Metal Mediated Reactions

Cyanation Reactions Using Hydrogen [C]cyanide

Palladium-mediated coupling reactions have allowed formation of various carbon-carbon bonds that were previously difficult to make. One example is the synthesis of nC-labeled aromatic [26] and vinylic [27] nitriles via the palladium-mediated reaction of [uC]cyanide and an aromatic or vinyl halide (Fig. 10.6).

Cross-Couplings Using [11C]Methyl Iodide

Palladium-mediated cross-coupling reactions are important in organic synthesis. The Stille reaction is a cross coupling of an organotin reagent with an organohalide and the related Suzuki reaction is a coupling of an organoboron compound with an organohalide [28]. Since many functional groups are tolerated during these reactions, protective groups are usually not needed. The Stille reaction has been selected for 11C-labeling of a wide array of different substances including some prostacyclin analogues (Fig. 10.7) [2,29].

Organocuprates

Coupling reactions with organocuprates were studied with the prime objective to develop methods for 11C-labeling of fatty acids in selected positions. Bis-Grignard reagents were used in coupling reactions with 11C-labeled alkyl iodides in the syntheses of a broad range of saturated fatty acids so that it was also possible to label the polyunsaturated fatty acid, arachidonic acid [30]. The lithium [11C]methyl(2-thienyl)cuprates were, for example, used in the syntheses of [11C]octane, [11C]acetophenone [31], [21-11C] progesterone [32] and [1a-methyl-11C]mesterolone [33] (Fig. 10.8).

Figure 10.6. Palladium-mediated cyanations.

^^^OCHs

OCH3

i\^SnBu3

Pd(0), "CH3I _

/

^CHs

HO OH

J

ho oh ^

Figure 10.7. Synthesis of a [11C] prostacyclin receptor analog by a Stille coupling.

Figure 10.7. Synthesis of a [11C] prostacyclin receptor analog by a Stille coupling.

UC-LabettingReactions Using[nC]Carbon Monoxide

Due to recent technical developments it is now possible to use [uC]carbon monoxide to synthesize various types of carbonyl compounds [34]. Since carbonyl groups are common in biologically interesting compounds the potential of [uC]carbon monoxide as a precursor in tracer synthesis is significant. This is further reinforced by the fact that carbonyl compounds are useful substrates for many chemical group transformations. Compounds where the uC-carbonyl group is bound to one or two carbon atoms have been produced using palladium-mediated reactions and compounds where the carbonyl group is bound to two heteroatoms (for example, ureas, carbamates and carbonates) by selenium-mediated reactions (Fig. 10.9). Protective groups are usually not needed and the syntheses can, in most cases, be carried out by a one-pot procedure [35].

Further work on the scope and limitation of using [11C]carbon monoxide in labeling synthesis is currently in progress in our laboratory.

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