Selective ¹⁹F-labeling of functionalized carboxylic acids with difluoromethyl diazomethane (CF₂HCHN₂)

The incorporation of fluorinated moieties into organic structures is a particularly powerful approach for generating compounds with useful biological applications in industry, pharmacology, and agriculture. Here, the recently developed reagent—CF₂HCHN₂—selectively esterifies carboxyl groups on organic molecules in the presence of other polar functional groups. The reaction is remarkably simple, proceeding at room temperature in chloroform without addition of a catalyst. The procedure allows “last-step” incorporation of a fluorinated ester moiety into organic structures, including bioorganic molecules such as peptides and proteins. The fluorinated ester can subsequently function as a ¹⁹F-probe in biomolecules, thereby enabling molecular size determination by diffusion ¹⁹F NMR experiments.