WO2016087879A1 - Formation of bonds by outer-sphere oxidative electrophilic fluorination - Google Patents

Abstract

There is described a method of fluorination of an alkenyl, alkynyl, aryl or isonitrile compound which comprises reacting an alkenyl, alkynyl, aryl or isonitrile compound with a metal-mediated outer-sphere electrophilic fluorinating (OSEF) agent.

Description

Formation of Bonds by Outer-Sphere Oxidative Electrophilic Fluorination

Field of the Invention

The present invention relates to a novel process for the fluorination of organic compounds.

More particularly, the present invention relates to a novel process for the fluorination of organic compounds, such as alkynes, alkenes and arenes using an electrophilic fluorination agent.

Background to the Invention

Organofluorine chemistry plays a key role in materials science, pharmaceuticals, agrochemicals and medical imaging. However, the formation of new carbon-fluorine bonds with controlled regiochemistry and functional group tolerance is synthetically challenging.

Fluorine-containing organic molecules are found in a wide range of applications from liquid crystals to blockbuster drugs such as fluoxetine and atorvastatin, but are of particular interest in pharmaceuticals, agrochemicals and medical imaging. The unique properties of C-F bonds, which can improve metabolic stability, bioavailability and lipophilicity, mean that around 30 % of all agrochemicals and 20 % of all pharmaceuticals now contain fluorine. In addition, the use of ¹⁸F-labelled compounds in positron emission tomography (PET) is a highly active and important area of medical imaging research.

As such, there is a synthetic requirement to develop simple, efficient (and in the case of ¹⁸F labelling, where the ¹⁸F half life is short, rapid) methods for the introduction of fluorine into organic molecules. Selective formation of new carbon-fluorine bonds, particularly in the presence of sensitive functional groups, is synthetically challenging.¹ There has been a focus in recent years on the development of new transition-metal-mediated C-F bond forming reactions, which offer significant potential for regioselectivity and atom- and step-economy under mild conditions. There have recently been some significant advances in metal-catalysed fluorination using fluoride salts as the fluorine source.^1"11

However, fluoride salts are often not ideal for the introduction of fluorine into organic molecules: in the presence of hydrogen-bonding solvents F^" is a poor nucleophile and when anhydrous, although a better nucleophile, is it also highly basic and thus can result in unwanted side reactions.

To circumvent these problems, a number of metal-catalysed electrophilic fluorination reactions have been developed, where C-F bonds are formed from latent sources of "F^"1"".¹' ^{12" 17} In the majority of these cases there is an initial metal-fluoride bond formation with concomitant oxidation of the metal, which then induces C-F reductive elimination or oxidises the substrate to form a radical that subsequently abstracts F^' from the metal. These are powerful strategies that are broadly applicable, but there are some limitations. Directing groups and/or pre-activation of the substrates (for example by formation of an aryl stannane, silane or boronic acid) are generally required to promote the reactions.^18"23 In addition, these systems have typically focussed on aryl C-F bond formation. As such, the development of new regio- and stereo- specific metal-mediated electrophilic fluorination reactions, without the need for directing and activating groups, is of great interest. Reactions that allow the construction of less common structural frameworks, for example those containing alkenyl or alkyl C-F bonds (especially chiral C(sp³)-F centres) are particularly interesting. Although examples of Lewis acidic metal-mediated C(sp³)-F bond formation have been reported,¹ these reactions often require highly activated substrates, typically those which form stabilised carbanions (e.g. β-diketones), which reduces potential substrate scope.

The development of new classes of metal-catalysed reactions is frequently informed by the observation of unusual stoichiometric organometallic reactivity and a comprehensive understanding of the key mechanistic steps involved in a given reaction, an example being the development of alkene metathesis catalysts.

Metal-mediated fluorination offers great potential to construct new fluorinated molecules, but even state-of-the-art approaches are limited in their substrate scope, often require activated substrates or do not allow access to desirable functionality, such as alkenyl C(sp²)-F or chiral C(sp³)-F centres.

The inventors have now developed a method for the formation of new aryl, alkenyl, alkyl and isonitrile C-F, C-CF₃ , C-SCF₃ and C-S0₂CF₃ bonds in the coordination sphere of a metal, such as, ruthenium, via an unprecedented outer-sphere electrophilic fluorination (OSEF) mechanism. The organometallic species involved are derived from non-activated substrates (for example, pyridine and terminal alkynes) and C-F bond formation occurs with full regio- and stereo- chemical control. Incorporation of this reactivity into stoichiometric or catalytic synthetic methodologies will significantly expand the range of fluorinated molecules available via metal-mediated fluorination. There are no examples of reactions in which it has been possible to use a source of F⁺ to incorporate fluorine directly (not via metal-fluorine bond formation) into an organic ligand bound to a redox-active transition metal, where C-F bond formation is facilitated by metal- ligand back donation or formal metal oxidation from the Mⁿ to the M⁽ⁿ⁺²⁾ oxidation state. Such a process is of particular interest given that metal complexes may significantly alter the reactivity of coordinated ligands and, as such, offer new methods for both initial C-F bond formation and subsequent functionalisation.

Summary to the Invention

The inventors have now developed a method for the formation of new aryl, alkenyl, alkyl and isonitrile C-F, C-CF₃ , C-SCF₃ and C-S0₂CF₃ bonds in the coordination sphere of a metal, such as, ruthenium, via an unprecedented outer-sphere electrophilic fiuorination (OSEF) mechanism; provided that the electrophilic fiuorination does not proceed via formation of an intermediate metal-fluorine bond and where C-F, C-CF₃, C-SCF₃ or C-S0₂CF₃ bond formation is facilitated by metal-ligand back donation or formal metal oxidation from the Mⁿ to the M⁽ⁿ⁺²⁾ oxidation state.

The present invention provides a novel method of fluorinating an organic compound using an electrophilic fluorinating agent.

Thus, according to a first aspect of the invention there is provided a method of fiuorination of an alkenyl, alkynyl, aryl or isonitrile compound which comprises of reacting an alkenyl, alkynyl, aryl or isonitrile compound with a metal-mediated outer-sphere electrophilic fluorinating (OSEF) agent. For the avoidance of doubt, the term "fluorination" shall include the introduction of one or more fluorine atoms to an organic or inorganic species, i.e. the formation of one or more C-F bonds; and/or the introduction of one or more trifluoromethyl (-CF₃) groups, i.e. the formation of C-CF₃ bonds.

In one embodiment of the invention there is provided a method which comprises the formation of one or more bonds selected from a C-F bond, a C-S-F bond and a C-S-CF₃ bond.

In a particular embodiment the "fluorination" comprises the introduction of a single fluorine atom, i.e. the formation of a single C-F bond; or the introduction of a single trifluoromethyl (-CF₃) group. Thus, in one aspect of the invention the method comprises the formation of a C-F bond. In another aspect of the invention the method comprises the formation of a C-CF₃ bond. In another aspect of the invention the method comprises the incorporation of multiple fluorine atoms by the formation of multiple C-F bonds. In another aspect of the invention the method comprises the incorporation of multiple trifluoromethyl (-CF₃) groups by the formation of multiple trifluoromethyl (C-CF₃) bonds.

In another aspect of the invention the method comprises the formation of one or more C-S-F bonds. For the avoidance of doubt, in the formation of one or more C-S-F bonds, S may also represent S0₂. Thus, the invention may comprise the formation of a single C-S-F bond or the formation of multiple C-S-F bonds. The invention may comprise the formation of one or more C-S-CF₃ bonds. Similarly, S may represent S0₂. The invention may comprise the formation of a single C-S-CF₃ bond or the formation of multiple C-S-CF₃ bonds. In the metal-mediated method of the invention the metal should be a redox active metal such that C-F, C-CF₃, C-S-F or C-S-CF₃ bond formation is facilitated by a metal that is capable of back donation or formal metal oxidation from the Mⁿ to the M⁽ⁿ⁺²⁾ oxidation state, provided that the electrophilic fluorination does not proceed via formation of an intermediate metal- fluorine bond as hereinbefore described.

In general, any metal capable of supporting ligands with the general features shown below (either as isolated species, or as intermediates in a stoichiometric or catalytic transformation) is susceptible to electrophilic fluorination by the outer-sphere electrophilic fluorination method of the present invention.

As part of a cyclic

system or not, may

contain elements other

than carbon or not,

cyclic system may be

aromatic or not

Metal vinyl species

(and their derivatives)

Where [M] = a metal fragment (as described above) and R, R' and R" are H, a carbon containing organic group, i.e. linear, branched or cyclic groups (including aromatic cyclic groups), or a heteroatom (such as N, O, S etc.) with associated functional groups.

Thus, the fluorination method of the present invention will generally comprise the use of a metal as hereinbefore described wherein the metal is in the form of a metal complex comprising one or more ligands bound to a metal centre. The method of the invention will generally comprise direct outer-sphere electrophilic fluorination of a ligand bound to the metal centre.

Exemplary metals include, but shall not be limited to, iron or one or more Platinum Group Metals, i.e. transition metals in groups 8, 9 and 10. Platinum Group Metals particularly comprise one or more of the metals iridium, osmium, palladium, platinum, rhodium and ruthenium. In an especially preferred aspect of the invention the Platinum Group Metal, is ruthenium.

Suitable ligands which may be used in the metal complex of the invention may comprise a "capping ligand", i.e. to a form "half- sandwich" metal complex, and one or more anionic or neutral ligands. When the metal complex comprises one or more anionic ligands, they are preferably mono-anionic. A suitable "capping ligand" is an aryl group or a tridentate ligand. Examples of aryl groups include, but shall not be limited to, C₅H₅, C₅Me₅, C6¾, C₇H₇ and the like. Examples of tridentate ligands include, tris(pyrazolyl) (Tp), and the like. Suitable anionic or neutral ligands include, but shall not be limited to, one or more of -CO, -CO2, phosphine, halide, pseudohalide, amine, -S(0)R⁴R⁵. If more than one anionic or neutral ligand is present, each of the anionic or neutral ligands may be the same or different.

The term halide as used herein shall include the term fluoride, chloride, bromide and iodide. Preferably the term halide is chloride.

The term phosphine as used herein shall include, inter alia, -PH₃ and -PR P^R³, in which R¹, R² and R³, which may be the same or different, are each alkyl C I to 20 or aryl or heteroatom- containing derivatives of these (e.g. pyridyl or imidazolyl). It may also include bi- and tri- dentate phosphine ligands as well as other multi-dentate analogues.

R⁴ and R⁵, which may be the same or different, are each hydrogen, alkyl CI to 20 or aryl or heteroatom-containing derivatives of these (e.g. pyridyl or imidazolyl).

The amount of the metal or metal complex may vary, depending upon the nature of the fluorinating agent, the organic compound, etc. The amount of the metal or metal complex may be stoichiometric or catalytic.

The method of the invention will generally comprise an outer-sphere electrophilic fluorinating agent (OSEF) as hereinbefore described with a latent source of "F⁺" or "CF₃ ⁺".

A latent source of "F⁺" will generally comprise an N-F fluorinating agent. Such N-F fluorinating agents include, but shall not be limited to: N-fluorosulfon/w/des, such as N- fluorobenzenesulfonimide (NFSI) and N-fluoro-o-benzenedisulfonimide (NFOBS); N- fluoropyridinium salts, including N-fluoropyridinium tetrafluoroborate ([C₅H₅ F][BF₄], from point onwards referred to as, [FPyr][BF₄]), tri-alkyl pyridinium tetrafluoroborates, such as, 1- fluoro-2,4,6-trimethylpyridinium tetrafluoroborate ([2,4,6-Me₃C₅H₂ F][BF₄], from this point onwards referred to as, [FTMP][BF ]), l-fluoro-2,4,6-trimethylpyridinium trifluoromethanesulfonate, 2,6-dichloro-l -fluoropyridinium trifluoromethanesulfonate or 1- fluoro 2,6-dichloropyridinium tetrafluoroborate; l,4-diazabicyclo[2.2.2]octane (DABCO) bis(ammonium) ions, such as l-chloromethyl-4-fluoro-l,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate (Selectfluor®); and N-fluoro-N'-(chloromethyl)triethylenediamine bis(tetrafluoroborate) and the like. Illustrative N-F fluorinating agents include:

N-fluoropyridinium salts

When the organic compound is a strongly nucleophilic substrate, such as, a metal alkynyl complex, then it is preferred that the latent source of "F⁺" is other than N-fluoropyridinium tetrafluoroborate.

More specifically, if the fluorinating agent is a tri-alkyl pyridinium tetrafluoroborate, such as, l-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate [2,4,6-Me₃C₅H₂NF][BF₄] it is desirable that the pKa of the conjugate acid of the substrate is lower than the pKa of [2,4,6- Me₃C₅H₂NF][BF₄] in the solvent system being used. The counter-anion would generally be weakly-coordinating to the metal such as OTf, [BF₄]^" _; [PF₆]^" or others.

It would be understood by the person skilled in the art that a range of organic solvents may suitably be used in the method of the present invention. Exemplary solvents include, but shall not be limited to CH₂C1₂ or NCMe/CH₂Cl₂.

Suitable electrophilic trifluoromethylation reagents include, but shall not be limited to, 5- (trifluoromethyl)dibenzothiophenium tetrafluoroborate (from this point onwards referred to as, Umemoto's reagent), 5-(trifluoromethyl)dibenzothiophenium trifluoromethanesulfonate and 3 ,3 -dimethyl- 1 -(trifluoromethyl)- 1 ,2-benziodoxole. A preferred trifluoromethylation reagent is 5-(trifluoromethyl)dibenzothiophenium tetrafluoroborate.

5-(trifluoromethyl)dibenzothiophenium tetrafluoroborate (Umemoto's reagent)

In addition to the formation of one or more C-F bonds and/or the introduction of one or more trifluoromethyl (-CF₃) groups, the invention will allow the introduction of trifluoromethanesulfenyl "-SCF₃", and trifluoromethanesulfonyl "-S0₂CF₃" groups to an organic or inorganic species from an electrophilic source of these groups via an OSEF-type mechanism.

Θ

[M]- -R [M]=C

E = SCF₃, S0₂CF₃

E' = CH, N, O, S etc

R, R', R" = alkyl, aryl - as part of a

cyclic system, or not, may contain

elements other than carbon, or

not; may be aromatic, or not etc The metal species defined elsewhere in the application will also be susceptible to this type of reactivity and the formation of new C-SCF₃ and C-SO₂CF3 bonds will occur in a similar way to C-F and C-CF₃ bond formation.

Ligands at the metal defined elsewhere in the application will also be susceptible to this type of reactivity.

Electrophilic sources of "-SCF₃" include, but shall not be limited to: trifluoromethanesulfenylchloride, ^ -trifluoro^OS^trifluoromethyl) ester ethane(thioperoxoic) acid, 1, 1, 1 -trifluoro-N-methyl-N-phenyl-methanesulfenylamide, £/s(trifluoromethyl)disulfide, 1 , 3 -dihydro-3 , 3 -dimethyl- 1 - [(trifluoromethyl)thio] - 1,2- benziodoxole or 2-[(trifluoromethyl)thio]-lH-isoindole-l,3(2H)-dione.

Electrophilic sources of "-S0₂CF₃" include, but shall not be limited to:, l, l, l-trifluoro-, l, l'- anhydride, 1, 1, 1 -trifluoro-N-phenyl-N-[(trifluoromethyl)sulfonyl]-methanesulfonic acid, trifluoro-methanesulfonylchloride.

Electrophilic Sources of "SCF₃"

F3C

The method of the invention is suitable for the synthesis of a variety of fluorinated compounds. However, the method is especially suitable for the synthesis of fluorinated vinylidene ligands. As vinylidene complexes are important intermediates in a range of metal catalysed reactions, access to fluorinated analogues will offer the potential for the formation of new fluorinated compounds.

The method of the invention is suitable for the introduction of fluorine into metal alkynyl (also called metal acetylide), metal alkenyl (metal vinyl) and related ligands systems, such as isonitriles.

A general example of the process of fluorinating a metal alkynyl is:

Where [M] is a metal-based fragment, such as (but not limited to), [M^XI^XL²)] (M = Mn, Re, Fe, Ru, Os, Rh, Ir); L is a facially capping ligand such as C₅H₅, C₅Me5, 0₆Η₆, C₇H₇, Tp, etc., L¹ = CO, phosphine, halide, etc. L² = same ligand set as L¹ may be the same or different in each case, L¹ and L² could also be part of the same bidentate ligand e.g. dppe (Ph₂PC₂H₄PPh₂)) - i.e. the full range of "half-sandwich metal alkynyl complexes"; and R, is H, a carbon containing organic group, i.e. a linear branched or cyclic group, or a heteroatom (such as N, O, S etc.) with associated functional groups. Octahedral complexes [MX(P)₄], [MX(CO)(P)₂] or [MX₂P₂]^" (M = Fe, Ru, Os, X = halide, carboxylate, P = phosphine ligand) and square planar [MX(P)₂] (M = Rh, Ir, X = halide, P = phosphine ligand) are included. More specific examples are:

[1 b] R = C₆H₄-4-CF₃ [2b][BF₄] R = C₆H₄-4-CF₃ [1 c] R = C₆H₄-4-OMe [2c][BF₄] R = C₆H₄-4-OMe [1 d] R = ^fBu [2d][NSI] R = 'Bu*

[1 ^adppe] [2a_dppe][NSI]

[3adpp_e] R - H [4a_dppe][NSI] R = H [3b_dppe] R = F [4b_dppe][NSI] R = F

' NFSI, Toluene, 0 °C, 45 min A general example of the process of fluorinating a metal alkenyl is:

in which the alkenyl may be tethered (via a functional group that is part of either R) to the metal wherein [M], R and X are the same as defined above, with the proviso that with the tether present we will need one fewer ligand than with a metal alkynyl.

A further general example of the process of alkene C-H fluorination and trifluoromethylation is:

[M] stoichiometric/catalytic

+ "F⁺" or "CF₃ ⁺ + [H. base]⁺

Where R contains a

directing group that can

bind to the metal (or not) wherein [M], R and R' are the same as defined above.

These two processes may be combined in the presence of a suitable nucleophile and an excess of electrophilic fluorinating agent to permit the incorporation of multiple fluorine atoms in the substrate. An example is:

wherein [M], R and R' are the same as defined above, EF is a source of fluoride and E is a cation, for example K⁺, Cs⁺, [ Et₄]⁺.

A specific example being:

Fluoro (and trifluoromethyl) vinylidenes can be envisaged to act as intermediates in a range of transformations that their non-fluorinated analogues are implicated in, for example, the following (F can be substituted for -CF₃ in all cases). Where a chiral centre is formed during the reaction it should be possible by careful choice of ligand to produce an enantioselective process.

a nti- Markovnikov

carboxylic acid addition

H formation

Nuc'

Specific examples in which the reactivity has been demonstrated include:

Ph

[2a][BF₄] [7] [8^Ph]

[4a_dppe][NSI] [18*_dppe][NSI] [8^H]

This reactivity with fluoride and pyridine is also observed with the analogous fluorovinylidene complex with dppe - [Ru^⁵-C₅H₅)(dppe)(=C=CPhF)][NSI], [2e_dpPe][NSI] - and with an [NSI]^" counter-ion in place of the [BF₄]^" illustrated above. The formation of [8^Ph] occurs via a-fluorophenylacetaldehyde, [8^Ph'] as described in the experimental section. The formation of [8^H] presumably occurs via a-fluoro acetaldehyde [8^Η'] as similarly observed with [8^Ph].

Substrates that will be susceptible to the related reactions of a vinyl complex include:

in which R, R' and R' ' would be understood by the person skilled in the art to comprise alkyl i.e. linear, branched or cyclic alkyl or aryl systems which themselves may contain heteroatoms and/or other functional groups.

A more specific example is:

A proposed general mechanism for this type of reaction is shown below (where X is a functional group capable of binding to the metal, R is an alkyl or aryl group, including alkyl or aryl groups containing additional functional groups and/or heteroatoms):

Furthermore, the direct fluorination of heterocyclic systems is envisaged, including transformations such as:

The method of the invention is also applicable to other examples which rely on the formal oxidation of the metal centre to support a change in the bonding of an organic ligand. For example:

Illustrative reactions include:

[1b] R = C₆H₄-4-CF₃ [2b][BF₄] R = C₆H₄-4-CF₃

[1c] R = C₆H₄-4-OMe [2c][BF₄] R = C₆H₄-4-OMe

[1d] R = 'Bu [2d][NSI] R = ¾u*

[1 a_dppe] [2a_dppe][NSI]

[1a] R= Ph [11a][BF₄] R

[1 b] R = C₆H₄-4-CF₃ 11b BF₄] R

[1a] R = Ph

(does not react with py)

* NFSI, Toluene, 0 °C, 45 min

[14][BF₄] R = P

DCM, rt,

1 week,

-HF

[16][BF₄]

According to a further aspect of the invention there is provided a compound comprising a fluorinated alkenyl, aryl or isonitrile compound prepared by reacting an alkenyl, alkynyl, aryl or isonitrile compound with a metal-mediated outer-sphere electrophilic fluorinating agent (OSEF) according to any one of the preceding claims.

Thus, in one aspect the invention provides a compound as hereinbefore described which is a fluorinated alkenyl compound. In another aspect the invention provides a compound as hereinbefore described, which is a fluorinated aryl compound. In yet another aspect the invention provides a compound as hereinbefore described which is a fluorinated isonitrile compound. A further illustrative example is the use of the ruthenium complex [Ru( ⁵-C₅H₅X- C≡CPh)(PPh₃)₂], [la], as it has shown that reaction of this species with electrophiles H⁺,²⁴ Cl₂, Br₂, 1₂,²⁵ leads to stable vinylidene complexes [Ru^⁵-C₅H₅)(=C=C{E}Ph)(PPh₃)₂]⁺ (E = H, CI, Br, I). As vinylidene complexes are important intermediates in a range of metal catalysed reactions, access to fluorinated analogues offers the potential for the formation of new fluorinated compounds.

Treatment of a CH₂C1₂ solution of [Ru^⁵-C₅H₅)(-C≡CPh)(PPh₃)₂], [la], with l-fluoro-2,4,6- trimethylpyridinium tetrafluoroborate [FTMP][BF₄] results in an instantaneous colour change from yellow to dark green from which the fluorinated vinylidene complex [Ru(n⁵- C₅H₅)(=C=CFPh)(PPh₃)₂][BF₄], [2a][BF₄], was isolated in excellent yield. When the reaction between [la] and [FTMP][BF ] was performed in an NMR tube using CD₂C1₂ solution, [2a][BF ], was found to be the sole phosphorus-containing product from the reaction. Complex [2a][BF ] could also be prepared in a one-pot procedure by treatment of the related vinylidene [Ru^⁵-C₅H₅)(=C=CHPh)(PPh₃)₂]⁺, [17a]⁺, with base to generate [la] in situ followed by reaction with [FTMP][BF ]. In a similar vein, reaction between [Ru(n⁵- C₅H₅)(-C≡C-C₆H₄-4-R)(PPh₃)₂], (R = CF₃ [lb], R = OMe [lc]), with [FTMP]BF gave [Ru^⁵-C₅H₅)(=C=CFC₆H₄-4-R)(PPh₃)₂][BF₄] (R = CF₃ [2b][BF₄], R = OMe [2c][BF₄]). Analogous reactivity to form [Ru^⁵-C₅H₅)(dppe)(=C=CPhF)][NSI], [2e_dppe][NSI], was also observed on the addition of NFSI to [la_dp_pe].

The identity of [2a][BF ] was confirmed by a combination of NMR spectroscopy, mass spectrometry and X-ray diffraction. In addition to the signals for the [BF ] counter-anion, the ¹⁹F NMR spectrum of [2a][BF₄] contained a singlet resonance at δ -208.7 and in the ^uC{¹n} NMR spectrum resonances for the vinylidene ligand were observed at as doublet of triplets δ 389.0 (²JCF = 39.3 Hz, ²Jcp = 16.2 Hz) for the metal-bound carbon atom and a doublet at δ 196.7 JC_F = 222.1 Hz). The fluorine-carbon couplings confirm the incorporation of the halogen into the organic ligand. It should be noted that these resonances are shifted ca. 30 ppm and 70 ppm downfield respectively when compared to the hydrogen- substituted analogue [17a]⁺ and that the metal bound carbon is observed at one of the lowest reported.

[1 b] R = C₆H₄-4-CF₃ [2b][BF₄] R = C₆H₄-4-CF₃

[1c] R = C₆H₄-4-OMe [2c][BF₄] R = C₆H₄-4-OMe

[1d] R = 'Bu [2d][NSI] R = ¾u*

* NFSI, Toluene, 0 °C, 45 min

Anion metathesis with an excess of NaPF₆ led to the formation of [2a][PF₆]. Crystals of this salt were grown by slow diffusion of Et₂0 into a CH₂C1₂ solution of the complex. Two separate batches of crystalline [2a][PF₆] were obtained one green, the other orange. Analysis of the two different sets of crystals by X-ray diffraction indicated that the [2a]⁺ cation was present in both cases, however, the orientation of the vinylidene ligand differed. As shown in Figure 1(a), for the green crystals, the fluorine substituent is orientated away from the cyclopentadienyl ring, whereas in Figure 1(b), the orange crystals, it is in the opposite orientation. There is a marked change in the geometry around the vinylidene ligand between the two isomers of the [2a]⁺ cation. In the case of the orange crystals, the angles around the β-carbon exhibit a marked deviation from the idealised sp²-hybridized geometry (C(6)-C(7)- F(l) 114.70(16) °, C(6)-C(7)-C(8) 132.55(17) °, C(8)-C(7)-F(l) 112.69(15) °,∑ = 359.94°), which when compared to the green isomer (C(6)-C(7)-F(l) 121.05(13) °, C(6)-C(7)-C(8) 121.02(13) °, C(8)-C(7)-F(l) 117.72(12) °,∑ = 359.79) indicate that the fluorine atom in the orange isomer is much closer to the metal-bound carbon atom of the ligand. Indeed, in the orange isomer, the vinylidene ligand shows a significant distortion from linearity (Ru(l)- C(6)-C(7) 164.20(15) °) whereas in the green isomer it is more typical for ruthenium vinylidene complexes (172.46(12) °). It should also be noted that the orientation of the phenyl substituent also changes between the two isomeric forms, notably in the green crystals the ring lies perpendicular to the plane of the vinylidene.

In order to gain further insight into the difference between the two isomeric forms of the complexes, the UV-visible spectra of the complexes were recorded in both the solid state (Figure 2a) and in CH2CI2 solution (Figure 2b). The spectra showed a difference in the position of max in the visible region (green 692 nm, orange 742 nm). The UV-visible spectra recorded after dissolution of both batches in CH2CI2 solution were essentially identical (Figure 2b). When coupled with the fact that only one species is observed in the NMR spectra of the complex, it is concluded that the two crystalline forms convert to the same species in solution.

In a similar manner to electrophilic fluorination, the electrophilic incorporation of -CF₃ groups into the framework of organic compounds is also desirable as it is frequently been used to inhibit hydrolysis of specific sites within drug molecules. With this in mind, the reaction between [la] and Umemoto's reagent, (a source of "CF₃ ⁺") was shown to result in the selective formation of [Ru^⁵-C₅H₅)(=C=CCF₃Ph)(PPh₃)₂][BF₄], [12][BF₄]. The ¹³C{1H} NMR spectrum of [12][BF₄] again indicated the presence of a vinylidene ligand with a triplet of quartets resonance at δ 340.0 (²Jpc = 15.2 Hz, _CF = 3.3 Hz,) and the structure was confirmed by a single crystal X-ray diffraction study. Therefore the addition of electrophilic fluorinating agents to ruthenium half- sandwich compounds appears to be a general pathway for the formation of both C-F and C-CF₃ bonds. It is evident from the NMR and absorption spectra that the introduction of a fluorine- sub stituent into the vinylidene ligand has a pronounced effect on the electronic structure of the complex when compared to the [17a]⁺ and [12]⁺. Notably in the ¹³C NMR spectrum there is a low field shift in resonance for the metal bound carbon and the lowest energy transition in the absorption spectrum is red-shifted (Table 1). In order to gain further insight into this effect halo-vinylidene complexes [Ru(rj⁵-C5H5)(=CC{E}C₆H₄-4-R)(PPh₃)₂]X were prepared (E = CI, R = H [17b'][BF₄]; E = Br, R = H [17c][BF₄]; E = Br, R = Br [17d][Br₃]; E = I, R = H [17e][I₃]) and details of their absorption and NMR spectra are presented in Table 1. In addition, the absorption spectra for all of the complexes were simulated using Time- Dependent Density Functional Theory.

Table 1

Table 1 Summary of C NMR data and lowest energy bands in the absorption spectra of vinylidene complexes. Experimental data were recorded at a concentration of ca. 1 mmol dm^"3 in CH₂CI₂ solution. * Denotes lowest energy absorption band not the band displaying maximum absorption. In the case of both mono- ([Ru(n⁵-L)(=CCHR)(PR₃)₂]⁺) (L = C₅H₅, R¹ = Me;²⁶ C₉H_7, R¹ = Ph)²⁷ and di- substituted [Ru^⁵-C₅H₅)(=C=C{R}Ph)(dppe)]⁺ vinylidenes,²⁸ reaction with NCMe has been shown to be a versatile route to reverse the alkyne-vinylidene transformation and generate [Ru(n⁵-L)(NCMe)(PPh₃)₂]⁺, (L = C₅H₅, [18]⁺) and the corresponding alkynes HC≡CR and PhC≡CR respectively. These studies have also permitted detailed kinetic insight into the nature of the alkyne-vinylidene interconversion.^26-28 However, heating a sample of

[2a]⁺ in NCMe-d₃ did not result in analogous reaction to form [18]⁺ and FC≡CPh. In this case, the major product from the reaction was [14a]BF₄ in which activation of one of the PPh₃ ligands and subsequent combination with the fluorovinylidene ligands has occurred. The ³¹P NMR spectrum of the reaction provides evidence that this is the case as two resonances were observed at δ 46.6 (dd, JPF = 48.6 Hz; ²J_PP = 4.2 Hz) and δ 42.3 (dd, JPF = 16.2 Hz; ²J_Pp = 4.7 Hz). The nature of the couplings to fluorine were confirmed by the observation of a resonance at δ -133.4 (ddd, JPF = 48.9 Hz; ²J_PF = 16.2 Hz; HF = 16.2 Hz) and a matching resonance was observed in the 1H NMR spectrum at δ 4.69 (ddd, JHF = 17.1 Hz; Jp_H = 5.0 Hz; J_PH = 1.7 Hz). The structure of [14a]BF₄ was also assigned on the basis of the large P-F coupling to the resonance at δ 46.6. Although additional products were observed on protracted heating, a complex related to [14a]BF₄ has been reported previous from the nucleophilic attack of PPh₃ at a coordinated vinylidene.²⁹ On heating a sample of [Ru^⁵-C₅H₅)(=C=CFPh)(dppe)]NSI [2a_dpPe][NSI] in d₃-MeCN, no phosphine activation was observed. This is presumably due to the bidentate coordination mode of dppe which disfavours the initial phosphine loss and hence prevents analogous reactivity.

The formation of [14a] [BF ] demonstrates that the fluorovinylidene ligands is bound strongly to the ruthenium.

[2a][BF₄] [14a][BF₄]

Although it is possible to prepare dinuclear fluorovinylidenes by the activation of suitable fluorocarbons,³⁰ the reaction between alkynyl complexes [1] with electrophilic fluorinating agent offers a highly selective and simply route for the direct formation of C-F and C-CF₃ bonds without any apparent involvement of the metal centre. The fluorinated vinylidene complexes [2]⁺ prepared in the study are more robust that the chloro-, bromo- and iodo- substituted analogues, which in our hands frequently decomposed to give [Ru(n⁵- C₅H₅)(CO)(PPh₃)₂]⁺. When combined with their unique electronic structure and the fact that no conversion to the alkyne FC≡CR was observed, these complexes clearly offer the opportunity for the incorporation of additional functionality into the organic ligand to prepare novel fluorinated compounds.

Another illustrative example is the formation, and subsequent fluorination, of the ruthenium vinyl pyridylidene ([20][PF₆]) and 1-ruthanaindolizine complexes [9] which are prepared by reaction of [Ru^⁵-C₅H₅)(PPh₃)(Pyr)₂][PF₆], [19][PF₆] with terminal alkynes.³¹

1 ,4-diazabicyclo[2.2.2]octane (DABCO)

DCM, 20 °C, 16 h

- [HDABCO]⁺

Reaction of [Ru( ⁵-C₅H₅)(PPh₃)(Pyr)₂][PF₆] with terminal alkynes to form complexes [20][PF₆] and [9].

C-F bond formation is promoted in the coordination sphere of Ru by treatment of [9] with a stoichiometric quantity of l-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate ([FTMP][BF₄]), FSI or Selectfluor® as a latent source of "F⁺". This resulted in the quantitative (by NMR) conversion of [9] to a new, bright-green complex characterised by single ³¹P{1H} (δ 47.2 ppm, ⁴J_PF = 7.7 Hz) and r|⁵-C₅H₅ 1H (5.37 ppm) resonances. The product also displayed a ¹⁹F resonance with a large HF coupling at δ -139.8 ppm ( HF = 52.0 Hz, ⁴JPF = 7.7 Hz). HRESIMS showed the presence of a cationic molecular ion at 696.1023 m/z, which is consistent with mono-fluorination of [9]. The spectroscopic data are not consistent with oxidative fluorination of the metal to form a Ru-F which would be expected to exhibit a significantly upfield ¹⁹F chemical shift of around δ -250 ppm. The magnitude of the observed HF coupling constant, which suggested two-bond coupling, and supported by X- ray crystallographic studies, indicates that electrophilic fluorination of [9] occurs at the 3- position on the 1-ruthanaindolizine ring leading to the formation of complex [10][BF₄]. Fluorination of [9] to produce [10]⁺ was also possible using alternative electrophilic fluorinating agents, including Selectfluor® and NFS!

[9] [10]⁺

Reaction of [9] with l-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate.

Single-crystal X-ray diffraction studies show the molecular structure of [10][BF₄] to contain a metallocyclic ring system similar to that seen in [9], but with the formation of a new C-F bond at C(l 1). The M-C bond to the pyridylidene ring in [10][BF ] is of a similar length to that in 2 (1.990(2) compared to 1.996(2) A), whereas the Ru-C bond to C(12) is significantly shorter (1.916(2) compared to 2.046(2) A) consistent with an increase in double bond character upon fluorination. The C(l 1)-C(12) bond is elongated in [10][BF ] compared to [9] (1.508(3) vs. 1.339(2) A), which is consistent with the formal loss of double bond character. Overall the most appropriate Lewis structure for [10]⁺ appears to be that shown, which invokes pyridylidene (rather than pyridyl) character to the Ru-C(6) bond and Schrock-type carbene character to C(12). This is supported by BO analysis. Although the BO reference structure for the cation [10]⁺ is based on a Ru-C(6) single bond, there is significant donation of metal-based electron density to the C(6)-N(l) π* orbital (occupation = 0.483 e^"; second order perturbation stabilisation energy = 83 kJ mol^"1) which gives considerable π character to this M-C bond. The Ru-C(12) bond in [10]⁺ is described as a double bond in the NBO reference structure (π-bond occupancy = 1.815 e^") and its Wiberg bond index is significantly larger than the equivalent Ru-C bond in [9] (1.067 vs. 0.665), consistent with significant Ru-C(12) multiple bond character in [10]⁺. Based on this Lewis structure Ru can be considered to have a formal oxidation state of +4 (with one Fischer-type and one Schrock- type carbene ligand present). As such, the electrophilic fluorination reaction is distinctly different from other previously reported metal-mediated electrophilic fluorination reactions.¹ It is oxidative (with regard to the metal), which is similar to related Pd chemistry,¹ but different to non-redox electrophilic fluorination reactions promoted by Lewis acidic metals (e.g. Ti).¹ However, unlike in the Pd cases the reaction produces an outer-sphere fluorination product, which we believe occurs without the involvement of a Ru-F intermediate.

Fluorination of the 3 -position on the 1-ruthanaindolizine ring in racemic [9] leads to the creation of a new stereogenic carbon centre C(l l) in [10][BF₄]. The reaction is diastereoselective, leading only to the diastereomer in which the C-F bond points towards the C₅H₅ ring. This is supported by NOESY experiments that show no cross-peak between H(l l) and the hydrogen atoms of the C₅H₅ ring. The single-crystal X-ray structure of

[10][BF₄] is enantiopure, containing only the RR enantiomer. This diastereoselectivity is driven by sterics: "F⁺" addition to the "inside" face of the 1-ruthanaindolizine ring is blocked by the three Ph groups on the phosphine. This is likely to be a kinetic, rather than thermodynamic, effect as the products of "F⁺" addition to the two faces are found to be essentially isoenergetic (-194 and -192 kJ mol^"1 for the "outside" and "inside" faces respectively, relative to [9] and [FTMP]⁺) in DFT studies {vide infra). The geometry around C(l l) is slightly distorted from ideal tetrahedral geometry and the C(l l)-F(l) bond length is rather long for a typical sp³ hybridised C-F bond at 1.403(2) A. Further reactivity of [10] [BF₄]

Interestingly, [10][BF₄] is susceptible to further electrophilic fluorination. When 2 equiv. of [FTMP][BF₄] are added to [9] in dichloromethane, [10][BF₄] is observed to form immediately in the NMR spectra and over a period of 24 h this species converts cleanly to a new complex [21][BF₄]. The characteristic ¹⁹F resonance for F(l) of [10][BF₄], observed at δ -139.8 ppm (dd, _HF = 52.0 Hz, _PF = 7.7 Hz), is replaced by two ¹⁹F resonances at δ -96.6 (d, ²J_FF = 233.1 Hz) and δ -78.0 (dd, ²J_FF = 233.1 Hz, ⁴J_PF = 6.6 Hz) ppm, which are strongly mutually coupled. HRESIMS showed the presence of a cationic molecular ion at 714.0920 m/z, which indicated that net deprotio-difluorination of [9] had taken place. The spectroscopic data and a subsequent single-crystal X-ray diffraction study showed that geminal difluorination of the 3 -position on the 1-ruthanaindolizine ring in 2 had taken place. This appears to occur as a two-stage process via formal "F⁺" addition to give [10][BF₄] and subsequent C-H activation (presumably via deprotonation of [10][BF₄] by free 2,4,6- trimethylpyridine (TMP) in the reaction mixture) and fluorination to give [21][BF₄]. Indeed, reaction of isolated [10][BF₄] with [FTMP][BF₄] does afford [21][BF₄].

r9i nor Γ21 Γ

Reaction of [9] with two equivalents of [FTMP][BF₄]. Conditions: + 2 equiv. [FTMP][BF₄], - TMP, -[HTMP][BF₄], CH₂C1₂ 20°C, 24 hours.

The molecular structure of [21][BF₄] displays similar metric parameters to [10][BF₄], with a Ru-C(6) distance (2.010(3) A} that is similar to the parent metallocycle [9], but with a significantly shorter Ru-C(12) distance ( 1.902(3) A} compared to [9]. As with [10][BF₄] this suggests some pyridylidene character at C(6) and significant Schrock-type carbene character at C(12) and both fluorinated products can be described by similar Lewis structures. The C-F bond lengths C(l l)-FQ) ( 1.374(3) A} and C(l l)-F(2) ( 1.353(3) A} in [21][BF₄]are significantly shorter than in [10][BF₄] and are more similar to typical sp³ C-F bond lengths, with slightly less distortion around C(l 1) from ideal tetrahedral angles.

Dissolution of [21][BF₄]in d₅-pyndine at room temperature led to the NMR signals associated with [21][BF ] slowly disappearing over the course of a week, along with the appearance of new signals attributed to [22 (³¹P δ = 61.4 ppm, ¹⁹F δ = -111.7 ppm), which is a fluorinated analogue of the 1-ruthanaindolizine complex [9]. The metallocycle [22] can also be formed independently by deprotonation of [10][BF ] with l,4-diazabicyclo[2.2.2]octane (DABCO) in CH₂C1₂. However, in the presence of [H.DABCO][BF₄] in CH₂C1₂ [22] is in equilibrium with a new a-fluorovinyl pyridylidene complex [23][BF ] and free DABCO, which results in dynamic behaviour that is rapid on the NMR timescale at room temperature. Cooling this mixture to 195K was not sufficient to freeze out all dynamic behaviour, but broad signals at ¹⁹F δ = -112 and ³¹P δ = 62 ppm associated with [22] can clearly be seen. Similar dynamic behaviour has been observed for [9].³¹ The dynamic behaviour of [22] can be prevented by dissolution in a basic solvent such as d₅-pyndine which allowed full characterisation by NMR spectroscopy.

[21 r [22] [23]⁺

Further reactivity of [21][BF₄]. (i) d₅-pyridine, 20 °C, 7 days, (ii) + DABCO, -[H.DABCO][BF₄], CD₂C1₂, 20°C or dissolution in d₅-pyridine. (iii) Equilibrium in the presence of [H.DABCO][BF₄] in CD₂C1₂, 20°C.

Formation of [22] from [21][BF ] is a very unusual observation, as "F⁺" has formally been lost from the CF₂ group in [21][BF₄] to form the l-ruthana-3-fluoroindolizine ring. This surprising observation may be linked to the formation of an additional ruthenium- containing species [24][BF ] during this reaction. The signals from this complex are observed to grow in the NMR spectra (³¹P δ = 43.2 ppm, ¹⁹F δ = -78.7 (d, ²J_FF = 208.5 Hz) and -67.6 (d, ²J_FF = 208.5 Hz) ppm) as the metallocycle [22] is formed (in an approximately 1 :0.7 ratio of [22] to

[24][BF ], based on ¹⁹F NMR integration). The presence of two, strongly mutually coupled fluorine environments suggests that the geminal CF₂ group is retained in [24][BF ] and that the symmetry of the system is such that these two fluorine atoms are chemically inequivalent. However, in contrast to [21][BF ] no P-F coupling is observed for either fluorine of the CF₂ group in [24][BF ]. The mass spectrum of this reaction clearly shows the presence of [22] and an additional ruthenium-containing species with m/z of 730.0872, assigned as [24][BF ]. The mass of this species suggests that [21][BF₄] has gained a single oxygen atom during this transformation to form [24][BF₄]. Although the precise nature of [24][BF₄] has not been unambiguously determined, we tentatively propose the ketone-containing structure shown in the figure above, which is consistent with the spectroscopic data. If [24][BF ] were formed by hydration of [21][BF ] (by adventitious water present in the ds-pyridine) then H₂ would formally be lost during this process. While it is unlikely that H₂ gas is formed, hydration may be coupled to the formal loss of "F⁺" from [21][BF ] during the formation of [22] to give an overall balanced reaction as follows:

2 [21][BF₄] + pyridine + H₂0 [22] + [24][BF₄] + [H.pyridine][BF₄] + HF

In support of this hypothesis, a broad N-H signal at δ 9.1 ppm, suggestive of [H. pyridine] [BF ], is seen in the 1H MR. The up field chemical shift of this proton compared to free [H. pyridine] [BF ] in pyridine and significant broadening of this signal can be attributed to dynamic proton exchange with [22] to form [23][BF ], in analogy to the [H.DABCO][BF ] reactivity described above. Although no evidence of HF (or related products) was seen in the spectra, it is possible that when formed this reacts with the glass reaction vessel and so is not visible in solution.

Mechanistic considerations

During the reactions above no Ru-F intermediates were observed spectroscopically. In order to investigate the possibility that a short-lived Ru-F intermediate is involved in the formation of [10][BF ] we undertook a low-temperature NMR study on the reaction and have probed the reaction mechanism using DFT studies. In the NMR study, [9] and [FTMP][BF ] were combined in CD₂C1₂ at 195 K and introduced to a pre-cooled NMR spectrometer at 195 K. 1H, ³¹P and ¹⁹F spectra were recorded as the spectrometer temperature was warmed to 295 K. The reaction appears not to proceed at temperatures below 245 K but at 265 K the reaction is essentially complete, suggesting relatively fast kinetics even at low temperatures. No potential reaction intermediates (Ru-F containing species or others) were observed at any temperature during these studies, which suggests that "F⁺" is either directly transferred to the site of fluorination or that only low energy transition states connect any potential intermediates from the reaction product [10][BF₄].

The mechanistic features of electrophilic fluorination reactions involving "F⁺" sources such as [FTMP][BF₄] or Selectfluor^® are the matter of some debate, and either single-electron transfer (SET) followed by rapid radical recombination or nucleophilic attack at the "F⁺" source seem likely to occur in different systems. A plot of the spin density of the radical cation [9]^-+, which would be initially formed by 1 -electron oxidation of [9] by the fluorinating agent as part of a SET-based mechanism, shows significant spin density on the 3-position of the ruthanindolizine ring and no spin density on the 2-position. As such, a SET-based mechanism involving direct outer-sphere electrophilic fluorination (OSEF) of the 3-position of the ruthanindolizine ring would be consistent with the observed regiochemistry. However, this does not rule out the possibility of a mechanism involving nucleophilic attack of the carbon at the 3-position of the ruthanindolizine ring on the "F⁺" source.

DFT studies support the suggestion that the formation of [10] [BF₄] does not proceed via a Ru-F complex and that direct fluorination of 9 is likely to be a low-energy process. The scheme below shows the potential energy surface (PES) for the possible fluorination products and their key interconversions.

Potential energy surface (PES) for the electrophilic fluorination reactions observed here. All data are at the PBE0-D3/def2-TZVPP//BP86/SV(P) level with solvation corrections applied in CH₂C1₂ (COSMO, ε = 8.93 for CH₂C1₂ at 25°C). E_SCF+ZPE energies (relative to [9] and [FTMPf) are shown below each state and Gibbs energies at 298.15 K are given in brackets below these. [Ru] = [Ru(rj⁵-C₅H₅)(PPh₃)].

It can be seen from the PES above that the formation of Ru-F-containing ions [27af and

[27b] is thermodynamically favoured over 9 and [FTMP]⁺ (by 158 kJ mol^"1 and 208 kJ mol^"1 respectively). However, the PES between these fluoride complexes and the observed product

[10]⁺ shows features that suggest that a Ru-F complex is not an intermediate in the formation of [10]⁺. [10]⁺ is not the thermodynamic product of "F⁺" migration from either Ru-F isomer to a carbon atom on the metallocycle. The thermodynamic product is [29Z]⁺, which is not observed experimentally, where the 2-position of the ruthanindolizine is fluorinated. [29Z]⁺ is also the kinetic product of "F⁺" migration, being formed via a transition state that lies 130 kJ mol^"1 higher in energy than the Ru-F complex [27b]⁺. The calculations suggest that there is a very significant barrier (+204 kJ mol^"1) to formation of the observed product [10]⁺ from

[27bf We assume here that interconversion between the two Ru-F isomers is possible and that the lowest energy isomer [27b]⁺ will be populated. Isomerisation to [27a]⁺ is then required to allow "F⁺" migration to form [10]⁺ with the observed stereochemistry. A barrier of this magnitude is not consistent with the rapid formation of [10]⁺ at 265 K, as seen in the low-temperature MR studies. The large barriers found in the DFT studies and suggestion that the unobserved complex [29Z]⁺ should be the favoured product from a Ru-F species suggests that another mechanism for the formation of [10]⁺ occurs in this system. Direct outer-sphere electrophilic fluorination (OSEF) of the 3-position of the ruthanindolizine ring in 2 seems likely. The PES for the formation of [21]⁺ from a Ru-F-containing intermediate is similar to that shown in the PES above and fluorination via an OSEF mechanism also seems likely here.

Direct fluorination of the 3-position of the ruthanindolizine ring in 9 by [FTMP]⁺ was investigated using relaxed PES scans (at the (RI-)PBE0/def2-TZVPP//(RI-)PBE0/SV(P) level) for the closed-shell singlet, triplet and singlet diradical states. The reaction pathways for all states proceed via relatively low energy barriers (AESCF* in CH₂CI₂ of 58, 27 and 23 kJ mol^"1 respectively) to form [10]⁺, which is consistent with the fast reaction and lack of intermediates observed experimentally. Interestingly, the open-shell pathways are found be lower in energy than the closed-shell pathway, which suggests that a SET mechanism may operate in this system (although care should be taken in interpreting the energies of the singlet diradical states, due to spin contamination). In any event, the low barriers to fluorination directly at the ligand contrasts markedly with the large barriers for C-F bond formation via a metal-fluoride intermediate, supporting the proposal that the reaction proceeds by an outer-sphere mechanism.

The present invention will now be described by way of example only with reference to the accompanying figures in which:

Figure 1 illustrates the solid state structures of the [2a]⁺ cation found in (a) green crystals and (b) orange crystals. Hydrogen atoms removed for clarity and thermal ellipsoids (where shown) are at the 50 % probability level;

Figure 2 illustrates the UV- visible spectra of the two isomers of complex [2][PF₆] recorded (a) in the solid state with the diffuse reflectance technique and (b) in CH₂CI₂ solution;

Figure 3 illustrates the variable temperature ¹⁹F NMR spectra of [10][BF₄] and DABCO (CF₃ region);

Figure 4 illustrates the variable temperature ¹⁹F NMR spectra of [10][BF₄] and DABCO; Figure 5 illustrates the variable temperature ¹⁹F NMR spectra of [10][BF₄] and DABCO (BF₄ region);

Figure 6 illustrates the variable temperature ³¹P NMR spectra of [10][BF₄] and DABCO;

Figure 7 illustrates the solid state structure of the cation [12]⁺, hydrogen atoms omitted for clarity, thermal ellipsoids (where shown) are at the 50 % probability level;

Figure 8 illustrates the solid state structure of the cation [10]⁺, most hydrogen atoms omitted for clarity, thermal ellipsoids (where shown) at the 50 % probability level;

Figure 9 illustrates the solid state structure of the cation [21]⁺, hydrogen atoms omitted for clarity, thermal ellipsoids (where shown) are at the 50 % probability level;

Figures 10(a) to (b) illustrate absorption spectra for certain specified complexes; and

Figures 11(a) to (d) illustrate solid state structures for certain specified complexes. Methods

General Methods

All air-sensitive experimental procedures were performed under an inert atmosphere of nitrogen using standard Schlenk line and glovebox techniques. Dichloromethane and pentane were purified with the aid of an Innovative Technologies anhydrous solvent engineering system. The CD₂CI₂ used for NMR experiments was dried over CaH₂ and degassed with three freeze-pump-thaw cycles. The solvent was then transferred into NMR tubes fitted with PTFE Young's taps or stored under a nitrogen atmosphere in the Glove Box. NMR spectra were acquired on a Jeol ECX-400 (Operating frequencies 1H 399.78 MHz, ³¹P 161.83 MHz, ¹⁹F 376.17 MHz, ¹³C 100.53 MHz), a Bruker AVANCE 500 (Operating frequencies 1H 500.13 MHz, ³¹P 202.47 MHz, ¹⁹F 470.69 MHz, ¹³C 125.77 MHz) or a Bruker AVANCE 700 (Operating frequencies 1H 700.13 MHz, ³¹P 283.46 MHz, ¹³C 176.07 MHz). ³¹P and ¹³C spectra were recorded with proton decoupling. Assignments were confirmed with the aid of 2D-COSY, NOESY, HMQC and HMBC experiments. Mass spectra were recorded on a Bruker micrOTOF using electrospray ionisation.

Calculations were performed at the (RI-)PBE0/def2-TZVPP//(RI-)BP86/SV(P) level (a methodology that we have validated in a related system)³² with the full ligand substituents used in the experimental study using TURBOMOLE version 6.4. Data presented includes dichloromethane solvation (using the COSMO method with ε = 8.93 for dichloromethane at 25°C). Single-point DFT-D3 corrections (on the (RI)-BP86/SV(P) geometries) have been applied at the PBE0-D3 level using Grimme's DFT-D3 (V3.0 Rev 2, with BJ-damping) program and data includes this correction. Gas-phase data are provided in the supplementary information. Both ZPE-corrected SCF energies {E_SCF+ZPE) and Gibbs energies at 298.15 K are shown and energies quoted are relative to [9] and [FTMP]⁺. E_SCF+ZPE data are discussed in the main section of the manuscript due to the difficulty in assessing entropy changes in solution from gas-phase calculations. Minima were confirmed as such by the absence of imaginary frequencies, and transition states were identified by the presence of one imaginary frequency with subsequent verification by DRC analyses. Vertical excitation energies were calculated using the ESCF module of TURBOMOLE (full TDDFT) on the (RI-)PBE0/def2- TZVPP optimised structures at the same level of theory. Tight SCF convergence criteria were used in these calculations. 50 singlet excitations were calculated for each state.

Direct fluorination of the 2-position of the ruthanindolizine ring in 9 by [FTMP]⁺ was investigated using relaxed PES scans (at the (RI-)PBE0/def2-TZVPP//(RI-)PBE0/SV(P) level). It was found that BP86/SV(P) geometry optimisations, as used in the other computational studies here, did not describe the geometries close to the transition state for the singlet closed-shell potential energy surface well and use of the hybrid PBEO functional for geometry optimisations was required. PES scans involved scanning along the reaction coordinate where a molecule of [FTMP]⁺ approaches the 2-position of the ruthanindolizine ring in 9. A series of input structures were generated where the C-F bond that is being formed was constrained to distances of between 4.0 and 1.4 A in 0.2 A steps, this was the only constraint applied. The geometries of these constrained structures were then optimised for the closed-shell singlet, triplet and singlet diradical states. Broken-symmetry singlet diradical states were obtained from the optimised triplet geometries using the "flip" function of the TURBOMOLE "define" script. This allows the user to select a localised alpha spin orbital involving a particular atom (Ru in this case) to become a beta spin orbital (or vice versa) to generate a broken symmetry (S = 0) state. Once suitable starting MOs had been obtained using this method, the geometries of the singlet diradical states were optimised from this point. Mulliken population analyses were performed on the converged wave functions to check that these did indeed correspond to the desired singlet diradical states. A summary of these data are given in the tables below, along with optimised xyz coordinates for each point along the reaction coordinate.

Synthetic Procedures

Example 1

Synthesis of [Ru(ti⁵-C₅H₅)(PPh₃)2(-C≡CPh)], [la]

Prepared as described in the literature.

Example 2

Synthesis of [Ru^⁵-C₅H₅)(PPh3)2(-C≡C-C₆H4-4-CF3], [lb]

An oven-dried Schlenk tube was charged with Ru^⁵-C₅H₅)(PPh₃)₂Cl [7] (250 mg, 0.33 mmol), 4-ethynyl-a,a,a-trifluorotoluene (86 μΐ, 0.5 mmol) and methanol (15 mL), and heated under reflux for 30 minutes. The reaction mixture was cannula filtered to remove undissolved starting material. To the red solution was added NaOMe (27 mg, 0.5 mmol) as a methanol solution (2 mL), to yield a bright yellow precipitate. The solvent was removed by cannula filtration, and the yellow powder dried under vacuum. Yield = 211 mg (72 %). 1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 4.35 (s, 5H, Hi), 7.12 (t, ³J_HH = 7.4 Hz, 12H, Hn), 7.16 (d, VHH = 8.3 Hz, 2H, H₅), 7.24 (t, ³J_HH = 7.4 Hz, 6H, H₁₂), 7.39 (d, 2H, ³J_HH = 8.3 Hz, H₆), 7.42 - 7.49 (m, 12H, ¾₀)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 85.4 (s, Ci), 114.3 (s, C₃), 123.8 (q, ²J_CF = 32.1 Hz, C₇), 124.6 (q, ³Jc_F = 3.7 Hz, C₆), 125.0 (q, ^lJ_CF = 270.2 Hz, C₈), 125.9 (t, ²J_CP = 24.6 Hz, C₂), 127.3 (t, sum ofJ_CP = 9.0 Hz, C_n), 128.6 (s, C₁₂), 130.3 (s, C₅), 133.7 (t, sum ofJ_CP = 9.7 Hz, Cio), 134.1 (s, C₄), 138.7 (m, ^lJ_CP + ³J_CP = 42.1 Hz, C₉)

1⁹F NMR (CD₂CI₂, 471 MHz, 295 K): δ -63.3 (s, F)

3¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 51.6 (s, PPh₃)

ESI-MS (m/z): Expected for C₅oH₄oF₃P₂Ru = 861.1609; Observed: 861.1600 [M+H⁺] (Error = 0.9 mDa)

Elemental Analysis: C5oH₃₉F₃P₂Ru Calc. /% C 69.84, H 4.57, Found /% C 69.36, H 4.43.

Example 3

Synthesis of [Ru(ti⁵-C₅H₅)(PPh₃)₂(-C≡C-C₆H4-4-OMe)], [lc]

An oven-dried Schlenk tube was charged with Ru^⁵-C₅H₅)(PPh₃)₂Cl [7] (250 mg, 0.33 mmol), 4-ethynylanisole (66 mg, 0.5 mmol) and methanol (15 mL), and heated under reflux for 30 minutes. The reaction mixture was cannula filtered to remove undissolved starting material. To the red solution was added NaOMe (27 mg, 0.5 mmol) as a methanol solution (2 mL), to yield a bright yellow precipitate. The solvent was removed by cannula filtration, and the yellow powder dried under vacuum. Yield = 218 mg (78 %)

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 3.77 (s, 3H, ¾), 4.32 (s, 5H, Hi), 6.72 (d, ³J_HH = 8.8 Hz, 2H, H₆), 7.05 (d, ³J_HH = 8.8 Hz, 2H, H₅), 7.11 (app. t, ³J_HH = 7.6 Hz, 12H, ¾), 7.22 (t, ³J_HH = 7.4 Hz, 6H, H₁₂), 7.46-7.54 (m, 12H, ¾₀)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 55.6 (s, C₈), 85.5 (s, Ci), 112.1 (t, ²J_CP = 24.9 Hz, C₂), 113.6 (s, C₃), 113.7 (s, C₆), 123.9 (s, C₄), 127.6 (t, sum ofJ_CP = 9.2 Hz, Cio_/11), 128.8 (s, C₁₂), 131.6 (s, C₅), 134.2 (t, sum of J_CP = 10.4 Hz, C_10/n), 139.5 (m, _Ρ + ³J_CP = 42.0 Hz, C₉), 156.4 (s, C₇)

³¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 51.6 (s, PPh₃)

ESI-MS (m/z): Expected for C₅oH₄₃OP₂Ru = 823.1827; Observed: 823.1841 [M⁺] (Error = 1.4 mDa)

Elemental Analysis: C₅oH₄₂OP₂Ru Calc. /% C 73.07, H 5.15, Found /% C 72.70, H 5.11.

Example 4

Synthesis of [Ru^⁵-C₅H₅)(PPh₃)₂(-C≡C-H)], [Id]

Prepared as described in the literature. (M. I. Bruce and A. G. Swincer, Australian Journal of Chemistry, 1980, 33, 1471-1483.). Example 5

Synthesis of [Ru^⁵-C₅H₅)(PPh₃)₂(-C≡C-H)], [le]

To Ru(rj⁵-C₅H5)(PPh₃)₂Cl [7] (250 mg, 0.34 mmol) suspended in tert-butanol (lOmL) was added ethynyltrimethylsilane (195 μΐ_^, 1.36 mmol) and ammonium hexafluorophosphate (112 mg, 0.68 mmol). The mixture was heated at 105 °C for 4.5 hours or until ³¹P MR of the reaction mixture indicated completion. The light orange solid was filtered in air through sinter and washed with diethyl ether (ca. 20 mL). The yellow/orange powder was dissolved in minimum amount of dichloromethane and filtered into excess stirring diethyl ether. The powder was filtered again and dried. Yield = 257 mg.

To an oven dried Schlenk tube was added the [Ru(=C=CH₂)^⁵-C₅H5)(PPh₃)₂][PF₆] (257 mg, 0.30 mmol) and l,8-bis(dimethylamino)naphthalene, N,N,N',N'-tetramethyl-l,8- naphthalenediamine (64 mg, 0.30 mmol), which were dissolved in dichloromethane (lOmL) and stirred at room temperature for 10 min. The solvent was removed in vacuo and a minimum amount of dichloromethane was added. The yellow solution was filtered and the filtrate was dried in vacuo to yield a yellow solid. Yield = 147 mg (69 %).

1H NMR (400 MHz, CD₂C1₂, 295 K): δ 1.81 (t, ⁴J_FP= 2.2 Hz, 1H, H₂), 4.18 (s, 5H, ¾), 7.22 (m, 3 OH, Ph)

³¹P NMR (162 MHz, CD₂C1₂, 295 K): δ 50.2 (s, PPh₃). Example 6

Synthesis of [Ru( ⁵-C₅H₅)(dppe)Cl], [7_dppe]

Prepared as described in the literature.

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 2.36 - 2.51 (m, 2H, Hi_0a/b), 2.56 - 2.73 (m, 2H, Hio_a/b), 4.57 (s, 5H, Hi), 7.13 - 7.20 (m, 4H, ar), 7.26 - 7.35 (m, 6H, ar), 7.42 - 7.49 (m, 6H, ar), 7.88 - 7.95 (m, 4H, ar)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 27.1 (m, C₁₀), 79.8 (t, J_CP = 2.4 Hz, Ci), 128.2 (app. t, sum of Jcp = 9.4 Hz, C3/4/7/8), 128.4 (app. t, sum of J_CP = 9.4 Hz, C3/4/7/8), 129.4 (s, C5/9), 129.9 (s, C5/9), 131.7 (app. t, sum ofJ_CP = 10.6 Hz, C3/4/7/8), 134.3 (app. t, sum ofJ_CP = 10.6

C₂ and C₆ could not be observed.

³¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 81.8 (s, PPh₃)

ESI-MS (m/z): Expected for C3iH₂₉ClNaP₂Ru = 623.0374; Observed: 623.0392 [M⁺] (Error = 1.8 mDa) Example 7

Synthesis of [Ru(q⁵-C₅H₅)(dppe)(-C≡C-Ph)], [la_dppe]

Prepared as described in the literature.

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 2.24 - 2.38 (m, 2H, Hi_6a/b), 2.60 - 2.78 (m, 2H, Hiea_/b), 4.80 (s, 5H, Hi), 6.35 - 6.39 (m, 2H, H₅), 6.77 - 6.82 (m, 1H, H₇), 6.85 - 6.91 (m, 2H, H₆), 7.23 - 7.34 (m, 10H, ar), 7.40 - 7.48 (m, 6H, ar), 7.88 - 7.95 (m, 4H, ar)

1³C NMR (CD₂CI₂, 125 MHz, 295 K): 27.7 (m, Ci_6a/b), 82.3 (t, J_CP = 2.3 Hz, Ci), 1 1 1.4 (s, C₃), 1 17.2 (²J_CP = 25.9 Hz, C₂), 122.8 (s, ar), 127.3 (s, ar), 127.6 (app. t, sum of Jcp = 10.0 Hz, C9/10/13/14), 127.9 (app. t, sum of J_CP = 9.0 Hz, C9/10/13/14), 128.9 (s, ar), 129.3 (s, ar), 130.0 (s, C₄), 130.1 (s, ar), 131.5 (app. t, sum ofJcp = 10.6 Hz, C9/10/13/14), 133.8 (app. t, sum ofJcp = 10.4 Hz, C9/10/13/14), 137.2 (m, C ₂), 142.2 (m, C_m2)

3¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 86.3 (s, PPh₃) Example 8

Synthesis of [Ru^⁵-C₅H₅)(dppe)(=C=CPhF)] [NSI], [2a_dpPe] [NSI]

A Young's NMR tube was charged with [Ru^⁵-C₅H₅)(dppe)(-C≡C-Ph)] (26 mg, 38 μιηοΐ) and NFSI (12 mg, 38 μιηοΐ) in CD₂CI₂ (0.5 mL). An immediate colour change was observed from yellow to bright green. Quantitative conversion was observed by 1H and ³¹P NMR spectroscopy and samples were used directly without isolation or further purification.

1H NMR (CD₂CI₂, 500 MHz, 295 K): δ 2.80 - 3.00 (m, 4H, Hi₆), 5.68 (s, 5H, Hi), 6.39 - 6.43 (m, 2H, H₅), 6.96 - 7.04 (m, 3H, H_6/7), 7.10 - 7.17 (m, 4H, ar), 7.21 - 7.26 (m, 4H, ar), 7.27 - 7.32 (m, 6H, ar), 7.34 - 7.44 (m, 10H, ar), 7.48 - 7.53 (m, 2H, ar), 7.76 - 7.77 (m, 2H, ar), 7.77 - 7.79 (m, 2H, ar)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 28.2 (m, C₁₆), 94.5 (s, Ci), 122.4 (s, C₅), 126.9 (s, ar), 128.1 (s, C₇), 128.2 (s, ar), 128.8 (s, C₆), 129.2 (app. t, sum ofJ_CP = 11.0 Hz, C9/10/13/14), 129.7 (app. t, sum ofJcp = 10.0 Hz, C9/10/13/14), 130.1 (s, ar), 131.7 (app. t, sum ofJcp = 10.8 Hz, C9/10/13/14), 132.1 (d, JCP = 4.0 Hz, ar), 132.8 (app. t, sum of J_CP = 11.4 Hz, C9/10/13/14), 134.2 - 135.3 (m, ar, C_8/i₂), 146.9 (s, ar), 193.4 (dt, ^CF = 225.7 Hz, ³J_CP = 6.3 Hz, C₃), 385.0 (m, C₂)

³¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 77.9 (s, PPh₃)

1⁹F NMR (CD₂CI₂, 471 MHz, 295 K): δ -210.8 (s, F₃) ESI-MS (m/z): Expected for C₃₉H₃₄FP₂R.U = 685.1168; Observed: 685.1147 [M⁺] (Error 2.1 mDa).

Example 9

Synthesis of [Ru( ⁵-C₅H₅)(dppe)(-C(NC₅H₅)=C(C₆H₅)F)][NSI], [15_dppe] [NSI]

An NMR tube was charged with [Ru^⁵-C₅H₅)(dppe)(=C=CPhF)][NSI] (15 mg, 23 μιηοΐ) and pyridine (1.8 μΐ, 23 μηιοΐ, 1 equiv.) in CD₂CI₂ (0.5 ml) and allowed to stand overnight, during which time a colour change was observed from green to red.

1H NMR (CD₂CI₂, 500 MHz, 295 K): δ 2.47 - 2.63 (m, 2H, Hi_9a/b), 3.00 - 3.19 (m, 2H, Hi_9a/b), 4.17 (s, 5H, Hi), 5.85 - 5.89 (m, 2H, ¾), 6.87 (app. t, ³J_HH = 7.8 Hz, 2H, H₉), 6.93 - 6.98 (m, 1H, ¾₀), 7.22 - 7.33 (m, 11H, ar), 7.35 - 7.40 (m, 6H, ar), 7.48 - 7.54 (m, 3H, ar), 7.54 - 7.59 (m, 4H, ar), 7.76 - 7.82 (m, 8H, ar), 7.82 - 7.87 (m, 2H, H₃), 7.94 (tt, ³J_HH = 7.7 Hz, ⁴J_HH = 1 4 Hz, 1H, H₅)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 29.7 (m, C₁₉), 85.0 (s, Ci), 127.0 (s, C₂₁), 127.3 (s, C₈), 127.4 (s, ar), 128.2 (s, C₂₂), 128.4 (s, ar), 128.5 (s, C₉), 128.7 (app. t, sum of J_CP = 9.2 Hz, C12/13/16/17), 129.0 (app. t, sum of J = 10.0 Hz, Cuns/ m), 129.8 (s, C₁₄), 130.2 (s, C₁₈), 130.3 (s, C₂₃), 131.5 (app. t, sum ofJ = 9.6 Hz, Cn_/nnem), 132.5 (app. t, sum ofJ = 9.6 Hz, C12/13/16/17), 137.4 (s, Cii/is), 142.6 (s, Cn/is), 142.7 (s, C₅), 145.0 (s, C₃), 146.7 (s, C₂₀), 151.9 (dt, ²J_CF = 84.7 Hz, ²J_CP = 16.4 Hz, C₂), 161.6 (dt, ^CF = 228.1 Hz, ³J_CP = 3.9 Hz, C₆) C₇ and Cio could not be observed.

³¹P NMR (CD2CI2, 202 MHz, 295 K): δ 91.1 (d, ⁴J_CF = 14.5 Hz, dppe)

1⁹F NMR (CD2CI2, 471 MHz, 295 K): δ -82.1 (t, ⁴J_CF = 14.5 Hz, F₆)

ESI-MS (m/z): Expected for C44H39F P2RU = 764.1580; Observed: 764.1563 [M⁺] (Error = 1.7 mDa)

Example 10

Synthesis of [Ru( ⁵-C₅H₅)(dppe)(-CF=C(C₆H₅)F)], [6_dppe]

An NMR tube was charged with [Ru^⁵-C₅H₅)(dppe)(CC{Ph}F)][NSI] (15 mg, 23 μιηοΐ) and TREAT.HF (3.7 μΐ, 23 μιηοΐ, 1 equiv.) in CD₂C1₂ (0.5 ml) and allowed to stand for 30 minutes, during which time a colour change was observed from green to yellow.

1H NMR (C₄D₈0, 500 MHz, 295 K): δ 2.56 - 2.80 (m, 4H, Hi₆), 4.65 (s, 5H, Hi), 6.75 (tt, ³J_HH = 7.3 Hz, ⁴J_HH = 1.3 Hz, 1H, H₇), 6.79 - 6.84 (m, 2H, H₅), 6.90 (app. t, ³J_HH = 7.6 Hz, 2H, H₆), 7.20 - 7.32 (m, 16H, dppe), 7.77 - 7.83 (m, 4H, dppe)

¹³C NMR (C₄D₈0, 125 MHz, 295 K): δ 30.1 (m, C₁₆), 84.1 (s, Ci), 124.0 (t, ³J_CF = 22.6 Hz, C₅), 124.0 (s, C₇), 127.5 (d, ⁴J_CF = 1.9 Hz, C₆), 128.1 (app. t, sum of J = 10.4 Hz, C₉/io/i3/i₄), 128.4 (app. t, sum of J = 9.0 Hz, C₉/io/i3/i₄), 129.1 (s, Cn/is), 129.7 (s, Cn/is), 131.6 (app. t, sum of J = 9.8 Hz, C9/10/13/M), 133.9 (app. t, sum ofJ = 10.7 Hz, C9/10/13/M), 134.6 (d, ²Jc_F = 30.7 Hz, C₄), 138.0 (m, C_8/i₂), 145.2 (m, C_8/i₂), 159.5 (dd, _¥ = 198.1 Hz, ²J_CF = 50.4 Hz,

C₃), 187.9 (ddt, \½ = 296.6 Hz, ²J_CF = 90.4 Hz, ³J_CP = 18.2 Hz, C₂)

³¹P NMR (C₄D₈0, 202 MHz, 295 K): δ 94.3 (dd, ³J_PF = 28.1 Hz, ⁴J_PF = 2.6 Hz, dppe)

¹⁹F NMR (C₄D₈0, 471 MHz, 295 K): δ -147.8 (d, ³J_FF = 111.5 Hz, F₃), -82,4 (dt, ³J_FF = 111.5

ESI-MS (m/z): Expected for C₃₉H₃₄F₂P₂Ru = 705.1220; Observed: 705.1192 [M+H⁺] (Error = 2.8 mDa)

Example 11

Synthesis of ₄]

An oven-dried ampoule was charged with [Ru(rj⁵-C₅H₅)(PPh₃)₂(-C≡CPh)] [la] (297 mg, 0.38 mmol) in dichloromethane (10 mL). l-Fluoro-2,4,6-trimethylpyridinium tetrafluoroborate (77.9 mg, 0.34 mmol) was added, and an immediate colour change was observed from yellow to green. The volume of solvent was reduced under vacuum to approximately 0.5 mL, and a green solid precipitated on the addition of excess diethyl ether. The solvent was then removed by cannula filtration and the dark green solid washed with diethyl ether, then dried under vacuum. Yield = 250 mg (82 %). 1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 5.45 (s, 5H, Hi), 6.98 - 7.05 (m, 14H, H₉/10, H_5/6), 7.22 - 7.28 (m, 13 H, H₉/10, H₇), 7.34 (t, J = 7.6 Hz, 2H, H_5/6), 7.40 - 7.46 (t, ³J_HH = 7.4 Hz, 6H, H„)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 96.7 (s, Ci), 122.3 (s, C_5/6), 124.3 (s, C_5/6), 129.1 (s, C₇), 129.1 (t, sum of J_CP = 10.6 Hz, C9/10), 131.6 (s, C_n), 133.6 (t, sum of J_CP = 10.6 Hz, C9/10), 139.0 (m, C₈), 150.7 (s, C₄), 196.7 (d, ^CF = 222.1 Hz, C₃), 389.0 (dt, ²J_CF = 39.3 Hz,

¹⁹F NMR (CD₂CI₂, 471 MHz, 295 K): δ -208.7 (s, F₃), -153.7 (BF₄ ^")

3¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 42.1 (s, PPh₃)

ESI-MS (m/z): Expected for C₄₉H₄₀FP₂Ru = 811.1627; Observed: 811.1656 [M⁺] (Error = 2.9 mDa)

Elemental Analysis: C₄₉H₄₀BF₅P₂Ru Calc. /% C 65.56, H 4.49, Found /% C 65.32 H 4.74.

Example 12

Synthesis of [Ru(q⁵-C₅H₅)(PPh3)2(=C=CFC₆H4-4-CF3)] [BF4], [2b] [BF₄]

An oven-dried ampoule was charged with Ru^⁵-C₅H5)(PPh₃)₂(-C≡C(C₆H₄-4-CF₃)) [lb] (148 mg, 0.17 mmol) in dichloromethane (5 mL). l-Fluoro-2,4,6-trimethylpyridinium tetrafluoroborate (35.2 mg, 0.15 mmol) was added, and an immediate colour change was observed from yellow to green. The volume of solvent was reduced under vacuum to approximately 0.5 mL, and a green solid precipitated on the addition of excess pentane. The solvent was then removed by cannula filtration and the dark green solid washed with diethyl ether, then dried under vacuum. Yield = 124 mg (75 %).

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 5.50 (s, 5H, Hi), 6.99 - 7.06 (m, 14H, H₅, Hio_/n), 7.24 - 7.31 (m, 12H, H_10/n), 7.44 (t, ³J_HH = 7.3 Hz, 6H, H₁₂), 7.50 (d, ³J_HH = 8.3 Hz, 2H, H₆) ¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 96.7 (s, Ci), 122.6 (s, C₅), 123.9 (q, \½ = 270.9 Hz, C₈), 125.4 (q, ³JcF = 3.8 Hz, C₆), 128.6 (t, sum of J_CP = 10.5 Hz, Cio/11), 129.5 (q, ²J_CF = 32.1 Hz, C₇), 131.5 (s, C₁₂), 132.9 (m, \½ + ³J_CP = 52.7 Hz, C₉), 133.3 (t, sum ofJ_CP = 10.4 Hz, Cio/11), 195.5 (d, CF = 221.0 Hz, C₃), 383.5 (m, C₂); C₄ cannot be observed.

1⁹F NMR (CD₂C1₂, 471 MHz, 295 K): δ -212.1 (s, F₃), -153.8 (BF₄ ^"), -64.1 (s, F₈)

3¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 41.0 (s, PPh₃)

ESI-MS (m/z): Expected for C₅oH₃₉F₄P₂Ru = 879.1501; Observed: 879.1540 [M⁺] (Error = 3.9 mDa)

Elemental Analysis: C5oH₃₉BF₈P₂Ru Calc. /% C 62.19, H 4.07, Found /% C 61.70, H 4.36.

Example 13

Synthesis of [Ru(q⁵-C₅H₅)(PPh3)2(=C=CFC₆H4-4-OMe)] [BF4], [2c][BF₄]

An oven-dried ampoule was charged with Ru(rj⁵-C5H5)(PPh₃)₂(-C≡C(C₆H₄-p-OMe)) [lc] (183 mg, 0.22 mmol) in dichloromethane (5 mL). l-Fluoro-2,4,6-trimethylpyridinium tetrafluoroborate (45.0 mg, 0.20 mmol) was added, and an immediate colour change was observed from yellow to green. The volume of solvent was reduced under vacuum to approximately 0.5 mL, and a green solid precipitated on the addition of excess pentane. The solvent was then removed by cannula filtration and the dark green solid washed with pentane, then dried under vacuum. Yield = 144 mg (70 %).

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 3.81 (s, 3H, ¾), 5.37 (s, 5H, Hi), 6.89 - 6.92 (m, 2H, H₆), 6.95 - 7.03 (m, 14H, H_10/n, H₅), 7.23 (app. t, ³J_HH = 8.1 Hz, 12H, H_10/n), 7.42 (t, ³J_HH = 7.4 Hz, 6H, H₁₂)

¹³C NMR (CD₂C1₂, 125 MHz, 295 K): δ 55.4 (s, C₈), 96.3 (s, Ci), 114.5 (s, C₆), 127.0 (s, C₅),

128.7 (t,∑J = 10.8 Hz, C₁₀/n), 131.2 (s, C₁₂), 133.2 (t,∑J = 10.6 Hz. C₁₀/n), 133.2 (m, C₉),

160.8 (s, C₇), 195.6 (d, ²J_CF = 225.4 Hz, C₃), 389.9 (m, C₂)

C₄ could not be observed.

¹⁹F NMR (CD₂C1₂, 471 MHz, 295 K): δ -212.1 (s, F₃), -153.8 (BF₄)

3¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 42.8 (s, PPh₃)

ESI-MS (m/z): Expected for C₅₀H₄₂FOP₂RU = 841.1733; Observed: 841.1749 [M⁺] (Error = 1.6 mDa)

Elemental Analysis: C₅₀H₄₂BF₅OP₂RU Calc. /% C 64.73, H 4.56, Found /% C 64.206, H 4.863. Example 14

Synthesis of [Ru^⁵-C₅H₅)(PPh₃)₂(=C=CFⁱBu)] [NSI], [2d] [NSI]

To an oven dried Schlenk tube [Ru^⁵-C₅H₅)(PPh₃)₂(-C≡C-^tBu)] [Id] (120 mg, 0.15 mmol) was added followed by toluene (ca. 10 mL) and cooled to 0°C. Separately a solution of FSI (58 mg, 0.18 mmol) in toluene was cooled to 0°C and added to the cold ruthenium solution. The solution was stirred for 15 minutes at 0°C before being allowed to warm to room temperature over 1 hour. The toluene was removed in vacuo and the green residue washed with toluene (1 x 5 mL) and pentane (2 x 5 mL). The green solid was dried in vacuo to yield the desired product. Yield = 138 mg (82 %).

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 1.03 (s, 9 H, H₅), 5.30 (s, 5 H, Hi), 6.97 (dd, ³J_HH = 8.0, 10.2 Hz, 12 H, H₇), 7.26 (t, ³J_HH = 7.3 Hz, 12 H, ¾), 7.43 (t, ³J_HH = 7.3 Hz, 6 H, H₉) ¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 27.6 (s, C₅), 33.2 (d, ³J_CF = 24.9 Hz, C₄), 96.1 (s, Ci), 129.0 (t, ³J_CP + ⁵Jc_P = 5.0 Hz, C₈), 130.8 (s, C₉), 133.7 (t, ³J_CP + ⁵J_CP = 5.1 Hz, C₈), 134.1 (m, C₆), 204.9 (d, 'JcF = 228.9 Hz, C₃), 392.6 (d, ³J_CF = 49.6 Hz, C₂)

1⁹F NMR (CD₂CI₂, 376 MHz, 295 K): δ -216.9 (s, F₃)

3¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 39.4 (s, PPh₃)

ESI-MS (m/z): Expected for C₄₇H₄₄FP₂Ru = 791.1940; Observed: 791.1914 [M⁺] (Error = 2.6 mDa)

Elemental Analysis: C₄₇H₄₄F₇P₃Ru Calc. /% C 60.32, H 4.74, Found /% C 60.10, H 4.71 UV-Vis: X_caax = 664 nm, ε = 715 mol^"1 dm² at a concentration of approximately 1 mmol dm^' and a path length of 1 cm; calculated 655 nm

Example 15

Synthesis of

33

Prepared as described in the literature

Example 16

Synthesis of

An oven dried Schlenk tube was charged with [RuCp*(PPh₃)2(=C=CFH)][BF₄] [4a] (100 mg, 0.1 1 mmol) and dissolved in THF (ca. 5 mL). An oven dried ampoule was charged with lithium bis(trimethylsilyl)amide (90 mg, 0.54 mmol) and dissolved in TFIF (ca. 5 mL). Both solutions were cooled to -78 °C and the lithium bis(trimethylsilyl)amide solution was transferred via cannula into the vinylidene solution. The reaction mixture was stirred for 20 minutes at -78 °C before being allowed to warm to room temperature over a further 20 minutes. The solvent was removed in vacuo, and the solid washed with pentane (ca. 5 mL). The solvent was removed in vacuo and this process was repeated once more to remove residual THF. A yellow solution was extracted using pentane (2 x 15 mL) and filtered via cannula. The solvent was removed in vacuo yielding a yellow solid. The yield was not determined (approximately 25 mg).

1H NMR (C₆D₆, 500.2 MHz, 295 K): δ 1.22 (bs, H₂), 6.86 (bs, H₇), 6.99 (bs, H_8/6), 7.70 (bs, ¾/₈).

Selected ¹³C NMR (C₆D₆, 125.8 MHz, 295 K): δ 9.5 (s, C₂), 92.6 (t, ²J_CP= 2.0 Hz, Ci), 94.2

(d,

12.2 Hz,

C₆), 138.0 ppm (t, _P +

18.5 Hz, C₅)

¹⁹F NMR (C₆D₆, 376.2 MHz, 295 K): δ -186.9 (t, ⁴J_PF= 5.0 Hz)

³¹P NMR (C₆D₆, 161.8 MHz, 295 K): δ 50.9 (d, ⁴J_PF= 5.0 Hz)

IR (ATR, υ/ cm^"1): 1959 (C≡C)

ESI-MS (m/z): Expected for C₄₈H₄₆FP₂Ru [M+H⁺]= 805.2096; Observed= 805.2083 [M + H⁺] (Error = 1.3 mDa)

Example 17

Synthesis of [Ru^⁵-C₅Me₅)(dppe)(-C≡C-H)], [3a_dpPe]

Prepared as described in the literature; sodium methoxide was used in place of sodium metal. (M. I. Bruce, M. A. Fox, P. J. Low, B. K. Nicholson, C. R. Parker, W. C. Patalinghug, B. W. Skelton and A. H. White, Organometallics, 2012, 31, 2639-2657)

Example 18

Synthesis of [Ru(ti⁵-C₅Me₅)(dppe)(-C≡C-F)], [3b_dppe]

To an oven dried Schlenk tube [Ru^⁵-C₅Me₅)(dppe)(=C=CHF)][NSI] [6a] (195 mg, 0.22 mmol) was added followed by THF (ca. 10 mL) and cooled to -78°C. Separately a THF solution of lithium /s(trimethylsilyl)amide (33 mg, 0.20 mmol in ca. 5 mL) was cooled to - 78 °C and cannula transferred into the cold ruthenium solution. The solution rapidly turned yellow and left to stir for 15 min at -78°C, then allowed to warm up to room temperature. A yellow solution was extracted with pentane and the solvent removed in vacuo to yield a yellow solid. Yield = 44 mg (30 %).

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 1.63 (t, ⁴J_HP= 1.4 Hz, 15 H, H₂), 1.86 (m, 2 H, ¾₃), 2.58 (m, 2 H, H₅), 7.06 (m, 8 H, H^), 7.24 (m, 8 H, H^), 7.83 (m, 4 H, H^)

Selected ¹³C NMR (CD₂C1₂, 125 MHz, 295 K): δ 10.0 (s, C₂), 29.3 (m, C₁₃), 91.7 (s, Ci), 1 1 1.4 (d, 332.2 Hz, C₄), 127.2 (t, J= 4.2 Hz, CA_T), 128.6 (s, CA_T), 128.7 (s, CA_T), 133.3 (t, J= 5.2 Hz, CA_T), 133.7 (t, J= 4.7 Hz, CA_T), 137.3 (d, J = 46.5 Hz, CA_T), 139.6 (d, J = 32.9

¹⁹F NMR (CD₂C1₂, 376 MHz, 295 K): δ -189.4 (t, ⁴J_FP= 4.8 Hz, F₄) ³¹P NMR (CD₂C1₂, 202 MHz, 295 K): δ 81.9 (d, ⁴J_FP= 4.8 Hz, dppe)

ESI-MS (m/z): Expected for C38H39FP2RU = 678.16 m/z; Observed: 678.13 m/z [M⁺]

UV-Vis: X_caax = 396 nm, ε = 10986 mol^"1 dm² at a concentration of approximately 1 mmol dm^"3 and a path length of 1 cm; calculated

= 430 nm

Example 19

Synthesis of

An oven-drie

[3] (32 mg, 0.04 mmol) was dissolved in a mixture of acetonitrile (2.5 mL) and dichloromethane (2.5 mL), to which a solution of Selectfluor® (12 mg, 0.04 mmol) in acetonitrile (2.5 mL) added. The mixture was shaken vigorously for ca. 5 minutes and left to stand for 10 minutes before being filtered through cotton wool. The solvent was removed in vacuo to afford a blue solid. Yield = 12 mg (34 %).

1H NMR (500 MHz, CD₂C1₂, 295 K): δ 1.28 (s, 15H, H₂), 7.25 (m, 30H, Ph), 8.60 (d, ²J_HF = 80.5 Hz, 1H, C₄)

¹³C NMR (125.77 MHz, CD₂C1₂, 295 K): δ 9.6 (s, C₂), 107.3 (s, Ci), 128.3 (s, C_6/7), 131.0 (s, C₈), 133.7 (s, C_6/7), 178.7 (d, \½ = 229.9 Hz, C₄), 367.9 (s, C₃).

1⁹F NMR (471 MHz, CD₂C1₂, 295 K): δ -236.1 (d, ²J_HF = 80.5 Hz, F₄), -152.9 (BF₄)

3¹P NMR (202 MHz, CD₂C1₂, 295 K): δ 51.5 (s, PPh₃) ESI-MS (m/z): Expected for C₄₆H₄8FP₂Ru = 805.2097; Observed = 805.2101 [M⁺] (Error = 0.4 mDa)

Example 20

Synthesis of [Ru(ti⁵-C₅Me₅)(PPh₃)2(=C=CF₂)] [NSI], [4b] [NSI]

7

An oven dried Schlenk tube was charged with a benzene-d⁶ solution of [RuCp*(PPh₃)₂(- C≡CF)] (approximately 25 mg in 2-3 mL) and cooled down to -78 °C. To the cooled solution was added NFSI (66 mg, 0.21 mmol) in toluene (ca. 5 mL). The solution was stirred for 20 minutes at -78 °C, and then allowed to warm up to room temperature over 20 minutes. The resultant dark green reaction mixture was filtered via cannula and the black/dark green solid washed with pentane. The solid was dried in vacuo; the yield was not determined.

1H NMR (CD₂C1₂, 399.8 MHz, 295 K): δ 1.27 (t, ³J_HP= 1.4 Hz, 15H, H₂), 7.00-7.35 ppm (m, ¾-¾).

¹⁹F NMR (CD₂C1₂, 376.2 MHz, 295 K): δ -135.2 ppm (s).

3¹P NMR (CD₂C1₂, 161.83 MHz, 295 K): δ 49.5 ppm (s).

MS-ESI (m/z): Expected for

823.2009 [M]⁺; Observed= 823.1996 [M]⁺ (1.3 mDa error) Example 21

Synthesis of [Ru^⁵-C₅Me₅)(dppe)(=C=CHF)] [NSI], [4a_dpPe] [NSI]

An oven dried Schlenk tube was charged with [RuCp*(dppe)(-C≡C-H)] [16] (160 mg, 0.24 mmol) which was then dissolved in toluene (ca. 5 mL) and cooled to -78°C. Separately a solution of NFSI (84.1 mg, 0.27 mmol) in toluene (ca. 5 mL) was prepared and added to the cold ruthenium solution. The solution was stirred for 15 minutes at -78°C before being allowed to warm to room temperature over lh. The green residue was isolated, and washed with toluene (lx 5 mL) and pentane (2 x 5 mL) before being dried in vacuo to yield a pale green solid. Yield = 195 mg (91 %).

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 1.59 (s, 15 H, H₂), 2.70 (m, 2 H, ¾₃), 2.94 (m, 2 H, H13), 7.09 (dd, ³J_HH = 10.8, 7.7 Hz, 4 H, HA_T), 7.29 (m, 8 H, H_Ar), 7.32 (d, ²J_HF= 80.2 Hz, 1 H, H₄), 7.49 (t, ³J_HH = 7.3 Hz, 8 H, HA_T)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 9.8 (s, C₂), 29.6 (m, C₁₃), 105.6 (s, Ci), 128.9 (t, J=

5.4 Hz, CA_T), 129.0 (t, J= 4.6 Hz, CA_T), 130.6 (d, J = 48.2 Hz, CA_T), 131.8 (s, CA_T), 132.0 (s,

CA_T), 132.1 (t, J= 5.3 Hz, CA_T), 132.7 (t, J= 5.0 Hz, CA_T), 134.5 (d, J= 58.0 Hz, CA_T), 173.9 (d,

¹JCF= 236.2 Hz, C₄), 362.8 (d, ³J_CF= 43.5 Hz, C₃)

¹⁹F NMR (CD₂CI₂, 376 MHz, 295 K): δ -235.8 (d, ²J_HF= 80.2 Hz, F₄)

³¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 76.4 (s, dppe)

ESI-MS (m/z): Expected for C₃8H₄oFP₂Ru = 679.1628 m/z; Observed: 679.1617 m/z [M⁺] (Error = 1.1 mDa) UV-Vis: X_caax = 601 nm, ε = 546 mol^"1 dm² at a concentration of approximately 1 mmol dm and a path length of 1 cm; calculated = 580 nm

Example 22

Synthesis of [Ru^⁵-C₅Me₅)(dppe)(=C=CF₂)] [NSI], [4b_dpPe] [NSI]

An oven dried Schlenk tube was charged with [RuCp*(dppe)(-C≡C-F)] [23] (44 mg, 0.07 mmol) dissolved in THF (ca. 5 mL) and cooled to -78°C. Separately a solution of NFSI (22.7 mg, 0.08 mmol) in THF (ca. 5 mL) was prepared and added to the cold ruthenium solution. The solution was stirred for 15 minutes at -78°C before being allowed to warm up to room temperature over lh. The solvent was removed in vacuo and the purple/red solid washed with toluene (2x 5 mL) and pentane (2 x 5 mL). The solid was dried in vacuo to yield the desired product. Yield = 32 mg (55 %).

Selected 1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 1.56 (t, ⁴J_HF= 1.3 Hz, 15 H, H₂), 2.72 (m, 2 H, H₁₃), 2.82 (m, 2 H, H₁₃)

Selected ¹³C NMR (CD₂C1₂, 125 MHz, 295 K): δ 9.8 (s, C₂), 29.7 (m, C₅), 106.9 (s, Ci), 231.3 (d,

22.5 Hz, C₃)

1⁹F NMR (CD₂C1₂, 376 MHz, 295 K): δ -134.0 (s, F₄)

3¹P NMR (CD₂C1₂, 202 MHz, 295 K): δ 75.2 (s, dppe) ESI-MS (m/z): Expected for C₄₇H₄₄FP₂R.U = 697.1543 m/z; Observed: 697.1545 m/z [M⁺] (Error = -0.2 mDa)

UV-Vis: X_caax = 693 nm, ε = 677 mol^"1 dm² at a concentration of approximately 1 mmol dm^"3 and a path length of 1 cm; calculated

= 698 nm.

Example 23

Synthesis of [Ru(ti⁵-C₅Me₅)(PPh₃)2(=CFCHF₂)] [BF₄], [5] [BF₄]

[Ru(n⁵-C₅Me5)(PPh₃)₂(-C≡CH)], [3] (78.2 mg, 0.1 mmol) was partially dissolved in ca. 5 mL acetonitrile and ca. 0.5 mL dichloromethane. Separately, Selectfluor® (35.3 mg, 0.1 mmol) was dissolved in ca. 5 mL acetonitrile and added to the solution of [3]. The solution immediately turned dark brown. The yield was not determined.

Adventitious fluoride resulted in the formation of [Ru^⁵-C₅H5)(PPh₃)₂(=CFCHF₂)][BF₄]

[5][BF₄] contributing approximately 9% to the total ruthenium containing complexes in the reaction mixture.

1H NMR (CD2CI2, 500 MHz, 295 K): δ 1.32 (s, 15H, C₂), 6.62 (td, ²J_HF = 54.4 Hz, ³J_HF = 18.6 Hz, 1H, H₄), 7.25 (m, 30H, Ph) ¹⁹F NMR (CD₂C1₂, 471 MHz, 295 K): δ -153.2 (BF₄ ^"), -132.6 (dd, ³J_FF = 29.8 Hz, ²J_HF = 54.4

Hz, F₄), 110.4 (dquin, ³J_HF = 18.6 Hz, ³J_PF,FF = 28.6 Hz, F₃)

³¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 46.5 (d, ³J_PF = 26.6 Hz, PPh₃)

ESI-MS (m/z): Expected for C₄₈H₄₆F₃P₂Ru = 843.2065; Observed: 843.2053 [M⁺] (Error = 1.2 mDa)

Example 24

Synthesis of (E)-[Ru(q⁵-C₅H₅)(PPh₃)2(CF=CFPh)], [6]

An oven-dried ampoule was charged with [Ru^⁵-C₅H₅)(PPh₃)₂(=C=CPhF)][BF₄], [2a][BF₄] (50 mg, 0.56 μιηοΐ) and tetramethylammonium fluoride (5.2 mg, 0.56 μιηοΐ) in dichloromethane (10 mL) and left to stir for 3 days.

Alternative Procedure: A Young's NMR tube was charged with [Ru(n⁵- C₅H₅)(PPh₃)₂(=C=CPhF)][BF₄], [2a][BF₄] (20 mg, 0.02 mmol) and TREAT.HF (triethylamine trihydrofluoride, 3.6 μΐ, 0.02 mmol) in deuterated tetrahydrofuran (0.5 mL), and the reaction turned from green to yellow. The NMR spectra reported were recorded 5 days after addition.

1H NMR (C₄D₈0, 500 MHz, 298 K): δ 4.39 (s, 5H, Hi), 6.81 - 7.82 (m, 50H, ¹³C NMR (C₄D₈0, 126 MHz, 298 K): δ 160.8 (dd, ^lJ _F = 197.3 Hz, ²J_CF = 51.7 Hz, C₂),

145.7 (dd, CF = 186.7 Hz, ²J_CF = 21.3 Hz, C₃), 140.4 (dd, J_CF = 20.8 Hz, J_CF = 19.3 Hz, C₄),

139.8 (m, C₈), 134.6 (app. t,∑J_CP = 10.4 Hz, C9_/10), 129.2 (s, Cn), 129.0 (s, C_6/7), 127.9 (app. t,∑ Jcp = 9.2 Hz, C9_/10), 124.3 (dd, ³J_CF = 10.2 Hz, ⁴J_CF = 8.2 Hz, C₅), 85.8 (d, ³J_CF = 1.8 Hz,

¹⁹F NMR (C₄D₈0, 471 MHz, 298 K): δ -146.8 (d, ³J_FF = 113.7 Hz, F₃), -72.6 (dt, ³J_FF = 113.7

³¹P NMR (C₄D₈0, 162 MHz, 298 K): δ 52.5 (dd, ³J_PF = 32.3 Hz, ⁴J_PF = 2.4 Hz)

Example 25

Synthesis of [Ru^⁵-C₅H₅)(PPh₃)₂Cl], [7]

24

Prepared as described in the literature

Example 26

Synthesis of phenylacetyl fluoride, [8^Ph]

5

An oven-dried Schlenk tube was charged with [Ru^⁵-C₅H₅)(PPh₃)₂(=C=CFPh)][BF₄],

[2a][BF₄] (230 mg, 0.26 mmol) and NBu₄Cl (142 mg, 0.51 mmol) in dichloromethane (10 mL) and left to stir for one week. The reaction was monitored by NMR spectroscopy. [8^Ph] can be isolated by sublimation using a cold finger filled with liquid nitrogen. The reaction is also possible using [Ru^⁵-C₅H₅)(PPh₃)₂(=C=CFPh)][NSI], [2a] [NSI] and [Ru(n⁵- C₅H₅)(dppe)(=C=CFPh)][NSI], [XXX] [NSI].

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 3.66 (d, ³J_HF = 1.6 Hz, 2H, H₂), 7.25 - 7.37 (m, 5H, Ph)

¹⁹F NMR (CD₂CI₂, 471 MHz, 295 K): 6 42.5 (t, ³JHF = 1 6 Hz,

Example 27

Reaction of [Ru^⁵-C₅H₅)(dppe)(=C=CPhF)] [NSI], [2a_dppe] [NSI] with 2 equivalents of NⁿBu₄Cl.H₂0

5

A Young's NMR tube was charged with [Ru^⁵-C₅H₅)(dppe)(=C=CPhF)][NSI] (30 mg, 30 μπιοΐ) and NBU₄CI.H₂O (17 mg, 60 μπιοΐ, 2 equiv.) in CD₂CI₂ (0.5 ml) and monitored by NMR spectroscopy. Immediately on addition of NⁿBu₄Cl, conversion of [Ru(n⁵- C₅H₅)(dppe)(=C=CPhF)][NSI], [2a_dppe][NSI] to [Ru(n⁵-C₅H₅)(dppe)Cl], [7_dppe] and a- fluorophenylacetaldehyde (PhCHFCHO, [8^Ph']) was observed, a-fluoro-phenylacetaldehyde was identified by comparison of ¹⁹F NMR data with literature values. Selected 1H NMR (CD₂C1₂, 400 MHz, 298 K): δ 9.72 (dd, ³J_HF = 7.6 Hz, ⁵J_HH = 0.7 Hz, Hi)

¹⁹F NMR (CD₂C1₂, 376 MHz, 298 K): δ -191.7 (dd, ²J_HF = 47.0 Hz, ³J_HF = 7.6 Hz, Fi)

After 6 days, the NMR spectra were recorded again. The dominant organic product was phenylacetyl fluoride, [8^Ph] .

Example 28

Synthesis of acetyl fluoride [8^H]

A FEP lined Young's NMR tube was charged with [Ru^⁵-C₅Me₅)(dppe)(=C=CHF)][NSI], (10 mg, ) in acetonitrile-d³ (0.5 mL) was heated at 70°C in an FEP lined Young's NMR tube for 7 days.

¹⁹F NMR (CD₂C1₂, 376.2 MHz, 295 K): δ 49.1 (q, J_FH = 7.2 Hz)

Example 29

Synthesis of [Ru( -C₅H₅)(PPh3)(C₅H₄NCHC{C₆H₄-4-CF3})], [9]

The synthesis was performed as described in the literature.³¹

Example 30

Synthesis of [Ru^⁵-C₅H₅)(PPh₃)(C₅H₄NCHFC{C₆H₄-4-CF₃})] [BF₄], [10] [BF₄]

9

An oven-dried ampoule was charged with [Ru( ⁵-C₅H₅)(PPh₃)(C₅H₄NCHC{C₆H₄-4-CF₃})]

[9], (20 mg, 30 μιηοΐ) and dichloromethane (2 mL). l-Fluoro-2,4,6-trimethylpyridinium tetrafluoroborate (6.1 mg, 27 μιηοΐ) was added drop wise as a dilute solution in dichloromethane (5 mL). The solution was allowed to stir for ca. forty minutes until the colour change from brown to green was deemed complete, and the volume of solvent reduced under vacuum to 0.5 mL. An excess of pentane was added via a cannula transfer to produce a green precipitate. This residue was washed with pentane (2 x 10 mL), and dried under vacuum to yield a dark green precipitate.

Yield = 7 mg (30 %). Alternative procedures:

Fluorination with Selectfluor®: An oven-dried ampoule was charged with [Ru(n⁵- C₅H5)(PPh3)(C5H₄NCHC{C6H₄-4-CF₃})] [9] (10 mg, 15 μιηοΐ) and dichloromethane (2 mL)., Selectfluor® (5 mg, 15 μιηοΐ) was added dropwise as a dilute solution in acetonitrile (2mL). The reaction mixture was stirred for ca. 60 minutes and then removed under vacuum. The green residue was redissolved in CD2CI2 (0.5 mL) and NMR spectra recorded.

Fluorination with NFSI: A Young's NMR tube was charged with [Ru(n⁵- C₅H5)(PPh₃)(C₅H₄NCHC{C₆H₄-4-CF₃})] [9] (10 mg, 15 μιηοΐ) and NFSI (5 mg, 15 μιηοΐ) in CD2CI2 (0.5 mL). NMR spectra were recorded after ca. 60 minutes.

1H NMR (CD2CI2, 500 MHz, 295 K): δ 4.71 (d, ²J_HF = 52.1 Hz, 1H, Hn), 5.37 (s, 5H, Hi),

7.06 (apparent t, ³J_HH = 6.8 Hz, 1H, H₉), 6.12 - 7.19 (m, 6H, PPh₃), 7.38 (d, ³J_HH = 8.2 Hz, 2H, H₁₄), 7.40 - 7.49 (m, 7H, PPh₃, ¾), 7.49 - 7.56 (m, 3H, H₅), 7.60 (d, 2H, ³J_HH = 8.2 Hz, Hi₅), 8.06 - 8.12 (m, 2H, ¾₀, H₇)

¹³C NMR (CD2CI2, 125 MHz, 295 K): δ 93.5 (s, Ci), 115.9 (d, ^lJ _F = 219.1 Hz, Cn), 120.0 (s, C₉), 124.0 (s, CM), 124.5 (q, \½ = 272.8 Hz, Cn), 125.8 (q,³J_CF = 3.8 Hz, Ci₅), 129.4 (d, JCP = 10.7 Hz, C3/4), 131.0 (q, ²J_CF = 32.65 Hz, Ci₆), 132.0 (d, ⁴J_CP = 2.4 Hz, C₅), 132.1 (d, ^lJ_CP= 51.9 Hz, C₂), 133.2 (d, J_CP = 10.8 Hz, C_3/4), 135.5 (s, C₈), 140.3 (s, C₇), 143.4 (d, ³J_CF =

1.7 Hz, Cio), 211.8 (d, ²J_CP = 15.9 Hz, C₆), 301.4 (d, ²J_CP = 8.1 Hz, C_i2)

Attempts to locate Ci₃ using a range of NMR techniques were unsuccessful.

¹⁹F NMR (CD2CI2, 471 MHz, 298 K): δ -153.3 (BF₄ ^"), -139.8 (dd, ²J_HF = 52.0 Hz, ⁴J_PF = 7.7 Hz, Fn), -64.2 (s, Fn)

³¹P NMR (CD2CI2, 202 MHz, 295 K): δ 47.2 (d, ⁴J_PF = 7.7 Hz, PPh₃) ESI-MS (m/z): Expected for C₃₇H₂₉F₄ P^{101 9}Ru = 696.1012; Observed: 696.1023 [M⁺] (Error = 1.1 mDa)

Elemental Analysis: C₃₇H₂₉BF₈ PRu Calc. /% C 56.79, H 3.74, N 1.79 Found /% C 56.347, H 3.727, N 1.738.

Example 31

Synthesis of [Ru( ⁵-C₅H₅)(PPh₃)₂(=C=C{C₅H₄N}Ph)] [BF₄], [11a] [BF₄]

A Young's NMR tube was charged with [Ru^⁵-C₅H₅)(PPh₃)₂(-C≡CPh)] [la] (40 mg, 45 μηιοΐ) and 1-f uoropyridinium tetrafluoroborate (8 mg, 45 μηιοΐ) in CD₂CI₂ (0.5 mL), and an immediate colour change was observed from yellow to red.

1H NMR (CD₂CI₂, 500 MHz, 295 K): δ 5.13 (s, 5H, Hi), 6.37 (dt, ³J_HH = 8.0 Hz, ⁴J_HH = 0.9 Hz, 1H, pyr) 6.74 - 7.53 (m, 68H, Ar), 7.86 (m, 1H, ¾).

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 96.4 (s, Ci), 120.5 (s, C₅/₇), 121.5 (s, C₅/₇), 128.6 (app. t, sum of J = 10.8 Hz, C_M/_IS), 129.2 (s, C12), 130.0 (Cio_/11), 131.3 (s, Ci₆), 131.7 (s, Cio_/11), 134.2 (app. t, sum ofJ = 10.3 Hz, C_M/_IS), 136.2 (s, C3/9), 136.7 (s, C₆), 148.4 (s, C₈), 153.9 (s, C₄) , 357.5 (t, ²Jcp = 16.2 Hz, C₂). Carbons 3, 9 and 13 could not be assigned and may be obscured.

³¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 41.5 (s, PPh₃) ESI-MS (m/z): Expected for Cs^M^R^ = 870.1987; Observed: 870.2024 [M⁺] (Error = 3.7 mDa).

Example 32

Synthesis of [Ru^⁵-C₅H₅)(=C=C{C₅H₄N}C6H4-4-CF3)(PPh3)2]BF4, [5b]BF₄.

A Young's NMR tube was charged with [Ru ^-CsHsXPPhsM-^C-Cei^-CFs)] [lb] (20 mg, 23 μηιοΐ) and 1-fluoropyridinium tetrafluoroborate (4 mg, 23 μηιοΐ) in CD₂CI₂ (0.5 mL), and an immediate colour change was observed from yellow to red.

1H NMR (CD₂CI₂, 500 MHz, 295 K): δ 5.18 (s, 5H, Hi), 6.37 (dt, ³J_HH = 8.0 Hz, ⁴J_HH = 0.8 Hz, 1H, H₅) 6.96 (ddd, ³J_HH = 7.6 Hz, ³J_HH = 4.8 Hz, ⁴J_HH = 1.0 Hz, 1H, H₇), 7.00 - 7.09 (m, 14H, H10, His_/ie), 7.18 (m, 12H, H_15/16), 7.40 (m, 6H, H₁₇), 7.49 (app. td, ³J_HH = 7.8 Hz, ⁴J_HH = 1.6 Hz, 1H, H₆), 7.55 (d, ³J_HH = 8.1 Hz, 2H, H„), 8.00 (m, 1H, ¾)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 95.7 (s, Ci), 120.9 (s, C₅), 122.0 (s, C₇), 124.4 (q, \½ = 272.7 Hz, C13), 126.7 (q, _¥ = 3.5 Hz, Cn), 128.8 (app. t, sum of J = 10.5 Hz, C₁₆), 131.5 (s, Cn), 133.0 (s, C₁₀), 133.8 (m, C₁₄), 134.1 (app. t, sum ofJ= 10.5 Hz, C₁₅), 135.7 (s, C₃), 137.1 (s, C₆), 148.8 (s, C₈), 153.4 (s, C₄), 354,9 (t, ²J_CP = 15.4 Hz, C₂). Carbons C₉ and Ci₂ could not be assigned and may be obscured.

¹⁹F NMR (CD₂C1₂, 376 MHz, 295 K): -62.6 (s, F13), -153.0 (BF₄ ^")

³¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 41.1 (s, PPh₃)

ESI-MS (m/z): Expected for C₅₅H₄₃F₃ P₂Ru⁺ = 938.1876; Observed: 938.1858 [M⁺] (Error = 1.8 mDa).

Example 33

Synthesis of [Ru^⁵-C₅H₅)(PPh3)2(=C=CCF₃Ph)] [BF4], [12][BF₄]

An oven-dried ampoule was charged with [Ru^⁵-C₅H₅)(PPh₃)₂(-C≡CPh)], [la] (190 mg, 0.24 mmol) in dichloromethane (10 mL). 5-(Trifluoromethyl)dibenzothiophenium tetrafluoroborate (73 mg, 0.22 mmol) was added, and allowed to stir for 4 hours. The mixture was cannula filtered to remove any residual 5-(trifluoromethyl)dibenzothiophenium tetrafluoroborate, and the volume of solvent was reduced under vacuum to approximately 0.5 mL. A red/orange solid precipitated on the addition of pentane. The solid was isolated by filtration and redissolved in minimum dichloromethane and precipitated with pentane and isolated by filtration a further three times. The solvent was then removed by cannula filtration and the solid dried under vacuum. Yield = 150 mg (66 %). 1H NMR (CD₂C1₂, 400 MHz, 295 K): δ 4.74 (s, 5H, Hi), 6.80 - 6.84 (m, 2H, H₅), 6.84 - 6.92

(m, 12H, Hio/n), 7.23 -7.31 (td, ³J_HH = 7.8 Hz, ⁴J_HH = 1.6 Hz, 12H, H₁₀/n), 7.31 - 7.37 (m,

2H, H₆), 7.42 (tt, VHH = 7.6 Hz, ⁴J_HH = 1.9 Hz, 1H, H₇), 7.48 (t, ³J_HH = 7.8 Hz, 6H, H₁₂)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 95.8 (s, Ci), 122.1 (q, _¥ = 272.7 Hz, C₈), 123.3 (s,

C₄), 126.3 (q, ²J_CF = 34.8 Hz, C₃), 128.7 (t, J = 10.6 Hz, Cio_/11), 129.4 (s, C₆), 129.8 (s, C₇),

131.4 (s, C₅), 131.5 (s, C₁₂), 133.2 - 132.4 (m, C₉), 133.6 (app. t, sum of J_CP = 10.6 Hz,

Cio/11), 340.0 (tq, ²J_CP = 15.2 Hz, ³J_CF = 3.3 Hz, C₂)

¹⁹F NMR (CD₂CI₂, 471 MHz, 295 K): δ -57.6 (s, F₈), -154.1 (BF₄ ^")

³¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 39.6 (s, PPh₃)

ESI-MS (m/z): Expected for C₅oH₄oF₃P₂Ru = 861.1595; Observed: 861.1611 [M+H⁺] (Error = 1.6 mDa)

Elemental Analysis: C₅oH₄oBF₇P₂Ru Calc. /% C 63.37, H 4.25 Found /% C 63.07, H 4.26.

Example 34

Synthesis of [Ru₂^-C₄H₂F)(ti⁵-C₅H₅)₂(PPh₃)₄] [BF₄], [13] [BF₄]

A mixture of Ru(C≡CH)^⁵-C₅H₅)(PPh₃)₂ [Id] (50 mg, 0.07 mmol) and l-fluoro-2,4,6,- trimethylpyridinium tetrafluoroborate (10 mg, 0.04 mmol) dissolved in dichloromethane (10 mL), was stirred at room temperature for 30 minutes. The resultant orange-brown solution was reduced to a minimum volume, and the orange-brown solid precipitated out with diethyl ether (25 mL). The orange-brown precipitate was washed further with diethyl ether (4 x 25 mL), filtered, and dried in vacuo to give an orange solid. Yield = 36 mg (37 %).

1H NMR (500 MHz, CD₂C1₂): δ 4.37 (s, 10H, Hi), 4.84 (d, ²J_HF = 57.6 Hz, 1H, H₂), 7.13 (m, 60 H, 12 x Ph), 7.45 (d, ⁴J_HF = 12.5 Hz, 1H, H₃)

Selected ¹³C NMR (126 MHz, CD₂C1₂): δ 89.4 (s, C₅H₅, Ci), 108.7 (d, ²J_CF = 233.1 Hz, C₂), 183.2 (d, ⁴J_CF = 25.1 Hz, C₃), 250.6 (dt, ³J_CF = 20.1 Hz, ³J_CP= 13.5 Hz, C₄)

1⁹F NMR (471 MHz, CD₂C1₂): δ -152.9 (BF₄ ^"), -138.7 (dd, ²J_HF = 57.6 Hz, ⁴J_HF = 12.5 Hz, F₂) ESI-MS (m/z): Expected for C₈₆H₇₂FP₄Ru₂ = 1451.2650; Observed = 1451.2703 [M⁺] (Error = 5.3 mDa)

Example 35

Synthesis of [Ru^⁵-C₅H₅)(PPh3)(-C₆H4-PPh2-^²-CH=CFPh})] [BF4], [14] [BF₄]

A Young's NMR tube was charged with [Ru(n⁵-C₅H₅)(PPh₃)₂(=C=CPhF)][BF₄], [2a][BF₄] (20 mg, 0.02 mmol) in d₃-acetonitrile (0.5 mL), and heated at 50 °C for around 2 weeks.

Selected 1H NMR (CD₃CN, 500 MHz, 295 K): δ 4.69 (ddd, ³J_HF = 16.9 Hz, ²J_PH = 5.0 Hz, ³JPH = 1.7 Hz, 1H, H₈), 4.95 (s, 5H, ¾) Selected ¹³C NMR (CD₃CN, 125 MHz, 295 K): δ 25.9 (ddd, ¹J_CP = 75.1 Hz, ²J_CF = 7.8 Hz, ²J_CP = 2.7 Hz, C₈), 92.7 (s, Ci), 113.7 (dt, ^CF = 243.0 Hz, ²J_CP = 5.6 Hz, C₉), 170.9 (dd, ²J_CP = 32.6 Hz, ²J_Cp = 16.6 Hz, C₂)

¹⁹F NMR (CD₃CN, 471 MHz, 295 K): δ -153.0 (BF₄ ^"), -143.4 (app. dt, ³J_PF = 48.6 Hz, ³J_HF = 16.9 Hz, ³Jp_F = 16.2 Hz, F₉)

³¹P NMR (CD₃CN, 202 MHz, 295 K): δ 42.3 (dd, ³J_PF = 16.2 Hz, ³J_PP = 4.4 Hz), 46.6 (dd, ³J_PF = 48.6 Hz, ³J_PP = 4.4 Hz)

ESI-MS (m/z): Expected for C49H40FP2RU = 811.1627; Observed: 811.1637 (Error = 1.0 mDa)

Example 36

Synthesis of [Ru( ⁵-C₅H₅)(PPh₃)2(-C(NC₅H₅)=C(C₆H₅)F)] [BF₄], [15][BF₄]

An oven-dried ampoule was charged with [Ru^⁵-C₅H₅)(PPh₃)₂(=C=CPhF)][BF₄], [2a] [BF₄] (65 mg, 7.2 μmol) and pyridine (1 mL), and left to stir for 20 minutes. The reaction mixture was then added via a syringe to rapidly stirring diethyl ether (15 mL), to precipitate an orange powder. The solid was isolated by cannula filtration and dried under vacuum. Yield = 40 mg

(57 %). 1H NMR (CD₂C1₂, 700 MHz, 275 K): δ 4.16 (s, 5H, Hi), 6.32 (d, ³J_HH = 7.6 Hz, 2H, ¾), 6.97 (apparent t, ³J_HH = 7.6 Hz, 2H, H₉), 7.02 (t, ³J_HH = 7.6 Hz, 1H, Hi₀), 7.19 (apparent t, ³J_HH = 7.4 Hz, 12H, H₁₃), 7.27 (t, ³J_HH = 7.4 Hz, 12H, H₁₂), 7.39 (t, ³J_HH = 7.4 Hz, 6H, H₁₄), 7.61 (apparent t, ³J_HH = 7.0 Hz, 2H, H₄), 8.07 (t, ³J_HH = 7.9 Hz, 1H, H₅), 8.27 (d, ³J_HH = 5.8 Hz, 2H, H₃)

¹³C NMR (CD₂CI₂, 176 MHz, 275 K): δ 84.9 (s, Ci), 127.2 (s, C₄), 127.8 (s, C_8/9), 128.1 (t, sum of Jcp = 8.6 Hz, C12/13), 128.6 (s, Cio), 128.7 (s, C_8/9), 129.8 (s, CM), 132.3 (d, ²J_CF = 32.8 Hz, C₇), 134.1 (t, sum of J_CP = 8.6 Hz, Cuns), 138.5 (t, \½ + ³J_Cp = 39.7 Hz, C_N), 142.6 (s, C₅), 145.4 (s, C₃), 149.6 (dt, ¹J_CF = 84.8, ³J_CP = 17.0 Hz, C₂), 164.5 (d, ^CF = 232.7 Hz, C₆) . ¹⁹F NMR (CD₂CI₂, 471 MHz, 293 K): δ -152.3 (BF₄ ^"), -71.1 (t, ⁴J_PF = 20.1 Hz, F₆)

3¹P NMR (CD₂CI₂, 202 MHz, 293 K): δ 44.0 (d, ⁴J_PF = 20.3 Hz, PPh₃)

ESI-MS (m/z): Expected for C₅₄H₄₅F P₂Ru = 890.2049; Observed: 890.2039 [M⁺] (Error = 1.0 mDa).

Example 37

Synthesis of [Ru( ⁵-C₅H₅)(PPh3)((C₅H₄N)C(C₅H₅N)=C(C₆H₅))][BF4], [16] [BF₄]

An oven-dried ampoule was charged with [Ru^⁵-C₅H₅)(PPh₃)₂(=C=CPhF)][BF₄], [2a] [BF₄] (65 mg, 7.2 μmol) and pyridine (1 mL), and left to stir for 3 days. The reaction mixture was then layered with pentane. The crystals were isolated by cannula filtration and dried under vacuum.

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 4.80 (s, 5H, Hi), 6.48 (d, ³J_HH = 6.2 Hz, 1H, H_8/8>), 6.64 (dd, ³J_HH = 8.2 Hz, ⁴J_HH = 1.1 Hz, 2H, ¾₃), 6.79 - 6.88 (m, 2H, H₄, ¾), 6.99 (tt, ³J_HH = 7.4 Hz, ⁴J_HH = 1.3 Hz, 1/2H, H14/15), 7.08 (t, ³J_HH = 7.4 Hz, 2/3/4H, Hi₄/_15> H19) 7.27 (br m, 6/7H, PPh₃), 7.39 (m, 6H, PPh₃, H₃), 7.66 (m, 1H, H_9/9>), 7.93 (m, 1H, Η9/9·), 8.22 (d, ³J_HH = 8.1 Hz, H₆), 8.33 - 8.39 (m, 2H, H_8/8>, ¾<>)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 85.1 (s, Ci), 115.3 (s, C₅), 124.8 (s, C₁₃), 125.5 (s, Cis), 126.2 (s, C₄), 128.2 (s, C_M), 128.3 (s, PPh₃), 128.5 (s, C9/9 , 129.2 (s, C9/9 , 12 .9 (s, PPh₃), 133.7 (br, PPh₃), 134.2 (s, C₃), 136.8 (d, ²J_CP = 42.2 Hz, C₁₆), 144.1 (s, C₆), 146.1 (s, C_8/8 , 146.4 (s, C_8/8 , 146.8 (s, C₁0), 150.5 (s, C₁₂), 199.1 (br, Cn), 218.0 (br, C₂)

3¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 60.0 (br, PPh₃).

ESI-MS (m/z): Expected for Q₁H₂₅D₉N₂PRU = 696.2063; Observed: 696.2084 [M⁺] (Error = 2.1 mDa)

Example 38

Synthesis of ] [BF₄]

Prepared as described in the literature. Example 39

Synthesis of F₄]

An oven-dried Schlenk tube was charged with [Ru(rj⁵-C₅H5)(PPh₃)₂(-C≡CPh)] [la] (50 mg, 0.063 mmol) in CH₂CI₂ (10 mL). To this solution was added sodium tetrafluoroborate (6.93 mg, 0.063 mmol) followed by N-chlorosuccinimide (8.45 mg, 0.063 mmol), resulting in a colour change from orange to bright green. After stirring for 1 minute the solution was transferred by cannula filtration to another oven-dried Schlenk tube, and the solvent was removed under vacuum. The residue was washed three times with diethyl ether and dried under vacuum leaving the green solid product. Yield = 8 mg (14 %).

1H NMR (CD₂CI₂, 700 MHz, 295 K): δ 5.31 (s, 5H, Hi), 6.97 (t, ³J_HH = 8.9 Hz, 12H, H9_/10), 7.10 (d, VHH = 7.5 Hz, 4H, H₅), 7.25 (t, ³J_HH = 7.3 Hz, 12H, H_9/10), 7.31 (t, ³J_HH = 7.5 Hz, 3H, H_6/7), 7.43 (t, ³JHH = 7.3 Hz, 6H, H_n), 7.46 (t, ³J_HH = 7.5 Hz, 3H, ¾_/7)

¹³C NMR (CD₂CI₂, 176 MHz, 295 K): δ 95.9 (s, Ci), 127.3 (s, C_3/4), 128.1 (s, C₅), 128.8 (app. t, sum ofJ_CP = 10.4 Hz, C9/10), 129.0 (s, C_6/7), 131.3 (s, C_n), 133.0-133.3 (m, ¹J_CP + ³J_CP = 52.3 Hz, C₈), 133.5 (app. t, sum of J_CP = 10.3 Hz, C9_/10), 133.6 (s, C_6/7), 139.4 (s, C_3/4), 353.5 (t, C₂)

ESI-MS (m/z): Expected for C₄₉H₄₀ClP₂Ru = 827.1332; Observed: 827.1306 [M+] (Error = 2.6 mDa) Example 40

Synthesis of F₄]

An oven-dried Schlenk tube was charged with [Ru(rj⁵-C₅H5)(PPh₃)₂(-C≡CPh)] [la] (50 mg, 0.063 mmol) in dichloromethane (10 mL). To this solution was added sodium tetrafluoroborate (6.93 mg, 0.063 mmol) followed by bromine (3.2

0.063 mmol), resulting in a colour change to bright green. After stirring for 1 minute the solution was transferred by cannula filtration into excess pentane producing a green precipitate. The solvent was removed by cannula filtration and the remaining green solid dried under vacuum. This was then extracted with the minimum amount of dichloromethane and recrystallized in excess pentane. The solvent was then removed by cannula filtration and the green solid product dried under vacuum. Yield = 14 mg (23 %).

1H NMR (CD₂C1₂), 500 MHz, 295 K): δ 5.29 (s, 5H, Hi), 6.98 (d, ³J_HH = 7.8 Hz, 12H, H₉), 7.05 (d, ³J_HH = 7.7 Hz, 2H, He), 7.09 (d, ³J_HH = 7.7 Hz, 2H, ¾), 7.27 (t, ³J_HH = 7.8 Hz, 12H, H10), 7.30 (t, ³J_HH = 7.1 Hz, 1H, H₇), 7.45 (t, ³J_HH = 7.2 Hz, 6H, H_n)

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): δ 95.7 (s, Ci), 123.7 (s, C_3/4), 127.6 (s, C_3/4), 128.8 (app. t, sum ofJ_CP, = 10.6 Hz, C9_/10), 129.2 (s, C_5/6/₇), 129.3 (s, C_5/6/₇), 129.4 (s, C_5/6/₇), 131.3 (s, C₁₁), 133.0-133.4 (app. t, ^cp and ³J_CP = 51.8 Hz, C₈), 133.6 (app. t, sum ofJ_CP = 5.3 Hz, C9/10), 340.3 (t,²J_CP = 16.0 Hz, C₂) ³¹P NMR (CD₂C1₂, 202 MHz, 295 K): δ 41.2 (s, PPh₃)

ESI-MS (m/z): Expected for C₄9H₄oBrP₂Ru = 871.0827; Observed: 871.0835 [M+] (Error = 0.8 mDa).

Example 41

Synthesis of [Ru(q⁵-C₅H₅)(PPh3)2(=C=CBrC₆H4-4-Br)] [Br3], [17d][Br₃]

An oven-dried Schlenk tube was charged with [Ru(rj⁵-C₅H₅)(PPh₃)₂(-C≡CPh)] [la] (100 mg, 0.126 mmol) in tetrahydrofuran (10 mL). Bromine (100

1.89 mmol) was added resulting in a colour change from orange to green. After 15 minutes stirring the solvent was removed by vacuum leaving a green solid. This was extracted with the minimum amount of dichloromethane and recrystallized in excess diethyl ether. The solvent was then removed by cannula filtration and the dark green crystals dried under vacuum. Yield = 47 mg (72 %).

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 5.30 (s, 5H, Hi), 6.93 (d, ³J_HH = 7.9 Hz, 2H, H₆), 6.97 (m, 12H, H₉), 7.27 (t, ³J_HH = 6.9 Hz, 12H, ¾₀), 7.39 (d, ³J_HH = 7.7 Hz, 2H, H₅), 7.47 (t, ³J_HH = 6.9 Hz, 6H, Hn).

¹³C NMR (CD₂C1₂, 125 MHz, 295 K): δ 96.1 (s, Ci), 123.1 (s, C_3/7), 123.2 (s, C_3/7), 126.8 (s, C₄), 128.9 (app. t, sum of J_CP, = 10.6 Hz, C9/10), 130.7 (s, C_5/6), 131.4 (s, Cn), 132.3 (s, C_5/6), 133.1 (app. t, ^ΟΡ + ³J_CP = 51.8 Hz, C₈), 133.6 (app. t, sum of J_CP = 10.6 Hz, C9/10), 339.3

³¹P NMR (CD₂C1₂, 202 MHz, 295 K): δ 40.9 (s, PPh₃)

ESI-MS (m/z): Expected for C₄9H₃₉Br₂P₂Ru = 950.9928; Observed: 950.9910 [M+] (Error = 1.8 mDa)

Example 42

Synthesis of [Ru(ti⁵-C₅H₅)(PPh₃)2(=C=CIPh)] [I₃], [17e] [I₃]

An oven-dried Schlenk tube was charged with [Ru^⁵-C₅H₅)(PPh₃)₂(-C≡CPh)] [la] (100 mg, 0.126 mmol) in dichloromethane (10 mL) . Iodine (85 mg, 0.335 mmol) was added resulting in an immediate colour change from orange to dark green. After stirring for 20 minutes the solvent was removed under vacuum leaving a dark green solid.

The dark green solid was extracted with the minimum amount of dichloromethane and recrystallized in excess diethyl ether. The solvent was then removed by cannula filtration and the dark green crystals dried under vacuum. Yield = 37 mg (29 %).

1H NMR (CD₂CI₂, 500 MHz, 295 K): δ 5.23 (s, 5H, Hi), 6.96-7.03 (m, 12H, ar), 7.23-7.31 (m, 17H, ar), 7.43-7.50 (m, 6H, ar) ^1JC NMR (CD₂C1₂, 125 MHz, 295 K): δ 95.2 (s, Ci), 128.8 (app. t, sum of J_CP, = 10.5 Hz, C9/10), 129.0 (s, C₇), 129.1 (s, C_3/4), 129.3 (s, C_5/6), 130.1 (s, C_5/6), 131.3 (s, Cn), 133.0 (s, C3/4), 133.0 - 133.6 (m, C₈), 133.7 (app. t, sum of J_CP, = 10.6 Hz, C9/10), 323.6 (t, ²J_CP = 16.0 Hz, C₂)

³¹P NMR (CD2CI2, 202 MHz, 295 K): δ 40.3 (s, PPh₃)

ESI-MS (m/z): Expected for C49H40IP2RU = 919.0688; Observed: 919.0698 [M+] (Error = 1.0 mDa)

Example 43

Synthesis of [Ru(ti⁵-C₅H₅)(NCMe)(PPh₃)₂][PF₆], [18][PF₆]

34

Prepared as described in the literature.

Example 44

Synthesis of [Ru(ti⁵-C₅H₅)(PPh₃)(Pyr)₂] [PF₆], [19] [PF₆]

31

Prepared as described in the literature. Example 45

Synthesis of (E)-[Ru( ⁵-C₅H₅)(PPh₃)(C₅H₄NCHC{C₆H4-4-CF₃})] [PF₆], [20] [PF₆]

Prepared as described in the literature.³¹

Example 46

Synthesis of [Ru( ⁵-C₅H₅)(PPh3)(C₅H₄NCF₂C{C6H4-4-CF3})] [BF4], [21] [BF₄]

An NMR tube with a PTFE J. Young's tap was charged with [Ru(n⁵- C₅H₅)(pPh3XC5¾NCHC{C6H4-4-CF3 })], [9], (20 mg, 30 μι^ηοΐ) and l-fluoro-2,4,6- trimethylpyridinium tetrafluoroborate (13.6 mg, 60 μιηοΐ) in CD₂CI₂ (0.5 mL). On addition of l-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate, an immediate colour change was observed from brown to green. The reaction mixture was allowed to stand for 24 hours, and monitored by NMR spectroscopy.

On complete conversion, the reaction mixture was transferred to a Schlenk tube, and an excess of pentane was added via a cannula transfer to produce a green precipitate. This residue was washed with further pentane (2 x 10 mL) by cannula filtration, and dried under vacuum to yield a dark green precipitate. Isolated yield = 9 mg (38 %).

1H NMR (CD₂C1₂, 500 MHz, 295 K): δ 5.35 (s, 5H, Hi), 7.07 (app. td, ³J_HH = 6.9 Hz, ⁴J_HH =

1.1 Hz, 1H, H₉), 7.12 - 7.19 (dd, ³J_HH = 8.2 Hz, ³J_Hp = 11.9 Hz, 6H, ¾/¾), 7.39 (d, ³J_HH =

8.2 Hz, 2H, H₁₄), 7.43 (app. td, ³J_HH = 7.8 Hz, ⁴J_Hp = 2.6 Hz, H3/H₄, ¾), 7.46 - 7.55 (m, 5H, H₅, His), 8.09 (d, ³JHH = 8.4 Hz, 1H, H₇), 8.14 (app. d, ³J_HH = 6.7 Hz, 1H, ¾<>) Resonances due to 2,4,6-trimethylpyridinium tetrafluoroborate([HTMP][BF₄]), which could not be removed from this sample by recrystallisation, have been omitted. Integrations are not shown where the [HTMP][BF₄] and [21] [BF₄] resonances overlap.

¹³C NMR (CD₂CI₂, 125 MHz, 295 K): 93.0 (s, Ci), 123.5* (C₁₇) 131.5* (Ci₆), 120.9 (s, C₉), 125.8 (s, Ci₄), 129.6 (d, J_CP = 10.7 Hz, C_3/4), 131.3 (d, ²J_CP = 51.5 Hz, C₂), 132.1 (s, C₅), 132.3* (C₁₁), 133.4 (d, J_CP = 11.1 Hz, C_3/4), 137.6 (s, C₁₀), 144.0 (s, C₇), 207.6* (C₆), 284.5* (C₁₂) (* = resonances located by ^: : ^{1 "}( ^' ; two-dimensional correlation spectra).

¹⁹F NMR (CD₂CI₂, 471 MHz, 295 K): δ -153.0 (BF₄ ^"), -98.3 (d, ²J_FF = 233.1 Hz, Fn), -79.7

(dd, ²J_FF = 233.1 Hz, ⁴J_PF = 6.6 Hz, Fn), -66.4 (s, C_n)

³¹P NMR (CD₂CI₂, 202 MHz, 295 K): δ 47.2 (d, ⁴J_PF = 6.6 Hz, PPh₃)

Attempts to locate C₈, Ci₃ and C₁₅ using a range of NMR techniques were unsuccessful. ESI-MS (m/z): Expected for C₃₇H₂₈F₅NP^{101 9}Ru = 714.0918; Observed: 714.0920 [M⁺]

(Error = 0.2 mDa)

Elemental Analysis: C₃₇H₂₈BF₉NPRu + 1 C₈Hi₂BF₄N ([HTMP][BF₄]) Calc. /% C 53.54, H 3.99, N 2.75. Found /% C 53.814, H 4.227, N 3.062. Complex [21][BF₄] could not be isolated cleanly without one equivalent of [HTMP][BF₄], which is formed during the deprotio-difluorination of metallocycle [9], as both [21][BF₄] and [HTMP][BF ] crystallise under identical conditions.

Example 47

Preparation of [Ru^⁵-C₅H₅)(PPh₃)(C₅H₄NCFC{C₆H₄-4-CF₃})], [22]

An NMR tube with a PTFE J. Young's tap was charged with [Ru(n⁵- C₅H5)(PPh₃)(C₅H₄NCF₂C{C₆H₄-4-CF₃})][BF₄], [21][BF₄], (6 mg) dissolved in pyridine-d₅ (0.5 mL). The reaction was monitored over 7 days, and produced a mixture of [Ru(n⁵- C₅H5)(PPh₃)(C₅H₄NCFC{C₆H₄-4-CF₃ })], [22], and the oxygen-containing complex, [24][BF ]. [22] can also be made independently from the dissolution of [10][BF ] in pyridine. Dissolution in d₅-pyndine allows full NMR characterisation to be recorded.

Characterisation of [Ru^⁵-C₅H₅)(PPh₃)(C₅H₄NCFC{C₆H4-4-CF₃})], [22]

1H NMR (NC₅D₅, 500 MHz, 295 K): 4.95 (s, 5H, Hi), 6.58 (td, ³J_HH = 6.7 Hz, ⁴J_HH = 1.2 Hz, 1H, H₉), 6.68 (m, 1H, ¾), 7.21 - 7.26 (m, 6H, H_3/4), 7.26 - 7.36 (m, 9H, H_3/4, H₅), 7.45 - 7.49 (m, 2H, ¾₄), 7.54 - 7.59 (m, 2H, ¾₅), 7.71 (d, ³J_HH = 6.4 Hz, H₇), 8.29 (d, ³J_HH = 8.1

¹³C NMR (NC₅D₅, 125 MHz, 295 K): 83.9 (s, Ci), 113.8 (s, C₉), 124.9 (q, ³J_CF = 3.8 Hz, Cis), 126.1 (q, ^lJ_CF = 271.6 Hz, C₁₇), 126.3 (s, C₈), 126.4 (q, ²J_CF = 31.8 Hz, Ci₆), 128.4 (d, JCP = 9.4 Hz, C_3/4), 129.8 (s, C₅), 129.8 (s, CM), 133.9 (d, J_CP = 10.8 Hz, C_3/4), 134.8 (s, C₇), 137.2 (d, ¹J_Cp = 41.4 Hz, C₂), 143.2 (s, C10), 146.9 (br, C12), 153.9 (br, C_i3), 215.1 (br, C₆) ¹⁹F NMR (NC₅D₅, 376 MHz, 295 K): -111.7 (s, Fn), -63.5 (s, F_n)

3¹P NMR (NC₅D₅, 202 MHz, 295 K): 61.5 (s, PPh₃)

ESI-MS (m/z): Expected for C₃₇H₂₈F₄ P^101'9Ru = 695.0939; Observed: 695.0961 [M⁺] (Error = 2.2 mDa)

Example 48

Characterisation of oxygen containing complex, [24] [BF₄]

Selected 1H NMR (NC₅D₅, 500 MHz, 295 K): δ 5.09 (s, ¾)

¹⁹F NMR (NC₅D₅, 471 MHz, 295 K): δ -153.0 (BF₄ ^"), -78.7 (d, ²J_FF = 208.5 Hz, CF₂), -67.6

(d, ²J_FF = 208.5 Hz, CF₂), -64.5 (s, CF₃)

³¹P NMR (NC₅D₅, 202 MHz, 295 K): δ 43.2 (s, PPh₃)

ESI-MS (m/z): Expected for C₃₇H₂₈F₅NOP^{101 9}Ru = 730.0872; Observed: 730.0872 [M⁺] (Error <0.05 mDa)

ATR IR (v /cm^"1): 528.1 (m), 697.6 (m), 1066.2 (s, C-F stretch), 1090.1 (s, C-F stretch), 1206.5 (m), 1324.4 (m), 1413.0 (w, C=C stretch), 1436.4 (w, C=C stretch), 1458.3 (w, C=C stretch), 1481.1 (w, C=C stretch), 1540.4 (w, C=C stretch), 1640.1 (m, C=0 stretch), 2991.0 (w, C-H stretch), 3124.5 (w, C-H stretch), 3184.5 (w, C-H stretch), 3303.9 (w, C-H stretch) Example 49

Synthesis of [fra«s-Ru(dppm)₂Cl(-C≡C-Ph)], [31]

Prepared as described in the literature.

(D. Touchard, P. Haquette, N. Pirio, L. Toupet and P. H. Dixneuf, Organometallics, 1993, 12, 3132-3139.)

Example 50

Synthesis of [ira«s-Ru(dppm)₂Cl(=C=CFPh)] [BF₄], [32] [BF₄]

An oven dried Schlenk tube was charged with [tra«s-Ru(dppm)₂Cl(-C≡C-Ph)], [39] (50 mg, 0.07 mmol) dissolved in DCM (ca. 5 mL); separately a solution of Selectfluor (22.7 mg, 0.08 mmol) in acetonitrile (ca. 5 mL) was prepared and transferred via cannula into the ruthenium solution. The solvent was stirred for 10 minutes before being filtered and the solvent was removed in vacuo. The green solid was washed with pentane (2 x 5 mL) and dried in vacuo. Yield was not determined. ¹⁹F NMR (CD₂C1₂, 376 MHz, 295 K): δ -221.8 (bs, F₃)

3¹P NMR (CD₂C1₂, 202 MHz, 295 K): δ -13.6 (s, dppm)

ESI-MS (m/z): Expected for C₅₈H₄₉CIFP₄RU = 1025.1507 m/z; Observed: 1025.1544 m/z [M⁺] (Error = -3.7 mDa)

Low temperature NMR study of the monofluorination reaction, [9] to [10][BF₄]

An NMR tube with a PTFE J. Young's tap was charged with [Ru(n⁵- C₅H5)(PPh3)(C₅H₄NCHC{C6H4-4-CF₃})], [9], (20 mg, 30 μιηοΐ) and CD₂C1₂ (0.5 mL). 1H, ¹⁹F and ³¹P NMR spectra were recorded. The NMR tube was then cooled in a dry ice/acetone bath and l-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate (6.7 mg, 30 μιηοΐ) added. The NMR spectra were then recorded at a range of temperatures from 195 K to 295 K.

No evidence of any reaction intermediates was observed.

³¹P NMR

After the addition of l-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate (F⁺), the initial spectra were recorded at 195 K, and evidence for the mono-fluorinated metallocycle

[10][BF₄] was obtained at this temperature (³¹P NMR: δ 47.7, br). The integration of this resonance did not increase, relative to [Ru^⁵-C₅H5)(PPh₃)(C₅H₄NCHC{C₆H4-4-CF₃})], [9], on warming the sample to 245 K. This suggests that the initial fluorination occurred on transferring the sample into the NMR spectrometer, during which time it may not have remained at low temperature. However, by 265 K, the signal for [Ru(n⁵- C₅H5)(PPh₃)(C₅H₄NCHC{C₆H4-4-CF₃})], [9], could no longer be observed, and the dominant species in the reaction mixture was [10][BF₄].

During the experiment, as the temperature was increased, the signal for [Ru(n⁵- C₅H5)(PPh₃)(C₅H₄NCHC{C₆H₄-4-CF₃})], [9], at around δ 62 ppm became broader. This could be due to reversible protonation and deprotonation with the solvent, as has been described previously. A small resonance was also observed at around δ 30.1 ppm, attributed to triphenylphosphine oxide. ^iyF NMR

Before the addition of F⁺, one resonance was observed at δ -63.3 ppm due to the CF₃ moiety of [Ru^⁵-C₅H5)(PPh₃)(C₅H₄NCHC{C₆H₄-4-CF₃})], [9]. ¹⁹F NMR spectra were recorded from 245 K onwards. On the addition of F⁺, the monofluorinated product [10][BF₄] could be observed at 245 K by the appearance of new resonances at δ 140.1 ppm (d, HF = 52.0 Hz) and an additional resonance in the -CF₃ region. The resonance for F⁺ was also visible at δ 16.3 ppm (s) and -153.6 (BF ^"). Spectra recorded at 265 K showed the characteristic resonance for [10][BF₄] was growing, and by 285 K, two small doublets were visible for the bisfluorinated product [21][BF₄] (δ -96.6, d, ²J_FF = 233.1 Hz and -78.0 dd, ²J_FF = 233.1 Hz, ⁴J_PF = 6.6 Hz).

Broadening of the resonance attributed to the -CF₃ group of 2 was also observed with increasing temperature, in correlation with the broadening of the ³¹P NMR resonance associated with this complex. A small resonance was also observed at δ -220.1 ppm, ²JH_F = 47.3 Hz. This has been attributed to 2-monofluoromethyl-4,6-dimethylpyridine formed by deactivation of the l-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate.

1H NMR

On the addition of F⁺, 2 sets of resonances were observed for the methyl groups of 2,4,6- trimethylpyridine. These could be due to 2,4,6-TMP, l-fluoro-2,4,6-TMP or l-proteo-2,4,6- TMP. By 265 K, only one set of resonances were present, suggesting that all of the F⁺ had been delivered. The cyclop entadienyl resonance for the initial metallocycle [Ru(n⁵- C₅H₅)(PPh₃)(C₅H₄NCHC{C₆H₄-4-CF₃})], [9], was observed at δ 4.79 ppm at 195 K, but broadened over time with increasing temperature as was observed in the ³¹P and ¹⁹F NMR spectra. By 265 K, this Cp resonance was no longer observed and the resonance for the mono-fluorinated [10] [BF₄] species became dominant.

X-Ray Crystallography

Diffraction data was collected using an Oxford Diffraction SuperNova diffractometer equipped with a single Molybdenum source using Mo-K_a radiation (0,71073 A) and an EOS CCD camera. The crystals were cooled with an Oxford Instruments Cryojet typically to 11 OK. Diffractometer control, data collection, initial unit cell determination, frame integration and unit-cell refinement was carried out with "CrysalisPro". Face-indexed absorption corrections were applied either using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm or analytical numeric absorption correction using a multifaceted crystal model based on expressions derived by Clark and Reid, implemented within "CrysalisPro". OLEX2 was used for overall structure solution, refinement and preparation of computer graphics and publication data. Using 01ex2, the structure was solved either with the Superflip structure solution program using Charge Flipping or the ShelXS structure solution program using Direct Methods. Refinement was carried out with the ShelXL refinement package using Least Squares minimisation. All non-hydrogen atoms were refined anisotropically. Unless stated otherwise, hydrogen atoms were placed using a "riding model" and included in the refinement at calculated positions.

Special refinement details

e^⁵~C₅H₅)(PPh3)₂(~C≡C-C₆H₄- -CF3)], [lb]. The CF₃ group was disordered and modelled in two positions, with refined occupancy of 0.860:0.140(8). The carbon-fluorine and fluorine-fluorine bond distances were restrained to 1.32 A and 2.12 A respectively.

[Ru( ⁵-C₅H₅)(PPh₃)₂(=C=CFPh)], [2a][PF₆], green form.

The dichloromethane of crystallization has a disordered chloride atom, which has been modelled in two positions with a refined occupancy ratio of 0.77:0.23(3).

[Ru(ti⁵-C₅H₅)(PPh₃)₂(=C=CFPh)], [2a][PF₆], orange form.

The PF₆ counter-ion was disordered (rotation about one F-P-F axis), and four fluorine atoms were modelled in two positions with occupancies of 0.957:0.043(3). The fluorine atoms of the minor component were restrained to be approximately isotropic and the distances between them were restrained to be equal. The ADP of opposite pairs of fluorine atoms in the minor component were constrained to be equivalent e.g. F4A and F6A.

[Ruto⁵-Cs¾)(PPh3)2(=C=CCF₃Ph)]BF4, [12] [BF₄],

The tetrafluoroborate anion was disordered, with three of the fluorines each modelled in two positions with refined occupancies of 0.903 :0,097(4). The dichloromethane of crystallisation was also disordered with one of the chlorines modelled in two positions with refined occupancies of 0.663 : 0.337(3 ) . [Ru( ⁵-C₅H₅)(PPh₃)₂(-C(NC₅H₅)=C(C₆H₅)F)] [BF₄], [15] [BF₄].

The BF4 was disordered and modelled in two positions. The occupancies were refined to 0.65:0.35 (4). The boron-fluorine bond lengths were restrained to 1.4 A and the fluorine- fluorine bond lengths were restrained to 2.285 A. Rii(i|⁵~C₅H_s)(PPh₃)₂(-C₅H₄N~C{NC₅H₅)=C(C₆H₅)~)] [BF₄], [16] [BF₄].

The structure was non-merohedrally twinned and modelled using 2-components. The asymmetric unit contained two complex cations, two tetrafluoroborate anions and a pyridine of crystallisation.

Structure of Ru^⁵-C₅H₅)(PPh₃)₂(-C C-C₆H₄-4-CF₃) [lb] is illustrated in Figure

Identification code [lb]

Empirical formula C₅₀H₃₉F₃P₂RU

Formula weight 859.82

Temperature 110.00(14) K

Crystal system monoclinic

Space group P2i/c

a 16.8756(3) A

b 15.1925(2) A

c 17.3468(4) A

a 90°

β 116.921(3)°

Y 90°

Volume 3965.46(16) A³

Z 4

Calculated Density 1.440 mg/mm³

Absorption Coefficient 0.526 mm^"1

F(000) 1760.0

Crystal size 0.3086 0.1372 ^χ 0.1372 mm³

Radiation ΜοΚα (λ = 0.71071)

2Theta range for data collection 5.906 to 60.482°

Index ranges -23 < h < 21, -21 < k < 20, -24 < 1 < 23 Reflections collected 22877

Independent reflections 10476 [R_int = 0.0296, R_sigma = 0.0420] Data/restraints/parameters 10476/12/515

Goodness-of-fit on F² 1.052

Final R indexes [1>=2σ (I)] Ri = 0.0324, wR₂ = 0.0724

Final R indexes [all data] Ri = 0.0437, wR₂ = 0.0781

Largest diff peak and hole 0.52/-0.49 e A^"3 Structure of [Ru(q⁵-C₅H₅)(PPh₃)2( C=CFPh)] [PF₆] [2a] [PF₆] green form is illustrated in Figure 1(a)

Identification code [2a] [PF₆] green form

Empirical formula C₅₀H₄₂CI₂F₇P₃RU

Formula weight 1040.71

Temperature 110.05(10) K

Crystal system orthorhombic

Space group Pbca

a 17.3578(2) A

b 14.44250(18) A

c 36.1516(4) A

a 90°

β 90°

Y 90°

Volume 9062.86(19) A³

Z 8

Calculated Density 1.525 mg/mm³

Absorption Coefficient 0.634 mm^"1

F(000) 4224.0

Crystal size 0.3612 0.0695 χ 0.0598 mm³

Radiation ΜοΚα (λ = 0.71073)

2Theta range for data collection 5.586 to 60.844°

Index ranges -24 < h < 22, -20 < k < 20, -48 < 1 < 51

Reflections collected 85888

Independent reflections 12862 [R_int = 0.0323, R_sigma = 0.0220]

Data/restraints/parameters 12862/1/578

Goodness-of-fit on F² 1.066

Final R indexes [1>=2σ (I)] Ri = 0.0267, wR₂ = 0.0601

Final R indexes [all data] Ri = 0.0320, wR₂ = 0.0628

Largest diff peak and hole 0.40/-0.49 e A^"3 Structure of

[2a] [PF₆] orange form is illustrated in Figure 1(b)

Identification code [2a] [PF₆] - orange form

Empirical formula C50H42.12CI2F6.88P3RU

Formula weight 1038.64

Temperature 110.05(10)

Crystal system orthorhombic

Space group Pbca

a 17.5524(3)

b 19.8953(4)

c 25.3282(5)

a 90

β 90

Y 90

Volume 8844.9(3)

Z 8

Calculated Density 1.560

Absorption Coefficient 0.650

F(000) 4216.6

Crystal size 0.3926 0.2659 ^χ 0.1639

Radiation ΜοΚα (λ = 0.71073)

2Θ range for data collection 5.702 to 64.422

Index ranges -19 < h < 25, -28 < k < 24, -28 < 1 < Reflections collected 33223

Independent reflections 14037 [R_int = 0.0297, R_sigma = 0.0380] Data/restraints/parameters 14037/30/604

Goodness-of-fit on F² 1.049

Final R indexes [1>=2σ (I)] Ri = 0.0318, wR₂ = 0.0730

Final R indexes [all data] Ri = 0.0444, wR₂ = 0.0806

Largest diff peak and hole 0.62/-0.57 Structure of [Ru -C₅H₅)(PPh3)(C₅H₄NCFHC{C6H4-4-CF3})] [BF4], [10] [BF₄] is illustrated in Figure 8

Identification code [10] [BF₄]

Empirical formula C₃₇H₂₉BF₈ PRu

Formula weight 782.46

Temperature 110.05(10) K

Crystal system monoclinic

Space group P2i

a 9.34095(17) A

b 17.7554(3) A

c 9.85967(18) A

a 90.00 °

β 102.9459(18) °

Y 90.00 °

Volume 1593.68(5) A³

Z 2

Calculated Density 1.631 mg/mm³

Absorption Coefficient 0.619 mm^"1

F(000) 788.0

Crystal size 0.1405 0.064 ^χ 0.054 mm³

Radiation ΜοΚα (λ = 0.7107)

2Θ range for data collection 5.9 to 64.66°

Index ranges -13 < h < 13, -25 < k < 26, -14 < 1 < Reflections collected 20566

Independent reflections 10120 [R_int = 0.0313, R_sigma = 0.0467] Data/restraints/parameters 10120/1/446

Goodness-of-fit on F² 1.035

Final R indexes [1>=2σ (I)] Ri = 0.0291, wR₂ = 0.0588

Final R indexes [all data] Ri = 0.0322, wR₂ = 0.0606

Largest diff peak and hole 0.52/-0.45 e A^"3

Flack parameter -0.028(14) Structure of [Ru(ti⁵-C₅H₅)(PPh₃)₂(=C=CCF₃Ph)] [BF₄] [12] [BF₄] is illustrated in Figure 7

Identification code [12] [BF₄]

Empirical formula C₅iH₄₂BCl₂F₇P₂Ru

Formula weight 1032.56

Temperature 110.05(10) K

Crystal system orthorhombic

Space group Pbca

a 17.8473(4) A

b 14.6795(3) A

c 35.2252(16) A

a 90°

β 90°

Y 90°

Volume 9228.6(5) A³

Z 8

Calculated Density 1.486 mg/mm³

Absorption Coefficient 0.589 mm^"1

F(000) 4192.0

Crystal size 0.2616 0.1943 x 0.1582 mm³

Radiation ΜοΚα (λ = 0.71073)

2Θ range for data collection 5.822 to 60.072°

Index ranges -25 < h < 20, -20 < k < 12, -36 < 1 < 49 Reflections collected 28548

Independent reflections 13431 [R_int = 0.0322, R_sigma = 0.0537] Data/restraints/parameters 13431/0/597

Goodness-of-fit on F² 1.107

Final R indexes [1>=2σ (I)] Ri = 0.0471, wR₂ = 0.0826

Final R indexes [all data] Ri = 0.0631, wR₂ = 0.0896

Largest diff peak and hole 1.14/-1.02 e A^"3 Structure of [Ru -C₅H₅)(PPh₃)₂(-C(NC₅H₅)=C(C₆H₅)F)][BF₄] [15] [BF₄] is illustrated in Figure 11(b)

Identification code [15][BF₄]

Empirical formula C₅₄H₄₅BF₅ P₂RU

Formula weight 976.73

Temperature 109.8(6) K

Crystal system triclinic

Space group P-l

a 11.6304(5) A

b 13.5851(7) A

c 15.1453(9) A

a 72.589(5)°

β 89.929(4)°

y 79.010(4)°

Volume 2237.5(2) A³

Z 2

Calculated density 1.450 mg/mm³

Absorption Coefficient 0.482 mm^"1

F(000) 1000.0

Crystal size 0.1731 0.1338 ^χ 0.0366 mm³

Radiation ΜοΚα (λ = 0.71071)

2Theta range for data collection 6.166 to 63.606°

Index ranges -13 < h < 16, -20 < k < 14, -21 < 1 < 18

Reflections collected 20403

Independent reflections 13479 [R_int = 0.0280, R_sigma = 0.0514]

Data/restraints/parameters 13479/20/614

Goodness-of-fit on F² 1.033

Final R indexes [1>=2σ (I)] Ri = 0.0355, wR₂ = 0.0769

Final R indexes [all data] Ri = 0.0474, wR₂ = 0.0829

Largest diff peak and hole 0.63/-0.43 e A^"3 Structure of Rufo -C₃H_s)(PP ₃)₂{-C₅H₄ -C( C_sH_s)==C{C₆H₅)-) [16] [BF₄] is illustrated in Figure 11(c)

Identification code [16][BF₄]

Empirical formula C43 5H36 5BF4N2 5PRU

Formula weight 813.10

Temperature 110.05(10) K

Crystal system triclinic

Space group P-l

a 9.6081(8) A

b 17.9440(7) A

c 21.3274(10) A

a 99.508(4) ⁰

β 101.789(6) °

y 90.366(5) ⁰

Volume 3547.0(4) A³

Z 4

Calculated Density 1.523 mg/mm³

Absorption Coefficient 0.545 mm^"1

F(000) 1660.0

Crystal size 0.4117 0.2117 x 0.0261 mm³

Radiation ΜοΚα (λ = 0.71073)

2Θ range for data collection 5.83 to 56.652°

Index ranges -12 < h < 10, -23 < k < 23, -28 < 1 < 27

Reflections collected 16538

Independent reflections 16538 [R_sigma = 0.0777]

Data/restraints/parameters 16538/636/956

Goodness-of-fit on F² 0.951

Final R indexes [1>=2σ (I)] Ri = 0.0560, wR₂ = 0.1396

Final R indexes [all data] Ri = 0.0922, wR₂ = 0.1545

Largest diff peak and hole 1.34/-2.03 e A^"3 Structure of [Ru -C₅H₅)(PPh3)(C₅H4NCF₂C{C₆H4-4-CF3})] [BF4] [21][BF₄] is illustrated in Figure 9

Identification code [21] [BF₄]

Empirical formula C₃₇H₂₈BF₉ PRU

Formula weight 800.45

Temperature 110.05(10) K

Crystal system monoclinic

Space group Cc

a 14.5269(2) A

b 12.30582(14) A

c 19.9237(3) A

a 90.00°

β 113.8435(17)°

Y 90.00°

Volume 3257.69(8) A³

Z 4

Calculated Density 1.632 mg/mm³

Absorption Coefficient 0.612 mm^"1

F(000) 1608.0

Crystal size 0.2484 0.1618 x 0.0793 mm³

Radiation Mo Κα (λ = 0.7107)

2Θ range for data collection 5.56 to 57.6°

Index ranges -19 < h < 16, -15 < k < 15, -24 < 1 < 26 Reflections collected 12746

Independent reflections 6049[R(int) = 0.0255]

Data/restraints/parameters 6049/2/451

Goodness-of-fit on F² 1.045

Final R indexes [1>=2σ (I)] Ri = 0.0247, wR₂ = 0.0497

Final R indexes [all data] Ri = 0.0261, wR₂ = 0.0510

Largest diff peak and hole 0.29/-0.28 e A^"3

Flack parameter 0.001(15) References

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0442P.WO.Spec(3)

Claims

Claims

1. A method of fluorination of an alkenyl, alkynyl, aryl or isonitrile compound which comprises reacting an alkenyl, alkynyl, aryl or isonitrile compound with a metal-mediated outer-sphere electrophilic fluorinating (OSEF) agent.

2. A method according to claim 1 which comprises the formation of one or more bonds selected from a C-F bond, a C-S-F bond and a C-S-CF₃ bond.

3. A method according to claims 1 or 2 which comprises the formation of one or more C-F bonds.

4. A method according to any one of claims 1 to 3 which comprises the introduction of a single fluorine atom.

5. A method according to any one of claims 1 to 3 which involves the incorporation of multiple fluorine atoms.

6. A method according to claims 1 or 2 which comprises the formation of one or more C-CF₃ bonds.

7. A method according to claims 1, 2 or 6 which comprises the introduction of a single trifluoromethyl (-CF₃) group.

8. A method according to claims 1, 2 or 6 which involves the incorporation of multiple trifluoromethyl (-CF₃) groups.

9. A method according to claims 1 or 2 which comprises the formation of one or more C-S-F bonds.

10. A method according to claims 2 or 9 wherein the S represents S0₂.

11. A method according to claim 9 which comprises the formation of a single C-S-F bond.

12. A method according to claim 9 which comprises the formation of multiple C-S-F bonds.

13. A method according to claims 1 or 2 which comprises the formation of one or more C-S-CFs bonds.

14. A method according to claim 13 wherein the S represents S0₂.

15. A method according to claim 13 which comprises the formation of a single C-S-CF₃ bonds.

16. A method according to claim 13 which comprises the formation of multiple C-S-CF₃ bonds.

17. A method according to any one of the preceding claims wherein the bond formation is facilitated by metal-ligand in which the metal is capable of back donation or formal metal oxidation from the Mⁿ to the M⁽ⁿ⁺²⁾ oxidation state.

18. A method according to any one of the preceding claims wherein comprising direct outer-sphere electrophilic fluorination of a ligand bound to a metal centre.

19. A method according to any one of the preceding claims wherein the metal comprises iron or one or more Platinum Group Metals.

20. A method according to any one of the preceding claims wherein the metal is selected from the group comprising one or more of iron, iridium, osmium, palladium, platinum, rhodium and ruthenium.

21. A method according to any one of the preceding claims wherein the metal comprises ruthenium.

22. A method according to any one of the preceding claims wherein the metal is in the form of a metal complex comprising a metal and a "capping ligand" and one or more monovalent or neutral ligands.

23. A method according to claim 22 wherein the "capping ligand" is an aryl group.

24. A method according to claims 22 or 23 wherein the "capping ligand" is selected from the group consisting of C₅H₅, C₅Me₅, C6¾, C₇H₇, tris(pyrazolyl).

25. A method according to claim 22 wherein the one or more monovalent or neutral ligands is selected from the group consisting of -CO, -C0₂, phosphine, halide, -S(0)R⁴R⁵, in which R⁴ and R⁵, which may be the same or different, are each hydrogen, alkyl CI to 20 or aryl.

26. A method according to claims 22 or 25 wherein the one or more monovalent or neutral ligand comprises chloride.

27. A method according to claims 22 or 25 wherein the one or more monovalent or

1 2 3 1 2 3

neutral ligand comprises -PH₃ and -PR R R , in which R , R and R , which may be the same or different, are each alkyl CI to 20 or aryl.

28. A method according to any one of the preceding claims wherein the amount of the metal or metal complex is stoichiometric.

29. A method according to any one of claims 1 to 27 wherein the amount of the metal or metal complex is catalytic.

30. A method according to any one of the preceding claims wherein the outer-sphere electrophilic fluorinating (OSEF) agent is in the form of an organo metallic complex with a latent source of "F⁺", "CF₃ ⁺", "SCF₃ ⁺", or "S0₂CF₃ ⁺".

31. A method according to any one of the preceding claims wherein the outer-sphere electrophilic fluorinating (OSEF) agent is in the form of an organo metallic complex with a latent source of "F⁺" or "CF₃ ⁺".

32. A method according to claim 30 or 31 wherein the latent source of "F⁺" comprises an N-F fluorinating agent.

33. A method according to claims 30 to 32 wherein the latent source of "F⁺" comprises one or more of N-fluorosulfon/w/des, such as N-fluorobenzenesulfonimide (NFSI) and N- fluoro-o-benzenedisulfonimide ( FOBS); N- fluoropyridinium salts, including N- fluoropyridinium tetrafluoroborate ([C₅H₅ F][BF₄]), tri-alkyl pyridinium tetrafluoroborates, such as, l-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate ([2,4,6-Me₃C₅H₂ F][BF₄]), 1- fluoro-2,4,6-trimethylpyridinium trifluoromethanesulfonate, 2,6-dichloro- 1 - fluoropyridimnium trifluoromethanesulfonate or l-fluoro 2,6-dichloropyridinium tetrafluoroborate; l,4-diazabicyclo[2.2.2]octane (DABCO) bis(ammonium) ions, such as 1- chloromethyl-4-fluoro- 1 ,4-diazoniabicyclo [2.2.2] octane bis(tetrafluoroborate (Selectfluor®); and N-fluoro-N'-(chloromethyl)triethylenediamine bis(tetrafluoroborate).

34. A method according to any one of claims 30 to 33 wherein the organic compound is a strongly nucleophilic substrate and the latent source of "F⁺" comprises one or more of N- fluorosulfon/w/des, such as N-fluorobenzenesulfonimide (NFSI) and N-fluoro-o- benzenedisulfonimide (NFOBS); N- fluoropyridinium salts, including tri-alkyl pyridinium tetrafluoroborates, such as, l-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate ([2,4,6- Me₃C₅H₂NF][BF ]), l-fluoro-2,4,6-trimethylpyridinium trifluoromethanesulfonate, 2,6- dichloro- 1 -fluoropyridimnium trifluoromethanesulfonate or l-fluoro 2,6-dichloropyridinium tetrafluoroborate; l,4-diazabicyclo[2.2.2]octane (DABCO) bis(ammonium) ions, such as 1- chloromethyl-4-fluoro- 1 ,4-diazoniabicyclo [2.2.2] octane bis(tetrafluoroborate (Selectfluor®); and N-fluoro-N'-(chloromethyl)triethylenediamine bis(tetrafluoroborate).

35. A method according to claims 30 or 31 wherein the latent source of "CF₃ ⁺" comprises one or more of 5-(trifluoromethyl)dibenzothiophenium tetrafluoroborate, 5- (trifluoromethyl)dibenzothiophenium trifluoromethanesulfonate and 3, 3 -dimethyl- 1- (trifluoromethyl)- 1 ,2-benziodoxole.

36. A method according to claims 30, 31 or 35 wherein the latent source of "CF₃ ⁺" comprises 5-(trifluoromethyl)dibenzothiophenium tetrafluoroborate.

37. A method according to claim 46 wherein the latent source of "SCF₃ ⁺" comprises one or more of trifluoromethanesulfenylchloride, 2,2,2-trifluoro-,OS'-(trifluoromethyl) ester ethane(thioperoxoic) acid, 1, 1, 1 -trifluoro-N-methyl-N-phenyl-methanesulfenylamide, £/s(trifluoromethyl)disulfide, 1 , 3 -dihydro-3 , 3 -dimethyl- 1 - [(trifluoromethyl)thio] - 1 ,2- benziodoxole and 2-[(trifluoromethyl)thio]-lH-isoindole-l,3(2H)-dione.

38. A method according to claim 46 wherein the latent source of "S0₂CF₃ ⁺" comprises one or more of 1, 1, 1-trifluoro-, 1, 1 '-anhydride, 1, 1, 1-trifluoro-N-phenyl-N- [ (trifluoromethyl) sulfonyl] -methanesulfonic acid, trifluoro-methanesulfonylchloride.

39. A method according to any one of the preceding claims which comprises fluorinating an alkynyl compound.

40. A method according to any one of claims 1 to 36 which comprises fluorinating an alkenyl compound.

41. A method according to any one of claims 1 to 36 which comprises fluorinating an aryl compound.

42. A method according to any one of claims 1 to 36 which comprises fluorinating an isonitrile compound.

43. A method according to according to claim 39 which comprises fluorinating an alkynyl compound:

wherein [M] is metal-based complex, such as, [M^XI^XL²)] (M = Mn, Re, Fe, Ru, Os, Rh, Ir; L is a facially capping ligand such as C₅H₅, C₅Me₅, 0₆Η₆, C₇H₇, Tp, etc., L¹ = CO, phosphine, halide, L² = same ligand set as L¹ may be the same or different in each case); and R, is H, a carbon containing organic group, i.e. linear branched or cyclic groups, or a heteroatom (such as N, O, S etc.) with associated functional groups.

44. A method according to according to claims 39 or 43 which comprises:

wherein R is an aryl group or hydrogen.

45. A method according to according to claim 40 which comprises fluorinating an alkenyl compound:

wherein [M] is metal-based complex, such as, [M^XI^XL²)] (M = Mn, Re, Fe, Ru, Os, Rh, Ir; L is a facially capping ligand such as C₅H₅, C₅Me₅, 0₆Η₆, C₇H₇, Tp, etc., L¹ = CO, phosphine, halide, L² = same ligand set as L¹ may be the same or different in each case); and R, is H, a carbon containing organic group, i.e. linear, branched or cyclic groups, or a heteroatom (such as N, O, S etc.) with associated functional groups.

46. A method according to according to claims 40 or 45 wherein the substrate is selected from the group consisting of:

A method according to according to claim 41 which comprises one of the processes:

48. A compound comprising a fluorinated alkenyl, aryl or isonitrile compound prepared by reacting an alkenyl, alkynyl, aryl or isonitrile compound with a metal-mediated outer- sphere electrophilic fluorinating (OSEF) agent according to any one of the preceding claims.

49. A compound according to claim 48 wherein the compound is a fluorinated alkenyl compound.

50. A compound according to claim 49 wherein the compound is a fluorinated aryl compound.

51. A compound according to claim 48 wherein the compound is a fluorinated isonitrile compound.

I l l

52. A method or compound as hereinbefore described with reference to the accompanying description and figures.

0442P.WO.Spec(3)