Communications
[
D ]toluene, [D ]DMF, [H ]toluene, or [H ]DMF. The iodoar-
In conclusion, the first efficient, exceptionally simple
procedure has been developed for the synthesis of
[(Ph P) Cu(CF )] (1). This complex has been fully charac-
8
7
8
7
ene substrate could not be the source of H, as the original
trifluoromethylation in neat PhI (see above) produced only
trace amounts of HCF . However, after 1 was heated with
D O in [H ]toluene (508C, 1 h), a characteristic signal from
CDF appeared in the F NMR spectrum as a 1:1:1 triplet at
3
3
3
[18]
terized in the solid state and in solution. Complex 1 is not
3
I
only the first NHC-free well-defined CF Cu complex that can
2
8
3
1
9
trifluoromethylate haloarenes, but it may also serve as a
3
d = À79.7 ppm with J(F,D) = 12.2 Hz. Although this result
starting material for the synthesis of other new CuÀCF
3
suggested that hydrolysis of 1 could be responsible for the
compounds such as 3. We believe that being easily accessible,
air-stable in the solid state, and having a long shelf life, 1 will
find further applications in synthetic and mechanistic studies.
side-formation of CHF , the residual water alone in the
3
solvents used (< 2 ppm for toluene and < 20 ppm in DMF)
could not account for the amounts of CHF produced in the
3
reactions. It was therefore presumed that CuÀCF3 bond
hydrolysis might have been caused by traces of water and SiÀ Experimental Section
OH moieties on the surface of the glass tubes used for the
reactions. Indeed, repeating some of the experiments in
1: A mixture of CuF
·3H O (0.33 g, 2.14 mmol) and PPh (2.24 g,
2 2 3
8.56 mmol) in MeOH (50 mL) was stirred under reflux in air until
most of the copper salt had dissolved (overnight). After the minute
presilylated (ClSiMe /toluene) tubes did minimize the pro-
3
amounts of residual solids were filtered off, the filtrate containing 2
duction of CHF , leading to improved yields of the desired
[13]
3
and Ph PO was evaporated to dryness on a rotary evaporator. The
3
products by approximately 10% (Table 2, entries 5, 7, and 8).
pale yellow solid residue was dried under vacuum (ca. 0.1 mm Hg)
overnight and treated with dry THF (4 mL) and CF SiMe (1.27 mL,
[
2,4]
As fully expected,
organic bromides were less reactive
3
3
[
19]
under similar conditions. Trifluoromethylated products were
formed upon treatment of 4-bromonitrobenzene, benzyl
bromide, and 2-bromonaphtalene with 1/tBu-bpy in only 25,
4 equiv) in a glove box. After the mixture was stirred for 2 h under
argon (HCF3 evolution observed), the white solid was quickly
separated by filtration in air, washed with dry THF (3 ꢂ 1 mL), then
with excess hexane, and dried under vacuum. The yield of 1 as a white
1
0, and 5% yield, respectively.
3
1
1
crystalline solid was 1.8 g (92%). NMR (CH
2
Cl
2
, 258C): P{ H} d =
Complex 3 was also found to efficiently trifluoromethy-
19
À0.8 ppm (br. s); F d = À26.2 ppm (s).
late iodoarenes in DMF at 808C in 60–85% yield (Table 3).
The choice of the solvent was determined by good solubility
of 3 in DMF. Improved yields were obtained in certain cases,
for example, for 4-trifluoromethylchlorobenzene (80%), 4-
trifluoromethylbenzonitrile (85%), and 2-trifluoromethylpyr-
idine (85%). Importantly, there is no need to use iodoarene
substrates in excess for efficient trifluoromethylation with 1
and 3 (Table 2 and Table 3). In contrast, the trifluorometh-
ylation of ArI with the only other reported well-defined
3
: A solution of phen (0.20 g, 1.09 mmol) in dry CH Cl (2 mL)
2 2
was added to a solution of 1 (1.0 g, 1.09 mmol) in dry CH Cl (8 mL).
2
2
All solids quickly dissolved to produce a red-orange solution. After
0 min, Et O (5 mL) was added to prompt crystallization of 3, with
3
2
subsequent addition of another 5 mL portion of Et O. The solid was
separated by decantation, washed with Et O (3 ꢂ 3 mL), and dried
under vacuum. The yield of 3 as orange-red crystals was 0.48 g (77%).
2
2
1
NMR (CD Cl , 258C): H d = 7.2–7.4 (m, 15H, PPh ), 7.6 (dd, J = 5
2
2
3
and 9 Hz, 2H, phen), 7.8 (br. s, 2H, phen), 8.3 (d, J = 7 Hz, 2H, phen),
1
9
9.0 ppm (br. s, 2H, phen); F d = À23.6 (major, s, CuCF ), À31.0 ppm
3
À
31
CuCF complexes (NHC-stabilized) can be high-yielding only
(minor, s, [Cu(CF
)
3
2
] );
P d = 2.0 ppm (br. s). Calcd. for
3
C H CuF N P: C 64.8, H 4.0, N 4.9; found: C 65.0, H 4.0, N 4.7.
when the aromatic substrate is present in a large (fivefold)
31 23
3
2
[10]
General procedure for aromatic trifluoromethylation with 1: In a
glovebox, a 5 mm NMR tube was charged with 1 (50 mg, 0.054 mmol),
ArI (0.060 mmol, 1.1 equiv), tBu-bpy (16 mg, 0.060 mmol, 1.1 equiv),
dry toluene (0.55 mL), and a stock solution of 4,4’-difluorobiphenyl
excess.
[
a]
Table 3: Trifluoromethylation with 3.
(internal standard) in toluene (0.05 mL). The tube was sealed with a
rubber septum and heated in an oil bath at 808C (Table 2). The
reaction was monitored by F NMR spectroscopy.
[
b]
19
Entry
Starting material
Product
Yield [%]
65
General procedure for aromatic trifluoromethylation with 3: In a
glovebox, a 5 mm NMR tube was charged with 3 (36 mg, 0.063 mmol),
ArI (0.070 mmol, 1.1 equiv), 4,4’-difluorobiphenyl (internal standard,
4–8 mg), and dry DMF (0.6 mL). The tube was sealed and heated in
an oil bath at 808C for 16 h. The mixture was analyzed by F NMR
spectroscopy.
1
2
3
4
5
6
7
8
9
60
1
9
65
80
Received: March 3, 2011
Revised: April 5, 2011
Published online: June 22, 2011
60
70
Keywords: copper · fluorine · haloarenes ·
85
.
aromatic trifluoromethylation · organometallic compounds
60
85
[
1] a) J. H. Clark, D. Wails, T. W. Bastock, Aromatic Fluorination,
CRC, Boca Raton, FL, 1996; b) P. Kirsch, Modern Fluoroorganic
Chemistry, Wiley-VCH, Weinheim, 2004; c) K. Uneyama, Orga-
nofluorine Chemistry, Blackwell, Oxford, 2006; d) I. Ojima,
[
8
a] Reaction conditions: 3 (0.06 mmol; [3]=0.1m), ArI (1.1 equiv), DMF,
08C, 16 h. [b] Yields determined by F NMR spectroscopy with 4,4’-
1
9
difluorobiphenyl as an internal standard.
7658
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 7655 –7659