Development of N-F fluorinating agents and their fluorinations: Historical perspective

Abstract

This review deals with the historical development of all N-F fluorinating agents developed so far. The unique properties of fluorine make fluorinated organic compounds attractive in many research areas and therefore fluorinating agents are important. N-F agents have proven useful by virtue of their easy handling. This reagent class includes many types of N-F compounds: perfluoro-N-fluoropiperidine, N-fluoro-2-pyridone, N-fluoro-N-alkylarenesulfonamides, N-fluoropyridinium salts and derivatives, N-fluoroquinuclidium salts, N-fluoro-trifluoromethanesulfonimide, N-fluoro-sultams, N-fluoro-benzothiazole dioxides, N-fluoro-lactams, N-fluoro-o-benzenedisulfonimide, N-fluoro-benzenesulfonimide, 1-alkyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane salts, N-fluoropyridinium-2-sulfonate derivatives, 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane salts, N-fluorodinitroimidazole, N-fluoro-trichloro-1,3,5-triazinium salt, N-F ethano-Tröger’s base derivatives, N-fluoro-methanesulfonimide, N-fluoro-N-arylarenesulfonamides, bisN-F salts such as N,N’-difluorobipyridinium salts and N,N’-difluoro-1,4-diazoniabicyclo[2.2.2]octane salts, and their many derivatives and analogs, including chiral N-F reagents such as optically active N-fluoro-sultam derivatives, N-fluoro-alkaloid derivatives, DABCO-based N-F derivatives, and N-F binaphthyldisulfonimides. The synthesis and reactions of these reagents are described chronologically and the review also discusses the relative fluorination power of each reagent and their mechanisms chronicling developments from a historical perspective.

Ring-opening fluorination of bicyclic azaarenes

“… 12 The use of other non-pyridinium based electrophilic fluorinating agents such as NFSI and Selectfluor® gave fluorinated products in high yields (entries 4 and 5). 13 …”

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

“…In the search for solid reagents compatible with mechanochemical techniques, we became interested in evaluating the behavior of N-fluorobenzenesulfonimide (NFSI) under ball-milling conditions. NFSI is a colorless crystalline powder (mp 114-116 °C), bench-stable, and an easy-to-handle reagent, which, due to its commercial availability, has been extensively used as a fluorinating agent in solution [7][8][9]. Additionally, NFSI has also been explored as an oxidant, amidation reagent [9][10][11], and phenylsulfonyl group transfer reagent [12,13].…”

anti‐Markovnikov Iodofluorination of Alkenes

“…Many N−F type reagents, such as Selectfluor, N ‐fluorobenzenesulfonimide (NFSI) and N‐fluoropyridinium salts, have served as mild fluorination reagents and can be considered as “F + ” equivalents [3] . Although the mechanism for fluorination with these N−F reagents remains a subject of considerable debate, as to whether a single‐electron transfer (SET) or a nucleophilic substitution (S N 2) mechanism is operating, [3c–e,4] the reagents have been widely used for the incorporation of a fluorine atom into a wide range of substrates, including arenes, [2j,5] alkenes [6] and alkanes [7] . Despite these outstanding accomplishments, convenient anti ‐Markovnikov fluorination of alkenes remains largely unexplored by using the N−F reagents.…”