The activation of carbon-fluorine (C-F) bonds is an important topic in synthetic organic chemistry. Metal-mediated and -catalyzed elimination of β- or α-fluorine proceeds under milder conditions than oxidative addition to C-F bonds. The β- or α-fluorine elimination is initiated from organometallic intermediates having fluorine substituents on carbon atoms β or α to metal centers, respectively. Transformations through these elimination processes (C-F bond cleavage), which are typically preceded by carbon-carbon (or carbon-heteroatom) bond formation, have been increasingly developed in the past five years as C-F bond activation methods. In this Minireview, we summarize the applications of transition-metal-mediated and -catalyzed fluorine elimination to synthetic organic chemistry from a historical perspective with early studies and from a systematic perspective with recent studies.

The disfavored 5-endo-trig cyclizations have been accomplished for 1,1-difluoro-1-alkenes with nitrogen, oxygen, sulfur, and carbon nucleophiles by taking advantage of the properties of fluorine. b,b-Difluorostyrenes bearing tosylamido, hydroxy, or methylsulfinyl group at the o-position undergo intramolecular nucleophilic substitution with a loss of the vinylic fluorine, leading to 2-fluorinated indole, benzo[b]furan, and benzo[b]thiophene in high yields. 1,1-Difluoro-1-butenes bearing homoallylic tosylamido, hydroxy, mercapto, or iodomethyl group also successfully cyclize via a 5-endo-trig process with the in situ generated intramolecular nucleophiles to afford 2-fluoro-2-pyrroline, 5-fluoro-2,3-dihydrofuran, 5-fluoro-2,3-dihydrothiophene, and 1-fluorocyclopentene. The two vinylic fluorines proved to be essential and play a critical role in these 'anti-Baldwin' cyclizations.

The nickel-mediated [3+2] cycloaddition of 2-trifluoromethyl-1-alkenes with alkynes afforded fluorine-containing multi-substituted cyclopentadienes in a regioselective manner. This reaction involves the consecutive two C-F bond cleavage of a trifluoromethyl or a pentafluoroethyl group through β-fluorine elimination.

The nickel-catalyzed defluorinative coupling of 2-trifluoromethyl-1-alkenes and alkynes with the aid of Et 3 SiH provides 1,1-difluoro-1,4-dienes under mild reaction conditions. This reaction involves selective allylic C(sp 3 )−F bond activation via β-fluorine elimination from nickelacyclopentenes.

Activation of the sp C-F bond in 2-trifluoromethyl-1-alkenes was accomplished through treatment with a Lewis acid. In the presence of an equimolar amount of EtAlCl , the (trifluoromethyl)alkenes readily underwent an S 1'-type reaction with arenes through a Friedel-Crafts-type mechanism via elimination of a fluoride ion to afford 3,3-difluoroallylated arenes in good yields. This selective activation of one C-F bond of the CF group provides a synthetic method for accessing biologically and synthetically important 1,1-difluoro-1-alkenes.

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Replacing the fluorine: 3‐Fluorinated pyrazoles were regioselectively synthesized by sequential substitution reactions of 2‐trifluoromethyl‐1‐alkenes (see scheme). SN2′‐type reactions of 2‐trifluoromethyl‐1‐alkenes with deprotonated tert‐butoxylcarbonyl‐ or arylhydrazines afforded 1,1‐difluoro‐1‐alkenes, which were tosylated and then treated with NaH to give the desired 3‐fluoropyrazoles.

The unique properties of fluorine substituents, leaving groups that also stabilize an α carbocation, are exploited in a high‐yielding synthesis of substituted [4]‐ to [6]helicenes in three or four steps from commercially available compounds: Two fused benzene rings are constructed in the title reaction of readily prepared 1,1‐difluoro‐1‐alkenes containing two aryl groups followed by dehydrogenation (see scheme).