Fluoroarenes aromatic substitution

Due to its strong activating effect in nucleophilic aromatic substitutions and to the possibility of its removal by decarbonylation, the aldehyde function has been used for the preparation of [ F]fluoroarenes not bearing electron-withdrawing substituents. Decarbonylations, possible in the presence of Pd/C [ 161 ], are more efficient in terms of time (15 min vs 1 h) and yields (80%) when using Wilkin-... 

Suzuki and co-workers achieve aromatic substitution of fluoroarenes with a variety of aldehydes in good yields [91, 92], Imidazolilydene carbene formed from 143 catalyzes the reaction between 4-methoxybenzaldehyde 22a and 4-fluoroni-trobezene 141 to provide ketone 142 in 77% yield (Scheme 20). Replacement of the nitro group with cyano or benzoyl results in low yields of the corresponding ketones. The authors propose formation of the acyl anion equivalent and subsequent addition to the aromatic ring by a Stetter-like process forming XXVIII, followed by loss of fluoride anion to form XXIX. 

Alkylation of Nitrile Derivatives. Tertiary benzylic nitriles were prepared from aryl fluorides and secondary nitrile anion. In the presence of 4 equiv of nitrile and 1.5 equiv of a base, the nucleophilic aromatic substitution of fluoroarenes led to tertiary benzylic nitriles (eq 36). KHMDS was the best base for this reaction, as LiHMDS and NaHMDS provided lower yields. The desired product was not observed when CS2CO3, LDA, or f-BuOK were used. "With KHMDS, the reaction proceeded in high yields with a variety of substrates. 

A comparison of the yields of para-substituted [18F]fluoroarenes indicate that (i) acetyl hypofluorite is an inferior fluorination agent for the fluorodegermylation reaction and (ii) the aromatic substituents have considerable influence over the reactivity of the fluorination. A decrease in the fluorodegermylation yield was observed with electron-withdrawing aromatic substituents. The electrophilic aromatic degermylation reaction is thought to proceed via a cr-complex intermediate (Scheme 3). It has been hypothesized that the yield of aryl fluoride is influenced to some extent by the aromatic substituents ability to stabilize the cr-complex intermediate. 

The arylation of fluoride with diaryliodonium salts has been extensively investigated because of the need for fluorine-18 labeled (hetero)aromatics in positron emission tomography (PET). [ F]Fluoroarenes with a wide range of substitution patterns can be prepared from advanced diaryliodonium salts at high temperatures in short reaction times, which is important because of the short half-life of F (110 min). Fluorination and radiofluoiination of diaryliodonimn salts have been reviewed several times in recent years [138—140], as have other strategies towards... 

---