Palladium-Catalyzed Direct Approach to α-Trifluoromethyl Alcohols by Selective Hydroxylfluorination of gem-Difluoroalkenes

Article abstract of DOI:10.1002/ejoc.201800468

A novel palladium-catalyzed selective hydroxylfluorination of gem-difluoroalkenes has been developed. By employing easily obtainable gem-difluoroalkenes and NFSI as the fluorine source, the scope, advantages, and limitations of this reaction were investigated. The reaction presents an efficient synthesis to afford a series of α-trifluoromethyl alcohols in good to excellent yields. Furthermore, this reaction probably proceeds via oxidation of Pd⁰ to Pd^II fluoride complex by NFSI, followed by fluoropalladation of gem-difluoroalkenes to generate an α-trifluoromethylbenzyl–Pd intermediate. And this strategy offers more possibilities for the construction of other bonds, such as C–C, C–N and C–S.

Full text of DOI:10.1002/ejoc.201800468

A Journal of
Accepted Article
Title: Palladium-Catalyzed Direct Approch to α-Trifluoromethyl Alcohols
by Selective Hydroxylfluorination of gem-Difluoroalkenes
Authors: Bin Zhang, Xiaofei Zhang, Jian Hao, and Chunhao Yang
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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the VoR from the journal website shown below when it is published
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800468
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800468
Supported by

10.1002/ejoc.201800468
European Journal of Organic Chemistry
COMMUNICATION
Palladium-Catalyzed Direct Approch to α-Trifluoromethyl
Alcohols by Selective Hydroxylfluorination of gem-
Difluoroalkenes
Bin Zhang,[a,b] Xiaofei Zhang,[a] Jian Hao,[b] and Chunhao Yang*[a]
Abstract: A novel palladium-catalyzed selective hydroxylfluorination
of gem-difluoroalkenes has been developed. By employing easily
obtained gem-difluoroalkenes and NFSI as the fluorine source, the
scope, advantages, and limitations of this reaction were well
investigated. The reaction presents an efficient synthesis to afford a
series of ɑ-trifluoromethyl alcohols in good to excellent yields.
Furthermore, this reaction probably proceeds via oxidation of Pd (0)
to Pd (II) fluoride complex by NFSI, followed by fluoropalladation of
gem-difluoroalkenes to generate an α-trifluoromethylbenzyl–Pd
intermediate. And this strategy offers more possibilities for the
constructing of other bonds, such as C-C, C-N and C-S.
As an alternative CF3 precursor, gem-difluoroalkenes have
attracted more and more attention in organic chemistry. However,
the further fluorination of gem-difluoroalkenes affording a CF3
group was very difficult in the past. This is because the CF3
carbanion formed from direct fluoride addition was found to be
Introduction
Because the trifluoromethyl (CF3) group can dramatically
modify the physical, chemical, and biological properties of
molecules, CF3-containing organic compounds have attracted
significant attention from researchers in medicinal and agriculture
chemistry.1 In particular, the introduction of CF3 into drug
candidates is able to enhance chemical and metabolic stability,
improve lipophilicity and bioavailability, and even increase the
protein-binding a nity.2 Consequently, it is not surprising that
numerous e orts have been devoted to the development of new
methodologies for the preparation of CF3-containing compounds.3
Furthermore, difunctionalization of alkenes, which involves the
introduction of two functional groups across a double bond,
represents a powerful method to construct diverse functionalized
molecules. In the past decade, the development of methods for
achieving difunctionalization of alkenes, including transition metal
catalysis and visible-light photocatalysis, have been reported in
organic synthesis.4 It is need to be pointed that some pioneering
and important works were reported by Liu and co-workers.5
Among these methods of achieving difunctionalization of alkenes,
the formation of a new C–CF3 bond has become an important
area and much effort has been made for the aim of developing
novel and efficient methods.6
Figure 1. Synthesis of CF3-containing compounds by difunctionalization of gem-
difluoroalkenes
unstable and is spontaneously quenched by proton abstraction.7,8
Recently, some novel methods for synthesis of CF3-containing
compounds by difunctionalization of gem-difluoroalkenes have
been reported (Figure 1). In 2014, Hu and coworkers reported a
novel silver(I)-fluoride-mediated homo-coupling reaction of gem-
difluoroalkenes (Figure 1, a).9 The key intermediate of this
protocol is benzylsilver complex which was formed from
nucleophilic addition of AgF to β, β-difluorostyrenes. This is the
first example of the reactivity of α-trifluoromethylbenzyl-silver
species. Later, Hu and coworkers carried out further exploration
and developed an original route for the synthesis of α-CF3 alkenes
and β-CF3 ketones via gem-difluoroalkenes fluorination and
silver-mediated alkenyl C-H functionalization in 2015 (Figure 1,
b).10 In addition, Loh and coworkers presented a different and
novel strategy based on palladium-catalyzed allylic alkylation by
caesium fluoride nucleophilic addition of gem-difluoroalkenes in
2016 (Figure 1, c).11 Furthermore, in 2017 Loh and coworkers
[a]
[b]
B. Zhang, X. Zhang, Prof. C. Yang
State Key Laboratory of Drug Research
Shanghai Institute of Materia Medica
Chinese Academy of Sciences, Shanghai 201203 (China)
E-mail: chyang@simm.ac.cn
B. Zhang, Prof. J. Hao
Department of Chemistry
Innovative Drug Research Center
Shanghai University, Shanghai 200436 (China)
Supporting information for this article is given at the end of the
document.
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10.1002/ejoc.201800468
European Journal of Organic Chemistry
COMMUNICATION
described the palladium-catalyzed fluoroarylation of gem-
difluoroalkenes and arylation with aryl halides (Figure 1, d).12 It is
worthy to note that the in situ generated α-CF3-benzylsilver, the
key intermediate, derived from the nucleophilic addition of silver
fluoride onto gem-difluoroalkenes. However, researches are still
confronted with many potential challenges, such as the low
stability of intermediates and their notorious reluctance to
participate in the transmetalation. These academic problems are
far less well investigated and required further study.
subsequent solvent screening indicated that this reaction did not
work in other solvents such as CH3CN, DMF and THF (entries 12-
15). Furthermore, when the reaction mixture was warmed to 40 °C,
the desired product 2a was obtained in the same yield (entry 16
vs entry 8).
Table 1. Optimization of Reaction Conditions[a]
Inspired by our recent work in fluorine chemistry,13 we designed
a
new strategy to construct α-trifluoromethyl alcohols via
palladium-catalyzed selective hydroxylfluorination of gem-
difluoroalkenes (Figure 1, e). As an effective fluorine source, N-
Fluorobenzenesulfonimide (NFSI) could be served to oxidize
Pd(0) to a Pd(II) fluoride complex. Different from the α-
trifluoromethylbenzyl-Ag species (Hu and Lohs’ work), the key
ent
ry
yield
[F]+
catalyst
PdCl2
ligand
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L1
L1
L1
L1
L1
additive
solvent
(%)[b]
1
2
NFSI
NFSI
NFSI
CF3COOH
CH3COOH
CF3COONa
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
68
trace
trace
20
intermediate
of
this
strategy
is
probably
the
α-
trifluoromethylbenzyl–Pd complex generated from fluoro-
palladation of gem-difluoroalkenes. Furthermore, CF3COOH, as
an additive, involves ligand exchange and affords the C–O bond
formation. As far as we know, α-trifluoromethyl alcohols can only
be prepared from trifluoromethylation of aldehyde and carbonyl
compounds or reduction of trifluoromethyl ketones.14,15 Compared
with existing methods, this new strategy has some significant
advantages: (i) easily available fluorine source comes from NFSI,
which serves as a good reagent ; (ii) only catalytic Pd is needed
and no other metal is participated in hydroxylfluorination of gem-
difluoroalkenes; (iii) based on the in-vestigation of the reaction
mechanism, this strategy offers more possibilities for the
constructing of other bonds, such as C-C, C-N and C-S. Therefore,
we envisioned that this new strategy is important and significant.
PdCl2
3
PdCl2
Selectf
luor
4
PdCl2
5
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
Pd(OAc)2
Pd(OCOCF3)2
Pd(PPh3)4
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
40
6
63
7
48
1,4-
dioxane
8
89
9
1,4-dioxane
1,4-dioxane
1,4-dioxane
CH3CN
21
10
11
12
13
14
15
56
60
Results and Discussion
trace
32
As we know, gem-difluoroalkenes could be easily obtained from
aldehydes or activated ketones in the presence of KI, Ph3P, and
methyl 2,2,-difluoro-2-(fluorosulfonyl)acetate (MDFA) under
moderate conditions.16 The study was initiated by exploring
reaction conditions for the hydroxylfluorination of 4-(2,2-
difluorovinyl)-1,1'-biphenyl (1a) (Table 1). Pleasingly, 68% yield of
2a was found when 1a was treated with 5 mol% of PdCl2, 7.5
mol% of L1, 2 equiv of NFSI and 5 equiv of CF3COOH at room
temperature under argon in 1,4-dioxane (entry 1). Notably, only
trace desired product was detected when CF3COOH was
replaced by CF3COONa or CH3COOH (entry 2 and entry 3) and it
was implied that strong acid with weaker nucleophilicity was
crucial for the formation of C–O bond. Then we investigated the
fluorine sources and found that Selectfluor was a less effective
fluorinating reagent for this tandem reaction (entry 4).
Subsequently, the exploration of different Pd salts, such as
Pd(OAc)2, Pd(OCOCF3)2, Pd(PPh3)4 and Pd(dba)2, led to the
discovery that Pd(dba)2 was the best choice for this process and
the desired product 2a could be obtained in 89% yield (entries 5-
8). By screening the ligands, such as L2, L3 and L4, L1 was
revealed to be the optimal ligand (entries 9-11). Although we
obtained desired compound with a yield of 32% in NMP, the
NMP
DMF
trace
0
THF
16[
1,4-dioxane
88
c]
[a] Reaction conditions: 1a (0.5 mmol), [F]+ (1.0 mmol), catalyst (5 mol%), ligand
(7.5 mol%), additive (2.5 mmol) in solvent (3.0 mL) at r.t. for 6 h under Ar. [b]
Isolated yields. [c] At 40 °C.
With the aforementioned optimized reaction conditions in hand
(Table 1, entry 8), we firstly investigated the substrates prepared
from aryl aldehydes, and the results are compiled in Scheme 1.
Gratifyingly, the reaction showed broad substrate compatibility,
and good functional group tolerance, including alkyl, fluoro, bromo,
and chloro could react with NFSI under the standard conditions to
a ord the corresponding α-trifluoromethyl alcohols in moderate
to excellent yields (2b-2f). Besides, gem-difluoroalkenes with the
electron-donating groups such as benzyloxy and phenoxy worked
well under the standard conditions (2g and 2h, 87% and 95%
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10.1002/ejoc.201800468
European Journal of Organic Chemistry
COMMUNICATION
yields, respectively). However, the substrate with the 2-pyridyl
group reacted with NFSI to deliver the corresponding product 2i
in 53% yield, which was lower than 2g and 2h. This result may be
be caused by poisoning of the catalyst. Similar result was
observed on 2W. To better understand the substitution electron
e ect, more substituents were carried out. Among them,
the exciting results obtained from this Pd-catalyzed
hydroxylfluorination of gem-difluorostyrenes, further application of
the optimized reaction conditions to hetero-aromatic gem-
difluoroalkenes were carried out. For example, the substrates with
benzofuran, benzo[b]thiophene, and thiophene delivered the
corresponding product 2s, 2t, and 2u in acceptable yields. In
order to reveal the practicability of this reaction, a gram-scale
reaction between 1g and NFSI was carried out, which gave
product 2g in 80% yield (Supporting Information).
Scheme 1. Palladium-Catalyzed Hydroxylfluorination of gem-difluoroalkenes
from Aromatic Aldehydes
On the basis of the literature reports on fluoroesterification of
styrenes17, a plausible reaction mechanism for palladium-
catalyzed hydroxylfluorination of gem-difluoroalkenes has been
proposed in Scheme 2. The reaction is initiated through oxidation
of Pd (0) by NFSI to give Pd (II) fuoride complex I, and
subsequence fuoropalladation of 1a offers the intermediate II.
Then, two possible paths are presented to address the
transformation from complex II to the high-valent Pd intermediate
V. The first pathway involves ligand exchange between II and
CF3COOH to yields intermediate III, and then subsequent
oxidation of III by NFSI generates the high-valent Pd intermediate
V (path a). For the second pathway, the transformation from Pd
complex II to IV is firstly via oxidation of Pd (II) species II to the
high-valent Pd interme-diate IV and subsequence undergoes
ligand exchange be-tween IV and CF3COOH (path b). Finally,
intermediate V undergoes reductive elimination to form the C–O
bond and get product VI, which is easily hydrolyzed to the
compound 2a.
Scheme 2. Possible Mechanism
[a] Conditions: 1 (0.4 mmol), NFSI (0.8 mmol), Pd(dba)2 (5 mol%), L1 (7.5 mol%),
CF3COOH (2.0 mmol), 1,4-Dioxane (2.0 mL), r.t., Ar. Isolated yields were
presented.
when the fluoro group present at different positions on the
aromatic ring, the lower yields were observed (2j, 2k, and 2m,
45%, 58% and 48% yields, respectively). Compared with the
fluoro-substituted substrates, the methyl group substitutions
showed higher yields (2k vs 2l, 45% vs 50% and 2m vs 2n, 58%
vs 71%). It is worth noting that whether the electron-donating
group or the electron-withdrawing group, ortho-substituted
substrates showed higher reactivity than meta isomer (2k vs 2m,
45% vs 58% and 2l vs 2n, 50% vs 71%). Next, we investigated
e ect of steric hindrance. Comparable yields were obtained when
we changed the substituents’ location. For example, the meta-
phenyl-substituted gem-difluorostyrene gave the corresponding
products 2o in 80% yields. However, the ortho-phenyl-substituted
gem-difluorostyrene do not convert well in this transformation and
only led to the formation of compound 2p in 42% yield due to the
bulky group’s effect. In addition, reactions of the substrate bearing
the naphthalene ring worked well under the standard conditions
(2q and 2r, 65% and 75% yields, respectively). Encouraged by
Conclusions
In summary, we have developed a Pd-catalyzed selective
hydroxylfluorination of gem-difluoroalkenes using NFSI as the
fluoride source. The reaction tolerated a range of different
substrates with a variety of functional groups. And the key
intermediate
of
this
strategy
is
probably
the
α-
trifluoromethylbenzyl–Pd complex generated from fluoro-
palladation of gem-difluoroalkenes. Meanwhile, the present
protocol also offered more possibilities for constructing other bond,
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10.1002/ejoc.201800468
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COMMUNICATION
4-(2,2-difluorovinyl)-1,1'-biphenyl (1a)18 White solid (164 mg, 76%). 1H
NMR (300 MHz, CDCl3) δ 7.64 – 7.54 (m, 4H), 7.50 – 7.30 (m, 5H), 5.32
(dd, J = 26.3, 3.8 Hz, 1H).
such as C-C, C-N and C-S bonds, the relative studies are
currently in progress.
4'-(2,2-difluorovinyl)-3-methyl-1,1'-biphenyl (1b) Clear liquid (172 mg,
75%). H NMR (300 MHz, CDCl3) δ 7.56 (d, J = 8.2 Hz, 2H), 7.44 – 7.28
1
Experimental Section
(m, 5H), 7.16 (d, J = 7.3 Hz, 1H), 5.31 (dd, J = 26.3, 3.6 Hz, 1H), 2.42 (s,
3H). 13C NMR (126 MHz, CDCl3) δ 156.3 (dd, J = 298.5, 288.4 Hz), 140.5
(s), 140.0 (s), 138.4 (s), 129.3 (t, J = 6.4 Hz), 128.8 (s), 128.2 (s), 128.0 –
127.8 (m), 127.8 (s), 127.4 (s), 124.1 (s), 82.0 (dd, J = 29.2, 13.6 Hz), 21.6
(s). 19F NMR (471 MHz, CDCl3) δ -81.97 (dd, J = 30.7, 26.5 Hz, 1F), -83.92
(dd, J = 31.0, 3.1 Hz, 1F). HRMS m/z (EI): calcd for [C15H12F2], 230.0907;
found 230.0900.
General Methods.
Unless otherwise noted, all solvents and other reagents are
commercially available and used without further purification. Thin layer
chromatography (TLC) employed glass 0.25 mm silica gel plates. Flash
chromatography columns were packed with 300-400 mesh silica gel in
petroleum ether. Nuclear magnetic resonance spectra (1H, 13C NMR and
19F NMR) were recorded on Varian Mercury- 300/400 and Varian Mercury-
400/500 spectrometers. High-resolution mass spectra (HRMS) were
performed on a Finnigan MAT 95 spectrometer. Melting points were
measured by Büchi 510 melting point apparatus without further corrected.
2-bromo-4'-(2,2-difluorovinyl)-1,1'-biphenyl (1c) Clear liquid (241 mg,
82%). 1H NMR (300 MHz, CDCl3) δ 7.66 (d, J = 7.0 Hz, 1H), 7.45 – 7.26
(m, 6H), 7.26 – 7.09 (m, 1H), 5.32 (dd, J = 26.2, 3.5 Hz, 1H). 13C NMR
(126 MHz, CDCl3) δ 156.5 (dd, J = 298.7, 288.7 Hz), 142.02 (s), 139.8 (s),
133.2 (s), 131.2 (s), 129.8 (s), 128.9 (s), 127.5 (s), 127.2 (dd, J = 6.3, 3.5
Hz), 122.6 (s), 82.0 (dd, J = 29.3, 13.5 Hz). 19F NMR (471 MHz, CDCl3) δ
-81.60 (dd, J = 29.7, 26.7 Hz, 1F), -83.55 (dd, J = 30.1, 3.0 Hz, 1F). HRMS
m/z (EI): calcd for [C14H9BrF2], 293.9856; found 293.9847.
General experimental procedure for the synthesis of gem-
difluoroalkenes16,18,19
A 5 mL, three necked round bottomed flask was equipped with a stir bar.
The vessel was flamed dried and then allowed to cool to room temperature.
Under the inert, nitrogen atmosphere, acetonitrile (2 mL) was added to the
vessel, and the temperature was increased to 70 oC. Then
triphenylphosphine (3 mmol), potassium iodide (2 mmol), and aldehyde (1
mmol) were added and let stir for 30 minutes. Methyl 2,2-difluoro-2-
(fluorosulfonyl)acetate (MDFA) (1.75 mmol) was then added slowly over a
period 10 minutes. The resulting mixture was stirred for three hours, a
nitrogen atmosphere being maintained until the end of the reaction. Then
the reaction was quenched with water and extracted with ethyl acetate.
The ethyl acetate was then removed by rotary evaporation. Product was
isolated from the slurry and separated from residual triphenylphosphine by
extraction 5 times with hexane (5 mL). The combined hexane extracts
were combined and concentrated. Additional impurities were removed via
column chromatography using a mixture of petroleum ether and ethyl
acetate to obtain pure product.
-(2,2-difluorovinyl)-4'-fluoro-1,1'-biphenyl (1d) White solid (204 mg,
87%). M.P. 86-88 °C. 1H NMR (300 MHz, CDCl3) δ 7.62 – 7.32 (m, 6H),
7.12 (t, J = 8.6 Hz, 2H), 5.30 (dd, J = 26.3, 3.6 Hz, 1H). 13C NMR (126
MHz, CDCl3) δ 162.1 (d, J = 246.7 Hz), 155.9 (dd, J = 298.5, 288.7 Hz),
138.4 (s), 136.2 (d, J = 3.1 Hz), 129.0 (t, J = 6.5 Hz), 128.1 (d, J = 8.0 Hz),
127.6 (dd, J = 6.3, 3.5 Hz), 126.8 (s), 115.3 (d, J = 21.5 Hz), 81.4 (dd, J =
29.3, 13.6 Hz). 19F NMR (471 MHz, CDCl3) δ -81.82 (dd, J = 30.1, 26.7 Hz,
1F), -83.70 (dd, J = 30.5, 3.0 Hz, 1F), -115.37 – -115.57 (m, 1F). HRMS
m/z (EI): calcd for [C14H9F3], 234.0656; found 234.0653.
4-chloro-4'-(2,2-difluorovinyl)-1,1'-biphenyl (1e) White solid (132 mg,
53%). M.P. 83-85 °C. 1H NMR (300 MHz, CDCl3) δ 7.52 (dd, J = 8.1, 5.3
Hz, 4H), 7.40 (d, J = 8.4 Hz, 4H), 5.31 (dd, J = 26.2, 3.6 Hz, 1H). 13C NMR
(151 MHz, CDCl3) δ 156.4 (dd, J = 298.7, 288.9 Hz), 138.9 (s), 138.49 (s),
133.50 (s), 129.7 (t, J = 6.5 Hz), 129.0 (s), 128.1 (s), 128.0 (dd, J = 6.3,
3.5 Hz), 127.1 (s), 81.8 (dd, J =29.3, 13.5 Hz). 19F NMR (471 MHz, CDCl3)
δ -81.47 – -81.73 (m, 1F), -83.46 (d, J = 29.8 Hz, 1F). HRMS m/z (EI):
calcd for [C14H9ClF2], 250.0361; found 250.0361.
General experimental procedure for the synthesis of α-
Trifluoromethyl Alcohols
4-(2,2-difluorovinyl)-4'-ethyl-1,1'-biphenyl (1f) White solid (161 mg,
66%). M.P. 113-115 °C.1H NMR (300 MHz, CDCl3) δ 7.62 – 7.47 (m, 4H),
7.39 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 5.31 (dd, J = 26.3, 3.8
Hz, 1H), 2.69 (q, J = 7.6 Hz, 2H), 1.27 (t, J = 7.6 Hz, 3H). 13C NMR (126
MHz, CDCl3) δ 155.9 (dd, J = 298.4, 288.3 Hz), 143.2 (s), 139.4 (s), 137.5
(s), 128.7 (t, J = 6.4 Hz), 128.0 (s), 127.6 (dd, J = 6.3, 3.5 Hz), 126.8 (s),
126.5 (s), 81.5 (dd, J = 29.2, 13.6 Hz), 28.1 (s), 15.2 (s). 19F NMR (471
MHz, CDCl3) δ -82.06 (dd, J = 31.0, 26.4 Hz, 1F), -84.01 (dd, J = 31.2, 3.0
Hz, 1F). HRMS m/z (EI): calcd for [C16H14F2], 244.1064; found 244.1056.
In a dried glass tube, Pd(dba)2 (0.02 mmol, 5 mol%), L1 (0.03 mmol, 7.5
mol%), NFSI (0.8 mmol), gem-difluoroalkene (0.4 mmol) were dissolved in
1,4-dioxane (2.0 mL), and then CF3COOH (2.0 mmol) was added. The
reaction mixture was stirred at 25
for 6 h under an argon atmosphere.
After the reaction completed, 10 drops of saturated aq. NaHCO3 were
added, and the reaction mixture was stirred for another 20 minutes. After
that, the solvent was removed under vacuum, and the residue was purified
by silica gel column chromatography with a gradient eluant of petroleum
ether and ethyl acetate to afford product.
1-(benzyloxy)-4-(2,2-difluorovinyl)benzene (1g) White solid (160 mg,
1
57%). H NMR (300 MHz, CDCl3) δ 7.45 – 7.30 (m, 5H), 7.28 – 7.19 (m,
A gram-scale experimental procedure for the synthesis of 1g.
2H), 6.94 (d, J = 8.6 Hz, 2H), 5.21 (dd, J = 26.3, 3.9 Hz, 1H), 5.06 (s, 2H).
In a dried round bottomed flask glass, Pd(dba)2 (0.25 mmol, 5 mol%),
L1 (0.375 mmol, 7.5 mol%), NFSI (10 mmol, 3.15 g), gem-difluoroalkene
1g (5 mmol, 1.23 g) were dissolved in 1,4-dioxane (25 mL), and then
CF3COOH (1.9 mL) was added. The reaction mixture was stirred at 25
1-(2,2-difluorovinyl)-4-phenoxybenzene (1h) Clear liquid (185 mg, 80%).
1H NMR (300 MHz, CDCl3) δ 7.38 – 7.24 (m, 4H), 7.10 (t, J = 7.4 Hz, 1H),
6.98 (dd, J = 12.4, 8.3 Hz, 4H), 5.23 (dd, J = 26.2, 3.8 Hz, 1H). 13C NMR
(126 MHz, CDCl3) δ 157.0 (s), 156.3 (s), 156.1(dd, J = 297.2, 287.5 Hz),
129.8 (s), 129.0 (dd, J = 6.3, 3.5 Hz), 125.3 (t, J = 6.3 Hz), 123.5 (s), 119.1
(s), 119.0 (s), 81.54 (dd, J = 29.4, 14.0 Hz). 19F NMR (471 MHz, CDCl3) δ
-83.58 (dd, J = 34.1, 26.1 Hz, 1F), -85.25 (dd, J = 34.0, 3.3 Hz, 1F). HRMS
m/z (EI): calcd for [C14H10F2O], 232.0700; found 232.0694.
for 10 h under an argon atmosphere. After the reaction completed,
saturated aq. NaHCO3 (5 mL) were added, and the reaction mixture was
stirred for another 30 minutes. After that, the solvent was removed under
vacuum, and the residue was purified by silica gel column chromatography
with a gradient eluant of petroleum ether and ethyl acetate to afford white
solid 2g (1.12 g, 80%).
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10.1002/ejoc.201800468
European Journal of Organic Chemistry
COMMUNICATION
2-(4-(2,2-difluorovinyl)phenyl)pyridine (1i) Yellow solid (173 mg, 80%).
M.P. 54-56 °C.1H NMR (300 MHz, CDCl3) δ 8.69 (d, J = 4.5 Hz, 1H), 7.97
(d, J = 8.3 Hz, 2H), 7.79 – 7.66 (m, 2H), 7.43 (d, J = 8.2 Hz, 2H), 7.28 –
7.17 (m, 1H), 5.33 (dd, J = 26.3, 3.6 Hz, 1H). 13C NMR (126 MHz, CDCl3)
δ 156.8 (s), 156.5 (dd, J = 299.1, 289.0 Hz), 149.7 (s), 137.2 (s), 136.8 (s),
131.1 (t, J = 6.5 Hz), 128.1 – 127.8 (m), 127.2 (s), 122.20 (s), 120.4 (s),
82.0 (dd, J = 29.3, 13.5 Hz). 19F NMR (471 MHz, CDCl3) δ -81.02 – -81.25
(m, 1F), -83.18 (dd, J = 29.0, 3.1 Hz, 1F). HRMS m/z (EI): calcd for
[C13H9F2N], 217.0703; found 217.0706.
298.4, 288.4 Hz), 141.8 (s), 140.9 (s), 130.9 (t, J = 6.4 Hz), 129.2 (s), 128.8
(s), 127.5 (s), 127.2 (s), 126.7 – 126.3 (m), 126.5 (s), 126.0 (s), 82.2 (dd,
J = 29.1, 13.5 Hz). 19F NMR (471 MHz, CDCl3) δ -81.82 (dd, J = 30.7, 26.4
Hz, 1F), -83.78 (dd, J = 30.8, 3.1 Hz, 1F). HRMS m/z (EI): calcd for
[C14H10F2], 216.0751; found 216.0745.
2-(2,2-difluorovinyl)-1,1'-biphenyl (1p) Clear liquid (86 mg, 40%). 1H
NMR (300 MHz, CDCl3) δ 7.60 (d, J = 7.2 Hz, 1H), 7.46 – 7.25 (m, 8H),
5.21 (dd, J = 26.1, 4.3 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 155.8 (dd, J
= 297.6, 287.1 Hz), 140.8 (d, J = 4.5 Hz), 140.3 (s), 129.7 (s), 129.1 (s),
127.9 (s), 127.7 (d, J = 9.4 Hz), 127.6 – 127.4 (m), 127.2 (s), 126.9 (s),
126.7 (s), 80.2 (dd, J = 30.2, 12.5 Hz). 19F NMR (471 MHz, CDCl3) δ -83.10
(dd, J = 31.7, 3.9 Hz, 1F), -84.91 (dd, J = 31.6, 26.3 Hz, 1F). HRMS m/z
(EI): calcd for [C14H10F2], 216.0751; found 216.0745.
5-(2,2-difluorovinyl)-2-fluoro-1,1'-biphenyl (1j) Clear liquid (140 mg,
1
60%). H NMR (300 MHz, CDCl3) δ 7.57 – 7.49 (m, 2H), 7.49 – 7.31 (m,
4H), 7.32 – 7.21 (m, 1H), 7.11 (t, J = 7.5 Hz, 1H), 5.28 (dd, J = 25.9, 3.7
Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 158.7 (d, J = 249.0 Hz), 156.2 (ddd,
J = 297.5, 288.3, 2.1 Hz), 135.4 (s), 130.2 – 129.9 (m), 129.4 (d, J = 14.2
Hz), 129.0 (d, J = 2.7 Hz), 128.5 (s), 128.1 (td, J = 8.1, 3.4 Hz), 127.9 (s),
126.7 (dd, J = 10.3, 6.2 Hz), 116.5 (d, J = 23.5 Hz), 81.3 (dd, J = 29.8, 13.9
Hz). 19F NMR (471 MHz, CDCl3) δ -82.95 (dd, J = 32.2, 26.0 Hz, 1F), -
84.35 (d, J = 32.4 Hz, 1F), -119.47 (s, 1F). HRMS m/z (EI): calcd for
[C14H9F3], 234.0656; found 234.0650.
2-(2,2-difluorovinyl)naphthalene (1q)18 Clear liquid (126 mg, 66%). 1H
NMR (300 MHz, CDCl3) δ 7.85 – 7.69 (m, 4H), 7.54 – 7.39 (m, 3H), 5.43
(dd, J = 26.3, 3.9 Hz, 1H).
1-(2,2-difluorovinyl)naphthalene (1r) Clear liquid (116 mg, 61%). 1H
NMR (300 MHz, CDCl3) δ 7.98 – 7.88 (m, 1H), 7.84 (dd, J = 6.3, 3.2 Hz,
1H), 7.77 (d, J = 8.2 Hz, 1H), 7.62 – 7.40 (m, 4H), 5.85 (dd, J = 24.4, 3.3
Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 156.3 (dd, J = 300.1, 292.4 Hz),
133.2 (s), 131.0 (d, J = 3.3 Hz), 128.3 (s), 127.6 (s), 126.2 – 126.1 (m),
126.0 (s), 125.6 (s), 125.1 (s), 123.3 (s), 78.3 (dd, J = 29.2, 15.6 Hz). 19F
NMR (471 MHz, CDCl3) δ -83.07 – -83.31 (m, 1F), -85.00 (dd, J = 29.1,
24.7 Hz, 1F). HRMS m/z (EI): calcd for [C12H8F2], 190.0594; found
190.0586.
4-(2,2-difluorovinyl)-2-fluoro-1,1'-biphenyl (1k) Clear liquid (168 mg,
1
72%). H NMR (300 MHz, CDCl3) δ 7.58 – 7.51 (m, 2H), 7.48 – 7.32 (m,
4H), 7.19 – 7.11 (m, 2H), 5.29 (dd, J = 25.8, 3.5 Hz, 1H). 13C NMR (126
MHz, CDCl3) δ 159.8 (d, J = 247.6 Hz), 156.6 (dd, J = 299.2, 289.8 Hz),
135.3 (s), 131.5 (dd, J = 15.1, 7.0 Hz), 130.8 (d, J = 4.1 Hz), 128.9 (d, J =
2.9 Hz), 128.5 (s), 127.8 (s), 127.7 (d, J = 15.6 Hz), 123.7 (dd, J = 9.3, 3.5
Hz), 115.1 (ddd, J = 24.9, 7.0, 3.3 Hz), 81.5 (dd, J = 30.1, 13.4 Hz). 19F
NMR (471 MHz, CDCl3) δ -80.35 (t, J = 26.6 Hz, IF), -82.52 (d, J = 28.1
Hz, 1F), -117.55 – -117.73 (m, 1F). HRMS m/z (EI): calcd for [C14H9F3],
234.0656; found 234.0648.
2-(2,2-difluorovinyl)benzofuran (1s)18 Clear liquid (112 mg, 62%). 1H
NMR (300 MHz, CDCl3) δ 7.53 – 7.39 (m, 2H), 7.22 (pd, J = 7.1, 1.3 Hz,
2H), 6.64 (s, 1H), 5.41 (dd, J = 25.1, 1.9 Hz, 1H).
4-(2,2-difluorovinyl)-2-methyl-1,1'-biphenyl (1l) Clear liquid (142 mg,
1
62%). H NMR (300 MHz, CDCl3) δ 7.45 – 7.37 (m, 2H), 7.37 – 7.28 (m,
2-(2,2-difluorovinyl)benzo[b]thiophene (1t) Yellow solid (102 mg, 52%).
M.P. 75-77 °C. 1H NMR (300 MHz, CDCl3) δ 7.82 – 7.74 (m, 1H), 7.70 (dd,
J = 6.8, 2.1 Hz, 1H), 7.39 – 7.26 (m, 2H), 7.19 (s, 1H), 5.62 (dd, J = 25.6,
2.1 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 156.1 (dd, J = 299.3, 291.0 Hz),
139.1 (s), 131.9 (t, J = 7.1 Hz), 124.1 (s), 124.0 (s), 122.8 (s), 122.2 (dd, J
= 7.1, 4.8 Hz), 121.6 (s), 77.9 (dd, J = 33.3, 16.5 Hz). 19F NMR (471 MHz,
CDCl3) δ -78.70 – -78.99 (m, 1F), -84.74 (d, J = 22.9 Hz, 1F). HRMS m/z
(EI): calcd for [C10H6F2S], 196.0158; found 196.0161.
3H), 7.24 – 7.20 (m, 3H), 5.28 (dd, J = 26.4, 3.9 Hz, 1H), 2.27 (s, 3H). 13
C
NMR (126 MHz, CDCl3) δ 156.3 (dd, J = 294.7, 284.6 Hz), 141.4 (s), 140.8
(s), 135.7 (s), 130.2 (s), 129.6 (dd, J = 5.8, 3.7 Hz), 129.4 – 129.2 (m),
129.1 (s), 128.2 (s), 126.9 (s), 125.0 (dd, J = 6.4, 3.3 Hz), 81.9 (dd, J =
29.0, 13.6 Hz), 20.51 (s). 19F NMR (471 MHz, CDCl3) δ -82.20 (dd, J =
31.5, 26.4 Hz, 1F), -84.13 (dd, J = 31.6, 3.2 Hz, 1F). HRMS m/z (EI): calcd
for [C15H12F2], 230.0907; found 230.0901.
4-(2,2-difluorovinyl)-3-fluoro-1,1'-biphenyl (1m) White solid (117 mg,
50%). M.P. 53-55 °C.1H NMR (300 MHz, CDCl3) δ 7.62 – 7.53 (m, 3H),
7.49 – 7.41 (m, 2H), 7.41 – 7.33 (m, 2H), 7.30 (d, J = 11.5 Hz, 1H), 5.55
(dd, J = 26.2, 3.6 Hz, 1H). 13C NMR (151 MHz, CDCl3) δ 159.7 (dd, J =
247.8, 5.9 Hz), 156.5 (dd, J = 298.1, 289.7 Hz), 141.9 (d, J = 7.9 Hz), 139.3
(d, J = 1.5 Hz), 128.9 (s), 128.7 (d, J = 6.8 Hz), 128.0 (s), 126.8 (s), 122.8
(d, J = 3.0 Hz), 117.0 (dt, J = 13.3, 6.7 Hz), 113.8 (d, J = 22.7 Hz), 74.6
(ddd, J = 32.8, 13.3, 7.0 Hz). 19F NMR (471 MHz, CDCl3) δ -80.78 (td, J =
26.1, 4.2 Hz, 1F), -81.27 – -81.42 (m, 1F), -117.26 (td, J = 11.5, 4.4 Hz,
1F). HRMS m/z (EI): calcd for [C14H9F3], 234.0656; found 234.0651.
3-(2,2-difluorovinyl)benzo[b]thiophene (1u)18 Clear liquid (123 mg,
63%). H NMR (300 MHz, CDCl3) δ 7.89 – 7.82 (m, 1H), 7.73 – 7.65 (m,
1H), 7.49 – 7.32 (m, 3H), 5.58 (dd, J = 25.7, 2.4 Hz, 1H).
1
2-(2,2-difluorovinyl)-5-phenylthiophene (1v) Clear liquid (169 mg, 76%).
1H NMR (300 MHz, CDCl3) δ 7.61 – 7.48 (m, 2H), 7.39 – 7.30 (m, 2H),
7.29 – 7.20 (m, 1H), 7.16 (dd, J = 3.7, 0.9 Hz, 1H), 6.91 (d, J = 3.7 Hz, 1H),
5.49 (dd, J = 25.8, 1.6 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 156.0 (dd, J
= 297.9, 289.8 Hz), 143.8 (dd, J = 6.3, 4.1 Hz), 134.0 (s), 131.7 – 131.1
(m), 129.0 (s), 127.6 (s), 127.2 – 126.7 (m), 125.6 (s), 123.2 (s), 77.9 (dd,
J = 33.4, 17.3 Hz). 19F NMR (471 MHz, CDCl3) δ -80.09 (t, J = 26.3 Hz,
1F), -87.28 (d, J = 26.6 Hz, 1F). HRMS m/z (EI): calcd for [C12H8F2S],
222.0315; found 222.0310.
4-(2,2-difluorovinyl)-3-methyl-1,1'-biphenyl (1n) Clear liquid (158 mg,
1
68%). H NMR (300 MHz, CDCl3) δ 7.58 (dd, J = 8.3, 1.2 Hz, 2H), 7.52 –
7.38 (m, 5H), 7.37 – 7.29 (m, 1H), 5.40 (dd, J = 25.5, 3.9 Hz, 1H), 2.35 (s,
3H). 13C NMR (126 MHz, CDCl3) δ 156.3 (dd, J = 297.2, 288.1 Hz), 140.68
(s), 140.1 (s), 136.2 (d, J = 4.0 Hz), 128.9 (s), 128.8 (s), 128.5 (d, J = 8.8
Hz), 128.2 – 127.7 (m), 127.4 (s), 127.0 (s), 124.9 (s), 79.2 (dd, J = 28.9,
14.6 Hz), 20.2 (s). 19F NMR (471 MHz, CDCl3) δ -83.46 (dd, J = 30.3, 3.4
Hz, 1F), -84.38 (dd, J = 29.8, 26.0 Hz, 1F). HRMS m/z (EI): calcd for
[C15H12F2], 230.0907; found 230.0901.
8-(2,2-difluorovinyl)quinoline (1w)19 Clear liquid (88 mg, 46%). 1H NMR
(300 MHz, CDCl3) δ 8.92 (dd, J = 4.2, 1.8 Hz, 1H), 8.15 (dd, J = 8.3, 1.7
Hz, 1H), 7.93 (d, J = 7.3 Hz, 1H), 7.72 (dd, J = 8.1, 1.1 Hz, 1H), 7.55 (t, J
= 7.8 Hz, 1H), 7.43 (dd, J = 8.3, 4.2 Hz, 1H), 6.75 (dd, J = 27.8, 4.2 Hz,
1H). 1-([1,1'-biphenyl]-4-yl)-2,2,2-trifluoroethan-1-ol (2a) White solid
(90 mg, 89%). M.P. 113-115 °C. 1H NMR (400 MHz, CDCl3) δ 7.67 – 7.52
(m, 6H), 7.45 (t, J = 7.5 Hz, 2H), 7.37 (t, J = 7.3 Hz, 1H), 5.12 – 5.04 (m,
1H), 2.61 (d, J = 4.4 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 142.1 (s),
139.9 (s), 132.5(s), 128.5 (s), 127.5 (s), 127.3 (s), 127.0 (s), 126.8 (s),
123.9 (q, J = 282.8 Hz), 72.2 (q, J = 32.0 Hz). 19F NMR (471 MHz, CDCl3)
3-(2,2-difluorovinyl)-1,1'-biphenyl (1o) Clear liquid (168 mg, 78%). 1H
NMR (300 MHz, CDCl3) δ 7.64 – 7.55 (m, 3H), 7.52 – 7.32 (m, 6H), 5.37
(dd, J = 26.2, 3.8 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 156.5 (dd, J =
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800468
European Journal of Organic Chemistry
COMMUNICATION
δ -78.16 (d, J = 6.5 Hz). HRMS m/z (EI): calcd for [C14H11F3O], 252.0762;
78.45 (d, J = 6.7 Hz). HRMS m/z (EI): calcd for [C14H11F3O2], 268.0711;
found 252.0753.
found 268.0705.
2,2,2-trifluoro-1-(3'-methyl-[1,1'-biphenyl]-4-yl)ethan-1-ol (2b) White
solid (87 mg, 82%). M.P. 57-59 °C.1H NMR (300 MHz, CDCl3) δ 7.59 (d, J
= 8.1 Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 7.40 – 7.27 (m, 3H), 7.17 (d, J =
6.6 Hz, 1H), 5.07 – 4.92 (m, 1H), 2.84 (s, 1H), 2.40 (s, 3H). 13C NMR (126
MHz, CDCl3) δ 142.7 (s), 140.3 (s), 138.5 (s), 132.8 (s), 128.7 (s), 128.5
(s), 128.0 (s), 127.9 (s), 127.4 (s), 125.1 (q, J = 281.0 Hz), 124.3 (s), 72.7
(q, J = 32.0 Hz), 21.5 (s). 19F NMR (471 MHz, CDCl3) δ -78.16 (d, J = 6.5
Hz). HRMS m/z (EI): calcd for [C15H13F3O], 266.0918; found 266.0920.
2,2,2-trifluoro-1-(4-(pyridin-2-yl)phenyl)ethan-1-ol (2i) White solid (54
mg, 53%). M.P. 141-143 °C.1H NMR (300 MHz, DMSO) δ 8.73 – 8.63 (m,
1H), 8.12 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 8.0 Hz, 1H), 7.90 (td, J = 7.7, 1.8
Hz, 1H), 7.61 (d, J = 8.3 Hz, 2H), 7.38 (ddd, J = 7.3, 4.8, 1.1 Hz, 1H), 6.91
(d, J = 5.6 Hz, 1H), 5.32 – 5.15 (m, 1H). 13C NMR (126 MHz, DMSO) δ
156.0 (s), 150.1 (s), 139.6 (s), 137.8 (s), 137 (s), 128.47 (s), 126.81 (s),
125.52 (q, J = 283.5 Hz), 123.22 (s), 120.87 (s), 70.66 (q, J = 30.5 Hz). 19
F
NMR (471 MHz, DMSO) δ -76.63 (d, J = 7.4 Hz). HRMS m/z (EI): calcd for
[C13H10F3NO], 253.0714; found 253.0715.
1-(2'-bromo-[1,1'-biphenyl]-4-yl)-2,2,2-trifluoroethan-1-ol (2c) Clear
liquid (96 mg, 73%). 1H NMR (300 MHz, CDCl3) δ 7.67 (d, J = 8.0 Hz, 1H),
7.54 (d, J = 8.1 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.41 – 7.28 (m, 2H), 7.27
– 7.17 (m, 1H), 5.08 (q, J = 6.4 Hz, 1H), 2.78 (s, 1H). 13C NMR (126 MHz,
CDCl3) δ 142.3 (s), 141.8 (s), 133.3 (s), 133.2 (s), 131.2 (s), 129.7 (s),
129.1 (s), 127.4 (s), 127.1 (s), 124.9 (q, J = 280.0 Hz), 122.5 (s), 72.7 (q,
J = 32.1 Hz). 19F NMR (471 MHz, CDCl3) δ -78.13 (d, J = 6.6 Hz). HRMS
m/z (EI): calcd for [C14H10BrF3O], 329.9867; found 329.9871.
2,2,2-trifluoro-1-(6-fluoro-[1,1'-biphenyl]-3-yl)ethan-1-ol (2j) Clear
liquid (58 mg, 54%). 1H NMR (300 MHz, CDCl3) δ 7.61 – 7.52 (m, 3H),
7.52 – 7.35 (m, 4H), 7.22 (dd, J = 17.4, 8.3 Hz, 1H), 5.06 (dd, J = 12.3, 6.2
Hz, 1H), 2.86 (s, 1H). 13C NMR (126 MHz, CDCl3) δ 160.3 (d, J = 250.4
Hz), 135.1 (s), 130.1 (d, J = 3.2 Hz), 129.5 (d, J = 14.2 Hz), 129.1 (d, J =
2.7 Hz), 128.6 (s), 128.1 (s), 128.0 (s), 124.2 (q, J = 282.1 Hz), 116.5 (d, J
= 23.7 Hz), 72.2 (q, J = 32.2 Hz). 19F NMR (471 MHz, CDCl3) δ -78.47 (d,
J = 6.5 Hz, 3F), -116.64 – -116.77 (m, 1F). HRMS m/z (EI): calcd for
[C14H10F4O], 270.0668; found 270.0668.
2,2,2-trifluoro-1-(4'-fluoro-[1,1'-biphenyl]-4-yl)ethan-1-ol (2d) White
solid (97 mg, 90%). M.P. 94-96 °C.1H NMR (500 MHz, CDCl3) δ 7.59 –
7.51 (m, 6H), 7.17 – 7.10 (m, 2H), 5.07 (q, J = 6.5 Hz, 1H), 2.80 (s, 1H).
13C NMR (126 MHz, CDCl3) δ 162.3 (d, J = 247.0 Hz), 141.1 (s), 136.0 (d,
J = 3.2 Hz), 132.5 (s), 128.3 (d, J = 8.1 Hz), 127.5 (s), 126.8 (s), 123.8 (q,
J = 282.2 Hz), 115.3 (d, J = 21.5 Hz), 72.2 (q, J = 32.1 Hz). 19F NMR (471
MHz, CDCl3) δ -78.28 (d, J = 6.4 Hz, 3F), -114.98 – -115.12 (m, 1F). M.P.
94-96 °C. HRMS m/z (EI): calcd for [C14H10F4O], 270.0668; found
270.0662.
2,2,2-trifluoro-1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethan-1-ol (2k) Clear
liquid (49 mg, 45%). 1H NMR (300 MHz, CDCl3) δ 7.57 – 7.51 (m, 2H),
7.51 – 7.34 (m, 4H), 7.31 (d, J = 9.3 Hz, 2H), 5.10 – 4.98 (m, 1H), 2.86 (d,
J = 4.3 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 159.7 (d, J = 248.9 Hz),
135.1 (s), 135.0 (s), 130.9 (d, J = 3.7 Hz), 130.3 (d, J = 13.6 Hz), 129.0 (d,
J = 2.8 Hz), 128.6 (s), 128.1 (s), 124.1 (q, J = 282.2 Hz), 123.4 (d, J = 2.8
Hz), 115.34 (d, J = 24.9 Hz), 72.05 (q, J = 32.1 Hz). 19F NMR (471 MHz,
CDCl3) δ -78.24 (d, J = 6.4 Hz, 3F), -116.82 – -116.97 (m, 1F). HRMS m/z
(EI): calcd for [C14H10F4O], 270.0668; found 270.0656.
1-(4'-chloro-[1,1'-biphenyl]-4-yl)-2,2,2-trifluoroethan-1-ol (2e) White
solid (88 mg, 77%). M.P. 117-119 °C. 1H NMR (300 MHz, CDCl3) δ 7.63 –
7.47 (m, 6H), 7.41 (d, J = 8.5 Hz, 2H), 5.07 (q, J = 6.4 Hz, 1H), 2.81 (s,
1H). 13C NMR (126 MHz, CDCl3) δ 141.2 (s), 138.8 (s), 133.9 (s), 133.3
(s), 129.1 (s), 128.4 (s), 128.0 (s), 127.2 (s), 124.3 (q, J = 282.1 Hz), 72.6
(q, J = 32.1 Hz). 19F NMR (471 MHz, CDCl3) δ -78.26 (d, J = 6.5 Hz). M.P.
117-119 °C. HRMS m/z (EI): calcd for [C14H10ClF3O], 286.0372; found
286.0368.
2,2,2-trifluoro-1-(2-methyl-[1,1'-biphenyl]-4-yl)ethan-1-ol (2l) Clear
liquid (53 mg, 50%). 1H NMR (300 MHz, CDCl3) δ 7.45 – 7.20 (m, 8H),
5.05 – 4.89 (m, 1H), 2.82 (s, 1H), 2.28 (s, 3H). 13C NMR (126 MHz, CDCl3)
δ 143.3 (s), 141.2 (s), 136.0 (s), 132.9 (s), 130.1 (s), 129.4 (s), 129.1 (s),
128.2 (s), 127.2 (s), 124.9 (s), 124.4 (q, J = 282.1 Hz), 72.8 (q, J = 32.0
Hz), 20.5 (s). 19F NMR (471 MHz, CDCl3) δ -78.06 (d, J = 6.6 Hz). HRMS
m/z (EI): calcd for [C15H13F3O], 266.0918; found 266.0918.
1-(4'-ethyl-[1,1'-biphenyl]-4-yl)-2,2,2-trifluoroethan-1-ol (2f) White solid
(78 mg, 70%). M.P. 111-113 °C. 1H NMR (300 MHz, CDCl3) δ 7.63 (d, J =
8.3 Hz, 2H), 7.57 – 7.48 (m, 4H), 7.30 (d, J = 8.1 Hz, 2H), 5.15 – 4.98 (m,
1H), 2.71 (q, J = 7.6 Hz, 2H), 2.64 (d, J = 4.4 Hz, 2H), 1.29 (t, J = 7.6 Hz,
3H). 13C NMR (126 MHz, CDCl3) δ 143.5 (s), 142.1 (s), 137.3 (s), 132.1
(s), 128.0 (s), 127.4 (s), 126.8 (s), 126.7 (s), 123.9 (q, J = 282.1 Hz), 72.3
(dd, J = 69.7, 26.5 Hz), 28.1 (s), 15.1 (s). 19F NMR (471 MHz, CDCl3) δ -
78.23 (d, J = 6.7 Hz). M.P. 111-113 °C. HRMS m/z (EI): calcd for
[C16H15F3O], 280.1075; found 280.1068.
2,2,2-trifluoro-1-(3-fluoro-[1,1'-biphenyl]-4-yl)ethan-1-ol (2m) White
solid (63 mg, 58%). M.P. 98-100 °C.1H NMR (300 MHz, CDCl3) δ 7.64 (t,
J = 7.7 Hz, 1H), 7.59 – 7.51 (m, 2H), 7.48 – 7.34 (m, 4H), 7.30 (dd, J =
11.4, 1.7 Hz, 1H), 5.42 (q, J = 6.3 Hz, 1H), 3.03 (s, 1H). 13C NMR (126
MHz, CDCl3) δ 160.7 (d, J = 248.4 Hz), 144.7 (d, J = 8.3 Hz), 139.1 (d, J
= 1.4 Hz), 129.0 (s), 128.3 (s), 127.1 (s), 124.2 (q, J = 281.9 Hz), 123.2 (d,
J = 2.9 Hz), 120.1 (d, J = 13.2 Hz), 114.1 (d, J = 22.8 Hz), 66.5 (qd, J =
33.5, 3.5 Hz). 19F NMR (471 MHz, CDCl3) δ -78.47 (t, J = 6.2 Hz, 3F), -
117.82 (dt, J = 18.0, 6.0 Hz, 1F). HRMS m/z (EI): calcd for [C14H10F4O],
270.0668; found 270.0663.
1-(4-(benzyloxy)phenyl)-2,2,2-trifluoroethan-1-ol (2g) White solid (98
mg, 87%). M.P. 108-110 °C.1H NMR (500 MHz, CDCl3) δ 7.46 – 7.36 (m,
6H), 7.33 (dd, J = 8.3, 6.0 Hz, 1H), 7.03 – 6.97 (m, 2H), 5.07 (s, 2H), 4.99
– 4.91 (m, 1H), 2.53 (d, J = 3.1 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ
159.4 (s), 136.3 (s), 128.5 (s), 128.4 (s), 127.8 (s), 127.2 (s), 126.1 (s),
124.3 (d, J = 282.8 Hz), 114.7 (s), 72.2 (q, J = 32.1 Hz),69.8 (s). 19F NMR
(471 MHz, CDCl3) δ -78.50 (d, J = 6.6 Hz). HRMS m/z (EI): calcd for
[C15H13F3O2], 282.0868; found 282.0862.
2,2,2-trifluoro-1-(3-methyl-[1,1'-biphenyl]-4-yl)ethan-1-ol (2n) Clear
liquid (75 mg, 71%). 1H NMR (300 MHz, CDCl3) δ 7.64 (d, J = 8.1 Hz, 1H),
7.60 – 7.50 (m, 2H), 7.50 – 7.27 (m, 5H), 5.41 – 5.21 (m, 1H), 2.73 (s, 1H),
2.41 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 142.2 (s), 140.4 (s), 137.0 (s),
131.5 (s), 129.4 (s), 128.9 (s), 127.7 (s), 127.6 (s), 127.2 (s), 125.2 (s),
124.8 (q, J = 282.5 Hz), 68.9 (q, J = 32.1 Hz), 19.5 (s). 19F NMR (471 MHz,
CDCl3) δ -77.57 (d, J = 5.0 Hz). HRMS m/z (EI): calcd for [C15H13F3O],
266.0918; found 266.0918.
2,2,2-trifluoro-1-(4-phenoxyphenyl)ethan-1-ol (2h) White solid (102 mg,
95%). M.P. 79-81 °C.1H NMR (300 MHz, CDCl3) δ 7.45 – 7.31 (m, 4H),
7.14 (ddd, J = 8.5, 2.2, 1.1 Hz, 1H), 7.06 – 6.97 (m, 4H), 5.03 – 4.92 (m,
1H), 2.73 (d, J = 2.1 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 158.6 (s),
156.5 (s), 129.9 (s), 129.0 (s), 128.4 (s), 124.3 (q, J = 282.1 Hz), 123.9 (s),
119.5 (s), 118.4 (s), 72.4 (q, J = 32.1 Hz). 19F NMR (471 MHz, CDCl3) δ -
1-([1,1'-biphenyl]-3-yl)-2,2,2-trifluoroethan-1-ol (2o) Clear liquid (80 mg,
80%). 1H NMR (300 MHz, CDCl3) δ 7.69 (s, 1H), 7.67 – 7.54 (m, 3H), 7.54
– 7.30 (m, 5H), 5.16 – 4.98 (m, 1H), 2.75 (d, J = 3.0 Hz, 1H). 13C NMR
(126 MHz, CDCl3) δ 141.8 (s), 140.5 (s), 134.5 (s), 129.1 (s), 128.9 (s),
128.4 (s), 127.7 (s), 127.2 (s), 126.3 (s), 124.2 (q, J = 282.5 Hz), 72.9 (q,
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10.1002/ejoc.201800468
European Journal of Organic Chemistry
COMMUNICATION
J = 32.0 Hz). 19F NMR (471 MHz, CDCl3) δ -78.20 (d, J = 6.8 Hz). HRMS
m/z (EI): calcd for [C14H11F3O], 252.0762; found 252.0750.
Acknowledgements
This work was financially supported by the SKLDR/SIMM
(SIMM1601ZZ-03 to C.Y.).
1-([1,1'-biphenyl]-2-yl)-2,2,2-trifluoroethan-1-ol (2p) Clear liquid (42 mg,
1
42%). H NMR (300 MHz, CDCl3) δ 7.79 – 7.70 (m, 1H), 7.50 – 7.34 (m,
5H), 7.34 – 7.25 (m, 3H), 5.19 – 5.06 (m, 1H), 2.61 (d, J = 2.6 Hz, 1H). 13
C
NMR (126 MHz, CDCl3) δ 143.0 (s), 140.0 (s), 131.9 (s), 130.4 (s), 129.3
(s), 129.2 (s), 128.4 (s), 128.1 (s), 127.6 (s), 127.3 (s), 124.6 (q, J = 284.2
Hz), 68.9 (q, J = 31.8 Hz). 19F NMR (471 MHz, CDCl3) δ -76.58 (d, J = 6.7
Hz). HRMS m/z (EI): calcd for [C14H11F3O], 252.0762; found 252.0757.
Keywords: hydroxylfluorination • gem-difluoroalkenes •
fluoropalladation • palladium-catalyzed
[1]
For selected recent articles and reviews, see: a) M. Shimizu, T. Hiyama,
Angew. Chem., Int. Ed. 2005, 44, 214-231. b) M. Schlosser, Angew.
Chem., Int. Ed. 2006, 45, 5432-5446. c) K. Müller, C. Faeh, F. Diederich,
Science 2007, 317, 1881−1886. d) J. Wang, M. Sánchez-Roselló, J. L.
Aceña, C. del Pozo, A. E. Sorochinsky, S. Fustero, V. A. Soloshonok, H.
Liu, Chem. Rev. 2014, 114, 2432-2506. e) Y. Zhou, J. Wang, Z. Gu, S.
Wang, W. Zhu, J. L. Aceña, V. A. Soloshonok, K. Izawa, H. Liu, Chem.
Rev. 2016, 116, 422-518. f) S. Preshlock, M. Tredwell, V. Gouverneur,
Chem. Rev. 2016, 116, 719–766.
2,2,2-trifluoro-1-(naphthalen-2-yl)ethan-1-ol (2q) Clear liquid (59 mg,
65%). 1H NMR (300 MHz, CDCl3) δ 7.99 – 7.77 (m, 4H), 7.53 (dd, J = 11.3,
7.4 Hz, 3H), 5.17 (dt, J = 12.8, 6.5 Hz, 1H), 2.77 (d, J = 4.4 Hz, 1H). 13C
NMR (126 MHz, CDCl3) δ 133.4 (s), 132.5 (s), 130.9 (s), 128.1 (s), 127.8
(s), 127.4 (s), 126.9 (s), 126.5 (s), 126.2 (s), 124.0(d, J = 282.4 Hz), 123.9
(s), 72.6 (q, J = 32.0 Hz). 19F NMR (471 MHz, CDCl3) δ -78.00 (d, J = 6.6
Hz). HRMS m/z (EI): calcd for [C12H9F3O], 226.0605; found 226.0602.
[2]
[3]
a) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev.
2008, 37, 320-330. b) W. K. Hagmann, J. Med. Chem. 2008, 51,
4359−4369. c) N. A. Meanwell, N. J. Med. Chem. 2011, 54, 2529−2591.
For selected recent reviews on trifluoromethylation reactions, see: a) V.
V. Grushin, Acc. Chem. Res. 2010, 43, 160–171. b) O.A. Tomashenko,
V. V. Grushin, Chem. Rev. 2011, 111, 4475-4521. c) X.F. Wu, H.
Neumann, M. Beller, Chem.–Asian J. 2012, 7, 1744-1754. d) A. Studer,
Angew. Chem. Int. Ed. 2012, 51, 8950–8958. e) L. Chu, F. L. Qing, Acc.
Chem. Res. 2014, 47, 1513−1522. f) C. Zhang, Adv. Synth. Catal. 2014,
356, 2895–2906. g) E. Merino, C. Nevado, Chem. Soc. Rev. 2014, 43,
6598-6608. h) P. Gao, X. Song, X. Liu, Y. Liang, Chem. Eur. J. 2015, 21,
7648–7661. i) X. H. Xu, K. Matsuzaki, N. Shibata, Chem. Rev. 2015,
115, 731−764. j) T. Chatterjee, N. Iqbal, Y. You, E. J. Cho, Acc. Chem.
Res. 2016, 49, 2284−2294. k) X. Pan, H. Xia, Wu, Org. Chem. Front.
2016, 3, 1163–1185.
2,2,2-trifluoro-1-(naphthalen-1-yl)ethan-1-ol (2r) Clear liquid (65 mg,
72%). H NMR (300 MHz, CDCl3) δ 8.03 (d, J = 8.2 Hz, 1H), 7.89 (d, J =
1
8.1 Hz, 2H), 7.81 (d, J = 7.2 Hz, 1H), 7.61 – 7.45 (m, 3H), 5.92 – 5.80 (m,
1H), 2.83 (s, 1H). 13C NMR (126 MHz, CDCl3) δ 133.3 (s), 130.7 (s), 129.8
(s), 129.6 (s), 128.6 (s), 126.4 (s), 125.5 (s), 125.4 (s), 124.8 (s), 124.3 (q,
J = 282.7 Hz), 122.4 (s), 68.5 (q, J = 32.3 Hz). 19F NMR (471 MHz, CDCl3)
δ -76.84 (d, J = 6.2 Hz). HRMS m/z (EI): calcd for [C12H9F3O], 226.0605;
found 226.0600.
1-(benzofuran-2-yl)-2,2,2-trifluoroethan-1-ol (2s) Clear liquid (36 mg,
1
42%). H NMR (300 MHz, CDCl3) δ 7.60 (d, J = 7.7 Hz, 1H), 7.51 (d, J =
8.2 Hz, 1H), 7.35 (t, J = 7.7 Hz, 1H), 7.27 (t, J = 7.3 Hz, 1H), 6.90 (s, 1H),
5.19 (q, J = 7.4 Hz, 1H), 3.03 (s, 1H). 13C NMR (126 MHz, CDCl3) δ 154.7
(s), 149.1 (s), 127.1 (s), 125.1 (s), 123.1 (s), 123.1 (q, J = 282.4 Hz), 121.3
(s), 111.3 (s), 106.6 (s), 67.5 (q, J = 34.2 Hz). 19F NMR (471 MHz, CDCl3)
δ -77.54 (d, J = 6.5 Hz). HRMS m/z (EI): calcd for [C10H7F3O2], 216.0398;
found 216.0393.
[4]
For selected recent reviews on difunctionalization of alkenes, see: a) V.
Kotov, C. C. Scarborough, S. S. Stahl, Inorg. Chem. 2007, 46, 1910-1923.
b) K. Muniz, C. H. Hovelmann, J. Streuff, J. Am. Chem. Soc. 2008, 130,
763-773. c) D. M. Schultz, J.P. Wolfe, Synthesis 2012, 44, 351-361. d)
S. R. Chemler, M. T. Bovino, ACS Catal. 2013, 3, 1076-1091. e) K. Koike,
M. Akita, Top Catal. 2014, 57, 967-974. f) H. Egami, M. Sodeoka, Angew.
Chem. Int. Ed. 2014, 53, 8294-8308. g) G. Bernadat, G. Masson, Synlett
2014, 25, 2842-2867. h) E. Merino, C. Nevado, Chem. Soc. Rev. 2014,
43, 6598-6608. i) G. Yin, X. Mu, G. Liu, Acc. Chem. Res. 2016, 49, 2413-
2423. j) J. Zhang, Y. An, J. Wu, Chem. Eur. J. 2017, 23, 9477–9480.
For selected recent articles and reviews, see: a) S. Qiu, T. Xu, J. Zhou,
Y. Guo, G. Liu, J. Am. Chem. Soc. 2010, 132, 2856–2857. b) R. I.
McDonald, G. Liu, S. S. Stahl, Chem. Rev. 2011, 111, 2981–3019. c) F.
Wang, X. Qi, Z. Liang, P. Chen, G. Liu, Angew. Chem. Int. Ed. 2014, 53,
1881–1886. d) J. Cheng, X. Qi, M. Li, P. Chen, G. Liu, J. Am. Chem.
Soc. 2015, 137, 2480−2483. e) Y. Yuan, H. Y. Wang, X. Mu, P. Chen,
PY. L. Guo, G. Liu, J. Am. Chem. Soc. 2015, 137, 2468−2471. f) C. Chen,
P. Chen, G. Liu, J. Am. Chem. Soc. 2015, 137, 15648−15651. g) M. Li,
F. Yu, X. Qi, P. Chen, G. Liu, Angew. Chem. Int. Ed. 2016, 55, 13843–
13848. h) F. Wang, Wang, X. Wan, Wu, P. Chen, G. Liu, J. Am. Chem.
Soc. 2016, 138, 15547−15550.
1-(benzo[b]thiophen-2-yl)-2,2,2-trifluoroethan-1-ol (2t) Yellow solid (42
mg, 46%). M.P. 79-81 °C. 1H NMR (300 MHz, CDCl3) δ 7.90 – 7.73 (m,
2H), 7.47 – 7.32 (m, 3H), 5.42 – 5.29 (m, 1H), 2.90 (d, J = 3.8 Hz, 1H). 13
C
NMR (126 MHz, CDCl3) δ 139.91 (s), 138.89 (s), 136.67 (s), 125.23 (s),
124.70 (s), 124.34 (s), 124.11 (s), 123.69 (q, J = 282.2 Hz), 122.43 (s),
69.90 (q, J = 33.9 Hz). 19F NMR (471 MHz, CDCl3) δ -78.19 (d, J = 6.1 Hz).
M.P. 79-81 °C. HRMS m/z (EI): calcd for [C10H7F3OS], 232.0170; found
232.0159.
[5]
1-(benzo[b]thiophen-3-yl)-2,2,2-trifluoroethan-1-ol (2u) Yellow solid
(35 mg, 38%). M.P. 77-79 °C. 1H NMR (500 MHz, CDCl3) δ 7.89 (t, J = 6.6
Hz, 2H), 7.67 (s, 1H), 7.45 – 7.36 (m, 2H), 5.48 – 5.39 (m, 1H), 2.76 (d, J
= 5.0 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 139.9 (s), 136.7 (s), 128.6 (s),
126.4 (s), 124.5 (s), 124.2 (s), 123.9 (q, J = 282.0 Hz), 122.5 (s), 121.7 (s),
68.0 (q, J = 33.3 Hz). 19F NMR (471 MHz, CDCl3) δ -77.34 (d, J = 6.4 Hz).
M.P. 77-79 °C. HRMS m/z (EI): calcd for [C10H7F3OS], 232.0170; found
232.0169.
[6]
For selected recent articles and reviews, see: a) R. Zhu, S. L. Buchwald,
J. Am. Chem. Soc. 2012, 134, 12462−12465. b) R. Zhu, S. L. Buchwald,
Angew. Chem. Int. Ed. 2013, 52, 12655–12658. c) Y. Yasu, T. Koike, M.
Akita, Org. Lett. 2013, 15, 2136–2139. d) S. H. Oh, Y. R. Malpani, N. Ha,
Y. Jung, S. B. Han, Org. Lett. 2014, 16, 1310−1313. e) H. Egami, M.
Sodeoka, Angew. Chem. Int. Ed. 2014, 53, 8294–8308. f) T. Takashi
Koike, M. Akita, J. Fluorine Chem. 2014, 167, 30–36. g) A. Carboni, G.
Dagousset, E. Magnier, G. Masson, Chem. Commun. 2014, 50,
14197−14200. h) A. Carboni, G. Dagousset, E. Magnier, G. Masson,
Synthesis 2015, 47, 2439–2445. i) B. Yang, X. Xu, F. Qing, Org. Lett.
2015, 17, 1906−1909. j) X. Yang, L. He, G. C. Tsui, Org. Lett. 2017, 19,
2,2,2-trifluoro-1-(5-phenylthiophen-2-yl)ethan-1-ol (2v) Clear liquid (35
mg, 49%).1H NMR (300 MHz, CDCl3) δ 7.63 – 7.56 (m, 2H), 7.43 – 7.27
(m, 3H), 7.22 (d, J = 3.8 Hz, 1H), 7.16 (d, J = 3.7 Hz, 1H), 5.32 – 5.18 (m,
1H), 2.73 (d, J = 4.2 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 145.9 (s),
134.7 (s), 133.3 (s), 128.6 (s), 128.1 (s), 127.7 (s), 125.5 (s), 123.3 (q, J =
282.1 Hz), 122.4 (s), 69.1 (q, J = 33.8 Hz). 19F NMR (471 MHz, CDCl3) δ -
78.54 (d, J = 6.2 Hz). HRMS m/z (EI): calcd for [C12H9F3OS], 258.0326;
found 258.0314.
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COMMUNICATION
2446−2449. k) W. Kong, H. An, Q. Song, Chem. Commun. 2017, 53,
8968−8971.
3164. i) G. K. Surya Prakash, Z. Zhang, F. Wang, S. Munoz, G. A. Olah,
J. Org. Chem. 2013, 78, 3300−3305. j) H. Cheng, Y. Pei, F. Leng, J. Li,
A. Liang, D. Zou, Y. Wu, Y. Wu, Tetrahedron Lett. 2013, 54, 4483–4486.
k) J. J. Song, Z. Tan, J. T. Reeves, F. Gallou, N. K. Yee, C. H.
Senanayake, Org. Lett. 2005, 7, 2193−2196. l) S. F. Zhu, W. Pang, C. H.
Xing, S. Z. Zhu,Chin. J. Chem. 2007, 25, 233−236.
[7]
[8]
[9]
L. Zhu, Y. Li, Y. Zhao, J. Hu, Tetrahedron Lett. 2010, 51, 6150−6152.
P. J. Riss, F. I. Aigbirhio, Chem. Commun. 2011, 47, 11873 11875.
B. Gao, Y. Zhao, C. Ni, J. Hu, Org. Lett. 2014, 16, 102−105.
[10] B. Gao, Y. Zhao, J. Hu, Angew. Chem. Int. Ed. 2015, 54, 638-642.
[11] P. Tian, C. Q. Wang, S. H. Cai, S. Song, L. Ye, C. Feng, T. P. Loh, J.
Am. Chem. Soc. 2016, 138, 15869−15872.
[15] For selected articles on reduction of trifluoromethyl ketones, see: a) Y.
Harauchi, C. Takakura, T. Furumoto, R. C. Yanagita, Y. Kawanami,
Tetrahedron: Asymmetry 2015, 26, 333–337. b) M. Zhao, W. Xie, C. Cui,
Chem. Eur. J. 2014, 20, 9259–9262. c) C. Guyon, E. Metay, N. Duguet,
M. Lemaire, Eur. J. Org. Chem. 2013, 24, 5439–5444. d) C. P. Casey, H.
Guan, J. Am. Chem. Soc. 2007, 129, 5816−5817. e) Q. Xuan, C. Zhao,
Q. Song, Org. Biomol. Chem. 2017, 15, 5140−5144. f) D. Sterk, M.
Stephan, B. Mohar, Org. Lett. 2006, 8, 5935−5938. g) G. Zhang, S. K.
Hanson, Chem. Commun. 2013, 49, 10151−10153. h) F. Jiang, K. Yuan,
M. Achard, C. runeau, Chem. Eur. J. 2013, 19, 10343−10352. i) S.
Kohtani, Y. Kamoi, E. Yoshioka, H. Miyabe, Catal. Sci. Technol. 2014, 4,
1084−1091. j) M. Calvillo-Barahona, C. Cordovilla, M. N. Genov, J. M.
Martínez-Ilarduya, P. Espinet, Dalton Trans. 2013, 42, 14576−14582.
[16] C. S. Thomoson, H. Martinez, W. R. Dolbier, J. Fluorine Chem. 2013,
150, 53- 59.
[12] H. J. Tang, L. Z. Lin, C. Feng, T. P. Loh, Angew.Chem.Int. Ed. 2017, 56,
9872−9876.
[13] a) B. Zhang, X. Zhang, J. Hao, C. Yang, Org. Lett. 2017, 19, 1780−1783.
b) J. Li, X. Zhang, H. Xiang, L. Tong, F. Feng, H. Xie, J. Ding, C. Yang,
J. Org. Chem. 2017, 82, 6795−6800. c) X. Zhang, C. Yang, Adv. Synth.
Catal. 2015, 357, 2721−2727. d) M. Jiang, F. Zhu, H. Xiang, X. Xu, L.
Deng, C. Yang, Org. Biomol. Chem. 2015, 13, 6935−6939. e) H. Xiang,
C. Yang, Org. Lett. 2014, 16, 5686−5689. f) X. Han, Z. Yue, X. Zhang, Q.
He, C. Yang, J. Org. Chem. 2013, 78, 4850−4856.
[14] For selected articles on trifluoromethylation of aldehyde and carbonyl
compounds, see: a) J. Sun, X. Peng, H. Guo, Tetrahedron Lett. 2015, 56,
797–800. b) H. Zhao, B. Qin, X. Liu, X. Feng, Tetrahedron 2007, 63,
6822–6826. c) G. K. Surya Prakash, J. Hu, G. A. Olah, Org. Lett. 2003,
5, 3253−3256. d) Y. Zhao, J. Zhu, C. Ni, J. Hu, Synthesis 2010, 11,
1899–1904. e) N. Miyake, T. Kitazume, J. Fluorine Chem. 2003, 122,
243–246. f) J. Kim, J. M. Shreeve, Org. Biomol. Chem. 2004, 2, 2728-
2734. g) K. Aikawa, W. Toya, Y. Nakamura, K. Mikami, Org. Lett. 2015,
17, 4996−4999. h) Y. Chang, C. Cai, Tetrahedron Lett. 2005, 46, 3161–
[17] H. Peng, Z. Yuan, H. Y. Wang, Y. L. Guo, G. Liu, Chem. Sci. 2013, 4,
3172–3178. [18]
J. Zheng, J. H. Lin, J. Cai, J. C. Xiao, Chem. - Eur.
J. 2013, 19, 15261−15266.
[19] J. Hu, X. Han, Y. Yuan, Z. Shi, Angew. Chem. Int. Ed. 2017, 56, 13342–
13346.
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
COMMUNICATION
Key Topic*
Text for Table of Contents
Author(s), Corresponding Author(s)*
Page No. – Page No.
Title
*one or two words that highlight the emphasis of the paper or the field of the study
Layout 2:
COMMUNICATION
gem-difluoroalkenes *
Bin Zhang,[a,b] Xiaofei Zhang,[a] Jian
Hao,[b] and Chunhao Yang*[a]
Page No. – Page No.
Title Palladium-Catalyzed Direct
Approch to α-Trifluoromethyl
Alcohols by Selective
Hydroxylfluorination of gem-
Difluoroalkenes
A mild and efficient synthesis of α-trifluoromethyl alcohols derivatives was achieved
via Pd-catalyzed selective hydroxylfluorination of gem-difluoroalkenes using NFSI
as the fluoride source.
*gem-difluoroalkenes, fluoropalladation
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