Iminosemiquinone radical ligands enable access to a well-defined redox-active CuII-CF3 complex

Article abstract of DOI:10.1039/c4cc04487h

The reaction of a copper complex bearing iminosemiquinone ligands with a CF₃⁺ source provides an unprecedented Cu ^II-CF₃ complex through ligand-based oxidation. Reactivity of this complex leads to nucleophilic trifluoromethylation of the ligand, suggesting an electronic interplay that results in a formal umpolung of the initial CF₃⁺. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc04487h

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Iminosemiquinone radical ligands enable
access to a well-defined redox-active
Cite this: Chem. Commun., 2014,
50, 10394
CuII–CF3 complex†‡
Received 12th June 2014,
Accepted 17th July 2014
Jeremy Jacquet,a Elise Salanouve,a Maylis Orio,b Herve Vezin,b
´ ´
´
Sebastien Blanchard,a Etienne Derat,a Marine Desage-El Murr*a and
´
Louis Fensterbank*a
DOI: 10.1039/c4cc04487h
www.rsc.org/chemcomm
The reaction of a copper complex bearing iminosemiquinone ligands capacity to perform two-electrons elementary steps. In line
with a CF3 source provides an unprecedented CuII–CF3 complex with our interest in application of non-innocent ligands to
+
through ligand-based oxidation. Reactivity of this complex leads to catalytically relevant methods,6 we were interested to see if
nucleophilic trifluoromethylation of the ligand, suggesting an electronic such ligands could be used to stabilize a Cu–CF3 species and
+
interplay that results in a formal umpolung of the initial CF3
.
possibly influence its chemical behaviour through electronic
participation. Among redox non-innocent ligands, the amido-
The widespread benefits of fluorinated molecules in drug phenolate motif has been widely explored, as chemists seek
design, materials and imaging to name a few have triggered to take advantage of its privileged redox properties. Indeed,
acute development of transition metal-catalyzed methods this ligand scaffold can accommodate two successive mono-
to introduce fluorinated motifs in molecules,1 among which electronic oxidation steps through a redox chemical interplay
trifluoromethylation is a fast developing area. Specifically, involving three distinct oxidation states (amidophenolate,
copper-catalyzed trifluoromethylation, relying on a cheaper iminosemiquinone and iminobenzoquinone). Such ligands
and more earth-abundant metal than palladium, iridium and have been successfully applied to several metal-catalyzed
ruthenium has attracted the attention of chemists.2 Copper- or -mediated processes associated with a variety of metals such
catalyzed methods have been developed using nucleophilic as iridium for hydrogen oxidation7 and cobalt for Negishi cross-
À
+
(CF3 ), electrophilic (CF3 ), and radical (CF3 ) sources. However, coupling.8 All these examples were found to involve ligand-based
the field has suffered from high catalyst loadings (often stoichio- redox events. Specifically, copper complexes bearing amido-
metric), harsh conditions and a limited scope. Recent improve- phenolate ligands9 behave as mimics of the galactose oxidase
ments have relied on the development of ligand-stabilized enzyme and were shown to oxidize primary alcohols into
well-defined copper complexes such as [PhenCuCF3] (Phen: aldehydes under aerobic conditions.10
ꢀ
phenanthroline), reported in 2011 by the Hartwig group and
Seeking to introduce a trifluoromethyl ligand on copper, we
termed Trifluoromethylatort for its striking performances.3 Other first tried to react the original deep-green [CuII(LꢀSQ)2] (complex [1],
significant developments have emerged from the combined use Scheme 1) with a nucleophilic CF3 source (TMSCF3). No reaction
of copper catalysis and in situ generation of CF3 radicals, thus occurred11 and this observation is consistent with the fact that
avoiding costly CF3 sources.4
Redox non-innocent ligands5 have been identified as pro-
mising partners in the development of catalytic methods using
non-noble metals by circumventing their tendency to engage
in monoelectronic redox events and promoting instead their
a
´
UPMC, CNRS, UMR 8232, Institut Parisien de Chimie Moleculaire (IPCM),
F-75005, Paris, France. E-mail: marine.desage-el_murr@upmc.fr,
louis.fensterbank@upmc.fr
b
ˆ
Laboratoire de Spectrochimie Infrarouge et Raman, UMR CNRS 8516 Batiment C5,
59655 Villeneuve d’Ascq Cedex, France
† Dedicated to Professor Iwao Ojima,
a leading pioneer in organofluorine
chemistry, on the occasion of his 70th birthday.
‡ Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4cc04487h
+
Scheme 1 Reaction of complex [1] with oxidants Br2 (ref. 12) and CF3
induces a ligand-based oxidation.
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complex [1] has been shown to behave rather as a nucleophile.12
Accordingly, switching to an electrophilic trifluoromethylating
agent proved to be successful, as the reaction of [1] with one
equivalent of the Umemoto reagent13 in CH2Cl2 at room
temperature under Ar induced a color change from deep green
to deep red. A dark red precipitate was filtered and the presence
of dibenzothiophene was detected in the filtrate, providing the
promising hint that the CF3 group had been abstracted from
the Umemoto reagent. The isolated complex (68% yield) was
analyzed by ESI mass spectrometry confirming the incorpora-
tion of a CF3 group with a molecular peak corresponding to that
expected for a [Cu(LBQ)2CF3]+ complex [3]. No clear NMR
spectra could be obtained, thus indicating that this species is
probably paramagnetic. In UV-vis spectroscopy (SI), the inter
valence charge transfer band (IVCT) at l = 795 nm, related to
the diradical character of CuLSQ2 is not observed for [3]. This
has been similarly observed when bromine was reacted onto
Fig. 2 2D-HYSCORE spectra of [3]. Experimental conditions: a frozen
CH2Cl2 sample of [3], T = 5 K. The spectrum was recorded for the B = 3357
G value of the ESE detected field sweep spectrum. The time delay was set
to 136 ns and a pulse length of 12 ns was used for p/2 pulses with 256 Â
256 points along t1 and t2 directions.
this complex,12 and can be related to the oxidation of both the with complex [2] and the first two reduction steps are likely to
À
LSQ ligand to the quinone LBQ form during the reaction.
be electrochemical chemical (EC) processes, with probable
To further assess the electronic structure of the product, the decoordination of the CF3 ligand upon successive monoreduc-
X-band EPR spectrum was recorded at 10 K in frozen CH2Cl2 tion of each ligand yielding the [Cu(LSQ)2] form and its electro-
(Fig. S2, ESI‡). This spectrum is clearly different from that of chemical signature, with recoordination of the CF3 moiety
the starting complex and exhibits a quasi axial symmetry with upon reoxidation of [Cu(LSQ)2] (see ESI‡).
some rhombic distorsion and the 63/65Cu hyperfine splittings
Thus, all evidence here points toward a similar reactivity of
characteristic of a single ion CuII complex featuring an unpaired [1] with bromine and the Umemoto reagent, i.e. oxidation of the
electron occupying a dx2Ày2 magnetic orbital, with no radical iminosemiquinone ligands to iminobenzoquinone with reduction
ligands contribution.9 Interestingly, while the g- and ACu-values of the reagent, forming either two bromide ions coordinated to a
(gi = 2.225, 2.065, 2.000 and ACi u = (182, 13.5, 9.5) Â 10À4 cmÀ1
)
CuII center or a trifuoromethyl anion linked to the copper. Pulse
are very similar to those of parent complex [2] ([CuLBQ2Br2]), EPR spectroscopy has been widely applied to materials science and
(gi = 2.205, 2.085, 2.02 and ACi u = (138, 3, 24) Â 10À4 cmÀ1), no biological systems to gain insight into the surroundings of para-
nitrogen superhyperfine couplings could be observed in our magnetic centers, and more recently to understand the reactivity of
case. This could be related to the difference in geometries molecular systems.14 Thus, to confirm the presence of the trifluoro-
between the trans-Br2 hexacoordinated complex and complex methyl ligand, pulsed EPR experiments were conducted on frozen
[3]. Thus, as was the case for the Br2 oxidation product, these CH2Cl2 samples of [3] (Fig. 2) using the 2D hyperfine-sublevel
results strongly suggest the presence of a CuII center in [3] correlation experiment (2D-HYSCORE, see the ESI‡ for details),15
coordinated with diamagnetic LBQ ligands. The cyclic voltam- which enables proper assignment of various couplings with a
mogram of [3] was recorded in CH2Cl2 with 0.1 M TBABF4 as the large number of nuclei (1H, 13C, 14N, or 19F).
supporting electrolyte (Fig. 1). The open circuit potential is
Besides the detection in the (+,+) quadrant of weakly
around 0.8 V per SCE. Upon reduction, the first two waves coupled 1H, 13C, 14N from the ligands (see ESI,‡ Fig. S5), of
appear composite and not fully reversible, while the two most much more significance here is the presence of a pair of cross-
negative waves are quasi reversible and correspond to those of peaks centered at n = 13.4 MHz in the (+,+) quadrant which are
[Cu(LSQ)2]. Again, this is very similar to the results obtained assigned to the 19F Larmor nuclear frequency. These symmetric
cross-peaks indicate a weak hyperfine coupling that is estimated
at 0.9 MHz and evidence the interaction between 19F centers of
the putative CF3 group with the unpaired electron of the system.
This is further confirmed by analyzing the specific features of the
HYSCORE pattern in the (+,À) quadrant that indicates a strong
hyperfine coupling from a 13C nucleus, estimated at 22 MHz
from the antidiagonal peak. This last result supports the
presence of a carbon center being directly attached to the
copper ion in [3], as expected if a CF3 ligand is being formed
upon the reaction with the Umemoto reagent. These experimental
data thus directly show the coordination of the CF3 group through
a metal–carbon bond in complex [3].
DFT calculations were undertaken to clarify the electronic
Fig. 1 Cyclic voltammogram of [3] in CH2Cl2.
structure of the new copper adduct. Complex [1] is known to be
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performed the reaction using exogenous ligand 6 as the sub-
strate, differing from the ligand by a tolyl group (Scheme 2,
right). Under these conditions, both 7 (8%) and 8 (27%), could
be isolated along with 4 (2%) and 5 (8%), indicating that
trifluoromethylation of the external substrate probably requires
ligand exchange at the copper center.
In summary, a new [CuII(LBQ)2CF3] complex was prepared
by reacting [CuII(LꢀSQ)2] with an electrophilic CF3 source. The
+
Fig. 3 DFT structures and spin density isosurfaces for complexes [1] and [3].
resulting two-electrons oxidation is sustained by the redox-
active ligands while the copper oxidation state is preserved.
Evidence for a Cu–CF3 bond and detailed electronic structure
has been assessed by combined cw and pulsed EPR spectro-
scopic measurements together with DFT studies. This complex
promotes trifluoromethylation at electrophilic sites while
an open-shell species exhibiting an anti-ferromagnetic cou-
pling between the ligand-based radicals, while one unpaired
electron is localized on copper (Fig. 3). Upon incorporation of
+
CF3 , the electronic description is totally modified: ligands are
+
originating from a CF3 source, performing a formal umpolung
closed-shell and copper is the only atom bearing a significant
amount of spin density (the remaining being on the CF3 group).
Thus, [3] can be described as a CuII adduct in which electrons
responsible for Cu–CF3 bonding originate from the ligand.
of the CF3 moiety. Although still limited in scope, this reactivity
is a proof-of-concept that redox-active ligands show potential
for future applications in trifluoromethylation.
The authors thank UPMC, CNRS, ANR (grant ANR-11-JS07-
004-01) and IUF (L.F.). The authors thank IR-RPE CNRS 3443,
the LabEx MiChem and RENARD network (CW X-band EPR
with Dr J.-L. Cantin, INSP (UMR 7588, CNRS – UPMC) and
pulsed EPR in Lille).
2d,3,16
Although CuICF3
17
and CuIIICF3 complexes18 have been
reported, complex [3] would be, to the best of our knowledge, the
first example of a CuIICF3 complex and we were therefore curious to
probe its reactivity. Stability tests (ESI,‡ Table S1) revealed that, upon
standing in CH3CN at rt for 18 h, a product identified as 4
(Scheme 2) was formed in 35% yield. Heating complex [3] in CH3CN
at 70 1C for 9 h resulted in isolation of distinct trifluoromethylated
adduct 5 in 54% yield. Full analysis of these products by NMR 1H,
13C, 19F and MS established that these products were trifluoro-
methylated quaternary analogues of the ligand in which a CF3 group
has been transferred to an electrophilic site. Independent heating of
4 in CH3CN at 70 1C results in full conversion to 5 in 3 h, therefore
suggesting that the CF3 transfer occurs selectively at the electrophilic
site of the carbonyl and that complex [3] could promote nucleophilic
Notes and references
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