Fluorodemetallation

The selective electrophilic aromatic substitution carried out by displacement of a metallic substituent (Hg, Sn) ( F-fluorodemetallation) using [ F]p2 or [ F]AcOF remains a method of choice to introduce a fluorine atom on a specific position. In the early preparations of [6- F]fluoro-L-DOPA, the reaction of a 6-substituted mercuric derivative with [ F]acetyl hypofluorite yielded the expected compound in 11 % yield [73,74]. Reaction of a mercuric precursor, free or on a modified polystyrene support P-CH2-COOHg(DOPA precursor) allows the preparation of [ F]fluoro-L-DOPA in an overall yield up to 23 %. The polymer supports are easily prepared, require no special treatment for storage and are convenient to use in automated production [75]. 

Fluorination of aromatic rings (other than those via carbanions described above) consists principally of fluorodehydrogenation and fluorodemetallation reactions, both ofwhich are thought to proceed via an arenium ion mechanism (Scheme 25) [85]. 

Scheme 25. The arenium ion mechanism of electrophilic fluorination of aromatic rings via fluorodehydrogenation or fluorodemetallation reactions.

The consistent poor regioselectivity in direct aromatic electrophilic fluorination has privileged the use of fluorodemetallation reactions. Tin clearly appears to... 

As has been exemplified in this chapter, fluorinations with fluorine-18 can be classified into two categories (1) the nucleophilic reactions, which usually involve no-carrier-added [ F]fluoride of high-specific radioactivity as its Kf FIF-K complex and include substitutions in the aliphatic and the /lomoaromatic series and (2) the electrophilic reactions, which mainly use moderately low-specific radioactivity molecular [ F]fluorine, or other reagents prepared from it, such as acetyl [ F] hypofluorite, and include addition across double bonds, reactions with carbanions and especially fluorodehydrogenation and fluorodemetallation reactions. 

H.H. Coenen, S.M. Moerlein, Regiospecific aromatic fluorodemetallation of group IVb metalloarenes using elemental fluorine or acetyl hypofluorite, J. Fluor. Chem. 36 (1987) 63-75. 

The fluorination of trimethylgermanium aromatics with elemental fluorine or acetyl hypo-fluorite results in fluorodemetalation to the corresponding fluoroaromatic compounds.The yields obtained are generally lower than those observed for the corresponding tin derivatives due to the stronger C-Ge bond this coupled with the high cost of germanium has resulted in little research in this area. 

Fluorodemetallation. Replacement of silyl and stannyl substituents from aryl-silanes and )3-trialkylstannyl enones is rapid. The latter reaction is effected in the presence of AgOTf as catalyst. 

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