Palladium-catalyzed direct α-arylation of α-fluoroketones: A straightforward route to α-fluoro-α-arylketones

Article abstract of DOI:10.1016/j.jfluchem.2011.08.004

The palladium-catalyzed direct α-arylation of both open-chain and cyclic α-fluoroketones by using P(o-tolyl)₃ or RuPhos as ligand and K₃PO₄·3H₂O as mild base has been developed. This method allows a variety of q

Full text of DOI:10.1016/j.jfluchem.2011.08.004

Journal of Fluorine Chemistry 133 (2012) 86–96
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Palladium-catalyzed direct
a
-arylation of
a-fluoroketones: A straightforward
route to -fluoro- -arylketones
a
a
Chen Guo a, Ruo-Wen Wang a, Yong Guo a, Feng-Ling Qing a,b,
*
a Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China
b College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North Renmin Lu, Shanghai 201620, China
A R T I C L E I N F O
A B S T R A C T
Article history:
The palladium-catalyzed direct
a-arylation of both open-chain and cyclic a-fluoroketones by using
Received 4 June 2011
P(o-tolyl)3 or RuPhos as ligand and K3PO4ꢀ3H2O as mild base has been developed. This method allows a
variety of quaternary -aryl- -fluoroketones to be easily prepared.
ß 2011 Elsevier B.V. All rights reserved.
Received in revised form 23 July 2011
Accepted 3 August 2011
Available online 10 August 2011
a
a
Keywords:
Direct
a-arylation
a
-Aryl-a-fluoroketones
Palladium-catalyzed reaction
1. Introduction
reaction conditions and required derivatization from the corre-
sponding -fluoroketones in advance.
The palladium-catalyzed direct -arylation of ketones, pio-
neered by Buchwald, Hartwig and Miura concurrently [7], has
become a general methodology for the synthesis of -arylketones.
This direct -arylation has also been expanded to the arylations of
a
Fluorinated compounds have been widely used as pharmaceu-
ticals and agrochemicals due to the fact that the introduction of
fluorine atom into organic molecules can alter their physical and
chemical properties and biological activities from structural
a
a
a
analogues in a dramatic way [1]. Recently,
a
-fluorocarbonyl
esters, lactones, amides and aldehydes [8]. However, to the best of
our knowledge, there are only two papers related to the palladium-
compounds have received a great deal of attention [2], because
they have been present as key moieties in many pharmaceutical
and bioactive molecules such as Solithromucin (CEM-101) and
Flindokalner (BMS 204352) [3]. Direct fluorination of
ketones was usually used for synthesis of quaternary
catalyzed direct arylation of
and co-workers described that the cyclic
directly coupled with aryl bromides, however the arylation of
open-chain -fluoroketone failed [6b]. Hartwig group reported the
palladium-catalyzed arylation of diethyl -fluoromalonate [9].
Herein, we describe the efficient and practical palladium-catalyzed
direct -arylation of both open-chain and cyclic -fluoroketones
with aryl halides (Scheme 1, path 4). This is a straightforward route
a
-fluorocarbonyl compounds. Shreeve
a
-fluoroketone could be
a
-aryl-
-aryl-
a
-
-
a
a
a
fluoroketones. Direct fluorination includes electrophilic fluorina-
tion of tertiary -aryl-ketones (Scheme 1, path 1) [4] and
nucleophilic fluorination of quaternary -hydroxy (halogen)
substituted -arylketones (Scheme 1, path 2) [5] by fluorinating
a
a
a
a
a
a
reagents. These transformations, however, have some practical
drawbacks, such as low functionality compatibility or high cost of
fluorinating reagents. Recently palladium-catalyzed arylation of
for synthesis of
scope.
a-aryl-
a
-fluoroketones with board substrate
monofluorinated silyl enol ethers of cyclic
presence of P(t-Bu)3 and TBAT has been found to give quaternary
-aryl- -fluoroketones in moderate yields (Scheme 1, path 3) [6].
a-fluoroketones in the
2. Results and discussion
Generally the direct
a
a
a
-arylation of ketones required a strong
But monofluorinated silyl enol ethers were quite unstable in many
base, such as potassium tert-butoxide [7,8,10]. However, we
noticed that -fluorinated ketones had suffered from the problem of
defluorination in harsh basic circumstances [11]. In consideration of
this particular character of -fluorinated ketones, our initial
studies were focused on screening the proper base for the coupling
of -fluoroketone with aryl halides in the presence of Pd(OAc)2
a
a
* Corresponding author at: Key Laboratory of Organofluorine Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345
Lingling Lu, Shanghai 200032, China. Tel.: +86 21 54925187; fax: +86 21 64166128.
E-mail address: flq@mail.sioc.ac.cn (F.-L. Qing).
a
(10 mol%)/PPh3 (20 mol%). As shown in Table 1, when potassium
tert-butoxide and KHMDS were used as bases, the Pd-catalyzed
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.08.004

C. Guo et al. / Journal of Fluorine Chemistry 133 (2012) 86–96
87
Scheme 1. Synthetic strategies to
a-aryl-a-fluoroketones.
reaction of open-chain
a
-fluoroketone 1 with 4-bromotoluene in
was not an effective ligand for the arylation of open-chain ketone 1
(entry 13). Although the cyclic -aryl- -fluoroketone 4a was also
formed in quantitative yield in the presence of ligand RuPhos
toluene at 80 8C led to the complete defluorination of the substrate
1 (Table 1, entries 1–2). 1 remained intact without defluorination
in the case of mild base anhydrous K3PO4 (entry 3). Gratifyingly,
a
a
(entry 14), P(o-tolyl)3 was chosen as the effective and low-cost
K3PO4ꢀ3H2O was an effective base for the
a
-arylation reaction,
ligand for the arylation of cyclic a-fluoroketones. Furthermore, it
providing 2a in 18% yield (entry 4). This result showed that water
in potassium phosphate plays an important role in the enhanced
reactivity of the catalyst, which has also been illustrated in recent
development of a water-mediated catalyst pre-activation protocol
[12]. The other advantages of the use of K3PO4ꢀ3H2O include the
easiness of handling because of its less hygroscopic property and
the expected good functionality tolerance due to its mild basicity.
After K3PO4ꢀ3H2O was chosen as suitable base, we continued to
screen other experimental factors. When xylene was used as
solvent instead of toluene and the reaction temperature was
elevated to 130 8C, the yield of 2a was increased to 46% (entry 5).
Ligands have been proved to profoundly alter the stability,
selectivity and reactivity of the metal complex [13]. Accordingly,
a series of phosphine ligands were screened. To our delight,
was found that that the arylations of both 1 and 3 could be
proceeded smoothly to give 2a and 4a respectively in high yields
when the loadings of Pd(OAc)2 and ligand were reduced to 5 mol%
and 10 mol%, respectively (entries 15–16).
With the optimized reaction conditions in hand, the scope of
the arylation of both open-chain and cyclic
aryl halides was investigated. As shown in Table 2, the arylation of
open-chain -fluoroketone 1 encompassed reactions of electron
a-fluoroketones with
a
neutral, electron rich, and electron poor aryl bromides. The
coupling of 1 with 1,4-dibromobenzene gave the double-arylated
compound 2f selectively in 84% yield without the formation of
mono-arylated compound, although the amount of 1,4-dibromo-
benzene was excess (2.0 equiv). The arylation of 1 with sterically
hindered 2-bromotoluene also proceeded smoothly to give
product 2k in 72% yield. Other phenyl halides were also examined
as substrates for the arylation of 1. The coupling of chlorobenzene
with 1 gave 2b in 95% yield. But reaction of iodobenzene with 1
gave 2b in only 51% yield.
Buchwald’s ligands [14], both RuPhos and XPhos, promoted the a-
arylation efficiently in xylene and 1 was completely converted to
2a at 130 8C for 8 h without formation of by-product (Table 1,
entries 9–10). It has been reported that the fluorinated silyl enol
ethers in palladium-catalyzed arylation and allylation is more
active than that of acyclic ones [6b,15]. As expected, the Pd-
The
a
-arylation of another two open-chain
a-fluoroketones 5
and 6 bearing different substituents on the
a
-position proceeded
catalyzed arylation of cyclic
a
-fluoroketone 3 with 4-bromoto-
smoothly under the optimum conditions for 1 (Scheme 2). The
coupling of 5 with bromobenzene provided 7 in 88% yield. Even the
luene by using PPh3 as ligand occurred with higher conversion (up
to 84%) comparing to the open-chain ketone 1, but the desired
product 4a was formed only in 45% yield (entry 11). Interestingly,
when bulky ligand P(o-tolyl)3 was used, the reaction of cyclic
ketone 3 with 4-bromotoluene in xylene at 130 8C proceeded
smoothly to give 4a in quantitative yield (entry 12), but P(o-tolyl)3
sterically hindered substrate
effectively to afford the arylated product 8 in 81% yield.
In succession, the scope of the -arylation of cyclic
6 went through the process
a
a-
fluoroketones 3 and 9 was summarized in Table 3. In consideration
of the higher reactivities of cyclic ketones, the amount of aryl
Scheme 2. Direct
a-arylation of 5 and 6 with bromobenzene.

88
C. Guo et al. / Journal of Fluorine Chemistry 133 (2012) 86–96
Table 1
Evaluation of bases and supporting ligands for Pd-catalyzed
a-arylation of a
-fluoroketones 1 and 3 with 4-bromotoluene.a
Entry
Ligand
Base
Product
Conversion (%)b
Yield (%)b
1c
PPh3
t-BuOK
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
4a
4a
2a
4a
2a
4a
100d
91d
N.R.e,f
18f
0
0
2c
PPh3
KHMDS
3c
PPh3
K3PO4
0
4c
PPh3
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
K3PO4ꢀ3H2O
18
5g
PPh3
57f
46
6g
Dppf
44f
59f
38
7g
JohnPhos
Xantphos
RuPhos
XPhos
59
8g
100
100
100
84f
82
9g
100
100
45
10g
11g
12g
13g
14g
15g,h
16g,h
PPh3
P(o-tolyl)3
P(o-tolyl)3
RuPhos
RuPhos
P(o-tolyl)3
100
50f
100
50
100
100
100
100
100
100
a
Reaction conditions: 10 mol% Pd(OAc)2, 20 mol% ligand, 2.0 equiv 4-bromotoluene, 2.0 equiv K3PO4ꢀ3H2O, solvent (0.20 molLꢁ1 of 1 or 3), at 0.2 mmol scale, 8 h.
b
c
d
e
f
Determined by 19F NMR using fluorobenzene as internal standard.
Toluene used as solvent at 80 8C.
1 underwent defluorination.
No reaction.
1 remained intact.
g
h
Xylene used as solvent at 130 8C.
5 mol% Pd(OAc)2 and 10 mol% ligand were used.
KHMDS =potassium bis(trimethylsilyl)amide.
bromide and K3PO4ꢀ3H2O were reduced to 1.2 equiv and 1.5 equiv,
a
a
-fluoro-1-indanone
-aryl- -fluoro-1-indalones 10 in moderate to good yields. It
should be noteworthy that the -arylations of 3 or 9 with 1,4-
dibromobenzene by using P(o-tolyl)3 as ligand gave a mixture of
9 with diverse aryl bromides provided
respectively. A number of
a
-aryl-a
-fluoro-1-tetralones 4 were
a
obtained in good to excellent yields by the arylation of
a
-fluoro-1-
a
tetralone 3 with aryl bromides. Similarly, the direct -arylations of
a
Scheme 3. Direct
a-arylation of non-fluorinated ketones.

C. Guo et al. / Journal of Fluorine Chemistry 133 (2012) 86–96
89
Table 2
Pd-catalyzed
a
-arylation of 1 with aryl bromides.a,b
2a: 88%
2d: 87%
2g: 93%
2b: 94%
2e: 82%
2c: 96%
2f: 84%
2i: 96%
2h: 95%
2k: 72%
2j: 85%
a
Reaction conditions: 5 mol% Pd(OAc)2, 10 mol% RuPhos, 2.0 equiv aryl bromide, 2.0 equiv K3PO4ꢀ3H2O, xylene (0.20 mol Lꢁ1 of 1), 130 8C, 8 h, at 1.0 mmol scale.
b
Isolated yield.
Table 3
Substrate scope of palladium catalyzed
a-arylation of cyclic
a
-fluoroketones 3 and 9.a,b
4a: 95%
4d: 75%
4b: 96%
4e: 84%
4c: 98%
4f: 44%
4g: 67%c
4j: 87%
4h: 85%
4k: 80%
4i: 84%
4l: 43%c
4m: 62%c
4p: 66%
4n: 94%
4o: 39%c
10b: 82%
10a: 81%

90
10c: 78%
C. Guo et al. / Journal of Fluorine Chemistry 133 (2012) 86–96
10d: 72%
10e: 72%
10f: 42%
10i: 81%
10l: 88%c
10g: 72%c
10j: 71%
10h: 67%
10k: 69%c
10n: 48%
10m: 68%
10o: 77%
a
Reaction conditions: 5 mol% Pd(OAc)2, 10 mol% P(o-tolyl)3, 1.2 equiv aryl bromide, 1.5 equiv K3PO4ꢀ3H2O, xylene (0.20 mol Lꢁ1 of 3 or 9), 130 8C, 8 h.
b
c
Isolated yields.
Isolated yields by the use of RuPhos (10 mol%) instead of P(o-tolyl)3.
mono-arylated compounds (4f and 10f) and double-arylated
were obtained with 1H decoupling. 19F NMR spectra were recorded
on a Bruker AM-300 spectrometer (CFCl3 as outside standard and
low field is positive). The following abbreviations were used to
explain the multiplicities: s = singlet, d = doublet, t = triplet,
q = quartet, m = multiplet. Infrared spectra were recorded on a
Bio-Rad FTS-185 system. LRMS analyses were performed on
Agilent 5973N (EI, 70 eV) and HRMS on Waters Micromass GCT
Premier.
compounds (4g and 10g) (4f/4g = 1.0/0.8, 10f/10g = 1.0/1.1) [16],
and the selectivity of the reaction was improved by using RuPhos
as ligand instead of P(o-tolyl)3 and the double-arylated compounds
4g and 10g were isolated as single products. It was found that
RuPhos was the more effective ligand than P(o-tolyl)3 for the
a-
arylation of 3 and 9 with aryl bromides bearing NO2, CN, ortho-F
groups and 3-bromothiophene and resulted in formation of
products 4l, 10k, 4m, 10l, 4o, 4p and 10o in higher yields.
Ketones 11, 12a and 12b were known compounds and their 1H,
13C NMR spectra were in accordance with those described in the
literature [17].
Furthermore, the a-arylation of non-fluorinated ketones in the
presence Pd(OAc)2/RuPhos catalytic system and weak base
K3PO4ꢀ3H2O also proceeded smoothly with high efficiency
(Scheme 3). The reaction of propiophenone with 4-bromotoluene
afford the mono-arylated product 11 exclusively in 91% yield,
while the arylation of cyclic substrate 1-indanone gave a mixture
of mono-arylated compound 12a (33%) and double-arylated
compound 12b (42%).
4.2. General procedure for Pd-catalyzed a-arylation of open-chain a-
fluoroketone 1 with aryl bromides
An oven-dried Schlenk tube containing a magnetic stirring bar
was charged with Pd(OAc)2 (11.2 mg, 0.05 mmol), RuPhos
(46.7 mg, 0.10 mmol), and K3PO4ꢀ3H2O (533 mg, 2.0 mmol). The
Schlenk tube was capped with a rubber septum and then
evacuated and backfilled with argon for three times. Xylene
(5 mL) was added through the septum via syringe and the resulting
3. Conclusion
In summary, we have developed a versatile method to prepare
a
-aryl-
a
-fluoroketones in moderate to excellent yields by
-arylation of -fluoroketones with
mixture was stirred at room temperature for 5 min. Then a-
palladium-catalyzed direct
a
a
fluoroketone 1 (1.0 mmol) and aryl bromide (2.0 mmol) were
added. The Schlenk tube was sealed and the reaction mixture was
heated at 130 8C with vigorous stirring for 8 h. The reaction
mixture was cooled to room temperature and quenched with H2O
(20 mL). The solution was extracted with ether (3 ꢂ 10 mL), and
the combined organic layers were washed with saturated brine,
dried over anhydrous sodium sulfate, filtered, and concentrated in
vacuo. The crude product was purified by flash column chroma-
tography on silica gel using petroleum ether/ethyl acetate (100/1)
as eluent.
structurally diverse aryl bromides. In view of all reagents used are
readily available and easy to handle, and the mild reaction
conditions, we believe that this method will provide a practical and
straightforward synthetic route to potentially bioactive
fluorocarbonyl compounds.
a-aryl-a-
4. Experimental
4.1. General
All reactions were carried out under an argon atmosphere. All
commercially available reagents were used without further
4.2.1. 2-Fluoro-1-phenyl-2-p-tolylpropan-1-one (2a) [6c]
1H NMR (300 MHz, CDCl3):
d
7.90 (d, J = 6.9 Hz, 2H), 7.30–7.48
(m, 5H), 7.18 (d, J = 8.1 Hz, 2H), 2.32 (s, 3H), 1.90 (d, J = 23.1 Hz,
3H). 13C NMR (100 MHz, CDCl3):
198.0 (d, J = 27.7 Hz), 138.1,
purification, unless specified otherwise.
a-Fluoroketones 1 [4j],
3 [4d], 5 [4j], 6 [4d] and 9 [4d] were prepared according to
literature procedures.
d
137.5 (d, J = 21.9 Hz), 134.5, 133.0, 130.3 (d, J = 5.1 Hz), 129.5,
128.2, 123.8 (d, J = 8.0 Hz), 101.3 (d, J = 183.7 Hz), 26.9 (d,
All new compounds were characterized by 1H NMR, 19F NMR,
13C NMR, and IR spectroscopy, in addition to high-resolution mass
spectroscopy. 1H NMR and 13C NMR spectra were recorded on a
Bruker AM-300 spectrometer and Varian MR-400, respectively. All
1H NMR experiments are reported in parts per million (ppm)
downfield of TMS. All 13C NMR spectra are reported in ppm and
J = 25.6 Hz), 21.1. 19F NMR (282 MHz, CDCl3):
d
ꢁ150.5 (q,
J = 24.0 Hz, 1F). IR (neat, cmꢁ1): 3059, 2989, 2935, 1688, 1448,
1268, 1105, 979, 725. MS (EI): m/z (%) 51 (9), 77 (28), 105 (100), 115
(15), 137 (98), 242 (3, M+). HRMS: Calcd. for C16H15FO: 242.1107;
found: 242.1112.

C. Guo et al. / Journal of Fluorine Chemistry 133 (2012) 86–96
91
4.2.2. 2-Fluoro-1,2-diphenylpropan-1-one (2b) [6c]
1H NMR (300 MHz, CDCl3):
7.90 (d, J = 7.8 Hz, 2H), 7.27–7.50
(m, 8H), 1.91 (d, J = 23.1 Hz, 3H). 13C NMR (100 MHz, CDCl3):
1687, 1511, 1253, 1180. MS (EI): m/z (%) 77 (14), 105 (14), 153
(100), 258 (2, M+). HRMS: Calcd. for C16H15FO2: 258.1056; found:
258.1055.
d
d
197.9 (d, J = 27.0 Hz), 140.4 (d, J = 21.8 Hz), 134.4 (d, J = 3.7 Hz),
133.0, 130.3 (d, J = 5.9 Hz), 128.9, 128.3, 128.2, 123.9 (d, J = 8.7 Hz),
101.3 (d, J = 184.5 Hz), 27.0 (d, J = 25.5 Hz). 19F NMR (282 MHz,
4.2.8. 2-(Biphenyl-4-yl)-2-fluoro-1-phenylpropan-1-one (2h)
1H NMR (300 MHz, CDCl3):
d
7.94 (d, J = 7.5 Hz, 2H), 7.31–7.61
CDCl3):
d
ꢁ150.5 (q, J = 22.8 Hz, 1F). IR (neat, cmꢁ1): 3062, 2990,
(m, 12H), 1.95 (d, J = 22.8 Hz, 3H). 13C NMR (100 MHz, CDCl3):
d
1689, 1448, 1269, 980, 698. MS (EI): m/z (%) 77 (32), 103 (11), 105
(100), 123 (18), 228 (1, M+). HRMS: Calcd. for C15H13FO: 228.0950;
found: 228.0946.
197.9 (d, J = 27.7 Hz), 141.3, 140.4, 139.4 (d, J = 21.9 Hz), 134.4 (d,
J = 2.9 Hz), 133.1, 130.3 (d, J = 5.8 Hz), 128.9, 128.3, 127.7, 127.6,
127.2, 124.4 (d, J = 8.7 Hz), 101.3 (d, J = 183.7 Hz), 26.9 (d,
J = 24.8 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ150.2 (q, J = 23.7 Hz,
4.2.3. 2-(4-tert-Butylphenyl)-2-fluoro-1-phenylpropan-1-one (2c)
1F). IR (neat, cmꢁ1): 3058, 3031, 2989, 2935, 1687, 1487, 1266,
1104, 980, 699. MS (EI): m/z (%) 77 (21), 105 (57), 178 (22), 199
(100), 304 (5, M+). HRMS: Calcd. for C21H17FO: 304.1263; found:
304.1265.
[6c]
1H NMR (300 MHz, CDCl3):
d
7.93 (d, J = 7.5 Hz, 2H), 7.32–7.49
(m, 7H), 1.92 (d, J = 22.8 Hz, 3H), 1.30 (s, 9H). 13C NMR (100 MHz,
CDCl3): 198.2 (d, J = 27.8 Hz), 151.3, 137.3 (d, J = 21.8 Hz), 134.5
d
(d, J = 3.7 Hz), 132.9, 130.3 (d, J = 5.9 Hz), 128.2, 125.7, 123.7 (d,
J = 8.0 Hz), 101.4 (d, J = 183.0 Hz), 34.6, 31.3, 26.9 (d, J = 24.8 Hz).
4.2.9. 2-Fluoro-2-(naphthalen-2-yl)-1-phenylpropan-1-one (2i)
1H NMR (300 MHz, CDCl3):
d
7.80–7.97 (m, 6H), 7.59 (dd, J = 8.7,
1.5 Hz, 1H), 7.41–7.49 (m, 3H), 7.30 (d, J = 7.5 Hz, 2H), 1.99 (d,
J = 23.1 Hz, 3H). 13C NMR (100 MHz, CDCl3):
197.9 (d, J = 27.0 Hz),
19F NMR (282 MHz, CDCl3):
d
ꢁ150.0 (q, J = 22.8 Hz, 1F). IR (neat,
cmꢁ1): 3060, 2964, 2906, 1688, 1269, 1107, 981, 704. MS (EI): m/z
(%) 77 (20), 105 (62), 149 (18), 164 (20), 179 (100), 284 (1, M+).
HRMS: Calcd. for C19H21FO: 284.1576; found: 284.1581.
d
137.9 (d, J = 21.8 Hz), 134.4 (d, J = 3.7 Hz), 133.2, 133.1, 133.0,
130.3 (d, J = 5.8 Hz), 128.9, 128.4, 128.3, 127.8, 126.6 (d, J = 3.7 Hz),
123.0 (d, J = 8.7 Hz), 121.6 (d, J = 8.0 Hz), 101.4 (d, J = 184.5 Hz),
4.2.4. 2-Fluoro-2-(4-fluorophenyl)-1-phenylpropan-1-one (2d)
27.0 (d, J = 25.5 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ150.1 (q,
1H NMR (300 MHz, CDCl3):
d
7.90 (d, J = 8.1 Hz, 2H), 7.44–7.50
(m, 3H), 7.35 (t, J = 7.5 Hz, 2H), 7.07 (t, J = 8.7 Hz, 2H), 1.91 (d,
J = 23.1 Hz, 3H). 13C NMR (100 MHz, CDCl3):
197.8 (d, J = 26.9 Hz),
J = 22.6 Hz, 1F). IR (neat, cmꢁ1): 3059, 2988, 2932, 1687, 1270,
1119, 981, 709. MS (EI): m/z (%) 77 (31), 105 (100), 152 (17), 173
(66), 179 (34), 278 (9, M+). HRMS: Calcd. for C19H15FO: 278.1107;
found: 278.1108.
d
162.6 (d, J = 246.5 Hz), 136.3 (dd, J = 21.9, 3.0 Hz), 134.3 (d,
J = 2.9 Hz), 133.2, 130.2 (d, J = 5.9 Hz), 128.3, 125.9 (t, J = 8.0 Hz),
115.8 (d, J = 21.9 Hz), 100.5 (d, J = 184.5 Hz), 27.0 (d, J = 25.5 Hz).
4.2.10. 2-Fluoro-1-phenyl-2-(4-(trifluoromethyl)phenyl)propan-1-
19F NMR (282 MHz, CDCl3):
d
ꢁ113.6 (m, 1F), ꢁ149.5 (q, J = 23.7 Hz,
one (2j) [6c]
1F). IR (neat, cmꢁ1): 3072, 2991, 2937, 1689, 1509, 1268, 1234, 838.
MS (EI): m/z (%) 51 (8), 77 (30), 101 (11), 105 (100), 141 (19), 246
(0.6, M+). HRMS: Calcd. for C15H12F2O: 246.0856; found: 246.0853.
1H NMR (300 MHz, CDCl3):
d
7.90 (d, J = 8.4 Hz, 2H), 7.61–7.68
(m, 4H), 7.50 (t, J = 7.2 Hz, 1H), 7.36 (t, J = 7.5 Hz, 2H), 1.94 (d,
J = 23.1 Hz, 3H). 13C NMR (100 MHz, CDCl3):
197.2 (d, J = 27.0 Hz),
d
144.3 (d, J = 21.8 Hz), 134.0 (d, J = 3.6 Hz), 133.4, 130.6 (d,
J = 32.8 Hz), 130.2 (d, J = 5.8 Hz), 128.4, 125.9 (dd, J = 3.6, 1.5 Hz),
124.3 (d, J = 8.7 Hz), 123.9 (q, J = 270.5 Hz), 100.5 (d, J = 186.7 Hz),
4.2.5. 2-(4-Chlorophenyl)-2-fluoro-1-phenylpropan-1-one (2e)
1H NMR (300 MHz, CDCl3):
d
7.90 (d, J = 7.8 Hz, 2H), 7.36–7.52
(m, 7H), 1.91 (d, J = 23.1 Hz, 3H). 13C NMR (100 MHz, CDCl3):
d
26.9 (d, J = 24.8 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ62.1 (s, 3F),
197.5 (d, J = 26.9 Hz), 139.0 (d, J = 21.9 Hz), 134.4, 134.2 (d,
J = 3.6 Hz), 133.2, 130.2 (d, J = 5.8 Hz), 129.1, 128.3, 125.4 (d,
J = 8.0 Hz), 101.4 (d, J = 185.2 Hz), 26.8 (d, J = 24.8 Hz). 19F NMR
ꢁ151.2 (q, J = 22.8 Hz, 1F). IR (neat, cmꢁ1): 3073, 2937, 1690, 1328,
1269, 1129, 708. MS (EI): m/z (%) 51 (9), 77 (41), 105 (100), 151 (7),
171 (5), 191 (6). HRMS: Calcd. for C16H12F4O: 296.0824; found:
296.0825.
(282 MHz, CDCl3):
d
ꢁ150.6 (q, J = 22.6 Hz, 1F). IR (neat, cmꢁ1):
3061, 2991, 2937, 1688, 1491, 1267, 1095, 980, 701. MS (EI): m/z
(%) 51 (7), 77 (26), 101 (9), 105 (100), 157 (10), 262 (0.6, M+).
HRMS: Calcd. for C15H12ClFO: 262.0561; found: 262.0567.
4.2.11. 2-Fluoro-1-phenyl-2-o-tolylpropan-1-one (2k)
1H NMR (300 MHz, CDCl3):
d
7.90 (d, J = 8.1 Hz, 2H), 7.13–7.50
(m, 7H), 2.30 (d, J = 1.8 Hz, 3H), 1.96 (d, J = 23.1 Hz, 3H). 13C NMR
(100 MHz, CDCl3): 197.1 (d, J = 26.3 Hz), 138.6 (d, J = 20.4 Hz),
4.2.6. 2,20-(1,4-Phenylene)bis(2-fluoro-1-phenylpropan-1-one) (2f)
d
1H NMR (300 MHz, CDCl3):
d
7.88 (d, J = 8.4 Hz, 4H), 7.46–7.53
(m, 6H), 7.34 (t, J = 7.5 Hz, 4H), 1.91 (d, J = 23.1 Hz, 6H). 13C NMR
(100 MHz, CDCl3): 197.8 (dd, J = 27.0, 5.9 Hz), 140.5 (d,
134.9 (d, J = 2.2 Hz), 134.3, 133.1, 132.4, 130.2 (d, J = 4.4 Hz), 128.6,
128.3, 126.2, 125.1 (d, J = 10.2 Hz), 100.9 (d, J = 179.3 Hz), 24.7 (d,
d
J = 25.5 Hz), 20.8 (d, J = 4.4 Hz). 19F NMR (282 MHz, CDCl3):
d
J = 21.9 Hz), 134.3 (d, J = 3.7 Hz), 133.2, 130.2 (d, J = 6.6 Hz),
128.2, 124.5 (d, J = 8.0 Hz), 101.2 (d, J = 185.2 Hz), 26.9 (d,
ꢁ141.5 (q, J = 23.7 Hz, 1F). IR (neat, cmꢁ1): 3065, 2993, 2937, 1693,
1448, 1265, 1101, 974, 710. MS (EI): m/z (%) 51 (8), 77 (27), 105
(100), 115 (15), 137 (34), 242 (5, M+). HRMS: Calcd. for C16H15FO:
242.1107; found: 242.1110.
J = 24.8 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ150.5 (q, J = 23.7 Hz,
1F), ꢁ150.8 (q, J = 23.7 Hz, 1F). IR (neat, cmꢁ1): 3068, 2993, 2932,
1685, 1267, 1099, 976, 704. MS (EI): m/z (%) 51 (5), 77 (29), 105
(100), 254 (13), 378 (2, M+). HRMS: Calcd. for C24H20F2O2:
378.1431; found: 378.1441.
4.2.12. 2-Fluoro-1,2-diphenylbutan-1-one (7)
1H NMR (300 MHz, CDCl3):
d
7.89 (d, J = 7.8 Hz, 2H), 7.28–7.52
(m, 8H), 2.36–2.56 (m, 1H), 2.10–2.31 (m, 1H), 0.93 (t, J = 7.5 Hz,
3H). 13C NMR (100 MHz, CDCl3):
198.5 (d, J = 27.7 Hz), 138.9 (d,
4.2.7. 2-Fluoro-2-(4-methoxyphenyl)-1-phenylpropan-1-one (2g)
d
1H NMR (300 MHz, CDCl3):
d
7.90 (d, J = 8.1 Hz, 2H), 7.30–7.48
(m, 5H), 6.90 (d, J = 8.1 Hz, 2H), 3.76 (s, 3H), 1.90 (d, J = 23.1 Hz,
3H). 13C NMR (100 MHz, CDCl3):
198.1 (d, J = 27.7 Hz), 159.6,
J = 22.6 Hz), 135.2 (d, J = 3.6 Hz), 132.9, 130.0 (d, J = 6.5 Hz), 128.7
(d, J = 1.5 Hz), 128.2, 124.2 (d, J = 9.5 Hz), 103.8 (d, J = 188.1 Hz),
d
32.8 (d, J = 23.3 Hz), 7.5 (d, J = 4.3 Hz). 19F NMR (282 MHz, CDCl3):
d
134.5 (d, J = 2.9 Hz), 133.0, 132.4 (d, J = 22.6 Hz), 130.2 (d,
J = 5.2 Hz), 128.2, 125.4 (d, J = 8.0 Hz), 114.3, 101.1 (d,
J = 183.0 Hz), 55.3, 26.8 (d, J = 25.6 Hz). 19F NMR (282 MHz, CDCl3):
ꢁ164.8 (t, J = 24.8 Hz, 1F). IR (neat, cmꢁ1): 3061, 2978, 2940, 1685,
1448, 1259, 974, 697. MS (EI): m/z (%) 51 (7), 77 (27), 105 (100), 137
(13), 242 (1, M+). HRMS: Calcd. for C16H15FO: 242.1107; found:
242.1112.
d
ꢁ148.2 (q, J = 22.8 Hz, 1F). IR (neat, cmꢁ1): 3062, 2936, 2837,

92
C. Guo et al. / Journal of Fluorine Chemistry 133 (2012) 86–96
4.2.13. 2-Fluoro-1,2,2-triphenylethanone (8)
31.2, 26.5 (d, J = 9.5 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ143.3 (t,
1H NMR (300 MHz, CDCl3):
d
7.91 (d, J = 7.5 Hz, 2H), 7.31–7.49
J = 8.7 Hz, 1F). IR (neat, cmꢁ1): 2965, 1692, 1603, 1220, 930, 831,
741. MS (EI): m/z (%) 90 (28), 118 (100), 281 (12), 296 (15, M+).
HRMS: Calcd. for C20H21FO: 296.1576; found: 296.1577.
(m, 13H). 13C NMR (100 MHz, CDCl3):
d
197.5 (d, J = 30.7 Hz), 139.1
(d, J = 22.6 Hz), 135.2 (d, J = 3.7 Hz), 133.0, 130.3 (d, J = 5.1 Hz),
128.7 (d, J = 1.4 Hz), 128.3, 128.1, 126.6 (d, J = 7.3 Hz), 102.9 (d,
J = 185.9 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ140.2 (s, 1F). IR (neat,
4.3.4. 2-Fluoro-2-(4-fluorophenyl)-3,4-dihydronaphthalen-1(2H)-
cmꢁ1): 3062, 3029, 1686, 1597, 1494, 1448, 1258, 1182, 848, 750,
696. MS (EI): m/z (%) 51 (6), 77 (24), 105 (100), 165 (33), 185 (57),
290 (0.3, M+). HRMS: Calcd. for C20H15FO: 290.1107; found:
290.1104.
one (4d)
1H NMR (300 MHz, CDCl3):
d 8.15 (d, J = 7.8 Hz, 1H), 7.54 (t,
J = 7.5 Hz, 1H), 7.32–7.41 (m, 3H), 7.24 (d, J = 8.1 Hz, 1H), 7.04 (t,
J = 8.4 Hz, 2H), 3.08–3.17 (m, 1H), 2.65–2.87 (m, 3H). 13C NMR
(100 MHz, CDCl3):
d 193.4 (d, J = 17.4 Hz), 163.1 (dd, J = 247.2,
4.3. General procedure for Pd-catalyzed
a
-arylation of cyclic
a
-
2.4 Hz), 143.0, 134.4, 132.7 (d, J = 26.0 Hz), 132.0, 128.9, 128.3 (d,
J = 14.2 Hz), 128.2, 127.3, 115.6 (d, J = 21.3 Hz), 95.4 (d,
J = 183.3 Hz), 35.4 (d, J = 24.5 Hz), 26.2 (d, J = 8.7 Hz). 19F NMR
fluoroketones 3 and 9 with aryl bromides
An oven-dried Schlenk tube containing a magnetic stirring bar
was charged with Pd(OAc)2 (11.2 mg, 0.05 mmol), P(o-tolyl)3
(282 MHz, CDCl3):
d
ꢁ112.5 (s, 1F), ꢁ144.6 (t, 1F) [18]. IR (neat,
cmꢁ1): 3062, 2944, 1699, 1600, 1514, 1190, 1162, 820, 743. MS
(EI): m/z (%) 90 (39), 118 (100), 238 (2), 258 (24, M+). HRMS: Calcd.
for C16H12F2O: 258.0856; found: 258.0854.
(30.4 mg, 0.10 mmol),
a-fluoroketone 3 or 9 (1.0 mmol) and
K3PO4ꢀ3H2O (399 mg, 1.5 mmol). The Schlenk tube was capped
with a rubber septum and then evacuated and backfilled with
argon for three times. Xylene (5 mL) was added through the
septum via syringe and the resulting mixture was stirred at room
temperature for 5 min. Then aryl bromide (1.2 mmol) was added.
The Schlenk tube was sealed and the reaction mixture was heated
at 130 8C with vigorous stirring for 8 h. The reaction mixture was
cooled to room temperature and quenched with H2O (20 mL). The
solution was extracted with ether (3 ꢂ 10 mL), and the combined
organic layers were washed with saturated brine, dried over
anhydrous sodium sulfate, filtered, and concentrated in vacuo. The
crude product was purified by flash column chromatography on
silica gel using petroleum ether/ethyl acetate (40/1) as eluent.
4.3.5. 2-(4-Chlorophenyl)-2-fluoro-3,4-dihydronaphthalen-1(2H)-
one (4e)
1H NMR (300 MHz, CDCl3):
d
8.15 (d, J = 7.8 Hz, 1H), 7.55 (td,
J = 7.2, 1.2 Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H), 7.24–7.35 (m, 5H), 3.10–
3.19 (m, 1H), 2.65–2.88 (m, 3H). 13C NMR (100 MHz, CDCl3):
d
193.0 (d, J = 19.0 Hz), 143.0, 135.6 (d, J = 23.3 Hz), 135.2 (d,
J = 2.9 Hz), 134.4, 131.9, 128.9, 128.8, 128.3 (d, J = 1.5 Hz), 127.5
(d, J = 6.6 Hz), 127.3, 95.3 (d, J = 183.8 Hz), 35.4 (d, J = 24.8 Hz), 26.1
(d, J = 8.8 Hz). 19F NMR (282 MHz, CDCl3):
1F). IR (neat, cmꢁ1): 3060, 2944, 1700, 1598, 1496, 1236, 1088, 898,
815, 746. MS (EI): m/z (%) 90 (34), 118 (100), 254 (1), 274 (17, M+).
HRMS: Calcd. for C16H12ClFO: 274.0561; found: 274.0568.
d
ꢁ147.3 (t, J = 10.4 Hz,
4.3.1. 2-Fluoro-2-p-tolyl-3,4-dihydronaphthalen-1(2H)-one (4a)
[6b]
4.3.6. 2-(4-Bromophenyl)-2-fluoro-3,4-dihydronaphthalen-1(2H)-
1H NMR (300 MHz, CDCl3):
d
8.16 (d, J = 7.8 Hz, 1H), 7.51 (t,
one (4f)
J = 7.5 Hz, 1H), 7.37 (t, J = 7.5 Hz, 1H), 7.13–7.26 (m, 5H), 3.02–3.10
(m, 1H), 2.63–2.88 (m, 3H), 2.31 (s, 3H). 13C NMR (100 MHz,
CDCl3):
1H NMR (300 MHz, CDCl3):
d
8.14 (d, J = 7.8 Hz, 1H), 7.21–7.56
(m, 7H), 3.11–3.17 (m, 1H), 2.64–2.87 (m, 3H). 13C NMR (100 MHz,
CDCl3): 192.9 (d, J = 19.0 Hz), 143.1, 136.1 (d, J = 23.4 Hz), 134.5,
d
194.2 (d, J = 18.2 Hz), 143.1, 139.2 (d, J = 2.9 Hz), 134.2,
d
133.5 (d, J = 22.6 Hz), 132.2, 129.4, 128.9, 128.1 (d, J = 1.4 Hz),
127.2, 126.2 (d, J = 5.8 Hz), 96.0 (d, J = 183.0 Hz), 35.3 (d,
J = 24.7 Hz), 26.5 (d, J = 8.7 Hz), 21.2. 19F NMR (282 MHz, CDCl3):
131.9, 131.8, 128.9, 128.3, 127.8 (d, J = 5.9 Hz), 127.4, 123.4 (d,
J = 3.0 Hz), 95.4 (d, J = 183.0 Hz), 35.4 (d, J = 24.0 Hz), 26.1 (d,
J = 8.8 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ147.1 (t, J = 11.3 Hz, 1F).
d
ꢁ143.2 (t, 1F) [18]. IR (neat, cmꢁ1): 3061, 3030, 2925, 1701, 1602,
IR (neat, cmꢁ1): 2928, 1698, 1601, 1488, 1234, 1073, 1010, 932,
741. MS (EI): m/z (%) 90 (34), 118 (100), 234 (9), 240 (12), 318, 320
(6, M+). HRMS: Calcd. for C16H12BrFO: 318.0056; found: 318.0055.
1455, 1308, 1221, 931, 816, 740. MS (EI): m/z (%) 90 (31), 118 (100),
133 (38), 162 (50), 254 (26, M+). HRMS: Calcd. for C17H15FO:
254.1107; found: 254.1105.
4.3.7. 2,20-(1,4-Phenylene)bis(2-fluoro-3,4-dihydronaphthalen-
4.3.2. 2-Fluoro-2-phenyl-3,4-dihydronaphthalen-1(2H)-one (4b)
1(2H)-one) (4g)
[6b]
1H NMR (300 MHz, CDCl3):
d
8.12 (dd, J = 7.8, 0.9 Hz, 2H), 7.53
(td, J = 7.8, 1.5 Hz, 2H), 7.33–7.39 (m, 6H), 7.24 (t, J = 7.5 Hz, 2H),
3.07–3.13 (m, 2H), 2.66–2.86 (m, 6H). 13C NMR (100 MHz, CDCl3):
193.3 (d, J = 19.0 Hz), 143.2, 138.0 (d, J = 24.8 Hz), 134.4, 132.0,
129.0, 128.1, 127.3, 126.3 (d, J = 5.8 Hz), 95.6 (d, J = 183.7 Hz), 35.6
(d, J = 24.8 Hz), 26.1 (d, J = 8.7 Hz). 19F NMR (282 MHz, CDCl3):
ꢁ147.6 (t, J = 10.4 Hz, 1F). IR (neat, cmꢁ1): 3064, 2941, 1697, 1602,
1456, 1311, 1235, 1074, 933, 738. MS (EI): m/z (%) 90 (48), 118
(100), 251 (11), 382 (21), 402 (3, M+). HRMS: Calcd. for C26H20F2O2:
402.1431; found: 402.1437.
1H NMR (300 MHz, CDCl3):
d
8.16 (d, J = 7.8 Hz, 1H), 7.51 (t,
J = 7.2 Hz, 1H), 7.33–7.40 (m, 6H), 7.21 (d, J = 7.5 Hz, 1H), 3.04–3.11
(m, 1H), 2.64–2.86 (m, 3H). 13C NMR (100 MHz, CDCl3):
193.9 (d,
d
d
J = 18.2 Hz), 143.2, 136.8 (d, J = 22.6 Hz), 134.3, 132.2, 129.2 (d,
J = 2.2 Hz), 128.9, 128.7, 128.1, 127.3, 126.1 (d, J = 5.8 Hz), 96.0 (d,
J = 183.0 Hz), 35.5 (d, J = 24.8 Hz), 26.4 (d, J = 9.4 Hz). 19F NMR
d
(282 MHz, CDCl3):
d
ꢁ144.6 (t, J = 12.4 Hz, 1F). IR (neat, cmꢁ1):
3063, 2939, 1698, 1602, 1449, 1307, 1233, 933, 698. MS (EI): m/z
(%) 90 (36), 118 (100), 133 (17), 162 (21), 240 (31, M+). HRMS:
Calcd. for C16H13FO: 240.0950; found: 240.0949.
4.3.8. 2-Fluoro-2-(4-methoxyphenyl)-3,4-dihydronaphthalen-
4.3.3. 2-(4-tert-Butylphenyl)-2-fluoro-3,4-dihydronaphthalen-
1(2H)-one (4h) [6b]
1(2H)-one (4c)
1H NMR (300 MHz, CDCl3):
d 8.15 (d, J = 7.8 Hz, 1H), 7.50 (t,
1H NMR (300 MHz, CDCl3):
d
8.17 (d, J = 7.5 Hz, 1H), 7.51 (t,
J = 7.8 Hz, 1H), 7.20–7.40 (m, 6H), 3.04–3.11 (m, 1H), 2.64–2.91 (m,
3H), 1.28 (s, 9H). 13C NMR (100 MHz, CDCl3):
194.1 (d,
J = 7.5 Hz, 1H), 7.25–7.38 (m, 3H), 7.19 (d, J = 7.5 Hz, 1H), 6.85 (d,
J = 8.7 Hz, 2H), 3.75 (s, 3H), 3.01–3.09 (m, 1H), 2.62–2.87 (m, 3H).
13C NMR (100 MHz, CDCl3):
d 194.3 (d, J = 17.5 Hz), 160.3 (d,
d
J = 18.3 Hz), 152.3 (d, J = 2.2 Hz), 143.2, 134.2, 133.4 (d,
J = 22.6 Hz), 132.3, 128.8, 128.1 (d, J = 1.5 Hz), 127.2, 126.0 (d,
J = 5.1 Hz), 125.6, 96.0 (d, J = 183.0 Hz), 35.3 (d, J = 25.5 Hz), 34.6,
J = 2.2 Hz), 143.0, 134.2, 132.2, 128.8, 128.0 (d, J = 1.4 Hz), 127.9 (d,
J = 5.1 Hz), 127.2, 114.1, 95.8 (d, J = 183.8 Hz), 55.3, 35.0 (d,
J = 25.5 Hz), 26.6 (d, J = 9.5 Hz). 19F NMR (282 MHz, CDCl3):
d

C. Guo et al. / Journal of Fluorine Chemistry 133 (2012) 86–96
93
ꢁ140.1 (t, 1F) [18]. IR (neat, cmꢁ1): 2936, 2839, 1701, 1604, 1515,
1253, 1184, 930, 832, 741. MS (EI): m/z (%) 90 (30), 118 (100), 250
(21), 270 (29, M+). HRMS: Calcd. for C17H15FO2: 270.1056; found:
270.1054.
J = 8.0 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ153.2 (t, J = 13.3 Hz, 1F).
IR (neat, cmꢁ1): 3066, 2932, 2230, 1697, 1601, 1455, 1307, 1237,
935, 826, 741. MS (EI): m/z (%) 84 (100), 86 (66), 90 (20), 118 (51),
265 (12, M+). HRMS: Calcd. for C17H12FON: 265.0903; found:
265.0900.
4.3.9. 2-(Biphenyl-4-yl)-2-fluoro-3,4-dihydronaphthalen-1(2H)-one
(4i)
4.3.14. 2-Fluoro-2-o-tolyl-3,4-dihydronaphthalen-1(2H)-one (4n)
1H NMR (300 MHz, CDCl3):
d
8.18 (d, J = 8.1 Hz, 1H), 7.30–7.56
(m, 11H), 7.21 (d, J = 7.5 Hz, 1H), 3.07–3.14 (m, 1H), 2.68–2.92 (m,
3H). 13C NMR (100 MHz, CDCl3):
193.8 (d, J = 17.5 Hz), 143.2,
142.1 (d, J = 2.2 Hz), 140.3, 135.7 (d, J = 22.6 Hz), 134.4, 132.2,
129.0, 128.9, 128.2, 127.8, 127.4, 127.3, 127.2, 126.7 (d, J = 5.8 Hz),
95.9 (d, J = 183.0 Hz), 35.4 (d, J = 24.8 Hz), 26.4 (d, J = 9.4 Hz). 19F
1H NMR (300 MHz, CDCl3):
d 8.17 (d, J = 7.8 Hz, 1H), 7.54 (t,
J = 7.8 Hz, 1H), 7.39 (t, J = 7.8 Hz, 1H), 7.07–7.28 (m, 5H), 3.14–3.22
(m, 1H), 2.73–2.91 (m, 2H), 2.51–2.61 (m, 1H), 2.35 (d, J = 1.8 Hz,
3H). 13C NMR (100 MHz, CDCl3):
d 192.8 (d, J = 19.7 Hz), 143.4,
136.3 (d, J = 21.1 Hz), 135.5 (d, J = 2.2 Hz), 134.1, 132.2, 131.9,
128.7, 128.5, 128.3, 127.2, 126.0 (d, J = 10.9 Hz), 125.5, 96.8 (d,
J = 179.3 Hz), 34.8 (d, J = 24.8 Hz), 25.7 (d, J = 6.5 Hz), 21.2 (d,
d
NMR (282 MHz, CDCl3):
d
ꢁ145.1 (t, J = 10.4 Hz, 1F). IR (neat,
cmꢁ1): 3062, 2960, 1693, 1598, 1488, 1238, 928, 766, 736. MS (EI):
m/z (%) 90 (28), 118 (100), 316 (38, M+). HRMS: Calcd. for C22H17FO:
316.1263; found: 316.1267.
J = 5.1 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ154.8 (dd, J = 24.3,
12.1 Hz, 1F). IR (neat, cmꢁ1): 3065, 3024, 2932, 1697, 1602, 1455,
1233, 931, 757. MS (EI): m/z (%) 90 (38), 118 (100), 234 (34), 254 (9,
M+). HRMS: Calcd. for C17H15FO: 254.1107; found: 254.1105.
4.3.10. 2-Fluoro-3,4-dihydro-2,20-binaphthyl-1(2H)-one (4j)
1H NMR (300 MHz, CDCl3):
d
8.21 (d, J = 7.5 Hz, 1H), 7.69–7.84
(m, 4H), 7.34–7.53 (m, 5H), 7.16 (d, J = 7.8 Hz, 1H), 3.03–3.08 (m,
1H), 2.68–2.89 (m, 3H). 13C NMR (100 MHz, CDCl3):
193.9 (d,
4.3.15. 2-Fluoro-2-(2-fluorophenyl)-3,4-dihydronaphthalen-1(2H)-
one (4o)
d
1H NMR (300 MHz, CDCl3):
d
8.15 (d, J = 7.8 Hz, 1H), 7.47–7.57
(m, 2H), 7.16–7.41 (m, 4H), 7.02–7.09 (m, 1H), 3.26–3.35 (m, 1H),
2.77–2.99 (m, 2H), 2.52–2.63 (m, 1H). 13C NMR (100 MHz, CDCl3):
J = 17.5 Hz), 143.1, 134.3, 133.9 (d, J = 21.9 Hz), 133.3 (d, J = 2.2 Hz),
132.7, 132.1, 128.9, 128.6, 128.4, 128.1, 127.6, 127.2, 126.8, 126.5,
125.9 (d, J = 6.5 Hz), 123.3 (d, J = 4.4 Hz), 96.1 (d, J = 183.8 Hz), 35.3
(d, J = 24.8 Hz), 26.3 (d, J = 9.5 Hz). 19F NMR (282 MHz, CDCl3):
ꢁ144.7 (t, 1F) [18]. IR (neat, cmꢁ1): 3059, 2937, 1693, 1601, 1307,
1227, 932, 819, 738. MS (EI): m/z (%) 90 (33), 118 (100), 270 (17),
290 (37, M+). HRMS: Calcd. for C20H15FO: 290.1107; found:
290.1104.
d
190.6 (d, J = 19.0 Hz), 159.1 (dd, J = 245.7, 5.1 Hz), 143.5, 134.1,
131.1, 130.4 (d, J = 8.0 Hz), 128.7 (d, J = 1.5 Hz), 127.4 (d, J = 3.6 Hz),
127.3 (d, J = 3.7 Hz), 127.2, 126.3 (dd, J = 23.3, 13.1 Hz), 124.3 (d,
J = 3.7 Hz), 115.9 (d, J = 21.2 Hz), 94.3 (dd, J = 180.1, 2.9 Hz), 35.0
(dd, J = 24.0, 3.0 Hz), 25.3 (d, J = 5.8 Hz). 19F NMR (282 MHz,
d
CDCl3):
d
ꢁ111.8 (s, 1F), ꢁ162.3 (dd, J = 34.7, 12.1 Hz, 1F). IR (neat,
cmꢁ1): 3069, 2932, 1693, 1602, 1490, 1454, 1281, 1229, 936, 759,
743. MS (EI): m/z (%) 90 (39), 118 (100), 238 (2), 258 (30, M+).
HRMS: Calcd. for C16H12F2O: 258.0856; found: 258.0858.
4.3.11. 2-Fluoro-2-(4-(trifluoromethyl)phenyl)-3,4-
dihydronaphthalen-1(2H)-one (4k) [6b]
1H NMR (300 MHz, CDCl3):
d
8.16 (d, J = 7.8 Hz, 1H), 7.39–7.64
(m, 6H), 7.28 (d, J = 8.1 Hz, 1H), 3.18–3.24 (m, 1H), 2.66–2.90 (m,
3H). 13C NMR (100 MHz, CDCl3):
192.3 (d, J = 18.2 Hz), 143.1,
4.3.16. 2-Fluoro-2-(thiophen-3-yl)-3,4-dihydronaphthalen-1(2H)-
d
one (4p)
141.5 (d, J = 22.6 Hz), 134.5, 131.8, 131.1 (d, J = 32.8 Hz), 128.9,
128.4, 127.4, 126.3 (d, J = 6.6 Hz), 125.5 (q, J = 3.6 Hz), 123.8 (q,
J = 271.2 Hz), 95.3 (d, J = 183.0 Hz), 35.7 (d, J = 24.1 Hz), 25.8 (d,
J = 8.7 Hz). 19F NMR (282 MHz, CDCl3):
J = 13.8 Hz, 1F). IR (neat, cmꢁ1): 3061, 2940, 1702, 1333, 1236,
1124, 845. MS (EI): m/z (%) 90 (38), 118 (100), 289 (6), 308 (29, M+).
HRMS: Calcd. for C17H12F4O: 308.0824; found: 308.0829.
1H NMR (300 MHz, CDCl3):
d
8.15 (d, J = 7.8 Hz, 1H), 7.51 (d,
J = 7.5 Hz, 1H), 7.31–7.39 (m, 2H), 7.15–7.23 (m, 3H), 3.05–3.11 (m,
1H), 2.65–2.95 (m, 3H). 13C NMR (100 MHz, CDCl3):
193.1 (d,
d
d
ꢁ63.2 (s, 3F), ꢁ151.6 (t,
J = 19.0 Hz), 143.0, 136.8 (d, J = 24.1 Hz), 134.3, 131.6, 128.8, 128.2
(d, J = 1.5 Hz), 127.2, 126.7, 125.8 (d, J = 2.9 Hz), 124.8 (d,
J = 7.3 Hz), 93.6 (d, J = 183.0 Hz), 34.9 (d, J = 24.8 Hz), 26.7 (d,
J = 9.5 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ138.4 (t, J = 9.3 Hz, 1F).
IR (neat, cmꢁ1): 3106, 2933, 1698, 1602, 1455, 1303, 1223, 919,
735. MS (EI): m/z (%) 90 (38), 118 (100), 226 (20), 246 (13, M+).
HRMS: Calcd. for C14H11FOS: 246.0515; found: 246.0523.
4.3.12. 2-Fluoro-2-(4-nitrophenyl)-3,4-dihydronaphthalen-1(2H)-
one (4l) [6b]
1H NMR (300 MHz, CDCl3):
d 8.23 (d, J = 8.4 Hz, 2H), 8.14 (d,
J = 7.8 Hz, 1H), 7.52–7.62 (m, 3H), 7.43 (t, J = 7.8 Hz, 1H), 7.32 (d,
J = 7.8 Hz, 1H), 3.28 (dt, J = 17.1, 5.4 Hz, 1H), 2.86–2.94 (m, 1H),
4.3.17. 2-Fluoro-2-p-tolyl-2,3-dihydro-1H-inden-1-one (10a)
1H NMR (300 MHz, CDCl3):
d 7.80 (d, J = 8.1 Hz, 1H), 7.70 (t,
2.65–2.76 (m, 2H). 13C NMR (100 MHz, CDCl3):
d
191.5 (d,
J = 7.5 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 7.25
(d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 3.62–3.77 (m, 2H), 2.32 (s,
J = 19.7 Hz), 148.1, 144.8 (d, J = 22.7 Hz), 143.1, 134.7, 131.4,
129.0, 128.6, 127.6, 126.8 (d, J = 8.0 Hz), 123.6, 95.1 (d,
J = 183.0 Hz), 35.8 (d, J = 24.0 Hz), 25.5 (d, J = 8.0 Hz). 19F NMR
3H). 13C NMR (100 MHz, CDCl3):
d 199.4 (d, J = 21.1 Hz), 150.3 (d,
J = 5.8 Hz), 138.5, 136.4, 134.6 (d, J = 24.8 Hz), 133.9, 129.4, 128.6,
126.4, 125.6, 124.5 (d, J = 8.0 Hz), 97.9 (d, J = 188.8 Hz), 41.6 (d,
(282 MHz, CDCl3):
d
ꢁ153.4 (dd, J = 18.6, 13.5 Hz, 1F). IR (neat,
cmꢁ1): 3077, 2938, 1697, 1602, 1521, 1348, 1237, 935, 853, 741.
MS (EI): m/z (%) 84 (55), 86 (36), 90 (46), 118 (100), 285 (36, M+).
HRMS: Calcd. for C16H12NFO3: 285.0801; found: 285.0804.
J = 24.1 Hz), 21.1. 19F NMR (282 MHz, CDCl3):
d
ꢁ156.9 (dd, J = 20.6,
12.1 Hz, 1F). IR (neat, cmꢁ1): 1733, 1607, 1211, 1090, 916, 738. MS
(EI): m/z (%) 196 (59), 197 (63), 207 (15), 225 (6), 240 (100, M+).
HRMS: Calcd. for C16H13FO: 240.0950; found: 240.0951.
4.3.13. 4-(2-Fluoro-1-oxo-1,2,3,4-tetrahydronaphthalen-2-
yl)benzonitrile (4m) [6b]
4.3.18. 2-Fluoro-2-phenyl-2,3-dihydro-1H-inden-1-one (10b)
1H NMR (300 MHz, CDCl3):
d
8.13 (d, J = 7.8 Hz, 1H), 7.38–7.67
(m, 6H), 7.30 (d, J = 7.8 Hz, 1H), 3.24 (dt, J = 17.1, 5.7 Hz, 1H), 2.81–
2.91 (m, 1H), 2.63–2.73 (m, 2H). 13C NMR (100 MHz, CDCl3):
1H NMR (300 MHz, CDCl3):
d
7.80 (d, J = 7.8 Hz, 1H), 7.70 (t,
J = 7.5 Hz, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.44 (t, J = 7.8 Hz, 1H), 7.32–
7.36 (m, 5H), 3.63–3.78 (m, 2H). 13C NMR (100 MHz, CDCl3):
d
d
191.8 (d, J = 19.0 Hz), 143.2, 142.9 (d, J = 22.6 Hz), 134.7, 132.3,
131.5, 129.0, 128.5, 127.5, 126.6 (d, J = 7.3 Hz), 118.3, 112.8 (d,
J = 1.4 Hz), 95.1 (d, J = 183.0 Hz), 35.6 (d, J = 24.0 Hz), 25.5 (d,
199.2 (d, J = 19.7 Hz), 150.3 (d, J = 5.1 Hz), 137.8 (d, J = 24.1 Hz),
136.5, 133.9, 128.7, 128.6, 128.5, 126.5, 125.6, 124.5 (d, J = 8.0 Hz),
97.9 (d, J = 188.8 Hz), 41.8 (d, J = 24.1 Hz). 19F NMR (282 MHz,

94
C. Guo et al. / Journal of Fluorine Chemistry 133 (2012) 86–96
CDCl3):
d
ꢁ157.9 (dd, 1F) [19]. IR (neat, cmꢁ1): 3063, 1728, 1609,
124.8 (ddd, J = 8.2, 4.1, 1.3 Hz), 97.6 (dd, J = 190.2, 0.8 Hz), 41.5
(dd, J = 23.9, 3.7 Hz). 19F NMR (282 MHz, CDCl3):
1F) [19]. IR (neat, cmꢁ1): 1717, 1605, 1466, 1260, 1211, 1076,
909, 747. MS (EI): m/z (%) 196 (45), 197 (36), 296 (13), 297 (13),
374 (100, M+). HRMS: Calcd. for C24H16F2O2: 374.1118; found:
374.1119.
1212, 1009, 920, 699. MS (EI): m/z (%) 178 (40), 179 (43), 196 (44),
197 (41), 206 (20), 226 (100, M+). HRMS: Calcd. for C15H11FO:
226.0794; found: 226.0796.
d
ꢁ157.8 (dd,
4.3.19. 2-(4-tert-Butylphenyl)-2-fluoro-2,3-dihydro-1H-inden-1-one
(10c)
1H NMR (300 MHz, CDCl3):
d
7.80 (d, J = 7.8 Hz, 1H), 7.69 (t,
4.3.24. 2-(Biphenyl-4-yl)-2-fluoro-2,3-dihydro-1H-inden-1-one
J = 7.5 Hz, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 7.36
(d, J = 9.0 Hz, 2H), 7.29 (d, J = 9.0 Hz, 2H), 3.62–3.82 (m, 2H), 1.28 (s,
d 199.4 (d, J = 21.1 Hz), 151.6 (d,
J = 1.5 Hz), 150.3 (d, J = 5.1 Hz), 136.4, 134.5 (d, J = 24.1 Hz), 133.9,
128.5, 126.4, 125.6, 124.4 (d, J = 8.0 Hz), 98.0 (d, J = 188.9 Hz), 41.6
(10h)
1H NMR (300 MHz, CDCl3):
d
7.84 (d, J = 7.8 Hz, 1H), 7.73 (t,
J = 7.5 Hz, 1H), 7.32–7.59 (m, 11H), 3.68–3.87 (m, 2H). 13C NMR
(100 MHz, CDCl3): 199.2 (d, J = 20.4 Hz), 150.3 (d, J = 5.9 Hz),
141.6, 140.5, 136.7, 136.5, 133.9, 128.9, 128.7, 127.6, 127.5, 127.1,
126.5, 125.8, 125.0 (d, J = 8.0 Hz), 97.8 (d, J = 188.9 Hz), 41.7 (d,
J = 24.0 Hz). 19F NMR (282 MHz, CDCl3):
10.4 Hz, 1F). IR (neat, cmꢁ1): 3053, 1727, 1429, 1210, 1086, 913,
836, 737, 694. MS (EI): m/z (%) 196 (21), 197 (20), 252 (28), 253
(22), 282 (16), 302 (100, M+). HRMS: Calcd. for C21H15FO:
302.1107; found: 302.1111.
9H). 13C NMR (100 MHz, CDCl3):
d
(d, J = 24.0 Hz), 34.6, 31.2. 19F NMR (282 MHz, CDCl3):
d
ꢁ157.0
(dd, J = 20.6, 10.4 Hz, 1F). IR (neat, cmꢁ1): 2958, 1722, 1609, 1431,
1302, 1104, 920, 836, 750. MS (EI): m/z (%) 91 (17), 196 (34), 197
(23), 267 (100), 268 (20), 282 (34, M+). HRMS: Calcd. for C19H19FO:
282.1420; found: 282.1431.
d
ꢁ157.4 (dd, J = 20.6,
4.3.20. 2-Fluoro-2-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-one
(10d)
4.3.25. 2-Fluoro-2-(naphthalen-2-yl)-2,3-dihydro-1H-inden-1-one
1H NMR (300 MHz, CDCl3):
d
7.81 (d, J = 7.8 Hz, 1H), 7.72 (t,
(10i)
J = 7.2 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.32–
7.37 (m, 2H), 7.01–7.06 (m, 2H), 3.70–3.76 (m, 2H). 13C NMR
1H NMR (300 MHz, CDCl3):
d
7.67–7.86 (m, 6H), 7.37–7.55 (m,
5H), 3.69–3.90 (m, 2H). 13C NMR (100 MHz, CDCl3):
d
199.3 (d,
(100 MHz, CDCl3):
d
198.9 (d, J = 20.4 Hz), 162.8 (d, J = 247.9 Hz),
J = 20.5 Hz), 150.4 (d, J = 5.1 Hz), 136.6, 135.0 (d, J = 24.1 Hz), 133.9,
133.1 (d, J = 21.1 Hz), 128.7 (d, J = 8.0 Hz), 128.3, 127.7, 126.6 (d,
J = 6.5 Hz), 126.5 (d, J = 1.5 Hz), 125.7, 123.9 (d, J = 8.8 Hz), 122.1 (d,
J = 7.3 Hz), 98.1 (d, J = 189.6 Hz), 41.8 (d, J = 24.1 Hz). 19F NMR
150.1 (d, J = 5.1 Hz), 136.6, 133.6, 133.3 (d, J = 2.9 Hz), 128.7, 126.6
(t, J = 8.0 Hz), 126.5 (d, J = 1.5 Hz), 125.7, 115.6 (d, J = 21.1 Hz), 97.5
(d, J = 189.6 Hz), 41.6 (d, J = 24.1 Hz). 19F NMR (282 MHz, CDCl3):
ꢁ113.5 (m, 1F), ꢁ155.7 (dd, 1F) [19]. IR (neat, cmꢁ1): 1736, 1507,
1225, 1082, 913, 738. MS (EI): m/z (%) 196 (44), 197 (25), 214 (36),
215 (40), 224 (16), 244 (100, M+). HRMS: Calcd. for C15H10F2O:
244.0700; found: 244.0704.
d
(282 MHz, CDCl3):
d
ꢁ156.8 (dd, J = 20.6, 10.4 Hz, 1F). IR (neat,
cmꢁ1): 1727, 1608, 1275, 1214, 1084, 915, 749. MS (EI): m/z (%) 226
(25), 228 (28), 246 (41), 247 (49), 256 (19), 276 (100, M+). HRMS:
Calcd. for C19H13FO: 276.0950; found: 276.0952.
4.3.21. 2-(4-Chlorophenyl)-2-fluoro-2,3-dihydro-1H-inden-1-one
4.3.26. 2-Fluoro-2-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-
(10e)
inden-1-one (10j)
1H NMR (300 MHz, CDCl3):
d
7.82 (d, J = 7.8 Hz, 1H), 7.73 (t,
J = 7.5 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.26–
7.34 (m, 4H), 3.70–3.75 (m, 2H). 13C NMR (100 MHz, CDCl3):
1H NMR (300 MHz, CDCl3):
d
7.83 (d, J = 8.1 Hz, 1H), 7.75 (t,
J = 7.8 Hz, 1H), 7.45–7.63 (m, 6H), 3.73–3.79 (m, 2H). 13C NMR
(100 MHz, CDCl3): 198.3 (d, J = 20.4 Hz), 150.2 (d, J = 5.1 Hz),
d
d
198.7 (d, J = 19.7 Hz), 150.1 (d, J = 5.1 Hz), 136.6, 136.2 (d,
J = 24.8 Hz), 134.7 (d, J = 1.4 Hz), 133.6, 128.9, 128.8, 126.5 (d,
J = 1.5 Hz), 126.0 (d, J = 8.0 Hz), 125.8, 97.4 (d, J = 190.3 Hz), 41.6 (d,
141.8 (d, J = 24.0 Hz), 136.8, 133.6, 130.8 (d, J = 32.1 Hz), 128.9,
126.5, 125.9, 125.7 (d, J = 3.7 Hz), 124.9 (d, J = 8.7 Hz), 123.9 (q,
J = 270.5 Hz), 97.4 (d, J = 190.3 Hz), 41.8 (d, J = 24.1 Hz). 19F NMR
J = 24.1 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ157.2 (dd, 1F) [19]. IR
(282 MHz, CDCl3):
d
ꢁ63.2 (s, 3F), ꢁ158.8 (dd, J = 17.2, 13.8 Hz, 1F).
(neat, cmꢁ1): 1734, 1490, 1212, 1086, 916, 742. MS (EI): m/z (%)
177 (21), 196 (74), 197 (47), 225 (23), 260 (100, M+), 262 (33).
HRMS: Calcd. for C15H10ClFO: 260.0404; found: 260.0407.
IR (neat, cmꢁ1): 1722, 1328, 1164, 1121, 1070, 842. MS (EI): m/z (%)
69 (27), 77 (23), 196 (57), 197 (33), 275 (14), 294 (100, M+). HRMS:
Calcd. for C16H10F4O: 294.0668; found: 294.0670.
4.3.22. 2-(4-Bromophenyl)-2-fluoro-2,3-dihydro-1H-inden-1-one
4.3.27. 2-Fluoro-2-(4-nitrophenyl)-2,3-dihydro-1H-inden-1-one
(10f)
(10k)
1H NMR (300 MHz, CDCl3):
d
7.82 (d, J = 7.5 Hz, 1H), 7.73 (t,
J = 7.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.45–7.49 (m, 3H), 7.21–7.26
(m, 2H), 3.69–3.75 (m, 2H). 13C NMR (100 MHz, CDCl3):
198.6 (d,
1H NMR (300 MHz, CDCl3):
d
8.21 (d, J = 8.7 Hz, 2H), 7.85 (d,
J = 7.5 Hz, 1H), 7.78 (t, J = 7.8 Hz, 1H), 7.59 (d, J = 7.5 Hz, 1H), 7.50–
7.55 (m, 3H), 3.75–3.88 (m, 2H). 13C NMR (100 MHz, CDCl3):
d
d
J = 20.5 Hz), 150.1 (d, J = 5.1 Hz), 136.9, 136.6, 133.6, 131.8, 128.8,
126.5, 126.3 (d, J = 8.8 Hz), 125.8, 122.8 (d, J = 1.4 Hz), 97.5 (d,
197.6 (d, J = 19.7 Hz), 150.0 (d, J = 5.1 Hz), 148.0, 144.9 (d,
J = 24.1 Hz), 137.0, 133.4, 129.1, 126.6, 126.0, 125.5 (d,
J = 8.8 Hz), 123.9, 97.4 (d, J = 191.0 Hz), 41.7 (d, J = 24.1 Hz). 19F
J = 189.6 Hz), 41.6 (d, J = 24.1 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ157.6 (dd, 1F) [19]. IR (neat, cmꢁ1): 1731, 1211, 1088, 916, 741.
MS (EI): m/z (%) 98 (34), 178 (35), 196 (100), 197 (50), 304 (66, M+),
306 (65, M+). HRMS: Calcd. for C15H10BrFO: 303.9899; found:
303.9903.
NMR (282 MHz, CDCl3):
d
ꢁ158.6 (dd, J = 20.9, 13.8 Hz, 1F). IR
(neat, cmꢁ1): 1722, 1601, 1518, 1349, 1213, 848, 732. MS (EI): m/z
(%) 176 (24), 178 (22), 196 (53), 271 (100, M+). HRMS: Calcd. for
C15H10NFO3: 271.0645; found: 271.0647.
4.3.23. 2,20-(1,4-Phenylene)bis(2-fluoro-2,3-dihydro-1H-inden-1-
4.3.28. 4-(2-Fluoro-1-oxo-2,3-dihydro-1H-inden-2-yl)benzonitrile
one) (10g)
(10l)
1H NMR (300 MHz, CDCl3):
d
7.68–7.81 (m, 4H), 7.43–7.55
(m, 4H), 7.33 (s, 4H), 3.68–3.74 (m, 4H). 13C NMR (100 MHz,
CDCl3): 198.8 (dd, J = 20.2, 3.7 Hz), 150.1 (dd, J = 7.0, 5.3 Hz),
1H NMR (300 MHz, CDCl3):
d
7.74–7.84 (m, 2H), 7.44–7.66
(m, 6H), 3.73–3.85 (m, 2H). 13C NMR (100 MHz, CDCl3):
(d, J = 19.7 Hz), 150.1 (d, J = 4.4 Hz), 143.0 (d, J = 24.8 Hz), 137.0,
133.4, 132.5, 129.0, 126.6, 125.9, 125.3 (d, J = 9.5 Hz), 118.3,
112.5, 97.4 (d, J = 191.0 Hz), 41.6 (d, J = 24.1 Hz). 19F NMR
d
197.8
d
138.0 (ddd, J = 24.4, 2.9, 1.6 Hz), 136.5 (d, J = 2.5 Hz), 133.6 (d,
J = 1.7 Hz), 128.6, 126.3 (dd, J = 3.3, 1.6 Hz), 125.7 (d, J = 1.2 Hz),

C. Guo et al. / Journal of Fluorine Chemistry 133 (2012) 86–96
95
(i) C. Bobbio, V. Gouverneur, Org. Biomol. Chem. 4 (2006) 2065–2075;
(j) Y. Hamashima, M. Sodeoka, Synlett (2006) 1467–1478;
(k) P.G. Cozzi, R. Hilgraf, N. Zimmermann, Eur. J. Org. Chem. (2007) 5969–5994;
(l) N. Shibata, T. Ishimaru, S. Nakamura, T. Toru, J. Fluorine Chem. 128 (2007)
469–483;
(m) J.-A. Ma, D. Cahard, Chem. Rev. 108 (2008) PR1–PR43;
(n) V.A. Brunet, D. O’Hagan, Angew. Chem. Int. Ed. 47 (2008) 1179–1182;
(o) M. Bella, T. Gasperi, Synthesis (2009) 1583–1614;
(p) M. Ueda, T. Kano, K. Maruoka, Org. Biomol. Chem. 7 (2009) 2005–2012;
(q) D. Cahard, X. Xu, S. Couve-Bonnaire, X. Pannecoucke, Chem. Soc. Rev. 39
(2010) 558–568;
(282 MHz, CDCl3):
d
ꢁ159.1 (dd, 1F) [19]. IR (neat, cmꢁ1): 3066,
2227, 1737, 1606, 1469, 1303, 1213, 1086, 916, 761. MS (EI):
m/z (%) 196 (19), 203 (29), 204 (35), 221 (28), 222 (28), 251
(100, M+). HRMS: Calcd. for C16H10NFO: 251.0746; found:
251.0750.
4.3.29. 2-Fluoro-2-o-tolyl-2,3-dihydro-1H-inden-1-one (10m)
1H NMR (300 MHz, CDCl3):
d 7.91 (d, J = 7.8 Hz, 1H), 7.70 (t,
J = 7.5 Hz, 1H), 7.45–7.50 (m, 2H), 7.36–7.39 (m, 1H), 7.19–7.27
(r) S. Lectard, Y. Hamashima, M. Sodeoka, Adv. Synth. Catal. 352 (2010) 2708–
2732;
(s) K. Shibatomi, Synthesis (2010) 2679–2702;
(m, 3H), 3.64–3.79 (m, 2H), 2.22 (s, 3H). 13C NMR (100 MHz,
CDCl3): d200.0 (d, J = 19.7 Hz), 150.2, 136.5, 136.4, 136.2, 135.0 (d,
J = 3.6 Hz), 134.4, 131.8, 128.5 (d, J = 9.5 Hz), 126.7, 125.9, 125.7,
125.4, 98.5 (d, J = 183.0 Hz), 42.0 (d, J = 26.2 Hz), 20.7 (d,
(t) A.M.R. Smith, K.K. Hii, Chem. Rev. 111 (2011) 1637–1656.
[3] (a) S.D. Putnam, M. Castanheira, G.J. Moet, D.J. Farrell, R.N. Jones, Diagn. Micro-
biol. Infect. Dis. 66 (2010) 393–401;
J = 2.9 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ151.6 (dd, J = 24.0,
(b) P. Hewawasam, V.K. Gribkoff, Y. Pendri, S.I. Dworetzky, N.A. Meanwell, E.
Martinez, C.G. Boissard, D.J. Post-Munson, J.T. Trojnacki, K. Yeleswaram, L.M.
Pajor, J. Knipe, Q. Gao, R. Perrone, J.E. Starrett Jr., Bioorg. Med. Chem. Lett. 12
(2002) 1023–1026.
18.9 Hz, 1F). IR (neat, cmꢁ1): 1720, 1604, 1466, 1244, 1007, 882,
732. MS (EI): m/z (%) 178 (39), 191 (42), 196 (67), 197 (46), 219
(40), 240 (100, M+). HRMS: Calcd. for C16H13FO: 240.0950; found:
240.0953.
[4] (a) T. Ishimaru, N. Shibata, T. Horikawa, N. Yasuda, S. Nakamura, T. Toru, M. Shiro,
Angew. Chem. Int. Ed. 47 (2008) 4157–4161;
˚
(b) H. Teare, E.G. Robins, E. Arstad, S.K. Luthra, V. Gouverneur, Chem. Commun.
(2007) 2330–2332;
(c) D. Enders, M.R.M. Hu¨ ttl, Synlett (2005) 991–993;
4.3.30. 2-Fluoro-2-(2-fluorophenyl)-2,3-dihydro-1H-inden-1-one
(d) S. Stavber, M. Jereb, M. Zupan, Synthesis (2002) 2609–2615;
(e) K. Mun˜iz, Angew. Chem. Int. Ed. 40 (2001) 1653–1656;
(f) D. Cahard, C. Audouard, J.-C. Plaquevent, N. Roques, Org. Lett. 2 (2000) 3699–
3701;
(g) Z. Liu, N. Shibata, Y. Takeuchi, J. Org. Chem. 65 (2000) 7583–7587;
(h) Y. Takeuchi, T. Suzuki, A. Satoh, T. Shiragami, N. Shibata, J. Org. Chem. 64
(1999) 5708–5711;
(i) Y. Takeuchi, Z. Liu, E. Suzuki, N. Shibata, K.L. Kirk, J. Fluorine Chem. 97 (1999)
65–67;
(j) S. Stavber, M. Zupan, Tetrahedron Lett. 37 (1996) 3591–3594;
(k) E. Differding, H. Ofner, Synlett (1991) 187–189;
(10n)
1H NMR (300 MHz, CDCl3):
d
7.87 (d, J = 7.5 Hz, 1H), 7.68 (t,
J = 7.2 Hz, 2H), 7.20–7.48 (m, 4H), 7.00 (t, J = 9.3 Hz, 1H), 3.56–3.77
(m, 2H). 13C NMR (100 MHz, CDCl3):
198.5 (d, J = 18.2 Hz), 158.6
d
(dd, J = 244.3, 6.6 Hz), 150.5, 136.5, 133.5, 130.3 (d, J = 8.0 Hz),
128.3, 127.1 (dd, J = 13.1, 3.7 Hz), 126.6, 126.1 (q, J = 12.4 Hz),
125.5, 124.4, 115.6 (dd, J = 20.4, 1.4 Hz), 95.5 (d, J = 184.4 Hz), 41.8
(dd, J = 26.2, 2.9 Hz). 19F NMR (282 MHz, CDCl3):
d
ꢁ113.8 (m, 1F),
ꢁ158.7 (dd, J = 24.3, 20.6 Hz, 1F). IR (neat, cmꢁ1): 1717, 1605, 1488,
1264, 1214, 775. MS (EI): m/z (%) 196 (57), 197 (33), 214 (24), 215
(24), 224 (22), 244 (100, M+). HRMS: Calcd. for C15H10F2O:
244.0700; found: 244.0701.
(l) E. Differding, R.W. Lang, Helv. Chim. Acta 72 (1989) 1248–1252.
[5] (a) G.A. Olah, J.T. Welch, Y.D. Vankar, M. Nojima, I. Kerekes, J.A. Olah, J. Org. Chem.
44 (1979) 3872–3881;
(b) J. Cousseau, P. Albert, J. Org. Chem. 54 (1989) 5380–5383;
(c) W. Zhang, J. Hu, Adv. Synth. Catal. 352 (2010) 2799–2804;
(d) J.P. Dickens, G.J. Ellames, N.J. Hare, K.R. Lawson, W.R. McKay, A.P. Metters, P.L.
Myers, A.M.S. Pope, R.M. Upton, J. Med. Chem. 34 (1991) 2356–2360;
(e) F.A. Davis, P. Zhou, C.K. Murphy, Tetrahedron Lett. 34 (1993) 3971–3974.
[6] (a) Y. Guo, J.M. Shreeve, Chem. Commun. (2007) 3583–3585;
(b) Y. Guo, B. Twamley, J.M. Shreeve, Org. Biomol. Chem. 7 (2009) 1716–1722;
(c) Y. Guo, G.H. Tao, A. Blumenfeld, J.M. Shreeve, Organometallics 29 (2010)
1818–1823.
[7] (a) M. Palucki, S.L. Buchwald, J. Am. Chem. Soc. 119 (1997) 11108–11109;
(b) B.C. Hamann, J.F. Hartwig, J. Am. Chem. Soc. 119 (1997) 12382–12383;
(c) T. Satoh, Y. Kawamura, M. Miura, M. Nomura, Angew. Chem. Int. Ed. 36 (1997)
1740–1742.
4.3.31. 2-Fluoro-2-(thiophen-3-yl)-2,3-dihydro-1H-inden-1-one
(10o)
1H NMR (300 MHz, CDCl3):
d
7.81 (d, J = 7.8 Hz, 1H), 7.68 (t,
J = 7.5 Hz, 1H), 7.31–7.51 (m, 4H), 7.11 (d, J = 5.1 Hz, 1H), 3.64–3.84
(m, 2H). 13C NMR (100 MHz, CDCl3):
198.6 (d, J = 19.7 Hz), 149.7
d
(d, J = 5.1 Hz), 138.1 (d, J = 27.0 Hz), 136.5, 133.5, 128.6, 126.9,
126.6, 125.6, 125.3 (d, J = 4.4 Hz), 123.0 (d, J = 7.3 Hz), 96.0 (d,
J = 187.4 Hz), 41.1 (d, J = 24.1 Hz). 19F NMR (282 MHz, CDCl3):
ꢁ147.3 (dd, J = 20.6, 10.4 Hz, 1F). IR (neat, cmꢁ1): 3108, 2927, 1728,
1609, 1303, 1213, 1085, 917, 736. MS (EI): m/z (%) 184 (41), 185
(68), 202 (33), 203 (63), 212 (26), 232 (100, M+). HRMS: Calcd. for
d
[8] (a) For reviews, see: M. Miura, M. Nomura, Top. Curr. Chem. 219 (2002) 212–241;
(b) D.A. Culkin, J.F. Hartwig, Acc. Chem. Res. 36 (2003) 234–245;
(c) A.C.B. Burtoloso, Synlett (2009) 320–327;
(d) F. Bellina, R. Rossi, Chem. Rev. 110 (2010) 1082–1146;
(e) C.C.C. Johansson, T.J. Colacot, Angew. Chem. Int. Ed. 49 (2010) 676–707;
(f) B. Schlummer, U. Scholz, in: L. Ackermann (Ed.), Modern Arylation Methods,
Wiley-VCH, Weinheim, Germany, 2009, pp. 69–120.
C13H9FOS: 232.0358; found: 232.0361.
[9] N.A. Beare, J.F. Hartwig, J. Org. Chem. 67 (2002) 541–555.
[10] (a) For Pd-catalyzed direct a-arylation reactions of carbonyl compounds by using
weak bases, see M. Lessi, T. Masini, L. Nucara, F. Bellina, R. Rossi, Adv. Synth. Catal.
353 (2011) 501–507;
Acknowledgment
We thank National Natural Science Foundation of China
(21072018, 20632008) for funding this work.
(b) F. Bellina, T. Masini, R. Rossi, Eur. J. Org. Chem. (2010) 1339–1344;
(c) A.S. Khartulyari, M.E. Maier, Eur. J. Org. Chem. (2007) 317–324;
(d) R. Martin, S.L. Buchwald, Angew. Chem. Int. Ed. 46 (2007) 7236–7239;
(e) J.M. Fox, X. Huang, A. Chieffi, S.L. Buchwald, J. Am. Chem. Soc. 122 (2000)
1360–1370;
References
(f) Y. Terao, T. Satoh, M. Miura, M. Nomura, Tetrahedron 56 (2000) 1315–1320.
[11] (a) H. Amii, K. Uneyama, Chem. Rev. 109 (2009) 2119–2183;
(b) R.N. Perutz, T. Braun, in: M.D. Mingos, R.H. Crabtree (Eds.), Comprehensive
Organometallic Chemistry III, Elsevier, Amsterdam, 2007 (Chapter 1.26 and
references cited therein).
[12] (a) B.P. Fors, P. Krattiger, E. Strieter, S.L. Buchwald, Org. Lett. 10 (2008) 3505–
3508;
(b) K. Dooleweerdt, B.P. Fors, S.L. Buchwald, Org. Lett. 12 (2010) 2350–2353.
[13] For a comprehensive discussion on the effect of ligand, see: E.C. Constable, Metals
and Ligand Reactivity: An Introduction to the Organic Chemistry of Metal
Complexes, Wiley-VCH, Weinheim, Germany, 1996.
[1] (a) M. Shimizu, T. Hiyama, Angew. Chem. Int. Ed. 44 (2005) 214–231;
(b) M. Schlosser, Angew. Chem. Int. Ed. 45 (2006) 5432–5446;
(c) J.-A. Ma, D. Cahard, J. Fluorine Chem. 128 (2007) 975–996;
(d) K. Mu¨ller, C. Faeh, F. Diederich, Science 317 (2007) 1881–1886;
(e) S. Purser, P.R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 37 (2008)
320–330;
(f) W.K. Hagmann, J. Med. Chem. 51 (2008) 4359–4369;
(g) K.L. Kirk, Org. Process Res. Dev 12 (2008) 305–321.
[2] (a) For reviews, see: F.A. Davis, P.V.N. Kasu, Org. Prep. Proced. Int. 31 (1999) 125–
145;
(b) K. Mikami, Y. Itoh, M. Yamanaka, Chem. Rev. 104 (2004) 1–16;
(c) H. Ibrahim, A. Togni, Chem. Commun. (2004) 1147–1155;
(d) M. Oestreich, Angew. Chem. Int. Ed. 44 (2005) 2324–2327;
(e) S. France, A. Weatherwax, T. Lectka, Eur. J. Org. Chem. (2005) 475–479;
(f) M. Marigo, K.A. Jørgensen, Chem. Commun. (2006) 2001–2011;
(g) G.K.S. Prakash, P. Beier, Angew. Chem. Int. Ed. 45 (2006) 2172–2174;
(h) P.M. Pihko, Angew. Chem. Int. Ed. 45 (2006) 544–547;
[14] R. Martin, S.L. Buchwald, Acc. Chem. Res. 41 (2008) 1461–1473, and references
cited therein.
[15] (a) S. Arai, M. Oku, T. Ishida, T. Shioiri, Tetrahedron Lett. 40 (1999) 6785–
6789;
(b) M. Nakamura, A. Hajra, K. Endo, E. Nakamura, Angew. Chem. Int. Ed. 44
(2005) 7248–7251;

96
C. Guo et al. / Journal of Fluorine Chemistry 133 (2012) 86–96
(c) E. Belanger, K. Cantin, O. Messe, M. Tremblay, J.-F. Paquin, J. Am. Chem.
Soc. 129 (2007) 1034–1035.
[16] The ratio of the mono-arylated compound to the double-arylated compound was
determined by 19F NMR spectrum of the reaction mixture.
[18] The fluorine appeared as a strong singlet peak with two shoulders on each side
which was difficult to assign the exact chemical shifts of them, the coupling
constant 3J(H-F) was not given.
[19] The fluorine appeared as doublet x doublet peak, in which the two central peaks
wereoverlapped,sothecouplingconstants3J(Htrans-F) and 3J(Hcis-F) werenotgiven.
[17] A. Ehrentraut, A. Zapf, M. Beller, Adv. Synth. Catal. 344 (2002) 209–217.