Solvent- A nd anion-dependent rearrangement of fluorinated carbene ligands provides access to fluorinated alkenes

Article abstract of DOI:10.1039/c9dt04307a

The construction of fluorocarbene ligands within the coordination sphere of transition metal complexes using sequential nucleophilic and electrophilic addition to a vinylidene complex is described. Reaction of [Ru(η⁵-C₅H₅)(dppe)(CCPhF)][N(SO₂Ph)₂] with [NMe₄]F results in nucleophilic attack of fluoride at the metal-bound carbon of the vinylidene ligand to give alkenyl complex [Ru(η⁵-C₅H₅)(dppe)(-CFCFPh)]. Subsequent eletrophilic fluorination with N-fluorobenzenesulfonimide (NFSI) results in the formation of the fluorinated carbene complex [Ru(η⁵-C₅H₅)(dppe)(CF-CHFPh)][N(SO₂Ph)₂]. The fluorocarbene complexes undergo rearrangement to liberate free fluorinated alkenes, a process governed by the choice of solvent and anion, representing a new metal-mediated route to fluorinated alkenes from alkynes.

Full text of DOI:10.1039/c9dt04307a

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Solvent- and anion-dependent rearrangement of
fluorinated carbene ligands provides access to
fluorinated alkenes†
Cite this: Dalton Trans., 2019, 48,
17655
Lewis M. Hall, Lucy M. Milner, Sam J. Hart, Adrian C. Whitwood,
Jason M. Lynam * and John M. Slattery
*
The construction of fluorocarbene ligands within the coordination sphere of transition metal complexes
using sequential nucleophilic and electrophilic addition to a vinylidene complex is described. Reaction of
[Ru(η5-C5H5)(dppe)(vCvCPhF)][N(SO2Ph)2] with [NMe4]F results in nucleophilic attack of fluoride at the
metal-bound carbon of the vinylidene ligand to give alkenyl complex [Ru(η5-C5H5)(dppe)(–CFvCFPh)].
Subsequent eletrophilic fluorination with N-fluorobenzenesulfonimide (NFSI) results in the formation of
the fluorinated carbene complex [Ru(η5-C5H5)(dppe)(vCF–CHFPh)][N(SO2Ph)2]. The fluorocarbene com-
plexes undergo rearrangement to liberate free fluorinated alkenes, a process governed by the choice of
solvent and anion, representing a new metal-mediated route to fluorinated alkenes from alkynes.
Received 11th September 2019,
Accepted 7th November 2019
DOI: 10.1039/c9dt04307a
rsc.li/dalton
Therefore, the synthesis of complexes bearing fluorinated
carbene, carbyne and vinylidene ligands has significant poten-
Introduction
Organofluorine chemistry has huge economic and societal tial to underpin the development of novel synthetic processes
importance in fields such as pharmaceuticals, agrochemicals, in organofluorine chemistry.5 However, the synthesis of metal
materials science and refrigerants. The introduction of fluo- complexes containing these ligands can be difficult and unse-
rine into biologically active molecules can result in advan- lective.6 For example, the synthetic routes to the majority of
tageous changes in lipophilicity and greater metabolic stabi- fluorocarbene complexes prepared to date (Scheme 1a) involve
lity. Fluoroalkyl and fluoroaryl groups are common in medic- the addition or activation of a (per)fluorinated organic com-
inal and agrochemicals and,1 in this context, fluoroalkenyl pound to an organometallic species to give a fluoroalkyl
moieties are used as mimics for amide bonds.2,3 In addition, complex, which forms the carbene on reduction7–10 or though
the use of fluoroalkenyls as refrigerants is becoming increas- spontaneous fluoride elimination.11–13 Although these routes
ingly important because molecules such as 2,3,3,3-tetrafluoro- have proved to be insightful, the lack of a general approach
propene have considerably lower global warming potentials has entailed that there are far fewer fluoro-substituted com-
than both chlorofluorocarbons (CFCs) and hydrofluorocarbons pounds compared to the vast number of related Fischer
(HFCs). There is therefore a desire to develop efficient and carbene complexes with methoxy or amino groups.
selective synthetic methods to prepare organofluorine com-
pounds, including fluoroalkenes.
An alternative and potentially powerful approach is to use a
“bottom-up” approach, which exploits the more established
Transition-metal complexes can support ligands such as activation of hydrocarbon substrates and then employs the
carbenes, carbynes and vinylidenes, which are usually short- resulting species as templates to assemble the fluorinated
lived in the absence of the metal. Access to these species has ligands. This could be achieved by forming C–F bonds within
enabled the discovery of many important catalytic reactions the coordination sphere of a metal complex with either a
including alkene and alkyne metathesis as well as C–H nucleophilic (F−) or electrophilic (formally “F+”) reagent. In a
functionalisation.4
number of recent studies, we have demonstrated that outer-
sphere electrophilic fluorination (OSEF) may be used to form
fluorine-substituted carbenes [B]+ (Scheme 1b),14 vinylidenes,15
[D]+ and alkynyl ligands [E] (Scheme 1c),16 all of which employ
widely available terminal alkynes as precursors. It was envisaged
that the OSEF protocol could be exploited to assemble poly-
fluorinated ligands within the coordination sphere of the metal.
For example, the well-established electrophilicity of the metal-
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.
E-mail: jason.lynam@york.ac.uk, john.slattery@york.ac.uk
†Electronic supplementary information (ESI) available. CCDC 1952189 and
1952190. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c9dt04307a
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Fig. 1 Structures of the cations (a) [4a]+ and (b) [5a]+ determined by
single crystal X-ray diffraction. Thermal ellipsoids (where shown) at the
50% probability level. Hydrogen atoms, except for H(7AA), omitted for
clarity. Ruthenium shown in pink, phosphorus orange, fluorine green,
carbon grey. Selected bond lengths (Å) and angles (°) for [4a]+ Ru(1)–
C(1), 1.872(2); C(1)–C(2), 1.540(3); C(1)–F(1A), 1.370(3); C(2)–F(2),
1.373(2); C(2)–F(3), 1.367(2); Ru(1)–C(1)–C(2), 132.25(26); Ru(1)–C(1)–
F(1), 125.40(15); C(1)–C(2)–F(2), 107.02(17); C(1)–C(2)–F(3), 109.99(17);
C(2)–C(1)–F(2), 102.21(17); F(2)–C(2)–F(3), 105.40(17); [5a]+ Ru(1)–C(6),
1.8416(3); C(6)–C(7A), 1.371(13); C(6)–F(1A), 1.462(10); C(7A)–F(2A),
1.47(2); Ru(1)–C(6)–C(7A), 137.4(6); Ru(1)–C(6)–F(1A), 121.2(4); C(6)–
C(7A)–F(2A), 109.5(11); C(7A)–C(6)–F(1A), 100.0(7).
Scheme 1 (a) Previously reported fluorinated carbene complexes (b)
OSEF reaction of a pyridylidene complex (c) synthesis of a fluorinated
alkynyl ligand using OSEF (d) synthetic strategy used in this work.
bound carbon atom in vinylidene ligands17 may permit the for-
mation of C–F bonds through addition of fluoride. This reaction
would then result in the generation of a difluoroalkenyl ligand
which may in turn be subjected to an OSEF reaction to give a
fluorocarbene complex (Scheme 1d).
Results and discussion
Sonication of
a
THF solution of [Ru(η5-C5H5)(dppe)
(vCvCPhF)][N(SO2Ph)2], [1a][N(SO2Ph)2] and four equivalents
of [NMe4]F resulted in the formation of a 1 : 1 mixture of E-
and Z-isomers of fluoroalkenyl complex [2a] (Scheme 2). The
Z-isomer was characterised on the basis of resonances in the
3
3
3
19F (δ −83.0, dt, JFF = 113 Hz JPF 28 Hz; δ −107.3, dt, JFF
=
=
113 Hz, JPF = 3 Hz) and 31P (δ 92.8, dd JPF = 28 Hz, JPF
4
3
4
3 Hz) NMR spectra. Resonances in the 13C{1H} NMR spectrum
1
3
2
at δ 188.2 (ddt JCF = 294 Hz, JCF = 89 Hz, JCP = 19 Hz) and
1
3
δ 158.8 (dd JCF = 198 Hz, JCF = 51 Hz) were assigned to the
α- and β-carbon atoms of the alkenyl ligand respectively. The
E-isomer exhibited a similar spectroscopic features but with a
Scheme 2 Synthesis of complexes with fluorinated alkenyl, [2a], and
carbene, [4a]+, ligands through successive nucleophilic and electrophilic
fluorination.
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3
smaller JFF coupling constant (10 Hz) as expected for two
mutually cis fluorine atoms.18
Metal complexes containing fluorinated alkenyl ligands
may be prepared from fluoroalkenes by oxidative addition and
transmetallation,19 or through C–H and C–F activation strat-
egies.20 However, the only other method for preparing these
ligands from non-fluorinated organic precursors involves the
electrophilic fluorination of a coordinated alkyne.21,22
By using TREAT·HF (Et3N·3HF) as the F− source it was poss-
ible to control the stereochemistry of this reaction, resulting in
the selective formation of Z-[2a] from [1a][N(SO2Ph)2], in d8-
THF solution. Treatment of the PPh3-containing complex [Ru
(η5-C5H5)(PPh3)2(vCvCPhF)][N(SO2Ph)2] [1b][N(SO2Ph)2] with
TREAT·HF resulted in the formation of both Z-[2b] and pre-
viously described [3b] (Scheme 2),15 which arises from C–H
bond activation of a PPh3 ligand. To avoid this side-reaction,
dppe-substituted complexes were used in subsequent studies.
In addition, [NMe4]F was used as the fluoride source since [2a]
could be isolated more readily in these cases: the resulting
chemistry was unaffected by using a mixture of E- and
Z-isomers of [2a].
By analogy to the reaction in Scheme 1b, it was anticipated
that addition of “F+” to [2a] would give a fluorine-substituted
carbene complex via OSEF. Addition of NFSI to a CH2Cl2 solu-
tion of [2a] resulted in a colour change from yellow to green and
formation of complex [4a][N(SO2Ph)2] (Scheme 2). The presence
of the carbene ligand was confirmed by NMR spectroscopy,
Scheme 3 Reaction of complex [2a] with HCl·Et2O to give [6a] and 7
(top). Photolysis of [2a] in CD2Cl2 solution (bottom).
which showed a low-field resonance in the 19F NMR spectrum on the β-carbon of the carbene ligand breaks the mirror sym-
for the CF group at δ 113.6 (tt, 1F, JFP = 33 Hz, JFF = 12 Hz) as metry of the molecule. The structure of cation24 [5a]+ was also
well as a related resonance for the CF2 group at δ −90.3 (d, 2F, confirmed by single-crystal X-ray diffraction (Fig. 1b). In a
3JFF = 11 Hz). A characteristic carbene resonance at δ 284.6 (d, similar fashion to [4a]+, the RuvC bond length is much shorter
3
3
1JCF = 399 Hz) was observed in the 13C{1H} NMR spectrum.
The single-crystal X-ray structure of [4a]PF6 (obtained by
(1.8416(3) Å) than in related methoxycarbene complexes.
The reaction of [2a] with HCl·Et2O showed a remarkable
salt metathesis from [4a][N(SO2Ph)2]) (Fig. 1a) confirmed the solvent dependence. Performing the reaction under identical
presence of the fluorocarbene ligand. The RuvC bond length, conditions, but substituting CD2Cl2 for THF did not afford [5a]
1.872(2) Å is significantly shorter than those in related Fischer Cl. Instead, rapid formation of [RuCl(η5-C5H5)(dppe)] [6a]
carbene complexes (e.g. the RuvC bond length in [Ru(η5- occurred with concomitant generation of the fluorinated alkene
C5H5)(dppe)(vC{OMe}CH2CO2Me)][PF6] is 1.933(4) Å).23 When E-7 which was identified on the basis of characteristic reso-
compared to fluorine, the methoxy group is a better π-donor to nances in the 19F NMR spectrum at δ −170.5 (dd, 3JFF = 125 Hz,
the carbene carbon due to closer orbital size matching and 3JHF = 6 Hz) and δ −177.6 (dd, 3JFF = 125 Hz, 2JHF = 75 Hz).
lower electronegativity. As a consequence, the methoxycarbene
The stereochemical outcome of this reaction gave some
complexes show less π-back-donation from the metal and insight into the potential mechanism of formation of 7. A 1 : 1
hence a longer MvC bond. A similar effect is observed in com- ratio of E- and Z-isomers of [2a] was used, as [Me4N]F was the
plexes such as [Ir(η5-C5Me5)(PMe3)(vCFCF2CF3)], which has a F− source for [2a] synthesis. Thus, the observation of only E-7,
IrvC bond length of 1.864(6) Å.10
on protonation implied that the mechanism does not involve
Given the successful electrophilic fluorination of [2a], its simple M–C bond protonolysis and that carbene [5a]+ was a
reaction with alternative electrophiles was explored in order to likely intermediate. Indeed, dissolution of [5a]Cl in THF
provide access to hydrofluorocarbene complexes. Treatment of resulted in immediate conversion to [6a] and E-7 (Scheme 3).
[2a] with HCl·Et2O in CD2Cl2 solution resulted in the for- In order to probe the effect of the anion on this process, [5a]
mation of [5a]Cl (Scheme 3). NMR spectroscopy clearly showed BF4 was prepared by reaction of [2a] with HBF4·OEt2 in CD2Cl2
the presence of a hydrofluorocarbene ligand with resonances solution (Scheme 3). In contrast to the chloride salt, dis-
in the 19F NMR spectrum for the CF group at δ 115.9 (dddd, 1F, solution of [5a]BF4 in THF solution did not result in any reac-
3JFF = 46, 3JPF = 43, 3JPF = 27, 3JHF = 8 Hz); and the CHF group at tion. However, addition of [nBu4N]Cl to a d8-THF solution of
2
3
δ −162.9 (apparent t, JHF = 46, JFF = 46 Hz). The 31P{1H} NMR [5a]BF4 resulted in rapid (<10 min) formation of [6a] and E-7.
spectrum exhibited two resonances at δ 84.6 and 89.5 with a
These data support a mechanistic picture (Scheme 4) in
mutual 19 Hz coupling, as the creation of a stereogenic centre which [5a]+ is formed by kinetically controlled protonation at
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Scheme 5 Reaction of complex [1a][N(SO2Ph)2] and [1b]BF4 with
HCl·Et2O in CD2Cl2 to give [11a]+ and [11b]+ respectively and in THF to
give [6a] and E-12.
Scheme 4 Reaction of complex [2a] with HCl·Et2O to give [6a] and 7
(top). Photolysis of [2a] in CD2Cl2 solution (bottom).
on exposure of the compounds to vacuum. In THF solution (or
with THF added to a CD2Cl2 solution), the reaction of [1a][N
(SO2Ph)2] with HCl results in formation of the free E-H(Cl)
CvC(F)Ph (12) and [6a] demonstrating that it was possible to
access tetra-substituted alkenes through this method.
the β-carbon of the alkenyl ligand of [2a]. The formation of
[6a] and E-7, which are presumably the thermodynamic pro-
ducts from the reaction, involves formal proton migration in
[5a]+. The solvent and anion dependence of this process may
be rationalised on the basis of an intermolecular deprotona-
tion/protonation pathway for proton migration, in which the
solvent-dependent pKa of HCl shifts the position of equili-
Conclusions
In conclusion, stepwise addition of nucleophiles and electro-
philes to ruthenium fluorovinylidene complexes results in the
rapid and selective formation of novel fluoroalkenyl and fluor-
ocarbene complexes. Fluorocarbene ligand rearrangement to
liberate free fluoroalkenes can be promoted by appropriate
brium between [5a]+ and
a
putative intermediate [8a]+
(Scheme 4a), prior to displacement of the alkene. The chloride
anion may be required to displace the alkene in [8a]+ and
provide a thermodynamic driving force for the reaction
through formation of the stable complex [6a].
solvent and anion selection through
a proton-migration
pathway. The new metal–ligand reactivity that allows for
unusual fluorinated ligand systems to be constructed in a
rational and controlled way from non-fluorinated substrates.
Further evidence for the key role of proton migration in the
formation of E-7 comes from the behaviour of the CF2Ph-sub-
stituted carbene complex [4a][N(SO2Ph)2]. Dissolution of this
complex in THF, with or without [nBu4N]Cl, resulted in no
fluoroalkene, F2CvC(F)Ph, formation, indicating that neither
fluorine nor phenyl migration occur under these conditions.
Fluoroalkenes may be displaced from [2a] by irradiation of
a CD2Cl2 solution of the complex (λ > 290 nm) for two hours.
Under these conditions, the formation of [6a], F2CvC(F)Ph (9)
and the chlorofluoroalkenes E- and Z-Cl(F)CvC(F)Ph (10) was
observed. However, this reaction was unselective, and a
number of other unidentified products were also detected. The
chlorofluoroalkene 10 presumably forms via the photochemi-
cal generation of chlorine atoms which then react with [2a].
A rational synthesis of mixed Cl/F-substituted alkenes is
also possible. Reaction of [1a][N(SO2Ph)2] or [1b]BF4 with HCl
in CD2Cl2 solution gave chlorine-substituted carbene com-
plexes [11a][N(SO2Ph)2] and [11b]BF4 respectively (Scheme 5).
This reaction is readily reversible: elimination of HCl occurs
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We are grateful to the EPSRC (studentship to LMM) and
University of York (studentship to LMH) for funding.
Notes and references
1 T. Besset, T. Poisson and X. Pannecoucke, Chem. – Eur. J.,
2014, 20, 16830–16845.
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2 H. Sakaguchi, Y. Uetake, M. Ohashi, T. Niwa, S. Ogoshi and 14 L. M. Milner, N. E. Pridmore, A. C. Whitwood, J. M. Lynam
T.
Hosoya,
J.
Am.
Chem.
Soc.,
2017,
139,
and J. M. Slattery, J. Am. Chem. Soc., 2015, 137, 10753–10759.
15 L. M. Milner, L. M. Hall, N. E. Pridmore, M. K. Skeats,
A. C. Whitwood, J. M. Lynam and J. M. Slattery, Dalton
Trans., 2016, 45, 1717–1726.
12855–12862.
3 S. Couve-Bonnaire, D. Cahard and X. Pannecoucke, Org.
Biomol. Chem., 2007, 5, 1151–1157.
4 D. G. Johnson, J. M. Lynam, N. S. Mistry, J. M. Slattery, 16 L. M. Hall, D. P. Tew, N. E. Pridmore, A. C. Whitwood,
R. J. Thatcher and A. C. Whitwood, J. Am. Chem. Soc., 2013,
135, 2222–2234.
J. M. Lynam and J. M. Slattery, Angew. Chem., Int. Ed., 2017,
56, 7551–7556.
5 R. P. Hughes, Eur. J. Inorg. Chem., 2009, 2009, 4591–4606.
17 J. M. Lynam, Chem. – Eur. J., 2010, 16, 8238–8247.
6 M. E. Slaney, M. J. Ferguson, R. McDonald and M. Cowie, 18 M. A. Cairns, K. R. Dixon and G. A. Rivett, J. Organomet.
Organometallics, 2012, 31, 1384–1396. Chem., 1979, 171, 373–385.
7 D. J. Harrison, S. I. Gorelsky, G. M. Lee, I. Korobkov and 19 A. K. Brisdon and K. K. Banger, J. Fluorine Chem., 1999,
R. T. Baker, Organometallics, 2013, 32, 12–15. 100, 35–43.
8 D. J. Harrison, G. M. Lee, M. C. Leclerc, I. Korobkov and 20 M. Talavera, C. N. von Hahmann, R. Müller, M. Ahrens,
R. T. Baker, J. Am. Chem. Soc., 2013, 135, 18296–18299.
9 R. P. Hughes, R. B. Laritchev, J. Yuan, J. A. Golen,
M. Kaupp and T. Braun, Angew. Chem., Int. Ed., 2019, 58,
10688–10692.
A. N. Rucker and A. L. Rheingold, J. Am. Chem. Soc., 2005, 21 J. Berger, T. Braun, T. Ahrens, P. Kläring, R. Laubenstein
127, 15020–15021. and B. Braun-Cula, Chem. – Eur. J., 2017, 23, 8886–8900.
10 J. Yuan, C. J. Bourgeois, A. L. Rheingold and R. P. Hughes, 22 J. Berger, T. Braun, R. Herrmann and B. Braun, Dalton
Dalton Trans., 2015, 44, 19528–19542. Trans., 2015, 44, 19553–19565.
11 G. R. Clark, S. V. Hoskins, T. C. Jones and W. R. Roper, 23 J. H. Bowie, M. I. Bruce, M. A. Buntine, A. S. Gentleman,
J. Chem. Soc., Chem. Commun., 1983, 719–721.
12 G. M. Lee, D. J. Harrison, I. Korobkov and R. T. Baker,
Chem. Commun., 2014, 50, 1128–1130.
D. C. Graham, P. J. Low, G. F. Metha, C. Mitchell,
C. R. Parker, B. W. Skelton and A. H. White,
Organometallics, 2012, 31, 5262–5273.
13 C. J. Pell, Y. Zhu, R. Huacuja, D. E. Herbert, R. P. Hughes 24 The crystal obtained was a mixture of [1a]+ and [5a]+
and O. V. Ozerov, Chem. Sci., 2017, 8, 3178–3186.
cations as well as [PF6]− and [SiF5]− anions.
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