Nucleophilic substitution on fluoroaromatic rings

Fluorine-activated aromatic nucleophilic substitutions are highly useful for the syntheses of functionalized and multisubstituted aromatic compounds via both inter- and 

The sterically small and inductively strong fluorine atom must play a crucial role at the last step of introducing a sixth substituent on penta-substituted benzenes. Hexa-substituted phenylthiobenzenes(34) [9],vinylthiobenzenes(35) [10],pyridinylbenzenes(36) [ 11 ],phe-noxybenzenes (37) [12], trifluoroethoxybenzenes (38) [12], and pentafluoroethylbenzenes 

Fluorine-activated coupling reagents for peptide synthesis 

Alkenyl and arylfluorides (F—C=C) are reactive and so one can imagine that the moiety of (F—C=X) (X=0, NR) should also be reactive. Acyl fluorides have greater stability than the corresponding chlorides toward neutral oxygen nucleophiles such as water and methanol, but appear to be equal reactivity toward anionic nucleophiles and amines [ 1 ]. Cyanuric fluoride 2 is a mild reagent for the preparation of acyl fluorides [2]. The protected amino acids can be transformed into the corresponding amino alcohols without racemization by the reduction of acyl fluorides 3 [3]. 

Generation of acyl fluorides of the protected amino acids and the in situ coupling for the peptide synthesis have been achieved by the use of fluoroformamidium salts, a new class of coupling reagents. Both 5 and 6 are easily prepared, and are nonhygroscopic, stable to handling under ordinary conditions, but reactive enough to transform carboxylic acids 8 to acyl fluorides 9 under very mild conditions, which can be coupled with amine 10 [4, 5], 

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Uneyama, K. Nucleophilic substitution on fluoroaromatic ring. Organofluorine Chemistry, Blackwell Publishing Oxford, UK, 2006. 

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