Diverse copper(iii) trifluoromethyl complexes with mono-, bi- and tridentate ligands and their versatile reactivity

Article abstract of DOI:10.1039/c8dt00291f

Cu(iii) trifluoromethyl complexes are proposed as essential intermediates for many copper-promoted trifluoromethylation reactions, but remain elusive and scarcely explored. We report herein the isolation and spectroscopic and X-ray crystallographic charac

Full text of DOI:10.1039/c8dt00291f

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Diverse copper(III) trifluoromethyl complexes with mono-, bi- and
tridentate ligands and their versatile reactivity†
Song-Lin Zhang*a, Chang Xiao and Hai-Xing Wana
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
First published on the web Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
5
complexes show excellent stability in solid state for at least
several weeks and are also stable in solutions under ambient
conditions. For the first time, reactivity of these isolated CuIII
55 CF3 complexes with arylboronic acids was studied to allow
efficient Cipso-trifluoromethylation of boronic acids in up to
quantitative yields under mild conditions.6a,b A novel syn-Nu-
trifluoromethylation across the triple bond of arylacetylenes
have been developed using phenCuIII(CF3)3 (1) in combination
60 with fluorides, phenoxides or alkoxides.6c Moreover, recent
excellent studies from Li group describe radical
trifluoromethylation of alkyl halides and cinnamic acids using
(bpy)Cu(CF3)3 (2) and zinc reagents.5 These studies highlight
the great potential of CuIII CF3 complexes in organic synthesis.
Cu(III) trifluoromethyl complexes are proposed as essential
intermediates for many copper-promoted trifluoromethylation
reactions, but remain elusive and scarcely explored. We report
10 herein the isolation, spectroscopic and X-ray crystallographic
characterization of diverse CuIII-CF3 complexes (6-10) with
varied coordinating motifs (mono-, bi- or tridentate) and formal
charges (neutral or monoanionic) for the ligand L (L is pyridine,
2,4,6-trimethylpyridine,
quinol-8-yloxide
or
2,6-bis(2Å-
15 pyridyl)pyridine). Square planar complexes 6, 7 and 9 show
rapid dynamic behavior in solution possibly due to the weak Cu-
CF3 bonds that can quickly dissociate and recombine CF3 radical.
In contrast, 10 with octahedral geometry is more rigid. Reactivity
studies show that except ion-pair complex 8, they are highly
20 reactive for the trifluoromethylation of arylboronic acids and C-
H bond of terminal alkynes. Furthermore, syn-fluoro- and -oxy-
trifluoromethylation across the triple bond of alkynes can be
achieved uisng 6 and CsF or NaOPh. These results greatly
expand the scope of isolated and well-characterized Cu(III) CF3
25 complexes, and establish their versatile reactivity properties that
may be widely involved in copper-mediated trifluoromethylation
reactions, which thus substantiate essential yet undeveloped
aspects of trifluoromethylation chemistry.
Previous studies: ref 6
L = phen, bpy
CF3SiMe3, AgF
DMF
CF3
CuIII
CF3
CF3
CuI/L
N
N
N
N
CuIII CF3
CF3
Room
Temperature
CF3
1
L = DPPE,
Xantphos
BINAP
2
trigonal bipyramidal
CF3
CuIII
CF3
F3C
P
P
P
P
CuI
L = pyridine
2,4,6-trimethylpyridine
8-hydroxyquinoline
terpyridine
F3C
ion-pair CuI/CuIII
3-5
This study:
Rare studies have thus far been reported on the isolation,
30 structural and reactivity properties of high-valent CuIII-CF3
complexes, key reactive intermediates proposed for a range of
copper-promoted trifluoromethylation reactions.1-2 This
largely hampers the understanding and establishment of
catalytic cycles of many trifluoromethylation reactions, and
35 rational design of new trifluoromethylation chemistry.
Challenges for obtaining isolated CuIII-CF3 complexes result
mainly from their thermal instability and fluxionality in the
reaction solution, as well as separation and purification
problems associated.3 As a result, only sporadic well-defined
40 CuIII CF3 complexes have been reported up to 2015, i.e.,
CF3
CuIII CF3
CF3
CF3
N
N
N
N
CuIII CF3
CuIII CF3
CF3
N
CF3
O
9
6
square planar
octahedral
10
CF3
N
CuIII CF3
CF3
CuIII
F3C
F3C
N
CuI
N
CF3
CF3
7
ion-pair CuI/CuIII
8
65
Scheme 1 Synthesis of diverse CuIII-CF3 complexes 6-10.
square
planar
(dithiocarbomate)CuIII(CF3)2,4a
ion-pair
It is remarkable to note that during our study mononuclear
(L)CuIII(CF3)3 complexes were selectively obtained with N,N-
[X]+[CuIII(CF3)4]Þ ([X]+
=
Ph4P+ or Bu4N+)4b,c and
(bpy)CuIII(CF3)3.4c The difficulty in obtaining stable CuIII CF3
complexes precludes insights into their reactivity
45 properties.4a,5,6
bidentate
ligand
L,
while
ion-pair
dinuclear
70 [(L)2CuI]+[CuIII(CF3)4]Þ were dominant using bisphosphine
ligand under otherwise identical conditions (Scheme 1, 1-2 vs
3-5).6a,b This finding implies apparent correlation between the
coordination structures of CuIII CF3 complexes and the type of
ancillary ligand. We were therefore prompted to investigate
75 other types of ligands with distinct coordinating properties,
aiming to ascertain the feasibility of CuIII CF3 complexes
adopting other distinct coordination structures. As a result of
this effort, we report herein a series of CuIII CF3 complexes 6-
Very recently, our continuous efforts6,7 have enabled the
isolation and characterization of either neutral (L)CuIII(CF3)3
(1-2 where
[(L)2CuI]+[CuIII(CF3)4]Þ complexes (3-5 where
L =
phen or bpy)6a or ion-pair dinuclear
L
is a
50 bisphosphine ligand: DPPE, BINAP or Xantphos) in both
solution and solid state (Scheme 1).6b These CuIII CF3
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10 containing pyridine and its derivatives featuring distinct
coordination structures (Scheme 1, red box). Their structural
properties in both solution and solid state, dynamic behaviour
in solution and versatile reactivity are investigated. These
results significantly expand the scope of isolated and well-
characterized CuIII CF3 complexes, and establish their
versatile reactivity properties that are fundamental to
trifluoromethylation chemistry.
5
Reaction of CuI/AgF with excess CF3SiMe3 in the presence
10 of
pyridine,
8-hydroxyquinoline
and
2,6-bis(2-
pyridyl)pyridine in DMF at room temperature allows the
selective formation and isolation of 6, 9 and 10 as yellow,
gray-black and fulvous solids in 57%, 30% and 35% yields
respectively (please see ESI† for workup and purification).
15 Interestingly, when 2,4,6-trimethylpyridine was used as the
ligand in DMF, both neutral 7 and ion-pair CuI/CuIII 8 were
obtained in isolated yields of 30% and 36%. 8 could be
selectively formed in 45% yield when performing the reaction
in acetonitrile.
Fig. 1 ORTEP drawing of 6•DMF (left) and 7 (right) at 30% probability.
50 All of the hydrogen atoms and disorders of methyl and fluorines are
omitted for clarity.
Crystals of 6 were able to be grown from slow evaporation
of
a mixed DMF/CH2Cl2/hexane solution of 6 at low
temperature. X-ray diffraction analysis10 shows that there is
55 one additional DMF solvent lying perpendicular to the square-
planar plane of 6 with Cu1-O1 bond length of 2.215(4) Å,
thus exhibiting a square pyramidal geometry (Fig. 1, left). Cu-
CF3 bonds cis to pyridine ligand (1.957(4) Å) are substantially
longer than the trans-Cu-CF3 bond (1.923(5) Å), possibly due
60 to the stronger trans influence of CF3 than that of neutral
pyridine. This is consistent with the computational results that
the cis-Cu-CF3 bond in 6 is weaker than the trans-Cu-CF3
bond. The Cu-pyridine bond length is 1.961(4) Å.
20
Room-temperature 19F NMR spectrum of 6 in CDCl3 shows
two broad singlets at -23.6 and -37.1 ppm in a 1:2 ratio.8 The
two signals sharpen significantly as the temperature lowers
down to 273 K, start to split at 253 K and evolve to apparent
septet and quartet from 238 K (Figs. S4-S6 in ESI†). The
25 temperature-variable 19F NMR behaviors of 6 indicate rapid
dynamic ligand exchange around the Cu(III) center on NMR
time scale which becomes more and more sluggish at lower
temperatures. As expected, 1H NMR of
6 shows only
7 shows slightly different 19F NMR compared to 6. At room
65 temperature, the trans-CF3 is still of broad singlet while the
cis-CF3s show apparent quartet splitting (coupling constant of
10.2 Hz). Calculation results show that BDE values are 14.4,
21.3 and 18.2 kcal/mol for cis-Cu-CF3, trans-Cu-CF3 and Cu-
N(2,4,6-trimethylpyrdine) respectively. Compared with 6, the
70 Cu-CF3 and Cu-pyridine bonds are slightly stronger in 7,
which might lead to a slower dynamic ligand exchange
following the mechanism shown in Scheme 2. In addition, the
significant steric demanding of 2,4,6-trimethylpyridine might
downfield shifted and broadened pyridine protons indicating
30 the coordination of pyridine to Cu(III) and its dynamic
behaviour. These NMR spectroscopic studies, elemental
analysis, IR (see ESI†) and X-ray crystallographic study (vide
infra) validate the assignment of 6. To our knowledge,
complex 6 represents the first example of square planar CuIII
35 CF3 complex containing a neutral monodentate ancillary
ligand.
17.3 kcal/mol
CF3
21.0 kcal/mol
also play
a role to partly hamper the ligand exchange
CF3
CF3
a
CuIII CF3
CuII CF3
CuIII CF3
CF3
75 dynamics. These results may rationalize the slight difference
of 19F NMR of 6 and 7. Crystal structure of 7 shows a good
square-planar geometry (Fig. 1, right). No additional DMF is
present, possibly due to the steric hindrance of the methyl
substituents that blocks the apical position.
N
N
N
a
b
CF3
CF3
12.5 kcal/mol
b
CF3
CuIII CF3
CF3
80
8 shows typical ion-pair CuI/CuIII structure (a singlet 19F at
ca -34.6 ppm and downfield shifted protons of pyridines). The
competitive formation of 7 and 8 and solvent-controlled
selectivity indicate that the steric hindrance of the ancillary
ligand and the solvent polarity are important factors of
N
Scheme 2 Dynamic ligand exchange suggested for complex 6 in solution.
Computational results9 show that bond dissociation free
40 energies (BDE) are 12.5 kcal/mol for Cu-CF3 bond cis to
pyridine, 21.0 kcal/mol for Cu-CF3 bond trans to pyridine and
17.3 kcal/mol for Cu-pyridine in 6 (Scheme 2). The low BDE
values of Cu-CF3 bonds suggest facile homolytic dissociation
of CF3 radical and a Cu(II) intermediate that can recombine to
45 regenerate 6 with exchanged CF3s (Scheme 2). This may
rationalize the dynamic behavior of 6 in solution and the
observation of broadening of the NMR resonances.
85 controlling the structure of CuIII CF3 complexes.
19F NMR spectrum of 9 at room temperature shows only
one broad singlet at -26.7 ppm, suggesting also rapid dynamic
exchange of the two CF3 ligands on NMR time scale (see
1
ESI† for more details). H NMR spectrum of 9 shows protons
90 of quinol-8-yloxide that are downfield shifted compared to
free 8-hydroxyquinoline. 9 features a monoanionic N,O-
bidentate ligand that forms a five-membered metallacycle.
The only analogous complex is aforementioned square planar
(dithiocarbomate)CuIII(CF3)2 reported by Burton et al. where a
2
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DOI: 10.1039/C8DT00291F
40 a Reaction conditions: 6 (0.1 mmol), 11a (0.2 mmol), additive (0.2 mmol),
4,4•-difluorobiphenyl (0.2 mmol, internal standard), DMF (1 mL), under
dry O2 atmosphere. b Yields determined by 19F NMR spectroscopy based
on 11a.
monoanionic S,S-chelate is bound to copper(III) to generate a
four-membered ring.4a
Complex 10 shows two 19F signals at -25.2 and -34.6 ppm
with well-resoluted septet and quartet splitting (with both
constants of 9.8 Hz) in a molar ratio of 1:2 at room
temperature. The symmetric structure of 10 reflected by 1H,
19F and 13C NMR resonances indicates that all three pyridine
arms are bound to the copper center, thus exhibiting a
distorted octahedral geometry. These features are quite similar
5
45
A putative mechanism rationalizing reaction of 6 with ary
boronic acids involves initial trifluoromethylation of a first
aryl boronic acids by 6 either via organometallic or radical
pathways. The resulting Cu-CF3 at lower oxidation state is
then oxidized by O2 to regenerate a CuIII-CF3 complex that
10 to the 19F NMR spectrum of 1 (phenCuIII(CF3)3) with distorted
trigonal bipyramidal geometry.6a DFT computational studies
confirm that complex 10 with a ꢀ3-bound terpyridine is stable
in singlet state in DMF, consistent with the experimental
characterization data. It is also more stable than a potential
15 isomer with a ꢀ2-bound terpyridine, i.e., with one non-ligated
bystanding pyridine arm.
The isolation and characterization of 6-10 together with 1-5
greatly expand the scope of well-characterized CuIII-CF3
complexes and demonstrate that distinct CuIII CF3 complexes
20 can be formed with different types of ancillary ligands. This
provides a basic platform for developing CuIII CF3 chemistry,
and is crucial for mechanistic elucidation of various copper-
promoted trifluoromethylation reactions.
50 undergoes trifluoromethylation with a second aryl boronic
acids.6a Fluoride salt can promote the transmetalation of aryl
boronic acids in both trifluoromethylation steps to help
transfer the aryl group. This mechanistic picture may
rationalize the experimental observations discussed above.
55
Next, various aryl and heteroaryl boronic acids were
subjected under the optimal conditions in entry 2 of Table 1.
Some selected examples are summarized in Table 2. Generally
good to quantititive yields were obtained with two exceptions
of 12i and 12k. The low yield of 12i shows the detrimental
60 ortho-steric effect whilst 12k may engage in the competing
coordination to copper with pyridine. A range of functional
groups could be tolerated, including alkyl, phenyl, methoxy,
hydroxy, chloro, cyano, acetyl and ester.
Reactivity properties of 6-10 were then studied to react with
25 arylboronic acids11 and terminal alkynes12. Reaction of 6 with
boronic acid 11a was optimized by screening different factors
including the additive, temperature and time effect on the
reaction yield (Table 1).13 Gratifyingly, without any additive,
Table 2 Substrate scope for reaction of 6 with various arylboronic acids a
CF3
KF (2 equiv), 50oC
CuIII
CF3
+
ArB(OH)2
N
CF3
Ar CF3
DMF (1 mL)
6h, O2
6
can react with two equivalents of 11a to produce
11
(0.2 mmol)
12
30 trifluoromethylated product 12a in 90% yield at 50 oC in 6
hours under dry O2 (entry 1).14 This high reactivity indicates
the competence of 6 as reactive intermediates for copper-
mediated trifluoromethylation of arylboronic acids. By adding
KF or NaF, this reaction can occur quantitatively (entries 2-3).
35 The dry O2 environment is preferred because under air or N2
the yields were much lower (entries 5-6). Finally, the
temperature is also important because the reaction became
much slower at room temperature (entry 8).
6 (0.1 mmol)
CF3
CF3
CF3
CF3
H3CO
Cl
12b, 99% (81%) 12c, 99% (61%)
CF3
NC
HO
12a, 99% (80%)
12d, 89%
CF3
CF3
CF3
O
H3C
O
12g, 88%
CF3
12e, 67%
12f, 94%
12h, 40%
CF3
CF3
Table 1 Reactivity study of complex 6 with arylboronic acid a
CF3
S
N
B(OH)2
CF3
O
CF3
12j, 99% (84%)
12l, 85%b
12i, 25%
12k, 7%
Additive, Temp, time
DMF
N
CuIII CF3
CF3
+
65 Reaction yields were determined by 19F NMR spectroscopy using 4,4•-
a
difluorobiphenyl (ca -117.0 ppm) as internal standard. b AgF, 3 h.
OCH3
OCH3
(0.1 mmol)
(0.2 mmol)
6
11a
12a
Under slightly different conditions (at 80 oC under air, see
ESI† for more optimization study of 7), 7 shows similar good
70 reactivity with various aryl and heteroaryl boronic acids and
tolerates a range of functional groups (Table 3). Moreoever, it
was pleasing to see that 1-naphthyl, 3-quinolyl and benzofuryl
boronic acids can be transformed to the corresponding
trifluoromethylated products 12o-q.
entry
Additive
T (oC)
Time (h)
Yield (%) b
1
2
3
4
5
6
7
8
Š
KF
NaF
Na2CO3
KF
KF
KF
KF
50
50
50
50
50
50
50
RT
6
6
6
6
6
6
3
3
90
99
99
78
56 (in air)
58 (in N2)
88
26
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Table 3 Substrate scope for reaction of 7 with various arylboronic acids ab
Table 5 C-H trifluoromethylation of terminal arylacetylenes by 6 ab
CF3
CuIII
CF3
CF3
KF (2 equiv), 80 o
C
KF ( 2 equiv.)
CuIII
CF3
N
CF3
+
N
CF3
ArB(OH)2
+
Ar
H
Ar
CF3
Ar CF3
DMF (1 mL)
6 h, air
DMF (1 mL)
100 oC, N2, 1 h
(0.1 mmol)
13
14
(0.1 mmol)
6
7 (0.1 mmol)
11 (0.2 mmol)
12
CF3
CF3
CF3
CF3
CF3
CF3
Cl
CF3
H3CO
12a, 99%
NC
H3CO
OHC
14b, 99% (64%)
CF3
NC
14a, 87% (61%)
14c, 57%
12b, 99%
12c, 92%
12d, 88%
CF3
CF3
CF3
CF3
CF3
O
O2N
Cl
O
F3C
14d, 65%
14e, 64%
14h, 46%
14f, 94%
O
O
12g, 98%
CF3
12m, 70%
12n, 99%
CF3
CF3
CF3
O
CF3
CF3
N
Br
H3C
14g, 93%
14i, 63%
N
12o, 96%
12p, 22%
12q, 91% (84%)
a
Reaction yields were determined by 19F NMR spectroscopy using 4,4•-
a Reaction conditions are similar as in Table 2, but is at 80 oC open to air.
b
difluorobiphenyl (ca -117.0 ppm) as internal standard.
Values in
25 parentheses are isolated yields using column chromatography.
In contrast, the ion-pair complex 8 is not reactive for
trifluoromethylation of aryl boronic acids after great efforts,
in generally less than 30% NMR yield (see Table S2 in ESI†
for more results). This observation is consistent with the
inertness of [phenCuI(PPh3)2]+[CuIII(CF3)4]Þ toward aryl
boronic acids, but contrasts to the high reactivity of ion-pair
Under the optimal conditions, complex 9 also shows good
reactivity with various aryl and heteroaryl boronic acids and
tolerates a range of functional groups, as summarized in Table
30 4. Moreoever, 1-naphthyl, 2-thiophenyl and benzofuryl
boronic acids can be efficiently transformed to the
corresponding trifluoromethylated heteroarenes.
C-H trifluoromethylation of terminal alkynes was also
studied for 6. After some screening of the conditions (see
35 Table S3 in ESI†), it was found that KF in DMF at 100 oC
under N2 is optimal for the C-H trifluoromethylation in 1
hours. Inert environment is required to avoid homo-coupling
of the terminal alkynes under O2. Table 5 shows some
examples of such C-H trifluoromethylation of terminal
40 alkynes. It should be pointed out that this is the first examples
of established C-H trifluoromethylation by CuIII-CF3
complexes.
5
10 CuI/CuIII complexes 3-5 (Scheme 1).6a,b These results indicate
that the reactivity of the ion-pair CuIII-CF3 complexes are
greatly influenced by the ancillary ligand on the CuI moiety,
and imply that they might exist as an inactive resting state and
the real active species are the neutral monodenate
15 LCuIII(CF3)3 complexes generated from them under
appropriate conditions.
Table 4 Substrate scope for reaction of 9 with various arylboronic acids ab
KF (2 equiv), 50oC
N
+
ArB(OH)2
Ar CF3
O
Cu CF3
Table 6 syn-Fluoro- and -oxy-trifluoromethylation of alkynes using 6 abc
DMF (1 mL)
6h, O2
CF3
9
11
(0.1 mmol)
12
F
CF3
H
CsF (5 equiv)
or
NaOPh (2 equiv)
(0.1 mmol)
CF3
CuIII
CF3
Ar
15
CF3
CF3
CF3
CF3
CF3
N
+
ArCôCH
or
100 oC, DMF (2 mL)
6-8 h, N2
PhO
Ar
CF3
H3CO
Cl
NC
13
(0.1 mmol)
H
6
(0.1 mmol)
16
12a, 79%
12b, 90% (83%)
12c, 99%
12d, 85%
CF3
F
CF3
H
F
CF3
H
CF3
CF3
F
CF3
H
F
CF3
H
CF3
O
H3C
O
O
O
12n, 81%
12g, 60%
12f, 50%
12l, 41%
OHC
NC
MeO
15a, 81% (55%)
O
CF3
15b, 63%
15c, 54%
15d, 83%
O
CF3
S
PhO
CF3
H
PhO
CF3
PhO
CF3
H
PhO
CF3
H
CF3
12o, 83%
12j, 96% (60%)
12q, 82%
H
Cl
a
Reaction yields were determined by 19F NMR spectroscopy using 4,4•-
difluorobiphenyl as internal standard. b Values in parentheses are isolated
20 yields using column chromatography.
Cl
16a, 99% (60%)
16b, 77%
16c, 63%
16d, 30%
4
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a
Reaction yields were determined by 19F NMR spectroscopy using 4,4•-
representative pyridine and its derivatives are prepared and
isolated at room temperature. They feature distinct
coordination properties with either mono-, di- or tridentate
ligand in neutral or monoanionic form. Reactivity studies
45 show that except 8, they are all highly reactive with aryl and
difluorobiphenyl as internal standard. b Values in parentheses are isolated
yields using column chromatography. c Reaction time: CsF 8 h; NaOPh 6
h.
5
By using CsF or NaOPh and extending the reaction time,
heteroaryl
boronic
acids
under
mild
conditions.
related
fluoro-trifluoromethylation6c
and
oxy-
Chemoselective C-H trifluoromethylation of terminal alkynes
and syn-fluoro- and –oxy-trifluoromethylation of the triple
bond of alkynes are also achieved using 6 or 10. These
50 structural and reactivity properties provide fundamental
information about organometallic Cu(III)-CF3 complexes that
greatly substantiates the basis of copper trifluoromethylation
chemistry.
trifluoromethylation of terminal alkynes15 were achieved
using 6, producing functionalized trifluoromethylated alkenes
10 with potential applications in pharmaceuticals and materials.
Some initial examples are shown in Table 6. The syn-
stereochemistry of products 15 are determined by the
characteristic vinylic proton with doublet of quartet splitting
and coupling constants of JHF of 33.9 Hz and JH-CF3 of 7.5
15 Hz, and the doublet and quartet splittings of the CF3 and F
appearing at ca -56 and -102 ppm in 19F NMR. These results
3
3
Conflicts of interest
indicate vicinal trans-configuration of H and F, and geminal 55 There are no conflicts of interest to declare.
position of H and CF3 on the double bond, which must be
assigned to the syn-difunctionalization products.
A possible mechanism for C-H trifluoromethylation of
Acknowledgements
20
This study was supported by the National Natural Science
Foundation of China (No. 21472068).
terminal alkynes by
6 and related fluoro- and oxy-
trifluoromethylation across triple bond is depicted in Scheme
3.6c CF3• generated from 6 adds to the triple bond of alkynes
to generate a vinyl radical (A), which upon SET to the CuII
Notes and references
25 intermediate produces a vinyl cation (B).15a,16 The vinyl cation
may deprotonate to give the Ar-CôC-CF3 product 14. 14 may
be attacked by nucleophilic reagents to give carbanion C that
can be protonated to give 15 or 16.17 Alternatively, vinyl
cation B may directly combine with nucleophilic reagents to
30 give the products 15 or 16 under appropriate conditions.18
a
60
Key Laboratory of Synthetic and Biological Colloids, Ministry of
Education, School of Chemical and Material Engineering, Jiangnan
University, Wuxi 214122, Jiangsu Province, China. Fax/Tel.: +86-510-
85917763; E-mail: slzhang@jiangnan.edu.cn
† Electronic Supplementary Information (ESI) available: Experimental
65 details, spectroscopic characterization data, crystallograpic study and
copies of 1H, 19F and 13C NMR spectra. See DOI: 10.1039/b000000x/
pyCuIII(CF3)3
1
2
For organofluorine chemistry and applications, see: (a) P. Kirsch,
Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim, Germany,
2004; (b) K. Müller, C. Faeh and F. Diederich, Science, 2007, 317,
1881; (c) S. Purser, P. R. Moore, S. Swallow and V. V. Gouverneur,
Chem. Soc. Rev., 2008, 37, 320; (d) Y. Jiang, H. Yu, Y. Fu and L. Liu,
Sci. China Chem., 2015, 58, 673.
For general reviews, see: (a) M. Schlosser, Angew. Chem., Int. Ed.,
2006, 45, 5432; (b) J.-A. Ma and D. Cahard, Chem. Rev., 2008, 108,
PR1; (c) T. Furuya, A. S. Kamlet and T. Ritter, Nature, 2011, 473,
470; (d) T. Liang, C. N. Neumann and T. Ritter, Angew. Chem., Int.
Ed., 2013, 52, 8214; (e) O. A. Tomashenko and V. V. Grushin, Chem.
Rev., 2011, 111, 4475; (f) C. Zhang, Org. Biomol. Chem., 2014, 12,
6580.
6
PyCuICF3
+ CF3
pyCuII(CF3)2
a
70
75
80
85
• CF3
CF3
H
CF3
H
•
Ar
H
+
SET
Ar
Ar
A
B
Fa or OPha
PhO/F
a
H+
PhO/F
Ar
CF3
H
H+
Fa or OPha
CF3
Ar
CF3
a
Ar
15/16
C
14
Scheme 3 Probable mechanism for reaction of 6 with terminal alkynes.
3
4
For Cu(III) chemistry, see: (a) A. J. Hickman and M. S. Sanford,
Nature, 2012, 484, 177; (b) A. Casitas and X. Ribas, Chem. Sci.,
2013, 4, 2301.
Finally, complex 10 was also able to trifluoromethylate
arylboronic acids and alkynes in 44% and 99% yields
35 (Scheme 4). Further efforts on reactivity of these CuIII-CF3
complexes are ongoing regarding the scope, mechanistic
aspects and development of other novel transformations.
For CuIII-CF3 complexes, see: (a) M. A. Willert-Porada, D. J. Burton
and N. C. Baenziger, J. Chem. Soc. Chem. Commun., 1989, 1633; (b)
D. Naumann, T. Roy, K.-F. Tebbe and W. Crump, Angew. Chem., Int.
Ed. Engl., 1993, 32, 1482; (c) A. M. Romine, N. Nebra, A. I.
Konovalov, E. Martin, J. Benet-Buchholz and V. V. Grushin, Angew.
Chem., Int. Ed., 2015, 54, 2745.
B(OH)2
CF3
KF (2 equiv), 50oC
+
(1)
90 5 (a) H. Shen, Z. Liu, P. Zhang, X. Tan, Z. Zhang and C. Li, J. Am.
Chem. Soc., 2017, 139, 9843; (b) X. Tan, Z. Liu, H. Shen, P. Zhang,
Z. Zhang and C. Li, J. Am. Chem. Soc., 2017, 139, 12430.
6
7
8
10
DMF (1 mL)
O2, 6h
OCH3
11a
OCH3
(0.1 mmol)
(0.2 mmol)
12a, 44%
(a) S.-L. Zhang and W.-F. Bie, RSC Adv., 2016, 6, 70902; (b) S.-L.
Zhang and W.-F. Bie, Dalton Trans., 2016, 45, 17588; (c) S.-L.
Zhang, H.-X. Wan and W.-F. Bie, Org. Lett., 2017, 19, 6372.
(a) S.-L. Zhang and Z.-Q. Deng, Phys. Chem. Chem. Phys., 2016, 18,
32664; (b) S.-L. Zhang, L. Huang and L.-J. Sun, Dalton Trans., 2015,
44, 4613.
H
CF3
(2)
KF (2 equiv), 100oC
95
+
10
H3CO
DMF (1 mL)
H3CO
N2, 1 h
(0.1 mmol)
13a (0.1 mmol)
14a, 99%
19F NMR of 6 in other deuterated solvents such as CD2Cl2, DMSO-d6
show similar two broad singlets at around -24 and -37 ppm at room
temperature.
Scheme 4 Reactivity of 10 with arylboronic acid and terminal alkyne.
In summary, CuIII trifluoromethyl complexes 6-10 with
100
40
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DOI: 10.1039/C8DT00291F
9
Computational results were derived from solution-phase optimization
using B3LYP method with a combined basis set of LANL2DZ for Cu
and 6-31g* for the other atoms in DMF.
10 CCDCs
1810661
and
1810662
contain
supplementary
5
10
15
20
25
crystallographic data for 6•DMF and 7, which can be obtained free of
charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
11 For selected copper-mediated trifluoromethylation of arylboronic
acids, see: (a) L. Chu and F.-L. Qing, Org. Lett., 2010, 12, 5060; (b)
T. D. Senecal, A. T. Parsons and S. L. Buchwald, J. Org. Chem.,
2011, 76, 1174; (c) T. Liu and Q. Shen, Org. Lett., 2011, 13, 2342; (d)
J. Xu, D.-F. Luo, B. Xiao, Z.-J. Liu, T.-J. Gong, Y. Fu and L. Liu,
Chem. Commun., 2011, 47, 4300; (e) C.-P. Zhang, J. Cai, C.-B. Zhou,
X.-P. Wang, X. Zheng, Y.-C. Gu and J.-C. Xiao, Chem. Commun.,
2011, 47, 9516; (f) B. A. Khan, A. E. Buba and L. J. Goossen,
Chem.–Eur. J., 2012, 18, 1577; (g) N. D. Litvinas, P. S. Fier and J. F.
Hartwig, Angew. Chem., Int. Ed., 2012, 51, 536; (h) T. Liu, X. Shao,
Y. Wu and Q. Shen, Angew. Chem., Int. Ed., 2012, 51, 540; (i) P.
Nova•k, A. Lishchynskyi and V. V. Grushin, Angew. Chem., Int. Ed.,
2012, 51, 7767; (j) Y. Ye and M. S. Sanford, J. Am. Chem. Soc., 2012,
134, 9034; (k) J. Xu, B. Xiao, C.-Q. Xie, D.-F. Luo, L. Liu and Y. Fu,
Angew. Chem., Int. Ed., 2012, 51, 12551.
12 For trifluoromethylation of C-H bond of terminal alkynes, see: (a) L.
Chu and F.-L. Qing, J. Am. Chem. Soc., 2010, 132, 7262; (b) D.-F.
Luo, J. Xu, Y. Fu and Q.-X. Guo, Tetrahedron Lett., 2012, 53, 2769;
(c) H. Serizawa, K. Aikawa and K. Mikami, Chem. Eur. J., 2013, 19,
17692; (d) L. He and G. C. Tsui, Org. Lett., 2016, 18, 2800.
13 For detailed reaction procedure and 19F NMR determination of
reaction yields, please refer to ESI†.
30 14 Reaction of 1 or 3 equivalents of 9a with 6 led to lower yields,
suggesting that two of the three CF3s in 6 can be introduced into the
products.
15 Oxy-trifluoromethylation, see: (a) R. Tomita, T. Koike and M. Akita,
Angew. Chem., Int. Ed., 2015, 54, 12923; (b) P. G. Janson, I.
35
40
45
50
Gaoneim, N. O. Ilchenko and K. J. Szab, Org. Lett., 2012, 14, 2882;
(c) H. Egami, R. Shimizu, S. Kawamura and M. Sodeoka,
Tetrahedron Lett., 2012, 53, 5503.
16 Similar mechanistic proposal, see: (a) Y.-L. Ji, J.-J. Luo, J.-H. Lin, J.-
C. Xiao and Y.-C. Gu, Org. Lett., 2016, 18, 1000; (b) Y. Xiang, Y.
Kuang and J. Wu, Org. Chem. Front., 2016, 3, 901; (c) A. Maji, A.
Hazra and D. Maiti, Org. Lett., 2014, 16, 4524; (d) A. Deb, S. Manna,
A. Modak, T. Patra, S. Maity and D. Maiti, Angew. Chem., Int. Ed.,
2013, 52, 9747.
17 Syn-selectivity citations, see: (a) C. L. Bumgardner, J. E. Bunch and
M.-H. Whangbo, Tetradedron Lett., 1986, 27, 1883; (b) C. L.
Bumgardner, J. E. Bunch and M.-H. Whangbo, J. Org. Chem., 1986,
51, 4082; (c) V. M. Muzalevskiy, V. G. Nenajdenko, A. V. Shastin,
E. S. Balenkova and G. Haufe, Synthesis, 2009, 13, 2249.
18 Another possible mechanism is suggested to involve the
recombination of the vinyl radical A to pyCuII(CF3)2, followed by ꢁ-
H elimination to give 14 and pyCuIII(H)(CF3)2 that can further
eliminate HCF3 observed experimentally.
6
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DOI: 10.1039/C8DT00291F
Ar CF3
ArB(OH)2
Ar
H
Ar
CF3
Ar
H
F
CF3
H
CsF or NaOPh
PhO
CF3
H
or
Ar
Ar
Novel square planar (L)CuIII(CF3)3 (L = pyridine, 2,4,6-trimethylpyridine) complexes are isolated
and characterized for the first time, which are fluxional in solution and versatile to enable various
transformations.