A new approach for a 11C-C bond formation: Synthesis of 17alpha-(3'-[11C]Prop-1-ynyl)-3-methoxy-3,17beta-estradiol


A new approach for a 11C-C bond formation: Synthesis of 17alpha-(3'-[11C]Prop-1-ynyl)-3-methoxy-3,17beta-estradiol

Wüst, F.; Zessin, J.

Introduction
To expand the scope of 11C-labelled compounds, novel 11C-C bond forming reactions gain more and more attention [1]. The versatile availability of [11C]methyl iodide makes this labelling precursor favourable in several transition-metal mediated cross-coupling reactions. In this contex, technically simple, high-yielding and functional group tolerating reactions are of particular interest. The Sonogashira copper-palladium catalysed coupling of terminal alkynes with aromatic and vinylic halides [2] represents such a reaction. To the best of our knowledge, the Sonogashira-reaction has not yet been employed in 11C-chemistry. Herein, we describe a modified Sonogashira-like reaction [3] for labelling the terminal alkyne group of the potent contraceptive steroid mestranol 1 with [11C]methyl iodide.

Results and Discussion
The classical conditions of the Sonogashira reaction (Pd0, CuI and TEA or DIPA as thebase) can not be employed for 11C-labelling with [11C]methyl iodide due to the rapid quaternization the amine base. Therefore, we tested alternative catalyst/base combinations. By using tetrakis(triphenylphosphine)-palladium(0) (TTPP), copper(I) iodide, and 1,8-bis(dimethylamino)naphthalene as a non-nucleophilic base, about 5% of [11C]methyl iodide was converted into [11C]2. Similar results were obtained using the catalyst TTPP and silver oxide as the base. However, in the reaction of 1 with tris-(dibenzylidineacetone)-dipalladium(0), triphenylarsine, and tetrabutylammonium fluoride, 42-53% of [11C]MeI was converted into [11C]2

Scheme 1: 11C-labelling of steroid 1

Conclusion
We developed a new method for a 11C-C bond formation employing the cross-coupling of terminal alkynes with [11C]methyl iodide via a Sonogashira-like reaction in sufficient radiochemical yields.

References
[1] B. Långström et al. Acta Chem. Scand. 53 (1999) 651-669.
[2] K. Sonogashira et al. Tetrahedron Lett. (1974) 4467-4470.

  • Poster
    Conference on Advances and Perspectives in Radiotracer Development, Rossendorf, 07.-08.03.2002

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