Radical Fluorination

Historically, only three atomic fluorine sources were accessible for radical fluorination: fluorine (F₂), hypochlorites (O–F based reagents), and XeF₂.

 Fluorine (F₂) was the most common source of atomic fluorine during this period. 

When compared to electrophilic and nucleophilic procedures, radical fluorination was hindered by its high reactivity as well as the difficulty in handling F₂ and the hypochlorite salts.

Because of the discovery of the capacity of electrophilic N–F fluorinating agents to operate as atomic fluorine sources, radical fluorination has experienced a resurgence in recent years.

Since then, a number of other techniques for the radical production of C–F bonds have been established. 

Using carboxylic acids and boronic acid derivatives as starting materials, radical addition to alkenes, as well as C–H and C–C bond activations, radical intermediates have been synthesised. 

New sources of atomic fluorine, such as metal fluoride complexes, are being discovered all the time.

Due to the fact that radical fluorination is an exergonic reaction, it is not thermodynamically advantageous.

Fluorinating reagents are useful tools in the synthesis of medicinal and agricultural chemicals, as well as other organic molecules. 

Due to the limited number of naturally occurring fluorine-containing compounds, it is important to incorporate fluorinated organic molecules into the syntheses at a certain step.

Decarboxylative Fluorination

In the presence of NFSI and Selectfluor, the thermolysis of t-butyl peresters has been employed to create alkyl radicals, which have been shown to be effective.

The intermediates of the radicals were fluorinated with high efficiency, revealing the capacity of the two electrophilic fluorinating agents to transfer fluorine to alkyl radicals in an effective manner.

Carboxylic acids can be employed as radical precursors in radical fluorination processes, and they are very effective. 

To produce fluoro decarboxylation, metal catalysts such as silver and manganese have been utilised in conjunction with organic solvents.

 It is also possible to activate the fluoro decarboxylation of carboxylic acids through the use of photoredox catalysis. 

More particularly, it has been demonstrated that phenoxyacetic acid derivatives undergo fluoro decarboxylation when subjected to ultraviolet irradiation or when exposed to ultraviolet irradiation with the aid of a photosensitizer.

Sources of Atomic Fluorine

Fluorine gas

Fluorine gas (F₂) can operate as both an electrophilic and an atomic source of fluorine, depending on the situation.

Because of the weak F–F bond strength (36 kcal/mol (150 kJ/mol)), homolytic cleavage is possible. 

It should be noted, however, that the reaction of F₂ with organic molecules is highly exothermic, and it can result in nonselective fluorinations and C–C cleavage, as well as explosions.

Reagents for the O–F reaction

Hypo fluorites have a weak O–F bond, which makes them difficult to work with. 

In the case of trifluoromethyl hypofluorite (CF₃OF), it is calculated to be 43.5 kcal/mol (182 kJ/mol) in energy density. 

By interacting separately created ethyl radicals from ethene and tritium in the presence of trifluoromethyl hypofluorite, it is proved that trifluoromethyl hypofluorite can transfer fluorine to alkyl radicals.

XeF₂

Since its discovery, xenon difluoride (XeF₂) has primarily been utilised in radical fluorination reactions, such as radical decarboxylative fluorination.

 In this Hunsdiecker-type reaction, xenon difluoride is used to generate both the radical intermediate and the fluorine transfer source, which are both produced by the reaction.

XeF₂ can also be used to generate aryl radicals from arylsilanes, as well as to act as an atomic fluorine source to produce aryl fluorides by combining with fluorine atoms.

Reagents with the letters N–F

However, it has recently been proven that selectfluor and N-fluorobenzenesulfonimide (NFSI) are capable of transferring fluorine to alkyl radicals, which is in contrast to their typical employment as electrophilic sources of fluorine.

As fluorine transfer agents for alkyl radicals, they are now widely used in industry.

Other sources

There have been several reports of radical fluorination utilising bromine trifluoride (BrF₃) and fluorinated solvents, among other methods. 

Following recent developments in radical fluorination, it has been demonstrated that in-situ produced metal fluoride complexes can also function as fluorine transfer agents to alkyl radicals.

Fluorination at the Atomic Level

Fluorination reactions of organic compounds involving radicals or radical ions are discussed. 

Fluorination techniques done through thermal or photoinduced radical/electron transfer mechanisms are examples of these technologies. 

Fluorination reactions of numerous families of organic compounds, including aliphatic and aromatic substrates, will be discussed in this context, among other things.

Fluorination is the procedure that allows plastic containers to be used to package a wide range of chemicals and solvents that would otherwise have to be packaged in glass.

 Fluorination is the technique that allows plastic containers to be used to package many different chemicals and solvents. 

The absence of fluorination can cause plastic containers to panel, distort, and degrade, resulting in product damage.

Conclusion

Fluorinated chemicals are important in pharmaceutical, agrochemical, and material chemistry, and the development of several methods for electrophilic and nucleophilic fluorination has resulted as a result of their widespread use. 

Radical fluorination is a promising supplementary method, but it has been limited in its application due to a scarcity of selective radical fluorinating agents in the marketplace. 

As a result of the recent discovery of easier-to-handle atomic fluorine sources, there have been major advancements in radical fluorination over the past several years.

Fluorinating agents are those in which the fluorine atom, which has a deficiency in electrons, acts as a chemically active species. 

An additional fluorinated building block is utilised as a fluorine source because it contains both a fluorine atom and an interchangeable functional group in a molecule, which makes it a versatile fluorine source.