Reaction of benzyne with fluorinated 1,3-dicarbonyl compounds

Article abstract of DOI:10.1016/j.jfluchem.2012.12.004

The insertion of fluorinated 1,3-dicarbonyl compounds to benzyne resulted in regioselective formation of various fluorinated 1,5-dicarbonyl compounds which are not readily available by other methods. Products include 2-trifluoroacetyl- and 2-(perfluoroalk

Full text of DOI:10.1016/j.jfluchem.2012.12.004

Journal of Fluorine Chemistry 146 (2013) 80–85
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Reaction of benzyne with fluorinated 1,3-dicarbonyl compounds
Muhammad Zahid a, Muhammad Farooq Ibad a, Zharylkasyn A. Abilov c, Peter Langer a,b,
*
a Institut fu¨r Chemie, Universita¨t Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b Leibniz-Institut fu¨r Katalyse e. V. an der Universita¨t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
c Al-Farabi Kazakh National University, Al-Farabi Ave. 71, 050040 Almaty, Kazakhstan
A R T I C L E I N F O
A B S T R A C T
Article history:
The insertion of fluorinated 1,3-dicarbonyl compounds to benzyne resulted in regioselective formation
of various fluorinated 1,5-dicarbonyl compounds which are not readily available by other methods.
Products include 2-trifluoroacetyl- and 2-(perfluoroalkanoyl)phenylacetic estres, 2-fluoro-2-phenyla-
cetic esters, 1-aryl-2-(2-trifluoroacetylphenyl)ethan-1-ones and other derivatives.
ß 2012 Elsevier B.V. All rights reserved.
Received 29 October 2012
Received in revised form 10 December 2012
Accepted 10 December 2012
Available online 19 December 2012
Keywords:
Arenes
Benzyne
Insertions
1,3-Dicarbonyl compounds
Fluorinated compounds
1. Introduction
Herein, we report a new and convenient synthesis of fluorinated
aceto- and benzophenones based on the reaction of benzyne with
Organofluorine molecules play an important role as synthetic
drugs [1]. 5-Fluorouracil was the first fluorinated drug which was
developed as an anti-tumor agent in 1957 [2]. The importance of
fluorine containing compounds is based on their metabolic
stability and lipophilicity and, thus, high bioavailability. The
incorporation of fluoroalkyl groups and particularly the trifluor-
omethyl (CF3) group in pharmaceutically and agrochemically
relevant molecules have a significant impact on their physical and
biological properties [3a]. Fluorinated aceto- and benzophenones,
containing a 1,5-dicarbonyl unit connected by a benzene moiety,
are of considerable relevance as synthetic intermediates in
medicinal chemistry. For example, benzophenone A, prepared
by a multistep synthetic synthesis starting from 3-(4-fluorophe-
nyl)propanoic acid, was used as a key intermediate during the
synthesis of fluorinated pteridines which were reported to act as
anti-viral drugs for the treatment of liver diseases (HCV) [3b].
fluorinated 1,3-dicarbonyl compounds. First evidence for the
existence of an aryne was reported in 1902 at the University of
Rostock: Stoermer and Kahlert observed the formation of 2-
ethoxybenzofuran on treatment of 3-bromobenzofuran with bases
in ethanol and postulated the formation of ortho-didehydroben-
zofuran [4a,b]. In 1927, Bachmann and Clarke suspected benzyne
as a reactive intermediate of the Wurtz-Fittig synthesis [4b,c].
Wittig, in 1942, suggested the existence of benzyne [4d]. During
the last 50 years, the discovery of benzyne had a strong impact in
the field of organic chemistry [5]. Despite the indirect evidence for
the existence of benzyne, a direct proof was not reported before
2001 [6]. Benzyne as a reagent in synthetic organic chemistry
suffered from several drawbacks, such as its high reactivity and the
harsh basic conditions required for its generation by the classic
protocol [5]. In 1983, Kobayashi described a mild method for the
generation of benzyne at moderate temperature which relies on a
fluoride-induced 1,2-elimination reaction of ortho-(trimethylsily-
l)aryltriflates [7]. Recently, Stoltz and coworkers reported the
Trifluoroacetophenone B, available by
a multistep synthesis
starting with 3-bromo-5-iodobenzoic acid, was reported to show
considerable activity against pain [3c]. Trifluoroacetophenone C,
which was also prepared in many steps, was reported to exhibit a
pronounced antithrombotic activity [3d] (Chart 1).
insertion of benzyne into $-bonds of 1,3-dicarbonyl compounds to
give (2-acylphenyl)acetates and related products [8]. It was
presumed that the reaction proceeds by formal [2+2] cycloaddition
and subsequent fragmentation. While benzyne insertions into
metal–metal, heteroatom–metal, heteroatom–heteroatom, car-
bon–metal, and carbon–heteroatom
before, the work of Stoltz represented the first mild and direct
insertion of benzyne into a carbon–carbon -bond. Herein, we
$-bonds had been reported
* Corresponding author at: Institut fu¨r Chemie, Universita¨t Rostock, Albert-
Einstein-Str. 3a, 18059 Rostock, Germany.
$
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.12.004

M. Zahid et al. / Journal of Fluorine Chemistry 146 (2013) 80–85
81
Table 1
F
F
F
Synthesis of 3a–j.
NO2
O
OMe
2,3
R1
R2
R3
Yield (%)a
NH2
O
O
O
F
F
a
b
c
d
e
f
Me
EtO
F
71
71
87
79
85
50
73
57
67
70
O
CF3
EtO
H
H
H
H
H
H
H
H
H
O
F
O
F
4-FC6H4
4-FC6H4
4-(NO2)C6H4
C3F7
MeO
EtO
F
Br
EtO
N
t-Bu
g
h
i
CF3
Ph
B
A
C
CF3
2-Naphthyl
Me
CF3
Chart 1. Some important fluorinated 1,5-dicarbonyl compounds.
j
CF3
2-Furyl
a
Yields of isolated products.
O
again 71% yield. This result shows that electron poor, CF3-
substituted -ketoesters can be successfully employed to give
trifluoroacetyl-substituted products. Starting with -ketoesters
2c,d, containing a fluorinated phenyl group, products 3c,d were
prepared. For comparison, we also studied the employment of
O
O
R1
R3
TMS
OTf
b
i
b
R2
R1
R3
b
-
O
R2
ketoester 2e which contains a (strong electron-withdrawing) nitro
substituent. Its reactions with 1 gave product 3e in 85% yield. The
1
2
3
synthesis of 3c–e shows that
b-ketoesters containing electron
Scheme 1. Synthesis of 3a–j. Conditions: i,
(1.0 mmol), MeCN (3 mL), 80 8C, 40–60 min.
1
(0.5 mmol), 2 (0.5 mmol), CsF
withdrawing aryl groups can be successfully used. This methodol-
ogy was successfully extended to fluorinated 1,3-diketones
producing high yields of the corresponding regioselective products
(Table 1). It was observed that fluorinated, trifluoromethyl- and
perfluoroalkyl-substituted ketoesters and diketones gave the
desired acyl-alkylation products in good yields. The coupling of
report what is, to the best of our knowledge, the first application of
this method to fluorinated 1,3-dicarbonyl compounds. The
transformations reported herein provide an efficient access to
fluorinated aceto- and benzophenones which contain a 1,5-
dicarbonyl unit connected by a benzene moiety. The products
are not readily available by other methods.
aryne precursor 1 with fluorinated
b-diketones 2f–j was also
examined. These -diketones reacted with 1 to produce side-chain
b
fluorinated ortho-disubstituted arenes 3f–j in good yields.
The formation of the products can be explained by the
mechanism suggested by Stoltz and coworkers [8]: The insertion
2. Results and discussion
The CsF mediated reaction of ethyl 2-fluoroacetoacetate (2a)
with ortho-(trimethylsilyl)aryltriflate 1, following the conditions
reported by Stoltz, afforded the fluorinated product 3a in 71% yield
(Scheme 1, Table 1). This result shows that the reaction is
compatible with the presence of a fluorine atom present at carbon
of benzyne into the a,b(C–C) single bond of the b-ketoesters and b-
diketones presumably proceeds by a domino [2+2] cycloaddition/
fragmentation reaction via intermediates A, B, and C (Scheme 2).
Related domino reactions were reported by other authors [9,10].
The structures of the products were independently verified by
2D-NMR experiments (COSY, HMBC, NOESY). Two regioisomers
have to be taken into account, namely, isomers D and E in case of
atom C-2 of the
b-ketoester. The reaction of ethyl 4,4,4-
trifluoroacetoacetate (2b) with 1 gave fluorinated product 3b in
O
R1
TMS
CsF
O
O
/ MeCN
R3
R2
R1
80°C,40-60 min
OTf
R3
O
R2
1
2
3
H
O
Cs
Cs
R1
R2
O
O
O
Cs
R2
R3
R1
R1
R3
R3
O
O
B
R2
C
A
Scheme 2. Mechanism proposed by Stoltz et al. [8] for the acyl-alkylation of benzyne.

82
M. Zahid et al. / Journal of Fluorine Chemistry 146 (2013) 80–85
Fig. 1. Possible regiomers of 3b.
3b (Fig. 1). For the CH2 group, no splitting (due to fluorine coupling)
was observed in the 13C NMR spectrum which suggests that isomer
D
is present. This structure was also supported by mass
fragmentation pattern. The base peak m/z = 187 gave some
evidence for a trifluoroacetyl group directly bonded to the benzene
moiety. This base peak is generated by sequential loss of an ethyl
group and CO2. In case of isomer E, two fragments should be
observed, i.e. one 1,1,1-trifluoropronoyl with m/z = 111 and a
second ethyl benzoate with m/z = 150. Both of these fragments
were found to be absent.
Fig. 3. HMBC, and NOESY interpretation of 3g (HMBC: single headed, COSY: double
headed).
3. Experimental
In the 13C NMR of 1,3-diketone 3g, again no long rang
splitting of the CH2 group was observed. Furthermore, the GC–
MS fragmentation pattern was in favor of isomer F (Fig. 2). The
structure was independently confirmed by 2D-NMR (Fig. 3). The
3.1. General remarks
Reactions were carried out under inert atmosphere (Argon).
Solvents for reactions were dried and distilled by standard
methods or purchased from Merck1, Aldrich1, Acros Organics1
,
carbonyl group resonating at
d
= 198.3 ppm showed a clear
HMBC interaction with the CH2 protons. In addition, an HMBC
coupling was also observed between an aromatic proton
and others whenever exclusion of water was desired. Solvents for
liquid chromatography and extraction were always distilled prior
to use and partly reused after fractional distillation (n-heptane,
ethyl acetate). Bruker AC 250, Bruker ARX 300, Bruker ARX 500. For
NMR characterization the one-dimensional 1H NMR, proton-
decoupled 13C NMR, and DEPT 135 spectra were collected. If
necessary other techniques (NOESY, COSY, HMQC, and HMBC)
were applied as well. All NMR spectra presented in this work, were
collected in DMSO-d6 and CDCl3 solution. All chemical shifts were
resonating at
d = 7.72 ppm and the carbon of the trifluoroacetyl
group which confirmed the direct bonding of the latter to the
aromatic ring (isomer F). The position of each proton and carbon
was located by NOESY, COSY and 1H NMR. The 19F coupling of
the carbon signals in the 13C NMR spectrum further supported
structure F.
The structure of 3e was also confirmed by 2D NMR experiments.
A clear HMBC correlation of the carbonyl carbon (
with two protons ( = 7.89 ppm) of the benzene ring, containing
the nitro group, and with one aromatic proton ( = 7.46 ppm) of the
d
= 196.2 ppm)
given in ppm. References (1H NMR): TMS (
CHCl3
= 7.26) were taken as internal standard. References (13
NMR): TMS ( = 0.0) or residual CHCl3 = 77.0) were taken as
d = 0.00) or residual
d
(
d
C
d
d
(d
second benzene ring were observed. The ester carbonyl carbon
showed a clear correlation with the protons of both CH2 groups
(d = 3.88, 3.95 ppm). To locate the exact position of the correlating
internal standard. Multiplicities are given as follows: s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet, br = broad signal.
More complex coupling patterns are represented by combinations
of the respective symbols. For example, td indicates a triplet of
protons, COSY and NOESY measurements were carried out (Fig. 4).
In conclusion, we have reported the reaction of fluorinated 1,3-
dicarbonyl compounds with benzyne. These reactions resulted in
the regioselective formation of various fluorinated acetophenones
and benzophenones containing a 1,5-dicarbonyl moiety connected
by a benzene ring. The products, such as 2-trifluoroacetyl- and 2-
(perfluoroalkanoyl)phenylacetic esters, 2-fluoro-2-phenylacetic
esters, or 1-aryl-2-(2-trifluoroacetylphenyl)ethan-1-ones, are of
pharmacological relevance and not readily available by other
methods.
Fig. 4. HMBC, NOESY and COSY interpretation of 3e (HMBC: single headed, COSY:
Fig. 2. Possible regiomers of 3g.
double headed; NOESY: single headed arrow beginning at the proton with d = 7.29).

M. Zahid et al. / Journal of Fluorine Chemistry 146 (2013) 80–85
83
doublets with the larger coupling constant associated with the first
symbol (here: triplet). Infrared Spectroscopy (IR): Nicolet 205 FT-
n-heptane) as a colorless oil (92 mg, 71%). 1H NMR (300 MHz,
CDCl3): = 1.18 (t, J = 7.15 Hz, 3H, CH3), 3.90 (s, 2H, CH2), 4.08 (q,
d
´
IR, Nicolet Protege 460 FT-IR Peaks are given the following
J = 7.15 Hz, 2H, CH2), 7.28 (dd, J = 7.6, 0.8 Hz, 1H, Ar), 7.38 (dt,
J = 7.7, 1.2 Hz, 1H, Ar), 7.53 (dt, J = 7.6, 1.3 Hz, 1H, Ar), 7.88 (dd,
assignments: w = weak, m = medium, s = strong, br = broad. Mass
Spectrometry (MS): AMD MS40, Varian MAT CH 7, MAT 731 (EI,
70 eV), Intecta AMD 402 (EI, 70 eV and CI), Finnigan MAT 95 (CI,
200 eV). High Resolution Mass Spectrometry (HRMS): Varian MAT
311, Intecta AMD 402. Elemental Analysis: LECO CHNS-932
Thermoquest Flash EA 1112. Melting Points: Micro heating table
HMK 67/1825 Kuestner (Bu¨chi Apparatus). Leitz Labolux 12 Pol
with heating table Mettler FP 90. Melting points are uncorrected.
Thin Layer Chromatography (TLC): Merck Silica gel 60 F254 on
aluminum foil from Macherey-Nagel. Detection was carried out
under UV light at 254 nm and 365 nm. As colorizing reagent the
following mixtures were used: 1–2/100 p-Anisaldehyde or
vanillin, 10/100 glacial acetic acid, 5/100 sulfuric acid, 83–84/
100 methanol. Column chromatography: column chromatography
was performed with Merck Silica Gel 60 or Macherey-Nagel Silica
Gel 60 (0.063–0.200 mm, 70–230 mesh). The finer Merck Silica Gel
60 (0.040–0.063 mm, 230–400 mesh) was chosen when appropri-
ate.
J = 7.8, 1.6 Hz, 1H, Ar); 19F NMR (63 MHz, CDCl3):
d
= ꢁ71.3 (s, 3F,
CF3); 13C NMR (75 MHz, CDCl3):
d = 14.1 (CH3), 40.1, 61.1 (CH2),
116.3 (q, JCF = 292.3 Hz, CF3), 127.6 (CH), 129.9 (C), 130.4 (q,
JCF = 3.8 Hz, CH, Ar), 133.1 (CH), 134.2 (CH), 137.2 (C), 170.6 (CO),
˜
182.5 (q, JCF = 34.7 Hz, CO); IR (ATR):
v
¼ 3218 (w), 1740 (m), 1465,
1405, 1268 (w), 1170 (s), 1097, 1030, 895 (m), 870, 846 (w), 773,
736, 712 (s), 612, 544 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) = 260
(10, [M]+), 215 (26), 214 (28), 191 (57), 187 (100), 137 (47), 135
(56), 119 (60), 90 (37), 89 (40); HRMS (EI): calcd. For C18H11O3F3
[M]+: 260.0659. Found: 260.0655.
3.5. Methyl 2-(2-(4-fluorobenzoyl)phenyl)acetate (3c)
Starting with 2-(trimethylsilyl)phenyl trifluoromethanesulfo-
nate (1) (186 mg, 0.63 mmol), methyl 3-(4-fluorophenyl)-3-
oxopropanoate (2c) (98 mg, 0.5 mmol), CsF (190 mg, 1.25 mmol)
in MeCN (3 mL), was heated up to 80 8C under argon for 45 min, 3c
was isolated after column chromatography (silica gel, 2% EtOAc in
n-heptane) as a colorless oil (118 mg, 87%). 1H NMR (300 MHz,
3.2. General procedure for the synthesis of compounds 3a–j
CDCl3):
Ar), 7.23–7.26 (m, 3H, Ar), 7.34–7.39 (m, 1H, Ar), 7.73 (dd, J = 5.4,
5.2 Hz, 2H, Ar); 19F NMR (63 MHz, CDCl3): = -105.3 (s, F); 13C NMR
(75 MHz, CDCl3): = 37.5 (CH2), 51.3 (CH3), 114.4 (d, JCF = 22.1 Hz,
d = 3.45 (s, 3H, CH3), 3.7 (s, 2H, CH2), 7.02 (t, J = 9.2 Hz, 2H,
A flame dried 100 mL round bottom flask equipped with
magnetic stir bar was charged with acetonitrile (3 mL). The
b
-
d
ketoester/ -diketone (0.4 mmol, 1.0 equiv.), 2-(trimethylsilyl)-
b
d
phenyl trifluoromethanesulfonate (1) (0.5 mmol, 1.25 equiv.),
and cesium fluoride (1.0 mmol, 2.5 equiv.) were sequentially
added to the flask. A septum was placed on the reaction vessel,
and the mixture was then heated at 80 8C for 45–60 min. When the
benzyne precursor was consumed by TLC analysis, the mixture was
extracted with brine (4 mL). The aqueous layer was back-extracted
with DCM (3ꢀ 4 mL). The organic layers were combined and dried
over Na2SO4. After filtration, the residue was concentrated under
reduced pressure and purified by flash chromatography.
CH, Ar), 125.4 (C), 125.6 (CH), 127.6 (C), 128.7, 129.9, 130.8 (CH),
132.1 (d, JCF = 9.4 Hz, CH, Ar), 132.8 (C), 133.1 (d, JCF = 2.9 Hz, CH,
Ar), 137.1, 164.6 (d, JCF = 250.3 Hz, C, Ar), 170.7, 190.5 (CO); IR
˜
(ATR):
v
¼ 2997 (w), 1732, 1656, 1595 (s), 1503, 1434, 1408 (w),
1267, 1223, 1147 (s), 1095, 1010, 941 (w), 918, 851 (m), 808, 783
(w), 741 (s), 632 (w), 600 (s) cmꢁ1; GC–MS (EI, 70 eV): m/z
(%) = 272 (6, [M]+), 213 (36), 212 (100), 183 (28), 123 (12), 95 (13);
HRMS (EI): calcd. For C16H13FO3 [M]+: 272.0843. Found: 272.0839.
3.6. Ethyl 2-(2-(4-fluorobenzoyl)phenyl)acetate (3d)
3.3. Ethyl 2-(2-acetylphenyl)-2-fluoroacetate (3a)
Starting with 2-(trimethylsilyl)phenyl trifluoromethanesulfo-
nate (1) (186 mg, 0.63 mmol), ethyl 3-(4-fluorophenyl)-3-oxopro-
panoate (2d) (105 mg, 0.5 mmol), CsF (190 mg, 1.25 mmol) in
MeCN (3 mL), was heated up to 80 8C under argon for 60 min, 3d
was isolated after column chromatography (silica gel, 2% EtOAc in
n-heptane) as a colorless oil (113 mg, 79%). 1H NMR (300 MHz,
Starting with 2-(trimethylsilyl)phenyl trifluoromethanesulfo-
nate (1) (186 mg, 0.63 mmol), ethyl 2-fluoro-3-oxobutanoate (2a)
(74 mg, 0.5 mmol), CsF (190 mg, 1.25 mmol) in MeCN (3 mL), was
heated up to 80 8C under argon for 45 min, 3a was isolated after
column chromatography (silica gel, 2% EtOAc in n-heptane) as a
colorless oil (80 mg, 71%). 1H NMR (300 MHz, CDCl3):
d
= 1.20 (t,
CDCl3):
d = 2.03 (t, J = 7.8 Hz, 3H, CH3), 4.79 (s, 2H, CH2), 4.94 (q,
J = 7.4 Hz, 3H, CH3), 2.54 (s, 3H, CH3), 4.15 (q, J = 7.7 Hz, 2H, CH2),
6.51 (d, J = 45.3 Hz, 1H, CH-F), 7.42 (t, J = 7.4 Hz, 1H, Ar), 7.53 (t,
J = 7.4 Hz, 1H, Ar), 7.73 (d, J = 8.2 Hz, Ar), 7.77 (d, J = 8.2 Hz, 1H, Ar);
J = 7.1 Hz, 2H, CH2), 8.04 (t, J = 10.1 Hz, 2H, CH, Ar), 8.24–8.29 (m,
3H, Ar), 8.36–8.42 (m, 1H, Ar), 8.76 (dd, J = 6.3, 3.9 Hz, 2CH, Ar); 19
F
NMR (63 MHz, CDCl3):
d
= ꢁ105.3 (s, F); 13C NMR (75 MHz, CDCl3):
19F NMR (63 MHz, CDCl3):
(75 MHz, CDCl3):
d
= ꢁ185.6 (s, 1F, CH-F); 13C NMR
d = 14.1 (CH3), 38.7, 60.8 (CH2), 115.4 (d, JCF = 21.5 Hz, CH, Ar),
d
= 14.0, 28.5 (CH3), 61.8 (CH2), 87.9 (d,
126.5, 129.7, 130.9, 131.8 (CH), 133.0 (d, JCF = 8.6 Hz, CH, Ar), 134.0
JCF = 177.2 Hz, CH), 126.9 (d, JCF = 14.3 Hz, CH, Ar), 128.8 (d,
JCF = 1.7 Hz, CH, Ar), 129.8 (CH), 132.6 (d, JCF = 1.4 Hz, CH, Ar), 135.1
(d, JCF = 18.7 Hz, C, Ar), 136.6 (d, JCF = 2.8 Hz, C, Ar), 168.1 (d,
˜
1599, 1368 (w), 1212, 1023 (s), 888 (m), 759, 695 (s) cmꢁ1; GC–MS
(EI, 70 eV): m/z (%) = 224 (5, [M]+), 195 (11), 177 (29), 149 (100),
105 (13), 77 (10); HRMS (EI): calcd. For C12H13O3F [M]+: 224.0849.
Found: 224.0850.
(C), 134.1 (d, JCF = 4.5 Hz, C, Ar), 138.5 (C), 165.7 (d, JCF = 248.6 Hz,
˜
C, Ar), 171.3, 198.5 (CO); IR (ATR):
v
¼ 2980 (w), 1730, 1656, 1595
(s), 1503 (m), 1446, 1408, 1368, 1333 (w), 1267, 1147 (s), 1094,
1026, 918, 850 (m), 783 (w), 741 (w), 688 (m), 601 (s) cmꢁ1; GC-MS
(EI, 70 eV): m/z (%) = 286 (3, [M]+), 257 (19), 241 (15), 213 (47), 212
(100), 183 (30), 165 (12); HRMS (EI): calcd. For C17H15FO3 [M]+:
286.0999; Found: 286.0992.
JCF = 25.5 Hz, CO), 200.7 (CO); IR (ATR):
v
¼ 2979 (w), 1731 (s),
3.7. Ethyl 2-(2-(4-nitrobenzoyl)phenyl)acetate (3e)
3.4. Ethyl 2-(2-(2,2,2-trifluoroacetyl)phenyl)acetate (3b)
Starting with 2-(trimethylsilyl)phenyl trifluoromethanesulfo-
nate (1) (186 mg, 0.63 mmol), ethyl 3-(4-nitrophenyl)-3-oxopro-
panoate (2e) (119 mg, 0.5 mmol), CsF (190 mg, 1.25 mmol) in
MeCN (3 mL), was heated up to 80 8C under argon for 60 min, 3e
was isolated after column chromatography (silica gel, 2% EtOAc in
n-heptane) as a colorless oil (133 mg, 85%). 1H NMR (300 MHz,
Starting with 2-(trimethylsilyl)phenyl trifluoromethanesulfo-
nate (1) (186 mg, 0.63 mmol), ethyl 4,4,4-trifluoro-3-oxobutano-
ate (2b) (92 mg, 0.5 mmol), CsF (190 mg, 1.25 mmol) in MeCN
(3 mL), was heated up to 80 8C under argon for 45 min, 3b was
isolated after column chromatography (silica gel, 2% EtOAc in

84
M. Zahid et al. / Journal of Fluorine Chemistry 146 (2013) 80–85
CDCl3):
d
= 1.07 (t, J = 6.9 Hz, 3H, CH3), 3.88 (s, 2H, CH2), 3.95 (q,
(s, 1H, Ar); 19F NMR (63 MHz, CDCl3):
NMR (75 MHz, CDCl3): d = 37.2 (CH2), 117.3 (q, JCF = 280 Hz, CF3),
d
= ꢁ71.3 (s, 3F, CF3); 13C
J = 5.9 Hz, 2H, CH2), 7.26–7.38 (m, 3H, Ar), 7.41–7.46 (m, 1H, Ar),
7.89 (d, J = 8.8 Hz, 2H, Ar), 8.22 (d, J = 9.8 Hz, 2H, Ar); 13C NMR
120.9 (C), 124.4, 126.7, 126.9, 127.9, 128.3, 128.6, 128.9, 129.1,
(75 MHz, CDCl3):
d
= 14.1 (CH3), 38.7, 60.9 (CH2), 123.4, 126.7 (CH),
129.4, 129.9 (CH), 132.5, 132.7, 134.6 (C), 135.9 (CH), 138.5 (C),
˜
129.1, 129.5 (C), 130.1, 131.1, 131.7, 132.1, 134.5, 137.1 (CH),
180.6 (q, JCF = 33.5 Hz, CO), 198.2 (CO); IR (ATR):
v
¼ 3058 (w),
˜
142.8, 150.0 (C), 171.2, 196.2 (CO); IR (ATR):
v
¼ 2980 (w), 1727,
1714 (m), 1654 (s), 1625, 1596 (m), 1571 1486, 1464, 1446, 1352
(w), 1291, 1275 (m), 1181, 1138 (s), 982 (w), 937 (s), 865, 825 (w),
784 (m), 750, 732, 663 (s), 602 (m), 574 (w) cmꢁ1; GC-MS (EI,
70 eV): m/z (%) = 342 (7, [M]+), 258 (100), 245 (34), 228 (24), 155
(45), 127 (100), 114 (34), 105 (37), 75 (9); HRMS (EI): calcd. For
1667 (s), 1601 (w), 1521 (s), 1445, 1406 (w), 1343, 1263, 1213,
1153 (s), 1025, 920, 866 (m), 850 (s), 821, 789 (w), 759 (m), 710 (s),
652 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) = 313 (7, [M]+), 296 (36),
268 (21), 267 (16), 240 (33), 239 (100), 194 (41), 165 (64); HRMS
(EI): calcd. For C17H15NO5 [M]+: 313.0945; Found: 313.0941.
C
20H13F3O2 [M]+: 342.0868; Found: 342.0869.
3.8. 3,3,4,4,5,5,5-Heptafluoro-1-(2-pivaloylphenyl)pentan-2-one (3f)
3.11. 1-(2-(2,2,2-Trifluoroacetyl)phenyl)propan-2-one (3i)
Starting with 2-(trimethylsilyl)phenyl trifluoromethanesulfo-
nate (1) (186 mg, 0.63 mmol), 6,6,7,7,8,8,8-heptafluoro-2,2-
dimethyloctane-3,5-dione (2f) (74 mg, 0.5 mmol), CsF (148 mg,
1.25 mmol) in MeCN (3 mL), was heated up to 80 8C under argon
for 50 min, 3f was isolated after column chromatography (silica
gel, 1% EtOAc in n-heptane) as a colorless oil (93 mg, 50%). 1H NMR
Starting with 2-(trimethylsilyl)phenyl trifluoromethanesulfo-
nate (1) (186 mg, 0.63 mmol), 1,1,1-trifluoropentane-2,4-dione
(2i) (77 mg, 0.5 mmol), CsF (103 mg, 1.25 mmol) in MeCN (3 mL),
was heated up to 80 8C under argon for 60 min, 3i was isolated after
column chromatography (silica gel, 2% EtOAc in n-heptane) as a
colorless oil (77 mg, 67%). 1H NMR (300 MHz, CDCl3):
d = 3.09 (s,
(300 MHz, CDCl3):
d
= 1.25 (s, 9H, 3CH3), 3.42 (s, 2H, CH2), 7.30 (d,
3H, CH3), 4.19 (s, 2H, CH2), 6.26 (d, J = 7.5 Hz, 1H, Ar), 6.37 (t,
J = 6.4 Hz,1H, Ar), 6.59 (t, J = 6.4 Hz,1H, Ar), 7.17 (d, J = 7.4 Hz, 1H,
J = 7.6 Hz, 1H, Ar), 7.36 (t, J = 8.6 Hz, 1H, Ar), 7.59 (t, J = 7.6 Hz, 1H,
Ar), 8.17 (d, J = 8.6 Hz, 1H, Ar); 19F NMR (63 MHz, CDCl3):
Ar); 19F NMR (63 MHz, CDCl3):
d
= ꢁ70.8 (s, 3F, CF3); 13C NMR
d
= ꢁ124.9 (m, CF2), ꢁ80.5 (m, CF2), ꢁ71.4 (CF3); 13C NMR
(75 MHz, CDCl3): d = 29.7 (CH3), 45.6 (CH2), 116.6 (q, JCF = 274.7 Hz,
CF3), 120.6 (C), 124.8, 127.5, 129.5, 134.7 (CH), 136.5 (C), 173.6 (q,
(75 MHz, CDCl3):
d
= 27.9 (3CH3), 35.6 (CH2), 66.1 (C), 99.7–
˜
101.2 (m, CF2), 105.8–106.2 (m, CF2), 119.1–120.3 (m, CF3), 125.5,
127.6, 129.3, 134.6 (CH), 136.8, 137.7 (C), 162.9, 196.3 (CO); IR
JCF = 34.5 Hz, CO), 193.1 (CO); IR (ATR):
v
¼ 2953 (w), 1585, 1402
(m), 1278, 1069 (s), 973 (m), 900, 796, 735, 694, 672 (s), 639, 555
(m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) = 230 (10, [M]+), 179 (32),
185 (14), 173 (41), 151 (100), 152 (10), 77 (51), 75 (14); HRMS (EI):
calcd. For C11H9F3O2 [M]+: 230.0555; Found: 230.0557.
˜
(ATR):
v
¼ 3233, 3065, 2228, 1591 (w), 1489, 1329 (m), 1165 (w),
1068, 929 (m), 857 (w), 779 (m), 747 (s) cmꢁ1; GC–MS (EI, 70 eV):
m/z (%) = 372 (6, [M]+), 202 (64), 188 (12), 187 (100), 169 (13), 160
(47), 145 (32), 131 (18), 89 (43); HRMS (EI): calcd. For C16H15F7O2
[M]+: 372.0960; Found: 372.0968.
3.12. 2,2,2-Trifluoro-1-(2-(2-(furan-2-yl)-2-
oxoethyl)phenyl)ethanone (3j)
3.9. 3-(2-Benzoylphenyl)-1,1,1-trifluoropropan-2-one (3g)
Starting with 2-(trimethylsilyl)phenyl trifluoromethanesulfo-
nate (1) (186 mg, 0.63 mmol), 4,4,4-trifluoro-1-(furan-2-yl)bu-
tane-1,3-dione (2j) (119 mg, 0.5 mmol), CsF (103 mg, 1.25 mmol)
in MeCN (3 mL), was heated up to 80 8C under argon for 50 min., 3j
was isolated after column chromatography (silica gel, 2% EtOAc in
n-heptane) as a colorless oil (99 mg, 70%). 1H NMR (300 MHz,
Starting with 2-(trimethylsilyl)phenyl trifluoromethanesulfo-
nate (1) (186 mg, 0.63 mmol), 4,4,4-trifluoro-1-phenylbutane-1,3-
dione (2g) (108 mg, 0.5 mmol), CsF (148 mg, 1.25 mmol) in MeCN
(3 mL), was heated up to 80 8C under argon for 45 min, 3g was
isolated after column chromatography (silica gel, 2% EtOAc in n-
heptane) as a colorless oil (107 mg, 73%). 1H NMR (300 MHz,
CDCl3):
J = 6.8 Hz, 1H, Ar), 7.42–7.46 (m, 2H, Ar), 7.81 (d, J = 8.8 Hz, 1H, Ar),
8.22 (d, J = 8.8 Hz, 1H, Ar); 19F NMR (63 MHz, CDCl3):
= ꢁ69.8 (s,
3F, CF3); 13C NMR (75 MHz, CDCl3):
= 43.7 (CH2), 112.6 (CH),
d = 5.42 (s, 2H, CH2), 6.71 (d, J = 5.9 Hz, 2H, Ar), 6.85 (t,
CDCl3):
2H, Ar), 7.59 (d, J = 7.6 Hz, 1H, Ar), 7.72 (t, J = 7.6 Hz, 2H, Ar), 7.89 (d,
J = 7.6 Hz, 1H, Ar); 19F NMR (63 MHz, CDCl3):
= ꢁ71.4 (s, 3F, CF3);
13C NMR (75 MHz, CDCl3):
= 37.1 (CH2), 112.4 (C), 116.3 (q,
d = 4.34 (s, 2H, CH2), 7.21–7.34 (m, 3H, Ar), 7.36–7.49 (m,
d
d
d
d
114.6 (q, JCF = 274.7 Hz, CF3), 118.4, 127.1, 127.5, 127.9, 128.5,
JCF = 292 Hz, C), 126.4, 128.3, 129.1 (CH), 129.7 (C), 130.2, 130.3,
128.9 (CH), 129.8 (C), 147.5 (CH), 151.4 (C), 184.2 (q, JCF = 34.5 Hz,
˜
130.5, 132.9, 133.1, 133.9 (CH), 136.7, 138.4 (C), 182.5 (q,
CO), 207.6 (CO); IR (ATR):
v
¼ 3150 (w), 1731 (s), 1642 (m), 1478
˜
JCF = 34.7 Hz, CO), 198.3 (CO); IR (ATR):
v
¼ 3062 (w), 1715 (m),
(s), 1549 (m), 1445 (m), 1228 (m), 1162 (m), 1003 (m), 815 (m), 746
(s) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) = 282 (2, [M]+), 213 (14), 212
(100), 184 (79), 128 (73), 89 (17); HRMS (EI): calcd. For C14H9F3O3
[M]+: 282.0504. Found: 282.0506.
1659 (s), 1596 (m), 1571, 1485 (w), 1447, 1269 (m), 1180, 1138 (s),
1000 (w), 935, 733, 698, 664, 639 (s) cmꢁ1; GC–MS (EI, 70 eV): m/z
(%) = 292 (48, [M]+), 195 (21), 187 (100), 165 (32), 105 (51), 77 (43),
75 (10); HRMS (EI): calcd. For C16H11F3O2 [M]+: 292.0711. Found:
292.0708.
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