Synthesis of trifluoromethyl ketones by palladium-catalyzed cross-coupling reaction of phenyl trifluoroacetate with organoboron compounds

Article abstract of DOI:10.1246/bcsj.74.371

Cross-coupling reaction of aryl trifluoroacetates with organoboron compounds catalyzed by palladium complexes gives trifluoromethyl ketones in moderate to excellent yields under mild conditions. The catalytic process has been designed on the basis of fundamental studies dealing with oxidative addition of phenyl trifluoroacetate to a Pd(0) complex to give a (phenoxo)(trifluoroacetyl)palladium(II) complex and its subsequent reaction with phenylboronic acid to liberate phenyl trifluoromethyl ketone. The catalytic cycle is proposed to be composed of (a) oxidative addition of the ester to give acyl(aryloxo)palladium intermediate, (b) the subsequent transmetallation with arylboron compounds, and (c) reductive elimination. Palladium(0) complexes, as well as catalysts prepared in situ from palladium acetate and 3 molar amounts of tributylphosphine or phosphite at room temperature, serve as convenient and effective catalysts. The process is applicable to a wide range of phenyl- and naphthylboronic acids to give various aryl trifluoromethyl ketones under mild conditions. Aryl perfluoroalkyl ketone derivatives can be similarly prepared in high yields from various phenyl perfluoroalkanecarboxylates and arylboronic acids.

Full text of DOI:10.1246/bcsj.74.371

© 2001 The Chemical Society of Japan
371
Bull. Chem. Soc. Jpn., 74, 371–376 (2001)
Synthesis of Trifluoromethyl Ketones by Palladium-Catalyzed Cross-
Coupling Reaction of Phenyl Trifluoroacetate with Organoboron
Compounds
Ryuki Kakino, Isao Shimizu, and Akio Yamamoto*
Department of Applied Chemistry, Graduate School of Science and Engineering and Advanced Research Institute
for Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555
(Received September 18, 2000)
Cross-coupling reaction of aryl trifluoroacetates with organoboron compounds catalyzed by palladium complexes
gives trifluoromethyl ketones in moderate to excellent yields under mild conditions. The catalytic process has been de-
signed on the basis of fundamental studies dealing with oxidative addition of phenyl trifluoroacetate to a Pd(0) complex
to give a (phenoxo)(trifluoroacetyl)palladium(II) complex and its subsequent reaction with phenylboronic acid to liberate
phenyl trifluoromethyl ketone. The catalytic cycle is proposed to be composed of (a) oxidative addition of the ester to give
acyl(aryloxo)palladium intermediate, (b) the subsequent transmetallation with arylboron compounds, and (c) reductive
elimination. Palladium(0) complexes, as well as catalysts prepared in situ from palladium acetate and 3 molar amounts of
tributylphosphine or phosphite at room temperature, serve as convenient and effective catalysts. The process is applicable
to a wide range of phenyl- and naphthylboronic acids to give various aryl trifluoromethyl ketones under mild conditions.
Aryl perfluoroalkyl ketone derivatives can be similarly prepared in high yields from various phenyl perfluoroalkanecar-
boxylates and arylboronic acids.
Cleavage of carbon-halogen bonds in organic halides pro-
moted by transition metal complexes, notably by palladium
complexes, has been extensively used in catalytic processes.1
In contrast, cleavage of carbon–oxygen bonds in oxygen-con-
taining organic compounds by transition metal complexes has
not been well exploited, except for the processes using allylic
esters.2 In our attempts to find new transition-metal-catalyzed
synthetic processes, we have been concerned with studies of
fundamental processes of the carbon-oxygen bond cleavage in
oxygen-containing organic compounds promoted by low va-
lent transition metal complexes.3,4,5 Our recent study revealed
that the C−O bonds in carboxylic anhydrides can be readily
cleaved on interaction with a Pd(0) complex 1 (Eq. 1).4
convert a variety of carboxylic anhydrides4b and carboxylic
acids6 into corresponding aldehydes under mild conditions
(Eq. 2).
(2)
Another type of C−O bond cleavage process of potential
utility in organic synthesis is the C−O bond cleavage of car-
boxylic esters. Recently, we reported that a palladium(0) com-
plex having basic and compact trimethylphosphine ligands re-
acted with aryl trifluoroacetates 2 under mild conditions to
cause the C−O bond cleavage between the acyl and the OAr
groups to give trans-(aryloxo)(trifluoroacetyl)bis(trimethyl-
phosphine)palladium(II) 3 (Eq. 3).5
(1)
(3)
Based on the fundamental studies on cleavage of the C−O
bonds in acid anhydrides on interaction with Pd(0) complexes,
we have developed novel catalytic hydrogenation processes to

372 Bull. Chem. Soc. Jpn., 74, No. 2 (2001)
New Catalytic Process Using C−O Bond Cleavage
If the oxidative addition process involving the acyl-aryloxy
bond cleavage in carboxylic esters can be combined with other
elementary processes such as transmetallation, olefin insertion,
and reductive elimination, we can anticipate development of
useful catalytic processes. The present paper is concerned with
the transmetallation of the acyl-aryloxy type complexes with
arylboron compounds and the application of the basic informa-
tion derived thereof to synthesis of aryl fluoroalkyl ketones cat-
alyzed by palladium complexes.
Results and Discussion
Reaction of trans-(Phenoxo)(trifluoroacetyl)bis(trime-
thylphosphine)-palladium(II) 3 with Phenylboronic Acid.
We first examined the possibility to replace the phenoxo
ligand in the trans-(phenoxo)(trifluoroacetyl)bis(trimethyl-
phosphine)palladium 3 generated by the acyl-OPh bond cleav-
age in phenyl trifluoroacetate on interaction with the Pd(0)
complex.5 In fact, we found that treatment of 3 with phenylbo-
ronic acid 4 at room temperature yielded phenyl trifluorometh-
yl ketone 5 in a good yield (Eq. 4). The result suggests that the
transmetallation of 3 with 4 takes place readily to give a (phe-
nyl)(trifluoroacetyl)palladium intermediate that further releas-
es ketone 5 rapidly on reductive elimination.
Scheme 1. Catalytic cycle for the formation of trifluo-
romethyl ketones.
Table 1. Effect of Catalysts on the Cross-Coupling Re-
action of Phenyl Trifluoroacetate with Phenylboronic
Acid
(4)
Run
Pd-catalyst
Yield/%a)
1
2
3
4
5
6
[Pd(dba)2]
0
38
53
36
9
+ 2PnBu3
+ 3PnBu3
+ 4PnBu3
+ DPPP
+ DPPB
On the basis of the result, we designed a catalytic cycle,
shown in Scheme 1, to convert the aryl trifluoroacetates into
trifluoromethyl ketones by combining the C-O bond cleavage
with transmetallation in a manner similar to the Suzuki–
Miyaura coupling process where the carbon−halogen cleavage
is involved.7,8
Trimethylphosphine is known to serve as an excellent ligand
to prepare the phosphine-coordinated model compounds, but it
is often not suitable for the real catalytic process. Therefore,
we examined the catalytic processes using other tertiary phos-
phine ligands.
40
7
[Pd(PPh3)4]
[Pd(OAc)2]
trace
8
9
0
61
82
70
51
76
33
20
16
20
+ 2PnBu3
+ 3PnBu3
+ 4PnBu3
+ 2P(OnBu)3
+ 3P(OnBu)3
+ 2PCy3
+ 3PCy3
+ 2PPh3
+ 3PPh3
10
11
12
13
14
15
16
17
Catalytic Process Converting Various Phenyl Perfluoro-
alkanecarboxylates into Aryl Perfluoroalkyl Ketones on In-
teraction with Arylboron Compounds Catalyzed by Palla-
18
Pd/C
0
dium Complexes. (1) Effect of Catalyst.
The catalytic
a) Determined by GC using nC14H30 as an internal standard.
cross-coupling process of phenyl trifluoroacetate with phenyl-
boronic acid was found to proceed in the presence of zerova-
lent palladium complexes such as [Pd(dba)2] (dba = diben-
zylideneacetone) in combination with tributylphosphine in ni-
trogen-containing polar solvents at 80 °C to afford phenyl trif-
luoromethyl ketone. Table 1 summarizes the effect of the cata-
lysts employed for the reaction.
Whereas the [Pd(dba)2] complex alone proved to be inactive,
addition of tributylphosphine gave good yields of the ketone.
Addition of three equivalents of P(nBu)3 per palladium devel-
oped a good yield. Increase in the amount of the tributylphos-

R. Kakino et al.
Bull. Chem. Soc. Jpn., 74, No. 2 (2001) 373
phine further to four equivalents caused a slight decrease in the
ketone yield. Employment of a bidentate ditertiary phosphine
ligand such as 1,2-bis(diphenylphosphino)propane (DPPP)
was not suitable, whereas the ditertiary phosphine ligands such
as 1,2-bis(diphenylphosphino)butane (DPPB) that form a larg-
er and more flexible chelate ring with the palladium center
gave a moderate yield of the ketone. These results suggest that
the role of the tertiary phosphine ligand is to stabilize and con-
trol the reactivity of the palladium center, but use of excess of
the monotertiary phosphine ligand or of a chelate ligand that
strongly binds to palladium should be avoided. The reason why
[Pd(PPh3)4] was not so effective may be due to coordination of
excess PPh3 ligands to hinder the catalytic process.
Higher yields can be obtained in polar solvents such as N,N-
dimethylformamide (DMF) and NMP than in less polar sol-
vents like dioxane and toluene, while acetonitrile was not ef-
fective.
(3) Scope and Limitation. Table 3 shows the applicability
of the process to substituted phenylboronic acids containing
various substituents at ortho-, meta-, and para-positions. Sub-
stitution with the methoxy group at the ortho position gave a
Table 3. Synthesis of Trifluoromethyl Ketones via the
Palladium-Catalyzed Cross-Coupling of Phenyl Trifluo-
roacetate with Arylboronic Acids
These results indicate that a Pd(0) complex serves as a cata-
lyst and suggest that the catalytic cycle is composed of some
processes between Pd(0) and Pd(II) species. However, in a real
system it is not necessary to use the palladium(0) complex, but
instead the mixed system of Pd(OAc)2 in combination with a
suitable ligand can be more convenient. It is known that the
palladium(II) acetate is reduced to a Pd(0) complex in a solu-
tion with formation of phosphine oxide mediated by water.9
The results shown in Table 1 indicate that Pd(OAc)2 used as the
catalyst precursor in combination with tributylphosphine or
tributyl phosphite serves as a good and convenient catalyst in
synthesis. Again, addition of an excess of the ligand had a dete-
riorating effect. Employment of more bulky tricyclohexylphos-
phine was less effective than use of tributylphosphine. Addi-
tion of triphenylphosphine was not suitable. Palladium on car-
bon was found ineffective as the catalyst.
Run
1
Boronic acid
Yield/%a),b)
81a)
2
3
4
68b)
78b)
84b)
(2) Effects of Solvents and Temperature.
Table 2
compares the reactions in various solvents in the presence
of Pd(OAc)2−3PnBu3 system. In 1-methyl-2-pyrrolidinone
(NMP), the yield of the phenyl trifluoromethyl ketone in-
creased on raising the reaction temperature from room temper-
ature to 60 and to 80 °C, whereas further increase to 100 °C
had a deteriorating effect.
5
6
0a)
74b)
0a)
Solvents used in the cross-coupling reaction had a consider-
able influence on the yields of phenyl trifluoromethyl ketone.
7
Table 2. Effect of Solvent and Temperature on the Cross-
Coupling Reaction of Phenyl Trifluoroacetate with
Phenylboronic Acid
8
66a)
17a)
66b)
72b)
0a)
9
10
11
12
Run
Temp/◦C
Solvent
Yield/%a)
1
2
3
4
5
6
7
8
r. t.
60
80
100
80
80
NMP
NMP
NMP
0
33
82
73
trace
0
NMP
dioxane
toluene
CH3CN
CMF
80
80
trace
63
n
a) Determined by GC using C14H30 as an internal standard.
b) Isolated yield
a) Determined by GC using nC14H30 as an internal standard.

374 Bull. Chem. Soc. Jpn., 74, No. 2 (2001)
New Catalytic Process Using C−O Bond Cleavage
somewhat lower yield, but the substituent such as methoxy and
methyl group at meta or para position gave good yields (Run
2−4, 6). Substitution with the two methoxy groups at ortho po-
sitions completely hindered the catalytic process, indicating
the steric hindrance of the two adjacent substituents (Run 5).10
Substitution with an electron-withdrawing group such as tri-
fluoromethyl group at the ortho position of phenylboronic acid
gave no ketone (Run 7), whereas substitution of the trifluorom-
ethyl group at the para position produced the corresponding ke-
tone in a poor yield (Run 9). On the other hand, the electron-
withdrawing substituent at the meta position gave a good yield
of ketone (Run 8). Other arylboronic acids such as 1-naphthyl-
and 2-naphthylboronic acids afforded the ketones in moderate
yields (Run 10 and 11), whereas 2-furylboronic acid yielded no
ketone (Run 12).
for synthesizing compounds less tolerant to the presence of a
base.
In the Suzuki−Miyaura coupling of aryl- and alkenyl halides
with aryl- and alkenylboronic acids or esters, addition of a base
such as NaOEt, KOAc, and NaOH is necessary to drive the re-
actions. The effect of addition of these bases was accounted for
as replacement of the halide ligand in the catalyst intermediate
with the alkoxide, carboxylate, or hydroxide that are more sus-
ceptible to the transmetallation with the oxophilic arylboronic
acids or esters than a halide. In the present case, on the other
hand, use of phenyl trifluoroacetate gives the (phenoxo)(tri-
fluroacetyl)palladium intermediate having the phenoxide
ligand suitable for the direct transmetallation process with the
oxophilic arylboronic acid.11
Conclusion
The palladium-promoted coupling process is applicable to
other phenyl perfluoroalkanecarboxylates. The synthesis with a
protocol similar to the one employed for phenyl trifluoroace-
tate gave perfluoroalkyl ketones in good yields, starting from
phenyl pentafluoropropionate and heptafluorobutyrate (Eq. 5).
On the basis of fundamental studies on oxidative addition of
phenyl trifluoroacetate with a Pd(0) complex to give the (phe-
noxo)(trifluoroacetyl)palladium type complex and its subse-
quent transmetallation process, we could devise a novel type of
catalytic process to convert aryl perfluoroalkanecarboxylates
and organoboron compounds into aryl perflluoroalkyl ketones
without using a base. Since suitable processes of synthesizing
biologically important fluorine-containing compounds are lim-
ited,12 the process provides a convenient new route to ketones
containing fluoroalkyl groups or their derivatives.13 The
present process as well as the process utilizing carboxylic
anhydrides14 may serve as a general route to unsymmetrical ke-
tones under mild conditions without using organic halides and
a base.
(5)
Organoboron compounds other than arylboronic acids were
also examined. Employment of sodium tetraphenylborate in a
quantity somewhat higher than equimolar amount in combina-
tion with the phenyl trifluoroacetate gave phenyl trifluorometh-
yl ketone in 59%. On the other hand, reduction in the amount
of the tetraphenyl borate to one-fourth caused a drop in the
yield down to 20%, suggesting that only a part of the four phe-
nyl groups in NaBPh4 is available for the transfer. Other phe-
nylboron compounds such as Bu4NBPh4 and 2-phenyl-1,3,2-
dioxaborinane were ineffective (Eq. 6).
Experimental
General Procedures. All manipulations were carried out un-
der argon atmosphere using Schlenk tube techniques. Solvents
were purified by the usual methods under argon. NMR spectra
1
were recorded on a JEOL Lambda 500 spectrometer for H (500
MHz, referenced to SiMe4 via residual solvent protons), 13C{1H}
(125 MHz, referenced to SiMe4 via the solvent resonance), and 19
F
(471 MHz, referenced to trifluoroacetic acid in CDCl3 as an exter-
nal standard) NMR. Coupling constants (J values) are given in
hertz (Hz), and spin multiplicities are indicated as follows: s (sin-
glet), d (doublet), t (triplet), m (multiplet), vt (virtual triplet), and
br (broad). Gas chromatographic analyses (GC) were carried out
on a GC-353 equipped with SE30. Low-resolution mass spectra
were obtained with a JEOL JMS-Automass 150 that is coupled
with gas chromatograph.
(6)
Reagents. All arylboronic acids were commercial products
and were used without further purification. Phenyl trifluoroacetate
purchased from Tokyo Kasei Kogyo Co. was distilled before use.
All aryl perfluoroalkanecarboxylates except for phenyl trifluoroac-
etate were synthesized by the reaction of trifluoroacetic anhydride,
pentafluoropropionic anhydride, and heptafluorobutyric anhydride
with the corresponding phenols in the presence of sodium hydride.
PnBu3 purchased from Kanto Kagaku Co. was distilled before use.
All tertiary phosphines except for PnBu3 and P(OnBu)3 were com-
mercial products and were used directly. Trans-[PdEt2(PMe3)2]15
and Pd(dba)216 were synthesized by literature methods. Pd(OAc)2
and 10% Pd/C were used as received from commercial suppliers.
Trans-[Pd(COCF3)(OPh)(PMe3)2] 3 was prepared as previ-
The main features of the catalytic processes are consistent
with a catalytic cycle composed of the elementary processes
shown in Scheme 1. Although the palladium-catalyzed cross-
coupling reaction of organic halides with organoboron com-
pounds generally requires the assistance of a base,7 no base is
required in the present reaction of phenyl trifluoroacetates with
arylboronic acids giving some advantage to the present system

R. Kakino et al.
Bull. Chem. Soc. Jpn., 74, No. 2 (2001) 375
ously reported5 by the reaction of [Pd(styrene)(PMe3)2]15 with
phenyl trifluoroacetate.
CF3), 113.4 (s, aromatic C), 56.5 (s, OCH3); 19F NMR (acetone-d6,
r. t., 471 MHz) δ –73.4 (s, CF3). GC-MS m/z (rel intensity) 204
(100), 135 (97), 105 (37), 92 (98). Found: C, 52.58; H, 3.20%.
Calcd for C9H7F3O2: C, 52.95; H, 3.46%.
Reaction of trans-[Pd(COCF3)(OPh)(PMe3)2] 3 with Phe-
nylboronic Acid 4 (Eq. 4).
To an N-methyl-2-pyrrolidinone
(NMP) solution (5 cm3) of trans-[Pd(COCF3)(OPh) (PMe3)2] (466
mg, 1.04 mmol), phenylboronic acid (127 mg, 1.04 mmol) was
added at room temperature. The mixture was stirred for 1.5 h at
room temperature. The GC and GC-MS analysis of the products
was performed with nC14H30 as an internal standard. Formation of
phenyl trifluoromethyl ketone (66%) was confirmed. CF3COC6H5
was characterized by GC-MS by comparing with an authentic
sample (Aldrich). GC-MS m/z (rel. intensity) 174 (55), 105 (100),
95 (15).
Effect of Catalyst (Table 1). A typical procedure is as fol-
lows (Run 3). An NMP solution (5 cm3) containing Pd(OAc)2
(11.8 mg, 0.0525 mmol), tributylphosphine (0.038 cm3, 15 mmol),
phenyl trifluoroacetate (0.15 cm3, 1.0 mmol), and phenylboronic
acid (148 mg, 1.21 mmol) in a 25 cm3 Schlenk tube was heated un-
der argon at 80 °C for 24 h.
Effect of Solvent and Temperature (Table 2). A typical pro-
cedure is as follows (Run 8). NMP solutions (5 cm3) containing
Pd(OAc)2 (11.7 mg, 0.052 mmol), tributylphosphine (0.038 cm3,
15 mmol), phenyl trifluoroacetate (0.15 cm3, 1.0 mmol), and phe-
nylboronic acid (149 mg, 1.22 mmol) in a 25 cm3 Schlenk tube
were heated under argon at room temperature, 60 °C, 80 °C, and
100 °C, respectively, for 24 h. The effects of solvents were exam-
ined in NMP, dioxane, toluene, acetonitrile, and DMF by carrying
out the synthesis at 80 °C.
Synthesis of Trifluoromethyl Ketones (Table 3). A typical
procedure is as follows (Run 4). An NMP solution (5 cm3) contain-
ing Pd(OAc)2 (11.5 mg, 0.051 mmol), tributylphosphine (0.038
cm3, 0.15 mmol), phenyl trifluoroacetate (0.15 cm3, 1.0 mmol),
and 4-methoxyphenylboronic acid (185 mg, 1.22 mmol) in a 25
cm3 Schlenk tube was heated under argon at 80 °C for four hours.
On cooling the reaction mixture, diethyl ether and H2O were add-
ed and the aqueous layer was extracted with diethyl ether. The
combined ether solution was dried (MgSO4) and the solvent was
evaporated in vacuo. Purification of the residue by column chro-
matography (hexane/Et2O = 9:1) gave the corresponding product
as a colorless oil (173 mg; yield 84%).
CF3COC6H4-3-OMe: Colorless oil (78%); 1H NMR (ace-
tone-d6, r. t., 500 MHz) δ 7.67–7.65 (m, 1H, aromatic H),
7.60–7.57 (m, 1H, aromatic H), 7.54 (br, 1H, aromatic H),
7.41–7.39 (m, 1H, aromatic H), 3.90 (s, 3H, OCH3);
13C{1H} NMR (acetone-d6, r. t., 125 MHz) δ 180.8 (q, 2JCF = 34.6
Hz, carbonyl C), 161.2 (s, aromatic C), 131.9 (s, aromatic C),
3
1
123.1 (q, JCF = 2.6 Hz aromatic C), 117.6 (q, JCF = 291.0 Hz,
CF3), 114.9 (q, 4JCF = 1.9 Hz, aromatic C), 56.0 (q, 7JCF = 2.8 Hz,
OCH3); 19F NMR (acetone-d6, r. t., 471 MHz) δ –70.0 (s, CF3).
GC-MS m/z (rel. intensity) 204 (100), 135 (97), 107 (86), 92 (92),
77 (99). Found: C, 52.86; H, 3.20%. Calcd for C9H7F3O2: C,
52.95; H, 3.46%.
1
CF3COC6H4-4-Me:13e Colorless oil (74%); H NMR (ace-
tone-d6, r. t., 500 MHz) δ 7.98 (d, 2H, 3JHH = 8.22 Hz aromatic H),
3
7.48 (d, 2H, JHH = 8.22 Hz aromatic H), 2.46 (s, 3H, CH3);
13C{1H} NMR (acetone-d6, r. t., 125 MHz) ꢀ 180.5 (q, 2JCF = 34.4
Hz, carbonyl C), 148.4 (s, aromatic C), 130.9 (s, aromatic C),
130.9 (q, 3JCF = 2.2 Hz, aromatic C), 128.2 (s, aromatic C), 117.8
(q, 1JCF = 291.2 Hz, CF3), 21.8 (s, CH3); 19F NMR (acetone-d6, r.
t., 471 MHz) δ –70.0 (s, CF3). GC-MS m/z (rel intensity) 188
(61), 119 (96), 91 (98).
CF3COC6H4-3-CF3: (66%); CF3COC6H4-3-CF3 was charac-
terized by GC-MS on comparison with an authentic sample (Ald-
rich). GC-MS m/z (rel intensity) 223 (14), 173 (100), 145 (98), 125
(13), 95 (20).
CF3COC6H4-4-CF3: (17%); CF3COC6H4-4-CF3 was charac-
terized by GC-MS on comparison with an authentic sample (Ald-
rich). GC-MS m/z (rel intensity) 223 (10), 173 (100), 145 (92), 125
(12), 95 (15).
CF3CO-1-C10H7:13b,e Colorless oil (66%); 1H NMR (ace-
tone-d6, r. t., 500 MHz) δ 8.75–8.74 (m, 1H, aromatic H),
8.35–8.33 (m, 1H, aromatic H), 8.29–8.27 (m, 1H, aromatic H),
8.08–8.07 (m, 1H, aromatic H), 7.76–7.71 (m, 2H, aromatic H),
7.69–7.66 (m, 1H, aromatic H); 13C{1H} NMR (acetone-d6, r. t.,
125 MHz) ꢀ 182.3 (q, 2JCF = 33.3 Hz, carbonyl C), 137.2 (s, aro-
matic C), 135.0 (s, aromatic C), 132.5 (q, 3JCF = 3.8 Hz, aromatic
C), 131.8 (s, aromatic C), 130.3 (s, aromatic C), 130.1 (s, aromatic
C), 128.1 (s, aromatic C), 127.2 (s, aromatic C), 125.7 (s, aromatic
CF3COC6H4-4-OMe:13e Colorless oil (84%); 1H NMR (ace-
tone-d6, r. t., 500 MHz) δ 8.22–8.06 (m, 2H, aromatic H),
7.99–7.09 (m, 2H, aromatic H), 3.96 (s, 3H, OCH3);
13C{1H} NMR (acetone-d6, r. t., 125 MHz) ꢀ 179.2 (q, 2JCF = 33.9
Hz, carbonyl C), 166.8 (s, aromatic C), 133.4 (q, 3JCF = 2.2 Hz, ar-
omatic C), 123.3 (s, aromatic C), 117.9 (q, 1JCF = 291.2 Hz, CF3),
115.7 (s, aromatic C), 56.4 (s, OCH3); 19F NMR (acetone-d6, r. t.,
471 MHz) δ –71.0 (s, CF3). GC-MS m/z (rel intensity) 204 (83),
135 (92), 107 (100), 92 (98), 77 (97). Found: C, 53.18; H, 3.38%.
Calcd for C9H7F3O2: C, 52.95; H, 3.46%.
1
C), 125.4 (s, aromatic C), 117.6 (q, JCF = 292.9 Hz, CF3);
19F NMR (acetone-d6, r. t., 471 MHz) δ –69.1 (s, CF3). GC-MS:
m/z (rel intensity) 224 (73), 155 (100), 127 (91).
CF3CO-2-C10H7:13e Yellow powder (72%); 1H NMR (ace-
tone-d6, r. t., 500 MHz) δ 8.75 (s, 1H, aromatic H), 8.25–8.23 (m,
1H, aromatic H), 8.14–8.12 (m, 1H, aromatic H), 8.06–8.05 (m,
2H, aromatic H), 7.79–7.76 (m, 1H, aromatic H), 7.71–7.68 (m,
1H, aromatic H); 13C{1H} NMR (acetone-d6, r. t., 125 MHz) ꢀ
180.9 (q, 2JCF = 34.4 Hz, carbonyl C), 137.4 (s, aromatic C), 133.9
(q, 3JCF = 2.8 Hz, aromatic C), 133.2 (s, aromatic C), 131.2 (s, aro-
matic C), 131.1 (s, aromatic C), 130.2 (s, aromatic C), 128.8 (s, ar-
omatic C), 128.5 (s, aromatic C), 128.0 (s, aromatic C), 124.7 (q,
The following trifluoromethyl ketones were synthesized by the
above general procedure.
CF3COC6H5:13c,d,e (81%); CF3COC6H5 was characterized by
GC-MS by comparison with an authentic sample (Aldrich). GC-
MS m/z (rel intensity) 174 (60), 105 (100), 95 (20).
1
4JCF = 1.6 Hz, aromatic C), 117.8 (q, JCF = 291.2 Hz, CF3);
1
CF3COC6H4-2-OMe: Yellow oil (68%); H NMR (acetone-
19F NMR (acetone-d6, r. t., 471 MHz) δ –70.3 (s, CF3). GC-MS
m/z (rel intensity) 224 (100), 155 (95), 127 (94).
d6, r. t., 500 MHz) δ 7.71–7.68 (m, 1H, aromatic H), 7.65–7.63
(m, 1H, aromatic H), 7.26–7.25 (m, 1H, aromatic H), 7.15–7.11
(m, 1H, aromatic H), 4.09 (s, 3H, OCH3); 13C{1H} NMR (acetone-
d6, r. t., 125 MHz) ꢀ 184.3 (q, 2JCF = 36.3 Hz, carbonyl C), 160.5
(s, aromatic C), 136.9 (s, aromatic C), 131.7 (s, aromatic C), 122.8
(s, aromatic C), 121.7 (s, aromatic C), 117.1 (q, 1JCF = 290.6 Hz,
Synthesis of Other Perfluoroalkyl Ketones (Eq. 5). Appli-
cability of the process for other phenyl perfluoroalkanecarboxy-
lates was examined. A typical procedure using phenyl heptafluo-
robutyrate is given below. An NMP solution (5 cm3) containing
Pd(OAc)2 (11.7 mg, 0.052 mmol), tributylphosphine (0.038 cm3,

376 Bull. Chem. Soc. Jpn., 74, No. 2 (2001)
New Catalytic Process Using C−O Bond Cleavage
0.15 mmol), heptafluorobutyrate (295 mg, 1.02 mmol), and 4-
methoxyphenylboronic acid (181 mg, 1.19 mmol) in a 25 cm3
Schlenk tube was heated under argon at 80 °C for four hours. After
the reaction mixture was cooled, diethyl ether and H2O were add-
ed and the aqueous layer was extracted with diethyl ether. The
combined ether solution was dried (MgSO4) and the solvent was
evaporated in vacuo. Purification of the residue by column chro-
matography (hexane/Et2O = 13:1) gave the corresponding product
as a colorless oil (271 mg; yield 87%).
6863 (1981); d) T. Yamamoto, J. Ishizu, and A. Yamamoto, Bull.
Chem. Soc. Jpn., 55, 623 (1982); e) T.Yamamoto, M. Akimoto, O.
Saito, and A. Yamamoto, Organometallics, 5, 1559 (1986); f) S.
Komiya, A.Yamamoto, and T.Yamamoto, Chem. Lett., 1981, 193;
g) K. Sano, T. Yamamoto, and A. Yamamoto, Chem. Lett., 1983,
115; h) K. Sano, T.Yamamoto, and A.Yamamoto, Bull. Chem. Soc.
Jpn., 57, 2741 (1984).
4
a) K. Nagayama, F. Kawataka, M. Sakamoto, I. Shimizu,
and A. Yamamoto, Chem. Lett., 1995, 367; b) K. Nagayama, F.
Kawataka, M. Sakamoto, I. Shimizu, and A. Yamamoto, Bull.
Chem. Soc. Jpn., 72, 573 (1999).
1
C3F7COC6H4-4-OMe: Colorless oil (87%); H NMR (ace-
tone-d6, r. t., 500 MHz) δ 8.09 (m, 2H, aromatic H), 7.18–7.11 (m,
2H, aromatic H), 3.96 (s, 3H, OCH3); 13C{1H} NMR (acetone-d6,
r. t., 125 MHz) δ 181.8 (t, 2JCF = 25.2 Hz, carbonyl C), 166.9 (s, ar-
omatic C), 133.7 (q, 3JCF = 3.6 Hz, aromatic C), 124.9 (s, aromatic
C), 118.7 (qt, 1JCF = 287.0 Hz, 2JCF = 34.0 Hz, CF3), 115.7 (s, aro-
matic C), 111.7 (tt, 1JCF = 268.0 Hz, 2JCF = 31.5 Hz, COCF2CF2),
112.3–107.2 (m, CF2CF2CF3), 56.4 (s, OCH3); 19F NMR (acetone-
d6, r. t., 471 MHz) δ –79.0 (t, 3JFF = 9.2 Hz, CF2CF2CF3), –111.7
(q, 3JFF = 9.2 Hz, CF2CF2CF3), –124.2 (s, COCF2CF2). GC-MS m/
z (rel intensity) 304 (100), 285 (32), 257 (31), 207 (7), 169 (22),
135 (93), 107 (98), 92 (97), 76 (99). Found: C, 43.54; H, 2.02%.
Calcd for C11H7F7O2: C, 43.44; H, 2.32%.
5
K. Nagayama, I. Shimizu, and A. Yamamoto, Bull. Chem.
Soc. Jpn., 72, 799 (1999).
6
K. Nagayama, I. Shimizu, and A. Yamamoto, Chem. Lett.,
1998, 1143.
7
For a recent review on palladium-catalyzed cross-coupling
reaction of organoboron compounds. a) N. Miyaura and A. Suzuki,
Chem. Rev., 95, 2457 (1995); b) A. Suzuki, J. Organomet. Chem.,
576, 147 (1999).
8
Palladium catalyzed cross-coupling reactions to give ke-
tones with acyl halides and organoboron compounds such as phe-
nylboronic acids and sodium arylborates have been reported. a) C.
S. Cho, K. Itotani, and S. Uemura, J. Organomet. Chem., 443, 253
(1993); b) N. A. Bumagin and D. N. Korolev., Tetrahedron Lett.,
40, 3057 (1999); c) M. Haddach and J. R. McCarthy, Tetrahedron
Lett., 40, 3109 (1999); d) G. W. Kabalka, R. R. Malladi, D. Tejedor,
and S. Kelley, Tetrahedron Lett., 41, 999 (2000). e) H. Chen and
M.-Z. Deng, Org. Lett., 2, 1649 (2000).
1
C2F5COC6H4-4-OMe: Colorless oil (86%); H NMR (ace-
tone-d6, r. t., 500 MHz) ꢀ 8.09 (m, 2H, aromatic H), 7.15 (m, 2H,
aromatic H), 3.96 (s, 3H, OCH3); 13C{1H} NMR (acetone-d6, r. t.,
2
125 MHz) ꢀ 181.9 (t, JCF = 26.0 Hz, carbonyl C), 166.9 (s, aro-
matic C), 133.5 (q, 3JCF = 3.4 Hz, aromatic C), 124.4 (s, aromatic
C), 118.7 (qt, 1JCF = 286.0 Hz, 2JCF = 35.4 Hz, CF3), 115.7 (s, aro-
matic C), 111.7 (tq, 1JCF = 268.6 Hz, 2JCF = 35.4 Hz, COCF2CF3),
56.4 (s, OCH3); 19F NMR (acetone-d6, r. t., 471 MHz) ꢀ –80.5 (s,
CF3), –113.7 (s, CF2CF3). GC-MS m/z (rel intensity) 254 (53), 207
(17), 157 (14), 135 (97), 107 (83), 92 (100), 76 (91). Found: C,
47.40; H, 2.51%. Calcd for C10H7F5O2: C, 47.26; H, 2.78%.
Cross-Coupling Reaction of Phenyl Trifluoroacetate with
Other Organoboron Compounds (Eq. 6). A typical procedure
using NaBPh4 is given below. An NMP solution (5 cm3) contain-
ing Pd(OAc)2 (11.8 mg, 0.0525 mmol), tributylphosphine (0.038
cm3, 15 mmol), phenyl trifluoroacetate (0.15 cm3, 1.0 mmol), and
sodium tetraphenylborate (416 mg, 1.22 mmol) in a 25 cm3
Schlenk tube was heated under argon at 80 °C for four hours. The
yields of phenyl trifluoromethyl ketone were determined by GC
using nC14H30 as an internal standard.
9
a) F. Ozawa, A. Kubo, and T. Hayashi, Chem. Lett., 1992,
2177; b) C. Amatore, A. Jutand, and M. A. M’Barki, Organometal-
lics, 11, 3009 (1992); c) T. Mandai, T. Matsumoto, J. Tsuji, and S.
Saito, Tetrahedron Lett., 34, 2513 (1993).
10 Cross-coupling reaction of sterically hindered arylboronic
acids with organic electrophiles is known to proceed ineffectively.
W. J. Thompson and J. Gaudino, J. Org. Chem., 49, 5237 (1984).
11 a) T. Ishiyama, M. Murata, and N. Miyaura, J. Org. Chem.,
60, 7508 (1995); b) N. Miyaura, K. Yamada, H. Suginome, and A.
Suzuki, J. Am. Chem. Soc., 107, 972 (1985). Reports on palladium-
catalyzed cross-coupling reaction of organic compounds with or-
ganoboron reagents under neutral conditions. c) T. Moriya, N.
Miyaura, and A. Suzuki, Synlett, 1994, 149; d) F. Sasaya, N.
Miyaura, and A. Suzuki, Bull. Korean Chem. Soc., 8, 329 (1987).
12 a) J. K. Liebman, A. Greenberg, and W. R. Dolbier, Jr.,
“Fluorine-containing Molecules, Structure, Reactivity, Synthesis,”
VCH, NewYork (1998); b) “Synthetic Fluorine Chemistry,” ed by
G. A. Olah, R. D. Chambers, and G. K. S. Prakash, John Wiley &
Sons, New York (1992); c) “Selective Fluorination in Organic and
Bioorganic Chemistry,” ed by J. T. Welsh, ACS Symposium Series
456 (1990).
13 The general methods for synthesizing of trifluoromethyl ke-
tones. a) J. -P. Bague, D. Bonnet-Delphon, Tetrahedron, 47, 3207
(1991); b) Y. Yokoyama and K. Mochida, Synlett, 1997, 907; c) J.
Wiedemann, T. Heiner, G. Mloston, G. K. S. Prakash, and G. A.
Olah, Angew. Chem., Int. Ed. Engl., 37, 820 (1998); d) R. P. Singh,
G. Cao, R. L. Kirchmeier, and J. M. Shreeve, J. Org. Chem., 64,
2873 (1999). e) T. Keumi, M. Shimada, M. Takahashi, and H.
Kitajima, Chem. Lett., 1990, 783.
This study was financially supported by grants from the
Ministry of Education, Science, Sports and Culture, and
Nippon Zeon Co., Ltd.
References
1
a) J. Tsuji, “Palladium Reagents and Catalysts, Innovations
in Organic Synthesis,” Wiley, Chichester (1995); b) J. P. Collman,
L. S. Hegedus, J. N. Norton, and R. G. Finke, “Principles and Ap-
plications of Organotransition Metal Chemistry,” University Sci-
ence Books, California (1987); c) A.Yamamoto, “Organotransition
Metal Chemistry,” Wiley-Interscience, NewYork (1986).
2
a) A.Yamamoto, Adv. Organometal. Chem., 34, 111 (1992);
b) Y. -S. Lin and A. Yamamoto, “Topics in Organometallic Chem-
istry,” ed by S. Murai, Springer, Berlin (1999), Vol. 3, pp. 161–192.
14 Results to be reported separately.
15 Y.-J. Kim, K. Osakada, A. Takenaka, and A. Yamamoto, J.
Am. Chem. Soc., 112, 1096 (1990).
16 T. Ukai, H. Kawazura, Y. Ishii, J. J. Bonnet, and J. A. Ibers,
J. Organomet. Chem., 65, 253 (1974).
3
a) J. Ishizu, T. Yamamoto, and A. Yamamoto, Chem. Lett.,
1976, 1091; b) T. Yamamoto, J. Ishizu, T. Kohara, S. Komiya, and
A. Yamamoto, J. Am. Chem. Soc., 102, 3758 (1980); c) T.
Yamamoto, J. Ishizu, and A. Yamamoto, J. Am. Chem. Soc., 103,