Metal-Catalyzed Fluoroacetyl Carbene Transfer from Sulfonium Salts

Area of Science:

• Organic Chemistry
• Organofluorine Chemistry
• Synthetic Methodology

Background:

• Organofluorine compounds are crucial in pharmaceuticals, materials, and agrochemicals.
• Fluorinated carbene transfer is a key strategy for introducing fluorine and forming new chemical bonds.
• Existing methods for ethyl fluoroacetyl carbene transfer are limited by the unavailability of suitable reagents.

Purpose of the Study:

• To develop a novel reagent for ethyl fluoroacetyl carbene transfer.
• To demonstrate the utility of this reagent in Doyle-Kirmse and cyclopropanation reactions.
• To provide an efficient method for synthesizing valuable monofluorinated products.

Main Methods:

• Synthesis of a novel fluoroacetyl sulfonium reagent: (2-ethoxy-1-fluoro-2-oxoethyl)(phenyl)(2,3,4,5-tetramethylphenyl)sulfonium tetrafluoroborate (1).
• Application of reagent 1 in Doyle-Kirmse reactions.
• Application of reagent 1 in cyclopropanation reactions using earth-abundant metal catalysts.

Main Results:

• Reagent 1 effectively serves as an alternative to the unavailable 2-diazo-2-fluoroacetate.
• The carbene transfer reactions proceed under mild conditions.
• Efficient synthesis of valuable monofluorinated products was achieved.

Conclusions:

• The novel fluoroacetyl sulfonium reagent provides a practical and effective method for ethyl fluoroacetyl carbene transfer.
• This methodology facilitates the synthesis of monofluorinated compounds under mild conditions with earth-abundant catalysts.
• The developed approach expands the toolkit for organofluorine synthesis, impacting drug discovery and materials science.