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Synthesis 2023; 55(06): 857-867
DOI: 10.1055/a-1983-5059
short review

Transformation of Tetrafluoroethylene Using Transition-Metal Complexes

Ryohei Doi
,
Yuyang Zhou
,
Sensuke Ogoshi∗
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Abstract

Tetrafluoroethylene (TFE) is an industrial organofluorine feedstock that is used predominantly to fabricate fluorinated polymers. TFE exhibits excellent potential as a building block for synthesizing organofluorine compounds, which are increasingly gaining attention as functional materials, pharmaceuticals, and agrochemicals. In particular, the use of transition-metal complexes in the transformation of TFE is of great interest, considering their widespread use in syntheses of organofluorine compounds over the last few decades. This review highlights studies on the transformation of TFE into organofluorine compounds using transition-metal complexes, except for polymerizations. Our review covers cross-coupling reactions via C–F bond cleavage, fluoroalkylation reactions, multicomponent couplings, and olefin metathesis.

1 Introduction

2 Palladium Complexes

3 Copper Complexes

4 Nickel Complexes

5 Ruthenium Complexes

6 Rhodium Complexes

7 Summary and Perspective


#

Key words

tetrafluoroethylene - palladium - copper - nickel - ruthenium - rhodium - organofluorine compounds
1

Introduction

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Ryohei Doi (left) was born in 1989 in Kobe, Japan. In 2016, he obtained his Ph.D. from Osaka University in 2016 under the direction of Prof. Sensuke Ogoshi. During his postgraduate studies, he spent some time in the group of Prof. Brian M. Stoltz (2015) at the California Institute of Technology. In 2016, he joined Prof. Sato’s group at Hokkaido University as an Assistant Professor. In 2021, he returned to the Ogoshi group as an Assistant Professor. He is currently working on synthetic studies of organofluorine compounds using transition-metal complexes. Yuyang Zhou (center) is a postgraduate student in the Ogoshi group at Osaka University (Japan). He received his B.Sc. degree from Osaka University in 2022. His current research focuses on the synthesis of fluoroalkyl compounds using copper complexes. Sensuke Ogoshi (right) received his Ph.D. from Osaka University in 1993 under the tutelage of Prof. Shinji Murai. During his postgraduate studies, he also worked with Prof. Lanny S. Liebeskind at Emory University (1991). In that year he joined the faculty at Osaka University as an Assistant Professor in the group of Prof. Hideo Kurosawa. In 1999, he was promoted to an Associate Professor, and in 2007 to Full Professor. In 1996–1997, he received JSPS Fellowship for Research Abroad to work in the research group of Prof. Jeffery M. Stryker at the University of Alberta (Canada). His work has been commended by several accolades, which include the CSJ Award for Young Chemists (1999) and The Japan Chemical Society Award for Creative Work (2013).

TFE may be somewhat unfamiliar to most synthetic chemists, despite its simple structure: all four hydrogen atoms of ethylene are replaced by fluorine atoms. TFE is produced on an industrial scale as a monomer for various fluorinated polymers. Given its extensive production and structural simplicity, why is TFE then arguably so unfamiliar to most synthetic chemists? The answer lies most likely in the sensitivity of TFE to air and shock.[1] [2] Furthermore, trace amounts of radical sources can initiate its polymerization, which often results in catastrophic pipeline jams. It is thus feasible to assume that the difficulties associated with handling TFE have tamed the appetite of the synthetic community for TFE.

Yet, despite these obstacles, there are obvious merits to the use of TFE in organic synthesis that should not be underestimated. Organofluorine compounds represent attractive synthetic targets in materials science, pharmaceuticals, and agrochemicals. Due to its simplicity, TFE is an ideal building block for the introduction of an organofluorine moiety into a variety of organic compounds. While other small gaseous fluorinated molecules have been employed in the synthesis of fluorinated organic compounds, the Montreal Protocol led to the abandonment of many of these, including 1,1,1,2-tetrafluoroethane (HFC-134a), due to their high global-warming potential or ozone-layer-depleting effect. In contrast, TFE has a low global warming potential and low ozone layer depletion effect. The global supply of TFE will continue due to its relatively minor environmental concerns and high demand as a fluoropolymer constituent. Therefore, the use of TFE represents a sustainable method for synthesizing organofluorine compounds.

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Figure 1 Synthetic methods for the generation of TFE on an industrial (A) and laboratory scale (B–D)

Both industrial- and laboratory-scale methods for the preparation of TFE have been developed. For industrial production, the thermolysis of chlorodifluoromethane (HCFC-22) has been established. Heating HCFC-22 to ~800 °C generates difluorocarbene that undergoes homocoupling to generate TFE, which is subsequently purified by distillation (Figure [1]A).[3] Thereafter, pure TFE can be used via a pressure cylinder. In some cases, the cylinder contains a stabilizer such as terpenes.[4] For laboratory use, several preparation protocols have been reported. For instance, the thermal depolymerization of poly(tetrafluoroethylene) furnishes TFE gas (Figure [1]B), although the reaction requires relatively high temperatures (600–650 °C).[5] Hu et al. have reported the treatment of TMSCF3 with sodium iodide as a facile preparative method for the generation of TFE (Figure [1]C).[6] Thrasher and co-workers have developed a thermolysis of a pentafluoropropanoate salt to give a gaseous mixture of TFE and CO2 (Figure [1]D).[7] These methods enable research on the synthetic chemistry of TFE in the laboratory: The door has already been opened!

In this review, we summarize the transformation of TFE into small molecules (not polymers) using transition-metal complexes.[8] The products derived from TFE are fluoroalkenes or tetrafluoroethylene-containing compounds.[9] We have classified the reactions according to the metal used, i.e., palladium (Section 2), copper (Section 3), nickel (Section 4), ruthenium (Section 5), or rhodium (Section 6). Some reactions are catalytic, while others are stoichiometric.


# 2

Palladium Complexes

Contemporary organic chemistry relies heavily on palladium complexes, mainly as catalysts. One of the major roles of palladium in synthetic organic chemistry is that of a catalyst for cross-coupling reactions.[10] [11] A catalytic cycle usually consists of the oxidative addition of aryl or alkenyl halides, transmetalation with an organometallic reagent, and reductive elimination to release the cross-coupling product. Aryl or alkenyl iodides and bromides have been used as electrophiles due to the relatively low strength of the carbon–iodine or carbon–bromine bond, which facilitates oxidative addition. State-of-the-art catalysts enable the use of aryl or alkenyl chlorides, which are generally cheaper and more readily available than the corresponding iodides or bromides.[12]

Cross-coupling reactions of aryl or alkenyl fluorides have also been developed, although most examples use activated aryl fluorides.[13] Therefore, applying a palladium-catalyzed cross-coupling strategy for functionalizing the C(sp2)–F bond of TFE would be desirable for synthesizing a variety of trifluorovinyl compounds.

2.1

Cross-Coupling Using Arylzinc Reagents

Trifluorovinyl-substituted arenes are important fluorinated monomers.[14] [15] For instance, an ion-exchange membrane uses (trifluorovinyl)arenes as a monomer. These compounds have been produced using the corresponding trifluorovinyllithium reagents generated by the treatment of 1,1,1,2-tetrafluoroethane (HFC-134a), which has a high global warming potential, with n-butyllithium at low temperatures. TFE would be a valuable alternative to HFC-134a, especially with respect to sustainability. Dixon has reported the direct coupling of organometallic species with TFE.[16] However, the trifluorovinyl product is also a good electrophile, which leads to the formation of multisubstituted products. In addition, strong nucleophiles such as organolithiums or Grignard reagents often lack broad functional group tolerance.

Our group has developed cross-coupling reactions of TFE with arylzinc reagents via C–F bond cleavage.[17] Arylzinc reagents show better functional group tolerance than the corresponding organolithium or Grignard reagents. Our group envisioned that these cross-coupling reactions could be achieved if palladium complexes, which are frequently used for cross-coupling reactions, could cleave one of the C–F bonds of TFE. Following the work of Kemmitt, who used lithium iodide to promote the oxidative addition of TFE to a Pt(0) complex,[18] we prepared Pd(0)–TFE complex 1 and treated it with LiI (Scheme [1]A). The reaction proceeded smoothly at room temperature to give trifluorovinyl palladium complex 2 in quantitative yield. The driving force of this reaction is the thermodynamically favored formation of lithium fluoride, which is insoluble in most solvents and precipitates from the reaction medium. We later clarified that other Lewis acids, such as MgBr2 and BF3, are also good promoters for this process.[19] These stoichiometric reactions led us to attempt catalytic cross-coupling reactions. In the presence of 0.01 mol% Pd catalyst and LiI, the cross-coupling reaction of TFE with an arylzinc reagent furnished the corresponding trifluorovinyl compound in good yield (Scheme [1]B).

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Scheme 1 Oxidative addition of TFE to Pt(0) using LiI (A) and Pd-catalyzed cross-coupling reaction of organozinc reagents with TFE (B, C)

A plausible reaction mechanism is shown in Scheme [1]C. Coordination of TFE to Pd(0) complex I gives TFE complex II. It should be noted here that TFE is highly electrophilic, leading to stabilization of the alkene–Pd bond via strong backdonation of the d 10 metal center. LiI promotes the oxidative addition step to generate a trifluorovinyl complex III. Transmetalation of intermediate III with the arylzinc reagent followed by reductive elimination releases the trifluorostyrene and regenerates the Pd(0) catalyst. When we tested alkylzinc reagents, the reaction led to the formation of a hydrodefluorinated product or a (trifluorovinyl)zinc reagent, which can be interpreted in terms of a reluctant reductive elimination of the alkyl palladium complex.[20] The alkylation reaction was thus achieved using a Grignard reagent without a metal catalyst.


# 2.2

Cross-Coupling Reactions Using Arylboron Reagents

Our group next developed the cross-coupling of TFE with arylboronic acid esters. Boron reagents are advantageous compared to the corresponding zinc reagents with respect to their stability in air. Pd-catalyzed cross-coupling reactions using an arylboronic acid (Suzuki–Miyaura coupling) usually require the addition of a base to activate the boron nucleophiles.[21] We conceived the idea that cross-coupling reactions of TFE with an arylboron reagent could potentially proceed without an external base since the palladium fluoride would be susceptible to transmetalation with a fluorophilic boron reagent. Therefore, we first heated Pd–TFE complex 5 to 100 °C and observed trifluorovinyl palladium complex 6 in the reaction mixture using 19F and 31P NMR spectroscopy (Scheme [2]A). Isolated complex 6 reacted with phenylboronic acid ester without an external base, producing α,β,β-trifluorostyrene in 75% yield. The importance of the Pd–F moiety is apparent from a comparison of the results of other trifluorovinyl palladium complexes bearing chloride, bromide, or iodide, which did not afford any coupling products. Based on these results, we conducted the catalytic reaction of TFE with arylboronic acid esters to give the corresponding trifluorovinyl compounds without the addition of base (Scheme [2]B). An optimization study revealed that PiPr3 is the best ligand for this catalytic reaction.

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Scheme 2 Base-free cross-coupling of TFE with arylboronic acid esters

# 2.3

Cross-Coupling Using Arylsilicon Reagents

Subsequently, we tested the reactivity of organosilicon reagents.[22] Treatment of trifluorovinyl palladium complex 6 with PhSi(OMe)3 furnished a mixture of 4 and trifluoroethylene (7; Scheme [3]). Compound 7 was generated via the transmetalation of a methoxy group, β-hydrogen elimination, and a reductive elimination. When we performed a catalytic reaction using PCy3 as the ligand at 100 °C, the desired 4 was obtained in 73% yield after 25 h. Monitoring the reaction mixture using 19F NMR spectroscopy indicated that the reaction is an autocatalytic process. We assumed that silyl fluoride generated in situ promotes the catalytic reaction. In fact, when we added 10 mol% FSi(OEt)3 as an additive, significant acceleration of the reaction was observed.

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Scheme 3 Base-free cross-coupling of TFE with organosilicon reagents

#
# 3

Copper Complexes

Fluoroalkyl copper complexes are useful reagents to introduce a fluoroalkyl chain into organic compounds. Here, we use the term ‘fluoroalkyl complex’ to refer to metal complexes that contain an M–CF2 moiety (M = metal). Fluoroalkyl metal complex are generally not very effective reagents or intermediates for fluoroalkylation reactions due to the low reactivity of the strong metal–fluoroalkyl bond and the thermal decomposition of such complexes via α- or β-fluorine elimination; fluoroalkyl copper complexes are an exception. McLoughlin and Thrower have reported the perfluoroalkylation of iodobenzenes in the presence of copper powder.[23] The reaction proceeds via a fluoroalkyl copper complex generated by the reductive cupration of perfluoroalkyl iodide with copper powder. The fluoroalkyl copper complex is thermally relatively stable, but readily furnishes perfluoroalkyl compounds upon treatment with electrophiles such as aryl iodides. The McLoughlin–Thrower reaction has been widely applied for the synthesis of a variety of (perfluoroalkyl)arenes. In this section, we describe the generation of fluoroalkyl copper complexes from TFE. The resulting fluoroalkyl copper reagents are transformed into fluoroalkyl compounds via coupling reactions or into 1,1,2-trifluorovinyl compounds via β-F elimination.

3.1

Carbocupration of TFE

Our group envisioned that the carbocupration of TFE could potentially generate a useful fluoroalkyl copper complex.[24] Our strategy was to generate an aryl copper complex via the transmetalation of an arylboronic acid ester with CuOtBu. This protocol avoids contamination with magnesium (from the Grignard reagent) or lithium salts, which promote β-fluorine elimination of the resulting fluoroalkyl copper complexes.[25] TFE pressurization of a solution of an aryl copper complex prepared via the reaction of CuOtBu and an arylboronic acid ester 8 in the presence of 1,10-phenanthroline (Phen) afforded fluoroalkyl copper complex 9 in good yield (Scheme [4]). The 19F NMR analysis indicated the existence of an equilibrium between the neutral and ionic forms of the complex. The crystallographic analysis of the neutral form of the fluoroalkyl complex revealed a trigonal-planar geometry. The fluoroalkyl complexes react with aryl iodide, benzyl chloroformate, and chlorophosphine, to give the corresponding coupling products 10–13. Finally, the complex was applied to the synthesis of a liquid crystal.

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Scheme 4 Synthesis and reactivity of a fluoroalkyl copper complex

# 3.2

Oxy- and Azacupration of TFE

Our group next investigated oxycupration and azacupration reactions using a similar strategy based on CuOtBu or CuMes. Deprotonation of PhOH with CuMes in the presence of Phen followed by TFE pressurization delivered fluoroalkyl copper 14 with a phenoxy group (Scheme [5]).[26] For the oxycupration of TFE, PhOCu(phen) was prepared by treating CuCl and NaOPh in DMF, i.e., without using the relatively sensitive CuOtBu. Fluoroalkyl copper complex 14 gives the corresponding ether 15 upon reaction with an aryl iodide. Hu and co-workers have also developed an oxycupration of TFE generated ex situ by treatment of TMSCF3 with NaI, followed by arylation using 1-iodo-4-nitrobenzene.[6] Our group has furthermore disclosed that imidazole is effective for the azacupration of TFE (Scheme [6]).[27] In this case, a one-pot reaction was achieved by mixing the sodium salt of imidazole 16, aryl iodide, CuCl, and Phen under pressurization with TFE. Stirring the solution at room temperature generates a fluoroalkyl copper complex, which is followed by coupling promoted by heating to afford compound 17 in moderate to good yields.

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Scheme 5 Oxycupration of TFE
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Scheme 6 One-pot coupling reaction via azacupration of TFE

# 3.3

Pentafluoroethylation Using TFE

The addition of fluoride to TFE can be expected to generate a pentafluoroethyl anion driven by the high electrophilicity of TFE. Hu and our group have independently envisioned that a combination of a fluoride anion and a copper salt under TFE pressurization could potentially generate a pentafluoroethyl copper complex that could serve as a precursor for pentafluoroethyl-substituted arenes (Scheme [7]).[6] [28] Hu has used TFE generated ex situ from TMSCF3 (Scheme [7]A). Introducing TFE into another chamber containing CsF, CuCl, Phen, and DMF furnished a pentafluoroethyl copper complex via fluorocupration, which in turn provides a variety of (pentafluoroethyl)arenes 18 via coupling with aryl iodides. In contrast, we used TFE gas supplied from a cylinder. In our case, it was important to perform the reaction without stirring to obtain the desired (pentafluoroethyl)arene 19 in a catalytic manner (Scheme [7]B). When we performed the reaction with vigorous stirring, oligomerization of TFE was promoted by the fluoride anion,[29] [30] which resulted in the formation of a complex reaction mixture. We also developed an acylation of pentafluoroethyl anions generated from TFE; however, this work, which does not involve a transition-metal complex, is beyond the scope of this review.[31]

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Scheme 7 Stoichiometric and a catalytic pentafluoroethylation of aryl iodides using TFE

# 3.4

Defluoroborylation and Defluorosilylation of TFE

Trifluorovinyl anion equivalents are building blocks for the introduction of a fluoroalkene moiety via a cross-coupling reaction. Using copper catalysis, we developed synthetic methods for (trifluorovinyl)boron and (trifluorovinyl)silane reagents via the defluorometalation of TFE.

In the presence of a catalytic amount of IPrCuOtBu (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene), the reaction of TFE and B2pin2 (pin = pinacolate) furnished a trifluorovinylboronic acid ester 20 in quantitative yield (Scheme [8]A).[32] We successfully isolated a putative reaction intermediate, i.e., trifluorovinyl copper complex 21, whose structure was determined by single-crystal X-ray diffraction analysis (Scheme [8]B). Treatment of isolated trifluorovinyl copper 21 with B2pin2 furnished trifluorovinylboron 20, indicating that the vinyl copper complex is the intermediate of the catalytic reaction.

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Scheme 8 Defluoroborylation of TFE using copper catalysis

Our group has also investigated the defluorosilylation of TFE using a copper catalyst.[33] For that purpose, we employed a silylborane 22 as the reductant. The selectivity of the defluoroborylation and defluorosilylation was controlled by the choice of ligand. Using an IPr complex selectively furnished the (trifluorovinyl)silane (Scheme [9]A). Based on several stoichiometric reactions, a possible reaction mechanism was proposed. The reaction is initiated by a transmetalation between IPrCuF and silylborane to give a well-defined silyl copper complex.[34] The silylcupration of TFE affords fluoroalkyl copper complex 24, which was supported by a stoichiometric reaction (Scheme [9]B). Subsequent β-fluorine elimination promoted by FBpin gives (trifluorovinyl)silane 23 and regenerates IPrCuF. It should also be noted here that in the absence of FBpin, the fluoroalkyl copper complex 24 thermally decomposes into PhMe2SiF and trifluorovinyl copper 21, which affords (trifluorovinyl)boron 20 upon reaction with silylborane 22.

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Scheme 9 Defluorosilylation of TFE using copper catalysis

# 3.5

Hydrodefluorination of TFE

Baker and co-workers have reported the hydrodefluorination of TFE using a P-ligated copper hydride complex as a catalyst (Scheme [10]).[35] In this reaction, tetramethyldisiloxane (TMDS) was used as a hydride source. The reaction gives hydrodefluorinated and hydrogenated products in a 2.5:1 ratio. Fluoroalkyl copper complex 25 was isolated using PMe2Ph as an ancillary ligand for copper.

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Scheme 10 Hydrodefluorination of TFE and the putative fluoroalkyl copper intermediate

#
# 4

Nickel Complexes

Reactions of TFE with Ni(0) complexes have been studied for decades. Historically, one of the most important reactions in this context is the oxidative cyclization of two molecules of TFE to give octafluoronickelacyclopentanes, an early example of which was reported by Stone and co-workers in 1970.[36] As the octafluoronickelacyclopentane unit is very stable, it has recently been used to investigate the properties of high-valent nickel complexes by Vicic[37] and Sanford.[38] However, such a high stability of the scaffold is not desirable in the context of catalytic transformations. In fact, only a single example of a hydrogenation has been achieved by incorporating this step in a catalytic cycle (Scheme [11]).[39] In the presence of a nickel/phosphite catalyst, the reaction of TFE and H2 produces 1,1,2,2,3,3,4,4-octafluorobutane. A cross-oxidative cyclization to forge a σ-bond between TFE and another unsaturated molecule would be a fascinating process. An oxidative cross-cyclization with ethylene has been reported by Pörschke and co-workers in 1991 (Scheme [12]),[40] who used nickel-TFE precursor 26 with a bulky diimine ligand. Other examples using a 2,3-naphthalyne complex have been presented by Bennett and co-workers (Scheme [13]).[41] [42] In this case, the reduction of the o-bromoaryl nickel complex 28 with sodium amalgam furnished naphthalyne complex 29, which reacts with TFE to form nickelacycle 30.

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Scheme 11 Catalytic coupling of two molecules of TFE with H2
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Scheme 12 Oxidative cyclization of TFE and ethylene on Ni(0) supported by a diimine ligand
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Scheme 13 Reaction of a Ni-naphthalyne complex with TFE

Our group has developed a variety of nickel-catalyzed transformations of unsaturated molecules via the formation of nickelacycles,[43] [44] with particular focus on the characterization of possible reaction intermediates. In this context, we wanted to explore the possibility of a catalytic transformation of TFE with unsaturated molecules using nickel catalysts. To our delight, we found various C–C bond-forming reactions between TFE and alkenes, alkynes, aldehydes, or imines.

4.1

Cross-Trimerization with Ethylene

We commenced our investigation on this subject by using TFE and ethylene,[45] but initially met the formation of an inert octafluoronickelacyclopentane as an obstacle to developing a catalytic cycle. Thus, our initial motivation for a stoichiometric reaction was to avoid pressurization of Ni(0) with TFE before pressurization with ethylene. Therefore, we treated Ni(cod)2/PPh3 with ethylene followed by pressurization with TFE which led to the quantitative formation of oxidative cross-cyclization complex 31 (Scheme [14]A). The complex was structurally characterized by X-ray crystallography. Further pressurization of this complex with ethylene resulted in the formation of 1,1,2,2-tetrafluorohex-5-ene (32). Using PCy3 instead of PPh3 enabled the catalytic cross-trimerization of two molecules of ethylene with one molecule of TFE with a TON of 13 (Scheme [14]B). A plausible reaction mechanism is shown in Scheme [14]C. Nickelacycle intermediate V reacts with ethylene via insertion into the Ni–C bond, β-hydrogen elimination, and reductive elimination to give 32.

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Scheme 14 Reaction of TFE and ethylene in the presence of Ni(0)

# 4.2

Cross-Trimerization of TFE, Ethylene, and Aldehydes

We next investigated the catalytic cross-trimerization reaction of TFE, ethylene, and aldehyde.[46] A natural population analysis of the corresponding nickelacycle intermediates indicated a relatively high nucleophilicity for the α-CH2 moiety of the nickelacycle. This hypothesis was experimentally supported by a stoichiometric reaction between nickelacycle 31 and benzaldehyde to give coupling product 33 (Scheme [15]A). Encouraged by these results, we added benzaldehyde to the reaction mixture of TFE, ethylene, and the Ni(cod)2/PCy3 catalyst, which led to the formation of the desired product 33 in 32% yield. The major byproduct was an ester generated by the Tischenko reaction of the aldehyde.[47] [48] After screening a variety of ligands, we discovered that the use of IPr gave 33 in high yield. By raising the reaction temperature to 150 °C, 33 was obtained in 98% yield together with a small quantity of the ester. To study the reaction mechanism, we treated Ni(cod)2 and IPr with ethylene and TFE, and obtained a novel octafluoronickelacycloheptane, which was structurally characterized by X-ray crystallography. The isolated complex did not react with the aldehyde, indicating that the complex is most likely not a reaction intermediate. The nickelacyclopentane can be expected to be a transient species that rapidly captures electrophiles such as the aldehyde or TFE.

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Scheme 15 Reaction of TFE, ethylene, and aldehyde in the presence of Ni(0)

# 4.3

Three-Component Coupling of TFE, Aldehyde, and Silane

We have also discovered that silanes serve as a useful reductant for nickelacycles generated via the oxidative cyclization of TFE and an aldehyde.[49] In the presence of a catalytic amount of Ni(cod)2 and PtBu3, the reaction of TFE, benzaldehyde, and HSiEt3 at room temperature resulted in the formation of silyl ether 34 in 71% yield (Scheme [16]A). To gain insight into the underlying reaction mechanism, stoichiometric reactions were performed. TFE pressurization of a hexane solution containing Ni(cod)2, PtBu3, and benzaldehyde delivered a five-membered oxanickelacycle 35 in 90% yield (Scheme [16]B). X-ray crystallography revealed that 35 forms a syn-dimer, one coordination site of which is occupied by the recrystallization solvent THF instead of the PtBu3 ligand in the crystals. Treatment of 35 with HSiEt3 in the presence of PtBu3 afforded 34 in 67% yield. The reaction is also applicable to N-sulfonyl imines.[50]

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Scheme 16 Reductive coupling of TFE and an aldehyde in the presence of a silane

# 4.4

Tetramerization

Subsequently our group investigated the addition of alkynes. In the presence of 10 mol% Ni(cod)2 and 40 mol% PCy3, cross-tetramerization of oct-4-yne, TFE, and ethylene furnished octa-1,3-diene 36a in quantitative yield (Scheme [17]).[51] When we used diphenylacetylene or 1-phenylhex-1-yne, the alkynes were rapidly consumed by cyclo-trimerization before pressurization with TFE and ethylene. To circumvent the undesired alkyne consumption, we used (η2-CF2=CF2)Ni(PCy3)2 (37) as the catalyst to obtain 36b and 36c in good yield. This reaction is also applicable to silylacetylenes.

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Scheme 17 Catalytic tetramerization of TFE, ethylene, and alkynes: a 10 mol% of 37 was used as the catalyst. b Regioisomer ratio: 77:23. c 20 mol% 37 was used. d Regioisomer ratio: 58:42

Our group also discovered a four-component cross-tetramerization reaction using TFE, ethylene, styrene, and alkyne (Scheme [18]). The reaction requires the addition of excess styrene to promote the oxidative cyclization between TFE, styrene, and Ni(0). The nickelacycle reaction intermediate, which was synthesized using TFE and styrene, was structurally characterized by X-ray crystallography.[52]

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Scheme 18 Four-component cross-tetramerization of TFE, ethylene, styrene, and alkyne
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Scheme 19 Catalytic four-component cross-tetramerization reaction of TFE, ethylene, alkyne, and aldehyde
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Scheme 20 Reaction of a nickelacycle with an alkyne and an aldehyde

Another example of a four-component cross-tetramerization reaction employs TFE, ethylene, alkyne, and aldehyde.[53] In the presence of 10 mol% Ni(cod)2 and 40 mol% PCy3, the reaction of oct-4-yne, p-tolualdehyde, TFE, and ethylene in toluene at 100 °C selectively produced 39 (Scheme [19]). Only small amounts of the TFE/ethylene/alkyne trimerization product and the ester from the dimerization of the aldehyde were found in the reaction mixture. Especially, thiophene-2-carbaldehyde gave the desired product 39d in good yield. The reaction does not require excess aldehyde or alkyne, unlike that of styrene (vide supra). Some stoichiometric reactions were performed to gain insight into the underlying reaction mechanism (Scheme [20]). Treatment of 31 with oct-4-yne and p-tolualdehyde in toluene at 100 °C delivers coupling product 40 in 75% yield. In this case, no cross-trimerization product was observed, indicating that the alkyne is more prone to insertion into Ni–CH2 than the aldehyde.


# 4.5

Metathesis

Baker and co-workers have disclosed an interesting transformation of TFE using a Ni–carbene complex.[54] Treatment of Ni=CFCF3 carbene complex 41 with TFE produced a mixture containing metallacyclobutane 42, Ni=CF2 carbene complex 43, and metathesis product hexafluoropropylene (44) (Scheme [21]) with a 42/43 ratio of approximately 9:1. DFT calculations revealed that a metallacyclobutane is not a reaction intermediate for hexafluoropropylene. Instead, the metathesis products, i.e., a Ni=CF2 carbene and hexafluoropropylene, were produced via a bicyclic transition state in which the Ni center adopts a tetrahedral geometry. A metallacyclobutane complex was generated via an open shell singlet diradical pathway.

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Scheme 21 Reaction of a Ni carbene complex with TFE

#
# 5

Ruthenium

Recently, the olefin metathesis reaction has been found to be applicable to TFE. Olefin metathesis is commonly used to synthesize a variety of alkenes in industry and academia. Application of a cross-metathesis reaction of TFE could potentially enable the efficient synthesis of difluoroalkenes. However, the intermediate ruthenium difluorocarbene complexes show low catalytic activity for ring-opening metathesis polymerization reactions.[55] Takahira and co-workers have developed a cross-metathesis reaction of TFE with vinyl ethers.[56] The vinyl ether also generates a Fischer carbene intermediate, which is thermodynamically favored. The strategy combines two thermodynamically stable carbenes, i.e., an alkoxycarbene and a difluorocarbene, to reduce the energy difference between the carbene intermediates in the catalytic cycle. After screening a set of ruthenium pre-catalysts, o-alkoxyphenyl methylidene complex 46 was found to provide difluoroalkene 47 in 69% yield (Scheme [22]). It should also be noted here that the cross-metathesis reaction using vinylidene fluoride was unsuccessful because the catalytic cycle requires the formation of a thermodynamically unfavored methylidene complex. This and other stoichiometric reactions support the hypothesis of a catalytic turnover between difluorocarbene and alkoxycarbene intermediates.

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Scheme 22 Ru-catalyzed cross-metathesis between an enol ether and TFE
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Scheme 23 Ru-based catalyst with a seven-membered NHC for cross-metathesis reactions between TFE and vinyl ethers

Recently, Akiyama, Nozaki, and co-workers have reported a novel ruthenium catalyst that bears a seven-membered NHC ligand 49, which catalyzes the cross-metathesis reaction between TFE and vinyl ether 48 with a TON of 4100 (Scheme [23]A).[57] The seven-membered NHC lowers the energy barrier via the destabilization of the difluoromethylidene species, which is supported by DFT calculations as well as by an analysis of the X-ray structure of the difluoromethylidene complex. The authors also directed their efforts to the modification of the reaction conditions, which revealed that a reaction with flowing TFE gives a higher turnover than that in a sealed reactor. The continuous flow of TFE efficiently removes vinylidene fluoride to shift the equilibrium toward the cross-metathesis product. During the investigation of the reaction conditions, the authors obtained an E/Z mixture of 1,2-dialkoxyethylene as undesired side products. The side products are generated via the cross-metathesis reaction between the alkoxyethylene and difluoroethylene products, indicating that increasing the concentration of TFE could potentially prevent this undesired pathway. The authors found ethyl acetate to be a suitable solvent that dissolves a relatively large amount of TFE (52.5 mM at 60 °C). Their optimized reaction conditions were applied to the synthesis of difluoroalkene 52 instead of difluoroenol ether (Scheme [23]B). The reaction was achieved using alkenyl methyl ether which forms volatile, and thus removable, 1,1-difluoro-2-methoxyethene (53).


# 6

Rhodium

The transformation of TFE using Rh has also been investigated. In 1970, Stone reported the formation of an octafluororhodacycle via the treatment of a Rh(I) complex with TFE.[58] Recently, Nozaki and co-workers have reported the crystal structure of an octafluororhodacycle 54 that bears a PBP pincer ligand (Scheme [24]).[59] It is worth noting here that, the Rh–C1 bond is longer than the Rh–C2 bond due to the strong trans influence of the boryl group. In addition, the Rh–C1 bond shows high reactivity; the complex reacts with H2, I2, and acids to yield 1,1,2,2,3,3,4,4-octafluorobutane and fluoroalkyl rhodium complexes 55 and 56, respectively. The authors also accomplished the catalytic preparation of 1,1,2,2,3,3,4,4-octafluorobutane via repeated pressurization with TFE and H2. Although the process requires external operation and affords low TON, it serves a proof-of-principle that rhodium complexes, which are frequently used as catalysts in organic synthesis, are suitable for the catalytic transformation of TFE.

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Scheme 24 Reaction of a Rh(I) complex with TFE and H2

# 7

Summary and Perspective

In this review, we have highlighted the transformation of TFE using homogeneous transition-metal complexes. The use of TFE is advantageous due to its low cost and environmental impact as well as its availability. Its simple structure and high electrophilicity are strong advantages in the context of synthetic chemistry. This review summarizes the catalytic transformations of TFE via the oxidative addition of C–F bond, as well as oxidative cyclization, and olefin metathesis reactions. While these processes are fundmental in haloalkene chemistry, their application to TFE is not straightforward. There remains substantial room for the development of further transformations of TFE using metal-based catalysts, especially of metals not discussed in this review.[60] [61] [62] [63]


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Conflict of Interest

The authors declare no conflict of interest.


Corresponding Author

Sensuke Ogoshi
Department of Applied Chemistry, Faculty of Engineering, Osaka University
Suita, Osaka 565-0871
Japan   

Publication History

Received: 13 October 2022

Accepted after revision: 15 November 2022

Accepted Manuscript online:
21 November 2022

Article published online:
20 December 2022

© 2022. Thieme. All rights reserved

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Ryohei Doi (left) was born in 1989 in Kobe, Japan. In 2016, he obtained his Ph.D. from Osaka University in 2016 under the direction of Prof. Sensuke Ogoshi. During his postgraduate studies, he spent some time in the group of Prof. Brian M. Stoltz (2015) at the California Institute of Technology. In 2016, he joined Prof. Sato’s group at Hokkaido University as an Assistant Professor. In 2021, he returned to the Ogoshi group as an Assistant Professor. He is currently working on synthetic studies of organofluorine compounds using transition-metal complexes. Yuyang Zhou (center) is a postgraduate student in the Ogoshi group at Osaka University (Japan). He received his B.Sc. degree from Osaka University in 2022. His current research focuses on the synthesis of fluoroalkyl compounds using copper complexes. Sensuke Ogoshi (right) received his Ph.D. from Osaka University in 1993 under the tutelage of Prof. Shinji Murai. During his postgraduate studies, he also worked with Prof. Lanny S. Liebeskind at Emory University (1991). In that year he joined the faculty at Osaka University as an Assistant Professor in the group of Prof. Hideo Kurosawa. In 1999, he was promoted to an Associate Professor, and in 2007 to Full Professor. In 1996–1997, he received JSPS Fellowship for Research Abroad to work in the research group of Prof. Jeffery M. Stryker at the University of Alberta (Canada). His work has been commended by several accolades, which include the CSJ Award for Young Chemists (1999) and The Japan Chemical Society Award for Creative Work (2013).
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Figure 1 Synthetic methods for the generation of TFE on an industrial (A) and laboratory scale (B–D)
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Scheme 1 Oxidative addition of TFE to Pt(0) using LiI (A) and Pd-catalyzed cross-coupling reaction of organozinc reagents with TFE (B, C)
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Scheme 2 Base-free cross-coupling of TFE with arylboronic acid esters
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Scheme 3 Base-free cross-coupling of TFE with organosilicon reagents
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Scheme 4 Synthesis and reactivity of a fluoroalkyl copper complex
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Scheme 5 Oxycupration of TFE
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Scheme 6 One-pot coupling reaction via azacupration of TFE
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Scheme 7 Stoichiometric and a catalytic pentafluoroethylation of aryl iodides using TFE
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Scheme 8 Defluoroborylation of TFE using copper catalysis
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Scheme 9 Defluorosilylation of TFE using copper catalysis
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Scheme 10 Hydrodefluorination of TFE and the putative fluoroalkyl copper intermediate
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Scheme 11 Catalytic coupling of two molecules of TFE with H2
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Scheme 12 Oxidative cyclization of TFE and ethylene on Ni(0) supported by a diimine ligand
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Scheme 13 Reaction of a Ni-naphthalyne complex with TFE
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Scheme 14 Reaction of TFE and ethylene in the presence of Ni(0)
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Scheme 15 Reaction of TFE, ethylene, and aldehyde in the presence of Ni(0)
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Scheme 16 Reductive coupling of TFE and an aldehyde in the presence of a silane
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Scheme 17 Catalytic tetramerization of TFE, ethylene, and alkynes: a 10 mol% of 37 was used as the catalyst. b Regioisomer ratio: 77:23. c 20 mol% 37 was used. d Regioisomer ratio: 58:42
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Scheme 18 Four-component cross-tetramerization of TFE, ethylene, styrene, and alkyne
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Scheme 19 Catalytic four-component cross-tetramerization reaction of TFE, ethylene, alkyne, and aldehyde
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Scheme 20 Reaction of a nickelacycle with an alkyne and an aldehyde
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Scheme 21 Reaction of a Ni carbene complex with TFE
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Scheme 22 Ru-catalyzed cross-metathesis between an enol ether and TFE
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Scheme 23 Ru-based catalyst with a seven-membered NHC for cross-metathesis reactions between TFE and vinyl ethers
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Scheme 24 Reaction of a Rh(I) complex with TFE and H2