Synthesis of 4‐[¹⁸F]fluoroiodobenzene and its application in sonogashira cross‐coupling reactions

Abstract

The first application of a Sonogashira cross‐coupling reaction in 18F chemistry has been developed. The reaction was exemplified by the cross‐coupling of terminal alkynes (ethynylcyclopentyl carbinol 6, 17α‐ethynyl‐3,17β‐estradiol 7 and 17α‐ethynyl‐3‐methoxy‐3,17β‐estradiol 8) with 4‐[18F]fluoroiodobenzene. 4,4′‐Diiododiaryliodonium salts were used as precursors for the synthesis of 4‐[18F]fluoroiodobenzene, enabling the convenient access to 4‐[18F]fluoroiodobenzene in 13–70% yield using conventional heating or microwave activation. The Sonogashira cross‐coupling of 4‐[18F]fluoroiodobenzene with terminal alkynes gave the corresponding 4‐[18F]fluorophenylethynyl‐substituted compounds [18F]‐9, [18F]‐10 and [18F]‐13 in yields up to 88% within 20 min of starting from 4‐[18F]fluoroiodobenzene. Copyright © 2003 John Wiley & Sons, Ltd.

Radical scavengers: A practical solution to the reproducibility issue in the fluoridation of diaryliodonium salts

“…These benefits have resulted in much recent interest in diaryliodonium salts as precursors to fluorine-18 arenes [10][11][12][13][14][15][16], however we, and others [12,16], have observed that the fluoridation results can be extremely variable, particularly in the case of electron-rich diaryliodonium salts. Despite the potential benefits the approach has for the introduction of fluorine-18 into aromatic systems the associated lack of reproducibility has severely limited the development and application of this approach to the production of fluorine-18 labelled radiopharmaceuticals.…”

Single-step syntheses of no-carrier-added functionalized [18F]fluoroarenes as labeling synthons from diaryliodonium salts

“…[ 18 F]4-Fluoroiodobenzene 33 and [ 18 F]fluorobromobenzene 34 have been prepared from the radiofluorination of diaryliodonium salts without noticeable concomitant halogen displacement. We have also previously observed resistance to aryl halogen displacement by S N Ar when in well-activated positions in (halopyridinyl)aryliodonium salts during their radio-fluorinations to produce [ 18 F]fluorohalopyridines.…”

Click synthesis of estradiol–cyclodextrin conjugates as cell compartment selective estrogens

“…Elaboration of EE 2 is readily achieved using palladium catalyzed Sonogashira cross coupling with halide reagents,24 allowing attachment of a benzaldehyde moiety for ACD conjugation. Subsequent reduction of benzaldehyde 4 gave the benzyl alcohol 5 that was used as a control compound.…”