Cu-Mediated Trifluoromethylation of Aromatic α-Diazo Esters with the Yagupolskii–Umemoto Reagent

Article abstract of DOI:10.1002/ejoc.201601196

Reductive trifluoromethylation of aromatic α-diazo esters at room temperature with the Yagupolskii–Umemoto reagent {[Ph₂SCF₃][OTf]; (2a)} in DMF in the presence of excess CuCl gave a variety of α-trifluoromethyl arylacetates in up to

Full text of DOI:10.1002/ejoc.201601196

A Journal of
Accepted Article
Title: Cu-Mediated Trifluoromethylation of Aromatic α-Diazo Esters by Yagupolskii-
Umemoto’s Reagent
Authors: Xiao-Qian Hu; Jia-Bin Han; Cheng-Pan Zhang
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Cu-Mediated Trifluoromethylation of Aromatic α-Diazo Esters by
Yagupolskii-Umemoto’s Reagent
Xiao-Qian Hu, Jia-Bin Han, and Cheng-Pan Zhang*[a]
Abstract: Room temperature reductive trifluoromethylation of
aromatic α-diazo esters by Yagupolskii-Umemoto’s reagent
([Ph2SCF3][OTf]) in DMF in the presence of excess CuCl furnished a
variety of α-trifluoromethyl arylacetates in up to 93% yield. The prior
reaction of [Ph2SCF3][OTf] (2a) with CuCl before addition of α-diazo
esters was imperative for the conversion, which might pre-generate
the key [Cu(I)CF3] intermediate according to the outcomes of the
control experiments. When the long-chain perfluoroalkyl
diphenylsulfonium triflates (2b-e) were employed instead of 2a, the
reaction of aromatic α-diazo ester under the same conditions
followed by treatment with NaHCO3 afforded a series of fluorinated
α,β-unsaturated esters in good yields. This protocol allows for a
facile, convenient, and practical access to α-trifluoromethyl
arylacetates and their analogues, implying that the “+Rfn” reagents
are compatible with α-diazo esters in the presence of an appropriate
reductant.
Shreeve and others, represent an important class of electrophilic
“+CF3” transfer reagents, which were initially applied to
trifluoromethylate multifarious nucleophiles.[3] Later, they were
confirmed to be effective participants in the reductive
trifluoromethylation of alkenes, alkynes, arenes, and other
systems.[4b] Compared to the cyclic Umemoto and Togni’s
reagents, the acyclic Yagupolskii-Umemoto’s reagents were
much less studied even though they have similar oxidative
properties.[4b] Recently, [Ar2SCF3][OTf] were used as powerful
arylation reagents in the Pd-catalyzed Suzuki-Miyaura and
Mizoroki-Heck-type reactions.[5] Despite the advances made,
[Ar2SCF3][OTf] still have a narrow scope of application in organic
synthesis in comparison with other “+CF3” reagents. Further
exploitation of [Ar2SCF3][OTf] is sought-after because these
reagents have advantages such as good stability, non-moisture
sensitivity, nonvolatility, easy preparation, and simple
handling.[3,4b]
Introduction
The last several decades have witnessed the explosive growth
of organofluorides.[1] Fluorine has emerged as one of the most
important elements in a large number of biological molecules
(e.g. pharmaceuticals and agrochemicals) and functional
materials.[1] Although it ranks 13th in abundance among all
elements in the earth's crust, the naturally-occurring fluorine-
containing organic compounds have been very rarely reported.[2]
Since the introduction of fluorine atoms into organic molecules
can impart a great many of unique chemical, physicochemical,
and biological properties, the development of highly effective
fluorination and fluoroalkylation methods to furnish the target
compounds is of great importance.[2] To date, the metal-
mediated direct trifluoromethylation has become one of the most
prevalent approaches to the synthesis of fluorine-containing
molecules,[2-4] which includes the traditionally nucleophilic,
electrophilc, and radical trifluoromethylation,[3] and the
contemporarily oxidative and reductive trifluoromethylation.[4] To
boost different sorts of trifluoromethylation, the development of
new CF3 transfer sources and the exploration of new property of
the known ones are of permanent significance.
On the other hand, α-diazo compounds have been widely
used in the construction of cyclopropanes, heterocycles, olefins,
and other useful molecules over the past few years.[6,7] The
direct functionalization of the non-fluorinated α-diazo compounds
by fluoroalkylation reagents has also achieved great success.[8]
For instance, the Cu-mediated trifluoromethylthiolation of α-
diazo
esters
by
AgSCF3,
the
Cu-mediated
gem-
difluoroolefination of diazo compounds by TMSCF3 or
−
Ph3P+CF2CO2 , the metal-free gem-difluoroolefination of diazo
compounds by TMSCF3 or TMSCF2Br, and the Ag-mediated
trifluoromethoxylation of α-diazo esters by “−OCF3” anion have
synthesized plenty of useful fluorine-containing building blocks.[8]
The CuI-mediated trifluoromethylation of α-diazo esters by
TMSCF3 / CsF was first disclosed by Hu and coworkers.[9a] This
method required the volatile and moisture-sensitive TMSCF3
reagent and a scavenger to “trap” the iodine anion, leading to
the operation less uncomplicated. Very recently, the Rh-
catalyzed geminal oxytrifluoromethylation of α-diazo ketones by
ROH and Togni’s reagent was reported, in late stage of which
proceeded via an electrophilic trifluoromethylation.[9b] Although
the Cu-mediated reductive Sandmeyer reaction of aryldiazonium
The Yagupolskii-Umemoto’s reagents ([Ar2SCF3][X]), first
synthesized by Yagupolskii et al and then modified by Umemoto,
[a]
X.-Q. Hu, J.-B. Han, Prof. Dr. C.-P. Zhang
School of Chemistry, Chemical Engineering and Life Science,
Wuhan University of Technology
205 Luoshi Road, Wuhan, China, 40003
E-mail: cpzhang@whut.edu.cn, zhangchengpan1982@hotmail.com
salts
and
5-(trifluoromethyl)-5H-dibenzo[b,d]thiophen-5-ium
(Umemoto’s reagent) was
trifluoromethanesulfonate
accomplished, the similar transformation of α-diazo esters with
“+CF3” reagents has never been reported.[9c-d] In consideration of
Supporting information for this article is given via a link at the end of
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European Journal of Organic Chemistry
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the easy preparation of [Ph2SCF3][OTf] and the versatility of α-
diazo compounds, we imagined whether the direct
trifluoromethylation of α-diazo esters by [Ph2SCF3][OTf] could
provide a convenient way to yield α-CF3 esters.
Results and Discussion
[+CF3]
source
2a
Yield
(3a, %)[c]
Indeed,
the
reaction
of
ethyl
2-diazo-2-(4-
Entry
[Cu] salts
1a : [+CF3] : [Cu][b]
methoxyphenyl)acetate (1a) with a mixture of trifluoromethyl
diphenylsulfonium triflate (2a) (2 equiv) and Cu powder (4 equiv)
in DMF, which was already reacted at 50 C for 2 h, provided
1[d]
2[e]
Cu powder
Cu / CuCl
1 : 2 : 4
1 : 2 : 4
13
7
o
2a
ethyl 3,3,3-trifluoro-2-(4-methoxyphenyl)propanoate (3a) in 13%
yield (entry 1, Table 1). The use of additive such as CuCl, CuBr,
CuI, CuSCN, or KI (1 equiv) in the reaction of 1a with 2a and Cu
powder gave comparable or lower yields of 3a (entry 2, Table 2
and SI). Encouragingly, if 2a (1.5 equiv) reacted with CuCl (2.25
equiv) for 15 min followed by treatment with 1a at room
temperature for another 5 h, 3a was synthesized in 46% yield
(entry 3, Table 1). Varying the amount of CuCl from 2.25 to 4.5
equiv, 3a was obtained in 66% yield (entry 4, Table 1). Notably,
reaction of 1a with a mixture of 2a (1.8 equiv) and CuCl (5.4
equiv) in DMF at room temperature under a N2 atmosphere
overnight gave 3a in 86% yield (75% isolated yield) (entry 5,
Table 1). Further increment of the molar ratio of CuCl to 2a did
not improve the yield of 3a (entries 6 and 7, Table 1). However,
slightly decreasing the amount of CuCl from 5.4 to 5.0 equiv in
the reaction with 2a (1.8 equiv) caused a lower yield of 3a (entry
8, Table 1). The prior reaction of 2a with CuCl was essential for
the entire conversion since the simultaneous addition of 1a, 2a,
and CuCl in DMF led to 3a in 17% yield (see SI-Table 6),
wherein the homo-coupling of 1a was predominant. If 2a was
treated with CuCl in DMF for 10-15 min before addition of 1a, 3a
was formed in 85-86% yield. Prolonging the reaction time of 2a
and CuCl from 15 to 30 min or longer lowered the yield of 3a.
CuBr was another suitable initiator for the reaction. When 1a
reacted with a mixture of 2a and CuBr in DMF at room
temperature overnight, 3a was constructed in 70% yield (entry 9,
Table 1). Other copper salts such as CuI, CuSCN, Cu(OAc)2,
IPrCuCl, CuOTf, and [(MeCN)4Cu]PF6 were less effective for the
reaction, which provided 3a in much lower yields (entries 10-15,
Table 1). Furthermore, addition of 0.1 mL of H2O (ca. 56 equiv)
to the reaction mixture of 1a, 2a, and CuCl in DMF afforded 3a
in a comparable yield (65% (entry 16) vs 66% (entry 4), Table 1),
suggesting that the moisture didn’t harm the reaction.
Nevertheless, if the reaction was run in air, only 12% of 3a was
obtained (entry 16, Table 1). Other electrophilic “+CF3” sources
such as Umemoto’s reagent (2a’) and Togni’s reagent (2a’’)
were also amenable to the conversion. Reaction of 1a with a
mixture of CuCl (4.5 equiv) and 2a’ or 2a’’ (1.5 equiv) in DMF
provided 3a in 63% or 45% yield, respectively (entries 18 and 19,
Table 1).
3[f]
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
CuCl
CuCl
1 : 1.5 : 2.25
1 : 1.5 : 4.5
1 : 1.8 : 5.4
1 : 1.9 : 5.7
1 : 2.0 : 6.0
1 : 1.8 : 5.0
1 : 1.8 : 5.4
1 : 1.8 : 5.4
1 : 1.8 : 5.4
1 : 1.8 : 5.4
1 : 1.8 : 3.6
46
66
4
5
CuCl
86 (75)
73
6
CuCl
7
CuCl
78
8
CuCl
73
9
CuBr
70
10
11
12
13
CuI
19
CuSCN
Cu(OAc)2
IPrCuCl
13
22
0
14
15
2a
2a
CuOTf
[(MeCN)4Cu]PF6
CuCl
1 : 1.5 : 4.5
1 : 1.5 : 4.5
1 : 1.5 : 4.5
1 : 1.8 : 5.4
1 : 1.5 : 4.5
1 : 1.5 : 4.5
25
23
65
12
63
45
16[g]
17[h]
18
2a
2a
CuCl
2a’
2a’’
CuCl
19
CuCl
[a] Reaction conditions: 2a, 2a’, or 2a’’ / Cu salt / DMF (2 mL) / r.t. / N2 / 10-15
min, then 1a (0.1 mmol) / DMF (1 mL) / r.t. / overnight. [b] Molar ratio. [c]
Yields were determined by HPLC using ethyl 3,3,3-trifluoro-2-(4-
methoxyphenyl)propanoate (3a) as the external standard (tR = 4.251 min, λmax
= 227.5 nm, CH3CN : H2O = 70 : 30 (v / v)). Isolated yield is depicted in the
parentheses. [d] Reaction conditions: 2a / Cu / DMF (2 mL) / 50 oC / N2 / 2 h,
then 1a (0.1 mmol) / DMF (1 mL) / 50 oC / overnight. [e] Reaction conditions:
2a / Cu / CuCl (1 equiv) / DMF (2 mL) / 50 oC / N2 / 2 h, then 1a (0.1 mmol) /
DMF (1 mL) / r.t. / overnight. [f] 5 h. Yield was determined by 19F NMR using
C6H5CF3 as an internal standard. [g] 0.1 mL of water was added with the
addition of 1a. [h] The reaction was run in air.
Next, a combination of α-diazo ester and a mixture of 2a (1.8
equiv) / CuCl (5.4 equiv) in DMF at room temperature overnight
was employed to test the scope of the reaction. To our delight,
various ethyl 2-diazo-2-arylacetates (1b-n) treated with
a
mixture of 2a, CuCl, and DMF under the standard conditions,
which was priorly reacted at room temperature for 10 min, gave
the corresponding ethyl 2-trifluoro-2-arylacetates (3b-n) in good
yields. The steric and electronic nature of the substituents on the
aryl groups had a considerable influence on the reaction. For
instance, treatment of ethyl 2-diazo-2-(p-tolyl)acetate (1c) and
Table 1 Trifluoromethylation of 1a by “+CF3” reagents in DMF in the presence
of Cu salts.[a]
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European Journal of Organic Chemistry
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[a] Reaction conditions: 2a (0.54 mmol) / CuCl (1.62 mmol) / DMF (3 mL) / r.t. /
N2 / 10 min, then 1 (0.30 mmol) / DMF (1.5 mL) / r.t. / overnight. [b] Yields
were determined by 19F NMR using ‒OTf anion as an internal standard.
ethyl 2-diazo-2-(m-tolyl)acetate (1d) with a mixture of 2a and
CuCl in DMF at room temperature under N2 overnight provided
3c in 59% yield and 3d in 69% yield, respectively, while the
reaction of ethyl 2-diazo-2-(o-tolyl)acetate (1e) under the same
conditions afforded 3e in 31% yield. Similarly, ethyl 2-diazo-2-
(naphthalen-2-yl)acetate (1m) reacted with a mixture of 2a, CuCl,
and DMF under the standard conditions to supply 3m in 85%
yield, and the reaction of ethyl 2-diazo-2-(naphthalen-1-
yl)acetate (1n) provided 3n in 45% yield. These results indicated
that the steric hindrance of aryl groups of α-diazo arylacetates
suppressed the reaction. In addition, the electron-donating
groups on the phenyl rings of alkyl 2-diazo-2-arylacetates (e.g.
1j and 1l) benefited the reaction, giving higher yields of the
desired products than the non-substituted congener (e.g. 1s).
However, when the highly electron-deficient ethyl 2-diazo-2-(4-
nitrophenyl)acetate (1o) reacted with a mixture of 2a, CuCl, and
DMF under the standard conditions, no desired product (3o) was
formed. Furthermore, reactions of the electron-rich α-diazo
heteroarylacetates such as ethyl 2-diazo-2-(thiophen-3-
yl)acetate (1p) and ethyl 2-diazo-2-(1-tosyl-indol-3-yl)acetate
(1q) with a mixture of 2a and CuCl in DMF afforded respective
3p in 88% yield and 3q in 93% yield. Besides, other alkyl α-
diazo esters such as methyl (1r), isopropyl (1t), propyl (1u), allyl
(1v), benzyl (1w), 2’,2’-difluoroethyl (1x), and 2’-fluoroethyl (1y)
2-diazo-2-phenylacetates were all successfully transformed,
which produced 3r and 3t-y in 39-70% yields. Unfortunately, the
reaction was less effective to aliphatic α-diazo esters as ethyl 2-
diazodecanoate (1z) and diethyl 2-diazomalonate (1a’) reacted
with 2a / CuCl under the standard conditions to give trace or
none of the desired products, which were determined by 19F
NMR analysis of the reaction mixture.
In addition to 2a, other long-chain perfluoroalkyl
diphenylsulfonium salts were investigated in the reaction (Table
3). It was distinctive that reaction of 1a or 1m with 2b under the
standard conditions gave a mixture of α-pentafluoroethylated
ester and β-F eliminated product, which were determined by
NMR spectroscopy (see SI). To prohibit the β-F elimination,
efforts were made by addition of water, Et3N•3HF, or CsF to the
reaction mixture of 1m and 2b. However, only a few changes in
the product distribution of the reaction were observed (see SI).
The previous report had disclosed that adventitious water in the
reaction of α-diazo ester and “CuCF3” could facilitate the
formation of trifluoromethylated product.[9a] Moreover, by simple
treatment of a reaction mixture of 1a and 2b with NaHCO3 in
DMF at room temperature for 24 h, ethyl 3,4,4,4-tetrafluoro-2-(4-
methoxyphenyl)but-2-enoate (3ab) was obtained in 75% yield.[10]
Similar results were also observed for 2c, 2d, and 2e, which
provided 3ac, 3ad, and 3ae in 78-88% yields. The molar ratio of
Z- and E-isomers of 3ab-ae was determined by 19F NMR
analysis of the isolated products.[11] Interestingly, when the
reaction mixture of 1a and 2a was treated with NaHCO3 in DMF
at room temperature for 24 h, 3a was recovered, suggesting the
ease of formation of β-F eliminated products with long-chain
perfluoroalkyl groups.
Table 3 CuCl-Mediated perfluoroalkylation of 1a by 2b-e in DMF.[a]
Table 2 CuCl-Mediated trifluoromethylation of α-diazo esters by 2a in DMF.[a]
[a] Reaction conditions: 1) 2b-e (0.54 mmol) / CuCl (1.62 mmol) / DMF (3 mL)
/ r.t. / N2 / 10 min, then 1a (0.30 mmol) / DMF (1.5 mL) / r.t. / overnight; 2)
NaHCO3 (0.9 mmol) / r.t. / N2 / 24 h. The molar ratio of Z- and E-isomers was
determined by 19F NMR analysis of the isolated products according to the
literatures.[11] 2b: Rfn = CF2CF3; 2c: Rfn = (CF2)3CF3; 2d: Rfn = (CF2)5CF3; 2e:
Rfn = (CF2)7CF3.
To probe the possible reaction mechanism, the control
experiments were performed (Scheme 1). A mixture of 2a, CuCl,
TEMPO (1.8 or 5.0 equiv), and DMF reacted at room
temperature for 10 min followed by addition of 1a provided 3a in
18% HPLC yield or 14% 19F NMR yield. Meanwhile, the TEMPO-
CF3 adduct was formed and determined by 19F NMR analysis of
the reaction mixture (see SI). Nevertheless, if TEMPO (5.0
equiv) was contemporaneously added with 1a to the reaction
mixture of 2a, CuCl, and DMF, which was already reacted at
room temperature for 10 min, 3a was obtained in 57% 19F NMR
yield. These results suggested that the radical process might be
involved in the reaction, which predominated at the beginning of
the reaction. Moreover, 19F NMR measurement of the reaction
mixture of 2a, CuCl, and DMF indicated that most of 2a was
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European Journal of Organic Chemistry
10.1002/ejoc.201601196
FULL PAPER
consumed in the first 20 min (see SI). Addition of D2O (0.1 mL)
to the reaction mixture of 1a and 2a / CuCl at the beginning of
the reaction or at the stage of adding 1a gave 3a in 74% or 71%
yield (90% deuterated form, Scheme 1), implying that the α-
proton of 3a is originated from the residual moisture in the
solvent.
benzylic position.[13d,13h] These results illustrated the reliability
and practicability of our method in the construction of tertiary
Cbenzylic-CF3 bonds.
Conclusions
In conclusion, we have found that aromatic α-diazo esters could
be trifluoromethylated by Yagupolskii-Umemoto’s reagent (2a) in
the presence of CuCl. The reaction at room temperature
furnished numerous α-trifluoromethyl arylacetates in good yields.
The prior reaction between 2a and CuCl before addition of α-
diazo esters was very necessary for the entire conversion. Using
perfluoroalkyl diphenylsulfonium triflates instead of 2a, the
reaction afforded a mixture of α-perfluoroalkylated and β-
defluorinated products, which was further treated with NaHCO3
to solely provide the β-defluorinated compounds. A plausible
reductive trifluoromethylation mechanism was suggested for the
reaction according to the outcomes of the control experiments
and the previous reports.[4b,12] This protocol is simply operational
without the use of extra iodine anion “scavenger”,9a which,
alternatively, supplies a facile and practical access to α-
trifluoromethyl arylacetates under mild conditions. Most
importantly, the reaction has demonstrated a good compatibility
of “+Rfn” reagents with α-diazo compounds in the presence of a
certain reductant.
Scheme 1 The control experiments of Cu(I)-mediated trifluoromethylation.
Based on the results above and the previous reports,[4b,12]
a
plausible reductive trifluoromethylation mechanism was
suggested for the reaction (Scheme 2). First, 2a is reduced by
CuCl via a single electron transfer (SET), generating I and Cu(II)
salt. Intermediate I is unstable which rapidly decomposes to
•CF3 radical and releases diphenyl sulfide. The •CF3 radical is
very easy to be reduced by a second equivalent of Cu(I) catalyst
‒
to form CF3 anion, which combines with another equivalent of
Cu(I) catalyst to produce [Cu(I)CF3]. Then [Cu(I)CF3] reacts with
α-diazo ester (1) yielding the insertion metal-complex (II), which
is protonated to eventually afford the trifluoromethylated product
(3). In the cases of perfluoroalkyl diphenylsulfonium salts, the β-
F elimination of the insertion metal-complex might compete with
the protonation, leading to a mixture of products. Nevertheless,
the exact details of the reaction mechanism are still unclear.
Experimental Section
Procedure A (typical): In a nitrogen-filled glovebox, an oven-dried tube
(20 mL) were charged with 2a (218 mg, 0.54 mmol), CuCl (160 mg, 1.62
mmol), and DMF (3 mL) with vigorous stirring. After 10 minutes, a
solution of 1 (0.30 mmol) in DMF (1.5 mL) was introduced via syringe.
The mixture was reacted at room temperature overnight and extracted
with dichloromethane (3 × 25 mL). The combined organic layers were
washed with H2O (3 × 50 mL), dried over anhydrous Na2SO4, and
concentrated to dryness under reduced pressure. The residue was
purified by column chromatography on silica gel using petroleum ether /
ethyl acetate = 20 : 1 (v / v) as eluents to give 3 as the desired product.
Ethyl 3,3,3-trifluoro-2-(4-methoxyphenyl)propanoate (3a),[9a] yellow oil, 59
mg, 75% yield. 1H NMR (500 MHz, CDCl3) δ 7.37 (d, J = 8.5 Hz, 2H),
6.92 (d, J = 8.0 Hz, 2H), 4.29-4.17 (m, 3H), 3.81 (s, 3H), 1.26 (t, J = 7.5
Hz, 3H). 19F NMR (471MHz, CDCl3) δ -68.1 (d, J = 8.5 Hz, 3F). 13C NMR
(100 MHz, CDCl3) δ 165.4 (q, J = 2.6 Hz), 159.3, 129.6, 122.8 (q, J =
278.3 Hz), 120.4, 113.3, 60.9, 54.2, 53.8 (q, J = 28.4 Hz), 12.8.
Scheme
2
A
proposed reaction mechanism for Cu(I)-mediated
trifluoromethylation of 1a with 2a
Ethyl 3,3,3-trifluoro-2-(3-methoxyphenyl)propanoate (3b), yellow oil, 50
mg, 64% yield. 1H NMR (500 MHz, CDCl3) δ 7.31 (t, J = 8.5 Hz, 1H),
7.03-7.01 (m, 2H), 6.94 (dm, J = 7.7 Hz, 1H), 4.31-4.17 (m, 3H), 3.82 (s,
3H), 1.26 (t, J = 7.5 Hz, 3H). 19F NMR (471MHz, CDCl3) δ -67.6 (d, J =
8.9 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 166.0 (q, J = 2.6 Hz), 159.9,
130.7, 129.9, 123.7 (q, J = 280.4 Hz), 121.8, 115.2, 114.7, 62.0, 55.5 (q,
J = 29.1 Hz), 55.3, 13.9. IR (KBr): 2984, 2841, 1748, 1603, 1587, 1494,
1467, 1439, 1373, 1349, 1315, 1265, 1152, 1109, 1076, 1026, 973, 945,
879, 840, 783, 718, 695, 602 cm-1. HRMS-EI (m/z) calcd. for C12H13F3O3:
262.0817, found: 262.0807.
Scheme 3 Synthesis of 3a from ethyl 2-bromo-2-(4-methoxyphenyl)acetate (4)
and TMSCF3 or 2a
It should be mentioned that trifluoromethylation of benzyl
halides and their derivatives (ArCH2X) at the benzylic position
has been well documented.[13] However, trifluoromethylation of
the analogues (ArCH(R)X) that possess substituents on the
benzylic carbon is scarcely known.[13] We found that ethyl 2-
bromo-2-(4-methoxyphenyl)acetate (4) reacted with TMSCF3 or
2a by the known procedures failing to give the desired product
(3a) (Scheme 3), although these procedures had successfully
trifluoromethylated the non-substituted benzyl halides at the
Ethyl 3,3,3-trifluoro-2-(p-tolyl)propanoate (3c),[9a] yellow oil, 41 mg, 55%
1
yield. H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 8.0 Hz, 2H), 7.22 (d, J =
8.0 Hz, 2H), 4.33-4.17 (m, 3H), 2.37 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H). 19
F
NMR (376MHz, CDCl3) δ -67.8 (d, J = 8.6 Hz, 3F). 13C NMR (100 MHz,
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European Journal of Organic Chemistry
10.1002/ejoc.201601196
FULL PAPER
CDCl3) δ 166.3 (q, J = 2.6 Hz), 139.2, 129.6, 129.3, 126.5, 123.8 (q, J =
277.5 Hz), 62.0, 55.2 (q, J = 28.5 Hz), 21.1, 13.9.
Ethyl 2-(4-acetamidophenyl)-3,3,3-trifluoropropanoate (3l), white solid, 65
mg, 75% yield, petroleum ether / ethyl acetate = 5 : 1 (v / v) as eluents for
Ethyl 3,3,3-trifluoro-2-(m-tolyl)propanoate (3d),[14a] yellow oil, 51 mg, 69%
yield. 1H NMR (400 MHz, CDCl3) δ 7.38-7.19 (m, 4H), 4.33-4.14 (m, 3H),
2.36 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H). 19F NMR (376MHz, CDCl3) δ -67.6
(d, J = 8.6 Hz, 3F). 13C NMR (100 MHz, CDCl3) δ 166.3 (q, J = 2.6 Hz),
138.7, 130.1, 130.0, 129.3, 128.8, 126.5, 123.8 (q, J = 278.4 Hz), 62.0,
55.5 (q, J = 28.4 Hz), 21.3, 13.9.
column chromatography. M.p.: 128-130oC. H NMR (500 MHz, CDCl3) δ
1
7.61 (s, 1H), 7.53 (d, J = 7.5 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 4.29-4.15
(m, 3H), 2.16 (s, 3H), 1.25 (t, J = 7.5 Hz, 3H). 19F NMR (471MHz, CDCl3)
δ -67.8 (d, J = 8.5 Hz, 3F). 13C NMR (100 MHz, CDCl3) δ 168.8, 166.2 (q,
J = 2.6 Hz), 138.9, 130.1, 124.9, 123.7 (q, J = 278.3 Hz), 120.1, 62.1,
54.9 (q, J = 28.4 Hz), 24.5, 13.9. IR (KBr): 3253, 1736, 1664, 1600, 1558,
1515, 1372, 1347, 1323, 1255, 1220, 1157, 1109, 1028, 844, 825, 763,
737, 530 cm-1. HRMS-EI (m/z) calcd. for C13H14F3NO3: 289.0926, found:
289.0923.
Ethyl 3,3,3-trifluoro-2-(naphthalen-2-yl)propanoate (3m), yellow solid, 72
mg, 85% yield. M.p.: 43-46oC. 1H NMR (500 MHz, CDCl3) δ 7.94 (s, 1H),
7.90-7.89 (m, 3H), 7.57-7.53 (m, 3H), 4.50 (q, J = 8.5 Hz, 1H), 4.34-4.20
(m, 2H), 1.27 (t, J = 7.0 Hz, 3H). 19F NMR (471MHz, CDCl3) δ -67.4 (d, J
= 8.5 Hz, 3F). 13C NMR (100 MHz, CDCl3) δ 166.2 (q, J = 3.4 Hz), 133.4,
133.2, 129.4, 128.8, 128.2, 127.7, 126.9, 126.8, 126.7, 126.3, 123.8 (q, J
= 278.3 Hz), 62.2, 55.6 (q, J = 28.5 Hz), 13.9. IR (KBr): 3476, 3060, 2957,
2926, 2854, 1918, 1748, 1636, 1601, 1511, 1465, 1374, 1347, 1261,
1214, 1159, 1109, 1027, 966, 923, 893, 861, 844, 817, 751, 666, 633,
621, 563 cm-1. HRMS-EI (m/z) calcd. for C15H13F3O2: 282.0868, found:
282.0872.
Ethyl 3,3,3-trifluoro-2-(o-tolyl)propanoate (3e),[9a] yellow oil, 23 mg, 31%
yield. 1H NMR (500 MHz, CDCl3) δ 7.58 (d, J = 7.5 Hz, 1H), 7.34-7.28 (m,
3H), 4.69 (q, J = 8.0 Hz, 1H), 4.33-4.19 (m, 2H), 2.47 (s, 3H), 1.28 (t, J =
7.5 Hz, 3H). 19F NMR (471MHz, CDCl3) δ -67.2 (d, J = 8.5 Hz, 3F). 13C
NMR (100 MHz, CDCl3) δ 166.6 (q, J = 2.6 Hz), 137.4, 130.9, 129.0,
128.4, 128.2, 126.6, 124.1 (q, J = 278.3 Hz), 61.9, 50.6 (q, J = 28.4 Hz),
19.9, 13.9.
Ethyl 2-(4-chlorophenyl)-3,3,3-trifluoropropanoate (3f),[9a] yellow oil, 41
mg, 51% yield. 1H NMR (500 MHz, CDCl3) δ 7.40-7.37 (m, 4H), 4.31-4.18
(m, 3H), 1.26 (t, J = 7.5 Hz, 3H). 19F NMR (471MHz, CDCl3) δ -67.7 (d, J
= 8.5 Hz, 3F). 13C NMR (100 MHz, CDCl3) δ 165.8 (q, J = 2.6 Hz), 135.5,
130.8, 129.2, 127.9, 123.5 (q, J = 278.3 Hz), 62.3, 54.9 (q, J = 29.3 Hz),
13.9.
Ethyl 2-(3-chlorophenyl)-3,3,3-trifluoropropanoate (3g),[9a] yellow oil, 43
1
mg, 54% yield. H NMR (400 MHz, CDCl3) δ 7.47 (s, 1H), 7.40-7.31 (m,
Ethyl 3,3,3-trifluoro-2-(naphthalen-1-yl)propanoate (3n),[9a] yellow oil, 38
mg, 45% yield. 1H NMR (500 MHz, CDCl3) δ 8.07 (d, J = 8.5 Hz, 1H),
7.92 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 7.5 Hz, 1H), 7.63 (t, J = 8.0 Hz, 1H),
7.57-7.51 (m, 2H), 5.27 (q, J = 8.0 Hz, 1H), 4.30-4.19 (m, 2H), 1.22 (t, J =
7.0 Hz, 3H). 19F NMR (376MHz, CDCl3) δ -66.7 (d, J = 8.6 Hz, 3F). 13C
NMR (100 MHz, CDCl3) δ 166.7 (q, J = 2.6 Hz), 134.1, 131.9, 130.0,
129.2, 127.3, 127.2, 126.1, 125.7, 125.3, 124.1 (q, J = 278.4 Hz), 122.5,
62.1, 49.9 (q, J = 28.4 Hz), 13.9.
Ethyl 3,3,3-trifluoro-2-(thiophen-3-yl)propanoate (3p), yellow oil, 62 mg,
88% yield. 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 2.0 Hz, 1H), 7.35
(dd, J = 4.8 Hz, J = 3.2 Hz, 1H), 7.17 (d, J = 4.8 Hz, 1H), 4.47 (q, J = 8.4
Hz, 1H), 4.32-4.18 (m, 2H), 1.28 (t, J = 7.2 Hz, 3H). 19F NMR (471MHz,
CDCl3) δ -68.0 (d, J = 8.5 Hz, 3F). 13C NMR (100 MHz, CDCl3) δ 165.8 (q,
J = 2.6 Hz), 128.8, 127.8, 126.3, 125.9, 123.4 (q, J = 278.4 Hz), 62.2,
51.2 (q, J = 29.3 Hz), 13.9. IR (KBr): 2986, 2924, 1469, 1447, 1397, 1373,
1347, 1264, 1231, 1206, 852, 786, 726, 694, 651, 597 cm-1. HRMS-EI
(m/z) calcd. for C9H9F3O2S: 238.0275, found: 238.0272.
3H), 4.32-4.17 (m, 3H), 1.27 (t, J = 7.2 Hz, 3H). 19F NMR (376MHz,
CDCl3) δ -67.5 (d, J = 8.6 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 165.6 (q,
J = 2.8 Hz), 134.8, 131.2, 130.1, 129.6, 129.5, 127.7, 123.4 (q, J = 280.4
Hz), 62.3, 55.1 (q, J = 29.1 Hz), 13.9.
Ethyl 2-(3-bromophenyl)-3,3,3-trifluoropropanoate (3h), yellow oil, 49 mg,
1
53% yield. H NMR (400 MHz, CDCl3) δ 7.61 (s, 1H), 7.55 (dm, J = 8.0
Hz, 1H), 7.40 (d, J = 7.6 Hz, 1H), 7.27 (t, J = 8.0 Hz, 1H), 4.32-4.17 (m,
3H), 1.27 (t, J = 7.2 Hz, 3H). 19F NMR (376MHz, CDCl3) δ -67.5 (d, J =
8.6 Hz, 3F). 13C NMR (100 MHz, CDCl3) δ 165.6 (q, J = 2.6 Hz), 132.5,
132.5, 131.4, 130.4, 128.1, 123.4 (q, J = 277.5 Hz), 122.8, 62.4, 55.1 (q,
J = 28.4 Hz), 13.9. IR (KBr): 2922, 1749, 1571, 1476, 1432, 1373, 1348,
1217, 1159, 1111, 1078, 1025, 999, 784, 713 cm-1. HRMS-EI (m/z) calcd.
for C11H10BrF3O2: 309.9816, found: 309.9812.
Methyl 2-(4-(tert-butyl)phenyl)-3,3,3-trifluoropropanoate (3i), yellow oil,
50 mg, 61% yield. 1H NMR (500 MHz, CDCl3) δ 7.42 (d, J = 8.0 Hz, 2H),
7.37 (d, J = 8.0 Hz, 2H), 4.32 (q, J = 8.5 Hz, 1H), 3.77 (s, 3H), 1.33 (s,
9H). 19F NMR (471MHz, CDCl3) δ -67.8 (d, J = 8.5 Hz, 3F). 13C NMR
(100 MHz, CDCl3) δ 166.8 (q, J = 2.6 Hz), 152.3, 129.1, 126.2, 126.0,
123.7 (q, J = 277.5 Hz), 55.0 (q, J = 28.5 Hz), 52.8, 34.6, 31.2. IR (KBr):
2962, 1755, 1438, 1362, 1304, 1224, 1203, 1155, 1110, 1012, 826 cm-1.
HRMS-EI (m/z) calcd. for C14H17F3O2: 274.1181, found: 274.1178.
Ethyl 2-(benzo[d][1,3]dioxol-5-yl)-3,3,3-trifluoropropanoate (3j), yellow oil,
Ethyl 3,3,3-trifluoro-2-(1-tosyl-1H-indol-3-yl)propanoate (3q), yellow oil,
119 mg, 93% yield, petroleum ether / ethyl acetate = 10 : 1 (v / v) as
eluents for column chromatography. 1H NMR (500 MHz, CDCl3) δ 8.01 (d,
J = 8.0 Hz, 1H), 7.86 (s, 1H), 7.80 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 8.0 Hz,
1H), 7.38 (t, J = 8.0 Hz, 1H), 7.31 (t, J = 8.0 Hz, 1H), 7.25 (d, J = 8.0 Hz,
2H), 4.60 (q, J = 8.0 Hz, 1H), 4.33-4.22 (m, 2H), 2.36 (s, 3H), 1.28 (t, J =
8.0 Hz, 3H). 19F NMR (471MHz, CDCl3) δ -67.5 (d, J = 8.5 Hz, 3F). 13C
NMR (100 MHz, CDCl3) δ 165.5 (q, J = 2.6 Hz), 145.4, 134.9, 134.7,
130.0, 129.3, 126.9, 126.7, 125.3, 123.7 (q, J = 278.4 Hz), 123.7, 119.4,
113.7, 110.6, 62.4, 47.4 (q, J = 30.1 Hz), 21.6, 13.9. IR (KBr): 3358, 3193,
2955, 2921, 2850, 1747, 1659, 1633, 1469, 1449, 1375, 1284, 1260,
1175, 1113, 1094, 1022, 981, 813, 762, 746, 704, 665, 618, 578 cm-1.
HRMS-EI (m/z) calcd. for C20H18F3NO4S: 425.0909, found: 425.0912.
Methyl 3,3,3-trifluoro-2-phenylpropanoate (3r),[14b] yellow oil, 39 mg, 59%
yield. 1H NMR (400 MHz, CDCl3) δ 7.45 (m, 2H), 7.41 (m, 3H), 4.35 (q, J
= 8.4 Hz, 1H), 3.77 (s, 3H). 19F NMR (376MHz, CDCl3) δ -67.7 (d, J = 8.6
Hz, 3F). 13C NMR (100 MHz, CDCl3) δ 166.6 (q, J = 2.6 Hz), 129.5, 129.4,
129.3, 129.0, 123.7 (q, J = 277.5 Hz), 55.4 (q, J = 28.4 Hz), 52.8.
Ethyl 3,3,3-trifluoro-2-phenylpropanoate (3s),[14c] yellow oil, 38 mg, 54%
yield. 1H NMR (500 MHz, CDCl3) δ 7.46 (m, 2H), 7.41 (m, 3H), 4.35-4.14
(m, 3H), 1.26 (t, J = 7.5 Hz, 3H). 19F NMR (471MHz, CDCl3) δ -67.7 (d, J
= 8.5 Hz, 3F). 13C NMR (100 MHz, CDCl3) δ 166.1 (q, J = 2.8 Hz), 129.5,
129.2, 128.9, 123.7 (q, J = 280.4 Hz), 62.1, 55.6 (q, J = 28.2 Hz), 13.9.
Isopropyl 3,3,3-trifluoro-2-phenylpropanoate (3t), yellow oil, 37 mg, 50%
1
57 mg, 69% yield. H NMR (400 MHz, CDCl3) δ 6.97 (s, 1H), 6.87 (dd, J
= 8.0 Hz, J = 1.2 Hz, 1H), 6.80 (d, J = 8.0 Hz, 1H), 5.98 (s, 2H), 4.30-4.15
(m, 3H), 1.26 (t, J = 7.2 Hz, 3H). 19F NMR (376MHz, CDCl3) δ -68.0 (d, J
= 8.6 Hz, 3F). 13C NMR (100 MHz, CDCl3) δ 166.2 (q, J = 2.5 Hz), 148.4,
148.1, 123.7 (q, J = 277.5 Hz), 123.6, 122.8, 109.5, 108.5, 101.5, 62.1,
55.1 (q, J = 28.4 Hz), 13.9. IR (KBr): 2919, 2852, 2129, 1748, 1633, 1611,
1447, 1396, 1374, 1348, 1244, 1153, 1025, 977, 933, 870, 808, 785, 733,
687, 598 cm-1. HRMS-EI (m/z) calcd. for C12H11F3O4: 276.0609, found:
276.0602.
Ethyl 2-([1,1'-biphenyl]-4-yl)-3,3,3-trifluoropropanoate (3k), white solid, 58
mg, 63% yield. M.p.: 59-61 oC. 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J =
8.0 Hz, 2H), 7.61 (d, J = 7.5 Hz, 2H), 7.54 (d, J = 8.0 Hz, 2H), 7.47 (t, J =
7.5 Hz, 2H), 7.39 (t, J = 7.5 Hz, 1H), 4.41-4.21 (m, 3H), 1.30 (t, J = 7.0
Hz, 3H). 19F NMR (471MHz, CDCl3) δ -67.5 (d, J = 8.5 Hz, 3F). 13C NMR
(100 MHz, CDCl3) δ 166.2 (q, J = 2.6 Hz), 142.2, 140.2, 129.9, 128.9,
128.3, 127.7, 127.6, 127.2, 123.8 (q, J = 278.4 Hz), 62.2, 55.3 (q, J =
28.4 Hz), 13.9. IR (KBr): 1743, 1412, 1375, 1346, 1303, 1252, 1206,
1166, 1104, 1028, 844, 825, 763, 734, 690, 665 cm-1. HRMS-EI (m/z)
calcd. for C17H15F3O2: 308.1024, found: 308.1012.
1
yield. H NMR (400 MHz, CDCl3) δ 7.46 (m, 2H), 7.40 (m, 3H), 5.11 (m,
1H), 4.29 (q, J = 8.4 Hz, 1H), 1.29 (d, J = 6.4 Hz, 3H), 1.19 (d, J = 6.4 Hz,
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European Journal of Organic Chemistry
10.1002/ejoc.201601196
FULL PAPER
3H). 19F NMR (376MHz, CDCl3) δ -67.6 (d, J = 8.6 Hz, 3F). 13C NMR
(100 MHz, CDCl3) δ 165.6 (q, J = 2.6 Hz), 129.6, 129.4, 129.1, 128.8,
123.8 (q, J = 278.3 Hz), 69.9, 55.8 (q, J = 28.4 Hz), 21.5, 21.3.
on silica gel using petroleum ether / ethyl acetate = 20 : 1 (v / v) as
eluents to give 3ab (66 mg, 75% yield), 3ac (92 mg, 78% yield), 3ad (121
mg, 82% yield), or 3ae (156 mg, 88% yield), respectively.
Propyl 3,3,3-trifluoro-2-phenylpropanoate (3u), yellow oil, 37 mg, 50%
yield. 1H NMR (400 MHz, CDCl3) δ 7.45 (m, 2H), 7.40 (m, 3H), 4.33 (q, J
= 8.4 Hz, 1H), 4.20-4.10 (m, 2H), 1.70-1.61 (m, 2H), 0.89 (t, J = 7.2 Hz,
3H). 19F NMR (376MHz, CDCl3) δ -67.6 (d, J = 8.6 Hz, 3F). 13C NMR
(100 MHz, CDCl3) δ 166.2 (q, J = 2.6 Hz), 129.5 (m), 129.5, 129.2, 128.9,
123.7 (q, J = 278.4 Hz), 67.6, 55.6 (q, J = 28.4 Hz), 21.7, 10.1. IR (KBr):
3477, 3071, 3037, 2971, 2930, 2857, 2109, 1748, 1500, 1458, 1393,
1355, 1259, 1217, 1153, 1109, 1056, 1034, 991, 933, 894, 846, 759, 699,
682, 596 cm-1. HRMS-EI (m/z) calcd. for C12H13F3O2: 246.0868, found:
246.0870.
Ethyl 3,4,4,4-tetrafluoro-2-(4-methoxyphenyl)but-2-enoate (3ab),
a
mixture of Z- and E-isomers, molar ratio of Z / E isomers = 1.09 : 1.00 (or
0.52 : 0.48), yellow oil, 66 mg, 75% yield. 1H NMR (400 MHz, CDCl3) δ
7.42 (d, J = 8.8 Hz, 0.82H), 7.25 (d, J = 8.8 Hz, 0.84H), 6.94 (d, J = 9.2
Hz, 0.78H), 6.91 (d, J = 8.8 Hz, 0.94H), 4.36-4.27 (m, 2H), 3.84 (s,
1.14H), 3.83 (s, 1.61H), 1.35-1.29 (m, 3H). 19F NMR (376 MHz, CDCl3) δ
-65.7 (d, J = 8.6 Hz, 1.59F), -68.6 (d, J = 10.5 Hz, 1.47F), -119.7 (q, J =
8.6 Hz, 0.52F), -134.0 (q, J = 10.5 Hz, 0.48F). 13C NMR (126 MHz,
CDCl3) δ 164.3, 163.9, 160.7, 160.5, 130.2, 130.1 (d, J = 5.4 Hz), 120.7,
120.4 (d, J = 4.5 Hz), 114.3, 114.0, 62.6, 62.4, 55.4, 55.3, 14.0, 13.8. IR
(KBr): 3359, 2961, 2924, 2848, 1738, 1609, 1575, 1514, 1466, 1423,
1372, 1340, 1295, 1259, 1232, 1204, 1180, 1150, 1111, 1028, 973, 918,
836, 808, 697, 665, 637, 545 cm-1. HRMS-ESI (m/z) calcd. for
[C13H13F4O3]+ ([M + H]+): 293.0801, found: 293.0795.
Allyl 3,3,3-trifluoro-2-phenylpropanoate (3v), yellow oil, 29 mg, 39% yield.
1H NMR (500 MHz, CDCl3) δ 7.46 (m, 2H), 7.41 (m, 3H), 5.87 (m, 1H),
5.28 (d, J = 17.4 Hz, 1H), 5.24 (d, J = 10.7 Hz, 1H), 4.68 (m, 2H), 4.36 (q,
J = 8.5 Hz, 1H). 19F NMR (471MHz, CDCl3) δ -67.6 (d, J = 8.5 Hz, 3F).
13C NMR (100 MHz, CDCl3) δ 165.8 (q, J = 2.6 Hz), 131.0, 129.5, 129.3,
129.0, 126.4, 123.7 (q, J = 278.3 Hz), 119.1, 66.4, 55.5 (q, J = 28.5 Hz).
IR (KBr): 2956, 2923, 2852, 2110, 1748, 1650, 1633, 1500, 1457, 1424,
1373, 1347, 1216, 1154, 1109, 990, 939, 848, 758, 700, 596 cm-1.
HRMS-EI (m/z) calcd. for C12H11F3O2: 244.0711, found: 244.0706.
Benzyl 3,3,3-trifluoro-2-phenylpropanoate (3w), yellow oil, 62 mg, 70%
Ethyl 3,4,4,5,5,6,6,6-octafluoro-2-(4-methoxyphenyl)hex-2-enoate (3ac),
a mixture of Z- and E-isomers, molar ratio of Z / E isomers = 2.12 : 1.00
1
(or 0.68 : 0.32), yellow oil, 92 mg, 78% yield. H NMR (400 MHz, CDCl3)
δ 7.43 (d, J = 8.8 Hz, 0.57H), 7.24 (d, J = 8.8 Hz, 1.18H), 6.94 (d, J = 8.8
Hz, 0.62H), 6.89 (d, J = 8.8 Hz, 1.20H), 4.34-4.26 (m, 2H), 3.84 (s,
0.91H), 3.82 (s, 1.81H), 1.33-1.29 (m, 3H). 19F NMR (376 MHz, CDCl3) δ
-80.7 (t, J = 8.6 Hz, 2.10F), -80.8 (t, J = 8.6 Hz, 0.97F), -113.3 (m,
1.57F ), -115.9 (m, 0.73F), -117.6 (m, 0.68F), -126.3 (m, 1.41F), -126.5
(d, J = 10.5 Hz, 0.69F), -131.6 (m, 0.32F). 13C NMR (100 MHz, CDCl3) δ
163.0, 162.9, 159.8, 159.4, 129.1 (m), 129.0 (d, J = 5.1 Hz), 124.2 (d, J =
12.9 Hz), 123.2 (d, J = 11.3 Hz), 119.9, 119.0 (d, J = 5.2 Hz), 113.3,
112.7, 61.5, 61.4, 54.3, 54.2, 13.0, 12.7. IR (KBr): 2963, 2938, 2845,
1741, 1610, 1575, 1514, 1466, 1446, 1356, 1232, 1186, 1116, 1028, 964,
837, 800, 748, 711, 603, 570 cm-1. HRMS-ESI (m/z) calcd. for
[C15H13F8O3]+ ([M + H]+): 393.0737, found: 393.0731.
1
yield. H NMR (500 MHz, CDCl3) δ 7.45 (m, 2H), 7.42 (m, 3H), 7.36 (m,
3H), 7.30 (m, 2H), 5.28 (d, J = 12.5 Hz, 1H), 5.20 (d, J = 12.0 Hz, 1H),
4.41 (q, J = 8.5 Hz, 1H). 19F NMR (471MHz, CDCl3) δ -67.5 (d, J = 8.5 Hz,
3F). 13C NMR (100 MHz, CDCl3) δ 166.0 (q, J = 2.5 Hz), 134.9, 129.5,
129.3, 129.2, 129.0, 128.6, 128.6, 128.2, 123.7 (q, J = 278.4 Hz), 67.7,
55.5 (q, J = 28.4 Hz). IR (KBr): 3068, 3036, 2959, 2925, 1748, 1499,
1457, 1382, 1351, 1216, 1153, 1107, 1006, 893, 849, 751, 698, 604 cm-1.
HRMS-EI (m/z) calcd. for C16H13F3O2: 294.0868, found: 294.0877.
2,2-Difluoroethyl 3,3,3-trifluoro-2-phenylpropanoate (3x), yellow oil, 40
1
mg, 50% yield. H NMR (400 MHz, CDCl3) δ 7.46-7.39 (m, 5H), 5.92 (tt,
Ethyl
3,4,4,5,5,6,6,7,7,8,8,8-dodecafluoro-2-(4-methoxyphenyl)oct-2-
2JHF = 54.8 Hz, J = 4.0 Hz, 1H), 4.47-4.27 (m, 3H). 19F NMR (376MHz,
CDCl3) δ -67.8 (d, J = 7.1 Hz, 3F), -125.8 (dq, 2JHF = 53.8 Hz, 3JHF = 12.0
Hz, 2F). 13C NMR (100 MHz, CDCl3) δ 165.4 (q, J = 2.5 Hz), 129.5, 129.4,
129.1, 128.6, 123.4 (q, J = 278.3 Hz), 112.1 (t, J = 240.4 Hz), 63.3 (t, J =
29.3 Hz), 55.2 (q, J = 28.5 Hz). IR (KBr): 3357, 3071, 3039, 2958, 2922,
2851, 1763, 1659, 1632, 1501, 1458, 1422, 1358, 1260, 1217, 1158,
1108, 1030, 969, 934, 896, 850, 760, 701, 596, 578 cm-1. HRMS-EI (m/z)
calcd. for C11H9F5O2: 268.0523, found: 268.0522.
enoate (3ad), a mixture of Z- and E-isomers, molar ratio of Z / E isomers
= 2.23 : 1.00 (or 0.69 : 0.31), yellow oil, 121 mg, 82% yield. 1H NMR (400
MHz, CDCl3) δ 7.44 (d, J = 8.8 Hz, 0.57H), 7.24 (d, J = 8.8 Hz, 1.22H),
6.94 (d, J = 9.2 Hz, 0.60H), 6.90 (d, J = 8.8 Hz, 1.23H), 4.34-4.26 (m, 2H),
3.84 (s, 0.87H), 3.82 (s, 1.88H), 1.33-1.29 (m, 3H). 19F NMR (376 MHz,
CDCl3) δ -80.8 (m, 3F), -112.4 (m, 1.58F), -114.9 (m, 0.70F), -117.5 (m,
0.69F), -122.1 (m, 2F), -122.9 (m, 2F), -126.1 (m, 2F), -131.4 (m, 0.31F).
13C NMR (126 MHz, CDCl3) δ 164.0, 163.9, 160.9, 160.4, 146.6 (t, J =
27.3 Hz), 144.5 (t, J = 28.2 Hz), 130.1, 130.0 (d, J = 5.4 Hz), 125.3 (d, J
= 13.6 Hz), 124.2 (d, J = 9.1 Hz), 120.9, 120.0 (d, J = 4.5 Hz), 114.3,
113.8, 62.5, 62.4, 55.3, 55.2, 14.0, 13.7. IR (KBr): 2964, 2940, 2844,
1739, 1610, 1513, 1467, 1446, 1363, 1331, 1237, 1205, 1143, 1030, 970,
890, 876, 860, 838, 812, 799, 728, 645, 586 cm-1. HRMS-ESI (m/z) calcd.
for [C17H13F12O3]+ ([M + H]+): 493.0673, found: 493.0667.
2-Fluoroethyl 3,3,3-trifluoro-2-phenylpropanoate (3y), yellow oil, 38 mg,
51% yield. 1H NMR (400 MHz, CDCl3) δ 7.46 (m, 2H), 7.41 (m, 3H), 4.64
(m, 1H), 4.53-4.30 (m, 4H). 19F NMR (471MHz, CDCl3) δ -67.7 (d, J = 8.5
2
3
Hz, 3F), -225.0 (tt, JHF = 45.7 Hz, JHF = 28.7 Hz, 1F). 13C NMR (100
MHz, CDCl3) δ 166.0 (q, J = 2.5 Hz), 129.5, 129.4, 129.0, 123.6 (q, J =
278.3 Hz), 80.7 (d, J = 169.8 Hz), 64.6 (d, J = 19.8 Hz), 55.3 (q, J = 29.3
Hz). IR (KBr): 3358, 3195, 3071, 3038, 2958, 2921, 2851, 1755, 1659,
1632, 1606, 1588, 1500, 1458, 1409, 1378, 1351, 1258, 1218, 1155,
1111, 1068, 1040, 1006, 981, 923, 900, 880, 833, 760, 701, 683, 596 cm-
1. HRMS-EI (m/z) calcd. for C11H10F4O2: 250.0617, found: 250.0625.
Ethyl3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-hexadecafluoro-2-(4-
methoxyphenyl)dec-2-enoate (3ae), a mixture of Z- and E-isomers, molar
ratio of Z / E isomers = 2.33 : 1.00 (or 0.70 : 0.30), yellow oil, 156 mg,
88% yield. 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 8.8 Hz, 0.57H), 7.24
(d, J = 8.4 Hz, 1.24H), 6.95 (d, J = 8.8 Hz, 0.59H), 6.90 (d, J = 8.4 Hz,
1.24H), 4.34-4.26 (m, 2H), 3.84 (s, 0.87H), 3.82 (s, 1.88H), 1.33-1.29 (m,
3H). 19F NMR (376 MHz, CDCl3) δ -80.8 (m, 3F), -112.3 (m, 1.56F), -
114.9 (m, 0.68F), -117.5 (m, 0.70F), -121.9 (m, 6F), -122.7 (m, 2F), -
126.1 (m, 2F), -131.4 (m, 0.30F). 13C NMR (100 MHz, CDCl3) δ 163.0,
162.9, 159.9, 159.4, 146.0 (t, J = 27.5 Hz), 143.3 (t, J = 28.4 Hz), 129.1
(d, J = 1.7 Hz), 129.0 (d, J = 6.0 Hz), 124.3 (d, J = 13.8 Hz), 119.9, 119.1
(d, J = 4.3 Hz), 113.3, 112.8, 61.5, 61.5, 54.3, 54.2, 13.0, 12.7. IR (KBr):
2963, 2940, 2844, 1740, 1610, 1575, 1514, 1466, 1446, 1368, 1291,
1238, 1212, 1148, 1035, 971, 862, 836, 801, 737, 708, 661, 532 cm-1.
HRMS-ESI (m/z) calcd. for [C19H13F16O3]+ ([M + H]+): 593.0609, found:
593.0603.
Procedure B: In a nitrogen-filled glovebox, an oven-dried tube (20 mL)
were charged with 2b (245 mg, 0.54 mmol), 2c (299 mg, 0.54 mmol), 2d
(353 mg, 0.54 mmol), or 2e (407 mg, 0.54 mmol), CuCl (160 mg, 1.62
mmol), and DMF (3 mL) with vigorous stirring. After 10 minutes, a
solution of 1a (66 mg, 0.30 mmol) in DMF (1.5 mL) was introduced via
syringe. The mixture was reacted at room temperature under a N2
atmosphere overnight. NaHCO3 (76 mg, 0.90 mmol) was added and the
resulting mixture was kept reacting at room temperature under N2 for
another 24 h. The mixture was extracted with dichloromethane (3 × 25
mL). The combined organic layers were washed with H2O (3 × 50 mL),
dried over anhydrous Na2SO4, and concentrated to dryness under
reduced pressure. The residue was purified by column chromatography
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European Journal of Organic Chemistry
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Tetrahedron 2004, 60, 4755-4763; f) D. V. Vorobyeva, A. K. Mailyan, A.
S. Peregudov, N. M. Karimova, T. P. Vasilyeva, I. S. Bushmarinov, C.
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3532.
Acknowledgements
We thank Wuhan University of Technology, the Natural Science
Foundation of Hubei Province (China) (2015CFB176), the
“Chutian Scholar” Program from Department of Education of
Hubei Province (China), the “Hundred Talent” Program of Hubei
Province, and the Wuhan Youth Chen-Guang Project for
financial support.
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Keywords: fluorine • copper • reduction • diazo compounds •
reaction mechanisms
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Entry for the Table of Contents (Please choose one layout)
Trifluoromethylation
FULL PAPER
Xiao-Qian Hu, Jia-Bin Han, and Cheng-
Pan Zhang*
Page No. – Page No.
Cu-Mediated Trifluoromethylation of
Aromatic α-Diazo Esters by
Yagupolskii-Umemoto’s Reagent
The first room temperature reductive trifluoromethylation of aromatic α-diazo esters
by Yagupolskii-Umemoto’s reagent ([Ph2SCF3][OTf]) in the presence of excess
CuCl furnished a variety of α-trifluoromethyl arylacetates in up to 93% yield. When
the long-chain perfluoroalkyl diphenylsulfonium triflates were employed instead of
2a, the reaction of α-diazo ester under the same conditions followed by treatment
with NaHCO3 afforded a series of fluorinated α,β-unsaturated esters in good yields.
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