Cross-Coupling Reactions as Valuable Tool for the Preparation of PET Radiotracers

Abstract

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 metalcatalyzed 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 grouptolerating incorporation of carbon-11 and fluorine-18 into target molecules. This review deals with design, application and improvement of transition metal-mediated carboncarbon as well as carbon-heteroatom cross-coupling reactions as a labeling feature with the focus on the preparation of radiolabeled compounds for molecular imaging.

Spirocyclic hypervalent iodine(III)-mediated radiofluorination of non-activated and hindered aromatics

“…Two arene substrates with the CF 3 pharmacophore (27 and 28) were successfully radiolabelled with 18 F at the meta-position in excess of 45% conversion. Compound 27 demonstrates compatibility with aryl halides and could be further functionalized via coupling reactions 30 33 ± 4% n = 3…”

Development of indazolylpyrimidine derivatives as high-affine EphB4 receptor ligands and potential PET radiotracers

“…The most commonly applied labeling method consists of the [ 11 C]methylation using [ 11 C]CH 3 I or [ 11 C]CH 3 OTf. 33,34 The original inhibitor contains an amine bound methyl group which is excellently suitable for the isotopic labeling with carbon-11. In first experiments, the optimal labeling conditions for the literature known compound 17 was investigated.…”

Nanocatalysts for Hiyama, Stille, Kumada, and Negishi C–C Coupling Reactions

“…23 Finally, a novel application of Stille coupling is related to the synthesis of 14 C-labeled medical tracers, which are used in positron emission tomography. 126 Speculations on the role of Pd(0) clusters in Stille coupling began as early as the 1990s. In a communication, Louie and Hartwig reported tri-o-tolylphosphane palladacycle-catalyzed Stille coupling between 4-bromoacetophenone and Me 3 SnPh; a 31 P NMR study indicated the presence of free as well as metal-bound P ligands, and it was assumed that unligated Pd(0) might play a definitive role in the mechanistic scenario.…”