Fluorocarbyne Insertion into Benzene Skeletons

Area of Science:

• Organofluorine Chemistry
• Synthetic Organic Chemistry

Background:

• Fluorinated synthons are crucial in organofluorine chemistry.
• Metal-fluorocarbyne synthons are underexplored compared to trifluoromethyl and difluorocarbene counterparts.

Purpose of the Study:

• To report the first application of metal-fluorocarbyne in organic synthesis.
• To enable concurrent fluorine incorporation and skeletal editing of arenes.

Main Methods:

• Fluorocarbyne-promoted skeletal editing reaction.
• Benzene transformation into monofluorinated cycloheptatrienes.
• Mechanistic studies including intermediate capture and DFT calculations.

Main Results:

• Achieved selective benzene activation and meta-insertion into cycloheptatrienes.
• Demonstrated broad functional group tolerance and compatibility with diverse arene substrates.
• Successfully applied to late-stage drug modification, enhancing solubility of tecovirimat.

Conclusions:

• This work introduces metal-fluorocarbyne as a versatile tool for fluorine incorporation and scaffold modification.
• The developed method offers a new pathway for synthesizing fluorinated compounds with potential pharmaceutical applications.