Transition‐Metal‐Mediated and ‐Catalyzed C−F Bond Activation by Fluorine Elimination

Abstract

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.

Regioselective, nucleophilic activation of C F bonds in o-fluoroanilines

“…In addition to pharmaceutically-active compounds, compounds containing radioisotope 18 F can be used in the bioimaging technique positron emission tomography (PET). 9,11 Figure 1.2: Examples of pharmaceuticals with fluorinated aniline functionalities.…”

Defluoroalkylation of sp3 C−F Bonds of Industrially Relevant Hydrofluoroolefins

“…[13][14][15] In contrast, methods for selective carboncarbon bond formation from vinylic trifluoromethyl groups are far less well advanced, likely due to the difficulty in controlling the reactivity of the adjacent C=C p-system. [16][17][18][19] Ito andc o-workers have reportedt he enantioselective defluoroalkylation of trifluoromethyl-substituted alkenes. [20] The key step in this report was the defluoroborylation of the substrateu sing ac hiral copper(I) catalyst.B oth racemic and enantioselective variants of this reactionh ave been widely studied.…”

“…In ar epresentative case,r eaction of 1 with 3,3,3-trifluoropropene is characterised by as hift of the resonance in the 11 BNMR spectrum from d B = 0.7 (br) ppm to d B = À21.4 (t, 1 J BH = 85 Hz) ppm. The product 2a is characterised by diagnostic 19 FNMR resonances at d F = À96.1 (d, 2 J FF = 65 Hz) and À99.1 (d, 2 J FF = 65 Hz) ppm. In the case of HFO-1234yf, two isomersd erived from substitution at the terminal (gÀ2c)a nd internal (bÀ2c')p ositionw ere observed in a9 :1 ratio.…”

“…Reaction of E-HFO-1234ze with 1 followedb ya ddition to naphthaldehyde and work-up led to the isolation of 3a.T he same product that formed fromt he defluoroalkylation of 3,3,3-trifluoropropene with this aldehyde. Monitoring the reaction as af unctiono f time allowed characterisation of the intermediate 2d.T he structure of 2d was furthers ubstantiated by derivatisation to form the 4-coordinate adduct 2d·DMAP.C ompound 2d·DMAP is af our-coordinate boron fluoride characterisedb yd iagnostic resonances at d B =+6.8 ppm and d F = À93.9 (d, 2 J FF = 63 Hz), À98.9 (d, 2 J FF = 63 Hz) and À188.4 (broad,B F) in the 11 BNMR and 19 FNMR spectrum, respectively. 2d is proposed to derive from ad ouble C-F bond functionalisation.…”

Tailoring Diindenochrysene through Intramolecular Multi‐Assemblies by C−F Bond Activation on Aluminum Oxide

“…Geodesic polyarenes constitute au nique groupo fp olycyclic aromatic hydrocarbons (PAHs) that contain pentagonsa nd possess ac oncave surface, [1][2][3] which formally can be considered as fragments of the fullerenec ages.A lthough the synthesis of the smallest representative, corannulene, has been known for more than fifty years, [4,5] organic chemistry still faces al ack of approaches that allow for af acile synthesis of this class of molecules. Amongt he main reasonsf or this are the substantial strain energies,w hich need to be overcome to create bowl-shaped geometry.T he following existinga p-proaches, such as flash-vacuum pyrolysis (FVP), [6] Pd-catalyzed arylation, [7][8][9] and coupling through CÀFb ond activation, [10][11][12][13][14] must be mentioned. Althought he first two methods face both low group tolerance and moderate yields, the last one often possess highs electivity and frequentlyl eads to nearly quantitative yields showingt olerance to variousf unctional groups.…”