Synthesis of 4-[¹⁸F]fluoroiodobenzene and its application in Sonogashira cross-coupling reactions

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, 17alpha-ethynyl-3,17beta-estradiol 7 and 17alpha-ethynyl-3-methoxy-3,17beta-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 starting from 4-[¹⁸F]fluoroiodobenzene.