Functionalization of Fluorinated Molecules by Transition-Metal

Review pubs.acs.org/CR

Functionalization of Fluorinated Molecules by Transition-MetalMediated C−F Bond Activation To Access Fluorinated Building Blocks Theresia Ahrens,‡ Johannes Kohlmann,‡ Mike Ahrens, and Thomas Braun* Humboldt-Universität zu Berlin, Department of Chemistry, Brook-Taylor-Straße 2, 12489 Berlin, Germany 3. C−F Activation and C-Heteroatom Bond Formation 3.1. Derivatization of Aromatic Compounds 3.2. Transformation of Metal-Bound Aromatic Building Blocks 3.3. Derivatization of Heteroaromatic Compounds 3.4. Reactions of Fluorinated Olefins and Alkyl Groups 4. Conclusions Author Information Corresponding Author Author Contributions Notes Biographies Acknowledgments References

CONTENTS 1. Introduction 2. C−F Activation and C−C Bond Formation 2.1. C−C Bond Formation at Polyfluorinated Benzene Derivatives 2.1.1. Transformation of C−F Bonds at Less Fluorinated Benzene Derivatives 2.1.2. Transformations of C−F Bonds at Highly Fluorinated Benzene Derivatives 2.2. C−C Bond Formation at Polyfluorinated Aromatics Supported by a Remote Group 2.2.1. Imine Functionalities as Directing Groups 2.2.2. Oxazoline Functionalities as Directing Groups 2.2.3. Pyridine Functionalities as Directing Groups 2.2.4. Nitro Functionalities as Directing Groups 2.2.5. Keto and Hydroxo Functionalities as Directing Groups 2.2.6. Derivatization of Metal-Bound Fluorinated Ligands 2.3. C−C Bond Formation at Polyfluorinated Heteroaromatics 2.3.1. Reactions at Nickel 2.3.2. Reactions at Palladium 2.3.3. Reactions at Rhodium 2.4. C−C Bond Formation at Polyfluorinated Olefins 2.4.1. Transformation of C−F Bonds at Less Fluorinated Olefinic Derivatives 2.4.2. Transformation of C−F Bonds at Perfluorinated Olefinic Derivatives © XXXX American Chemical Society

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1. INTRODUCTION Fluorinated organic compounds increasingly gain importance in numerous areas of chemistry and everyday life. Building blocks which contain fluorinated entities are of high significance in areas such as materials science, catalysis, medicine, and biochemistry.1 This is because the reactivity and properties of molecules and ions can change dramatically in the presence of fluorinated moieties.1,2 Therefore, there is a growing demand for the development of unprecedented routes to access fluorinated molecules and building blocks, and even to design new scaffolds. One approach consists of a transition-metalmediated synthesis, preferably by a catalytic process.3 This can involve fluorination reactions as well as the introduction of fluorinated functionalities, or alternatively, fluorinated compounds can be derivatized selectively at a transition-metal center to obtain the desired building blocks.1e,h−j,n,r,3−7 For the latter, the activation of C−F bonds has emerged to be an interesting methodology.5b,8 Poly- or perfluorinated molecules, which might be readily available by fluorination methods, can be derivatized in a unique way via the cleavage of a carbon− fluorine bond. One apparent approach involves hydrodefluorination processes, i.e. the transformation of a C−F bond into a C−H bond.5g,8,9 These are to some extent of interest, because of the environmentally persistent nature of chlorofluorocarbons or

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Special Issue: 2015 Fluorine Chemistry

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Received: May 14, 2014

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dx.doi.org/10.1021/cr500257c | Chem. Rev. XXXX, XXX, XXX−XXX

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fluorocarbons, and hydrodefluorination can be regarded as a promising key step for dehalogenation.10 In addition, hydrodefluorination can also provide new building blocks and C−H bonds at polyfluorinated aromatics can be used for further C−H functionalization.11 There are several reviews on transition-metal-mediated C−F bond activation, and some of them cover hydrodefluorination reactions explicitly.5b,8 Yet, C− F bonds at a polyfluorinated molecule can also be derivatized selectively by the replacement of the fluorine atom by organic moieties. Many of these conversions consist of C−C coupling reactions, such as catalytic cross-coupling reactions. Even more, C−O, C−S, C−N, C−P, and carbon−halogen bond formations were also reported, although the latter three reactions are often not catalytic. The catalytic introduction of silyl or boryl groups by the generation of C−Si and C−B bonds must be considered as very stimulating, because they provide unique opportunities for further derivatization reactions to access compounds of higher value. Thermodynamically, C−F bonds are very strong, and in order to make C−F bond cleavage steps feasible, other strong element−fluorine bonds have to be formed.12 This includes the formation of H−F, Si−F, B−F, Al−F, P−F, and transition-metal−fluorine bonds.8w,x In particular, for crosscoupling reactions at Ni, Pd, or Pt, a metal fluorido complex is often generated by oxidative addition. A subsequent transmetalation step gives fluoride salts, or again B−F, Sn−F, and Zn−F bonds are formed. It is interesting that the strength of the C−F bond in fluorobenzene is stronger than in hexafluorobenzene, but there is a decrease in the C−H bond strength when comparing pentafluorobenzene and benzene. Therefore, hydrodefluorination reactions are more feasible for highly fluorinated aromatics and less so for the less fluorinated ones.13 This review deals with transition-metal-mediated C−F bond activations which involve a cleavage of a C−F bond in polyfluorinated molecules and its transformation into carbon− element bonds, excluding hydrodefluorination or defluorination reactions. The transformations comprise stoichiometric and catalytic conversions, but often the stoichiometric reactions can also be considered as key steps for the development of a catalytic cycle. When appropriate, key steps of a putative catalytic process will be discussed and mechanistic studies can be of great importance, in part to explain selectivities. Especially, the carbon−fluorine bond cleavage step is of considerable interest.8g,h,l,s,w,x,9d,13d,14 Transformations of monofluorinated molecules are not covered, because this does not lead to fluorinated products. However, selected examples for reactions are mentioned for which the new fluorinated building blocks still coordinate at the metal center. A comprehensive review on C−F bond activation in organic synthesis was published by Amii and Uneyama in 2009.8m However, the recent remarkable progress in the transitionmetal-mediated synthesis of fluorinated entities is not the emphasis there. The activation of C−F bonds was also reviewed thoroughly earlier by Kiplinger, Richmond, and Osterberg in another comprehensive paper.8a Another paper by Weaver on the C−F activation and functionalization of perfluoro- and polyfluoroarenes appeared recently.8aa

2. C−F ACTIVATION AND C−C BOND FORMATION 2.1. C−C Bond Formation at Polyfluorinated Benzene Derivatives

Nakamura et al. described a nickel-based catalytic process, which involves the selective transformation of less and highly fluorinated benzene derivatives.15 On using the tridentate phosphine ligand 2 it was shown that a selective substitution of one fluorine atom can be achieved by cross-coupling reactions with in situ generated aryl- and alkyl-zinc reagents (Scheme 1). Scheme 1. Selected Examples for Nickel-Mediated CrossCoupling Reactions of Poly- and Perfluorobenzenes with Aryl Zinc Reagents with the Phosphine Ligand 2; Suggested Transition State 4 for the C−F Bond Cleavage Step

The ligand 2 bears two phosphanyl groups and one alkoxide moiety in contrast to the previously reported phosphine ligand 3 with only one phosphanyl and one alkoxide group.16 For all polyfluorobenzenes, a substitution at the C−F moiety which has only one neighboring fluorine substituent is preferred over an activation of a C−F bond which has two adjacent C−F bonds. In contrast, transformations with 3 as a ligand at a nickel center lead to di- or polysubstitution products in the presence of PhMgBr, presumably due to pronounced “ring walking” of the initial product, which is still bound at the metal center. The “ring walking” tendency in this catalyst/product complex, which makes it hard to achieve a substitution of only one C−F bond, was explained by strong back-donation from the transition metal. The C−F insertion was calculated to be quite facile with an activation energy of approximately 6 kcal/ mol. Thus, mechanistically, it was presumed that the ligands 2 B


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and 3 are able to coordinate both the Ni and a Zn (or Mg) center and that both metals are involved in the activation of the C−F bond (see Scheme 1, 4). Subsequently, the catalyst/ product complex is formed, from which a product elimination occurs to liberate a Ni(0) species. Whereas the bidentate ligand 3 allows “ring walking” of the aromatic product in the catalyst/ product complex and further C−F activation, the tridentate nature of ligand 2 prevents “ring walking” and additionally favors the formation of the Ni(0) species. Concerning the C−F activation step, the proposed mechanism was supported by DFT calculations for an activation with a nickel complex bearing ligand 3.16b 2.1.1. Transformation of C−F Bonds at Less Fluorinated Benzene Derivatives. In a pioneering work, Kumada et al. showed in 1973 that nickel-catalyzed cross-coupling reactions at aryl monofluorides are feasible.17 Since then numerous cross-coupling reactions of monofluoroaromatics have been developed, but these lead not to fluorinated products. In 2001, Herrmann et al. reported on a catalytic Kumada−Tamao-type C−C cross-coupling reaction by C−F bond activation on using an in situ generated Ni/NHC (NHC = N-heterocyclic carbene) complex as a catalyst and aryl Grignard compounds (Scheme 2).18 Although only mono-

Scheme 3. Examples for Cross-Coupling Reactions of Polyfluorobenzenes with 4-MeC6H4MgBr To Give Monoand Disubstituted Benzene Derivatives

Scheme 2. Kumada−Tamao Cross-Coupling Reaction of a CF3-Substituted Monofluorobenzene with Aryl Grignard Reagents

obtained with [PdCl2(dppf)] (6, dppf = 1,1′-bis(diphenylphosphino)ferrocene) as catalyst under reflux conditions. Likewise, a monocoupling of 1,2,3- or 1,3,5-trifluorobenzene is achieved with the catalysts 6 and [PdCl2(PPh3)2] (7), respectively. Higher loadings of the catalyst [NiCl2(dppp)] (8, dppp = 1,3bis(diphenylphosphino)propane) and an excess of the aryl Grignard reagent lead selectively to the dicoupling product of 1,2,3-trifluorobenzene at the 1- and 3-position. Ackermann et al. reported on nickel-catalyzed cross-coupling reactions of nonactivated fluoroarenes with aryl Grignard compounds using heteroatom-substituted secondary phosphine oxide ligand precursors such as the diamidophosphine sulfide 9 (Scheme 4).21 It was shown that a single C−F activation at 1,4difluorobenzene is possible with yields up to 57%. Interestingly, it was also found that a monofluorinated cross-coupling product is furnished with 1-chloro-4-fluorobenzene as substrate. Thus, the C−Cl bond activation is favored over the C−F bond activation. In some cases a reverse chemoselectivity was reported in the literature.22 A coordination of the nickel center by two phosphine sulfide ligands was proposed, which is stabilized by hydrogen bonding in 10.23 By deprotonation of 10 with an aryl Grignard compound, the catalytically active heterobimetallic complex 11 is formed.21 In a comparable cross-coupling reaction Jin and Fang et al. showed that, with NiCl2·6H2O (12) and the diamidophosphine oxide 13 as ligand precursor, the coupling of 1,3-difluorobenzene with PhMgBr at room temperature gives selectively the monofluorobenzene derivative (Scheme 5).24 The facile activation of C−F bonds was explained by the formation of Ni/ Mg bimetallic complex species, for which the metal centers act in a cooperative fashion to achieve the C−F bond cleavage. 2.1.2. Transformations of C−F Bonds at Highly Fluorinated Benzene Derivatives. An early report from 1979 covers the stoichiometric homocoupling reactions of polyfluorophenyl entities by the decomposition of the pentafluorophenylsamarium compound [Sm(C 6 F 5 ) 2 ] (14). 25 Although samarium is a lanthanide, these reactions might be

fluorobenzene substrates were applied, CF3-group substituted products were obtained in high yields on using the appropriate starting compounds. Because a 1:1 ligand-to-metal ratio leads to the best results, it was concluded that the catalytically active species is an in situ formed 12-electron Ni(0) complex, in which the metal center is coordinated by only one NHC ligand (5, ligand precursor). Hammett correlation plots of σ−-values suggest that the reactions most probably proceed via a polar reaction pathway. In contrast, for a ligand-free catalyst such as NiCl2 there are strong indications for a radical reaction pathway, because homocoupling products are formed in large quantities. Note also in that context that recent studies indicate that Kumada−Tamao cross-coupling might have to be reassessed since some reactions also proceed in the absence of transition metal complexes.8m,19 Catalytic nickel- or palladium-catalyzed Kumada−Tamao cross-coupling reactions to give less fluorinated benzene derivatives by selective C−F bond activation were described by Saeki and Tamao et al.20 Representative examples are depicted in Scheme 3. The best results for a coupling of 1,2difluorobenzene with 4-methylphenylmagnesium bromide are C


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phenyl homocoupling products such as C12F9H or C18F13H are formed. The coupling products result from thermal decomposition reactions of 14 via fluoride elimination reactions accompanied by the formation of benzyne species, and insertion of the latter into C−F bonds at polyfluoroarylsamarium compounds such as 16 or 17 (Scheme 6). Subsequent hydrogen abstraction from the solvent tetrahydrofuran leads to the final products. However, the conversions are much more complicated than described here in brief, as also a series of isomeric coupling products and additional lower fluorinated polyfluorophenyl coupling products were observed. Jones and co-workers described the zirconium-mediated polymerization of C6F6 by heating a solution of [Cp2Zr(C6F5)2] (18) in the presence of C6F6 (Scheme 7).26 It was

Scheme 4. Kumada−Tamao Cross-Coupling Reactions of 1,4-Difluorobenzene with Aryl Grignard Reagents with the Phosphine Sulfide 9 as Ligand Precursor; Generation of the Active Heterobimetallic Species 11

Scheme 7. Zirconium-Mediated Polymerization of C6F6

Scheme 5. Kumada−Tamao Cross-Coupling Reaction of 1,3Difluorobenzene with PhMgBr Employing the Ligand Precursor 13

worth mentioning within this review. Complex 14 was obtained by transmetalation at 0 °C using the mercury compound [Hg(C6F5)2] (15, Scheme 6). If this transmetalation reaction is performed at room temperature in tetrahydrofuran, polyfluoro-

demonstrated that by thermal decomposition of 18 a benzyne species is formed, which can be captured by a reaction with furan or the solvent tetrahydrofuran. The generation of [Cp2ZrF(C6F5)] (19) is also observed. In the presence of additional C6F6, the formation of tetrafluorobenzyne leads to the polymerization of C6F6 at a high initial rate that slows down significantly with the reaction time. If a radical initiator is added, the decrease in the reaction rate can be prevented, whereas a radical inhibitor slows down the reaction even more. It was suggested that two competing reaction mechanisms have to be considered. A rapid radical chain mechanism initiated by an impurity in 18 which imparts the generation of a Zr(III) radical species (20, Scheme 7), and a slower pathway which involves the formation of tetrafluorobenzyne. The rapid pathway was explained by the homolytic cleavage of a C−F bond of C6F6 by 20 to give 19. The reaction of the resulting C6F5 radical species with 18 results in the regeneration of 20 together with the formation of the homocoupling product C12F10. Similar transformation steps give the polymerization product. Concerning the pathway involving tetrafluorobenzyne, a mechanism similar to the findings of Vince25 was proposed, assuming that such benzyne species are able to undergo insertion reactions into metal aryl bonds.

Scheme 6. Homocoupling Reaction of Polyfluorophenyl Entities by Decomposition of [Sm(C6F5)2] (14)

D


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A tantalum-catalyzed approach to access highly fluorinated benzene derivatives by C−F bond transformation was reported by Takahashi et al.27 TaCl5 (21) was used as a catalyst for the cross-coupling reactions of hexafluorobenzene or pentafluorotoluene with 2-phenylethylmagnesium chloride to afford selectively the corresponding monocoupling products (Scheme 8). A rearrangement of the Grignard reagent takes place during

Scheme 10. Synthesis of a Perfluoroaromatic Zinc Compound and Its Reactions with Br2 and CuCl2

Scheme 8. TaCl5-Catalyzed Transformations of C−F Bonds at Hexafluorobenzene and Pentafluorotoluene

species by the reaction with Br2 or into the homocoupling products by the treatment with CuCl2 (Scheme 10). The nickel-catalyzed Suzuki−Miyaura cross-coupling reactions of perfluoroarenes with boronic acids which were described by Radius et al. had to be considered as a breakthrough.30 The nickel carbene complex [Ni2(i-Pr2Im)4(cod)] (23, i-Pr2Im = 1,3-di(isopropyl)imidazole-2-ylidene, cod = 1,5-cyclooctadiene, Scheme 11) is a source for [Ni(iPr2Im)2].31 The latter is highly active for the activation of C6F6 to yield the fluorido complex trans-[Ni(i-Pr2Im)2F(C6F5)] (24) by oxidative addition. Likewise, it is possible to activate the C−F bond at the trans-position to a perfluorinated substituent in perfluoroarenes such as in octafluorotoluene to give trans[Ni(i-Pr2Im)2F(4-CF3C6F4)] (25). Complex 23 can also be used as a catalyst for Suzuki-type cross-coupling reactions of perfluorinated substrates (Scheme 11). With aryl boronic acids and NEt3 as a base, C−F activation occurs exclusively at the trans-positions to give the corresponding biaryl products. The reactions can also be performed under Kumada-type conditions with aryl Grignard reagents instead of boronic acids, but the yields are significantly lower. Mechanistic studies on the C−F activation suggest a precoordination of the aromatic system at the nickel center which is followed by a concerted oxidative addition of the C−F bond.32 This assumption was supported by DFT calculations, kinetic experiments, and the isolation and structural characterization of the 1,2-η2-octafluoronaphthalene complex [Ni(i-Pr2Im)2(1,2-η2-C10F8)] (26), which serves as a reaction intermediate within the C−F activation reaction at octafluoronaphthalene (Scheme 11). Ogoshi et al. reported in 2013 a base-free version of this Suzuki−Miyaura cross-coupling reaction on using the nickel complex 23 as catalyst and aryl boronates instead of aryl boronic acids (Scheme 12).33 Li et al. observed a stoichiometric cobalt-mediated C−C coupling reaction of octafluorotoluene with bromobenzene (Scheme 13).34 Concerning the C−C bond formation step in the reaction of [Co(4-CF3C6F4)(PMe3)3] (29) with bromobenzene, a binuclear oxidative addition of bromobenzene to 29 was proposed, to yield [CoBr(4-CF3C6F4)(PMe3)3] (30) and an unstable phenyl complex from which the coupling product is formed via a reductive elimination. It was also found that complex 29 is an isolable intermediate of a very unusual C−F activation reaction of octafluorotoluene at the electron-rich complex [Co(PMe3)4] (31). This C−F activation reaction was investigated more closely, and it was possible to isolate and structurally characterize the two compounds 29 and [Co(4-

the reaction. In an independent experiment it was shown that the isomerization occurs already at the metal center prior to the coupling reaction. For pentafluorotoluene, the C−F activation is highly regioselective and only takes place at the 4-position. Using higher amounts of the Grignard reagent, double C−F bond activation at hexafluorobenzene occurs and the paradiorganyl tetrafluorobenzene is formed (Scheme 8). Platonov et al. investigated the hydrodefluorination of perfluorinated xylenes with Zn(Cu)/DMF/H 2O in the presence of 1-hexene (Scheme 9). They also isolated in Scheme 9. Hydrodefluorination of Perfluorinated paraXylene with Zn(Cu)/DMF/H2O

minor amounts a product for which a C−F bond of one of the benzylic CF3-groups was alkylated by the reaction with 1hexene.28 No further hydrodefluorination occurs at this CF2 moiety. Mechanistically, an electron-transfer process which involves benzylic radical anions was proposed for the hydrodefluorination step. In this context it should also be mentioned that perfluoroaromatic organozinc compounds were reported by Miller in 2000.29 They can be prepared from perfluorinated CN- or CF3-functionalized benzene derivatives and Zn in the presence of catalytic amounts of SnCl2 (Scheme 10). The authors claim that SnCl2 is needed in order to shift the Ar2Zn/ ArZnHal (Hal = F, Cl) equilibrium toward the desired ArZnHal species. In the presence of SnCl2 no ArZnF species is formed, because of a F/Cl-exchange. The reactions can be accelerated by ultrasound. It was further demonstrated that the perfluoroaromatic organozinc compounds such as 4CF3C6F4ZnCl (22) can be converted into the brominated E


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In 2014 Ohashi and Ogoshi reported a Pd(0)-catalyzed cross-coupling reaction of perfluoroarenes such as hexafluorobenzene and octafluorotoluene with a large variety of in situ generated diaryl zinc compounds as second coupling agents.35 [Pd(PCy3)2] (33) turned out to be the best catalyst for the conversions, and it was found that the presence of the additive LiI is decisive in order to obtain the desired cross-coupling products (Scheme 14). Stoichiometric studies revealed that the C−F activation of the polyfluoroarene C6F6 by 33 in the presence of LiI leads to the pentafluorophenylpalladium(II) iodide complex trans-[PdI(C6F5)(PCy3)2] (34) presumably by oxidative addition followed by a halogen exchange reaction. Note that the oxidative addition of hexafluorobenzene at [Pd(PCy3)2] (33) was demonstrated by Grushin et al. earlier in 2005.36 Surprisingly, only small amounts of the cross-coupling product are obtained in the stoichiometric reaction of 34 with Ph2Zn in the presence of LiI, whereas the reaction proceeds smoothly under catalytic conditions. It was suggested that phosphine-dissociation might be involved to give a threecoordinate transient species [PdI(C6F5)(PCy3)], which should easily undergo transmetalation in the presence of the diaryl zinc reagent. To support this hypothesis, the pyridine-stabilized compound [PdI(C6F5)(PCy3)(py)] (35, py = pyridine) was synthesized, and indeed, the cross-coupling product with Ph2Zn was obtained in high yields, but again only in the presence of LiI (Scheme 14). From these findings, it was concluded that the additive LiI further activates the zinc organic compound, most probably via the formation of a zincate species Li[ZnAr2I].

Scheme 11. C−F Activation of Perfluoroarenes and Suzuki− Miyaura Cross-Coupling Reactions of Octafluorotoluene and Decafluorobiphenyl with Boronic Acids; Isolated Intermediate 26 from the C−F Activation Reaction at Octafluoronaphthalene

2.2. C−C Bond Formation at Polyfluorinated Aromatics Supported by a Remote Group

Transition-metal-mediated C−F bond functionalization reactions of fluoroaromatics can be highly regioselective with respect to an adjacent directing group. Such directing group effects offer a remarkable potential for the functionalization of polyfluorinated substrates, because the C−F bond cleavage− which is a key step−is facilitated and controlled by the remote group and as a consequence usually occurs at the ortho-position. 2.2.1. Imine Functionalities as Directing Groups. The first C−F bond activation steps at polyfluoroaryl imines at platinum were studied by Crespo and Martinez et al. on using the binuclear complex [Pt(Me)2(μ-SMe2)]2 (36).8y,37 The reactions give access to the unstable platinum(IV) fluorido complexes 37 by formation of a metallacyle comprising the CN-group (Scheme 15). The bond activation step selectively proceeds at the C−F bond which is at the ortho-position to the imine moiety, which serves as a directing group. C−F bond activation also occurs in the presence of weaker C−H bonds at the 3-, 4-, or 5-position in the substrate. However, a C−H bond at the 2-position leads to C−H activation and not to C−F bond cleavage. Further, no carbon−halogen bond activation occurs at a nitrogen-bound benzylic group. Kinetic and mechanistic studies on the C−F bond activation step revealed a plausible reaction pathway for the activation of highly fluorinated aryl imines (Scheme 15).37b,c Initially, [Pt(Me)2(μ-SMe2)]2 (36) is coordinated by the nitrogen atom of the imine to yield the complexes 38. Dissociation of the SMe2 ligand results in the formation of the three-coordinated intermediates 39.37b The C−F bond activation at 39 is believed to proceed intramolecularly via a concerted oxidative addition.37b,38 The slow formation of complex 40 with a mutually cis-arrangement of the aryl and fluorido ligand is followed by an isomerization to give

Scheme 12. Suzuki−Miyaura Cross-Coupling Reaction of Perfluoroarenes with Aryl Boronates

CF3-η2-C6F3)(PMe3)3] (32) (Scheme 13). It was proposed that, after dissociation of a phosphine ligand and the precoordination of the aromatic system to the Co(0) fragment, an insertion into the C−F bond at the para-position occurs via oxidative addition, followed by a reduction with phosphine, to yield the Co(I) intermediate 29. In the presence of free PMe3, F2PMe3 is formed. Subsequently, a second C−F activation takes place to give the aryne cobalt complex 32. F


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Scheme 13. C−F Activation and C−C Coupling Reaction of Octafluorotoluene with Bromobenzene at Cobalt

Scheme 14. Cross-Coupling Reactions of Perfluoroarenes with Aryl Zinc Compounds in the Presence of LiI

Scheme 15. Proposed Mechanism for the C−F Bond Activation of Polyfluorophenyl Imines at the Platinum Complex 36

the trans-derivatives.39 The coordination of SMe2 finally leads to the platinum(IV) complexes 37. Earlier studies suggest a trans-arrangement of the aryl and SMe2 ligand in 37.37b Love et al. initially investigated catalytic cross-coupling reactions of the polyfluoroaryl imine 2,4,6-C6F3H2CH NCH2Ph with organolithium, -silicon, and -zinc nucleophiles using the platinum(II) complex [Pt(Me)2(μ-SMe2)]2 (36) as precatalyst.8p,39b,40 They found Me2Zn to be a powerful methylation reagent in Csp2−Csp3 Negishi couplings. A broad range of functionalized phenyl imines were synthesized.

Catalytic methylation by C−F bond activation at the aryl ring occurs selectively at the 2-position with respect to the aryl bound imine group (Scheme 16). A second reaction of the functionalized 3,4,5,6-tetrafluoro-2-methylphenyl imine with Me2Zn gives the dimethylated derivative. For an unsymmetrical fluorine substitution pattern at the aryl ring in 2,3,6trifluorophenyl imine, the C−F bond derivatization at the ortho-position to the imine group and to a fluorine atom is favored. Note that seemingly no catalytic methylation was found at a difluorinated phenyl derivative with two fluorine G


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Scheme 16. Catalytic Methylation of Polyfluoroaryl Imines in the Presence of the Platinum Complex 36

Scheme 17. Possible Mechanism for the ortho-Methylation of Polyfluoroaryl Imines Employing [Pt(Me)2(μ-SMe2)]2 (36) as Precatalyst

methylation reaction instead of [Pt(Me)2(μ-SMe2)]2 (36).40b−d The authors believe that both complexes 41 and 42 as well as 36 form the same active species 39, whereas 36 is the most active precatalyst. Note that methoxylation reactions of substrates with imine or heterocyclic moieties as directing groups are also feasible (see section 3.1).40d,41 Studies on the mechanism provided remarkable in-depth insight into this catalytic coupling reaction (Scheme 17).37b,c,39b,40d,e Initial coordination of the imines to 36 gives the mononuclear complex 38. Subsequently, dissociation of the SMe2 ligand gives the catalytically active species 39 (see also Scheme 15). This three-coordinated intermediate undergoes oxidative addition of the imine to form the platinum(IV) compound 43. The transmetalation with Me2Zn yields 44 and may liberate MeZnF. Finally, reductive elimination furnishes

atoms at the ortho-positions. Thus, the reactivity of the C−F bond is assumed to be influenced by the electron-withdrawing effect of fluorine atoms at the highly fluorinated phenyl ring whereby at least three fluorine atoms are necessary for a successful conversion.37b In addition, other electron-withdrawing substituents such as nitrile and bromo groups can be beneficial as well. A phenyl imine with a chlorine and a fluorine atom at the ortho-positions was also applied in a coupling reaction, but the conversion involves a C−Cl bond activation step (see also section 2.1.1). No reaction occurs at trifluoromethyl groups at the ortho-position. Molecules with N-bound 4-bromobenzyl, 2-chlorobenzyl, or phenyl groups instead of a benzyl group can also be employed. Note that cis/ trans-[PtCl2(SMe2)2] (41) and cis-[PtCl2(dmso)2] (42) (dmso = dimethyl sulfoxide) can be used as precatalysts in the H


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gives the monomethylated compounds as major products in most cases. The selective monomethylation of 2,6-difluorophenyl imine derivatives using 48 was reported, whereas similar reactions with 49 give nonfluorinated compounds through dimethylation. Fluorinated phenyl imine derivatives undergo Suzuki− Miyaura cross-couplings with 4-methoxyphenylboronic acid in the presence of a base, PPh3, and [Ni(cod)2] (46) as a precatalyst (Scheme 19).43b Substitution of fluorine atoms which are located at the 2- and the 6-position of the phenyl ring lead to difunctionalized compounds, whereas a hydrogen atom at the 6-position is not affected. The authors suggested that the second cross-coupling of compounds with two ortho-fluorine atoms proceeds in competition with, or faster than, the prior one, since monoarylated compounds were neither observed as intermediates nor obtained as the final products. However, a different behavior was found for 2,3,6-trifluorophenyl imine which undergoes only one C−F activation at the 2-position to yield the difluoro derivative. Hydrolysis of the imines gives access to the corresponding aldehydes. A 2,4-difluorophenyl imine was additionally treated with a variety of arylboronic acids bearing electron-withdrawing or electron-donating groups, such as for instance 4-trifluoromethylphenylboronic acid (Scheme 19). Furthermore, a detailed study of Negishi cross-couplings reveals the potential of [NiCl2(PEt3)2] (47) as precatalyst in C−F bond functionalization reactions of polyfluorophenyl imine derivatives.43c Several catalytic Csp3−Csp2 couplings were successfully accomplished on employing diorganozinc reagents, such as for example Et2Zn, or organozinc halides. Thus, a broad range of organozinc bromides were generated in situ and applied in the functionalization reactions. The tolerance toward many functional and protective groups such as phenyl esters is high (Scheme 20). Note that there are no indications for competitive β-hydrogen elimination reactions. Catalytic C−F bond cleavage reactions of polyfluorophenyl imine derivatives, which exhibit a varying substitution pattern, proceed with a chemo- and regioselectivity similar to those of the reactions in the presence of [Ni(cod)2] (46) and PPh3 (see also Scheme 19). Thus, dialkylation occurs at compounds with fluorine atoms at the 2- and the 6-position of the phenyl ring, whereas a hydrogen atom at the 6-position is tolerated. Remarkably, unsymmetrically ortho-derivatized aldehydes can be synthesized by stepwise nickel-mediated cross-couplings of a 2,3,6-trifluorophenyl imine derivative (Scheme 21).43c One possibility includes an initial Suzuki−Miyaura reaction with 4methoxyphenylboronic acid in the presence of [Ni(cod)2] (46), PPh3, and a base which gives the monoarylated coupling product. Further derivatization proceeds with R2Zn (R = Me, Et, Ph) mediated by [NiCl2(PEt3)2] (47). Another reaction pathway is based on two successive Negishi cross-coupling reactions of the 2,3,6-trifluorophenyl imine derivative with stoichiometric amounts of BnZnBr followed by Et2Zn (Scheme 21). Li and co-workers described the C−F activation of difluoroaryl imines in the presence of [Co(Me)(PMe3)4] (48) which yields the octahedral cobalt complexes 49, 50, and 51 bearing both PMe3 ligands in the axial positions (Scheme 22).11g Again, the C−F bond activation occurs selectively at the ortho-position to the imine remote functionality. In the presence of CO, the acetyl derived imines are liberated and the cobalt carbonyl complex 52 is formed. The authors suggest that the 19-electron cobalt(0) complex 52

the methylated aryl imine products. This step is followed by coordination of another equivalent of the imine reagent regenerating complexes 39. Note that the catalytically active species 39, 43, and 44 are expected to be in equilibria with the resting states 38, 37, and 45 by coordination of SMe2. Importantly, Love et al. showed that the rate-determining step presumably depends on the degree of fluorination of the substrate.40e It is generally assumed that electron-deficient fluorinated ligands form stronger M−C bonds which might in turn lead to a stabilization of high oxidation states at transition metals.13b,14k,42 Thus, a C−F bond activation step of highly fluorinated imines may proceed rapidly to generate more stable platinum(IV) complexes. A subsequent reductive elimination step might then be rather slow and would be rate-determining. Less fluorinated compounds may behave dissimilarly, and the oxidative addition is regarded to be the rate-limiting process. Catalytic conversions favor the formation of monomethylated phenyl imines with high selectivity, because highly fluorinated imine reactants undergo C−F bond activation faster than their in situ generated less fluorinated analogs.8p,37b,40a,d Nevertheless, platinum-mediated cross-coupling reactions are limited to imines which possess at least three electronwithdrawing groups at the aryl ring, and do not bear a hydrogen atom at the 2- or 6-position, because otherwise C−H bond activation occurs followed by methane elimination. The employment of nickel complexes such as [Ni(cod)2] (46) and [NiCl2(PEt3)2] (47) in Suzuki−Miyaura and Negishi crosscoupling reactions overcomes these limitations as described below.43 Selective dimethylation reactions of pentafluorophenyl imines which bear diverse N-bound substituents such a 2chlorophenyl group are achieved applying the nickel complex [Ni(Me)2(PMe3)3] (48) and Me2Zn (Scheme 18).43a The derivatizations proceed via two ortho-selective C−F bond activation reactions. The use of [Ni(PMe3)4] (49) instead of 48 Scheme 18. Selected Examples for a Di- or Monomethylation of Pentafluorophenyl Imines Employing the Nickel Catalysts 48 and 49

I


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Scheme 19. General Reaction Scheme for Nickel-Mediated Suzuki-Miyaura Cross-Coupling Reactions of Polyfluoroaryl Imines

Scheme 20. General Reaction Scheme for Negishi-Type Cross-Coupling Reactions of Polyfluoroaryl Imines on Using the Nickel Precatalyst 47

Pioneering work on C−F bond activation and concomitant C−C bond formation reactions at tungsten carbonyl complexes was reported by Richmond et al.8a,45 The treatment of [W(CO)3(EtCN)3] (55) with a variety of less and highly fluorinated Schiff bases was studied. A selected example is depicted in Scheme 24. The oxidative addition of the ligand precursor 56 yields the tungsten fluorido complex 57, as it was also confirmed by X-ray crystallography.8a,45a,c,d Note that the C−F bond activation occurs at the ortho-position to the κ2(N,N)-chelating unit of 56. Complex 57 was further reacted with internal alkynes.45f,g Treatment of 57 with hexafluoro-2butyne at elevated temperatures selectively yields complex 58 which features a cis-arrangement for the fluorido ligand, the inserted alkyne, and one carbonyl ligand. In contrast, UV irradiation of 57 and the alkyne at room temperature gives the

is formed together with [CoF2]n by disproportionation of [CoF(CO)2(PMe3)2], which might be the intermediate carbonyl complex after release of the acetyl imine. A reaction of complex 51 with CO gives the carbonyl insertion product 53 which is supposed to be an intermediate in the formation of the C−C coupling product. In contrast, treatment of a pentafluorophenyl imine derivative with [Co(PMe3)4] (31) affords the formation of the paramagnetic cobalt(II) fluorido complex 54 (Scheme 23).44 The tetragonal-pyramidal structure of 54 with the nitrogen atom at the axial position was confirmed by X-ray spectroscopy. Moreover, a catalytic reaction of the imine with Me2Zn, RZnCl (R = Bn, Cy), or PhZnBr in the presence of [Co(PMe3)4] (31) gives the coupling products. J


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Scheme 21. Functionalization of N-(2,3,6-Trifluorobenzylidene)benzylamine by Suzuki−Miyaura and Negishi Cross-Coupling Reactions

Scheme 22. Functionalization of Difluorophenyl Imines Employing [Co(Me)(PMe3)4] (48)

Scheme 24. Derivatization of the Tungsten(0) Complex 55

Scheme 25. Postulated Mechanism for C−F Bond Activation at the Tungsten(0) Complex 55

Scheme 23. Dialkylation or -arylation of a Pentafluoroarylimine Derivative Using [Co(PMe3)4] (31)

migratory-insertion complex 59 with the fluorido ligand cis to both carbonyl ligands and trans to the inserted alkyne. 59 readily isomerizes into 58 upon heating. The authors proposed a mechanism for the oxidative addition step which is based on the employment of the chelating ligand 60 which differs from 56 by the phenyl ring in the backbone (Scheme 25).8a,45b The reaction of 60 with [W(CO)3(EtCN)3] (55) is much faster compared to the C−F bond activation with 56 yielding 57 (see also Scheme 24).8a,45a,c,d Initially, it was observed that two nitriles at the

tungsten(0) complex 55 are replaced by the Schiff base 60 to give 61. It was suggested that the loss of another EtCN ligand results in the 16-electron intermediate 62 which undergoes oxidative addition of the C−F bond to form complex 63.8a The latter step presumably proceeds via a concerted oxidative addition and is considered to be rate-limiting. Generally, the rate of the C−F bond activation benefits from a high degree of K


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fluorination at the phenyl ring at 56 and 60, as it is suggested by studies with difluorinated compounds. 2.2.2. Oxazoline Functionalities as Directing Groups. Catalytic Suzuki−Miyaura cross-couplings of polyfluoroaryl oxazolines by C−F bond activation at the ortho-position to the directing group were thoroughly studied by Shen and Lu et al.46 Treatment of 2-(pentafluorophenyl)oxazoline with a variety of arylboronic acids affords the ortho-monoarylated products in the presence of [PdCl2(MeCN)2] (64) as catalyst, dppf as ligand, and Cs2CO3 as a base (Scheme 26). Treatment of 2-

Scheme 27. Oxazolinyl-Directed C−F Bond Functionalization of Fluorobenzenes on Employing the Precatalysts 36 and 47

Scheme 26. Suzuki−Miyaura Cross-Coupling Reactions of Polyfluorophenyl Oxazolines 2.2.3. Pyridine Functionalities as Directing Groups. Shen and Lu et al. investigated the applicability of other functional groups as directing groups.47 The reaction of 2(pentafluorophenyl)pyridine with a variety of benzoxazole derivatives affords the cross-coupling products via selective C− F bond activations at the ortho-position with respect to the 2pyridyl group (Scheme 28). These couplings are performed in the presence of [PdCl2(MeCN)2] (64), dppbz (1,2-bis(diphenylphosphino)benzene) and LiOt-Bu. The derivatizations proceed via selective C−F bond activation steps and C−H bond cleavage steps in the presence of LiOt-Bu. Note that the conversions are successful in xylene as solvent, whereas no product formation is observed in polar, aprotic solvents such as dimethylacetamide. Pyridines with a varying degree of fluorination are useful substrates. Reaction of benzoxazoles with 2-(2,3,6-trifluorophenyl)pyridine, which exhibits an unsymmetrical fluorine substitution pattern, leads to selective bond activation at the 2-position as described previously for 2,3,6-trifluorophenyl imine and -oxazoline derivatives (see also Schemes 16, 19−21, 26). Reactions with the less fluorinated 2(2,6-difluorophenyl)pyridine require harsher conditions to give the corresponding products, whereas no coupling was achieved on employing the monofluorinated 2-(2-fluorophenyl)pyridine. These reaction routes are not limited to conversions of fluorophenylpyridines with oxazolines. Additionally, thiazoles, benzothiazoles, benzoimidazoles, oxazoles, and oxadiazoles with alkyl and aryl substituents can be used for the cross-couplings. The nickel complex [NiCl2(PEt3)2] (47) was additionally applied in the selective benzylation by C−F functionalization of a 2,4-difluorophenyl substrate bearing the 4-methylpyridin-2-yl remote group (Scheme 29).43c Tobisu and Chatani et al. described Suzuki−Miyaura crosscoupling reactions of aryl fluorides which bear an orthodirecting pyridyl group by using the precatalyst [Ni(cod)2] (46) and tertiary phosphines such as PCy3.48 With boronic esters in the presence of CsF, substrates such as 2,6-difluoro-1pyridin-2-ylbenzene are selectively activated at the orthoposition to the pyridyl group (Scheme 30). Concerning the directing effect of the 2-pyridyl group, it was proposed that a cyclometalated intermediate 65 might be formed subsequently to a C−F activation step, which also facilitates the rate-limiting oxidative addition of the aryl C−F bond to the Ni center. It is worth mentioning that fluorinated benzene derivatives can also be obtained by using a fluorinated boronic ester in a crosscoupling reaction with a monofluorinated benzene substrate (Scheme 30). 2.2.4. Nitro Functionalities as Directing Groups. The applicability of a nitro directing group was investigated at less fluorinated arenes by Suzuki−Miyaura cross-coupling reactions on using arylboronic acids.49 4-Fluoro-3-nitro-α,α,α-trifluoro-

(pentafluorophenyl)oxazoline with the sterically hindered 2methoxyphenylboronic acid leads to product formation in lower yields compared to reactions with its 3-methoxy and 4methoxy derivatives. In addition, other phenyl oxazolines with a varying degree of fluorination were applied for Suzuki−Miyaura cross-coupling reactions. Analogous to reactions with an imine directing group (see above), it was found that highly fluorinated oxazolines undergo a faster oxidative addition than less fluorinated substrates. Moreover, C−F bond activation is favored over C−H bond activation at the ortho-position. The 2,3,6-trifluorophenyl derivative with an unsymmetrical fluorine substitution pattern is selectively activated at the ortho-position to a fluorine atom and the imine. Note that no reaction was observed for 2-(2,6-difluorophenyl)oxazoline. Oxazoline entities can also serve as remote groups in catalytic Negishi cross-coupling reactions.40d,43c Thus, the platinum precatalyst 36 and the nickel complex 47 promote selective methylation or benzylation reactions of 2,4-difluorobenzene and 2,4,6-trifluorobenzene derivatives at the 2-position with respect to the directing group (Scheme 27). L


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Scheme 28. Selected Examples for C−C Coupling Reactions by C−F and C−H Bond Cleavage

Scheme 29. C−F Bond Functionalization of a Fluorobenzene with a Pyridine Remote Group Employing the Nickel Catalyst 47

Scheme 30. Suzuki−Miyaura Cross-Coupling Reactions of 2Pyridyl-benzenes with Aryl Boronates

toluene can selectively be functionalized at the 4-position on employing phenylboronic acids in the presence of [Pd2(dba)3] (66, dba = dibenzylideneacetone), PMe3, and Cs2CO3 (Scheme 31). The use of 2-methylphenylboronic acid yields the corresponding product in lower yields, possibly due to the steric hindrance of the methyl substituent. The replacement of the nitro substituent at the 3-position by a methyl ester does not result in any reaction, which gives evidence for the directing function of the nitro group. Ab inito calculations of the C−F bond activation step within the model reaction of 1-fluoro-2-nitrobenzene with [Pd(PH3)2] (67) show that a coordination of the nitro group to the palladium influences the activation energy of the C−F insertion step.49,50 Two plausible reaction pathways are conceivable (Scheme 32). It is proposed that either the C−F activation step proceeds via a concerted oxidative addition to yield 68 or an initial nucleophilic attack of the palladium center gives a Meisenheimer-type intermediate 69. The latter could yield the cationic palladium complex 70 by loss of fluoride. The C−C coupling reaction could then be imparted by either complex 68 or 70.51

Efficient and regioselective Suzuki−Miyaura cross-couplings of highly fluorinated nitrobenzene derivatives with aryl boronic acids were reported on using [Pd(PPh3)4] (71) as catalyst and potassium fluoride immobilized on alumina as a base.52 However, the stoichiometric reaction of pentafluoronitrobenzene with 71 furnishes the C−F bond activation product 72 (Scheme 33). M


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Scheme 34. Selective Suzuki−Miyaura Cross-Coupling Reactions of Polyfluoroarenes Bearing a Nitro Directing Group

Scheme 31. Suzuki−Miyaura Cross-Couplings of 4-Fluoro-3nitrobenzotrifluoride

Scheme 32. Possible Intermediates of the C−F Bond Activation Step at 1-Fluoro-2-nitrobenzene (ab Initio Calculations)

Scheme 33. Selective C−F Bond Activation of Pentafluoronitrobenzene

Scheme 35. Palladium-Mediated Sonogashira CrossCoupling of Polyfluoroarenes with a Nitro Directing Group

Several arylboronic acids and esters were employed for the catalytic functionalization of pentafluoronitrobenzene (Scheme 34). The regioselectivity of the C−F bond functionalization was further studied by the reaction of a phenylboronic ester with tetrafluoronitrobenzenes, which exhibit a varying fluorine substitution pattern. In all cases, C−F bonds at the orthoposition with respect to the nitro group were phenylated. As was observed for imines and oxazolines as remote groups, the unsymmetrically substituted 2,3,4,6-tetrafluoronitrobenzene reacts selectively by bond functionalization at the 2-position. The authors assume that nitro groups and fluorine atoms at an ortho-position are beneficial for a C−F activation step via an initial nucleophilic attack of the palladium center directed by the nitro group. Consequently, a derivatization at the 6-position does not proceed, since no ortho-neighboring fluorine atom is present. Note that trifluorophenylnitrobenzenes were used in this reaction as well (Scheme 34). The perfluorinated molecules are more reactive than their less fluorinated analogues, presumably because of the lower electrophilicity of the aromatic ring, which is caused by a lower degree of fluorination. Moreover, the palladium(0) complex [Pd(PPh3)4] (71) mediates regioselective Sonogashira-type cross-coupling reactions of pentafluoronitrobenzene with phenylacetylene (Scheme 35).53 Interestingly, the cross-coupling reaction

proceeds in the absence of a base to yield selectively the activation product at the ortho-position to the nitro group, whereas a reaction in the presence of KF/alumina affords a complex mixture of products. Treatment of 2,3,4,5-tetrafluoronitrobenzene with alkyne derivatives also results in C−F bond functionalization at the ortho-position to the NO2-moiety (Scheme 35). 2,3,4,6-Tetrafluoronitrobenzene reacts in a N


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similar manner. Possibly, the fluorine atom at the 3-position favors the C−F bond activation step, as previously discussed for Suzuki−Miyaura cross-coupling reactions of highly fluorinated nitrobenzenes. 2.2.5. Keto and Hydroxo Functionalities as Directing Groups. Regioselective C−F bond derivatization reactions also proceed selectively at the ortho-position to a keto group. The complex [Co(acac)2] (73) (acac = acetylacetonate) mediates reactions of 2,3,4,5,6-pentafluorobenzophenone with aryl cuprates resulting in a functionalization at both ortho-positions (Scheme 36).54 Note that 4-fluorostyrene and Bu4NI are required for a successful conversion.

Kumada−Tamao cross-coupling reactions with [PdCl2(PCy3)2] (75) as catalyst.57 Treatment of 2,4-difluorophenol with PhMgBr or 4-FC6H4MgBr furnishes the diphenyl products by selective C−F bond cleavage at the ortho-position (Scheme 38). Scheme 38. Ortho-Selective Kumada−Tamao CrossCoupling of Fluorophenoles

Scheme 36. Ortho-Selective Catalytic Functionalization of Fluoroaryl Ketones

In Suzuki−Miyaura cross-coupling reactions with [Ru(H)2(CO)(PPh3)3] (74) as catalyst, a C−F bond functionalization ortho to the keto group of polyfluoroarylketones was achieved with PhB(O2C5H10) and CsF (Scheme 37).55 The reactions

Similar results are obtained in the reaction of 2,5difluorophenol with 4-MeC6H4MgBr. Further variation of the remote group revealed that a hydroxymethyl directing group can promote the cross-coupling reaction as well, whereas a methoxy entity slows down the reaction significantly and lowers the yield of the coupling product. Thus, the authors speculate that a protic directing group is necessary for a rapid conversion although the ortho-preference in bond activation remained in the presence of the methoxy group. Note that reacting 2-fluoro4-chlorophenol with PhB(OH)2 selectively furnishes the C−F bond activation product. Moreover, it is believed that a 3-fold excess of the Grignard reagent is needed, since deprotection of the hydroxyl group is required prior to the coupling.57b Csp3−Csp2 ortho-selective derivatization of 2,4-difluorophenol is achieved in Kumada−Tamao cross-coupling reactions on employing a long-chain alkyl Grignard reagent and [NiCl2(dippbz)] (76) (dippbz = 1,2-bis[di(4-isopropylphenyl)phosphine]benzene) as a nickel(II) catalyst (Scheme 39).58

Scheme 37. Ruthenium-Mediated Cross-Coupling of Fluorophenyl Ketones

Scheme 39. Nickel-Mediated Catalytic Alkylation of 2,4Difluorophenol

proceed in the presence of trimethylvinylsilane which is believed to activate the catalyst 74.56 The reaction with 2′fluoro-6′-trifluoromethylacetophenone affords the activation of the C−F bond in the 2′-position without affecting the trifluoromethyl group. Employing the highly fluorinated 2′,3′,4′,5′,6′-pentafluoroacetophenone results in selective phenylation at both C−F bonds at the ortho-positions. Tandem functionalization of ortho-C−F and ortho-C−H bonds was realized for 2′,3′,4′,5′-tetrafluoroacetophenone. The authors believe that the generation of the silyl alkyl group is the result of a C−H bond cleavage. Selective C−F bond functionalizations of fluoroarenes with a hydroxy group as the directing group were achieved in

Noteworthy, no β-hydrogen elimination was observed as a side reaction. The authors speculate that the intermediary formation of a Mg−O bond by deprotonation of the hydroxy group with the Grignard reagent is essential to achieve high efficiencies. Extensive studies were additionally done in order to demonstrate the high selectivity for an ortho-functionalization using dihalophenols which bear different halogen atoms and by O


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Scheme 40. Intramolecular Derivatization of Rhodium Complex 77

using mixtures of monosubstituted phenols. The influence of the intrinsic reactivity order of the halogens is weaker than the directing effects of the hydroxy group. 2.2.6. Derivatization of Metal-Bound Fluorinated Ligands. Saunders et al. investigated intramolecular C−C bond formation reactions which lead to ligands with cyclopentadienyl phosphine moieties at rhodium and iridium centers as well as benzyl linked phosphines at ruthenium.59 An example for such a C−C coupling in the ligand sphere of a rhodium complex is shown in Scheme 40.59a,b,i,k The reaction is initiated by deprotonation of the Cp* ligand of 77, which presumably results in the formation of the η4-fulvene complex 78 or the corresponding carbanion 79. A nucleophilic intramolecular attack of the methylene functionality of 78 at a C−F bond located at the ortho-position to a phosphorus atom would consequently afford the formation of 80 as an intermediate. A subsequent second C−F activation reaction finally gives complex 81. A comparable reaction was published by Hughes et al. on employing a cobalt Cp*-complex, and an analogous mechanism was suggested.60 The deprotonation of 77 occurs with stoichiometric amounts of 1,8-bis(dimethylamino)naphthalene (proton sponge) which results in a quantitative conversion to give 81. Substoichiometric loads of the proton sponge furnish a mixture of 80 and 81, whereas the latter represents the major compound. It is presumed that the fluoride, which is released in the cause of the reaction, acts as a base as well. This is consistent with a reaction which employs Bu4NF as a base, which also yields 81. The complexes 82−86 represent additional examples for products of intramolecular C−C bond formation reactions within the ligand sphere at rhodium, iridium, and ruthenium (Scheme 41).

Scheme 41. Selected Examples for Transition-Metal Complexes Furnished by Intramolecular C−C Bond Formation in Their Coordination Sphere

by C−C cross-coupling reactions yielding fluorinated substrates are less common (refs 5g, 8m, w, x, 9a−j, l−n, r, and 62). 2.3.1. Reactions at Nickel. [Ni(PEt3)4] or [Ni(cod)2] (46) in the presence of PEt3 react with pentafluoropyridine to yield the square-planar nickel(II) fluorido complex 87 as the predominant species (Scheme 42).8f,63 Remarkably, a C−F Scheme 42. Formation of the Nickel Complexes 87 and 88 by C−F Bond Activation of Pentafluoropyridine or 2,3,5,6Tetrafluoropyridine

2.3. C−C Bond Formation at Polyfluorinated Heteroaromatics

Nearly all transition-metal-mediated C−C functionalization reactions of heteroaromatics by C−F bond activation are based on catalysts which contain a palladium, nickel, or rhodium center. Pentafluoropyridine and 2,3,5,6-tetrafluoropyridine turn out to be excellent reactants and are employed in several studies. Regioselective C−F bond activations at the 2- or 4position with respect to the nitrogen atom are often found. The observed selectivity may depend not only on the nature of the transition-metal complex but also on the substrate itself. The C−F activation step may also be assisted by additional metalbound ligands such as phosphines.14k,o,x,61 Although many C−F bond functionalization reactions to give hydrodefluorination products are known, derivatization reactions of heteroaromatics

bond cleavage occurs at the 2-position of the perfluorinated pyridine. Minor products are probably derivatives, which are metalated at either the 3- or 4-position. The complex [Ni(η2C5NF5)(PEt3)2], which is presumably an intermediate, was detected by low-temperature NMR spectroscopy.8f,63b Mechanistically, several possibilities were discussed for the C−F bond cleavage step, such as an initial electron transfer, a nucleophilic attack of the metal, a concerted mechanism, and a phosphine assisted pathway.8f,61d,63b The first two are not consistent with an activation at the 2-position. DFT calculations at [Ni(PMe3)2] (89) indicate that a phosphine assisted pathway P


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Scheme 43. Activation of Pentafluoropyridine; Computed Reaction Pathway for the Formation of Complex 92; Experimental Results with the Bisphosphine Nickel Complex 93

Scheme 44. C−F Bond Activation at Pentafluoropyridine and 2,3,5,6-Tetrafluoropyridine Using Either i-Pr2PCH2CH2OMe or iPr2PCH2CH2NMe2 as Phosphines and [Ni(cod)2] (46)

fluorido complex 92. It is noteworthy that coordination of the nitrogen lone pair of the reacting pentafluoropyridine to the metal center has a stabilizing influence on the intermediate for a bond activation at the 2-position. Note that although pentafluoropyridine is not a Brønsted base, transition-metal complexes in which pentafluoropyridine coordinates via the

leads to C−F bond activation at the 2-position (Scheme 43).61d Initial η2-precoordination of pentafluoropyridine yields 90. The C−F bond cleavage proceeds by transfer of the fluorine atom from the carbon to the phosphorus atom to give the metallophosphorane nickel(II) intermediate 91. Then, migration of the fluorine atom to the nickel center furnishes the Q


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Scheme 45. Cross-Coupling Reactions Using the Nickel Complex 87

nitrogen atom at the metal center are known.64 However, a different result is obtained by reacting pentafluoropyridine with [Ni(η2-C14H10)(PEt3)2] (93) as a {Ni(PEt3)2} synthon (Scheme 43). This conversion yields the mono- and dinuclear nickel pyridyl complexes 87 and 94 as C−F bond activation products. Moreover, there are indications for the formation of the η2-coordinated complexes 95, 96, and 97 as intermediates.63b However, based on kinetic studies as well as on DFT calculations, the authors speculate that other reaction pathways than a phosphine-assisted mechanism or a concerted oxidative addition pathway may operate. The reaction of [Ni(cod)2] (46) and PEt3 with 2,3,5,6tetrafluoropyridine yields the complex trans-[NiF(2-C5NF3H)(PEt3)2] (88) (see Scheme 42).63a No nickel pyridyl species with the metal at the 4-position was detected for the conversion at ambient temperature. Johnson et al. showed that treatment of 2,3,5,6-tetrafluoropyridine with the {Ni(PEt3)2} synthon 93 at lower temperatures gives the intermediate C−H activation product trans-[Ni(H)(4-C5NF4)(PEt3)2] as the major product whereas 88 is formed at room temperature with high regioselectivity.63b They presumed that the C−F bond cleavage proceeds via a concerted oxidative addition mechanism, since cis-[NiF(2-C5NF3H)(PEt3)2] was observed as an intermediate within the formation of 88. Braun et al. investigated nickel-mediated C−F bond activation and cross-coupling reactions on using hemilabile coordinating phosphine ligands. Literature data suggested that transition-metal complexes bearing monodentate ligands might catalyze cross-coupling reactions less efficiently than systems based on chelate ligands.65 Addition of pentafluoropyridine to [Ni(cod)2] (46) in the presence of i-Pr2PCH2CH2OMe in excess results in the generation of the bisphosphine compounds 98 and 99 in a 1:8 ratio (Scheme 44).66 Using i-Pr2PCH2CH2OMe in stoichiometric amounts leads neither to products with bidentate κ2-(P,O)-geometry nor to a change in the ratio of complex 98 to 99. In accordance with these observations, employment of 2,3,5,6-tetrafluoropyridine with i-Pr2PCH2CH2OMe and [Ni(cod)2] (46) gives trans-[NiF(2-C5NF3H){κ1-(P)-i-Pr2PCH2CH2OMe}2] (100) as the only organometallic product. However, treatment of [Ni(cod)2] (46) with i-Pr2PCH2CH2NMe2 and pentafluoropyridine affords the nickel(II) complexes 101 and 102 in a 2:1 ratio. In a similar manner, trans-[NiF(2-C 5 NF 3 H){κ 2 -(P,N)-i-Pr 2 PCH 2 CH2NMe2}] (103) was generated by using 2,3,5,6-tetrafluoropyridine. The chelating coordination mode of i-Pr2PCH2CH2NMe2 was confirmed by X-ray crystallography. Transition-metal fluorido complexes often show an increased reactivity compared to their bromido and chlorido analogs (refs 1o, 8a, j, 22a, b, 30, 32, 66, and 67). For example, trans-[PdF(4C5NF4)(Pi-Pr3)2] (104) exhibits some reactivity in the Stille cross-coupling reaction of pentafluoropyridine whereas trans[PdCl(2-C5NF4)(Pi-Pr3)2] shows no catalytic activity as

described later (see section 2.3.2).67j Thus, C−F activation via an oxidative addition mechanism can be an essential key step for realizing sophisticated C−C cross-coupling reactions of highly fluorinated aromatics. Perutz et al. accomplished further derivatization reactions at the nickel fluorido complex 87. A transmetalation with Me2Zn results in the formation of trans-[Ni(Me)(2-C5NF4)(PEt3)2] (105) (Scheme 45).67d Upon exposure to air of the latter, the C−C coupling product 2-MeC5NF4 is generated. In the presence of CO, [Ni(CO)2(PEt3)2] (106) and 2-(COMe)C5NF4 are obtained. An insertion−migration process into the nickel−methyl bond is most likely the initial step, since no reaction takes place between complex 87 and CO. It was suggested, that the reductive elimination of 2-acyl-3,4,5,6tetrafluoropyridine is initiated by coordination of a second CO molecule to the transition-metal center. In a stoichiometric reaction of Bu3SnCHCH2 with the nickel fluorido complex 87 the C−C cross-coupling product 107 is furnished (Scheme 46).68 [Ni{η2-2-C5NF4(CH CH2)}(PEt3)2] (108) and the C−F activation product 109 were identified as intermediates by NMR spectroscopy. Scheme 46. Reaction of trans-[NiF(2-C5NF4)(PEt3)2] (87) with Bu3SnCHCH2

In accordance with these stoichiometric conversions, pentafluoropyridine reacts with Bu3SnCHCH2 in the presence of catalytic amounts of the nickel complex 87, Cs2CO3, and PEt3, to yield 3,4,5,6-tetrafluoro-2-vinylpyridine (TON = 4) (Scheme 47).68 Likewise, pyridines, which bear preferentially a phenyl group at the ortho-position to the nitrogen atom, are yielded by R


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Scheme 47. Catalytic Stille and Suzuki−Miyaura Cross-Coupling Reactions of Pentafluoropyridine

Scheme 48. Catalytic Stille and Suzuki−Miyaura Cross-Coupling Reactions of 2,3,5,6-Tetrafluoropyridine

Suzuki−Miyaura-type cross-coupling reactions with TONs of 6−8 employing the monodentate bisphosphine catalysts 98 and 99.66 With the catalysts 101 and 102, which bear a chelating phosphine, 3,5-difluoro-2,4,6-triphenylpyridine was generated with a TON of 8. Similarly to the reaction of pentafluoropyridine with Bu3SnCHCH2, 2-vinyl-3,5,6-trifluoropyridine can be synthesized selectively by a Stille-type coupling of 2,3,5,6-tetrafluoropyridine in the presence of the nickel complex 87 (TON = 5) (Scheme 48).68 The usage of the nickel complex 103 as a precursor generates 3,5-difluoro-2,6-diphenylpyridine in a Suzuki−Miyaura-type coupling reaction with a TON of 7.66 However, the bisphosphine complex 100 catalyzes this conversion more efficiently with a TON of 40 (based on the C−F activation steps). In addition, other boronic acids have been applied successfully in this aryl−aryl coupling reactions. Furthermore, [Ni(cod)2] (46) reacts with 5-chloro-2,4,6trifluoropyrimidine in the presence of PPh3 to yield trans[NiF(4-C4N2ClF2)(PPh3)2] (110) as the major product and its chlorido derivative trans-[NiCl(4-C4N2F3)(PPh3)2] in small amounts (Scheme 49).22a,b With Pi-Pr3 or PCy3 as phosphine ligands, the comparable C−F bond activation products 111 and 112 are furnished, whereas C−Cl bond cleavage is obtained

Scheme 49. C−F Bond Activation at 5-Chloro-2,4,6trifluoropyrimidine in the Presence of [Ni(cod)2] (46) and Different Phosphines

with PEt3 as ligands (complex 113). This chemoselectivity may be attributed to the steric demand of the phosphine ligand. Note that a comparable reaction employing [Pd(PPh3)4] (71) causes C−Cl bond activation. S


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A derivatization of the nickel pyrimidyl complex 110 was achieved by treatment with an excess of TolB(OH)2 which results in a slow formation of the cross-coupling product 5chloro-2-fluoro-4,6-ditolylpyrimidine and small amounts of [Ni(PPh3)4] (Scheme 50).22b The formation of the diaryl

Scheme 52. Suzuki−Miyaura Cross-Coupling Reactions of Monofluorinated Purine (2′-Deoxy)nucleosides

Scheme 50. C−C Bond Formation Reaction to Yield 5Chloro-2-fluoro-4,6-ditolylpyrimidine

2.3.2. Reactions at Palladium. The regioselective C−F bond activation at pentafluoropyridine at the 4-position was achieved by a stepwise treatment of [Pd(Me)2(tmeda)] (115) (tmeda = N,N,N′,N′-tetramethylethylenediamine) with Pi-Pr3 and the pyridine (Scheme 53).14f The reaction gives [PdF(4-

pyrimidine proceeds via the fluorido complex 114 which was detected as an intermediate by NMR spectroscopy. Thus, the oxidative addition of an intermediate 5-chloro-2,6-difluoro-4tolylpyrimidine which gives 114 is presumably faster than the subsequent second transmetalation with TolB(OH)2. Note that treatment of trans-[NiF(4-C4N2ClF2)(PCy3)2] (111) with TolB(OH)2 yields only traces of the 5-chloro-2-fluoro-4,6ditolylpyrimidine. In addition, nickel-catalyzed Suzuki−Miyaura cross-coupling reactions of pyrimidines were explored. Diarylpyrimidines are generated by the reaction of 5-chloro-2,4,6-trifluoropyrimidine with boronic acids in the presence of the nickel complex 110 as catalyst, Cs2CO3 as base, and PPh3 (Scheme 51).22b On

Scheme 53. C−F Bond Activation of Pentafluoropyridine at Palladium in the Presence of Pi-Pr3

Scheme 51. Catalytic Suzuki−Miyaura Cross-Coupling Reactions of 5-Chloro-2,4,6-trifluoropyrimidine

C5NF4)(Pi-Pr3)2] (104). It was shown by 31P NMR spectroscopy that the 14-electron complex [Pd(Pi-Pr3)2] (116) is formed as an intermediate prior to the C−F bond activation step. A comparable reaction with [Pd(PCy3)2] (33) gives [PdF(4-C5NF4)(PCy3)2]. Note that the palladium complexes 116 and 33 do not react with 2,3,5,6-tetrafluoropyridine, neither by C−H nor by C−F activation. These observations are in sharp contrast to the results found at nickel complexes (see above Schemes 42, 44, and 48). Note that at the Pt complexes [Pt(PR3)2] (R = i-Pr, Cy) an addition of the C−F bond of pentafluoropyridine across the Pt−P bond occurs to give trans[Pt(R)(4-C5NF4)(PR3)(PFR2)] whereas the hydrido complex cis-[Pt(H)(4-C5NF4)(PCy3)2] is furnished by treatment of [Pt(PCy3)2] with 2,3,5,6-tetrafluoropyridine.14f Addition of i-Pr2PCH2CH2OMe to the palladium(II) complex 115 led to formation of the bisphosphine palladium(0) species 117 in which both phosphines are bound in a monodentate fashion (Scheme 54) as it was also found for [Pd{κ1-(P)-(dmobp)}2] (dmobp = di-tert-butyl(2,6dimethoxybenzyl)phosphine).65b,67r DFT calculations on trans-

employing PhB(OH)2, TolB(OH)2, or 4-CF3C6H4B(OH)2, a diarylation is found, whereas the reaction with MesB(OH)2 (Mes = 2,4,6-trimethylphenyl) gives the mono- and disubstituted pyrimidines (32%, 16%) respectively. Note that the fluorido complexes trans-[NiF(4-C4N2ClF2)(PR3)2] (111, R = Cy; 112, R = i-Pr) do not represent suitable catalysts. Interestingly, the chlorido complex trans-[NiCl(4-C4N2ClF2)(PPh3)2], which can be prepared by reaction of 110 with Me3SiCl, also shows no catalytic activity. It was assumed that the higher reactivity of the fluorido complex 110 is crucial for the transmetalation step (refs 1o, 8a, j, 22a, b, 30, 32, 66, 67, 67m, and o−s). Moreover, nickel-catalyzed Suzuki−Miyaura cross-coupling reactions of monofluorinated purine (2′-deoxy)nucleosides with 4-fluorophenylboronic acid in the presence of [Ni(cod)2] (46), an Arduengo carbene, and K3PO4 as a base were reported (Scheme 52).69

Scheme 54. C−F Bond Activation on Pentafluoropyridine at 117

T


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[Pd{κ1-(P)-i-Pr2PCH2CH2OMe}2] (117) reveal that a chelating κ2-(P,O)-geometry is also less favored in the gas phase. However, complex 117 is a suitable starting compound for a C−F bond activation reaction at pentafluoropyridine to yield 118 within 4 h at room temperature. The molecular structure of 118 was confirmed by X-ray crystallography. A stoichiometric reaction of the palladium fluorido complex trans-[PdF(4-C5NF4)(Pi-Pr3)2] (104) and Bu3SnCHCH2 furnishes [Pd(Pi-Pr3)2] (116) and the C−C coupling product 2,3,5,6-tetrafluoro-4-vinylpyridine (Scheme 55).67j The reaction

Scheme 57. C−F Bond Activation Reaction of Pentafluoropyridine at [Rh(H)(PEt3)4] (119) or [Rh(H)(PEt3)3] (120)

Scheme 55. C−C Bond Formation To Give 2,3,5,6Tetrafluoro-4-vinylpyridine

avoided by employing [Rh(H)(PEt3)3] (120) as a reactant.68 Possible mechanisms for the activation of pentafluoropyridine at the 4-position may include a nucleophilic attack of the metal at the substrate or an electron transfer pathway.14c,71 An oxidative addition mechanism to give a rhodium(III) intermediate was tentatively excluded, because no competing reductive elimination of 2,3,5,6-tetrafluoropyridine and [RhF(PEt3)3] was observed. Note that, as mentioned above, the C−F bond activation of pentafluoropyridine at nickel and palladium(0) complexes yields fluorido complexes by oxidative addition, whereas no such compound is formed on employing the rhodium complexes 119 and 120. A derivatization of the metalated pyridine in [Rh(4C5NF4)(PEt3)3] (121) is possible by adding an excess of either CO or MeI (Scheme 58).70b The reactivity of complex 121 is in part influenced by the strong M−C(Pyridyl) bond.13b,42c Thus, an approximately square-planar rhodium(I) carbonyl derivative 122 is formed upon exposure to CO. No C−C bond between the pyridyl and carbonyl ligand by insertion−migration is formed, as it is observed for other anionic nonfluorinated aryl ligands.72 However, the generation of the square-pyramidal compound trans-[RhI(COMe)(4C5NF4)(PEt3)2] (123) reveals that an insertion of the carbonyl ligand can be achieved after oxidative addition of MeI to complex 122. By heating 123 in a CO-enriched atmosphere, 4acetyl-2,3,5,6-tetrafluoropyridine is formed by reductive elimination. It is assumed that elevated temperatures are needed to overcome the high M−C(pyridyl) bonding energy within 123. No acetyl iodide is formed, as is found for other Rh(III) acyl iodido complexes.72c,73 Complex 121 reacts with MeI, yielding the square-pyramidal rhodium(III) complex 124. This reaction is reversible when PEt3 is added. In the presence of CO, the octahedral complex 125 releases the C−C coupling product 4methyl-2,3,5,6-tetrafluoropyridine at elevated temperatures by formation of the rhodium(I) species 126. Treatment of complex 125 with PEt3 gives 122 and [PEt3Me]I. The transarrangement of the carbonyl and methyl ligand in complex 125 prohibits the generation of an acyl ligand as found for 123. Nevertheless, 125 is not stable in solution and slowly forms the insertion product 123. It was suggested that the conversion of 125 to 123 could take place via 122.

is comparable to the treatment of the nickel fluorido complex 87 with Bu3SnCHCH2, but, however, a different isomer of the fluorinated pyridine is formed (see above Scheme 46). The authors did not succeed in accessing 2,3,5,6-tetrafluoro-4vinylpyridine by treatment of pentafluoropyridine with vinyllithium. In a catalytic Stille coupling reaction on using trans-[PdF(4C5NF4)(Pi-Pr3)2] (104) as a catalyst, 2,3,5,6-tetrafluoro-4vinylpyridine is generated with a TON of 6 by reaction of pentafluoropyridine with Bu3SnCHCH2 (Scheme 56).67j Scheme 56. Catalytic Stille and Suzuki−Miyaura CrossCoupling Reactions of Pentafluoropyridine

Notably, the chlorido complex trans-[PdCl(2-C5NF4)(PiPr3)2] does not catalyze this reaction, which is in accordance with the results found for the nickel complex trans-[NiCl(4C4N2ClF2)(PPh3)2] as described above. Furthermore, Suzuki− Miyaura cross-coupling reactions of boronic acids and pentafluoropyridine proceed in the presence of the palladium(II) fluorido complex 118 and a base (Scheme 56).67r The products 2,3,5,6-tetrafluoro-4-phenylpyridine and 2,3,5,6-tetrafluoro-4tolylpyridine are formed catalytically with TONs of 12 and 9, respectively. A stoichiometric reaction of PhB(OH)2 with complex 118 furnishes the metal complex trans-[Pd{κ1-(P)-iPr2PCH2CH2OMe}2] (117) and the cross-coupling product. 2.3.3. Reactions at Rhodium. A selective C−F bond activation at pentafluoropyridine at the 4-position is achieved by employing either [Rh(H)(PEt3)4] (119) or [Rh(H)(PEt3)3] (120) to yield the pyridyl complex 121 (Scheme 57).70 Both complexes are in equilibrium in the presence of phosphine. A reaction of free phosphine and pentafluoropyridine can be

2.4. C−C Bond Formation at Polyfluorinated Olefins

2.4.1. Transformation of C−F Bonds at Less Fluorinated Olefinic Derivatives. α-Fluorostyrenes can be synthesized by a variation of a Heck reaction with [Pd(OAc)2] (127) as catalyst starting from 1,1-difluoroethylene and aryl iodides (Scheme 59).74 Mechanistically, it was proposed that an insertion of the fluoroalkene occurs after the oxidative addition of the aryl iodide at the Pd(0) center. MNDO calculations (MNDO = Modified Neglect of Diatomic Overlap) on di- and U


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Scheme 58. Rhodium-Mediated Cross-Coupling Reactions of Complex 121 with MeI and CO

reactions can also be performed with trifluoroethylene, and (Z)-α,β-difluorostyrene is generated as the main product in the reaction with iodobenzene. Ichikawa and Minami et al. reported a palladium-catalyzed cross-coupling reaction of a 1-fluorovinylzirconocene with aryl iodides.751-Fluorovinylzirconocenes 128 can be obtained by treatment of difluoroolefins F2CCHX with {Cp2Zr}. The latter is accessible from zirconocene dichloride and buthyllithium. The in situ reaction of 128 with aryl iodides in the presence of catalytic amounts of [Pd2(dba)3] (66) and PPh3 and an excess of ZnI2 leads to the coupling products (Scheme 60).

Scheme 59. Arylation of Polyfluorinated Alkenes with Iodobenzenes; Schematic Representation of the Charge Controlled Insertion Step

Scheme 60. Palladium-Catalyzed Cross-Coupling Reactions of 1-Fluorovinylzirconocenes

Saeki and Tomao et al. found that 1-(2,2-difluoroethenyl)naphthalene can be coupled with the arylzinc reagent 4MeC6H4ZnCl.20 With [PdCl2(dppp)] (129) as catalyst, the (Z)-isomer of the monocoupling product was obtained in 70% yield (Scheme 61). Whereas the dicoupled, fluorine-free product was formed as the major byproduct, the (E)-isomer of the monocoupling product was not observed. Cowie et al. reported the iridium-mediated synthesis of cisdifluoropropylene and 2-fluoropropylene from trifluoroethylene or 1,1-difluoroethylene, respectively.76 In a stoichiometric reaction of the cationic dinuclear iridium complex [Ir2(CH3)(CO)2(dppm)2]+ (130, dppm = 1,1-bis(diphenylphosphino)methane, counterion: [CF3SO3]−) with trifluoroethylene or 1,1-difluoroethylene, the fluoroolefin-bridged compounds [Ir2(CH3)(CO)2(μ-CHFCF2)(dppm)2]+ (131) or [Ir2(CH3)(CO)2(μ-CH2CF2)(dppm)2]+ (132) are obtained (Scheme 62).77 Subsequent fluoride ion abstraction by trimethylsilyl triflate at low temperature affords the corresponding fluorovinyl

trifluoroethylene suggest that the insertion step is charge controlled; thus the negatively charged carbon atom (the lowor nonfluorinated one) is coordinated to the metal center. A βfluorine elimination finally affords the fluorinated styrene and a Pd(II) compound. However, the regeneration of a Pd(0) species, which is necessary to complete a catalytic cycle, is ambiguous. It was also found that the products of a β-hydride eliminationβ,β-difluorostyrenesare formed only in traces and that acceptor-substituted aryl iodides as substrates almost quantitatively yield the biphenyl coupling products. The V


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Scheme 61. Cross-Coupling of 1-(2,2Difluoroethenyl)naphthalene with 4-MeC6H4ZnCl

Scheme 63. Palladium-Mediated Synthesis of RingFluorinated Indene

Scheme 62. Iridium-Mediated Synthesis of cisDifluoropropylene and 2-Fluoropropylene from Trifluoroethylene or 1,1-Difluoroethylene

Scheme 64. Palladium-Catalyzed Synthesis of 4Difluoromethylene-substituted 1-Pyrrolines

tion and subsequent β-fluorine elimination. PPh3 finally reduces the formed palladium(II) species and closes the catalytic cycle. Following a related approach, Ichikawa et al. recently reported a stoichiometric nickel-mediated [3 + 2] cycloaddition of 2-trifluoromethyl-1-alkenes with alkynes leading to fluorinecontaining multisubstituted cyclopentadienes at [Ni(cod)2] (46) in the presence of PCy3 (Scheme 65).80 This reaction presumably proceeds via coordination of the alkene and alkyne moiety to the nickel center, oxidative cyclization, β-fluorine elimination, 5-endo insertion and again β-fluorine elimination, and formation of the fluorinated cyclopentadiene derivative as well as of NiF2.

products [Ir 2 (CH 3 )(CF 3 SO 3 )(CO) 2 (μ−η 1 :η 2 -CFCFH)(dppm)2]+ (133) and [Ir2(CH3)(CF3SO3)(CO)2(μ−η1:η2CFCH2)(dppm)2]+ (134). Treatment of 133 and 134 with CO liberates cis-difluoropropylene or 2-fluoropropylene, respectively, and the dicationic Ir-pentacarbonyl complex [Ir2(CO)5(dppm)2]2+ (135) is formed. Overall, metal−metal cooperativity is employed to activate fluoroolefinic substrates and to transform fluoroethylenes into fluoropropylenes by the net replacement of a fluorine atom by a methyl group. A palladium-mediated method for the synthesis of a ringfluorinated indene via a Heck-type 5-endo-trig cyclization promoted by vinylic fluorines was reported by Ichikawa et al.78 Treatment of an aryl triflate with stoichiometric amounts of [Pd(PPh3)4] (71) and PPh3 in DMA and subsequent addition of PhSH afford the 3-fluoroindene via oxidative addition of the aryl triflate to the palladium(0) species and the subsequent 5-endo-trig cyclization (Scheme 63). Ichikawa et al. also reported the synthesis of 4-difluoromethylene-1-pyrrolines via a palladium-catalyzed 5-endo Hecktype cyclization.79 4-Difluoromethylene-1-pyrrolines can be obtained selectively from o-pentafluorobenzoyloxime derivatives in the presence of catalytic amounts of [Pd(PPh3)4] (71) and equimolar amounts of PPh3 (Scheme 64). Mechanistically, the palladium(0) species undergoes an oxidative addition of the O-pentafluorobenzoyloxime moiety followed by 5-endo cycliza-

Scheme 65. Nickel-Mediated [3 + 2] Cycloaddition of 2Trifluoromethyl-1-alkenes with Alkynes

W


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2.4.2. Transformation of C−F Bonds at Perfluorinated Olefinic Derivatives. Ohashi and Ogoshi et al. described a Negishi-type catalytic transformation of tetrafluoroethylene based on C−F bond activation reactions.81 A stoichiometric reaction of tetrafluoroethylene with [Pd(η2-C2H4)(PPh3)2] (136) leads to the replacement of the ethylene ligand by tetrafluoroethylene to yield [Pd(η2-C2F4)(PPh3)2] (137, Scheme 66). Addition of LiI induces the cleavage of one

Scheme 67. Suzuki−Miyaura Cross-Coupling Reactions of Tetrafluoroethylene, Hexafluoropropylene and α,αDifluoroethylene with Aryl Boronates; Complex 139 as the Intermediate Oxidative Addition Product of Tetrafluoroethylene Using the Phosphine Ligand PCy3

Scheme 66. C−F Activation of Tetrafluoroethylene and C−C Coupling Reactions with Aryl Zinc Compounds in the Presence of LiI

transformations of hexafluoropropylene were observed in the coordination sphere of the metal. Treatment of hexafluoropropylene with [Ni(PMe3)4] (49) leads to the π-coordination of the fluoroalkene and the formation of the complex [Ni{η2CF(CF3)CF2}(PMe3)3] (141) (Scheme 68). X-ray crystallo-

C−F bond to give LiF and the trifluorovinylpalladium(II) iodide species trans-[PdI(η1-CFCF2)(PPh3)2] (138). Further treatment of 138 with Ph2Zn in the presence of LiI affords the cross-coupling product. Similar to the findings for the transformations of perfluoroarenes by a comparable protocol35 (see section 2.2.), LiI was found to be essential for the C−F activation step and it significantly facilitates the transmetalation step. Catalytic reactions proceed at 40 °C with catalyst loadings of 0.01 mol % of [Pd2(dba)3] (66) in the presence of LiI for various aryl zinc compounds, which were prepared in situ from ZnCl2 and a Grignard reagent. In comparable reaction sequences tetrafluoroethylene was derivatized by Suzuki−Miyaura cross-coupling reactions on using aryl boronates instead of aryl zinc compounds.33 As a consequence the substrate scope was significantly enlarged toward derivatives containing nitro, aldehyde, ester, and cyano functions. Furthermore, in addition to tetrafluoroethylene, hexafluoropropylene and α,α-difluoroethylene were successfully applied in a coupling reaction with a 1-naphtyl-boronate. With PCy3 or Pi-Pr3 as ligands instead of PPh3, no LiI or any acid is needed to promote the crucial C−F bond activation/oxidative addition step (Scheme 67). Mechanistically, the oxidative addition product of tetrafluoroethylene trans-[PdF(η1-CF CF2)(PCy3)2] (139), which was also characterized crystallographically, is suggested to play an essential role. Stoichiometric, Lewis acid promoted C−F bond activation and transformation reactions of hexafluoropropylene by nickel phosphine complexes were reported by Li et al. in 2013.82 Although the final reductive elimination step to obtain the derivatized fluoroorganic compounds was not described, the reactions are of interest, because multiple C−F bond

Scheme 68. Nickel-Mediated Stoichiometric, Lewis Acid Promoted C−F Bond Activation and Transformation Reactions of Hexafluoropropylene

graphic data suggest that the coordination mode of the fluoroalkene in 141 is best described as a metallacyclopropane structure. Addition of ZnCl2 to 141 triggers the C−F oxidative addition step, and the nickel chlorido species trans-[NiCl{η1C(CF3)CF2}(PMe3)2] (142) is formed. Interestingly, the reaction of 142 with 2 equiv of phenylethylmagnesium bromide leads to a subsequent C−F bond activation to furnish trans[NiBr{CF3CHC(CH2CH2C6H5)}(PMe3)2] (143). Mechanistically, a combination of C−F bond activation reactions, a X


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transmetalation, and reductive elimination steps were proposed to explain the generation of 143.

Scheme 70. Catalytic Arylthiolation of Hexafluorobenzene (Major Products Are Shown) and of Selected Less Fluorinated Benzene Derivatives

3. C−F ACTIVATION AND C-HETEROATOM BOND FORMATION 3.1. Derivatization of Aromatic Compounds

A remarkable catalytic C−F bond derivatization of highly and less fluorinated acetophenones as well as of a less fluorinated phenyloxazoline was reported by Murai et al. in 1998.83 Exposure of the fluorinated substrates to the cationic complex [Rh(cod)2][BF4] (144) in the presence of hexamethyldisilane leads to a selective C−F bond transformation of pentafluoroand 2,6-difluoroacetophenone to give ortho-trimethylsilylacetophenones (Scheme 69). The C−F bond activation at the orthoScheme 69. Catalytic Silylation of Pentafluoroacetophenone, 2,6-Difluoroacetophenone, and Difluorophenyloxazoline

position to the keto group is presumably promoted by the fivecentered intermediate 145, in which the coordination of the carbonyl group to the metal center controls the regioselectivity. For the less fluorinated oxazoline, products of monosilylation and bissilylation along with two hydrolysis products are obtained. Yamaguchi et al. developed an interesting strategy for a rhodium-catalyzed arylthiolation of polyfluorobenzenes.84 In the presence of catalytic amounts of [Rh(H)(PPh3)4] (146) and dppbz a broad range of fluorobenzenes undergo C−F activation followed by C−S bond formation upon treatment with diaryl disulfides to yield thioethers (Scheme 70). Addition of free PPh3 is essential, because the phosphine acts as a trapping agent to give F2PPh3. The authors assumed a rapid fluoride transfer from the metal center to the phosphorus atom of the PPh3. There is a preference to form derivatives with two thiolate groups in a mutually para-position at hexafluorobenzene. In addition, difluorido compounds with the fluorine atoms in the para-position are favorably generated. The degree of thiolation varies and depends on the ratio of fluorobenzenes to disulfides. Monofluorinated substrates were also derivatized, but this results in nonfluorine containing organosulfur products. Note that the reaction of hexafluorobenzene with thiolates such as ArSNa results in the complete defluorination

furnishing C6(SAr)6 without the presence of any transition metal.85 However, selective transformations at the aromatic ring and often functional group tolerance can be achieved in transition-metal-mediated reactions. In comparable conversions the scope for the C−S bond functionalization of pentafluorobenzene was demonstrated at a variety of substrates bearing different functional groups.86 The transformations catalyzed by the rhodium complex 146 give diaryl sulfides and were achieved by employing several sulfur sources. Thus, treatment of various pentafluorobenzenes with S8 or di-tert-butyl tetrasulfide in the presence of dppbz and HSiBu3 affords the diaryl sulfides under mild conditions (Scheme 70). This methodology was extended to prepare unsymmetrical diaryl sulfides. Another approach to access polyfluorinated aryl- and benzylthioethers consists of a copper bromide catalyzed C−S bond formation via C−F bond activation. Zhou, Jiang, and Y


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withdrawing groups lead to a different reaction pattern. With Cl-substituted aryl thiols the bis- and monoarylthiolation products are furnished, whereas NO2- and benzothiazol-2-ylsubstituted aryl thiols favor exclusively a single C−F bond activation at the para-position with respect to the hydrogen atom. Mechanistically, the authors postulated an initial attack of the aryl thiol at Cu to give a copper-thiolato-complex. This is in contrast to the assumed involvement of a copper−fluoridospecies in comparable transformations.87 In the presence of O2 as an oxidant and 148 as a ligand, tetrafluorophenoxithiines were synthesized by thiolation of pentafluorobenzene on treatment with aryl thiols or diaryl disulfides (Scheme 73).89 The formation of the heterocyclic compounds was achieved by a C−F functionalization at the ortho-position subsequently to a C−H activation step. Love et al. demonstrated that the platinum complex [Pt(Me)2(μ-SMe2)]2 (36) is a suitable precatalyst for crosscoupling reactions of fluorinated aryl imines (see above section 2.2.1). The scope of this approach was extended by the development of platinum-catalyzed methoxylations based on C−F bond activation steps.41 On treatment with tetramethoxysilane the binuclear compound 36 catalyzes the transformation of C−F into C−O bonds at various fluorinated benzene derivatives which bear a variety of directing groups (Scheme 74).90 Except at the ortho-positions to the directing group, additional functional groups such as chlorine and bromine are tolerated which underlines the versatility of this approach. It was found that, in addition to the imine groups, oxazoline and imidazole moieties promote the methoxylation reaction. For these conversions a 2,4,6-trifluoro substitution pattern at the phenyl moiety is required (see Scheme 74). When compared with the mechanistic considerations for the catalytic methylation reactions (see above section 2.2.1), a significant difference for the methoxylation was observed. Substrates that showed no reactivity in stoichiometric C−F activation reactions are not necessarily unsuitable for a catalytic methoxylation, indicating a dissimilar reaction mechanism which presumably involves no Pt(IV)−fluorido species.40a,c−e Cao et al. reported on an oxygen-promoted method for C−O bond functionalization employing a nickel catalyst.91 The reactions of arylboronic acids and a variety of polyfluoroarenes in the presence of [Ni(acac)2] (1) and traces of O2 afford unsymmetrical biaryl ethers in good yields (Scheme 75). It was suggested that 1 and the arylboronic acids generate phenols in situ via an intermediate hydrogen peroxide. Further reactions with electron-deficient polyfluorinated arenes furnish the Oarylated polyfluoroarenes via an SNAr pathway. In order to determine the source of the incorporated oxygen atom, experiments with labeled 18O were carried out. They confirm O2 as the oxygen source and not water or the phenylboronic acid. It was found that less fluorinated arenes such as monofluorobenzene, 1,4-difluorobenzene, or 1,3,5-trifluorobenzene fail to react, which is a limitation of the substrate scope. Another example of C−O bond functionalization of fluorobenzenes was recently provided by Weng et al.92 The palladium complex [Pd(OAc)2] (127) catalyzes the reaction of pentafluorobenzene in the presence of AgNO3 with a wide range of phenols to yield the fluorinated aryl ethers (Scheme 76). The C−F activation followed by C−O bond formation at the para-position to the hydrogen atom demonstrates the high chemo- and regioselectivity of this catalytic reaction.

Chen accomplished the catalytic regioselective functionalization of polyfluoroarenes with aryl thioacetates and benzyl thioacetate.87 Treatment of aryl or benzyl thioacetates with polyfluorobenzenes in the presence of catalytic amounts of the copper salt and L-proline affords polyfluoroaryl and -benzyl thioethers (Scheme 71). The authors tentatively suggested the Scheme 71. Copper-Catalyzed Aryl- and Benzylthiolation of Selected Polyfluorobenzenes

initial formation of a copper(III) fluoride species via a selective C−F bond activation which reacts further to yield the thiolation product. In analogy to the polythiolation reactions mentioned above, the pattern with two fluorine atoms in a para-position at the phenyl moieties in the products is again preferred. A comparable achievement was demonstrated by Yu and Shi.88 They accomplished the copper-catalyzed thiolation of pentafluorobenzene by C−F and/or C−H bond activation. The treatment of polyfluoroarenes with various aryl thiols and diaryl disulfides generates thioethers in the presence of a catalytic amount of CuBr (147) along with DDQ (2,3-dichloro-5,6dicyano-1,4-benzoquinone) and 1,10-phenanthroline·H2O as additives (Scheme 72). The products of a double arylthiolation which are formed by an additional C−H bond cleavage, as well as monothioethers, were obtained on employment of nonactivated aryl thiols. In contrast, aryl thiols bearing electronScheme 72. Copper-Catalyzed Arylthiolation of Pentafluorobenzene

Z


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Scheme 73. Copper-Catalyzed Arylthiolation of Pentafluorobenzene in the Presence of Oxygen

Scheme 74. Catalytic Methoxylation Reactions on Using Directing Groups

Scheme 77. Suggested Mechanism for the PalladiumCatalyzed Formation of Polyfluorinated Aryl Ethers

Early transition metals are known to be efficient catalysts for hydrodefluorination reactions,8w,x whereas little is known about their ability to promote the replacement of fluorine by a heteroatom. However, Deck et al. reported a rare case of a stoichiometric C−F bond derivatization by C−N bond formation mediated by an early transition-metal center.93 Treatment of pentafluorophenylcyclopentadiene and pentafluorophenylindene with 2 equiv of [Ti(NMe2)4] (151) affords the doubly aminated arylcyclopentadiene and arylindene after hydrolysis, respectively (Scheme 78). The authors assume that the ortho-selectivity of the C−F bond activation step is due to an intramolecular nucleophilic substitution mechanism by the

Scheme 75. Nickel-Catalyzed Formation of Unsymmetrical Polyfluorinated Biaryl Ethers

Scheme 76. Palladium-Catalyzed Formation of Polyfluorinated Aryl Ethers

Scheme 78. Titanium-Mediated Ortho-Selective C−F Amination of Pentafluorophenylcyclopentadiene and Pentafluorophenylindene

Mechanistically, the authors suggest an initial nucleophilic attack at the fluorinated substrate by a Pd(0) metal center which generates the Meisenheimer-type intermediate 149 (Scheme 77). After the C−F activation step, AgNO3 serves as a fluoride trap to afford AgF. Coordination of the phenol and deprotonation followed by reductive elimination liberates the fluorinated aryl ether as well as the Pd(0) intermediate. AA


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titanium-bound amino moiety. It was suggested that the fourcentered transition state 152 plays a crucial role in this conversion. A few analogous examples of fluorine/amine exchange reactions by early transition-metal complexes of molybdenum, hafnium, and zirconium have been reported, but in contrast to the former, the fluorinated building blocks remained coordinated at the metal center.94

Scheme 80. C−F Bond Derivatization at Metal-Bound Pentafluorophenyl Phosphine Ligands

3.2. Transformation of Metal-Bound Aromatic Building Blocks

Several examples which cover an external attack of a nucleophilic oxygen atom at fluorinated organic ligands have been described. However, in these cases the derivatized fluorinated ligands are still bound to the metal center. Selected examples for C−F bond functionalization are shown in Scheme 79.14t,95 para-fluorine atoms at a perfluorinated group by reactions with either NaOCH3 or NaSCH3. In the coordination sphere of the metal the C−O or C−S bond formation at the para-position seems to be enhanced and results in the generation of [CpRe(NO){P(4-C6F4XCH3)3}(CO2CH3)][BF4] (162, X = O, S). Note that intermolecular C−F bond transformations of metal-bound perfluorinated phosphine ligands are scarce.59s,97 Torrens and Arroyo et al. studied the thermolysis reaction of various osmium(III) and osmium(IV) polyfluorophenylthiolato complexes.95a,b,98 For instance, the reaction of the osmium(III) complex [Os(SC6F5)3(PMe2Ph)2] (163) with an aqueous solution of KOH in acetone affords [Os(SC6F5){κ3-(O,S,S)(2-SC6F4)-2-SC6F4O}(PMe2Ph)2] (164) at room temperature (Scheme 81).95a The solid state structure of 163 exhibits a

Scheme 79. Selected Examples for C−F Bond Functionalization by an Attack of Oxygen Nucleophiles

Scheme 81. Intramolecular Osmium-Promoted C−F Bond Activation Followed by Subsequent C−S and C−O Bond Formation Reactions

short metal−fluorine distance [2.531(6) Å].98,99 This interaction results in an activated ortho-C−F bond, and therefore the carbon atom can be considered more electrophilic making the C−F bond vulnerable for nucleophilic attacks by the thiolate sulfur atom. In addition, the treatment of the osmium(IV) complex [Os(SC6F4H)4(PPh3)] (165) with an aqueous solution of KOH affords [Os(SC6F4H)2(κ2-(O,S)-2-SC6F3HO)(PPh3)] (166) via an ortho-C−F bond activation at the polyfluorothiolate ligand and replacement of a fluorine atom by an oxygen atom (Scheme 81).95a Furthermore, Torrens et al. investigated a metal-promoted intramolecular C−F activation reaction which involves an orthoselective nucleophilic fluorine displacement at a polyfluorinated

Gladysz et al. described a C−F bond cleavage reaction of a pentafluorophenyl phosphine ligand bound to a cationic cyclopentadienylrhenium complex.96 Treatment of [CpRe(NO)(NCCH3)(CO)][BF4] (160) with P(C6F5)3 in the absence of a solvent at 140 °C leads to the formation of [CpRe(NO){P(C6F5)3}(CO)][BF4] (161, Scheme 80). Complex 161 undergoes then a nucleophilic displacement of the AB


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Scheme 82. Intramolecular Ortho-Selective C−F Bond Activation and C−S Bond Formation

Scheme 83. C−O Bond Functionalization at Silver and Rhodium NHC Complexes

aromatic ligand by a phosphanyl moiety.100 Treatment of [Pb(4-SC6F4H)2] (167) with trans-[PtCl2(PR3)2)] (168) [R3 = Ph2C6F5, Ph(C6F5)2] results in the formation of a mixture of the platinum complexes cis/trans-[Pt(4-SC6F4H)2(PR3)2] (169), the thiolato-bridged binuclear complexes cis/trans[Pt2(μ-4-SC6F4H)2(4-SC6F4H)2(PR3)2] (170), and [Pt(4SC6F4H)2{1,2-C6F4(4-SC6F4H)(PR3)}] (171) (Scheme 82). Free phosphine promotes the cis/trans isomerization at the square-planar platinum complexes 169, which convert into the thiolato bridged bimetallic complexes 170. It was suggested that an interaction between the platinum center and the aromatic fluorine atom in cis/trans 170 promotes the C−F bond cleavage step and a nucleophilic attack of the thiolate moiety. However, the fate of the fluoride is unclear. A few other examples for related reactions dealing with intramolecular transition-metalpromoted nucleophilic displacements of fluorine atoms at the ortho-position of the ligand-bound polyfluorobenzene moieties were reported in the literature and were covered recently by a review by Lledós.8v,14t,95a,98,101 Saunders et al. reported on regioselective nucleophilic C−F bond displacement reactions at rhodium- or silver-bound NHC ligands which bear a tetrafluoropyridyl moiety.102 The reaction of the carbene precursor with silver oxide in CD3OD leads to the intermediate formation of 172 which undergoes a nucleophilic attack by methoxide at the ortho-position to the pyridyl ring nitrogen atom to furnish the silver complex 173 (Scheme 83). In contrast, the Rh(III) complex 175, which is generated by the treatment of the NHC carbene with the

rhodium complex [Cp*RhCl(μ-Cl)]2 (174) in the presence of silver oxide, showed a different regioselectivity toward C−F bond activation. An attack of an O-nucleophile occurred at the less activated meta-position of the tetrafluoropyridyl group to yield 176. The authors proposed an intramolecular mechanism involving the formation of an intermediate rhodium hydroxo complex, whereas an intermolecular mechanism is assumed for the C−O bond transformation at the silver complex. 3.3. Derivatization of Heteroaromatic Compounds

Unique fluorinated pyrimidines or pyridines can be obtained by derivatization reactions in the coordination sphere of nickel. Thus, 5-chloro-2,4,6-trifluoropyrimidine converts in the presence of PCy3 and [Ni(cod)2] (46) selectively into the C−F activation product trans-[NiF(4-C4N2ClF2)(PCy3)2] (111, Scheme 84).22a Notably, a C−Cl bond activation was achieved by using the sterically less demanding phosphine PEt3 instead Scheme 84. Synthesis of trans-[NiF(4-C4N2ClF2)(PCy3)2] (111) and Reaction with Iodine

AC


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hydroxydifluoropyrimidine in the coordination sphere of the palladium center was suggested. In contrast, the treatment of 180 with pentafluoropyridine in the presence of substoichiometric amounts of water leads to the formation of the compound [{Pd(Me)}2(μ-F){μ−κ2-(P,P)(Cy2PCH2PCy2)}2][OC5NF4] (183) which comprises a binuclear palladium A-frame complex as a cation and a tetrafluoropyridyloxy anion (Scheme 86).67i It is presumed that a palladium-mediated nucleophilic substitution of a fluorine atom by a hydroxyl group at the 4-position of the heterocycle generates initially 4-hydroxytetrafluoropyridine and HF. The latter reacts further with 180 to afford a mixture of [Pd(Me)(OC5NF4)(dcpm)] (184) and [PdF(Me)(dcpm)] (185), which in turn furnishes 183 (Scheme 87). Note that the reaction of 180 with pentafluoropyridine in the presence of an excess of water leads directly to the formation of 184. Alternatively, binuclear complexes such as [{PdF(Me)}2{μ−κ2(P,P)-dcpm} 2 ] (186) or [{Pd(Me)} 2 (μ-F){μ−κ 2 -(P,P)dcpm}2][F] (187) might react with 4-hydroxytetrafluoropyridine to give 183 and HF. In an independent experiment, 187 was prepared by treatment of 180 with Et3N·3HF as the HF source. Only a few examples of palladium complexes with a fluorido ligand in a bridging mode as in the case of 183 and 187 are known.105 In a comparable conversion, the pyridyloxy complex [Pd(Me)(OC5NF4)(tmeda)] (188) was obtained by starting from the palladium complex [Pd(Me)2(tmeda)] (115) on treatment with pentafluoropyridine in the presence of water (Scheme 88).106 Et3N can be added as an HF trap to increase the yield. Mechanistically, the reaction may again proceed via the formation of the intermediate 4-hydroxytetrafluoropyridine, which further reacts with 115 to give 188 and methane. The development of a cyclic process was achieved by reaction of 188 with ClSiMe3 to afford the pyridine 4-C5NF4(OSiMe3) and the chlorido complex [PdCl2(tmeda)] (189) by cleavage of the metal−oxygen bond. Further reaction of 189 with MeLi closes the cyclic process. A stoichiometric transformation of pentafluoropyridine was achieved by treatment of the C−F activation product 104 with the disilane FMe2SiSiMe2F (Scheme 89) to give 4-silyltetrafluoropyridine.67j In contrast, reactions of 104 with tertiary silanes such as HSiPh3 or boranes such as HBpin furnish the hydrodefluorination product 2,3,5,6-tetrafluoropyridine.67r,107 Milstein et al. demonstrated in 1994 that rhodium silyl complexes are suitable for C−F bond activation reactions.71a,b Further investigations by Marder and Perutz revealed the potential of these conversions for C−F bond borylation reactions.67k Treatment of the highly reactive rhodium(I) silyl complex [Rh(SiPh3)(PMe3)3] (190) with pentafluoropyridine yields the isomeric tetrafluoropyridyl complexes [Rh(2C5NF4)(PMe3)3] (191) and [Rh(4-C5NF4)(PMe3)3] (192) in a 3:1 ratio as well as the fluorosilane FSiPh3 (Scheme 90). Note that the favored activation at the 2-position is usually harder to achieve.63a The hydrodefluorination product 2,3,4,5tetrafluoropyridine was obtained by treatment of 191 with the hydrogen source HSiPh3. Interestingly 192 failed to react and showed no reactivity toward the hydrosilane. In addition, the reaction of an in situ generated mixture of 191 and 192 with 2 equiv of the diborane B2cat2 (B2cat2 = 2,2′-bibenzo[d][1,3,2]dioxaborole) affords the pyridyl boronate esters along with the triboryl complex [Rh(Bcat)3(PMe3)3] (193). The latter is presumably generated from the intermediate rhodium(I) boryl complex [Rh(Bcat)(PMe3)3]. A catalytic conversion could not

of PCy3 (see also section 2.3.1). Treatment of 111 with iodine furnishes 5-chloro-2,6-difluoro-4-iodopyrimidine. In addition, a reaction of 46 with 2,4,6-trifluoropyrimidine in the presence of PEt3 selectively gave the C−F activation product trans-[NiF(2-C4N2F2H)(PEt3)2] (177).103 Treatment of the fluorido complex 177 with an excess of 2,4,6trifluoropyrimidine and CsOH·H2O in THF results in the regioselective formation of 178 (Scheme 85). The subsequent reaction with HCl liberates the pyrimidin-4-one by cleavage of the Ni−N bond in 178 as well as trans-[NiCl(2-C4N2F2H)(PEt3)2] (179). Scheme 85. Synthesis of the Fluorido Complex 177 and Its Reactivity towards 2,4,6-Trifluoropyrimidine

Braun et al. studied the reactivity of the palladium complex [Pd(Me)2(dcmp)] (180) (dcpm = bis(dicyclohexylphosphino)methane) toward 2,4,6-trifluoropyrimidine in the presence of water and NEt3 (Scheme 86).104 In contrast to Scheme 86. Reactivity of 180 with 2,4,6-Trifluoropyrimidine and Pentafluoropyridine in the Presence of Water

the reactions at nickel (see above), the palladium-mediated reaction results in an activation at the 2- and 4-position to give [Pd(Me){2-OC4N2F2H}(dcpm)] (181) and [Pd(Me){4C4N2F2(O)H}(dcpm)] (182) in a 1:1 ratio. Note that the 4position in 2,4,6-trifluoropyrimidine is considered to be more susceptible to a nucleophilic attack.19c When the reaction is performed in the absence of the base, a change in the regioselectivity is observed that leads to the generation of 181 as the only activation product. The initial formation of a AD


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Scheme 87. Possible Mechanism for the Generation of the Cationic Palladium Complex 183 Which Exhibits an A-Frame Structure

be established because complex 193 seems to be a thermodynamic sink. Nevertheless, the catalytic borylation of pentafluoropyridine at the 2-position was accomplished by using the highly reactive rhodium(I) boryl complex [Rh(Bpin)(PEt3)3] (194).108 This complex is capable of activating pentafluoropyridine exclusively at the 2-position.61b,c In the presence of B2pin2 (4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-(1,3,2-dioxaborolane), 194 catalyzes the selective borylation of pentafluoropyridine (Scheme 91). Derivatization reactions of pentafluoropyridine at the 4-

Scheme 88. A Cyclic Process for the C−O Functionalization of Pentafluoropyridine

Scheme 91. Ortho-Selective C−F Bond Activation and Borylation of Pentafluoropyridine with the Rhodium(I) Boryl Complex 194 as Key Intermediate

Scheme 89. C−Si Bond Formation at Pentafluoropyridine

Scheme 90. C−F Bond Borylation of Pentafluoropyridine

position proceed by a radical pathway, nucleophilic attack, or cross-coupling reactions, whereas C−F bond functionalizations at the 2-position are less common and have to be considered as more challenging (refs 19c, 66, 67d, i, j, r, 68, 70b, 106, 107, and 109). Even carbon−fluorine bond activation steps of pentafluoropyridine at the 2-position are very rare.14x,19c,61d,67k,109a,110 DFT calculations on the model complex [Rh(Bpin)(PMe3)3] (196) suggest a boryl-assisted C−F activation pathway, which involves a direct transfer of fluorine onto the boron center via a four-membered transition state (Scheme 92).108 The latter is more accessible than the alternative reaction route via a concerted oxidative addition at the 2-position. The calculations reveal that the initially formed η2-intermediate 197 undergoes the C−F activation via the four-centered transition state 198 in which a F−Bpin interaction is presumed to form thereafter 199. The loss of FBpin results in the formation of the C−F AE


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Scheme 92. Computed Reaction Pathway for the Boron-Assisted C−F Activation of Pentafluoropyridine at the 2-Position at the Model Complex [Rh(Bpin)(PMe3)3] (196); the Rh-N Distance Is Given in Å

activation product 191. The ortho-selectivity can in part be attributed to the stabilizing interaction between the pyridine nitrogen atom and the rhodium atom which exhibit a noticeable short distance in the transition state 198. Related calculations on the silyl complex [Rh{Si(OMe)3}(PMe3)3] showed a similar preference for a C−F bond cleavage of pentafluoropyridine at the 2-position via a comparable transition state.14x The complex with the metal center at the ortho-position [Rh(2-C5NF4)(PMe3)3] (191) is about 13 kcal/mol less stable than the reaction product of an activation at the para-position [Rh(4C5NF4)(PMe3)3] (192). Comparable ligand-assisted C−F activation steps to give P−F bonds are described in the literature (refs 4i, 8q, s, w, x, 14f, k, o, x, 36, 61a−d, and 111).

Scheme 94. Possible Mechanism for the Formation of 201

3.4. Reactions of Fluorinated Olefins and Alkyl Groups

A scarce conversion of C−F bonds into C−S bonds was described by Hughes and co-workers. The reaction of the cationic iridium aqua complex [Cp*Ir(CF 2CF 3)(H 2O)(PMe3)][BF4] (200) with hydrogen sulfide yields a mixture of stereoisomers of [Cp*Ir{κ2-(S,S)-SCH(CF3)S}(PMe3)] (201) and [Cp*Ir{κ2-(S,S)-SCH(CF3)SCH(CF3)S}PMe3)] (202, Scheme 93).112

The reactivity of α-C−F bonds in metal perfluoroalkyl compounds to give C−C, C−H, and other C−heteroatom bonds has been reviewed.5b,c,8j,114 Thus, an intramolecular C− C bond formation reaction via C−F bond activation at [Cp*Ir(C3F7)(CHCH2)(PMe3)] (209) was also investigated.115 Treatment of the iridium complex 209 with the Brønsted acid 2,6-lutidinium iodide yields the η1-allyl complex 210 (Scheme 95). The authors believe that the reaction proceeds via α-C−F bond activation followed by a vinyl group migration, rearrangement of the allyl ligand, and association of iodide. Intermediates of this conversion were characterized using a 2,6-lutidinium salt of a weakly coordinating [BArF4]− anion (ArF = 3,5-bis(trifluoromethyl)phenyl). The reaction with 209 at room temperature gives the η3-allyl intermediate 211 as the major product which slowly converts into its isomer 212 within several hours. Noteworthy, the reaction of the cationic complex 212 with iodide yields complex 210. Thus, the cation in 212 can be regarded as an intermediate in this conversion. Moreover, a reaction of 209 with [LutH][BArF4] at −50 °C furnishes the derivative 213 along with 212. At −20 °C, 213 isomerizes rapidly into 211. Thus, the authors expect 213 to be the kinetic product whereas 212 may be the thermodynamic intermediate. Hughes et al. showed that the C−F bond activation step as well as the C−C bond formation proceed diastereoselectively, whereas the rearrangement of the

Scheme 93. C−F Bond Functionalization of the Cationic Iridium Complex 200 with H2S

The authors propose a mechanism which is based on the studies of hydrolysis reactions of α-C−F bonds at the rhodium perfluoroalkyl complexes [Cp*Rh(CF2RF)(H2O)][BF4] (RF = CF2CF3, C6F5) by a water ligand.112,113 The elimination of HF from the intermediate complex 203 is followed by an intramolecular attack of the sulfur atom at a carbene moiety (Scheme 94). The formation of the S−C bond and the subsequent elimination of a second HF molecule generates the cationic intermediate thioacyl complex 206. A subsequent nucleophilic attack of an additional H2S molecule and liberation of a proton is ensued by a rearrangement reaction of the κ2(S,C)-ligand in 208 furnishing finally 201. The generation of 202 is harder to explain and presumably involves the participation of a second iridium center.112 AF


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to a phosphine migration to afford the metallabicyclic complex 215 (Scheme 96).118 It was suggested that the reaction may proceed via either a fluorocarbene or a carbocation intermediate which is attacked by the more nucleophilic phosphine group of the chelate P,S-ligand. Interestingly, further reactivity studies revealed that a subsequent reaction with 2,6dimethylphenyl isocyanide induces a ring-opening reaction to yield 216. Overall, Ni−S, Ni−C, and β-C−F bonds are cleaved, whereas P−F and CC bonds are formed. The phosphorusbound fluorine atom can be abstracted on using MeSiOTf, which furnishes the more stable complex 217. Notably, the hydrolysis reaction of 215 is (E)-selective and liberates the fluoroalkene (E)-1,2,3,3,4,4-hexafluoro-1-butene (Scheme 96). Apart from α-C−F bond functionalization reactions, treatment of the perfluorometallacyclobutane complex [CpCo(κ2(C,C)-CF2CF2CF2)(PPh2Me)] (218) with [HPPh2Me][NTf2] affords the phosphonium metallacycle [CpCo{κ2-(C,C)CF2CF(PPh2Me)CF2}(PPh2Me)] (219) by a β-C−F bond activation pathway (Scheme 97).5j The authors proposed the

Scheme 95. Intramolecular Derivatization of the Iridium Complex 209

Scheme 97. Lewis Acid Promoted β-C−F Bond Transformation at the Perfluorometallacyclobutane Complex 218 allyl ligand and the coordination of the iodide result in a loss of stereochemical information regarding the product 210. Note that the same research group also investigated mechanisms of comparable diastereoselective intramolecular coupling reactions at iridium with methyl and phenyl ligands instead of vinyl groups.116 The solid-state structures of complexes 209, 210, and 212 were determined by X-ray crystallography. Older work includes the generation of α-carbon−halogen bonds as well as various hydrolysis reactions of α-C−F bonds.60,114a,c,117 However, C−F bonds at fluoroalkyl ligands can additionally be converted into C−P bonds. The treatment of [Ni(C4F8)(PEt3)2] with BF3 yields the phosphonium ylide [Ni(BF4){κ2-(C,C)-CF(PEt3)CF2CF2CF2}(PEt3)] via α-C−F bond derivatization.114b Baker et al. recently provided a related example for an α-C−F bond transformation. The perfluorometallacycle nickel complex 214 undergoes α-C−F bond activation after treatment with the Lewis acid Me3SiOTf prior

formation of an intermediate perfluoroallyl complex 220 along with HF. The former is trapped through a nucleophilic attack of the free phosphine to give 219. The cationic fluorovinyl nickel complex trans-[Ni(CF CF2)(CNt-Bu)(PEt3)2][BArF4] (221) reacts with NaBArF4 and PEt3 to afford the dicationic complex trans-[Ni{CFCF-

Scheme 96. Ligand-Induced Ring-Opening Reaction via Lewis Acid Promoted C−F Bond Activation

AG


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(PEt3)}(CNt-Bu)(PEt3)2][BArF4]2 (222) bearing a phosphonioethenyl ligand (Scheme 98). In this case the C−F activation also occurs also at a remote position of a metallaolefin.119

Scheme 100. Palladium-Catalyzed Heck-Type 5-endo-trig Cyclization Reactions of 1,1-Difluoroalkenes

Scheme 98. C−F Bond Activation at the Cationic Fluorovinyl Complex 221

Mechanistically, it was proposed that the replacement of the fluorine atom of the trifluorovinyl ligand may be initiated by a nucleophilic attack at the β-position by free phosphine (Scheme 99). The carbanionic charge at the α-carbon of 223 is

Scheme 101. C−F Bond Activation Reactions of Hexafluoropropene at Rhodium Complexes

Scheme 99. Possible Mechanism for the Displacement of Fluorine at the Trifluorovinyl Ligand in 221 by Free Phosphine

presumably stabilized by the metal center. Subsequently, the reaction proceeds via either an intermediate vinyl phosphorane 224 or a direct elimination of fluorine at the β-carbon of 223 resulting in the formation of 222. The palladium-mediated synthesis of ring-fluorinated indenes via a Heck-type 5-endo-trig cyclization of 1,1-difluoro-1-alkenes was already discussed in section 2.4.1 (Scheme 63).78 An analogous approach was used to synthesize 5-fluoro-3Hpyrroles by C−N coupling reactions.120 In the presence of a catalytic amount of the palladium complex [Pd(PPh3)4] (71) and a stoichiometric amount of PPh3 various 3,3-difluoroallyloxime derivatives undergo a Heck-type 5-endo-trig cyclization reaction to afford ring-fluorinated 3-H-pyrroles (Scheme 100). The free phosphine is required in order to reduce the intermediate {PdF(OCOC6F5)} species to Pd(0) which closes the catalytic cycle. As outlined above, the reactivity of various rhodium hydrido complexes in a number of C−F bond activation reactions was extensively studied,121 and in particular the stoichiometric and catalytic conversion of hexafluoropropene.61b,c,67n,o,122 Thus, the hydrido complexes cis-fac-[Rh(H)2(Bpin)(PEt3)3] (225), [Rh(H)(PEt3)3] (120), cis-fac-[Rh(H)2(SiPh3)(PEt3)3] (226), and [Rh(H)(PEt3)4] (119) react with hexafluoropropene to give the pentafluoropropenyl complex [Rh{(Z)-CFCF(CF3)}(PEt3)3] (227) and FBpin, HF, or FSiPh3 (Scheme 101). The additional formation of the phosphorane Et3P(F){(Z)-CFCF(CF3)} was observed together with 119.122c For the reaction of 226 with hexafluoropropene the involvement of

an intermediate rhodium(I) silyl complex [Rh(SiPh 3)(PEt3)3],14x,71a,b,123 which might be generated by loss of H2, is conceivable, although this compound could not be detected by monitoring the reaction by NMR spectroscopy. An alternative pathway consists of the liberation of HSiPh3 to give 227, which is in equilibrium with 226. A further metalmediated reaction of HSiPh3 with HF could explain the formation of FSiPh3. The C−F activation employing the rhodium(I) boryl complex 194 is less selective, and the activation of hexafluoropropene at the 2- and 3-position to afford 227 and the isomeric C−F activation product [Rh{C(CF3)CF2}(PEt3)3] (228) in a 2:7 ratio as well as FBpin was observed (Scheme 101). As mentioned in the introduction, the thermodynamic driving force for all conversions is the formation of another strong element−fluorine bond, e.g. a H−F, Si−F, or B−F bond.12 AH


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Scheme 102. Postulated Mechanism for the C−F Bond Activation of Hexafluoropropene by 120

reacts with the fluorinated substrate to yield trifluoropropyl1,3,2-dioxaborolanes and the C−F activation product 227. This conversion completes again a cyclic process which led to the development of a catalytic transformation. Complex 120 catalyzes the C−F bond borylation of hexafluoropropene in the presence of excess HBpin to yield a mixture of fluoroalkyl dioxaborolanes in reasonable yields (Scheme 105).67n,o

For the activation by 120, the authors assumed that the most likely mechanism for the C−F activation step involves a Meisenheimer-type intermediate 229, which is generated by a nucleophilic attack of the metal center at the fluorinated propene (Scheme 102).122c Liberation of fluoride and the subsequent deprotonation at the rhodium center then might give complex 227 together with HF. Treatment of the C−F activation product 227 with an excess of HSiPh3 in the presence of hexafluoropropene results in the formation of (3,3,3-trifluoropropyl)silane and 226 (Scheme 103). Since 226 is in equilibrium with 120 and the latter is a

Scheme 105. Catalytic C−F Bond Transformation of Hexafluoropropene into Borylated Trifluoropropanes

Scheme 103. Cyclic Process for Conversion of Hexafluoropropene into (3,3,3-Trifluoropropyl)silanes

The intermediate formation of 3,3,3-trifluoropropene can be considered as an important key step in both borylation and silylation reactions of hexafluoropropene. Either a hydrosilylation or hydroboration step at the 3,3,3-trifluoropropene might furnish the silylated or borylated derivatives. However, the authors also provided some evidence for dehydrogenative silylation or borylation reaction pathways.

suitable starting compound for C−F bond cleavage reactions, this completes a cyclic process for the activation of hexafluoropropene. Based on these findings, rare examples for catalytic C−F bond functionalizations of highly fluorinated olefins were developed that lead to fluorinated compounds of higher value and not simply to hydrodefluorination products.122d,e However, hydrodefluorination steps are apparently involved in the catalytic transformations. Conversions of hexafluoropropene with several tertiary silanes, e.g. HSiPh3, HSiEt3, HSi(OMe)3, in the presence of 227 lead selectively to 3,3,3-trifluoropropylsilanes at room temperature with a TON up to 90 (Scheme 104). The

4. CONCLUSIONS In conclusion, C−F activation of highly fluorinated molecules can be an inspiring tool to access unique fluorinated building blocks. The approach involves hydrodefluorination reactions; element−carbon bonds other than C−H bonds can also be generated. The latter are the focus of this review. Many of the conversions presented above involve a transformation of a C−F bond into a C−C bond. The coupling reactions are frequently mediated by Ni, Pd, and Pt, and most of them are catalytic. The cross-coupling processes involve mainly Kumada−Tamao, Suzuki−Miyaura, and Negishi-type couplings. In some cases metal fluorido complexes were identified as products of an oxidative addition, which might be a crucial step to realize a putative catalytic cycle. Heterocycles and aromatic compounds which possess a remote group as a directing function are easier to activate than aromatics which are simply fluorinated. For the former, the regioselectivity of the activation often depends not only on the nature of the transition-metal complex but also often on the substrate itself. So far, a functionalization of fluorinated heteroaromatics is limited to nitrogen based compounds. Nevertheless, for highly fluorinated benzene derivatives, palladium-catalyzed Suzuki−Miyaura coupling reactions and couplings which use in situ generated diaryl zinc compounds in the presence of LiI can be considered as breakthroughs. Transition-metal iodido complexes are formed as intermediates

Scheme 104. Rhodium-Catalyzed Silylation of Hexafluoropropene

reactions can be performed either with an excess of silane or in the presence of a mixture of dihydrogen and silane. Note that when dihydrogen solely was employed as the hydrogen source instead of tertiary silane, the hydrodefluorination product 1,1,1trifluoropropane was formed instead of a silyl derivative.122a−c In a related unprecedented example for a C−F bond transformation of hexafluoropropene, HBpin was employed as a hydrogen source. Thus, in the presence of HBpin complex 225 AI


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tion reactions is by far more explored than any other C−F bond

Scheme 106. Examples for Fluorinated Products of Fluoralkyl C−F Activation and C−C Coupling Reactions Using Silylium or Alumylium Catalysts125d,f,h−j

transformations.8,9 C−F bond functionalizations of alkanes by transition-metal complexes are practically nonexistent and restricted to intramolecular derivatizations of fluorinated alkyl groups. Remarkably, reactions mediated by main group compounds might open up new opportunities in the future. Hydrodefluorination reactions of alkanes can be mediated by highly Lewis acidic silylium or alumylium ions, but C−C coupling reactions were also achieved.8n,o,19j,125 Fluorinated compounds are accessible, for instance, by activation of benzylic C−F bonds and subsequent Friedel−Crafts-type reactions with benzyl carbenium ions, or even by alkylative defluorination reactions (Scheme 106). Aromatic C−F bonds remain untouched in these transformations.125f

AUTHOR INFORMATION Corresponding Author

*Phone: +49-03-2093-3913. Fax: +49-03-2093-7468. E-mail: [email protected]. Author Contributions ‡

These authors contributed equally.

Notes

after the C−F bond activation step by replacement of a fluorido ligand. On the other hand, fluorido complexes can also be crucial to complete a catalytic process, because of the higher reactivity of a fluorido ligand at d8-complexes.67 Noteworthy, a considerable understanding of the reaction mechanisms was achieved for platinum-catalyzed Negishi reactions with polyfluoroaryl imines. Examples of cross-coupling reactions of fluorinated olefins by C−F activation are scarce, but highly fluorinated alkenes were derivatized by palladium-catalyzed Suzuki−Miyaura coupling reactions. The transformation of C−F bonds into other moieties excluding C−H and C−C bonds is rather sophisticated. Catalytic C−S and C−O bond formation reactions at aromatic compounds were performed, but the mechanisms of these processes are often less understood. Again some of these conversions proceed in the presence of directing groups at the organic substrate. Interestingly, the sources for the oxygen atom can be water or dioxygen. The catalytic generation of C−Si and C−B bonds is noteworthy, because the products might be very useful starting compounds for further transformations. In most of the cases rhodium complexes were applied as catalysts. The silylation of fluorinated acetophenones and less fluorinated phenyloxazoline as well as the borylation of pentafluoropyridine at the ortho-position can be considered as spin-offs. Rare reactions with olefins include the conversion of perfluoropropene into borylated and silylated trifluoropropene derivatives. Note that although carbon−fluorine bond activation reactions of fluoroalkenes have been thoroughly studied in the past decades,10,14g,20,124 their functionalization via hydrodefluorina-

The authors declare no competing financial interest. Biographies

Theresia (Resi) Ahrens studied chemistry at the Humboldt-Universität zu Berlin. In 2012, she received her diploma, and currently she pursues her Ph.D. studies under the supervision of Prof. Thomas Braun also at the Humboldt-Universität zu Berlin. Her research is focused on the transition-metal-mediated C−F activation of fluorinated molecules. She is a scholar holder of the DFG Research Training Group (Graduiertenkolleg 1582) “Fluorine as Key Element“. AJ


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Thomas Braun studied chemistry at the Julius-Maximilians-Universität Würzburg and received his Ph.D. under the supervision of Helmut Werner. After postdoctoral work with Pierre Dixneuf (Rennes) and Robin Perutz (York), he obtained his habilitation with Peter Jutzi as mentor at the University of Bielefeld. In 2007, he was appointed Professor of Inorganic Chemistry at the Humboldt-Universität zu Berlin. Thomas Braun received the Wöhler Award for Young Scientists in 2006 and the RSC Fluorine Chemistry Prize in 2007. From 2010 to 2012 he served as the chair of the GDCh Fluorine Chemistry division and is since 2009 vice-chair of the DFG Research Training Group GRK 1582 “Fluorine as the Key Element”. From 2010 to 2012 he was head of the department of chemistry at the Humboldt-Universität. His major interests are in fluorine chemistry as well as organometallic and coordination chemistry with an emphasis on the catalytic activation of small molecules. Recently he also turned his attention to heterogeneous catalysis.

Johannes Kohlmann was born in Lutherstadt Wittenberg, Germany in 1987. He studied chemistry at the Humboldt-Universität zu Berlin and Uppsala University. During his one-year stay abroad in Sweden, he completed an extended research internship in the field of inorganic chemistry (ERASMUS Programme). In 2013, he received his diploma in chemistry. Currently, he is working on his Ph.D. in the research group of Prof. Thomas Braun at the Humboldt-Universität zu Berlin. His research interests include the functionalization of fluorinated molecules by homogeneous catalysis taking into account their application in a bioorganic context. Johannes Kohlmann is a member of the Cluster of Excellence “Unifying Concepts in Catalysis” (UniCat) funded by the Deutsche Forschungsgemeinschaft.

ACKNOWLEDGMENTS We thank the Research Training Group “Fluorine as a Key Element” and the Cluster of Excellence “Unifying Concepts in Catalysis” (UniCat) funded by the Deutsche Forschungsgemeinschaft. M.A. thanks the “Fonds der Chemischen Industrie”. We are grateful to MSc. Lada Zámostná for thorough proofreading of the manuscript. REFERENCES (1) (a) Welch, J. T.; Eswarakrishnan, S. Fluorine in Bioorganic Chemistry; John Wiley & Sons: 1991. (b) Banks, R. E.; Smart, B. E.; Tatlow, J. C. Organofluorine Chemistry: Principles and Commercial Applications; Springer: 1994. (c) Nakajima, T.; Ž emva, B.; Tressaud, A. Advanced Inorganic Fluorides: Synthesis, Characterization and Applications; Elsevier Science: Amsterdam, 2000. (d) Banks, R. E. Fluorine Chemistry at the Millennium: Fascinated by Fluorine; Elsevier: Amsterdam, 2000. (e) Hiyama, T. Organofluorine Compounds: Chemistry and Applications; Springer: 2000. (f) Ameduri, B.; Boutevin, B. Well-Architectured Fluoropolymers: Synthesis, Properties and Applications; Elsevier Science: 2004. (g) Jeschke, P. ChemBioChem 2004, 5, 570. (h) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity and Applications; Wiley-VCH: Weinheim, 2004. (i) Chambers, R. D. Fluorine in Organic Chemistry; Blackwell, 2004. (j) Soloshonok, V. A., Ed. Fluorine-Containing Synthons; ACS Symposium Series 911; American Chemical Society: Washington, DC, 2005. (k) Nakajima, T.; Groult, H. Fluorinated Materials for Energy Conversion; Elsevier: 2005. (l) Gladysz, J. A.; Curran, D. P.; Horvath, I. T. Handbook of Fluorous Chemistry; Wiley-VCH: Weinheim, 2006. (m) Müller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881. (n) Paquette, L. A. Handbook of Reagents for Organic Synthesis: Fluorine-Containing Reagents; Wiley: New York, 2007. (o) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320. (p) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359.

Mike Ahrens was born in Nürnberg in 1979. He studied chemistry at the Friedrich-Alexander Universität Erlangen-Nürnberg and the Humboldt-Universität zu Berlin. He graduated in Berlin and received his doctorate degree in 2008 under the supervision of Prof. Erhard Kemnitz. After a postdoctoral stay in France at the École Nationale Supérieure d’Ingénieurs de Caen (ENSICAEN) under the guidance of Prof. Marco Daturi, he worked as a group head at the Fraunhofer Research Institution for Polymeric Materials and Composites (PYCO) in Teltow. In 2011, he returned to his alma mater and joined the group of Prof. Thomas Braun at the Humboldt-Universität zu Berlin, first as a postdoctoral researcher, and from 2012 as a permanent research scientist. His research interests combine the fields of heterogeneous and homogeneous catalysis, focusing on the activation of strong bonds by the generation of catalytically active surface sites. AK


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(q) Tressaud, A.; Haufe, G. Fluorine and Health: Molecular Imaging, Biomedical Materials and Pharmaceuticals; Elsevier Science: 2008. (r) Uneyama, K. Organofluorine Chemistry; Wiley, 2008. (s) Bégué, J. P.; Bonnet-Delpon, D. Bioorganic and Medicinal Chemistry of Fluorine; John Wiley & Sons, Inc.: Hoboken, New York, 2008. (t) Petrov, V. A. Fluorinated Heterocyclic Compounds: Synthesis, Chemistry, and Applications; Wiley: 2009. (u) Tressaud, A. Functionalized Inorganic Fluorides: Synthesis, Characterization and Properties of Nanostructured Solids; Wiley: 2010. (v) O’Hagan, D. J. Fluorine Chem. 2010, 131, 1071. (w) Lee, E.; Kamlet, A. S.; Powers, D. C.; Neumann, C. N.; Boursalian, G. B.; Furuya, T.; Choi, D. C.; Hooker, J. M.; Ritter, T. Science 2011, 334, 639. (x) Tredwell, M.; Gouverneur, V. Angew. Chem. 2012, 124, 11590. (y) Tredwell, M.; Gouverneur, V. Angew. Chem., Int. Ed. 2012, 51, 11426. (z) Stenhagen, I. S. R.; Kirjavainen, A. K.; Forsback, S. J.; Jorgensen, C. G.; Robins, E. G.; Luthra, S. K.; Solin, O.; Gouverneur, V. Chem. Commun. 2013, 49, 1386. (2) (a) Reichenbacher, K.; Suss, H. I.; Hulliger, J. Chem. Soc. Rev. 2005, 34, 22. (b) O’Hagan, D. Chem. Soc. Rev. 2008, 37, 308. (3) Braun, T. Organometallics 2012, 31, 1213. (4) Selected examples for fluorination reactions: (a) Grushin, V. V. Chem.Eur. J. 2002, 8, 1006. (b) Bobbio, C.; Gouverneur, V. Org. Biomol. Chem. 2006, 4, 2065. (c) Watson, D. A.; Su, M.; Teverovskiy, G.; Zhang, Y.; Garcia-Fortanet, J.; Kinzel, T.; Buchwald, S. L. Science 2009, 325, 1661. (d) Gouverneur, V. Science 2009, 325, 1630. (e) Brown, J. M.; Gouverneur, V. Angew. Chem. 2009, 121, 8762. (f) Brown, J. M.; Gouverneur, V. Angew. Chem., Int. Ed. 2009, 48, 8610. (g) Furuya, T.; Klein, J. E. M. N.; Ritter, T. Synthesis 2010, 2010, 1804. (h) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (i) Grushin, V. V. Acc. Chem. Res. 2010, 43, 160. (j) Yoshida, S. J. Synth. Org. Chem., Jpn. 2010, 68, 755. (k) Wang, W.; Jasinski, J.; Hammond, G. B.; Xu, B. Angew. Chem. 2010, 122, 7405. (l) Wang, W.; Jasinski, J.; Hammond, G. B.; Xu, B. Angew. Chem., Int. Ed. 2010, 49, 7247. (m) Engle, K. M.; Mei, T.-S.; Wang, X.; Yu, J.-Q. Angew. Chem. 2011, 123, 1514. (n) Engle, K. M.; Mei, T.-S.; Wang, X.; Yu, J.-Q. Angew. Chem., Int. Ed. 2011, 50, 1478. (o) Furuya, T.; Ritter, T. J. Synth. Org. Chem., Jpn. 2011, 69, 48. (p) Furuya, T.; Kamlet, A. S.; Ritter, T. Nature 2011, 473, 470. (q) Vigalok, A. Organometallics 2011, 30, 4802. (r) Hollingworth, C.; Gouverneur, V. Chem. Commun. 2012, 48, 2929. (s) Mankad, N. P.; Toste, F. D. Chem. Sci. 2012, 3, 72. (t) Liu, G. Org. Biomol. Chem. 2012, 10, 6243. (u) Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chem. 2013, 125, 8372. (v) Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214. (w) Kläring, P.; Braun, T. Angew. Chem. 2013, 125, 11302. (x) Kläring, P.; Braun, T. Angew. Chem., Int. Ed. 2013, 52, 11096. (y) Ma, J.-A.; Li, S. Org. Chem. Front. 2014, 1, 712. (z) Emer, E.; Pfeifer, L.; Brown, J. M.; Gouverneur, V. Angew. Chem. 2014, 126, 4265. (aa) Emer, E.; Pfeifer, L.; Brown, J. M.; Gouverneur, V. Angew. Chem., Int. Ed. 2014, 53, 4181. (5) (a) Shen, Q.; Hammond, G. B. Org. Lett. 2001, 3, 2213. (b) Hughes, R. P. Eur. J. Inorg. Chem. 2009, 4591. (c) Hughes, R. P. J. Fluorine Chem. 2010, 131, 1059. (d) Kuhnel, M. F.; Lentz, D. Dalton Trans. 2010, 39, 9745. (e) Orbach, M.; Choudhury, J.; Lahav, M.; Zenkina, O. V.; Diskin-Posner, Y.; Leitus, G.; Iron, M. A.; van der Boom, M. E. Organometallics 2011, 31, 1271. (f) Gil-Rubio, J.; Guerrero-Leal, J.; Blaya, M.; Vicente, J.; Bautista, D.; Jones, P. G. Organometallics 2011, 31, 1287. (g) Slaney, M. E.; Ferguson, M. J.; McDonald, R.; Cowie, M. Organometallics 2012, 31, 1384. (h) Sgarbossa, P.; Scarso, A.; Strukul, G.; Michelin, R. A. Organometallics 2012, 31, 1257. (i) Adams, J. J.; Arulsamy, N.; Roddick, D. M. Organometallics 2012, 31, 1439. (j) Harrison, D. J.; Lee, G. M.; Leclerc, M. C.; Korobkov, I.; Baker, R. T. J. Am. Chem. Soc. 2013, 135, 18296. (6) (a) Ojima, I.; Okabe, M.; Kato, K.; Kwon, H. B.; Horvath, I. T. J. Am. Chem. Soc. 1988, 110, 150. (b) Uneyama, K.; Amii, H. J. Fluorine Chem. 2002, 114, 127. (c) Liu, T.; Shen, Q. Eur. J. Org. Chem. 2012, 2012, 6679. (d) Landelle, G.; Panossian, A.; Pazenok, S.; Vors, J. P.; Leroux, F. R. Beilstein J. Org. Chem. 2013, 9, 2476. (e) Barata-Vallejo, S.; Postigo, A. Coord. Chem. Rev. 2013, 257, 3051. (f) Chu, L.; Qing, F.-L. Acc. Chem. Res. 2014, 47, 1513.

(7) (a) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97, 757. (b) Koller, R.; Stanek, K.; Stolz, D.; Aardoom, R.; Niedermann, K.; Togni, A. Angew. Chem. 2009, 121, 4396. (c) Koller, R.; Stanek, K.; Stolz, D.; Aardoom, R.; Niedermann, K.; Togni, A. Angew. Chem., Int. Ed. 2009, 48, 4332. (d) Lundgren, R. J.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49, 9322. (e) Lundgren, R. J.; Stradiotto, M. Angew. Chem. 2010, 122, 9510. (f) Tomashenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111, 4475. (g) Bakhmutov, V. I.; Bozoglian, F.; Gómez, K.; González, G.; Grushin, V. V.; Macgregor, S. A.; Martin, E.; Miloserdov, F. M.; Novikov, M. A.; Panetier, J. A.; Romashov, L. V. Organometallics 2011, 31, 1315. (h) Morandi, B.; Cheang, J.; Carreira, E. M. Org. Lett. 2011, 13, 3080. (i) Amii, H. J. Synth. Org. Chem., Jpn. 2011, 69, 752. (j) Fujikawa, K.; Fujioka, Y.; Kobayashi, A.; Amii, H. Org. Lett. 2011, 13, 5560. (k) Kondo, H.; Oishi, M.; Fujikawa, K.; Amii, H. Adv. Synth. Catal. 2011, 353, 1247. (l) Wu, X.-F.; Neumann, H.; Beller, M. Chem.Asian J. 2012, 7, 1744. (m) Feng, C.; Loh, T. P. Chem. Sci. 2012, 3, 3458. (n) Studer, A. Angew. Chem. 2012, 124, 9082. (o) Studer, A. Angew. Chem., Int. Ed. 2012, 51, 8950. (p) Chen, P. H.; Liu, G. S. Synthesis 2013, 45, 2919. (q) Danoun, G.; Bayarmagnai, B.; Grünberg, M. F.; Gooßen, L. J. Angew. Chem. 2013, 125, 8130. (r) Danoun, G.; Bayarmagnai, B.; Grünberg, M. F.; Gooßen, L. J. Angew. Chem., Int. Ed. 2013, 52, 7972. (s) Lishchynskyi, A.; Berthon, G.; Grushin, V. V. Chem. Commun. 2014, 50, 10237. (8) (a) Kiplinger, J. L.; Richmond, T. G.; Osterberg, C. E. Chem. Rev. 1994, 94, 373. (b) Burdeniuc, J.; Jedicka, B.; Crabtree, R. H. Chem. Ber. 1997, 130, 145. (c) Richmond, T. In Activation of Unreactive Bonds and Organic Synthesis; Murai, S., Ed.; Springer: Berlin, Heidelberg, 1999; Vol. 3. (d) Richmond, T. G. Angew. Chem. 2000, 112, 3378. (e) Richmond, T. G. Angew. Chem., Int. Ed. 2000, 39, 3241. (f) Braun, T.; Perutz, R. N. Chem. Commun. 2002, 2749. (g) Jones, W. D. Dalton Trans. 2003, 3991. (h) Mazurek, U.; Schwarz, H. Chem. Commun. 2003, 1321. (i) Braun, T.; Perutz, R. N. In Perspectives in Organometallic Chemistry; Screttas, C. G., Steele, B. R., Eds.; Royal Soc Chemistry: Cambridge, 2003. (j) Torrens, H. Coord. Chem. Rev. 2005, 249, 1957. (k) Perutz, R. N.; Braun, T. In Comprehensive Organometallic Chemistry III; Mingos, D. M. P., Crabtree, R. H., Eds.; Elsevier: Oxford, 2007. (l) Macgregor, S. A. Chem. Soc. Rev. 2007, 36, 67. (m) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119. (n) Meier, G.; Braun, T. Angew. Chem. 2009, 121, 1575. (o) Meier, G.; Braun, T. Angew. Chem., Int. Ed. 2009, 48, 1546. (p) Sun, A. D.; Love, J. A. Dalton Trans. 2010, 39, 10362. (q) Braun, T.; Wehmeier, F. Eur. J. Inorg. Chem. 2011, 613. (r) Paquin, J.-F. Synlett 2011, 2011, 289. (s) Clot, E.; Eisenstein, O.; Jasim, N.; Macgregor, S. A.; McGrady, J. E.; Perutz, R. N. Acc. Chem. Res. 2011, 44, 333. (t) Johnson, S. A.; Hatnean, J. A.; Doster, M. E. Prog. Inorg. Chem.; Wiley: 2011. (u) Klahn, M.; Rosenthal, U. Organometallics 2012, 31, 1235. (v) Nova, A.; Mas-Ballesté, R.; Lledós, A. Organometallics 2012, 31, 1245. (w) Kuehnel, M. F.; Lentz, D.; Braun, T. Angew. Chem. 2013, 125, 3412. (x) Kuehnel, M. F.; Lentz, D.; Braun, T. Angew. Chem., Int. Ed. 2013, 52, 3328. (y) Crespo, M. Organometallics 2012, 31, 1216. (z) Keyes, L.; Love, J. A. In C−H and C−X Bond Functionalization: Transition Metal Mediation; Ribas, X., Ed.; The Royal Society of Chemistry: 2013. (aa) Weaver, J.; Senaweera, S. Tetrahedron 2014, http://dx.doi.org/10.1016/j.tet.2014.06.004. (9) For some recent papers on hydrodefluorination, see: (a) Choi, J.; Wang, D. Y.; Kundu, S.; Choliy, Y.; Emge, T. J.; Krogh-Jespersen, K.; Goldman, A. S. Science 2011, 332, 1545. (b) Yow, S.; Gates, S. J.; White, A. J. P.; Crimmin, M. R. Angew. Chem. 2012, 124, 12727. (c) Yow, S. H.; Gates, S. J.; White, A. J. P.; Crimmin, M. R. Angew. Chem., Int. Ed. 2012, 51, 12559. (d) Fischer, P.; Gotz, K.; Eichhorn, A.; Radius, U. Organometallics 2012, 31, 1374. (e) Li, J.; Zheng, T.; Sun, H.; Li, X. Dalton Trans. 2013, 42, 13048. (f) Zámostná, L.; Ahrens, M.; Braun, T. J. Fluorine Chem. 2013, 155, 132. (g) Lv, H.; Cai, Y.-B.; Zhang, J.-L. Angew. Chem. 2013, 125, 3285. (h) Lv, H.; Cai, Y.-B.; Zhang, J.-L. Angew. Chem., Int. Ed. 2013, 52, 3203. (i) He, Y.; Chen, Z.; He, C. Y.; Zhang, X. G. Chin. J. Chem. 2013, 31, 873. (j) Konnick, M. M.; Bischof, S. M.; Periana, R. A.; Hashiguchi, B. G. Adv. Synth. Catal. 2013, 355, 632. (k) Sabater, S.; Mata, J. A.; Peris, E. Nat. Commun. 2013, 4, 2553. (l) Baumgartner, R.; Stieger, G. K.; McNeill, AL


Chemical Reviews

Review

K. Environ. Sci. Technol. 2013, 47, 6545. (m) Chen, Z.; He, C. Y.; Yin, Z.; Chen, L.; He, Y.; Zhang, X. Angew. Chem. 2013, 125, 5925. (n) Chen, Z.; He, C. Y.; Yin, Z.; Chen, L.; He, Y.; Zhang, X. Angew. Chem., Int. Ed. 2013, 52, 5813. (o) Ohashi, M.; Shibata, M.; Saijo, H.; Kambara, T.; Ogoshi, S. Organometallics 2013, 32, 3631. (p) Xu, W.; Sun, H.; Xiong, Z.; Li, X. Organometallics 2013, 32, 7122. (q) Akiyama, T.; Atobe, K.; Shibata, M.; Mori, K. J. Fluorine Chem. 2013, 152, 81. (r) Arevalo, A.; Tlahuext-Aca, A.; Flores-Alamo, M.; Garcia, J. J. J. Am. Chem. Soc. 2014, 136, 4634. (s) Zhang, H.; Lin, J.-H.; Xiao, J.-C.; Gu, Y.-C. Org. Biomol. Chem. 2014, 12, 581. (10) (a) Peterson, A. A.; McNeill, K. Organometallics 2006, 25, 4938. (b) Peterson, A. A.; Thoreson, K. A.; McNeill, K. Organometallics 2009, 28, 5982. (11) (a) Harper, R. J.; Soloski, E. J.; Tamborski, C. J. Org. Chem. 1964, 29, 2385. (b) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 8754. (c) Lafrance, M.; Shore, D.; Fagnou, K. Org. Lett. 2006, 8, 5097. (d) Do, H.-Q.; Daugulis, O. J. Am. Chem. Soc. 2008, 130, 1128. (e) Nakao, Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc. 2008, 130, 16170. (f) Doster, M. E.; Hatnean, J. A.; Jeftic, T.; Modi, S.; Johnson, S. A. J. Am. Chem. Soc. 2010, 132, 11923. (g) Li, H.; Liu, J.; Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Org. Lett. 2010, 13, 276. (h) Zhang, X.; Fan, S.; He, C.-Y.; Wan, X.; Min, Q.-Q.; Yang, J.; Jiang, Z.-X. J. Am. Chem. Soc. 2010, 132, 4506. (i) Wei, Y.; Su, W. J. Am. Chem. Soc. 2010, 132, 16377. (j) René, O.; Fagnou, K. Org. Lett. 2010, 12, 2116. (k) Li, Z.; Zhang, Y.; Liu, Z.-Q. Org. Lett. 2011, 14, 74. (l) Guihaumé, J.; Halbert, S.; Eisenstein, O.; Perutz, R. N. Organometallics 2011, 31, 1300. (m) Chen, F.; Min, Q.-Q.; Zhang, X. J. Org. Chem. 2012, 77, 2992. (n) Johnson, S. A.; Doster, M. E.; Matthews, J.; Shoshani, M.; Thibodeau, M.; Labadie, A.; Hatnean, J. A. Dalton Trans. 2012, 41, 8135. (o) Bernhammer, J. C.; Huynh, H. V. Organometallics 2012, 31, 5121. (p) Yan, T.; Bheeter, C. B.; Doucet, H. Eur. J. Org. Chem. 2013, 2013, 7152. (q) Yan, T.; Chen, L.; Bruneau, C.; Dixneuf, P. H.; Doucet, H. J. Org. Chem. 2013, 78, 4177. (12) Luo, Y.-R. Comprehensive handbook of chemical bond energies; CRC Press: 2010. (13) (a) Maron, L.; Werkema, E. L.; Perrin, L.; Eisenstein, O.; Andersen, R. A. J. Am. Chem. Soc. 2005, 127, 279. (b) Clot, E.; Mégret, C.; Eisenstein, O.; Perutz, R. N. J. Am. Chem. Soc. 2009, 131, 7817. (c) Namazian, M.; Coote, M. L. J. Fluorine Chem. 2009, 130, 621. (d) Macgregor, S. A.; McKay, D.; Panetier, J. A.; Whittlesey, M. K. Dalton Trans. 2013, 42, 7386. (14) (a) Belt, S. T.; Helliwell, M.; Jones, W. D.; Partridge, M. G.; Perutz, R. N. J. Am. Chem. Soc. 1993, 115, 1429. (b) Crespo, M.; Martinez, M.; de Pablo, E. J. Chem. Soc., Dalton Trans. 1997, 1231. (c) Edelbach, B. L.; Jones, W. D. J. Am. Chem. Soc. 1997, 119, 7734. (d) Su, M.-D.; Chu, S.-Y. J. Am. Chem. Soc. 1997, 119, 10178. (e) Braun, T.; Cronin, L.; Higgitt, C. L.; McGrady, J. E.; Perutz, R. N.; Reinhold, M. New J. Chem. 2001, 25, 19. (f) Jasim, N. A.; Perutz, R. N.; Whitwood, A. C.; Braun, T.; Izundu, J.; Neumann, B.; Rothfeld, S.; Stammler, H. G. Organometallics 2004, 23, 6140. (g) Clot, E.; Megret, C.; Kraft, B. M.; Eisenstein, O.; Jones, W. D. J. Am. Chem. Soc. 2004, 126, 5647. (h) Terao, J.; Begum, S. A.; Shinohara, Y.; Tomita, M.; Naitoh, Y.; Kambe, N. Chem. Commun. 2007, 855. (i) Begum, S. A.; Terao, J.; Kambe, N. Chem. Lett. 2007, 36, 196. (j) Schaub, T.; Fischer, P.; Steffen, A.; Braun, T.; Radius, U.; Mix, A. J. Am. Chem. Soc. 2008, 130, 9304. (k) Nova, A.; Erhardt, S.; Jasim, N. A.; Perutz, R. N.; Macgregor, S. A.; McGrady, J. E.; Whitwood, A. C. J. Am. Chem. Soc. 2008, 130, 15499. (l) Nova, A.; Mas-Balleste, R.; Ujaque, G.; Gonzalez-Duarte, P.; Lledos, A. Chem. Commun. 2008, 3130. (m) Johnson, S. A.; Taylor, E. T.; Cruise, S. J. Organometallics 2009, 28, 3842. (n) Kraft, B. M.; Clot, E.; Eisenstein, O.; Brennessel, W. W.; Jones, W. D. J. Fluorine Chem. 2010, 131, 1122. (o) Goodman, J.; Macgregor, S. A. Coord. Chem. Rev. 2010, 254, 1295. (p) Panetier, J. A.; Macgregor, S. A.; Whittlesey, M. K. Angew. Chem. 2011, 123, 2835. (q) Panetier, J. A.; Macgregor, S. A.; Whittlesey, M. K. Angew. Chem., Int. Ed. 2011, 50, 2783. (r) Hatnean, J. A.; Johnson, S. A. Organometallics 2012, 31, 1361. (s) Jin, Y. Z.; Wang, Y. C.; Geng, Z. Y.; Wang, H. J.; Gan, Y. Z. J. Organomet. Chem. 2012, 717, 195. (t) Dub, P. A.; Wang, H.; Matsunami, A.; Gridnev, I. D.; Kuwata, S.;

Ikariya, T. Bull. Chem. Soc. Jpn. 2013, 86, 557. (u) Gianetti, T. L.; Bergman, R. G.; Arnold, J. J. Am. Chem. Soc. 2013, 135, 8145. (v) Ni, F.; Lee, C. C.; Hwang, C. S.; Hu, Y. L.; Ribbe, M. W.; McKenna, C. E. J. Am. Chem. Soc. 2013, 135, 10346. (w) Lu, Y. Q.; Sun, H. J.; Zhang, D. J.; Li, X. Y. Comput. Theor. Chem. 2013, 1018, 115. (x) Raza, A. L.; Panetier, J. A.; Teltewskoi, M.; Macgregor, S. A.; Braun, T. Organometallics 2013, 32, 3795. (15) Nakamura, Y.; Yoshikai, N.; Ilies, L.; Nakamura, E. Org. Lett. 2012, 14, 3316. (16) (a) Yoshikai, N.; Mashima, H.; Nakamura, E. J. Am. Chem. Soc. 2005, 127, 17978. (b) Yoshikai, N.; Matsuda, H.; Nakamura, E. J. Am. Chem. Soc. 2009, 131, 9590. (17) Kiso, Y.; Tamao, K.; Kumada, M. J. Organomet. Chem. 1973, 50, C12. (18) (a) Böhm, V. P. W.; Gstöttmayr, C. W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem. 2001, 113, 3500. (b) Böhm, V. P. W.; Gstottmayr, C. W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem., Int. Ed. 2001, 40, 3387. (19) For selected examples, see: (a) Pummer, W. J.; Wall, L. A. Science 1958, 127, 643. (b) Banks, R. E.; Burgess, J. E.; Cheng, W. M.; Haszeldine, R. N. J. Chem. Soc. 1965, 575. (c) Brooke, G. M. J. Fluorine Chem. 1997, 86, 1. (d) Layeva, A. A.; Nosova, E. V.; Lipunova, G. N.; Charushin, V. N. Russ. Chem. Bull. 2008, 57, 947. (e) Garg, S.; Twamley, B.; Zeng, Z.; Shreeve, J. n. M. Chem.Eur. J. 2009, 15, 10554. (f) Matsubara, K.; Ishibashi, T.; Koga, Y. Org. Lett. 2009, 11, 1765. (g) Sharma, B.; VanDerveer, D. G.; Liff, S. M.; Smith, D. W., Jr. Tetrahedron Lett. 2013, 54, 3609. (h) Liu, C.; Cao, L.; Yin, X.; Xu, H.; Zhang, B. J. Fluorine Chem. 2013, 156, 51. (i) Xiong, Y.; Wu, J. J.; Xiao, S. H.; Xiao, J.; Cao, S. J. Org. Chem. 2013, 78, 4599. (j) Lu, F.; Sun, H.; Du, A.; Feng, L.; Li, X. Org. Lett. 2014, 16, 772. (k) Sharma, B.; Hill, S. C.; Liff, S. M.; Pennington, W. T.; Smith, D. W. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 232. (l) Sun, Y.; Sun, H.; Jia, J.; Du, A.; Li, X. Organometallics 2014, 33, 1079. (20) Saeki, T.; Takashima, Y.; Tamao, K. Synlett 2005, 1771. (21) Ackermann, L.; Wechsler, C.; Kapdi, A. R.; Althammer, A. Synlett 2010, 294. (22) (a) Sladek, M. I.; Braun, T.; Neumann, B.; Stammler, H. G. J. Chem. Soc., Dalton Trans. 2002, 297. (b) Steffen, A.; Sladek, M. I.; Braun, T.; Neumann, B.; Stammler, H. G. Organometallics 2005, 24, 4057. (c) Crespo, M.; Martinez, M.; Sales, J. J. Chem. Soc., Chem. Commun. 1992, 822. (23) (a) Ackermann, L.; Althammer, A. Org. Lett. 2006, 8, 3457. (b) Ackermann, L. Synlett 2007, 507. (24) Jin, Z.; Li, Y.-J.; Ma, Y.-Q.; Qiu, L.-L.; Fang, J.-X. Chem.Eur. J. 2012, 18, 446. (25) Deacon, G. B.; Koplick, A. J.; Raverty, W. D.; Vince, D. G. J. Organomet. Chem. 1979, 182, 121. (26) Edelbach, B. L.; Kraft, B. M.; Jones, W. D. J. Am. Chem. Soc. 1999, 121, 10327. (27) Guo, H. Q.; Kong, F. Z.; Kanno, K.; He, J. J.; Nakajima, K.; Takahashi, T. Organometallics 2006, 25, 2045. (28) Krasnov, V. I.; Platonov, V. E.; Beregovaya, I. V.; Shohegoleva, L. N. Tetrahedron 1997, 53, 1797. (29) Miller, A. O.; Krasnov, V. I.; Peters, D.; Platonov, V. E.; Miethchen, R. Tetrahedron Lett. 2000, 41, 3817. (30) Schaub, T.; Backes, M.; Radius, U. J. Am. Chem. Soc. 2006, 128, 15964. (31) Schaub, T.; Radius, U. Chem.Eur. J. 2005, 11, 5024. (32) Schaub, T.; Fischer, P.; Steffen, A.; Braun, T.; Radius, U.; Mix, A. J. Am. Chem. Soc. 2008, 130, 9304. (33) Ohashi, M.; Saijo, H.; Shibata, M.; Ogoshi, S. Eur. J. Org. Chem. 2013, 443. (34) Zheng, T.; Sun, H.; Chen, Y.; Li, X.; Dürr, S.; Radius, U.; Harms, K. Organometallics 2009, 28, 5771. (35) Ohashi, M.; Doi, R.; Ogoshi, S. Chem.Eur. J. 2014, 20, 2040. (36) Macgregor, S. A.; Roe, D. C.; Marshall, W. J.; Bloch, K. M.; Bakhmutov, V. I.; Grushin, V. V. J. Am. Chem. Soc. 2005, 127, 15304. (37) (a) Crespo, M.; Martinez, M.; Sales, J.; Solans, X.; Font-Bardia, M. Organometallics 1992, 11, 1288. (b) Crespo, M.; Martinez, M.; AM


Chemical Reviews

Review

Sales, J. Organometallics 1993, 12, 4297. (c) Crespo, M.; Martinez, M.; de Pablo, E. J. Chem. Soc., Dalton Trans. 1997, 1231. (38) Ryabov, A. D. Chem. Rev. 1990, 90, 403. (39) (a) Bernhardt, P. V.; Gallego, C.; Martinez, M. Organometallics 2000, 19, 4862. (b) Wang, T.; Love, J. A. Organometallics 2008, 27, 3290. (40) (a) Wang, T.; Alfonso, B. J.; Love, J. A. Org. Lett. 2007, 9, 5629. (b) Buckley, H. L.; Sun, A. D.; Love, J. A. Organometallics 2009, 28, 6622. (c) Sun, A. D.; Love, J. A. J. Fluorine Chem. 2010, 131, 1237. (d) Keyes, L.; Sun, A. D.; Love, J. A. Eur. J. Org. Chem. 2011, 3985. (e) Wang, T.; Keyes, L.; Patrick, B. O.; Love, J. A. Organometallics 2012, 31, 1397. (41) Buckley, H. L.; Wang, T.; Tran, O.; Love, J. A. Organometallics 2009, 28, 2356. (42) (a) Bryndza, H. E.; Fong, L. K.; Paciello, R. A.; Tam, W.; Bercaw, J. E. J. Am. Chem. Soc. 1987, 109, 1444. (b) Hartwig, J. F. Inorg. Chem. 2007, 46, 1936. (c) Evans, M. E.; Burke, C. L.; Yaibuathes, S.; Clot, E.; Eisenstein, O.; Jones, W. D. J. Am. Chem. Soc. 2009, 131, 13464. (d) Tanabe, T.; Brennessel, W. W.; Clot, E.; Eisenstein, O.; Jones, W. D. Dalton Trans. 2010, 39, 10495. (43) (a) Yang, X.; Sun, H.; Zhang, S.; Li, X. J. Organomet. Chem. 2013, 723, 36. (b) Sun, A. D.; Love, J. A. Org. Lett. 2011, 13, 2750. (c) Sun, A. D.; Leung, K.; Restivo, A. D.; Laberge, N. A.; Takasaki, H.; Love, J. A. Chemistry 2014, 20, 3162. (44) Lu, F.; Sun, H.; Li, X. Chin. J. Chem. 2013, 31, 927. (45) (a) Richmond, T. G.; Osterberg, C. E.; Arif, A. M. J. Am. Chem. Soc. 1987, 109, 8091. (b) Richmond, T. G. Coord. Chem. Rev. 1990, 105, 221. (c) Osterberg, C. E.; King, M. A.; Arif, A. M.; Richmond, T. G. Angew. Chem. 1990, 102, 960. (d) Osterberg, C. E.; King, M. A.; Arif, A. M.; Richmond, T. G. Angew. Chem., Int. Ed. 1990, 29, 888. (e) Lucht, B. L.; Poss, M. J.; King, M. A.; Richmond, T. G. J. Chem. Soc., Chem. Commun. 1991, 400. (f) Kiplinger, J. L.; King, M. A.; Arif, A. M.; Richmond, T. G. Organometallics 1993, 12, 3382. (g) Kiplinger, J. L.; King, M. A.; Fechtenkötter, A.; Arif, A. M.; Richmond, T. G. Organometallics 1996, 15, 5292. (h) Kiplinger, J. L.; Richmond, T. G.; Arif, A. M.; Dücker-Benfer, C.; van Eldik, R. Organometallics 1996, 15, 1545. (46) Yu, D.; Shen, Q.; Lu, L. J. Org. Chem. 2012, 77, 1798. (47) Yu, D.; Lu, L.; Shen, Q. Org. Lett. 2013, 15, 940. (48) Tobisu, M.; Xu, T.; Shimasaki, T.; Chatani, N. J. Am. Chem. Soc. 2011, 133, 19505. (49) Widdowson, D. A.; Wilhelm, R. Chem. Commun. 2003, 578. (50) Jakt, M.; Johannissen, L.; Rzepa, H. S.; Widdowson, D. A.; Wilhelm, R. J. Chem. Soc., Perkin Trans. 2 2002, 576. (51) Negishi, E.; Liu, F. Palladium- or nickel-catalyzed cross-coupling with organometals containing zinc, magnesium, aluminum, and zirconium; Wiley-VCH, Inc.: New York, 1998. (52) Cargill, M. R.; Sandford, G.; Tadeusiak, A. J.; Yufit, D. S.; Howard, J. A. K.; Kilickiran, P.; Nelles, G. J. Org. Chem. 2010, 75, 5860. (53) Cargill, M. R.; Sandford, G.; Kilickiran, P.; Nelles, G. Tetrahedron 2013, 69, 512. (54) Korn, T. J.; Schade, M. A.; Wirth, S.; Knochel, P. Org. Lett. 2006, 8, 725. (55) Kawamoto, K.; Kochi, T.; Sato, M.; Mizushima, E.; Kakiuchi, F. Tetrahedron Lett. 2011, 52, 5888. (56) Ueno, S.; Mizushima, E.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2006, 128, 16516. (57) (a) Manabe, K.; Ishikawa, S. Synthesis 2008, 2645. (b) Ishikawa, S.; Manabe, K. Synthesis 2008, 3180. (58) Wang, J.-R.; Manabe, K. Org. Lett. 2009, 11, 741. (59) (a) Atherton, M. J.; Fawcett, J.; Holloway, J. H.; Hope, E. G.; Karacar, A.; Russell, D. R.; Saunders, G. C. J. Chem. Soc., Chem. Commun. 1995, 191. (b) Atherton, M. J.; Fawcett, J.; Holloway, J. H.; Hope, E. G.; Karacar, A.; Russell, D. R.; Saunders, G. C. J. Chem. Soc., Dalton Trans. 1996, 3215. (c) Fawcett, J.; Friedrichs, S.; Holloway, J. H.; Hope, E. G.; McKee, V.; Nieuwenhuyzen, M.; Russell, D. R.; Saunders, G. C. J. Chem. Soc., Dalton Trans. 1998, 1477. (d) Atherton, M. J.; Holloway, J. H.; Hope, E. G.; Saunders, G. C. J. Organomet.

Chem. 1998, 558, 209. (e) Atherton, M. J.; Fawcett, J.; Holloway, J. H.; Hope, E. G.; Martin, S. M.; Russell, D. R.; Saunders, G. C. J. Organomet. Chem. 1998, 555, 67. (f) Atherton, M. J.; Fawcett, J.; Holloway, J. H.; Hope, E. G.; Russell, D. R.; Saunders, G. C. J. Organomet. Chem. 1999, 582, 163. (g) Nieuwenhuyzen, M.; Saunders, G. C. J. Organomet. Chem. 2000, 595, 292. (h) Bellabarba, R. M.; Saunders, G. C. J. Fluorine Chem. 2001, 112, 139. (i) Bellabarba, R. M.; Nieuwenhuyzen, M.; Saunders, G. C. J. Chem. Soc., Dalton Trans. 2001, 512. (j) Bellabarba, R. M.; Nieuwenhuyzen, M.; Saunders, G. C. Inorg. Chim. Acta 2001, 323, 78. (k) Bellabarba, R. M.; Nieuwenhuyzen, M.; Saunders, G. C. Organometallics 2002, 21, 5726. (l) Bellabarba, R. M.; Saunders, G. C.; Scott, S. Inorg. Chem. Commun. 2002, 5, 15. (m) Bellabarba, R. M.; Nieuwenhuyzen, M.; Saunders, G. C. Organometallics 2003, 22, 1802. (n) Bellabarba, R. M.; Saunders, G. C. Polyhedron 2004, 23, 2659. (o) Nieuwenhuyzen, M.; Saunders, G. C.; Smyth, E. C. M. S. Organometallics 2006, 25, 996. (p) Marr, A. C.; Nieuwenhuyzen, M.; Pollock, C. L.; Saunders, G. C. Inorg. Chem. Commun. 2006, 9, 407. (q) Barnes, N. A.; Brisdon, A. K.; Nieuwenhuyzen, M.; Pritchard, R. G.; Saunders, G. C. J. Fluorine Chem. 2007, 128, 943. (r) Marr, A. C.; Nieuwenhuyzen, M.; Pollock, C. L.; Saunders, G. C. Organometallics 2007, 26, 2659. (s) Pollock, C. L.; Saunders, G. C.; Smyth, E. C. M. S.; Sorokin, V. I. J. Fluorine Chem. 2008, 129, 142. (t) McGibbon, A.; Nieuwenhuyzen, M.; Saunders, G. C. J. Fluorine Chem. 2011, 132, 495. (60) Hughes, R. P.; Lindner, D. C.; Rheingold, A. L.; Yap, G. P. A. Organometallics 1996, 15, 5678. (61) (a) Erhardt, S.; Macgregor, S. A. J. Am. Chem. Soc. 2008, 130, 15490. (b) Teltewskoi, M.; Panetier, J. A.; Macgregor, S. A.; Braun, T. Angew. Chem. 2010, 122, 4039. (c) Teltewskoi, M.; Panetier, J. A.; Macgregor, S. A.; Braun, T. Angew. Chem., Int. Ed. 2010, 49, 3947. (d) Nova, A.; Reinhold, M.; Perutz, R. N.; Macgregor, S. A.; McGrady, J. E. Organometallics 2010, 29, 1824. (e) Jiao, E.; Xia, F.; Zhu, H. Comput. Theor. Chem. 2011, 965, 92. (62) Sabater, S.; Mata, J. A.; Peris, E. Nat. Commun. 2013, 4, 2553. (63) (a) Cronin, L.; Higgitt, C. L.; Karch, R.; Perutz, R. N. Organometallics 1997, 16, 4920. (b) Hatnean, J. A.; Johnson, S. A. Organometallics 2012, 31, 1361. (64) (a) Bell, S. L.; Chambers, R. D.; Musgrave, W. K. R.; Thorpe, J. G. J. Fluorine Chem. 1971, 1, 51. (b) Emara, A. A. A.; Schrobilgen, G. J. J. Chem. Soc., Chem. Commun. 1988, 257. (c) Holtcamp, M. W.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 1997, 119, 848. (d) Archibald, S. J.; Braun, T.; Gaunt, J. A.; Hobson, J. E.; Perutz, R. N. J. Chem. Soc., Dalton Trans. 2000, 2013. (e) Huhmann-Vincent, J.; Scott, B. L.; Kubas, G. J. Inorg. Chem. 1999, 38, 115. (65) (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 9722. (b) Weissman, H.; Shimon, L. J. W.; Milstein, D. Organometallics 2004, 23, 3931. (c) Atkinson, R. C. J.; Gibson, V. C.; Long, N. J.; White, A. J. P.; Williams, D. J. Organometallics 2004, 23, 2744. (d) Kwong, F. Y.; Chan, A. S. C. Synlett 2008, 1440. (e) Lundgren, R. J.; Peters, B. D.; Alsabeh, P. G.; Stradiotto, M. Angew. Chem. 2010, 122, 4165. (f) Lundgren, R. J.; Peters, B. D.; Alsabeh, P. G.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49, 4071. (g) Lundgren, R. J.; Sappong-Kumankumah, A.; Stradiotto, M. Chem.Eur. J. 2010, 16, 1983. (66) Breyer, D.; Berger, J.; Braun, T.; Mebs, S. J. Fluorine Chem. 2012, 143, 263. (67) (a) Doherty, N. M.; Hoffmann, N. W. Chem. Rev. 1991, 91, 553. (b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (c) Murphy, E. F.; Murugavel, R.; Roesky, H. W. Chem. Rev. 1997, 97, 3425. (d) Braun, T.; Parsons, S.; Perutz, R. N.; Voith, M. Organometallics 1999, 18, 1710. (e) Nilsson, P.; Plamper, F.; Wendt, O. F. Organometallics 2003, 22, 5235. (f) Vicente, J.; Gil-Rubio, J.; Guerrero-Leal, J.; Bautista, D. Organometallics 2004, 23, 4871. (g) Pierrat, P.; Gros, P.; Fort, Y. Org. Lett. 2005, 7, 697. (h) Burling, S.; Elliott, P. I. P.; Jasim, N. A.; Lindup, R. J.; McKenna, J.; Perutz, R. N.; Archibald, S. J.; Whitwood, A. C. Dalton Trans. 2005, 3686. (i) Braun, T.; Steffen, A.; Schorlemer, V.; Neumann, B.; Stammler, H. G. Dalton Trans. 2005, 3331. (j) Braun, T.; Izundu, J.; Steffen, A.; Neumann, B.; Stammler, H.-G. Dalton Trans. 2006, 5118. (k) Lindup, AN


Chemical Reviews

Review

R. J.; Marder, T. B.; Perutz, R. N.; Whitwood, A. C. Chem. Commun. 2007, 3664. (l) Steffen, A.; Braun, T.; Neumann, B.; Stammler, H.-G. Angew. Chem. 2007, 119, 8828. (m) Steffen, A.; Braun, T.; Neumann, B.; Stammler, H.-G. Angew. Chem., Int. Ed. 2007, 46, 8674. (n) Braun, T.; Ahijado Salomon, M.; Altenhöner, K.; Teltewskoi, M.; Hinze, S. Angew. Chem. 2009, 121, 1850. (o) Braun, T.; Ahijado Salomon, M.; Altenhoener, K.; Teltewskoi, M.; Hinze, S. Angew. Chem., Int. Ed. 2009, 48, 1818. (p) Fawcett, J.; Harding, D. A. J.; Hope, E. G.; Singh, K.; Solan, G. A. Dalton Trans. 2009, 6861. (q) Coleman, K. S.; Fawcett, J.; Harding, D. A. J.; Hope, E. G.; Singh, K.; Solan, G. A. Eur. J. Inorg. Chem. 2010, 2010, 4130. (r) Breyer, D.; Braun, T.; Kläring, P. Organometallics 2012, 31, 1417. (s) Kläring, P.; Jungton, A.-K.; Braun, T.; Müller, C. Eur. J. Inorg. Chem. 2012, 2012, 1430. (68) Braun, T.; Perutz, R. N.; Sladek, M. I. Chem. Commun. 2001, 2254. (69) Liu, J.; Robins, M. J. Org. Lett. 2005, 7, 1149. (70) (a) Yoshida, T.; Thorn, D. L.; Okano, T.; Otsuka, S.; Ibers, J. A. J. Am. Chem. Soc. 1980, 102, 6451. (b) Noveski, D.; Braun, T.; Neumann, B.; Stammler, A.; Stammler, H.-G. Dalton Trans. 2004, 4106. (71) (a) Aizenberg, M.; Milstein, D. Science 1994, 265, 359. (b) Aizenberg, M.; Milstein, D. J. Am. Chem. Soc. 1995, 117, 8674. (c) Whittlesey, M. K.; Perutz, R. N.; Moore, M. H. Chem. Commun. 1996, 787. (72) (a) Siedle, A. R.; Newmark, R. A.; Pignolet, L. H. Organometallics 1984, 3, 855. (b) Macdougall, J. K.; Simpson, M. C.; Cole-Hamilton, D. J. Polyhedron 1993, 12, 2877. (c) Gonsalvi, L.; Adams, H.; Sunley, G. J.; Ditzel, E.; Haynes, A. J. Am. Chem. Soc. 1999, 121, 11233. (73) Rankin, J.; C. Benyei, A.; J. Cole-Hamilton, D.; D. Poole, A. Chem. Commun. 1997, 1835. (74) Heitz, W.; Knebelkamp, A. Makromol. Chem., Rapid Commun. 1991, 12, 69. (75) Fujiwara, M.; Ichikawa, J.; Okauchi, T.; Minami, T. Tetrahedron Lett. 1999, 40, 7261. (76) (a) Anderson, D. J.; McDonald, R.; Cowie, M. Angew. Chem. 2007, 119, 3815. (b) Anderson, D. J.; McDonald, R.; Cowie, M. Angew. Chem., Int. Ed. 2007, 46, 3741. (77) Ristic-Petrovic, D.; Anderson, D. J.; Torkelson, J. R.; McDonald, R.; Cowie, M. Organometallics 2003, 22, 4647. (78) Ichikawa, J.; Sakoda, K.; Mihara, J.; Ito, N. J. Fluorine Chem. 2006, 127, 489. (79) Ichikawa, J.; Nadano, R.; Ito, N. Chem. Commun. 2006, 4425. (80) (a) Ichitsuka, T.; Fujita, T.; Arita, T.; Ichikawa, J. Angew. Chem., Int. Ed. 2014, 53, 7564. (b) Ichitsuka, T.; Fujita, T.; Arita, T.; Ichikawa, J. Angew. Chem. 2014, 126, 7694. (81) Ohashi, M.; Kambara, T.; Hatanaka, T.; Saijo, H.; Doi, R.; Ogoshi, S. J. Am. Chem. Soc. 2011, 133, 3256. (82) Xu, W.; Sun, H.; Xiong, Z.; Li, X. Organometallics 2013, 32, 7122. (83) Ishii, Y.; Chatani, N.; Yorimitsu, S.; Murai, S. Chem. Lett. 1998, 157. (84) Arisawa, M.; Suzuki, T.; Ishikawa, T.; Yamaguchi, M. J. Am. Chem. Soc. 2008, 130, 12214. (85) Macnicol, D. D.; Mallinson, P. R.; Murphy, A.; Sym, G. J. Tetrahedron Lett. 1982, 23, 4131. (86) Arisawa, M.; Ichikawa, T.; Yamaguchi, M. Org. Lett. 2012, 14, 5318. (87) Zhou, Q.; Zhang, B.; Du, T.; Gu, H.; Jiang, H.; Chen, R. Tetrahedron 2012, 68, 4233. (88) Yu, C.; Zhang, C.; Shi, X. Eur. J. Org. Chem. 2012, 1953. (89) Yu, C.; Hu, G.; Zhang, C.; Wu, R.; Ye, H.; Yang, G.; Shi, X. J. Fluorine Chem. 2013, 153, 33. (90) Keyes, L.; Sun, A. D.; Love, J. A. Eur. J. Org. Chem. 2011, 3985. (91) Zhang, J.; Wu, J.; Xiong, Y.; Cao, S. Chem. Commun. 2012, 48, 8553. (92) Sun, L.; Rong, M.; Kong, D.; Bai, Z.; Yuan, Y.; Weng, Z. J. Fluorine Chem. 2013, 150, 117.

(93) Deck, P. A.; Konate, M. M.; Kelly, B. V.; Slebodnick, C. Organometallics 2004, 23, 1089. (94) (a) Cochran, F. V.; Bonitatebus, P. J.; Schrock, R. R. Organometallics 2000, 19, 2414. (b) Schrock, R. R.; Adamchuk, J.; Ruhland, K.; Lopez, L. P. H. Organometallics 2003, 22, 5079. (c) Hoyt, H. M.; Michael, F. E.; Bergman, R. G. J. Am. Chem. Soc. 2004, 126, 1018. (95) (a) Arroyo, M.; Bernes, S.; Ceron, M.; Cortina, V.; Mendoza, C.; Torrens, H. Inorg. Chem. 2007, 46, 4857. (b) Mendoza, C.; Bernes, S.; Torrens, H.; Arroyo, M. Organometallics 2010, 29, 2646. (c) Scharf, A.; Goldberg, I.; Vigalok, A. Organometallics 2012, 31, 1275. (d) Gandioso, A.; Valle-Sistac, J.; Rodriguez, L.; Crespo, M.; FontBardia, M. Organometallics 2014, 33, 561. (96) Mohr, W.; Stark, G. A.; Jiao, H.; Gladysz, J. A. Eur. J. Inorg. Chem. 2001, 925. (97) Battioni, P.; Brigaud, O.; Desvaux, H.; Mansuy, D.; Traylor, T. G. Tetrahedron Lett. 1991, 32, 2893. (98) Arroyo, M.; Bernes, S.; Brianso, J. L.; Mayoral, E.; Richards, R. L.; Rius, J.; Torrens, H. J. Organomet. Chem. 2000, 599, 170. (99) Plenio, H. Chem. Rev. 1997, 97, 3363. (100) Villanueva, L.; Arroyo, M.; Bernes, S.; Torrens, H. Chem. Commun. 2004, 1942. (101) (a) Uson, R.; Fornies, J.; Espinet, P.; Garcia, A.; Tomas, M.; Focesfoces, C.; Cano, F. H. J. Organomet. Chem. 1985, 282, C35. (b) Park, S.; Pontierjohnson, M.; Roundhill, D. M. J. Am. Chem. Soc. 1989, 111, 3101. (c) Park, S.; Pontierjohnson, M.; Roundhill, D. M. Inorg. Chem. 1990, 29, 2689. (102) Pachal, S. R.; Saunders, G. C.; Weston, J. K. Inorg. Chim. Acta 2013, 394, 558. (103) (a) Braun, T.; Foxon, S. P.; Perutz, R. N.; Walton, P. H. Angew. Chem. 1999, 111, 3543. (b) Braun, T.; Foxon, S. P.; Perutz, R. N.; Walton, P. H. Angew. Chem., Int. Ed. 1999, 38, 3326. (104) Braun, T.; Schorlemer, V.; Neumann, B.; Stammler, H. G. J. Fluorine Chem. 2006, 127, 367. (105) (a) Kemmitt, R. D. W.; Peacock, R. D.; Stocks, J. J. Chem. Soc. A 1971, 846. (b) Grushin, V. V.; Marshall, W. J. Angew. Chem. 2002, 114, 4656. (c) Grushin, V. V.; Marshall, W. J. Angew. Chem., Int. Ed. 2002, 41, 4476. (d) Grushin, V. V.; Marshall, W. J. Organometallics 2007, 26, 4997. (106) Braun, T.; Rothfeld, S.; Schorlemer, V.; Stammler, A.; Stammler, H. G. Inorg. Chem. Commun. 2003, 6, 752. (107) Breyer, D.; Braun, T.; Penner, A. Dalton Trans. 2010, 39, 7513. (108) (a) Teltewskoi, M.; Kallaene, S. I.; Braun, T.; Herrmann, R. Eur. J. Inorg. Chem. 2013, 2013, 5762. (b) Kallane, S. I.; Braun, T.; Braun, B.; Mebs, S. Dalton Trans 2014, 43, 6786. (109) (a) Archibald, S. J.; Braun, T.; Gaunt, J. A.; Hobson, J. E.; Perutz, R. N. J. Chem. Soc., Dalton Trans. 2000, 2013. (b) Chambers, R. D.; Hoskin, P. R.; Sandford, G.; Yufit, D. S.; Howard, J. A. K. J. Chem. Soc., Perkin Trans. 1 2001, 2788. (c) Chambers, R. D.; Hoskin, P. R.; Kenwright, A. R.; Khalil, A.; Richmond, P.; Sandford, G.; Yufit, D. S.; Howard, J. A. K. Org. Biomol. Chem. 2003, 1, 2137. (110) (a) Adamson, A. J.; Jondi, W. J.; Tipping, A. E. J. Fluorine Chem. 1996, 76, 67. (b) Benmansour, H.; Chambers, R. D.; Hoskin, P. R.; Sandford, G. J. Fluorine Chem. 2001, 112, 133. (c) Piglosiewicz, I. M.; Kraft, S.; Beckhaus, R.; Haase, D.; Saak, W. Eur. J. Inorg. Chem. 2005, 938. (d) Jager-Fiedler, U.; Arndt, P.; Baumann, W.; Spannenberg, A.; Burlakov, V. V.; Rosenthal, U. Eur. J. Inorg. Chem. 2005, 2842. (111) (a) Blum, O.; Frolow, F.; Milstein, D. J. Chem. Soc., Chem. Commun. 1991, 258. (b) Grushin, V. V.; Marshall, W. J. J. Am. Chem. Soc. 2004, 126, 3068. (c) Macgregor, S. A.; Wondimagegn, T. Organometallics 2007, 26, 1143. (112) Hughes, R. P.; Smith, J. M.; Incarvito, C. D.; Lam, K. C.; Rhatigan, B.; Rheingold, A. L. Organometallics 2002, 21, 2136. (113) Hughes, R. P.; Lindner, D. C.; Rheingold, A. L.; LiableSands, L. M. J. Am. Chem. Soc. 1997, 119, 11544. (114) See also: (a) Clark, G. R.; Hoskins, S. V.; Roper, W. R. J. Organomet. Chem. 1982, 234, C9. (b) Burch, R. R.; Calabrese, J. C.; Ittel, S. D. Organometallics 1988, 7, 1642. (c) Brothers, P. J.; Roper, W. AO


Chemical Reviews

Review

R. Chem. Rev. 1988, 88, 1293. (d) Hughes, R. P.; Smith, J. M. J. Am. Chem. Soc. 1999, 121, 6084. (e) Garratt, S. A.; Hughes, R. P.; Kovacik, I.; Ward, A. J.; Willemsen, S.; Zhang, D. H. J. Am. Chem. Soc. 2005, 127, 15585. (115) Hughes, R. P.; Laritchev, R. B.; Zakharov, L. N.; Rheingold, A. L. J. Am. Chem. Soc. 2005, 127, 6325. (116) Hughes, R. P.; Zhang, D.; Zakharov, L. N.; Rheingold, A. L. Organometallics 2002, 21, 4902. (117) (a) Reger, D. L.; Dukes, M. D. J. Organomet. Chem. 1978, 153, 67. (b) Richmond, T. G.; Shriver, D. F. Organometallics 1983, 2, 1061. (c) Richmond, T. G.; Crespi, A. M.; Shriver, D. F. Organometallics 1984, 3, 314. (d) Richmond, T. G.; Shriver, D. F. Organometallics 1984, 3, 305. (e) Michelin, R. A.; Facchin, G.; Ros, R. J. Organomet. Chem. 1985, 279, C25. (f) Appleton, T. G.; Berry, R. D.; Hall, J. R.; Neale, D. W. J. Organomet. Chem. 1989, 364, 249. (g) Michelin, R. A.; Ros, R.; Guadalupi, G.; Bombieri, G.; Benetollo, F.; Chapuis, G. Inorg. Chem. 1989, 28, 840. (h) Koola, J. D.; Roddick, D. M. Organometallics 1991, 10, 591. (i) Hughes, R. P.; Rose, P. R.; Rheingold, A. L. Organometallics 1993, 12, 3109. (j) Burrell, A. K.; Clark, G. R.; Rickard, C. E. F.; Roper, W. R. J. Organomet. Chem. 1994, 482, 261. (k) Hughes, R. P.; Lindner, D. C.; Liable-Sands, L. M.; Rheingold, A. L. Organometallics 2001, 20, 363. (118) Giffin, K. A.; Harrison, D. J.; Korobkov, I.; Baker, R. T. Organometallics 2013, 32, 7424. (119) Braun, T.; Blocker, B.; Schorlemer, V.; Neumann, B.; Stammler, A.; Stammler, H. G. J. Chem. Soc., Dalton Trans. 2002, 2213. (120) Sakoda, K.; Mihara, J.; Ichikawa, J. Chem. Commun. 2005, 4684. (121) (a) Noveski, D.; Braun, T.; Neumann, B.; Stammler, A.; Stammler, H. G. Dalton Trans. 2004, 4106. (b) Braun, T.; Noveski, D.; Ahijado, M.; Wehmeier, F. Dalton Trans. 2007, 3820. (122) (a) Braun, T.; Noveski, D.; Neumann, B.; Stammler, H.-G. Angew. Chem. 2002, 114, 2870. (b) Braun, T.; Noveski, D.; Neumann, B.; Stammler, H. G. Angew. Chem., Int. Ed. 2002, 41, 2745. (c) Noveski, D.; Braun, T.; Schulte, M.; Neumann, B.; Stammler, H. G. Dalton Trans. 2003, 4075. (d) Braun, T.; Wehmeier, F.; Altenhöner, K. Angew. Chem. 2007, 119, 5415. (e) Braun, T.; Wehmeier, F.; Altenhoener, K. Angew. Chem., Int. Ed. 2007, 46, 5321. (123) Thorn, D. L.; Harlow, R. L. Inorg. Chem. 1990, 29, 2017. (124) (a) Watson, P. L.; Tulip, T. H.; Williams, I. Organometallics 1990, 9, 1999. (b) Peterson, T. H.; Golden, J. T.; Bergman, R. G. Organometallics 1999, 18, 2005. (c) Huang, D. J.; Bollinger, J. C.; Streib, W. E.; Folting, K.; Young, V.; Eisenstein, O.; Caulton, K. G. Organometallics 2000, 19, 2281. (d) Kraft, B. M.; Lachicotte, R. J.; Jones, W. D. J. Am. Chem. Soc. 2000, 122, 8559. (e) Kirkham, M. S.; Mahon, M. F.; Whittlesey, M. K. Chem. Commun. 2001, 813. (f) Kraft, B. M.; Jones, W. D. J. Am. Chem. Soc. 2002, 124, 8681. (g) FerrandoMiguel, G.; Gerard, H.; Eisenstein, O.; Caulton, K. G. Inorg. Chem. 2002, 41, 6440. (h) Renkema, K. B.; Werner-Zwanziger, U.; Pagel, M. D.; Caulton, K. G. J. Mol. Catal. A: Chem. 2004, 224, 125. (i) Huang, D. J.; Renkema, K. B.; Caulton, K. G. Polyhedron 2006, 25, 459. (j) Yamada, S.; Noma, M.; Konno, T.; Ishihara, T.; Yamanaka, H. Org. Lett. 2006, 8, 843. (k) Engman, M.; Diesen, J. S.; Paptchikhine, A.; Andersson, P. G. J. Am. Chem. Soc. 2007, 129, 4536. (l) Narumi, T.; Tomita, K.; Inokuchi, E.; Kobayashi, K.; Oishi, S.; Ohno, H.; Fujii, N. Org. Lett. 2007, 9, 3465. (m) Rieth, R. D.; Brennessel, W. W.; Jones, W. D. Eur. J. Inorg. Chem. 2007, 2839. (n) Yamada, S.; Takahashi, T.; Konno, T.; Ishihara, T. Chem. Commun. 2007, 3679. (o) Kühnel, M. F.; Lentz, D. Angew. Chem. 2010, 122, 2995. (p) Kuhnel, M. F.; Lentz, D. Angew. Chem., Int. Ed. 2010, 49, 2933. (q) Kuehnel, M. F.; Schlöder, T.; Riedel, S.; Nieto-Ortega, B.; Ramírez, F. J.; López Navarrete, J. T.; Casado, J.; Lentz, D. Angew. Chem. 2012, 124, 2261. (r) Kuehnel, M. F.; Holstein, P.; Kliche, M.; Krueger, J.; Matthies, S.; Nitsch, D.; Schutt, J.; Sparenberg, M.; Lentz, D. Chem.Eur. J. 2012, 18, 10701. (s) Kuehnel, M. F.; Schloeder, T.; Riedel, S.; Nieto-Ortega, B.; Ramirez, F. J.; Lopez Navarrete, J. T.; Casado, J.; Lentz, D. Angew. Chem., Int. Ed. 2012, 51, 2218. (125) (a) Vol’pin, M. E.; Shevchenko, N. y. V.; Bolestova, G. I.; Zeifman, Y. V.; Fialkov, Y. A.; Parnes, Z. N. Mendeleev Commun. 1991,

1, 118. (b) Scott, V. J.; Celenligil-Cetin, R.; Ozerov, O. V. J. Am. Chem. Soc. 2005, 127, 2852. (c) Panisch, R.; Bolte, M.; Mueller, T. J. Am. Chem. Soc. 2006, 128, 9676. (d) Douvris, C.; Stoyanov, E. S.; Tham, F. S.; Reed, C. A. Chem. Commun. 2007, 1145. (e) Klahn, M.; Fischer, C.; Spannenberg, A.; Rosenthal, U.; Krossing, I. Tetrahedron Lett. 2007, 48, 8900. (f) Douvris, C.; Ozerov, O. V. Science 2008, 321, 1188. (g) Perutz, R. N. Science 2008, 321, 1168. (h) Gu, W.; Haneline, M. R.; Douvris, C.; Ozerov, O. V. J. Am. Chem. Soc. 2009, 131, 11203. (i) Ali, M.; Liu, L.-P.; Hammond, G. B.; Xu, B. Tetrahedron Lett. 2009, 50, 4078. (j) Douvris, C.; Nagaraja, C. M.; Chen, C.-H.; Foxman, B. M.; Ozerov, O. V. J. Am. Chem. Soc. 2010, 132, 4946. (k) Duttwyler, S.; Douvris, C.; Fackler, N. L. P.; Tham, F. S.; Reed, C. A.; Baldridge, K. K.; Siegel, J. S. Angew. Chem. 2010, 122, 7681. (l) Duttwyler, S.; Douvris, C.; Fackler, N. L. P.; Tham, F. S.; Reed, C. A.; Baldridge, K. K.; Siegel, J. S. Angew. Chem., Int. Ed. 2010, 49, 7519. (m) Klare, H. F. T.; Oestreich, M. Dalton Trans. 2010, 39, 9176. (n) Gu, W.; Ozerov, O. V. Inorg. Chem. 2011, 50, 2726. (o) Allemann, O.; Duttwyler, S.; Romanato, P.; Baldridge, K. K.; Siegel, J. S. Science 2011, 332, 574. (p) Gusev, D. G.; Ozerov, O. V. Chem.Eur. J. 2011, 17, 634. (q) Luehmann, N.; Hirao, H.; Shaik, S.; Mueller, T. Organometallics 2011, 30, 4087. (r) Caputo, C. B.; Stephan, D. W. Organometallics 2012, 31, 27. (s) Schulz, A.; Villinger, A. Angew. Chem. 2012, 124, 4602. (t) Schulz, A.; Villinger, A. Angew. Chem., Int. Ed. 2012, 51, 4526. (u) Takikawa, H. J. Synth. Org. Chem., Jpn. 2012, 70, 395. (v) Ahrens, M.; Scholz, G.; Braun, T.; Kemnitz, E. Angew. Chem. 2013, 125, 5436. (w) Ahrens, M.; Scholz, G.; Braun, T.; Kemnitz, E. Angew. Chem., Int. Ed. 2013, 52, 5328. (x) Caputo, C. B.; Hounjet, L. J.; Dobrovetsky, R.; Stephan, D. W. Science 2013, 341, 1374. (y) Azhakar, R.; Roesky, H. W.; Wolf, H.; Stalke, D. Chem. Commun. 2013, 49, 1841. (z) Stahl, T.; Klare, H. F. T.; Oestreich, M. ACS Catal. 2013, 3, 1578. (aa) Stahl, T.; Klare, H. F. T.; Oestreich, M. J. Am. Chem. Soc. 2013, 135, 1248. (ab) Pan, B.; Gabbai, F. P. J. Am. Chem. Soc. 2014, 136, 9564.

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