Synthesis of Dideuterofluoroarene 3 ΔF(D)-NMR Reporter-Resolvers for Structural, Mechanistic, and Kinetic Studies

3,5-Dideutero-4-fluorophenyl compounds are generated by ipso-functionalization of (4-fluorophenyl)trimethylsilane-d2, prepared in >99 atom % isotopic purity, on a multigram scale, by selective H/D exchange at the C–H sites, ortho to fluorine, using a Lochmann–Schlosser superbase and MeOD. The 3,5-dideutero-4-fluorophenyl “reporter-resolver” system has an isotope shift, ΔδF, in the range of 0.5 to 0.6 ppm. It enables in situ 19F NMR spectroscopic reaction monitoring of crossover, entrainment, ratiometric heavy atom KIEs, and unambiguous structural assignments and integrations via three NMR-active nuclei.