Electrophilic Fluorination withN–FReagents

Abstract

The synthesis of selectively fluorinated molecules is an important challenge in organic chemistry. This topic has received considerable attention because of the utility of fluorinated compounds in a wide variety of disciplines. There are three types of fluorination depending on whether the fluorine atom is radical, anionic, or cationic. Fluorine radicals are of little synthetic use because of the difficulties in controlling their reactivity. Fluorine is utilized in nucleophilic as well as electrophilic fluorinations Molecular fluorine is the simplest reagent of this type, however, its safe handling is difficult. Stable, selective reagents are crucial to the development of electrophilic fluorination. N‐F reagents have emerged as generally safer and easier to handle selective sources of electrophilic fluorine. N‐F reagents offer a range of fluorinating powers and some are available commercially. Two classes are known: neutral N‐F reagents and quaternary ammonium N‐F reagents (quaternary salts are usually the more powerful). N‐F reagents popularity arises because they posses a long shelf life, several are commercially available, and they can be handled safely in glassware. The drawback is the preferential use of molecular fluorine for their preparation. This article deals with the preparation and the use of all types of electrophilic fluorinating agents possessing the N‐F moiety.

Strategies for nucleophilic, electrophilic, and radical trifluoromethylations

“…A wide range of Lewis acids as well as combinations of Lewis acid and ligand were screened in the reaction with non-enolisable aromatic aldehydes. TiF 4 /DMF, Ti(OPr-i) 4 /DMF, and Cu(OAc) 2 /dppe/toluene were among the best initiators evaluated in the nucleophilic trifluoromethylation of aromatic aldehydes (Scheme 13). Obviously, the next step will be the screening of chiral ligands for enantioselective nucleophilic trifluoromethylation reaction.…”

“…Ketone titanium ate enolates were generated from ketone and LDA or from the corresponding silyl enol ether and n-BuLi (Scheme 46-a). The use of excess amounts of LDA and Ti(O-iPr) 4 in the generation of titanium ate enolates from cyclic and acyclic aliphatic ketones is crucial to obtain moderate to good yields [136,137]. Highly basic lithium enolates are also applicable to radical trifluoromethylation.…”

“…By contrast, fluorine atom(s) can be introduced in a late stage of a synthetic plan, basically, either by ionic (nucleophilic or electrophilic), or radical reaction. The introduction of a single fluorine atom has received considerable attention due to the development of easy-to-handle fluorinating agents and efficient experimental conditions [4]. Monofluorination is a carbon-fluorine bond forming reaction.…”

Metal-free synthesis of α,α-difluorocyclopentanone derivatives via regioselective difluorocyclopropanation/VCP rearrangement of silyl dienol ethers

“…[3][4][5][6] However, these methods suffer from drawbacks relating to the requirement of time-consuming processes such as carbon-skeleton construction and fluorine installation as well as the use of expensive fluorinating reagents.…”

Development and applications of novel HF-based fluorination reagents : DMPU-HF.

“…Over the years a variety of synthetic protocols for this class of compounds have been developed. They can be prepared from their corresponding carbonyl compounds or through various derivatives such as oximes and dithiolanes, 62 electrophilic fluorinations of unsaturated compounds and enolates, 63 free-radical additions of halodifluoroalkanes to olefins, 64 and nucleophilic difluoromethylations of aldehydes and ketones. 65 Other approaches involve methods that utilize fluorinated compounds as synthons.…”