Palladium catalyzed direct α-arylation of α,α- difluoroketones with aryl bromides

Article abstract of DOI:10.1016/j.jfluchem.2012.05.001

The palladium-catalyzed direct α-arylations of α,α- difluoroketones with diverse aryl bromides have been developed by using rac-BINAP as ligand and Cs₂CO₃ as a mild base in xylene. This method provides an efficient and straightforward access to a variety of α-aryl-α,α-difluoroketones with broad substrate scope.

Full text of DOI:10.1016/j.jfluchem.2012.05.001

Journal of Fluorine Chemistry 143 (2012) 135–142
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Palladium catalyzed direct
a
-arylation of a,a-difluoroketones with aryl bromides
Chen Guo a, Ruo-Wen Wang 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-arylations of a,a-difluoroketones with diverse aryl bromides have
Received 31 March 2012
Received in revised form 28 April 2012
Accepted 1 May 2012
been developed by using rac-BINAP as ligand and Cs2CO3 as a mild base in xylene. This method provides
an efficient and straightforward access to a variety of
scope.
a
-aryl-
a
,a
-difluoroketones with broad substrate
Available online 9 May 2012
ß 2012 Elsevier B.V. All rights reserved.
Keywords:
Direct arylation
Difluoroketones
Palladium-catalyzed reaction
1. Introduction
imines) [4], acetylenes [5] and alkenyl diboronate esters [6] using
a variety of N-F reagents [7] is one of important methods for the
The modification of organic molecules with fluorine can alter
their physical and chemical properties and biological activities in a
dramatic way. As a result, fluorinated compounds have been
widely used as pharmaceuticals and agrochemicals [1]. Especially,
incorporation of a gem-difluoromethylene group into an organic
molecule has also been used as a strategy for modification of
biologically active compounds [2]. The gem-difluoromethylene
group (CF2) not only enhances the acidity of its vicinal hydroxyl,
amino and thiol groups, but also may significantly improve the
preparation of quaternary
Path 1). Nucleophilic fluorination of
monohydrazone [9] or -dithiane [10] derivatives with N,N-
diethylaminosulfur trifluoride (DAST), bis(2-methoxyethyl)ami-
nosulfur trifluoride (Deoxofluor), IF or BrF3 produces a variety of
a
-aryl-
a
,
a
-difluoroketones (Scheme 1,
a
-diketones [8], their
a-
a
quaternary
merer-type desulfurization–fluorination of
pounds [11] and fluorination of -diazo compounds [12] by IF5 or
F2 had also been reported for the synthesis of -aryl-
a
-aryl-
a
,a
-fluoroketones (Scheme 1, Path 2). Pum-
a
-thiocarbonyl com-
a
a
a,a-
biological stability. For example,
a
,
a
-difluoroketone A79285 is an
difluoroketones. These transformations, however, have some
practical drawbacks, such as poor functional compatibility and
the use of expensive fluorinating reagents.
excellent inhibitor of HIV-1 aspartic protease, as the strong
electron withdrawing CF2 group dramatically increases the
electronphilicity of its vicinal carbonyl group, and then the readily
hydrated difluoroketone could mimic the tetrahedral intermediate
that formed during biological hydrolysis of the peptide bond
(Fig. 1) [3].
An alternative strategy employed fluorinated building blocks
for the synthesis of
Biju had developed a simple methodology for the synthesis of
various -(hetero)aryl- -difluoroketones by the reaction of
organolithium reagents with -difluoro-N-methoxy-N-methyl
amides (Weinreb amides) [13]. Pd-catalyzed arylation of
difluorosilyl enol ethers in the presence of P(t-Bu)3 and Bu3SnF had
been investigated for the synthesis of -aryl- -difluoroketones
a-aryl-a,a-difluoroketones (Scheme 1, Path 3).
a
a,a
Among gem-difluoromethylene-containing compounds, qua-
a,a
ternary
in many compounds of biological activities. Accordingly, several
methods had been developed for the preparation of quaternary
aryl- -difluoroketones via direct fluorination methods or
a
-aryl-
a,
a
-difluoroketone could be an important moiety
a,a-
a
-
a
a,a
a
,
a
by Shreeve’s group [14]. However, silyl enol ethers are unstable
and excess amount of them are required in the coupling reaction to
achieve good yields.
building block strategies (Scheme 1). Electrophilic fluorination
of carbonyl compounds (including their equivalents such as
The palladium-catalyzed direct
pounds [15] has become a general method for the synthesis of
aryl ketones, -aryl esters, -aryl lactones, -aryl amides and a
a-arylation of carbonyl com-
a
-
-
a
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. Fax: +86 21 64166128.
aryl aldehydes [16]. Recently, we have developed a practical and
efficient route to -aryl- -fluoroketones by palladium-catalyzed
direct -arylation of -monofluorinated ketones with structurally
a
a
a
a
E-mail address: flq@mail.sioc.ac.cn (F.-L. Qing).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.05.001

136
C. Guo et al. / Journal of Fluorine Chemistry 143 (2012) 135–142
promoted the arylation effectively to give 2a in 39% yield (entry 5).
In the case of strong base sodium tert-butoxide, hemiacetal 3 was
the dominant species and compound 5 was also formed in 11%
yield from self-Aldol reaction of 1 [19].
Recently, it has been found that ligands profoundly alter the
stability, selectivity and reactivity of transition metal complexes
catalyzed reaction [20]. To improve both the conversion of 1 and
yield of 2a, we next examined a series of phosphine ligands. The
use of bulky and electron-rich Buchwald ligands SPhos and XPhos
[21] significantly promoted the
a-arylation of 1 and the hydrated
by-products were inhibited simultaneously, but starting material 1
was not completely consumed yet (entries 8–9). The use of
DavePhos and JohnPhos resulted in lower yield of 2a (entries 10–
11). Monodentate ligands and bidentate ligands showed similar
catalytic efficiencies as SPhos and XPhos in the
a-arylation
Fig. 1. Structure of A79285,
a difluoroketone inhibitor of HIV-1 protease in
reactions (entries 12–16), although they could promote the
reductive elimination of fluoroalkyl palladium(II) intermediates
[22]. To our delight, when BINAP [23] was used as the ligand, the
desired product 2a was formed in 90% yield with full conversion of
1 (entry 17). When the arylation was carried out at 100 8C, both the
conversion of 1 and yield of 2a were decreased (entry 18).
With the optimized reaction conditions in hand, the scope of
dehydrated and hydrated form [3a].
diverse aryl bromides [17]. Encouraged by these results, we
envisioned that the palladium-catalyzed arylations of
difluoroketones could provide an atom-economic access to
aryl-
1, Path 4). Herein, we describe the direct
difluoroketones with aryl halides as a straightforward route for
synthesis of -aryl- -difluoroketones.
a
,
a-
a
-
a
,a
-difluoroketones by C–H bond functionalization (Scheme
-arylation of
a
a
,
a
-
the direct a-arylation reaction of a,a-difluoro-1-phenylethanone
1 with aryl bromides was investigated. As shown in Table 2, this
method was applicable to a wide variety of substituted aryl
bromides with either electron-withdrawing or electron-donating
a
a,a
substitutions, providing
a-aryl-a,a-difluoro-1- phenylethanones
2. Results and discussion
2a–2k in moderate to good yields. Surprisingly, when 4-
bromotoluene, 4-tert-butylbromobenzene and 1-bromo-4-meth-
oxybenzene were used as the coupling partner, the arylation of
We began our study with the
a-arylation of a, a-difluoro-1-
phenylethanone 1 with bromobenzene as a model reaction (Table
1). Our initial efforts were focused on base screening using
Pd(OAc)2 (10 mol%)/RuPhos (20 mol%) as the catalytic system, as
the catalytic system Pd(OAc)2 (10 mol%)/RuPhos (20 mol%) was
a,a-difluoro-1-phenylethanone 1 gave the desired products 2b, 2c
and 2f respectively, but compound 2a was formed as the by-
product. Compound 2f was isolated from 2a by silica-gel column
chromatography. Compounds 2b and 2c were not separable from
2a as they have very similar polarities, and were eventually
identified by GC–MS. The mechanism for the formation of side-
product 2a in these reactions is not well understood at this point.
When di-halo-substituted benzenes (1-fluoro-4-bromobenzene
and 1-chloro-4-bromobenzene) were used as substrates, the cross-
coupling products (2g and 2h) were formed via the activation of C–
Br bond selectively with small amount of 2a as inseparable
contaminant. The reaction of 1 with 1,4-dibromobenzene gave
high efficient for direct a-arylation of a-monofluorinated ketones
[17]. As shown in Table 1, when K3PO4Á3H2O and anhydrous K3PO4
were used as base, the Pd-catalyzed arylation in xylene at 130 8C
led to the formation of the arylation product 2a in low yield, and
only half amount of 1 was converted (Table 1, entries 1–2). It is
noteworthy that two hemiacetals [18] 3 and 4 were produced
easily as the hydrated byproduct from starting material 1 and
product 2a respectively. Starting material 1 remained intact in the
presence of mild bases Na2CO3 and K2CO3 (entries 3–4). Cs2CO3
Scheme 1. Synthetic strategies to
a-aryl-a,a-difluoroketones.

C. Guo et al. / Journal of Fluorine Chemistry 143 (2012) 135–142
137
Table 1
Evaluation of bases and supporting ligands for Pd-catalyzed
a
-arylation of a,a
-difluoroketone 1 with bromobenzene.a
O
Pd(OAc)2 (10%)
Ligand (20%)
Br
H
+
F
F
Base (2 equiv)
Xylene (0.2 M), 130 oC, 7 h
(2 equiv)
1
O
O
F2HC OH
HO OR
CHF2
RO OH
+
+
+
F
F
F F
F
F
2a
3
4
5
α-Arylation product
Hydration adduct
Aldol adduct
X=Cy, R1=R2=Oi-Pr, R3=H
X=Cy, R1=R2=OMe, R3=H
X=Cy, R1=R2=R3=i-Pr
RuPhos
SPhos
XPhos
PX2
R2
R1
X=Cy, R1=NMe2, R2=R3=H DavePhos
X=t-Bu, R1=R2=R3=H
JohnPhos
R3
PPh2
PPh2
Ph2P-(CH2)4-PPh2
O
O
PPh2
PPh2
PPh2
PPh2
Dppb
Xantphos
DPEphos
BINAP
Entry
Base
Ligand
Conversion of 1 (%)b
Yield of 2a (%)b
1
K3PO4Á3H2O
K3PO4
RuPhos
RuPhos
RuPhos
RuPhos
RuPhos
RuPhos
RuPhos
SPhos
57
56
54
51
74
53
86
83
87
65
63
78
75
75
76
82
100
62
14
15
Trace
8
2
3
Na2CO3
K2CO3
4
5
Cs2CO3
CsOAcc
t-BuONa
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
39
0
6
7d
8
9
57
64
16
18
51
40
43
47
53
90
25
9
XPhos
10
11
12
13
14
15
16
17
18f
DavePhos
JohnPhos
e
PPh3
e
P(t-Bu)3
Dppb
Xantphos
DPEphos
BINAP
BINAP
19F NMR data:
d
(ppm) 2a: À96.9 (s); 3: À130.1, À131.5 (AB, J = 277, 56 Hz); 4: À108.7, À109.6 (AB, J = 245 Hz); 5: À115.6, À117.6 (AB, J = 282 Hz), À129.8, À131.4 (AB, J = 290,
54 Hz).
a
Reaction conditions: Pd(OAc)2 (10 mol%), ligand (20 mol%), 1 (1 equiv.), bromobenzene (2 equiv.), base (2 equiv.), xylene (0.2 M of 1), 130 8C, 7 h.
b
c
d
e
f
Determined by 19F NMR using fluorobenzene as internal standard.
Generated in situ by Cs2CO3 (2 equiv.) and AcOH (4 equiv.).
11% Aldol adduct 5 was observed.
40% Ligand was used.
Toluene used as solvent at 100 8C.
mono-arylated compound 2i in 83% yield without the formation of
Under the standard reaction conditions, the
difluoro-1-(naphthalen-2-yl)ethanone 6 with diverse aryl bro-
mides gave -aryl- -difluoro-1-(naphthalen-2-yl) ethanones
7a–7h in moderate to good yields. It was also found that 7a was
formed as a by-product in the case of using 4-bromotoluene, 4-tert-
butylbromobenzene and 1-bromo-4-methoxybenzene as coupling
a-arylations of a,a-
double-arylated compound. The arylation of 1 with sterically
hindered 2-bromotoluene also proceeded smoothly to afford
product 2k in 52% yield.
a
a,a
The scope of the
a-arylation of a,a-difluoroketones 6 and 8 had
also been investigated and the results were summarized in Table 3.

138
C. Guo et al. / Journal of Fluorine Chemistry 143 (2012) 135–142
Table 2
Pd-catalyzed direct
a
-arylation of 1 with structurally diverse aryl bromides.a
O
H
O
Pd(OAc)2 (10%)
R
rac-BINAP (20%)
R
+
F
F
F F
Cs2CO3 (2 equiv)
Br
Xylene (0.2 M), 130 oC, 12 h
(2 equiv)
2
1
Me
t-Bu
O
O
O
F
F
F
F
F F
2a: 88%
2b: 79%c (17% 2a)
2c: 72%c (16% 2a)
Ph
OMe
O
O
O
F
F
F
F
F F
2d: 85%
2e: 90%
2f: 53%d (17% 2a)
F
Cl
Br
O
O
O
F
F
F
F
F F
2g: 61%c (7% 2a)
2h: 60%c (trace 2a)
2i: 83%e
CF3
O
O
F
F
F
F
Me
2j: 68%
2k: 52%
a
Reaction conditions: Pd(OAc)2 (10 mol%), BINAP (20 mol%), 1 (1 equiv.), aryl bromide (2 equiv.), Cs2CO3 (2 equiv.), xylene (0.2 M of 1), 130 8C, 12 h.
bIsolated yield.
cInseparable with 2a by silica-gel column chromatography.
dSeparable with 2a by column chromatography.
eNo double-arylated product was found.
partners. The
Fortunately, the cross-coupling reaction of 8 with aryl bromides
proceeded smoothly in mesitylene at 160 8C to afford a series of
aryl- -difluoro-1-(4-methoxyphenyl) ethanones in good
a
-arylation of
a
,
a
-difluoroketone 8 failed at 130 8C.
4. Experimental
a
-
4.1. General
a
,a
9
yields. Similarly, compound 9a was formed as a by-product when
4-bromotoluene, 4-tert-butylbromobenzene and 1-bromo-4-
All reactions were carried out under an argon atmosphere. All
commercially available reagents were used without further
methoxybenzene were used as coupling partners for
of -difluoroketone 8.
a
-arylation
purification, unless specified otherwise. a,a-Difluoroketones 1, 6
a
,a
and 8 were prepared according to literature procedures [4d].
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
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
3. Conclusion
In summary, we have developed a versatile method to prepare
-aryl- -difluoroketones in moderate to good yields by
palladium-catalyzed direct -arylation of -difluoroketones
with structurally diverse aryl bromides. This method provides a
a
a,a
a
a,a
practical and straightforward synthetic route to
difluorocarbonyl compounds.
a-aryl-a,a-

C. Guo et al. / Journal of Fluorine Chemistry 143 (2012) 135–142
139
Table 3
Substrate scope of palladium catalyzed
a-arylation of a,a
-difluoroketones 6 and 8.a
Pd(OAc)2 (10%)
rac-BINAP (20%)
Cs2CO3 (2 equiv)
Br
O
O
R
H
+
R
Ar
Ar
Xylene (0.2 M)
130 oC, 8 h (for 6)
or
F
F
F
F
(2 equiv)
Ar = 2-Naphthyl
Ar = 4-MeO-Ph 8
Ar = 2-Naphthyl
Ar = 4-MeO-Ph
6
7
9
Mesitylene (0.2 M)
o
8
160 C, 12 h (for
)
Me
t-Bu
O
F
O
O
F
F
F
F F
7a: 85%
7b: 63%c (16% 7a)
7c: 65%c (16% 7a)
F
OMe
Ph
O
O
O
F
F
F F
F
F
7d: 74%
7e: 56%d (22% 7a)
7f: 73%
CF3
O
O
O
F
F
F
F
F
F
Me
MeO
7g: 64%
7h: 65%
9a: 63%
Me
t-Bu
Ph
O
O
O
F
F
F
F
F F
MeO
MeO
MeO
9b: 80%e (16% 9a)
9c: 82%f (13% 9a)
9d: 77%
OMe
F
CF3
O
O
O
F
F
F
F
F F
MeO
MeO
MeO
9e: 69%f (22% 9a)
9f: 75%
9g: 52%
a
Reaction conditions: Pd(OAc)2 (10 mol%), BINAP (20 mol%), 6 or 8 (1 equiv.), aryl bromide (2 equiv.), Cs2CO3 (2 equiv.), xylene (0.2 M), 130 8C, 8 h (for 6) or mesitylene
(0.2 M), 160 8C, 12 h (for 8).
bIsolated yield.
cInseparable with 7a by silica-gel column chromatography.
dSeparable with 7a after column chromatography.
eInseparable with 9a by silica-gel column chromatography.
fSeparable with 9a after column chromatography.

140
C. Guo et al. / Journal of Fluorine Chemistry 143 (2012) 135–142
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.
4.2.5. 2,2-Difluoro-2-(naphthalen-2-yl)-1-phenylethanone (2e)
1H NMR (300 MHz, CDCl3):
7.85–8.12 (m, 6H), 7.40–7.68 (m,
6H). 13C NMR (100 MHz, CDCl3):
189.1 (t, J = 31.3 Hz), 134.2,
132.6, 132.3, 130.3 (t, J = 2.9 Hz), 129.0, 128.8, 128.7, 127.9, 127.8,
127.0, 126.0 (t, J = 6.6 Hz), 122.1 (t, J = 6.1 Hz), 117.2 (t,
d
d
4.2. General procedure for Pd-catalyzed
difluoroketone with aryl bromides
a
-arylation of
a
,
a-
J = 251.5 Hz). 19F NMR (282 MHz, CDCl3):
d
À97.4 (s, 2F). IR (neat,
cmÀ1): 1707, 1596, 1188, 1107. MS (EI): m/z (%) 77 (32), 105 (100),
177 (13), 282 (4, M+). HRMS: Calcd. for C18H12F2O: 282.0856;
found: 282.0853.
An oven-dried Schlenk tube containing a magnetic stirring bar
was charged with Pd(OAc)2 (11.2 mg, 0.05 mmol), rac-BINAP
(62.3 mg, 0.10 mmol), and Cs2CO3 (326 mg, 1.0 mmol). The
Schlenk tube was capped with a rubber septum and then
evacuated and backfilled with argon for three times. Xylene
(2.5 mL) was added through the septum via syringe and the
resulting mixture was stirred at room temperature for 15 min.
4.2.6. 2,2-Difluoro-2-(4-methoxyphenyl)-1-phenylethanone (2f)
1H NMR (300 MHz, CDCl3):
d
8.01 (d, J = 8.1 Hz, 2H), 7.52–7.59
(m, 3H), 7.42 (t, J = 8.1 Hz, 2H), 6.94 (d, J = 8.4 Hz, 2H), 3.81 (s, 3H).
13C NMR (100 MHz, CDCl3):
189.2 (t, J = 31.4 Hz), 161.6, 134.1,
d
132.3, 130.3 (t, J = 2.9 Hz), 128.6, 127.3 (t, J = 5.8 Hz), 125.2 (t,
J = 24.8 Hz), 117.1 (t, J = 250.9 Hz), 114.3, 55.4. 19F NMR (282 MHz,
Then a,a-difluoroketone (0.5 mmol) and aryl bromide (1.0 mmol)
were added. The Schlenk tube was sealed and the reaction mixture
was heated at 130 8C with vigorous stirring for 12 h. The reaction
mixture was cooled to room temperature and quenched with H2O
(20 mL). The solution was extracted with ether (3 Â 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/diethyl ether (40/1) as
eluent.
CDCl3):
d
À95.9(s, 2F). IR(neat, cmÀ1):2928, 1704, 1600, 1508, 1264,
1178. MS (EI): m/z (%) 77 (30), 105 (74), 157 (100), 262 (5, M+).
HRMS: Calcd. for C15H12F2O2: 262.0805; found: 262.0807. Anal.
Calcd. for C15H12F2O2: C, 68.70; H, 4.61. Found: C, 69.02; H, 4.94.
4.2.7. 2,2-Difluoro-2-(4-fluorophenyl)-1-phenylethanone (2g)
1H NMR (300 MHz, CDCl3):
d
8.03 (d, J = 7.2 Hz, 2H), 7.58–7.63
(m, 3H), 7.46 (t, J = 7.2 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H). 13C NMR
(100 MHz, CDCl3): 188.8 (t, J = 31.4 Hz), 164.2 (d, J = 249.3 Hz),
134.4, 132.1, 130.3 (t, J = 2.9 Hz), 128.7, 128.1 (dt, J = 8.8, 5.8 Hz),
125.7 (t, J = 5.9 Hz), 116.7 (t, J = 252.3 Hz), 116.0 (d, J = 22.6 Hz). 19
NMR (282 MHz, CDCl3):
d
4.2.1. 2,2-Difluoro-1,2-diphenylethanone (2a)
F
1H NMR (300 MHz, CDCl3):
d
8.03 (d, J = 7.5 Hz, 2H), 7.56–7.63
d
À92.7 (s, 2F), À105.2 (s, 1F). IR (neat,
(m, 3H), 7.41–7.47 (m, 5H). 13C NMR (100 MHz, CDCl3):
d
189.0 (t,
cmÀ1): 1701, 1607, 1511, 1237, 1134. MS (EI): m/z (%) 77 (42), 105
(100), 145 (11), 250 (0.16, M+). HRMS: Calcd. for C14H9F3O:
250.0605; found: 250.0602.
J = 30.6 Hz), 134.2, 133.2 (t, J = 25.5 Hz), 132.2, 130.9, 130.3 (t,
J = 2.9 Hz), 128.9, 128.7, 125.7 (t, J = 5.9 Hz), 117.0 (t, J = 252.3 Hz).
19F NMR (282 MHz, CDCl3):
d
À97.2 (s, 2F). IR (neat, cmÀ1): 1704,
1597, 1450, 1255, 1135. MS (EI): m/z (%) 77 (43), 105 (100), 127
(10), 232 (0.23, M+). HRMS: Calcd. for C14H10F2O: 232.0700; found:
232.0702. Anal. Calcd. for C14H10F2O: C, 72.41; H, 4.34. Found: C,
72.49; H, 4.37.
4.2.8. 2-(4-Chlorophenyl)-2,2-difluoro-1-phenylethanone (2h)
1H NMR (300 MHz, CDCl3):
d
8.02 (d, J = 8.4 Hz, 2H), 7.42–7.63
(m, 7H). 13C NMR (100 MHz, CDCl3):
d
188.6 (t, J = 30.6 Hz), 137.3 (t,
J = 2.2 Hz), 134.4, 132.0, 131.7 (t, J = 25.5 Hz), 130.3 (t, J = 2.9 Hz),
129.2, 128.8, 127.3 (t, J = 5.8 Hz), 116.7 (t, J = 253.0 Hz). 19F NMR
4.2.2. 2,2-Difluoro-1-phenyl-2-p-tolylethanone (2b)
(282 MHz, CDCl3):
1252, 1135. MS (EI):m/z (%) 77 (38), 105 (100), 161 (6). HRMS: Calcd.
d
À97.8 (s, 2F). IR (neat, cmÀ1): 1702, 1598, 1492,
1H NMR (300 MHz, CDCl3):
d
8.01 (d, J = 7.5 Hz, 2H), 7.40–7.62
(m, 5H), 7.25 (d, J = 8.1 Hz, 2H), 2.37 (s, 3H). 13C NMR (100 MHz,
CDCl3): 189.2 (t, J = 30.6 Hz), 141.2, 134.1, 130.3 (t, J = 2.9 Hz),
130.0, 128.9, 128.7, 128.6, 125.6 (t, J = 5.9 Hz), 117.1 (t,
J = 251.6 Hz), 21.3. 19F NMR (282 MHz, CDCl3):
for C14H9ClF2O: 266.0310; found: 266.0306.
d
4.2.9. 2-(4-Bromophenyl)-2,2-difluoro-1-phenylethanone (2i)
d
À97.5 (s, 2F).
1H NMR (300 MHz, CDCl3):
d
8.03 (d, J = 7.2 Hz, 2H), 7.59–7.62
IR (neat, cmÀ1): 1701, 1597, 1259, 1123, 817. MS (EI): m/z (%) 77
(31), 105 (100), 141 (9), 246 (2, M+). HRMS: Calcd. for C15H12F2O:
246.0856; found: 246.0857. Anal. Calcd. for C15H12F2O: C, 73.16; H,
4.91. Found: C, 73.61; H, 5.00.
(m, 3H), 7.44–7.49 (m, 4H). 13C NMR (100 MHz, CDCl3):
d
188.6 (t,
J = 30.6 Hz), 134.4, 132.1, 130.3 (t, J = 2.9 Hz), 128.8, 127.5 (t,
J = 5.9 Hz), 125.6, 116.7 (t, J = 252.3 Hz). 19F NMR (282 MHz,
CDCl3):
d
À98.0 (s, 2F). IR (neat, cmÀ1): 1692, 1594, 1252, 1122.
MS (EI): m/z (%) 77 (29), 105 (100), 205, 207 (3), 310, 312 (0.19, M+).
4.2.3. 2-(4-tert-Butylphenyl)-2,2-difluoro-1-phenylethanone (2c)
HRMS: Calcd. for C14H9BrF2O: 309.9805; found: 309.9801.
1H NMR (300 MHz, CDCl3):
d
8.03 (d, J = 7.8 Hz, 2H), 7.41–7.63
(m, 7H), 1.31 (s, 9H). 13C NMR (100 MHz, CDCl3):
d
189.2 (t,
4.2.10. 2,2-Difluoro-1-phenyl-2-(4-
J = 30.6 Hz), 154.3, 134.1, 130.3 (t, J = 2.9 Hz), 128.9, 128.6, 125.8,
125.4 (t, J = 5.8 Hz), 117.2 (t, J = 251.6 Hz), 34.9, 31.2. 19F NMR
(trifluoromethyl)phenyl)ethanone (2j)
1H NMR (300 MHz, CDCl3):
d
8.06 (d, J = 7.5 Hz, 2H), 7.74 (s, 4H),
7.63 (t, J = 7.5 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H). 13C NMR (100 MHz,
CDCl3): 188.4 (t, J = 31.3 Hz), 136.8 (t, J = 24.0 Hz), 134.6, 133.1 (d,
(282 MHz, CDCl3):
d
À97.4 (s, 2F). IR (neat, cmÀ1): 1704, 1597,
1266, 1124. MS (EI): m/z (%) 77 (29), 105 (100), 183 (6), 288 (1, M+).
HRMS: Calcd. for C18H18F2O: 288.1326; found: 288.1327. Anal.
Calcd. for C18H18F2O: C, 74.98; H, 6.29. Found: C, 75.44; H, 6.18.
d
J = 32.8 Hz), 131.9, 130.3 (t, J = 2.9 Hz), 128.8, 126.5 (t, J = 5.9 Hz),
125.8 (q, J = 3.6 Hz), 123.6 (q, J = 270.5 Hz), 116.5 (t, J = 253.0 Hz).
19F NMR (282 MHz, CDCl3):
d
À63.5 (s, 3F), À98.3 (s, 2F). IR (neat,
4.2.4. 2-(Biphenyl-4-yl)-2,2-difluoro-1-phenylethanone (2d)
cmÀ1): 1713, 1596, 1337, 1121, 1072. MS (EI): m/z (%) 77 (35), 84
1H NMR (300 MHz, CDCl3):
d
8.06 (d, J = 7.5 Hz, 2H), 7.38–7.68
(m, 12H). 13C NMR (100 MHz, CDCl3):
189.0 (t, J = 30.6 Hz), 134.2,
132.0 (t, J = 24.8 Hz), 130.3 (t, J = 2.9 Hz), 128.9, 128.8, 128.7, 128.6,
(100), 86 (60), 105 (75), 281 (0.75, [M–F]+). HRMS: Calcd. for
d
C
C
15H9F4O [M–F]+: 281.0590; found: 281.0589. Anal. Calcd. for
15H9F5O: C, 60.01; H, 3.02. Found: C, 60.55; H, 3.24.
128.0, 127.6, 127.3, 126.2 (t, J = 5.8 Hz), 117.1 (t, J = 251.6 Hz). 19
F
NMR (282 MHz, CDCl3):
1243, 1050. MS (EI): m/z (%) 77 (34), 105 (100), 130 (16), 308 (2,
M+). HRMS: Calcd. for C20H14F2O: 308.1013; found: 308.1010.
d
À97.7 (s, 2F). IR (neat, cmÀ1): 1702, 1613,
4.2.11. 2,2-Difluoro-1-phenyl-2-o-tolylethanone (2k)
1H NMR (300 MHz, CDCl3):
8.05 (d, J = 7.8 Hz, 2H), 7.22–7.64
(m, 7H), 2.34 (s, 3H). 13C NMR (100 MHz, CDCl3):
188.8
d
d

C. Guo et al. / Journal of Fluorine Chemistry 143 (2012) 135–142
141
(t, J = 31.4 Hz), 136.9 (t, J = 3.7 Hz), 134.1, 132.4, 132.0, 131.8,
130.8, 130.3 (t, J = 3.0 Hz), 128.6, 126.1 (t, J = 8.0 Hz), 125.9, 117.6
(t, J = 251.5 Hz), 20.0. 19F NMR (282 MHz, CDCl3):
(neat, cmÀ1): 1701, 1597, 1448, 1237, 1117. MS (EI): m/z (%) 77
(29), 105 (100), 141 (7), 246 (2, M+). HRMS: Calcd. for C15H12F2O:
246.0856; found: 246.0859.
4.2.17. 2,2-Difluoro-2-(4-fluorophenyl)-1-(naphthalen-2-
yl)ethanone (7f)
d
À96.5 (s, 2F). IR
1H NMR (300 MHz, CDCl3):
d
8.61 (s, 1H), 8.03 (d, J = 8.7 Hz, 1H),
7.93 (d, J = 8.1 Hz, 1H), 7.83–7.88 (m, 2H), 7.52–7.67 (m, 4H). 13C
NMR (100 MHz, CDCl3):
d 188.7 (t, J = 30.6 Hz), 164.2 (d,
J = 251.5 Hz), 136.0, 133.0 (t, J = 3.6 Hz), 132.3, 130.1, 129.5,
129.3, 128.6, 128.0–128.2 (m), 127.8, 127.1, 124.9 (t, J = 2.2 Hz),
4.2.12. 2,2-Difluoro-1-(naphthalen-2-yl)-2-phenylethanone (7a)
116.9 (t, J = 252.2 Hz), 116.1, 115.9. 19F NMR (282 MHz, CDCl3):
d
1H NMR (300 MHz, CDCl3):
d
8.61 (s, 1H), 8.05 (d, J = 8.7 Hz, 1H),
À96.3 (s, 2F), À109.4 (m, 1F). IR (neat, cmÀ1): 1705, 1624, 1514,
1228, 591. MS (EI): m/z (%) 127 (69), 155 (100), 300 (2, M+). HRMS:
Calcd. for C18H11F3O: 300.0762; found: 300.0759.
7.83–7.93 (m, 3H), 7.46–7.68 (m, 7H). 13C NMR (100 MHz, CDCl3):
d
188.9 (t, J = 30.6 Hz), 135.9, 133.4 (t, J = 24.8 Hz), 133.0, 132.3,
131.0, 130.1, 129.5, 129.4, 128.9, 128.6, 127.8, 127.0, 125.7 (t,
J = 5.8 Hz), 125.0, 117.2 (t, J = 251.6 Hz). 19F NMR (282 MHz,
4.2.18. 2,2-Difluoro-1-(naphthalen-2-yl)-2-(4-
CDCl3):
d
À96.5 (s, 2F). IR (neat, cmÀ1): 1701, 1627, 1266, 1108,
(trifluoromethyl)phenyl)ethanone (7g)
926, 699. MS (EI): m/z (%) 127 (65), 155 (100), 282 (4, M+). HRMS:
1H NMR (300 MHz, CDCl3):
d
8.65 (s, 1H), 8.05 (d, J = 8.7 Hz, 1H),
7.97 (d, J = 8.1 Hz, 1H), 7.86–7.92 (m, 2H), 7.73–7.81 (m, 4H), 7.55–
7.68 (m, 2H). 13C NMR (100 MHz, CDCl3):
188.3 (t, J = 30.8 Hz),
Calcd. for C18H12F2O: 282.0856; found: 282.0857.
d
4.2.13. 2,2-Difluoro-1-(naphthalen-2-yl)-2-p-tolylethanone (7b)
136.9 (t, J = 25.3 Hz), 136.1, 133.0 (t, J = 3.9 Hz), 132.3, 130.1, 129.6,
129.1, 128.8, 127.8, 127.2, 126.5 (t, J = 6.4 Hz), 125.8 (q, J = 4.0 Hz),
124.8, 123.6 (q, J = 270.1 Hz), 116.7 (t, J = 253.5 Hz). 19F NMR
1H NMR (300 MHz, CDCl3):
d 8.59 (s, 1H), 8.03 (d, J = 8.1 Hz,
1H), 7.90 (d, J = 7.8 Hz, 1H), 7.80–7.85 (m, 2H), 7.46–7.59 (m,
4H), 7.25 (d, J = 8.7 Hz, 1H), 2.35 (s, 3H). 13C NMR (100 MHz,
(282 MHz, CDCl3):
d
À63.5 (s, 3F), À97.7 (s, 2F). IR (neat, cmÀ1):
CDCl3):
d
189.1 (t, J = 31.4 Hz), 141.3, 135.9, 133.0, 132.3, 131.0,
1712, 1333, 1121, 1070. MS (EI): m/z (%) 127 (71), 145 (17), 155
(100), 350 (1, M+). HRMS: Calcd. for C19H11F5O: 350.0730; found:
350.0736.
130.5 (t, J = 26.3 Hz), 130.1, 129.6, 129.3, 128.9, 128.5, 127.8,
127.0, 125.7 (t, J = 5.8 Hz), 125.1, 117.4 (t, J = 252.3 Hz), 21.4. 19
F
NMR (282 MHz, CDCl3):
d
À96.9 (s, 2F). IR (neat, cmÀ1): 1706,
1627, 1266, 1043, 765. MS (EI): m/z (%) 127 (62), 155 (100), 296
(2, M+). HRMS: Calcd. for C19H14F2O: 296.1013; found:
296.1014.
4.2.19. 2,2-Difluoro-1-(naphthalen-2-yl)-2-o-tolylethanone (7h)
1H NMR (300 MHz, CDCl3):
d
8.62 (s, 1H), 8.07 (d, J = 8.7 Hz, 1H),
7.83–7.93 (m, 3H), 7.70 (d, J = 7.5 Hz, 1H), 7.51–7.64 (m, 2H), 7.22–
7.40 (m, 3H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3):
188.7 (t,
d
4.2.14. 2-(4-tert-Butylphenyl)-2,2-difluoro-1-(naphthalen-2-
J = 31.4 Hz), 137.0 (t, J = 2.9 Hz), 135.9, 133.0 (t, J = 2.9 Hz), 132.3,
132.1, 132.0 (t, J = 22.6 Hz), 130.8, 130.1, 129.6, 129.3, 128.5, 127.8,
127.0, 126.2 (t, J = 8.0 Hz), 126.0, 125.0, 117.4 (t, J = 251.6 Hz), 20.1.
yl)ethanone (7c)
1H NMR (300 MHz, CDCl3):
d
8.62 (s, 1H), 8.05 (d, J = 9.0 Hz,
1H), 7.92 (d, J = 7.8 Hz, 1H), 7.81–7.86 (m, 2H), 7.46–7.61 (m, 6H),
1.30 (s, 9H). 13C NMR (100 MHz, CDCl3):
189.1 (t, J = 30.6 Hz),
19F NMR (282 MHz, CDCl3):
d
À95.9 (s, 2F). IR (neat, cmÀ1): 1701,
d
1626, 1460, 1227, 1104. MS (EI): m/z (%) 127 (71), 155 (100), 296
(2, M+). HRMS: Calcd. for C19H14F2O: 296.1013; found: 296.1017.
154.3, 135.9, 133.0 (t, J = 3.6 Hz), 132.3, 130.7 (t, J = 24.8 Hz),
130.1, 129.6, 129.3, 128.9, 128.5, 127.8, 127.0, 125.9, 125.5 (t,
J = 5.8 Hz), 125.1, 117.4 (t, J = 251.6 Hz), 34.9, 31.2. 19F NMR
4.2.20. 2,2-Difluoro-1-(4-methoxyphenyl)-2-phenylethanone (9a)
(282 MHz, CDCl3):
d
À96.8 (s, 2F). IR (neat, cmÀ1): 2964, 1701,
1H NMR (300 MHz, CDCl3):
d
8.03 (d, J = 9.0 Hz, 2H), 7.60–7.62
(m, 2H), 7.45–7.47 (m, 3H), 6.91 (d, J = 9.3 Hz, 2H), 3.86 (s, 3H). 13
NMR (100 MHz, CDCl3): 187.4 (t, J = 29.9 Hz), 164.4, 133.6 (t,
1626, 1270, 1107. MS (EI): m/z (%) 127 (70), 155 (100), 173 (17),
338 (0.58, M+). HRMS: Calcd. for C22H20F2O: 338.1482; found:
338.1486.
C
d
J = 24.8 Hz), 132.9 (t, J = 2.9 Hz), 130.8, 128.8, 125.6 (t, J = 5.9 Hz),
125.1, 117.1 (t, J = 250.8 Hz), 114.0, 55.5. 19F NMR (282 MHz,
4.2.15. 2-(Biphenyl-4-yl)-2,2-difluoro-1-(naphthalen-2-yl)ethanone
CDCl3):
d
À96.7 (s, 2F). IR (neat, cmÀ1): 2928, 1696, 1601, 1264,
(7d)
1128. MS (EI): m/z (%) 77 (24), 92 (15), 135 (100), 262 (0.31, M+).
1H NMR (300 MHz, CDCl3):
d
8.66 (s, 1H), 8.08 (d, J = 8.4 Hz, 1H),
7.96 (d, J = 8.1 Hz, 1H), 7.85–7.91 (m, 2H), 7.38–7.76 (m, 11H). 13
NMR (100 MHz, CDCl3): 188.9 (t, J = 31.6 Hz), 143.9, 140.0, 136.0,
HRMS: Calcd. for C15H12F2O2: 262.0805; found: 262.0803.
C
d
4.2.21. 2,2-Difluoro-1-(4-methoxyphenyl)-2-p-tolylethanone (9b)
133.0 (t, J = 4.0 Hz), 132.3, 132.1 (t, J = 25.3 Hz), 130.1, 129.6, 129.4,
128.9, 128.6, 128.0, 127.8, 127.6, 127.3, 127.0, 126.2 (t, J = 5.5 Hz),
1H NMR (300 MHz, CDCl3):
d
8.02 (d, J = 8.7 Hz, 2H), 7.49 (d,
J = 7.8 Hz, 2H), 7.25 (d, J = 7.8 Hz, 2H), 6.90 (d, J = 8.7 Hz, 2H), 3.84
(s, 3H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3):
187.5 (t,
125.0, 117.3 (t, J = 252.0 Hz). 19F NMR (282 MHz, CDCl3):
d
À97.1 (s,
d
2F). IR (neat, cmÀ1): 1698, 1627, 1266, 1049, 747. MS (EI): m/z (%)
J = 29.9 Hz), 164.3, 132.9 (t, J = 2.9 Hz), 130.8 (t, J = 24.8 Hz), 129.5,
128.8, 125.5 (t, J = 5.9 Hz), 125.1, 117.2 (t, J = 250.8 Hz), 114.0, 55.5,
127 (65), 155 (100), 203 (7, [M–NapCO]+). HRMS: Calcd. for
C
13H9F2 [M–NapCO]+: 203.0672; found: 203.0675.
21.3. 19F NMR (282 MHz, CDCl3):
2936, 1698, 1600, 1264, 1121. MS (EI): m/z (%) 77 (14), 92 (10), 135
(100), 276 (0.31, M+). HRMS: Calcd. for C16H14F2O2: 276.0962;
found: 276.0965.
d
À96.3 (s, 2F). IR (neat, cmÀ1):
4.2.16. 2,2-Difluoro-2-(4-methoxyphenyl)-1-(naphthalen-2-
yl)ethanone (7e)
1H NMR (300 MHz, CDCl3):
d
8.59 (s, 1H), 8.04 (d, J = 8.4 Hz, 1H),
7.93 (d, J = 8.1 Hz, 1H), 7.84–7.88 (m, 2H), 7.52–7.65 (m, 4H), 6.96
(d, J = 8.7 Hz, 1H), 3.82 (s, 3H). 13C NMR (100 MHz, CDCl3):
189.2
4.2.22. 2-(4-tert-Butylphenyl)-2,2-difluoro-1-(4-
d
methoxyphenyl)ethanone (9c)
(t, J = 31.3 Hz), 161.6, 135.9, 132.9 (t, J = 3.6 Hz), 132.3, 130.0,
129.6, 129.3, 128.5, 127.8, 127.3 (t, J = 5.8 Hz), 127.0, 125.4 (t,
J = 24.8 Hz), 125.1 (t, J = 2.2 Hz), 117.3 (t, J = 250.8 Hz), 114.3, 55.4.
1H NMR (300 MHz, CDCl3):
d
8.04 (d, J = 8.7 Hz, 2H), 7.54 (d,
J = 8.1 Hz, 2H), 7.46 (d, J = 8.1 Hz, 2H), 6.90 (d, J = 8.7 Hz, 2H), 3.84
(s, 3H), 1.31 (s, 9H). 13C NMR (100 MHz, CDCl3):
187.6 (t,
d
19F NMR (282 MHz, CDCl3):
1614, 1519, 1275, 1180. MS (EI): m/z (%) 127 (18), 135 (100), 155
(30), 312 (1, M+). HRMS: Calcd. for C19H14F2O2: 312.0962; found:
312.0963.
d
À96.0 (s, 2F). IR (neat, cmÀ1): 1697,
J = 30.6 Hz), 164.3, 154.1, 132.9 (t, J = 2.9 Hz), 130.6 (t, J = 24.8 Hz),
125.8, 125.4 (t, J = 5.9 Hz), 125.1, 117.3 (t, J = 250.8 Hz), 114.0, 55.5,
34.9, 31.2. 19F NMR (282 MHz, CDCl3):
d
À98.6 (s, 2F). IR (neat,
cmÀ1): 2963, 1696, 1601, 1508, 1263, 1140. MS (EI): m/z (%) 77

142
C. Guo et al. / Journal of Fluorine Chemistry 143 (2012) 135–142
(12), 92 (8), 135 (100), 318 (0.16, M+). HRMS: Calcd. for
19H20F2O2: 318.1431; found: 318.1435.
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(c) J.-A. Ma, D. Cahard, Journal of Fluorine Chemistry 128 (2007) 975–996;
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methoxyphenyl)ethanone (9d)
1H NMR (300 MHz, CDCl3):
d
8.07 (d, J = 8.7 Hz, 2H), 7.67 (s, 4H),
7.57 (d, J = 7.8 Hz, 2H), 7.37–7.47 (m, 3H), 6.92 (d, J = 8.7 Hz, 2H),
3.85 (s, 3H). 13C NMR (100 MHz, CDCl3):
187.4 (t, J = 29.8 Hz),
d
(f) W.K. Hagmann, Journal of Medicinal Chemistry 51 (2008) 4359–4369;
(g) K.L. Kirk, Organic Process Research and Development 12 (2008) 305–321.
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327–351.
164.5, 143.8, 140.0, 132.9 (t, J = 2.9 Hz), 132.4 (t, J = 24.8 Hz), 129.0,
128.0, 127.5, 127.3, 126.1 (t, J = 5.9 Hz), 125.0, 117.2 (t,
J = 251.6 Hz), 114.1, 55.6. 19F NMR (282 MHz, CDCl3):
d
À96.5 (s,
2F). IR (neat, cmÀ1): 1694, 1602, 1270, 1177. MS (EI): m/z (%) 77
[3] (a) A.M. Silva, R.E. Cachau, H.L. Sham, J.W. Erickson, Journal of Molecular Biology
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(16), 92 (10), 135 (100), 338 (0.26, M+). HRMS: Calcd. for
(b) D. Schirlin, S. Baltzer, J.M. Altenburger, C. Tarnus, J.M. Remy, Tetrahedron 52
(1996) 305–318.
C
21H16F2O2: 338.1118; found: 338.1115.
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1782;
4.2.24. 2,2-Difluoro-1,2-bis(4-methoxyphenyl)ethanone (9e)
1H NMR (300 MHz, CDCl3):
8.02 (d, J = 9.0 Hz, 2H), 7.52 (d,
J = 8.7 Hz, 2H), 6.94 (d, J = 9.0 Hz, 2H), 6.90 (d, J = 9.0 Hz, 2H), 3.85
(s, 3H), 3.81 (s, 3H). 13C NMR (100 MHz, CDCl3):
187.6 (t,
J = 30.6 Hz), 164.3, 161.4, 132.9 (t, J = 2.9 Hz), 127.2 (t, J = 5.9 Hz),
125.7 (t, J = 25.5 Hz), 125.1, 117.2 (t, J = 250.9 Hz), 114.2, 114.0,
d
(b) C.C. Kotoris, M.-J. Chen, S.D. Taylor, Journal of Organic Chemistry 63 (1998)
8052–8057;
(c) D.W. Konas, J.K. Coward, Organic Letters 1 (1999) 2105–2107;
(d) I. Pravst, M. Zupan, S. Stavber, Synthesis (2005) 3140–3146.
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(c) M. Zupan, J. Iskra, S. Stavber, Journal of Organic Chemistry 60 (1995) 259–260;
(d) S. Stavber, M. Zupan, Synlett (1996) 693–694.
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(c) R.P. Singh, J.M. Shreeve, Accounts of Chemical Research 37 (2003) 31–44;
(d) P.T. Nyffeler, S.G. Duron, M.D. Burkart, S.P. Vincent, C.-H. Wong, Angewandte
Chemie International Edition 44 (2005) 192–212.
d
55.5, 55.4. 19F NMR (282 MHz, CDCl3):
d
À95.3 (s, 2F). IR (neat,
cmÀ1): 2925, 1689, 1600, 1255, 1175. MS (EI): m/z (%) 77 (15), 92
(11), 135 (100), 292 (1, M+). HRMS: Calcd. for C16H14F2O3:
292.0911; found: 292.0915.
4.2.25. 2,2-Difluoro-2-(4-fluorophenyl)-1-(4-
methoxyphenyl)ethanone (9f)
[8] (a) W.J. Middleton, E.M. Bingham, Journal of Organic Chemistry 45 (1980) 2883–
2887;
1H NMR (300 MHz, CDCl3):
d
8.03 (d, J = 8.7 Hz, 2H), 7.57–7.62
(m, 2H), 7.14 (t, J = 8.4 Hz, 2H), 6.92 (d, J = 9.0 Hz, 2H), 3.87 (s, 3H).
13C NMR (100 MHz, CDCl3):
187.1 (t, J = 30.6 Hz), 164.5, 164.1 (d,
(b) G. Ha¨gele, A. Haas, Journal of Fluorine Chemistry 76 (1996) 15–19;
(c) G.S. Lai, G.P. Pez, R.J. Pesaresi, F.M. Prozonic, H. Cheng, Journal of Organic
Chemistry 64 (1999) 7048–7054;
d
J = 249.4 Hz), 132.9 (t, J = 3.0 Hz), 129.5 (d, J = 26.2 Hz), 127.9–
128.1 (m), 124.9, 116.8 (t, J = 252.3 Hz), 116.0, 115.8, 114.1, 55.6.
(d) R.P. Singh, J.M. Shreeve, Organic Letters 3 (2001) 2713–2715;
(e) R.P. Singh, J.M. Shreeve, Journal of Organic Chemistry 66 (2001) 6263–6267;
(f) R.P. Singh, J.M. Shreeve, Journal of Organic Chemistry 68 (2003) 6063–6065.
[9] S. Rozen, D. Zamir, Journal of Organic Chemistry 56 (1991) 4695–4700.
[10] O. Cohen, S. Rozen, Tetrahedron 64 (2008) 5362–5364.
[11] (a) T. Fukuhara, S. Hara, Synlett (2009) 198–200;
(b) S. Ayuba, N. Yoneda, T. Fukuhara, S. Hara, Bulletin of the Chemical Society of
Japan 75 (2002) 1597–1603.
19F NMR (282 MHz, CDCl3):
d
À95.6 (s, 2F), À108.9 (m, 1F). IR (neat,
cmÀ1): 2925, 1691, 1601, 1509, 1264, 1133. MS (EI): m/z (%) 77
(20), 92 (14), 135 (100), 280 (0.17, M+). HRMS: Calcd. for
C
15H11F3O2: 280.0711; found: 288.0713.
[12] T.B. Patrick, J.J. Scheibel, G.L. Cantrell, Journal of Organic Chemistry 46 (1981)
3917–3918.
4.2.26. 2,2-Difluoro-1-(4-methoxyphenyl)-2-(4-
[13] P. Biju, Synthetic Communications 38 (2008) 1940–1945.
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[15] (a) M. Palucki, S.L. Buchwald, Journal of the American Chemical Society 119
(1997) 11108–11109;
(trifluoromethyl)phenyl)ethanone (9g)
1H NMR (300 MHz, CDCl3):
d
8.06 (d, J = 8.7 Hz, 2H), 7.73 (s, 4H),
6.94 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H). 13C NMR (100 MHz, CDCl3):
d
(b) B.C. Hamann, J.F. Hartwig, Journal of the American Chemical Society 119
(1997) 12382–12383;
(c) T. Satoh, Y. Kawamura, M. Miura, M. Nomura, Angewandte Chemie Interna-
tional Edition 36 (1997) 1740–1742.
186.7 (t, J = 29.9 Hz), 164.7, 137.2 (t, J = 24.7 Hz), 132.9 (t,
J = 2.9 Hz), 126.4 (t, J = 5.9 Hz), 125.7 (q, J = 3.6 Hz), 124.7, 123.6
(q, J = 270.5 Hz), 116.6 (t, J = 253.8 Hz), 114.2, 55.6. 19F NMR
(282 MHz, CDCl3):
d
À62.7 (s, 3F), À97.2 (s, 2F). IR (neat, cmÀ1):
[16] (a) F. Bellina, R. Rossi, Chemical Reviews 110 (2010) 1082–1146;
(b) C.C.C. Johansson, T.J. Colacot, Angewandte Chemie International Edition 49
(2010) 676–707.
[17] C. Guo, Y. Guo, R.-W. Wang, F.-L. Qing, Journal of Fluorine Chemistry 133 (2012)
86–89.
2936, 1693, 1601, 1326, 1267, 1131, 616. MS (EI): m/z (%) 77 (15),
92 (11), 135 (100), 330 (0.12, M+). HRMS: Calcd. for C16H11F5O2:
330.0679; found: 330.0675.
[18] M. Matsui, K. Yamada, K. Funabiki, Tetrahedron 61 (2005) 4671–4677.
[19] T. Brigaud, P. Doussot, C. Portella, Chemical Communications (1994) 2117–2118.
[20] E.C. Constable, Metals and Ligand Reactivity: An Introduction to the Organic
Chemistry of Metal Complexes, Wiley-VCH, Weinheim, Germany, 1996.
[21] R. Martin, S.L. Buchwald, Accounts of Chemical Research 41 (2008) 1461–1473,
and references cited therein.
[22] V.V. Grushin, W.J. Marshall, Journal of the American Chemical Society 128 (2006)
12644–12645.
[23] R.N. Loy, M.S. Sanford, Organic Letters 13 (2011) 2548–2551.
Acknowledgments
We thank National Natural Science Foundation of China
(21072018, 20632008) and National Basic Research Program
of China (973 Program, No. 2012CB821600) for funding this
work.