%0 Journal Article
%T Isotopologues of potassium 2,2,2-trifluoroethoxide for applications in positron emission tomography and beyond.
%A Zhao Q
%A Telu S
%A Jana S
%A Morse CL
%A Pike VW
%J Nat Commun
%V 15
%N 1
%D 2024 Jul 10
%M 38987549
%F 17.694
%R 10.1038/s41467-024-49975-7
%X The 2,2,2-trifluoroethoxy group increasingly features in drugs and potential tracers for biomedical imaging with positron emission tomography (PET). Herein, we describe a rapid and transition metal-free conversion of fluoroform with paraformaldehyde into highly reactive potassium 2,2,2-trifluoroethoxide (CF3CH2OK) and demonstrate robust applications of this synthon in one-pot, two-stage 2,2,2-trifluoroethoxylations of both aromatic and aliphatic precursors. Moreover, we show that these transformations translate easily to fluoroform that has been labeled with either carbon-11 (t1/2 = 20.4 min) or fluorine-18 (t1/2 = 109.8 min), so allowing the appendage of complex molecules with a no-carrier-added 11C- or 18F- 2,2,2-trifluoroethoxy group. This provides scope to create candidate PET tracers with radioactive and metabolically stable 2,2,2-trifluoroethoxy moieties. We also exemplify syntheses of isotopologues of potassium 2,2,2-trifluoroethoxide and show their utility for stable isotopic labeling which can be of further benefit for drug discovery and development.