Triarylselenonium Triflates Provide Efficient Access to No-Carrier-Added Ortho-, Meta-, and Para-[18F]Fluoroarenes

Abstract

[¹⁸F]Fluoroarenes feature prominently as radiotracers for biomedical imaging with positron emission tomography (PET). We report the syntheses of a wide range of triphenylselenonium triflates and demonstrate their reactivity towards cyclotron-produced [¹⁸F]fluoride (t_1/2 = 109.8 min; β⁺, 97%) for producing no-carrier-added (NCA) [¹⁸F]fluoroarenes. Triphenylselenonium triflates having a single strong p-electron-withdrawing group gave substituted [¹⁸F]fluoroarenes in high yields (72-90%). Salts having a m-nitro, chloro, or methyl substituent produced the substituted [¹⁸F]fluoroarenes in lower but still useful yields (22-32%). A strong 'ortho effect' occurred in the radiofluorination of triphenylselenonium triflates with an o-substituent (Cl or Me), which induced moderately high yields (62 and 65%). In a head-to-head comparison, triarylselenonium triflates performed as well and in some cases better than the corresponding triarylsulfonium triflates, especially for producing ¹⁸F-labeled electron-rich arenes. p-Anisyl groups proved to be effective spectator groups for the radiofluorination of triarylselenonium triflates. Thus, the radiofluorination of aryl(di-p-anisyl)selenonium triflates gave high yields (55-98%) of [¹⁸F]fluoroarenes carrying an o-, p-, or m-halo, or alkyl substituent. Quantum computational analysis accords with a reductive elimination type mechanism. Finally, the utility of aryl(di-p-anisyl)phenylselenonium triflates for radiofluorination was demonstrated by producing known PET-like tracers, for example [¹⁸F]FPEB, and a [¹⁸F]canagliflozin fragment; the yield of [¹⁸F]FPEB from an aryl(di-p-anisyl)phenylselenonium triflate precursor was remarkably high (97%). In conclusion, substituted triarylselenonium triflates, and especially aryl(di-p-anisyl)selenonium triflates, are a useful addition to the range of precursors that can be considered for producing NCA o-, m-, and p-¹⁸F-labeled fluoroarenes as new PET tracers.