Synthesis of Aryl Fluorides

M.J. Adam, J.M. Berry, L.D. Hall, B.D. Pate, T. Ruth, The cleavage of aryl-metal bonds by elemental fluorine—Synthesis of aryl-fluorides. Can. J. Chem. 61 (1983) 658-660. 

The nucleophilic displacement of halogens in aromatic compounds by fluorine is aided by utilizing an appropriate catalyst. Polymer-supported aminopyridinium salts have been found to be versatile catalysts for the synthesis of aryl fluorides. The advantage of the catalyst is that it can be recycled and used again. l-Chloro-4-nitrobenzene (3) is converted to l-fluoro-4-nitrobenzene (4) in 71 % isolated yield using this method. The catalyst used has the structure 5.91... 

Table 4. Synthesis of Aryl Fluorides by Reaction of Aryltrialkyltin Derivatives with Electrophilic Fluorinating Reagents and with Elemental Fluorine...

The possibility of the synthesis of aryl fluorides by thermal decomposition of diaryliodonium tetrafluorobo-rates was first demonstrated by Van der Puy in 1982 [70]. It was found that the reactions of diphenyliodonium salts with different anions (BF4, CFsCOO", TsO , Cl ) in DMF in the presence of KF upon heating afford fluorobenzene in 11-85% yield. The lowest yield (11%) was observed in the reaction of diphenyliodonium chloride with KF in DMF at 115 °C, while the thermolysis of Ph2l+BF4 in the presence of KF at 160-170 °C without solvent gave PhF in 85% yield. The formation of benzene (2-9%) due to a parallel radical decomposition process was also observed in all these reactions [70],... 

Doebele M, Vanderheiden S, Jung N, Braese S (2010) Synthesis of aryl fluorides on a solid support and in solution by utilizing a fluorinated solvent. Angew Chem Int Ed 49(34) 5986-5988... 

Anbarasan P, Neumann H, Beller M (2010) Efficient synthesis of Aryl fluorides. Angew Chem Int Ed 49(12) 2219-2222... 

SCHEME 7.47 Synthesis of aryl fluorides by treatment of aryl Grignard reagents with F+ [79]. 

The silver-promoted/catalyzed treatment of arylstannanes with electrophilic fluorine was effective method for the synthesis of aryl fluorides [82, 83]. Some of the early reports used an excess of the silver reagents to promote the reactions (Scheme 7.48). F-TEDA-PFg was an effective F+ source for these reactions, and the conditions were remarkably mild. One of the most attractive aspects of this chemistry was the speed of the reactions. 

The Sandmeyer reaction cannot be applied to fluorides (see Secs. 8.6 and 10.4) and the cuprous catalyst is not necessary for the synthesis of aryl iodides for reasons given in Sections 8.6 and 10.6. 

Both aromatic and aliphatic fluoroformates 7 can be readily prepared from phenols or alcohols and carbonyl difluoride and treated with sulfur tetrafluoride without isolation. Hydrogen fluoride evolved in the reaction of hydroxy compounds with carbonyl di fluoride serves as a catalyst for the consecutive reaction with sulfur tetrafluoride.15<)-162 This provides a general, convenient, direct synthesis of aryl and alkyl trifluoromethyl ethers 5 from phenols and alcohols. When the intermediate fluoroformate 7 is isolated prior to treatment with sulfur tetrafluoride, at least one mole equivalent of hydrogen fluoride is necessary to promote the fluorination reaction. 159 163 Representative examples of the conversion of hydroxy compounds 6 into trifluoromethyl ethers 5 via intermediate fluoroformates 7 are given (for other examples 7 -> 5, see Houben-Weyl, Vol. E4, pp 628. 629). 

Friedel-Crafts alkylation has been used in an important synthesis of aryl C-glycosides, which are potent anti-tumor agents, from glycosyl fluorides (equation 99)65 661. The reaction takes place rapidly in dichloromethane, at room temperature using a novel zirconium complex and silver perchlorate combination catalyst. A similar alkylation has been performed by replacing the aromatic compound with either a silyl enol ether or an allylic compound using silver triflate as the catalyst662,663. 

The advantages of the synthesis of aryl halides from diazonium salts will be discussed in detail in Sec. 25.3. Aryl fluorides and iodides cannot generally be prepared by direct halogenation. Aryl chlorides and bromides can be prepared by direct halogenation, but, when a mixture of 0- and p isomers is obtained, it is difficult to isolate the pure compounds because of their similarity in boiling point. Diazonium salts ultimately go back to nitro compounds, which are usually obtainable in pure form. 

For synthesis of ary fluoride is added to the Suzuki and StUU t the catalytic system c prepared by coupling o the other terminus, and accomplished with in s For access to aryl boron or that of aryl iodides ... 

Another more recent synthesis of aryl difluorophosphines involves dehydrofluorination of an aryltrifluorophosphorane with potassium fluoride at 100°-120°C (84). 

A series of new phosphinooxazoline ligands have been recently prepared and tested in the asymmetric Heck reaction. Synthesis of the ligands involved the aromatic nucleophilic substitution of aryl fluorides with phosphide nucleophile generated from the corresponding phosphine and KHMDS (eq 49). The reaction proceeded in good yields, but proved to be more sluggish with electron-rich aryl fluorides and failed completely when the addition of electron-deficient phosphines was attempted. 

Give examples of the use of arenediazonium salts in diazo coupling reactions and in the synthesis of aryl chlorides, bromides, iodides, fluorides, and nitriles. 

Although acid fluorides are a versatile class of compounds, their preparation requires limited kinds of starting compounds and fluorinating agents, which are hard to handle. A new method for the synthesis of acid fluoride by the carbonylation of aryl iodides in the presence of CsF has been reported (Table 5).P9],[30]... 

Feiring AE (1979) Chemistry in hydrogen fluoride. 7. A novel synthesis of aryl trifluoromethyl ethers. J Org Chem 44 2907-2910. doi 10.1021/jo01330a017... 

Historically, aryl fluorides were prepared by either Balz-Schiemann-type reactions or though the Halex process [70-75], Although a number of these procedures were quite successful, many of them required the use of toxic reagents or harsh conditions. To address these issues and provide practical routes to aryl fluorides, a host of alternative protocols have been developed [6, 76-78]. In addition to this work, a number of methods for the synthesis of aryl halides have been developed. The following sections will highlight several practical versions. 

---