A quantitative reactivity scale for electrophilic fluorinating reagents.

Area of Science:

• Organic Chemistry
• Fluorination Chemistry

Background:

• Electrophilic N-F fluorination is vital for introducing fluorine into aliphatic compounds for drug discovery.
• Current N-F reagent selection relies on empirical methods due to a lack of quantitative electrophilicity data.

Purpose of the Study:

• To establish an experimentally determined kinetic reactivity scale for ten N-F fluorinating reagents.
• To provide quantitative data for selecting appropriate N-F reagents in synthetic chemistry.

Main Methods:

• A kinetic reactivity scale was developed using ten N-F fluorinating reagents in acetonitrile (CH3CN).
• Para-substituted 1,3-diaryl-1,3-dicarbonyl derivatives were employed to measure relative and absolute rate constants.
• A spectrophotometric method was utilized to report reactivity.

Main Results:

• A reactivity scale spanning eight orders of magnitude was established for the tested N-F reagents.
• The study quantified the electrophilicities of Selectfluor™, NFSI, Synfluor™, and N-fluoropyridinium salts.
• A novel form of tautomeric polymorphism was discovered using the dicarbonyl scaffold.

Conclusions:

• The developed reactivity scale offers a quantitative basis for N-F fluorination reagent selection.
• This work enhances the predictability and efficiency of electrophilic fluorination in organic synthesis.
• The findings facilitate optimized fluorine incorporation in pharmaceutical research and development.