¹⁸F‐Labeling of Aryl‐SCF₃, ‐OCF₃ and ‐OCHF₂ with [¹⁸F]Fluoride

Abstract

We report that halogenophilic silver(I) triflate permits halogen exchange (halex) nucleophilic 18F‐fluorination of aryl‐OCHFCl, ‐OCF2Br and ‐SCF2Br precursors under mild conditions. This AgI‐mediated process allows for the first time access to a range of 18F‐labeled aryl‐OCHF2, ‐OCF3 and ‐SCF3 derivatives, inclusive of [18F]riluzole. The 18F‐labeling of these medicinally important motifs expands the radiochemical space available for PET applications.

A Convenient Synthesis of Difluoroalkyl Ethers from Thionoesters Using Silver(I) Fluoride

“…Prominent among these approachesi sf luorodesulfurization [9] using highly reactive fluorinating agents including SF 4 gas [9b] or BrF 3 [9c] (Type I), or combinations of oxidizinga gents with hydrofluorica cid (Type II). [1b, 9a, 10] Alternatively, both DAST and DeoxoFluor( Type III) [11] have demonstrated utility in the deoxyfluorination or fluorodesulfurization of esters [12] or thionoesters, [12][13] respectively.A sastrategic alternative, the rearrangement of heteroaryl ketones using XeF 2 and HF/pyr [5b] or displacemento fb romide from a,a-difluoro-a-bromo esters [14] and amides [15] (e.g., 7!11)a re also employed for the synthesis of difluoroalkyl ethers (e.g., 4) [6] and heterobenzylic difluoro ethers (e.g., 5). [7] Unfortunately,m any of the reagents relevant to the synthesis of difluoroalkyl ethers are toxic, dangeroust o handle, and react violently with water.O wing to this extreme reactivity,u se of theser eagents is often limited to substrates devoid of unprotected functional groupsa nd under strictly anhydrous reaction conditions.…”

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…[158] Subsequently,t hey also found that AgOTf could promote the formation of ab road array of 18 F-labeled aryl-CF 3 and aryl-CF 2 Hc ompounds from the corresponding aryl-CF 2 Br and aryl-CHFCl precursors (Scheme 29 A). [158] Subsequently,t hey also found that AgOTf could promote the formation of ab road array of 18 F-labeled aryl-CF 3 and aryl-CF 2 Hc ompounds from the corresponding aryl-CF 2 Br and aryl-CHFCl precursors (Scheme 29 A).…”

Radiosynthesis of [ 18 F]ArylSCF 2 H Using Aryl Boronic Acids, S -(Chlorofluoromethyl)benzenesulfonothioate and [ 18 F]Fluoride

“…6,7 As a result, the demand for structurally complex 18 F-labeled tracers continues to grow. 8 In recent years, numerous methods that allow broader access to 18 F-labeled (hetero)aryl and alkyl fluorides, [9][10][11][12][13][14][15][16][17] as well as new 18 F-motifs including [ 18 F]CF 3 , 18-22 [ 18 F]CF 2 H, [23][24][25][26] [ 18 F]OCF 3 , 27 [ 18 F]OCF 2 H, 27 and [ 18 F]SCF 3 , [27][28][29][30][31] have emerged. Methods for the preparation of structurally diverse [ 18 F]ArSCF 2 H have not been reported despite studies reporting that the difluoromethylthio group can be beneficial for pharmacokinetic and physicochemical properties such as metabolic stability, thermodynamic stability, and lipophilicity.…”