Utilising Sodium-Mediated Ferration for Regioselective Functionalisation of Fluoroarenes via C?H and C?F Bond Activations

Article abstract of DOI:10.1002/anie.201709750

Pairing iron bis(amide) Fe(HMDS)₂ with Na(HMDS) to form new sodium ferrate base [(dioxane)_0.5?NaFe(HMDS)₃] (1) enables regioselective mono and di-ferration (via direct Fe?H exchange) of a wide range of fluoroaromatic substrates under mild reaction conditions. Trapping of several ferrated intermediates has provided key insight into how synchronised Na/Fe cooperation operates in these transformations. Furthermore, using excess 1 at 80 °C switches on a remarkable cascade process inducing the collective twofold C?H/threefold C?F bond activations, where each C?H bond is transformed to a C?Fe bond whereas each C?F bond is transformed into a C?N bond.

Full text of DOI:10.1002/anie.201709750

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
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Accepted Article
Title: Utilising Sodium-Mediated Ferration for Regioselective
Functionalisation of Fluoroarenes via C-H and C-F Bond
Activations
Authors: Eva Hevia, Lewis C. H. Maddock, Tracy Nixon, Alan R
Kennedy, Michael R Probert, and William Clegg
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201709750
Angew. Chem. 10.1002/ange.201709750
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10.1002/anie.201709750
Angewandte Chemie International Edition
COMMUNICATION
Utilising Sodium-Mediated Ferration for Regioselective
Functionalisation of Fluoroarenes via C-H and C-F Bond
Activations
Lewis C. H. Maddock,[a] Tracy Nixon,[a] Alan R. Kennedy,[a] Michael R. Probert,[b] William Clegg,[b] and
Eva Hevia*[a]
Abstract: Pairing iron bis(amide) Fe(HMDS)2 with Na(HMDS) to
form new sodium ferrate base [(dioxane)0.5·NaFe(HMDS)3] (1)
enables regioselective mono and di-ferration (via direct Fe-H
exchange) of a wide range of fluoroaromatic substrates under mild
reaction conditions. Trapping of several ferrated intermediates has
provided key insight into how synchronised Na/Fe cooperation
operates in these transformations. Furthermore using excess 1 at
80oC switches on a remarkable cascade process inducing the
collective 2-fold C-H/3-fold C-F bond activations, where each C-H
bond is transformed to a C-Fe bond whereas each C-F bond is
transformed into a C-N bond.
its sodium congener, we disclose (i) a new methodology for
regioselective functionalisation of fluoroarenes which occurs via
direct ferration of these aromatic scaffolds, and (ii) an
unprecedented ate-mediated C-F bond activation process for C-
N bond conversion.
While naturally occurring fluoroarenes are rare, synthetic forms
are extremely valuable building blocks. Thus developing
methods allowing the incorporation of these units into more
complex molecular scaffolds is highly important.[8] Interestingly,
deprotonation of these molecules via organolithium bases still
remains a challenge, primarily due to the exceptionally fragile
stability of generated intermediates, which even at cryogenic
conditions can eliminate LiF, to form benzyne intermediates as
well as engaging in complex cascade processes involving
autometallation.[9] Also, even when low polarity metallators are
used, fluoride elimination cannot be halted as shown recently by
our group on alumination of fluoroarenes using trans-metal-
trapping Li/Al combinations, where metallated products
decompose at room temperature.[10]
Attracted by low cost, high natural abundance and low toxicity of
the metal, organoiron chemistry continues to expand as
increasing focus is directed towards sustainable practices.
Though iron complexes have demonstrated proficiency in a
myriad of cornerstone organic bond forming transformations
under both stoichiometric and catalytic regimes, an area that
remains surprisingly scant is deprotonative metallation.[1] Metal-
hydrogen exchange (metallation) is one of the World’s most
practiced reactions.[2] Alkyllithium or lithium amide reagents
dominated metallation for decades, but recently new bimetallic
systems have gained prominence as more efficient, more
chemoselective alternatives.[3] Only limited advances have been
made in direct ferration of aromatic molecules. For example,
Mongin used an in situ 1:3, FeBr2:LiTMP stoichiometry for
ferration of substituted pyridines, though Fe(II)/Fe(III) or
Fe(II)/Fe(IV) couples were proposed to interfere, leading to
homocoupling side reactions.[4] Knochel similarly prepared
trimetallic (TMP)2Fe·2MgCl2·4LiCl in situ to ferrate a range of
functionalised arenes to form diaryl Fe(II) compounds.[5]
Significantly, the identities of the iron intermediates involved in
this challenging chemistry were not identified. A case where
structural elucidation proved possible was Mulvey’s
regioselective 2-fold ferration of benzene at the 1,4-positions by
the sodium ferrate [(TMEDA)NaFe(TMP)2(CH2SiMe3)], which
affords an iron-host inverse crown complex.[6]
F
SiMe3
Me3Si
Na
Me3Si
SiMe3
SiMe3
SiMe3
N
N
N
SiMe3
SiMe3
D
Na
F
Fe
N
Fe
N
D
D
F
RT, 12h,
benzene
F
Me3Si
SiMe3
1
D = 1,4-dioxane
2
I2
F
F
)
3 2
Fe{N(SiMe3)2}2
iMe
N(S
Na
I
3a
(84%)
X
X
F
Scheme 1. Sodium-mediated ferration of 1,3-difluorobenzene by
F
[(dioxane)0.5NaFe(HMDS)3] (1)
We started the study by preparing the sodium tris(amido)ferrate
[(dioxane)0.5·NaFe(HMDS)3] (1) in an isolated crystalline yield of
64% by co-complexing Na(HMDS), Fe(HMDS)2 and dioxane
from a 1:1:1 mixture in benzene.[11] X-ray crystallography
confirmed the bimetallic constitution of 1, made up by two
{NaFe(HMDS)3} fragments connected via a Na-dioxane-Na
bridge (see SI for details). Reacting 1,3-difluorobenzene with
equimolar 1 at room temperature effected a colour change from
a green to brown solution. Cooling this solution afforded
heteroleptic [(dioxane)·NaFe(HMDS)2(1,3-F2-C6H3)] (2) in 67%
yield. In 2 the aromatic substrate is metallated at its C2 position
between the F substituents. Electrophilic interception of 2 with
iodine affords 1,3-difluoro-2-iodobenzene 3a in 84% yield
(Scheme 1).
While iron bis-amide, Fe(HMDS)2 [HMDS = N(SiMe3)2], has
been reported as a useful precursor to access low-coordinate Fe
complexes,[7] the low polarity of its Fe-N bonds makes it, a priori,
unsuitable for C-H metallation applications. Breaking new
ground in this field, by pairing this seemingly toothless base with
[a]
Dr. L.C. H. Maddock, Dr. T. Nixon, Dr. A. R. Kennedy, Prof. E. Hevia
WestCHEM, Department of Pure and Applied Chemistry
University of Strathclyde
295 Cathedral Street, Glasgow, G1 1XL (UK)
E-mail :eva.hevia@strath.ac.uk
In 2 Fe forms a  bond at the 2-position of the aromatic ligand
[Fe-C14, 2.1157(18) Å]; whereas Na interacts with one F [Na-F1,
2.3437(13) Å] (Fig 1).[12] Both metals are also connected by an
[b]
Dr. M. R. Probert, Prof. W. Clegg
Chemistry, School of Natural and Environmental Sciences,
Newcastle University, Newcastle upon Tyne, NE1 7RU, UK
Supporting information for this article is given via a link at the end of
the document
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10.1002/anie.201709750
Angewandte Chemie International Edition
COMMUNICATION
HMDS bridge. Fe completes its coordination sphere by bonding
−100oC, where competition studies between this substrate and
to a terminal HMDS, while Na is solvated by two dioxane fluorobenzene show a clear preference for the former.[18]
molecules.
Table 1 Ferration of fluoroarenes using sodium ferrate 1.[a]
Emphasising the cooperativity between sodium and iron inherent
in the reactivity of mixed-metal base 1, neither homometallic
Na(HMDS) or Fe(HMDS)2 on their own can deprotonate 1,3-
difluorobenzene (Scheme 1). Thus 2 can be regarded as a
product of sodium-mediated ferration, with Fe actioning the
deprotonation, but sodium being essential for this reaction to
occur. Interestingly, it should also be noted that ferrated
intermediate 2 is remarkably robust and does not decompose
even when refluxed in C6D6 at 80°C for 24h.
F
F
I
(i) [(dioxane)0.5NaFe{N(SiMe3)2}3] (1)
16 h, benzene, T
(ii) I2
FG
I
FG
I
F
F
I
F
I
F
F
F
F
F
OCH3
3b
3c
3d
3e
(50oC, 74%)[b] (0oC, 58%)[c]
(50oC, 78%
)
(RT, 80%)
I
I
I
I
F
F
I
F
F
F
F
F
Br
F
F
F
Br
F
I
Br
3f
F
3g
(RT, 91%)
3i
3h
(RT, 85%)[d]
(0oC, 80%)
(0oC, 68%)[c,d]
I
I
I
F
F
F
F
F
F
OMe
CN
I
Figure 1 Monomeric, dinuclear structure of ferrate 2 with H atoms omitted for
clarity and displacement ellipsoids displayed at 50% probability level.
3k
(50oC, 45%)[c,e]
3l
3j
(50oC,40%)[f]
(RT, 88%)[d]
[a]
Reactions carried out with in situ prepared 1 in benzene. Unless otherwise
stated, stoichiometric amounts of base and substrate and a five molar excess
of iodine were used (see SI for details). Yields are of isolated products, see SI
Encouraged by this initial reactivity, we extended this approach
to a range of fluoroaromatic substrates. Reactions were carried
out in benzene, allowing mixtures to stir overnight prior to I2
quenching (Table 1). Each metallation occurred at a position
adjacent to at least one fluorine atom, affording iodo-
fluoroarenes 3b-l in good to excellent yields (40-91%). While
Holland has reported that Fe(II) complexes can promote C-F
bond activation processes when treated with perfluorinated
arenes,[13] here, selective Fe-H exchange reactions are
observed. This C-H chemoselectivity also contrasts with
previous studies using Fe(0) systems where C-F bond activation
is usually preferred.[14] Consistent with the different degree of C-
[b]
[c]
for details.
Fluorobenzene was used as solvent in the reaction.
Yield
[d]
determined by 1H NMR using ferrocene as internal standard. Carried out
using 2 equivalents of 1. [e] 5 days, using 2 equivalents of 1. [f] 2 days.
To shed more light on these intriguing findings, we next
investigated key metallated intermediates 4a and 4b (Fig. 2),
resulting from diferration of 1,3,5-trifluorobenzene and 1,2,4,5-
tetrafluorobenzene prior to electrophilic interception.
H
bond activation in the fluoroarenes studied,[15] those
substrates with only one F atom required harsher reaction
conditions (50oC) (3b, 3e, 3k and 3l in Table 1, 40-74% yields),
whereas other Fe-H exchanges occur at RT or 0°C (3c, 3d and
3f-3i in Table 1, yields 58-91%). Interestingly, even in substrates
possessing other ortho-directing groups such as 4-fluoroanisole
or 4-fluorobenzonitrile, ortho-metallation at the F substituent is
preferred (3k and 3l in Table 1). These regioselectivities are
opposite to those reported for lithiation of 4-fluoroanisole by
nBuLi in THF at −78°C[16] or for 4-fluorobenzonitrile using related
heterobimetallic (TMP)2Fe·2MgCl2·4LiCl.[5] Contrasting with
many lithiation reactions, where excess metallating reagent
leads to complex mixtures of products,[17] here stoichiometric
control is seen as two equivalents of 1 regioselectively di-ferrate
1,3,5-trifluorobenzene, 1,4-dibromo-2,5-difluorobenzene and
1,2,5,6-tetrafluorobenzene, furnishing 3h, 3i and 3j in 68, 85 and
88% yields respectively.
Figure 2 Molecular structures of complexes 4a (left) and 4b (right). Hydrogen
atoms (except H4 in 4a), minor disorder at one SiMe3 in 4b and a molecule of
co-crystallised benzene solvent in 4a are omitted for clarity. Displacement
ellipsoids displayed at 30% probability level.[19]
Both structures bear a strong resemblance to that of 2, with the
Fe centres occupying positions previously filled by H atoms
(mean Fe-C distance, 2.110 and 2.134 Å for 4a and 4b
respectively), whereas each Na atom binds datively with one F
at the ortho positions (mean Na-F distance, 2.335 and 2.297 Å
for 4a and 4b respectively). The distinct bonding preferences of
Fe and Na in these structures, tying up C and F lone pairs
respectively, must contribute to the unusual room temperature
stability of these potentially hypersensitive fluoroaryl dianions.
Steric stabilization of the Fe-C bonds via the bulky HMDS
Interestingly, 1 failed to react with related chloroarenes, which
also contain relatively activated H’s, such as 1,3
dichlorobenzene, even under harsh conditions (50°C, 24h). This
s
lack of reactivity contrasts with Schlosser’s work using BuLi at
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10.1002/anie.201709750
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groups is presumably another factor. As far as we can ascertain,
4a represents the first structurally defined example of
dimetallation of 1,3,5-trifluorobenzene whereas for 1,2,4,5-
tetrafluorobenzene only two examples have been reported,
though neither were made via direct metal-H reactions.[20]
Previous studies of heterobimetallic amide bases such as alkali-
metal zincates have shown that metallation regioselectivities can
be influenced by coordination of the substrate to the alkali-metal
prior to the metallation step.[21] A similar scenario could be
envisaged here, where initially the fluoroarene could coordinate
to Na in 1 via a dative Na-F bond similar to those seen in 2, 4a
and 4b, bringing its adjacent H into close proximity to the
anionically-activated ferrate {Fe(HMDS)3} moiety, priming the
intramolecular Fe-H exchange. Na···F interactions could
therefore hold the key to the ortho-F selectivity/reactivity
witnessed for all substrates studied (vide supra), whereas lack of
such interactions could be a factor in the inertness of 1 with
chloroarenes.
Exploring the ferrating limits of 1, we next pondered if the three
H atoms in 1,3,5-trifluorobenzene are exchangeable by Fe
centres. Thus reacting the fluoroarene with excess 1 at 80°C
(Scheme 2) gave a solution colour change from green to dark
yellow and the formation of a precipitate. Cooling this solution
gave yellow crystals of unimetallic iron complex [1,3-
{Fe(HMDS)}2-2,4,6-(HMDS)2-C6H] (5a) in 87% yield, where the
fluoroarene has undergone an extraordinary 2-fold C-H/3-fold C-
F activation, five bond-breaking process (Scheme 2).[22] This
approach could also be extended to 1,2,3,5-tetrafluorobenzene
magnetic properties.[23] As far as we can ascertain 5a-5c are the
first dinuclear systems containing two pseudo-linear Fe centres
to be structurally defined.
Figure 3 Molecular structure of 5a. Hydrogen atoms (except H4) are omitted
for clarity. Displacement ellipsoids displayed at 50% probability level.
While C-F bond activation of fluoroarenes by transition metals
has been much investigated, to date, iron has shown limited
promise in this area.[8,12,14] It should also be noted that methods
for C-F/C-N conversion are scarce, confined mainly to
nucleophilic aromatic substitution of activated fluoro-
aromatics.[24] Here, the synergic power of this Na/Fe bimetallic
partnership allows conversion of three C-F fluoroarene bonds
into three new C-N bonds as well as two direct Fe-H exchanges
(Scheme 2). Filtrate analysis from the reaction of 1,3,5-
trifluorobenzene and 3 equivalents of 2 showed the presence of
Fe(HMDS)2·(dioxane) complex and HMDS(H), while formation of
precipitated NaF was confirmed by 19F NMR in D2O.
Furthermore, it was found that 5a can also be prepared in
excellent yield (90-95%) by treating diferrated product 4a with
one equivalent of sodium ferrate 1 or just one equivalent of
Na(HMDS) at 80°C. Even more revealing, heating 4a on its own
in benzene for over an hour at 80°C also furnished 5a albeit in a
significantly lower yield (58%).
and
1-bromo-2,4,6-trifluorobenzene,
furnishing
bis(iron)
compounds 5b and 5c (Scheme 2).
Me3Si SiMe3
F
Me3Si
SiMe3
SiMe3
N
N
N
H
H
[(D)0.5NaFe{N(SiMe3)2}3] (1)
Me3Si
Fe
Fe
3 eq, 80oC, 1h
F
F
SiMe3
- 3 NaF, -Fe{N(SiMe3)2}2
(D= 1,4-dioxane)
Me3Si
N
Me3Si
N
X
SiMe3
X
While this type of reactivity is unprecedented in transition-metal
chemistry, Schlosser reported the conversion of 1,3,5-
trifluorobenzene into 1,3,5-tris(tert-butyl)benzene using excess
tBuLi via dilithiated aryl intermediates.[9] Reflecting on that and
our experimental findings, we propose that C-F bond activation
products 5 form as a consequence of a cascade process, which
takes place at 80°C. In a first step, differration of the fluoroaryl
(e.g. 1,3,5-trifluorobenzene in Scheme 3) by 2 equivalents of 1
will occur to form sodium ferrate 4a. While this compound is
stable at room temperature (vide supra), at 80oC it reacts to give
5a, via an unstoppable domino of alternating NaF and
Fe(HMDS)2 eliminations and subsequent Fe(HMDS)2 additions
to benzyne intermediates. The existing Na…F contacts in 4a
may contribute to facilitate the activation of the relevant C-F
bonds under these reaction conditions.[25] Each diferrated
intermediate should be less stable than its precursor (III>II>I>4a
in Scheme 3), as this fast sequence of reactions does not stop
until the three F atoms are replaced by HMDS groups, affording
5a, where now the low-coordinate Fe centres are protected by
bulky HMDS groups on the aryl ring.[26] It should be noted that to
facilitate the last NaF/ Fe(HMDS)2 elimination step (III→5a,
Scheme 3), requires co-complexation of II with one Na(HMDS)
equivalent. The sodium amide can be provided by a third
X= H, 5a (87%); X= F, 5b (47%);
X= Br, 5c (46%)
Scheme 2. Two-fold C-H/ three-fold C-F activation processes of 1,3,5
trifluorobenzenes.
The molecular structures of 5a-c were established by X-ray
crystallographic studies (see SI for full details and Fig. 3 for 5a).
Since 5a-c are isostructural, only 5a is discussed. Containing a
1,3-diferrated-pentasubstituted aryl ring, where each F atom of
1,3,5-trifluorobenzene has been replaced by HMDS, 5a displays
two low-coordinate Fe centres, each bonded to one C of the
aromatic ring (mean Fe-C distance, 2.024 Å) and a terminal
HMDS, adopting an unusual near-linear coordination (with C-Fe-
N bond angles of 159.43(1) and 161.06(12)° for Fe1 and Fe2
respectively). Each Fe also forms a long-range contact with a
neighboring HMDS attached to the aryl ring (mean
Fe···N(HMDS)ring, 2.389 Å). While these contacts are notably
more elongated than those observed for HMDS groups directly
attached to Fe (mean Fe-N distance, 1.919 Å), they are
significant enough to induce the distortion from linearity
observed in the Fe geometries. It should be noted that two-
coordinate iron (II) complexes are scarce in coordination
chemistry, although they have already demonstrated unique
equivalent of
1
(which explains the detection of
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10.1002/anie.201709750
Angewandte Chemie International Edition
COMMUNICATION
[6]
[7]
P. Albores, L. M. Carella, W. Clegg, P. Garcia-Alvarez, A. R. Kennedy,
J. Klett, R. E. Mulvey, E. Rentschler, L. Russo, Angew. Chem. 2009,
121, 3231; Angew. Chem. Int. Ed. 2009, 48, 3317.
Fe(HMDS)2·(dioxane) complex with three equivalents of 1), by
some unreacted 4a or by adding an extra equivalent of
Na(HMDS) to 4a. Interestingly, contrasting with these results,
when diferrated intermediate 4b, whose Fe centres reside at the
1,4-positions of the fluoroaryl anion, is reacted with an excess of
1 and heated at 80°C, no reaction was observed, hinting that the
proximity of the Fe centres within the ring must also play a role
in facilitating this activation process.
C. G. Werncke, P. C. Bunting, C. Duhayon, J. R. Long, S. Bontemps, S.
Sabo-Etienne, Angew. Chem. 2014, 127, 247; Angew. Chem. Int. Ed.
2014, 54, 245.
[8]
[9]
T. Ahrens, J. Kohlmann, M. Ahrens, T. Braun, Chem. Rev. 2015, 115,
931.
M. Schlosser, L. Guio, F. Leroux, J. Am. Chem. Soc. 2001, 123, 3822.
NR2
NR2
F
[10] R. McLellan, M. Uzelac, A. R. Kennedy, E. Hevia, R. E. Mulvey, Angew.
Chem. 2017, 129, 9694; Angew. Chem. Int. Ed. 2017, 56, 9566.
[11] a) L. C. H Maddock, T. Cadenbach, A. R. Kennedy, I. Borilovic, G.
Aromi, E. Hevia, Inorg. Chem. 2015, 54, 9201. b) L. C. H Maddock, I.
Borilovic, J. McIntyre, A. R. Kennedy, G. Aromi, E. Hevia, Dalton Trans.
2017, 46, 6683.
F
NR2
Fe
F
2 [(D)0.5NaFe(NR2)3] ]
80oC, C6H6
Fe
- Fe(NR2)2
Fe
NR2
R2N
Na
NR2
Na
D
D
- NaF
elimination
F
Na
D
D
F
F
F
D
F
D
4a
Na-mediated-
differation
Fe(NR2)2
addition
F
NR2
Fe
F
F
R2N
NR2
Fe
R2N
R2N
[12] For a review on the coordination chemistry of the CF unit in
Fe
R2N
Na(NR2)2
Fe
Fe
NR2
Fe(NR2)2
- Fe(NR2)2
fluorocarbons see: H. Plenio, Chem. Rev. 1997, 97, 3363.
[13] J. Vela, J. M. Smith, Y. Yu, N. A. Ketterer, C. J. Flaschenriem, R. J.
Lachicotte, P. L. Holland, J. Am. Chem. Soc. 2005, 127, 7857.
[14] For a reviews on competition between C-H/C-F bond activations see: O.
Eisenstein, J. Milani, R. N. Perutz, Chem. Rev. 2017, 117, 8710.
[15] Hyla-Kryspin, S. Grimme, H. H. Büker, N. M. M. Nibbering, F. Cotter, M.
Schlosser, Chem. Eur. J. 2005, 1251.
Na
D
NR2 addition
R2N
D
R2N
F
(II)
- NaF
(I)
elimination
co-complexation
D
D
Na
R2N
Fe
NR2
F
NR2
NR2
R2N
NR2
Fe
Fe
Fe
Fe(NR2)2
Fe
- Fe(NR2)2
R2N
addition
[16] M. Schlosser, Angew. Chem. 1998, 110, 1538; Angew. Chem. Int. Ed.
1998, 110, 1496.
R2N
NR2
R2N
R2N
NR2
NR2
- NaF
(III)
5a
elimination
[17] A. Orthaber, C. Seidel, F.Belaj, Jörg H. Albering, R. Pietschnig, U.
Ruschewitz, Inorg. Chem. 2010, 49, 9350.
Scheme 3. Proposed cascade mechanism for formation of 5a (D= dioxane,
R= SiMe3).
[18] M. Schlosser, E. Marzi, F. Cottet, H. H. Büker, N. M. M. Nibbering,
Chem. Eur. J. 2001, 3511.
[19] 4a and 4b form complex 2D-network structures with propagation
occurring via their dioxane molecules which connect to neighbouring
[(Na2Fe2(HMDS)4(diarenide)] units, see SI.
To conclude, by exploiting synergistic effects in sodium ferrate
chemistry, we have unveiled a new regioselective method for the
direct ferration of a wide range of fluoroarenes under mild
reaction conditions as well as a novel type of C-F bond
activation process. Isolation of metallated intermediates have
shed light on how Na ions and Fe centres can cooperate in a
synchronised manner to promote chemical transformations
which neither sodium or iron amides are capable of facilitating
on their own.
[20] a) T. Schaub, P. Fischer, T. Meins, U. Radius, Eur. J. Inorg. Chem.
2011, 3122. b) R. Chukwu, A. D. Hunter, B. D. Santarsiero, J. L.
Atwood, J. Chassaignac, Organometallics, 1992, 11, 589.
[21] D. R. Armstrong, V. L. Blair, W. Clegg, S. H. Dale, J. Garcia-Alvarez, G.
W. Honeyman, E. Hevia, R. E. Mulvey, L. Russo, J. Am. Chem. Soc.
2010, 132, 9480.
[22] Hydrolysis of 5a afforded tri-substituted benzene [1,3,5-(HMDS)3-C6H3]
(6) in a 71% yield which was fully characterized by 1H, 13C NMR and
elemental analysis. Its solid structure was established by X-ray
crystallographic studies (see SI for details).
[23] P. P. Power, Chem. Rev. 2012, 112, 3482 and references therein.
[24] a) X. Xu, J. Jia, H.Sun, Y. Liu, W. Xu, Y. Shi, D. Zhang, X. Li, Dalton
Trans., 2013, 42, 3417. b) T. Zheng, J. Li, S. Zhang, B. Xue, H. Sun, X.
Li, O. Fuhr, D. Fenske, Organometallics, 2016, 35, 3538.
Acknowledgements
We are grateful to the ERC (Stg-2011 MixMetApps to EH) for
funding and to Diamond Light Source for access to single-crystal
synchrotron diffraction facilities on beamline I19 (award
MT11145). We also thank Professor Robert E. Mulvey and Dr.
Charles T. O’Hara for their insightful comments.
[25] Li…F interactions have been proposed to play a major role in the C-F
bond activation of CF3H by Li enolates, see: T. Iida, R. Hashimoto, K.
Aikawa, S. Ito, K. Mikami, Angew. Chem. 2012, 124, 9673; Angew.
Chem. Int. Ed. 2012, 51, 9535.
[26] Attempts to trap any of the proposed intermediates by hydrolysis
resulted in the isolation of variable amounts of [1,3,5-(HMDS)3-C6H3] (6)
(see SI) and 1,3,5-trifluorobenzene.
Keywords: metallation, iron, mixed-metal chemistry; C-F bond
activation, alkali-metals
[1]
[2]
For an authoritative review on Fe-mediated C-H bond activation see: R.
Shang, L. Ilies, E. Nakamura, Chem. Rev. 2017, 117, 9086.
J. Clayden, Organolithiums: Selectivity for Synthesis, Pergamon,
Elsevier Science Ltd., Oxford, 2002.
[3]
[4]
F. Mongin, A. Harrison-Marchand, Chem. Rev. 2013, 113, 7563.
E. Nagaradja, F. Chevallier, T. Roisnel, V. Jouikov, F. Mongin,
Tetrahedron, 2012, 68, 3063.
[5]
S. H. Wunderlich, P. Knochel, Angew. Chem. 2009, 121, 9897; Angew.
Chem. Int. Ed. 2009, 48, 9717
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10.1002/anie.201709750
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
R2
NR2
N
L. C. H. Maddock, T. Nixon, A. R.
Kennedy, M. R. Probert, W. Clegg and
E. Hevia*
F
R2N
NR2
Na
Fe NR2
Fe
Fe
H
H
N
(1)
3 eq
R2
R2N
NR2
F
F
- Fe(NR2)2
- 3 Na F
X
Page No. – Page No.
X
(X =H, F, Br; R= SiMe3)
2-fold C-H/ 3-fold C-F
bond activation!
Utilising Sodium-Mediated Ferration
for Regioselective Functionalisation
of Fluoroarenes via C-H and C-F
Bond Activations
High Five! Exploiting bimetallic cooperation, sodium tris(amido) ferrate 1 induces
the collective cleavage of five (three C-F and two C-H) bonds of trifluoroarene
substrates via a cascade activation process.
This article is protected by copyright. All rights reserved.