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.
Eliminate to activate: Metal‐mediated and ‐catalyzed elimination of β‐ or α‐fluorine proceeds under mild conditions, starting from organometallic intermediates with fluorine substituents on the carbon atoms β or α to the metal centers, respectively. Recently, these elimination processes have been used in the development of a variety of methods for activating C−F bonds.
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.
An efficient two-step method for synthesizing 2-(trifluoromethyl)- and 2-(difluoromethyl)benzoheteroles bearing various substituents was developed. Commercially available HFO-1224yd(
) or HFO-1233yd(
...) underwent the Suzuki-Miyaura coupling with arylboronic acids (acid esters) bearing a nucleophilic moiety at the
position to yield the corresponding β-fluoro-β-(trifluoromethyl)- or β-fluoro-β-(difluoromethyl)styrenes, respectively. Treatment of the obtained styrenes with potassium phosphate induced nucleophilic 5-
-
cyclization to provide the corresponding 2-trifluoromethylated or 2-difluoromethylated indoles and benzofurans, as well as benzothiophenes.
Air‐ and thermally stable tropone–triarylborane 1 : 1 complexes were synthesized in excellent yields by treating tropones, including benzo‐fused derivatives, with an equimolar amount of B(C6F5)3. NMR ...and X‐ray analyses and DFT calculations including nuclear independent chemical shift (NICS) and anisotropy of the induced current density (ACID) studies revealed that the tropone–triarylborane complexes have betaine structures consisting of tropylium and borate moieties and that their aromaticity depends on the number of fused benzene rings.
Air‐ and thermally stable tropone–triarylborane 1:1 complexes were synthesized in excellent yields by treating tropones, including benzo‐fused derivatives, with an equimolar amount of B(C6F5)3. NMR and X‐ray analyses and DFT calculations revealed that the tropone–triarylborane complexes have betaine structures consisting of tropylium and borate moieties and that their aromaticity depends on the number of fused benzene rings.
Nickel‐catalyzed reductive cross‐coupling of allylic difluorides with aryl iodides was achieved via allylic C−F bond activation. Based on this protocol, a series of γ‐arylated monofluoroalkenes were ...synthesized in moderate to high yields with high Z‐selectivities. Mechanistic studies suggest that the C−I bonds of the aryl iodides and the C−F bonds of the allylic difluorides were cleaved via oxidative addition and β‐fluorine elimination, respectively, where the oxidative addition of less reactive C−F bonds was avoided to permit their transformation.
Nickel‐catalyzed reductive cross‐coupling of allylic difluorides with aryl iodides was achieved via allylic C−F bond activation. Based on this protocol, a series of γ‐arylated monofluoroalkenes were synthesized in moderate to high yields. Mechanistic studies suggest that the C−I bonds of the aryl iodides and the C−F bonds of the allylic difluorides were cleaved via oxidative addition and β‐fluorine elimination, respectively.
Rather crafty: 1,1‐Difluoroallenes bearing an aryl group and a cyclopentene moiety undergo indium(III)‐catalyzed Friedel–Crafts‐type cyclization with subsequent ring expansion and dehydrogenation to ...afford fluorinated polycyclic aromatic hydrocarbons in high yields. The introduction of an Ar group was effected by in situ halogenation of the intermediary indium species and a subsequent Suzuki–Miyaura reaction.
Ascending and Descending: A combination of two helical molecules and two twisting covalent axes in the form of a macrocycle conjures an illusory molecular object that has a seemingly impossible ...molecular structure, that is, an endlessly descending circle that consists of an sp2‐carbon network, which can be regarded as the molecular expression of Penrose stairs (see picture).
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