, and electrophilic trifluoromethylation reagents.
• The quantitative regeneration and recycling of the borazine Lewis acid highlight the economic and environmental benefits of this approach.