Small Molecule Radiopharmaceuticals – A Review of Current Approaches <s> Suzuki Reactions <s> 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. <s> BIB001 </s> Small Molecule Radiopharmaceuticals – A Review of Current Approaches <s> Suzuki Reactions <s> Abstract: The increasing application of positron emission tomography (PET) in nuclear medicine has stimulated the extensive development of a multitude of new radiotracers and novel radiolabeling procedures with the most prominent short-lived positron emitters carbon-11 and fluorine-18. Radiolabeling with these radionuclides represents a remarkable challenge. Special attention has to be paid to synthesis time and specific labeling techniques due to the short physical half life of the respective radionuclides 11 C (t 1/2 = 20.4 min) and 18 F (t 1/2 = 109.8 min). In the past, numerous transition metal-catalyzed reactions were employed in organic chemistry, even though only a handful of these coupling reactions were adopted in radiochemical practice. Thus, the implementation of modern synthesis methods like cross-coupling reactions offers the possibility to develop a wide variety of novel radiotracers. The introduction of catalysts based on transition metal complexes bears a high potential for rapid, efficient, highly selective and functional group-tolerating incorporation of carbon-11 and fluorine-18 into target molecules. This review deals with design, application and improvement of transition metal-mediated carbon-carbon as well as carbon-heteroatom cross-coupling reactions as a labeling feature with the focus on the preparation of radiolabeled compounds for molecular imaging. <s> BIB002
The Suzuki coupling is based on the conjugation of boron substrates (alkylborane/benzylborane/alkenylboranes) with alkyl halide leading to C-C bond formation or C-X bond formation  BIB002 . General Optimized conditions  BIB002 Cyclopentylcarbinol BIB001 steroid precursors R'= OH, OMe BIB001 FiGURe 9 | Selected radiopharmaceuticals developed using Sonogashira coupling. Structures referenced in  BIB002  BIB001 Pd(PPh3)2Cl2(catalyst), K2CO3(base) and DMSO (solvent) (ii) aryltriflate + alkyl boronic acid (reactant) with bases such as tetra-butylammonium fluoride or aryltriflate + aromatic boronic acid (reactant) with bases such as potassium tertbutoxide. Lithium bromide (promoter) may also be added. Fluorine Labeling Advantages are (a) borane derivatives that are less toxic than the stannous substrates, (b) organoborane has relatively high reactivity, especially in the presence of a base or a fluoride anion, (c) compatible with a wide variety of functionalities, and (d) water tolerant.