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Despite these notable advances, most strategies rely upon
using the costly Me3SiCF3 reagent or gaseous HCF3, which is
hard to handle in most academic laboratories, and Et3N·3HF or
Et3N·HCl to stabilize the CuCF3 reagent.
The use of readily available, convenient, and inexpensive al-
ternatives, such as trifluoroacetic acid (TFA) and its deriva-
tives,[4b,30–32] as the trifluoromethyl source for the preparation
of trifluoromethylarenes is an attractive prospect. Trifluorome-
thylation of aryl iodides with CuCF3 formed by decarboxylation
of methyl trifluoroacetate has been reported.[12e,33] Vicic and
co-workers also reported the preparation of (NHC)–copper–tri-
fluoroacetate complexes for decarboxylative trifluoromethyl-
ation of aryl halides.[34] However, despite their economically
benign nature, the reaction suffers from some disadvantages,
such as high operating temperatures (160–1808C), lack of prac-
ticability, and poor substrate scope. Very recently, Zhang and
co-workers reported an Ag-catalyzed radical CÀH trifluorome-
thylation of arenes with TFA as the trifluoromethylating re-
agent.[35] This method avoids prefunctionalization of the sub-
strate, but has low regioselectivity and limited functional-
group compatibility. Therefore, to match the increasing scien-
tific and practical demands, it is still of continued interest and
great importance to develop convenient and efficient methods
for arene trifluoromethylation. In this context, our group re-
Scheme 2. Strategies for the synthesis of trifluoromethylarenes (pin=pina-
colato).
diazonium salts (Scheme 2c), and palladium-,[17] copper-,[18] and
silver-catalyzed[19]/mediated[20] trifluoromethylation of aromatic
CÀH bonds (Scheme 2d).
In addition, the use of copper reagents in trifluoromethyl-
ation reactions has attracted much interest due to their good
reactivity, low toxicity, and good regiospecificity.[21] Since the
pioneering work of McLoughlin and Thrower in 1969 related to
the reductive coupling of aryl halides with perfluoroalkyl io-
dides in the presence of copper metal,[22] CuCF3 reagents have
been extensively studied and applied in stoichiometric trifluo-
romethylation reactions of aryl halides.[23] For example, Vicic
and co-workers reported the first thermally stable and well-de-
fined complexes of the type [Cu(CF3)(NHC)] (NHC=N-heterocy-
clic carbene), which were obtained from the reaction of
[CuCl(NHC)] with KOtBu followed by treatment with Me3SiCF3
at room temperature (Scheme 3a).[24] Hartwig and co-workers
cently developed an efficient copper-catalyzed trifluoromethyl-
[36]
ation of aryl iodides by using Me3SiCF3
and related
copper reagents for the synthesis of fluorinated organic com-
pounds.[37] Herein, we report the synthesis of complexes
[Cu(O2CCF3)(phen)] and [Cu(phen)2][O2CCF2Cl] and their suc-
cessful application to the trifluoromethylation and difluorome-
thylation of (hetero)aryl halides and phenols to furnish trifluo-
romethylarenes and (hetero)aryl difluoromethyl ethers, respec-
tively, in good yields.
Results and Discussion
Synthesis and structural studies
The reactions of copper tert-butoxide (prepared in situ from
CuCl and NaOtBu) with diimine ligand (1–2 equiv) and subse-
quent addition of TFA or chlorodifluoroacetic acid in THF at
room temperature afforded neutral copper–trifluoroacetate
complex [Cu(O2CCF3)(phen)] (1a), ionic complex [Cu-
(Me2phen)2][(O2CCF3)] (1b), or chlorodifluoroacetate complexes
[Cu(L)2][O2CCF2Cl] (2a–c; L=bpy, Me2bpy, and phen, respec-
tively) (Scheme 4). All these complexes were air stable in solu-
tion and in the solid state for several hours. These complexes
are soluble in DMF, CH3CN, and CH2Cl2, but insoluble in ben-
zene and toluene. Furthermore, these new trifluoroacetato and
chlorodifluoroacetato complexes are amenable to large-scale
synthesis (ꢀ3 g).
Scheme 3. Methods for the synthesis of copper trifluoromethylating re-
agents.
prepared the 1,10-phenanthroline (phen) ligated complex
[Cu(CF3)(phen)] by the reaction of copper tert-butoxide and
phen with Me3SiCF3 in benzene (Scheme 3b).[25] Grushin and
co-workers obtained the triphenylphosphine-coordinated com-
plex [Cu(CF3)(Ph3P)3] by heating a solution of CuF2·3H2O and
Ph3P in methanol at reflux temperature, followed by reaction
with Me3SiCF3 in THF (Scheme 3c);[26] they subsequently re-
ported the synthesis of CuCF3 derivatives from the reaction of
CuCl and KOtBu with fluoroform (Scheme 3d).[27] Mikami and
Hu also independently reported direct synthesis of the CuCF3
reagent from cuprate and trifluoromethyl ketone derivatives[28]
or phenyl trifluoromethyl sulfones, respectively[29] (Scheme 3e).
These copper reagents reacted with aryl iodides, bromides,
boronic acids, and boronate esters to give benzotrifluorides.
1
Complexes 1a, 1b, and 2a–c were characterized by H, 13C,
and 19F NMR spectroscopy, IR spectroscopy, and elemental
analysis. The IR spectrum of the crystalline product 1a shows
intense bands at n˜ =1674 (C=O) and 1434 cmÀ1 (CÀO), which
indicates h1-O monodentate coordination to the copper center.
Complex 1a exhibits a diagnostic resonance in the 19F NMR
Chem. Eur. J. 2016, 22, 2075 – 2084
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