Organocatalytic reactions of α-trifluoromethylated esters with terminal alkenes at room temperature

Article abstract of DOI:10.1021/jo402212j

CF₃-containing esters smoothly reacted with electron-deficient alkenes in the presence of a phosphine (2-dicyclohexylphosphino-2′, 4′,6′-triisopropylbiphenyl) organocatalyst at room temperature in an aerobic atmosphere. These Michael reactions efficiently provided products with a CF₃ quaternary carbon center.

Full text of DOI:10.1021/jo402212j

Article
pubs.acs.org/joc
Organocatalytic Reactions of α‑Trifluoromethylated Esters with
Terminal Alkenes at Room Temperature
Qi Wang,†,‡ Feng Huan,† Haiming Shen,† Ji-Chang Xiao,† Min Gao,† Xianjin Yang,*,†
Shun-Ichi Murahashi,*,§ Qing-Yun Chen,*,† and Yong Guo*,†
†Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling
Road, Shanghai 200032, P. R. China
‡Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130
Meilong Road, Shanghai 200237, P. R. China
§Department of Chemistry, Okayama University of Science, 1-1, Ridai-cho, Okayama 700-0005, Japan
S
* Supporting Information
ABSTRACT: CF3-containing esters smoothly reacted with
electron-deficient alkenes in the presence of a phosphine (2-
dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl) organocata-
lyst at room temperature in an aerobic atmosphere. These
Michael reactions efficiently provided products with a CF3
quaternary carbon center.
The substrate was extended to the reaction of acrylonitrile and
2m using an iridium catalyst.6g The scope of the alkylation of
1b is extremely narrow, probably because of the lack of suitable
conditions.
INTRODUCTION
■
Quaternary carbon centers are frequently found as an
important structural motif in various naturally occurring,
biologically active compounds, so synthetic studies of such
units have been extensively performed in recent years.1
Fluorinated compounds have also attracted great interest
because fluorine often endows organic molecules with many
important properties such as high lipophilicity, bioavailability,
and metabolic stability.2,3 However, very few methods for the
construction of trifluoromethylated all-carbon quaternary
centers have been reported,3−6 possibly because β-defluorina-
tion occurs, forming an alkene, when an anion is generated α to
a CF3 group. Until now, there have been a few examples of
reactions that successfully prevent the defluorination of α-CF3
carbanions and their equivalent building blocks,7 including
reactions with aldehydes at low temperature,8 enol-mediated
reactions,9 palladium-catalyzed allylic alkylation,6c−f,10 and
iridium/ruthenium-catalyzed Michael addition.6g Despite
these efforts, versatile reactions that require mild conditions
are still much needed.
Organic synthesis using metal-free low-molecular-weight
organic molecules as catalysts, which is now commonly
known as organocatalysis, has developed rapidly in the past
decade.11 Organocatalysts are readily accessible, insensitive to
oxygen and moisture, and nontoxic, so they have become
important complements to metal catalysts. In 2009, we
reported that trifluoromethylated compounds reacted with
alkenes under catalysis by iridium or ruthenium complexes,
giving adducts in good to excellent yields.6g Interestingly, when
we conducted some control experiments to exclude some
reaction pathways, we found that i-Pr3P also promoted the
reaction, although much less efficiently. This observation
encouraged us to optimize the conditions by using organo-
catalysis for the same transformation (Scheme 1).12
It is assumed that the addition reaction proceeds through
nucleophilic addition to the alkene of a CF3-containing
Unlike the case of nonfluorinated nucleophiles such as
dimethyl malonate, alkylation at the methide position of the
trifluoromethylated malonate 1b is hard because β-elimination
of fluoride occurs when a carbanion is formed. Ishikawa and
Yokozawa reported the successful methylation of 1b using MeI
in the presence of a large excess of CsF. However, higher
temperatures were required for the slightly less reactive benzyl
and allyl bromides.6a Fuchigami and Nakagawa improved the
procedure by using electrogenerated bases with a quaternary
ammonium cation and extended the reaction to CH3I, n-BuI,
PhCH2Br, p-NO2C6H4CH2Br, p-NO2C6H4CH2Cl, and CH2
CHCH2Br.6b A high-temperature pyridine-promoted Michael
reaction of 1b with methyl vinyl ketone (2m) was reported.6a
Scheme 1. Design of Organocatalyzed Michael Reactions of
CF3-Containing Esters
Received: October 4, 2013
© XXXX American Chemical Society
A
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carbanion; β-fluoride elimination from the carbanion is a
competing side reaction, and this seems to be hard to
avoid.6a,b,7 However, theoretically, the generation of a β-
fluorinated carbanion is faster than its defluorination.13 We
therefore wondered if it is possible to optimize the reaction
conditions to prohibit the β-fluoride elimination pathway. In
this article, we report the results of our work on phosphine-
catalyzed Michael reactions of CF3-containing esters. To the
best of our knowledge, this is the first example of a room-
temperature Michael reaction with α-trifluoromethylated
nucleophiles, catalyzed by neutral organocatalysts.14
bases such as triethylamine, 1,8-diazabicyclo[5,4,0]undec-7-ene
(DBU), and tert-butoxide, which promoted the reactions but
gave much lower conversions and/or much lower yields (Table
1, entries 5−8). The low yields may be the result of ready β-
defluorination of substrate 1a under the effects of these bases.
Reactions in polar solvents such as DMF, acetonitrile,
dichloromethane, and methanol gave higher yields than those
in less polar solvents such as THF and toluene (Table 1, entries
9−13). Reaction in an aerobic atmosphere was as effective as
that under N2, and anhydrous DMF was not necessary (Table
1, entry 1). These results mean that the reaction is easy to
handle.
RESULTS AND DISCUSSION
With the optimal conditions in hand, the alkene reactant
scope was tested (Table 2). The reactions of various aryl vinyl
■
We began by screening the reaction conditions of 1a with
phenyl vinyl ketone (2a) at room temperature (Table 1). After
Table 2. Michael Addition of Vinyl Ketones and Esters with
1
Table 1. Screening of Reaction Conditions
a
b
entry
1
R1
R2
Ph (2a)
3
yield (%)
CF3 (1a)
3a
3b
3c
3d
3e
3f
94
75
76
68
72
88
82
90
60
96
72
77
91
88
90
47
89
53
51
93
73
68
76
83
c
2
CF3 (1a)
4-ClC6H4 (2b)
4-BrC6H4 (2c)
4-NO2C6H4 (2d)
4-CF3C6H4 (2e)
4-MeC6H4 (2f)
4-MeOC6H4 (2g)
3-MeOC6H4 (2h)
3-NO2C6H4 (2i)
2-naphthyl (2j)
2-thienyl (2k)
2-furyl (2l)
3
CF3 (1a)
4
CF3 (1a)
5
CF3 (1a)
6
CF3 (1a)
7
CF3 (1a)
3g
3h
3i
8
CF3 (1a)
9
CF3 (1a)
a
b
b
entry
catalyst
mol %
solvent
conv (%)
yield (%)
10
11
12
CF3 (1a)
3j
c
1
XPhos
Me3P
10
10
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
toluene
CH2Cl2
THF
100
53
98 (94)
30
CF3 (1a)
3k
3l
2
CF3 (1a)
c
3
nBu3P
PPh3
10
100
100
54
76
13
CO2Me (1b)
CO2Me (1b)
CO2Me (1b)
CO2Me (1b)
CO2Me (1b)
CO2Me (1b)
CO2Me (1b)
CF3 (1a)
2-naphthyl (2j)
3-NO2C6H4 (2i)
4-ClC6H4 (2b)
4-MeOC6H4 (2g)
Me (2m)
3m
3n
3o
3p
3q
3r
c
4
10
83
14
d
c
5
MeONa
Et3N
100
100
100
10
1
15
c
6
89
45
15
52
65
88
63
82
85
16
c
c
c
,
,
,
d
7
DBU
100
70
17
18
19
20
21
22
23
24
e
e
8
tBuOK
XPhos
XPhos
XPhos
XPhos
XPhos
Et (2n)
9
10
100
100
100
100
100
n-pent (2o)
3s
d
e
10
11
12
13
10
Me (2m)
3t
10
CF3 (1a)
Et (2n)
3u
3v
3w
3x
e
10
MeCN
MeOH
CF3 (1a)
n-pent (2o)
d
d
10
CO2Me (1b)
CF3 (1a)
PhO (2p)
a
PhO (2p)
The reactions were carried out with 1a (0.2 mmol) and phenyl vinyl
a
ketone 2a (0.6 mmol, 3 eqiv) in the presence of a catalyst in 0.4 mL of
The reactions were carried out with 1a (0.2 mmol) and phenyl vinyl
ketone 2a (0.6 mmol) in the presence of 10 mol % XPhos in DMF
solvent at room temperature under a nitrogen atmosphere.
b
Conversions and yields were determined by 19F NMR spectroscopy
b
c
d
(0.4 mL) at room temperature. Isolated yields. 4 equiv of alkene. 10
e
using 4-(trifluoromethyl)anisole as an internal standard. Yield of
mol % (4-MeOC6H4)3P instead of XPhos. 20 mol % (4-
c
isolated product is shown in parentheses. Under an aerobic
MeOC6H4)3P instead of XPhos.
d
atmosphere. Another unidentified fluorinated product was observed.
ketones generated the corresponding products in moderate to
excellent yields (Table 2, entries 1−16). Electron-donating and
electron-withdrawing groups (Cl, Br, NO2, CF3, Me, or MeO)
at the para or meta positions of the aryl ring of 2 were tolerated
(Table 2, entries 2−9, 14−16). When 1a (R1 = CF3) was used,
electron-rich aryl vinyl ketones were more reactive as Michael
acceptors and gave higher yields than those obtained with
electron-deficient aryl vinyl ketones (Table 2, entries 7, 8 vs 4,
5, and 9). However, when 1b (R1 = CO2Me) was used, the
reactivity was reversed, and the electron-deficient aryl vinyl
extensive screening of organic bases and solvents, we found that
2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPhos)
promoted the reaction with extremely high efficiency, with
100% conversion of starting fluorinated material and 98% yield
based on 19F NMR spectroscopic monitoring (Table 1, entry
1). Other phosphines such as trimethylphosphine, tri-n-
butylphosphine, and triphenylphosphine were less effective
(Table 1, entries 2−4). The weak nucleophilicity of XPhos may
prevent telomerization of the alkene. We also tested some other
B
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Scheme 2. Proposed Mechanism
ketone gave higher yields (Table 2, entries 14, 15 vs 16). This
means that a slight change in structure may affect the results
significantly. Functional groups (naphthyl, thienyl, and furyl)
were compatible (Table 2, entries 10−13) with the reaction.
Alkyl vinyl ketones were also examined. For these substrates,
we found that (4-MeOC6H4)3P was a better catalyst than
XPhos. The yields of the reactions of substrates with long alkyl
chains were slightly lower (Table 2, entries 17−22). When n-
pentyl vinyl ketone was used, the yields decreased to 51% and
68% (Table 2, entries 19 and 22).
Although phosphine catalysis of Michael additions is known
for nonfluorinated nucleophiles,15 reactions using fluorinated,
particularly α-trifluoromethylated, nucleophiles have not been
researched and discussed. One solution, which increases the
lifetime of the fluorinated anion and simultaneously reduces
defluorination, is to install electron-withdrawing group(s) to
stabilize the anion; another solution is to use bulky counter
cations.7a,16 The metallic counter cations (M+) of the normal
bases used to generate the carbanions of 1a/1b assist
defluorination. In contrast, bulky cations impede elimination
of fluoride. The phosphine-catalyzed Michael reactions of
stabilized nucleophiles have been researched extensively. Initial
conjugate addition by a phosphine to an activated alkene results
in the formation of a phosphonium carbanion. Proton transfer
gives an intermediate carbanion A, which reacts with another
molecule of alkene to afford the product (Scheme 2).15 In our
study, we rationalize that the fluorinated nucleophilic anion is
paired with a bulky quaternary phosphonium cation. Moreover,
three electron-withdrawing groups increase the stability of the
anions of 1a/1b. As a result of a combination of these two
factors, defluorination is suppressed, and the adduct is obtained
smoothly.
Quaternary carbon centers exist in many pharmaceutical
molecules, for example, gemfibrozil.17 An acid 4 was obtained
after hydrolysis of 3a, and the -C(CF3)2COOH motif of 4 is a
fluorinated -C(CH3)2COOH unit present in gemfibrozil
(Scheme 3). The pKa of 4 was 4.00 in ethanol/H2O (3:1 by
volume). This acidity is higher than those of most of carboxylic
acids because of the electron-withdrawing effect of the two
trifluoromethyl groups.18 The property brought by fluorine
atoms2 is potential for drug design, and further research of
biological activity will be done in due course.
The reactions of α,β-unsaturated ester 2p proceeded under
the optimized conditions to give the adducts in good yields
(Table 2, entries 23 and 24).
However, the alkene substrate scope is not wide and is
limited to terminal alkenes such as aryl vinyl ketones, alkyl vinyl
ketones, and a phenyl acrylate. Poor yields were obtained when
methyl acrylate, acrylonitrile, and acrolein were used, probably
due to polymerization side reaction. The reactivity of the
Michael acceptor is crucial in this reaction. Also, the acidity of
the trifluoromethylated nucleophile is important. The reaction
did not occur when CF3CH2CO2Me, which has low acidity, was
used. Overall, this reaction requires a weak phosphine, an
extremely active alkene, and a highly acidic nucleophile.
In the reaction catalyzed by an iridium/ruthenium complex,
the reaction of 1a/1b with acrylonitrile occurred at room
temperature because the cyano group ligand promotes C−H
activation. However, the reaction with methyl vinyl ketone
required a high temperature.6g In contrast, the phosphine-
promoted Michael reaction of 1a/1b was successful with many
α,β-unsaturated carbonyl compounds at room temperature. In
this sense, the current work is complementary to that using
organometallic complex catalysis.
C
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mp 42.2 °C; 1H NMR (300 MHz, CDCl3) δ 7.95 (d, J = 7.8 Hz, 2H),
7.59 (t, J = 7.2 Hz, 1H), 7.48 (t, J = 7.2 Hz, 2H), 3.91 (s, 3H), 3.14 (t,
J = 7.8 Hz, 2H), 2.65 (t, J = 7.8 Hz, 2H); 19F NMR (282 MHz,
CDCl3) δ −66.2 (s); 13C NMR (100 MHz, CDCl3) δ 197.0, 162.8,
136.3, 133.5, 128.8, 128.0, 122.7 (q, J = 281.0 Hz), 60.4 (m), 54.1,
33.0, 22.9; IR (KBr) ν 2962.7, 2896.2, 1760.1, 1693.1, 1450.0, 1235.9,
1058.9, 747.3, 689.8; MS (ESI) m/z 365 [M + Na]+; HRMS (ESI-
FTICR-MS) calcd for C14H12F6O3Na [M + Na]+ 365.0583, found
365.0582.
Scheme 3. Transformation of Michael Adduct 3a
5-Oxo-5-(4-chlorophenyl)-2,2-bis(trifluoromethyl)pentanoic
Acid Methyl Ester (3b). XPhos (9.5 mg, 0.02 mmol), DMF (0.4
mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate (1a, 42.0
mg, 0.2 mmol), 1-(4-chlorophenyl)prop-2-en-1-one (2b, 99.6 mg, 0.6
mmol) were used. The mixture was stirred for 1 h. Yield: 56.4 mg
(75%). White solid; mp 61.0 °C; 1H NMR (300 MHz, CDCl3) δ 7.89
(d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 3.92 (s, 3H), 3.11 (t, J =
7.8 Hz, 2H), 2.63 (t, J = 7.8 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ
−66.2 (s); 13C NMR (100 MHz, CDCl3) δ 195.8, 162.8, 140.0, 134.5,
129.4, 129.0, 122.6 (q, J = 282.9 Hz), 60.5 (m), 54.1, 32.9, 22.7; IR
(KBr) ν 2934.1, 2856.3, 1758.7, 1693.8, 1589.3, 1300.0, 1193.9,
1056.9, 999.6, 803.0; MS (EI) m/z 376 [M]+; HRMS (EI-TOF-MS)
calcd for C14H11ClF6O3 [M] 376.0301, found 376.0306.
5-Oxo-5-(4-bromophenyl)-2,2-bis(trifluoromethyl)pentanoic
Acid Methyl Ester (3c). XPhos (9.5 mg, 0.02 mmol), DMF (0.4
mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate (1a, 42.0
mg, 0.2 mmol), 1-(4-bromophenyl)prop-2-en-1-one (2c, 126.6 mg, 0.6
mmol) were used. The mixture was stirred for 1 h. Yield: 64.0 mg
(76%). White solid; mp 85.9 °C; 1H NMR (300 MHz, CDCl3) δ 7.81
(d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 3.91 (s, 3H), 3.10 (t, J =
7.8 Hz, 2H), 2.63 (t, J = 7.8 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ
−66.2 (s); 13C NMR (100 MHz, CDCl3) δ 196.1. 162.6, 134.9, 132.0,
129.5, 128.7, 122.6 (q, J = 282.9 Hz), 60.5 (m), 54.1, 32.9, 22.7; IR
(KBr) ν 2971.6, 2886.5, 1760.3, 1693.4, 1576.5, 1299.8, 997.6, 769.4,
663.2; MS (EI) m/z 420 [M]+; HRMS (EI-TOF-MS) calcd for
C14H11BrF6O3 [M] 419.9796, found 419.9795.
CONCLUSION
■
In conclusion, we have developed phosphine-catalyzed Michael
reactions of CF3-containing esters with alkenes. Although
limited to active Michael acceptors and highly acidic
trifluoromethylated nucleophiles, these reactions with α,β-
unsaturated carbonyl compounds such as (hetero)aryl vinyl
ketones, alkyl vinyl ketones, and phenyl acrylate proceeded
efficiently at room temperature, providing many fluorinated
compounds with a CF3-containing quaternary carbon center.
After our successful use of organometallic catalysis in 2009, we
now provide another method of suppressing defluorination of
α-trifluoromethylated compounds in C−C bond-forming
reactions, using organocatalysis. Future work will focus on
enantioselective organocatalytic reactions of α-trifluoromethy-
lated compounds with nonterminal alkenes.
EXPERIMENTAL SECTION
■
General Experiment Details. All reagents were commercially
available and used without further purification except aryl vinyl
ketones, which were prepared according to a reported method.19 All
reactions were carried out in open vessels under aerobic atmosphere.
All solvents were purified according to standard methods prior to use.
Melting points were determined by differential scanning calorimetry
(DSC) measurements. NMR spectra were obtained on 300 MHz
5-Oxo-5-(4-nitrophenyl)-2,2-bis(trifluoromethyl)pentanoic
Acid Methyl Ester (3d). XPhos (9.5 mg, 0.02 mmol), DMF (0.4
mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate (1a, 42.0
mg, 0.2 mmol), 1-(4-nitrophenyl)prop-2-en-1-one (2d, 106.2 mg, 0.6
mmol) were used. The mixture was stirred for 1 h. Yield: 52.6 mg
1
(68%). White solid; mp 116.3 °C; H NMR (300 MHz, CDCl3) δ
1
8.34 (d, J = 8.4 Hz, 2H), 8.12 (d, J = 8.1 Hz, 2H), 3.93 (s, 3H), 3.19 (t,
J = 7.8 Hz, 2H), 2.66 (t, J = 7.8 Hz, 2H); 19F NMR (282 MHz,
CDCl3) δ −66.1 (s); 13C NMR (100 MHz, CDCl3) δ 195.8, 162.8,
150.9, 140.6, 129.2, 124.2, 122.8 (q, J = 294.9 Hz), 60.4 (m), 54.4,
33.8, 22.8; IR (KBr) ν 3118.5, 3076.2, 2967.6, 2853.4, 1745.6, 1694.1,
1526.3, 1445.2, 1297.0, 1008.6, 860.1, 808.5, 674.0; MS (ESI) m/z 410
[M + Na]+; HRMS (ESI-FTICR-MS) calcd for C14H11F6NO5Na [M +
Na]+ 410.0434, found 410.0438.
spectrometers and recorded at 25 °C. Chemical shifts for H NMR
spectra are reported in ppm downfield from TMS, chemical shifts for
13C NMR spectra are recorded in ppm relative to internal chloroform
(δ 77.0 ppm for 13C), and chemical shifts for 19F NMR are reported in
ppm downfield from fluorotrichloromethane (CFCl3). Coupling
constants (J) are reported in hertz. The terms m, s, d, t, and q refer
to multiplet, singlet, doublet, triplet, and quartet, respectively. 13C
NMR was broad-band decoupled from hydrogen nuclei. Infrared
spectra (IR) were recorded with an infrared spectrometer; absorbance
frequencies are given at maximum intensity in cm−1. The mass
analyzer type uesd for the HRMS is time-of-flight mass spectrometry
(TOF-MS) or Fourier transform ion cyclotron resonance mass
spectrometry (FTICR-MS). Column chromatography was performed
using silica gel (mesh 300−400).
5-Oxo-5-(4-trifluoromethylphenyl)-2,2-bis(trifluoromethyl)-
pentanoic Acid Methyl Ester (3e). XPhos (9.5 mg, 0.02 mmol),
DMF (0.4 mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate
(1a, 42.0 mg, 0.2 mmol), 1-(4-(trifluoromethyl)phenyl)prop-2-en-1-
one (2e, 120 mg, 0.6 mmol) were used. The mixture was stirred for 1
1
h. Yield: 59.0 mg (72%). White solid; mp 71.8 °C; H NMR (300
MHz, CDCl3) δ 8.06 (d, J = 8.1 Hz, 2H), 7.75 (d, J = 8.1 Hz, 2H),
3.92 (s, 3H), 3.17 (t, J = 7.8 Hz, 2H), 2.66 (t, J = 7.8 Hz, 2H); 19F
NMR (282 MHz, CDCl3) δ −63.2 (s, 3F), −66.2 (s, 6F); 13C NMR
(100 MHz, CDCl3) δ 196.1, 162.6, 145.4, 138.8, 128.4, 125.8 (q, J =
3.7 Hz), 122.6 (q, J = 277.3 Hz), 122.1 (q, J = 280.2 Hz), 60.2 (m),
54.0, 33.2, 22.5; IR (KBr) ν 2923.9, 2853.5, 1755.4, 1698.7, 1490.3,
1195.3, 1081.8, 856.7, 775.6, 542.9; MS (EI) m/z 410 [M]+; HRMS
(EI-TOF-MS) calcd for C15H11F9O3 [M] 410.0564, found 410.0567.
5-Oxo-5-(4-methylphenyl)-2,2-bis(trifluoromethyl)-
pentanoic Acid Methyl Ester (3f). XPhos (9.5 mg, 0.02 mmol),
DMF (0.4 mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate
(1a, 42.0 mg, 0.2 mmol), 1-p-tolylprop-2-en-1-one (2f, 87.6 mg, 0.6
mmol) were used. The mixture was stirred 1 h. Yield: 62.7 mg (88%).
Colorless oil; 1H NMR (300 MHz, CDCl3) δ 7.85 (d, J = 8.1 Hz, 2H),
7.28 (d, J = 8.1 Hz, 2H), 3.91 (s, 3H), 3.11 (t, J = 7.8 Hz, 2H), 2.63 (t,
General Procedure of Michael Addition Reaction. To a
solution of phosphine (0.01 or 0.02 mmol) in DMF (0.4 mL) were
added α-trifluoromethylated compounds (1, 0.2 mmol) and α,β-
unsaturated ketone or ester (2, 0.6 or 0.8 mmol). The mixture was
stirred at room temperature for the time indicated. The reaction was
monitored by 19F NMR spectroscopy. After that, the reaction mixture
was diluted with water and extracted with EtOAc. The extract was
washed with brine, dried over Na2SO4, and then concentrated in
vacuo. The residue was purified by flash column chromatography on
silica gel (petroleum ether/EtOAc) to yield the desired product.
5-Oxo-5-phenyl-2,2-bis(trifluoromethyl)pentanoic Acid
Methyl Ester (3a). XPhos (9.5 mg, 0.02 mmol), DMF (0.4 mL),
methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate (1a, 42.0 mg, 0.2
mmol), 1-phenylprop-2-en-1-one (2a, 79.2 mg, 0.6 mmol) were used.
The mixture was stirred for 1 h. Yield: 64.2 mg (94%). White solid;
D
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J = 7.8 Hz, 2H), 2.42 (s, 3H); 19F NMR (282 MHz, CDCl3) δ −66.2
(s); 13C NMR (100 MHz, CDCl3) δ 196.7, 163.0, 144.4, 133.8, 129.4,
128.1, 122.7 (q, J = 288.4 Hz), 60.7 (m), 54.1, 32.7, 23.0, 21.6; IR
(KBr) ν 2961.8, 2928.3, 1760.4, 1686.0, 1608.8, 1449.4, 1297.0,
1058.2, 1003.2, 802.4; MS (ESI) m/z 379 [M + Na]+; HRMS (ESI-
FTICR-MS) calcd for C15H14F6O3Na [M + Na]+ 379.0739, found
379.0743.
5-Oxo-5-(4-methoxylphenyl)-2,2-bis(trifluoromethyl)-
pentanoic Acid Methyl Ester (3g). XPhos (9.5 mg, 0.04 mmol),
DMF (0.4 mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate
(1a, 42.0 mg, 0.2 mmol), 1-(4-methoxyphenyl)prop-2-en-1-one (2g,
97.2 mg, 0.6 mmol) were used. The mixture was stirred 1 h. Yield: 61.0
mg (82%). White solid; ; mp 56.6 °C;1H NMR (300 MHz, CDCl3) δ
7.93 (d, J = 8.7 Hz, 2H), 6.95 (d, J = 8.7 Hz, 2H), 3.91 (s, 3H), 3.88
(s, 3H), 3.08 (t, J = 7.8 Hz, 2H), 2.63 (t, J = 7.8 Hz, 2H); 19F NMR
(282 MHz, CDCl3) δ −66.2 (s); IR (KBr) ν 2928.7, 2963.2, 2843.8,
1759.1, 1682.9, 1601.7, 1512.0, 1300.0, 1246.7, 1173.5, 1056.7, 843.2,
728.0; MS (ESI) m/z 373 (M + H)+; HRMS (ESI-FTICR-MS) calcd
for C15H14F6O4Na [M + Na]+ 395.0689, found 395.0705.
2.64 (t, J = 7.8 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ −66.2 (s);
13C NMR (100 MHz, CDCl3) δ 189.9, 162.8, 143.3, 134.1, 132.1,
128.2, 122.6 (q, J = 287.3 Hz), 60.5 (m), 54.1, 33.5, 22.7; IR (KBr) ν
2994.0, 2898.2, 1750.4, 1668.7, 1553.6, 1406.8, 1225.3, 1065.2, 865.7,
699.5, 553.9; MS (EI) m/z 348 [M]+; HRMS (EI-TOF-MS) calcd for
C12H10F6O3S [M] 348.0255, found 348.0254.
5-Oxo-5-(2-furyl)-2,2-bis(trifluoromethyl)pentanoic Acid
Methyl Ester (3l). XPhos (9.5 mg, 0.02 mmol), DMF (0.4 mL),
methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate (1a, 42.0 mg, 0.2
mmol), 1-(furan-2-yl)prop-2-en-1-one (2l, 73.2 mg, 0.6 mmol) were
used. The mixture was stirred for 1 h. Yield: 51.1 mg (77%). Colorless
oil; 1H NMR (300 MHz, CDCl3) δ 7.60 (m, 1H), 7.24 (m, 1H), 6.56
(m, 1H) 3.91 (s, 3H), 3.02 (t, J = 7.8 Hz, 2H), 2.61 (t, J = 7.8 Hz,
2H); 19F NMR (282 MHz, CDCl3) δ −66.2 (s); 13C NMR (100 MHz,
CDCl3) δ 186.1, 162.6, 152.1, 146.5, 122.6 (q, J = 285.8 Hz), 117.2,
112.4, 60.5 (m), 54.1, 32.7, 22.4; IR (KBr) ν 2968.2, 2931.0, 2856.2,
1752.0, 1683.3, 1441.3, 1300.6, 1270.7, 1234.0, 1070.8, 809.1, 755.6,
519.0, 474.1; MS (EI) m/z 332 [M]+; HRMS (EI-TOF-MS) calcd for
C12H10F6O4 [M] 332.0483, found 332.0485.
5-Oxo-5-(3-methoxylphenyl)-2,2-bis(trifluoromethyl)-
pentanoic Acid Methyl Ester (3h). XPhos (9.5 mg, 0.02 mmol),
DMF (0.4 mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate
(1a, 42.0 mg, 0.2 mmol), 1-(3-methoxyphenyl)prop-2-en-1-one (2h,
97.2 mg, 0.6 mmol) were used. The mixture was stirred for 1 h. Yield:
67.0 mg (90%). White solid; mp 74.6 °C; 1H NMR (300 MHz,
CDCl3) δ 7.51 (m, 2H), 7.39 (t, J = 8.1 Hz, 1H), 7.39 (d, J = 6.6 Hz,
1H), 3.91 (s, 3H), 3.87 (s, 3H), 3.13 (t, J = 7.8 Hz, 2H), 2.64 (t, J =
7.8 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ −66.2 (s); 13C NMR
(100 MHz, CDCl3) δ 197.0, 159.9, 137.7, 129.6, 122.7 (q, J = 287.9
Hz), 120.5, 119.7, 118.1, 112.4, 60.4 (m), 55.3, 53.9, 32.8, 22.8; IR
(KBr) ν 3009.5, 2973.1, 2842.3, 1755.1, 1694.5, 1599.7, 1562.0,
1261.1, 1191.3, 1041.9, 955.9, 783.2.0, 684.9, 601.8; MS (ESI) m/z
373 (M + H)+; HRMS (ESI-FTICR-MS) calcd for C15H14F6O4Na [M
+ Na]+ 395.0689, found 395.0694.
Dimethyl 2-(3-(Naphthalen-2-yl)-3-oxopropyl)-2-
(trifluoromethyl)malonate (3m). XPhos (23.8 mg, 0.05 mmol),
DMF (1 mL), methyl dimethyl 2-(trifluoromethyl)malonate (1b,
100.0 mg, 0.5 mmol), 1-(naphthalen-2-yl)prop-2-en-1-one (2m, 364.0
mg, 2 mmol) were used. The mixture was stirred for 4 h. Yield: 173.8
mg (91%). White solid; mp 100.1 °C; 1H NMR (300 MHz, CDCl3) δ
8.47 (s, 1H), 8.04−7.97 (m, 2H), 7.91−7.86 (m, 2H), 7.64−7.53 (m,
2H), 3.86 (s, 6H), 3.34 (t, J = 7.5 Hz, 2H), 2.69 (t, J = 7.5 Hz, 2H);
19F NMR (282 MHz, CDCl3) δ −67.0 (s); 13C NMR (100 MHz,
CDCl3) δ 197.6, 165.3, 135.6, 133.7, 132.4, 129.7, 129.6, 128.6, 128.5,
127.7, 126.8, 123.6, 123.5 (q, J = 277.0 Hz), 62.7 (q, J = 25.3 Hz),
53.6, 33.7, 25.2; IR (KBr) ν 3059.8, 2958.0, 2916.1, 1742.2, 1682.9,
1436.8, 1276.9, 1187.6, 1072.0, 794.9; MS (ESI) m/z 383.1 [M + 1]+;
HRMS (ESI-FTICR-MS) calcd for C19H18F3O5 [M + 1]+ 383.1101,
found 383.1110.
5-Oxo-5-(3-nitrophenyl)-2,2-bis(trifluoromethyl)pentanoic
Acid Methyl Ester (3i). XPhos (9.5 mg, 0.02 mmol), DMF (0.4 mL),
methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate (1a, 42.0 mg, 0.2
mmol), 1-(3-nitrophenyl)prop-2-en-1-one (2i, 106.2 mg, 0.6 mmol)
were used. The mixture was stirred for 1 h. Yield: 46.4 mg (60%).
White solid; mp 79.9 °C;1H NMR (300 MHz, CDCl3) δ 8.76 (s, 1H),
8.46 (d, J = 7.9 Hz, 1H), 8.29 (d, J = 7.9 Hz, 1H), 7.71 (t, J = 7.9 Hz,
1H), 3.95 (s, 3H), 3.20 (t, J = 7.8 Hz, 2H), 2.67 (t, J = 7.8 Hz, 2H);
19F NMR (282 MHz, CDCl3) δ −66.3 (s); 13C NMR (100 MHz,
CDCl3) δ 194.9, 162.6, 137.4, 133.5, 130.2, 127.7, 122.7 (q, J = 285.8
Hz), 60.1 (m), 54.3, 33.3, 22.7; IR (KBr) ν 3080.5, 2971.1, 2928.6,
2886.3, 1760.4, 1690.2, 1538.8, 1355.9, 1243.1, 1114.2, 1070.1, 736.2,
654.5, 519.7; MS (ESI) m/z 410 [M + Na]+; HRMS (ESI-FTICR-
MS) calcd for C14H11F6NO5Na [M + Na]+ 410.0434, found 410.0444.
5-Oxo-5-(naphthalen-2-yl)-2,2-bis(trifluoromethyl)-
pentanoic Acid Methyl Ester (3j). XPhos (9.5 mg, 0.02 mmol),
DMF (0.4 mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate
(1a, 42.0 mg, 0.2 mmol), 1-(naphthalen-2-yl)prop-2-en-1-one (2j,
109.2 mg, 0.6 mmol) were used. The mixture was stirred for 1 h. Yield:
75.2 mg (96%). White solid; mp 80.1 °C;1H NMR (300 MHz,
CDCl3) δ 8.46 (s, 1H), 8.01 (t, J = 8.7 Hz, 2H), 7.90 (t, J = 7.2 Hz,
2H), 7.66−7.55 (m, 2H), 3.93 (s, 3H), 3.28 (t, J = 8.1 Hz, 2H), 2.67
(t, J = 8.1 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ −66.1 (s); 13C
NMR (100 MHz, CDCl3) δ 197.2, 163.1, 136.0, 133.7, 132.7, 129.9,
129.8, 128.9, 128.8, 128.0, 127.1, 123.8, 122.9 (q, J = 282.0 Hz), 60.4
(m), 54.3, 33.2, 23.2; IR (KBr) ν 3021.7, 2967.2, 1760.3, 1683.3.2,
1517.6, 1471.4, 1266.1, 1233.1, 1165.6, 1060.7, 764.2, 635.7, 596.7;
MS (ESI) m/z 415 [M + Na]+; HRMS (ESI-FTICR-MS) calcd for
C18H14F6O3Na [M + Na]+ 415.0739, found 415.0760.
Dimethyl 2-(3-(4-Nitrophenyl)-3-oxopropyl)-2-
(trifluoromethyl)malonate (3n). XPhos (23.8 mg, 0.05 mmol),
DMF (1 mL), methyl dimethyl 2-(trifluoromethyl)malonate (1b,
100.0 mg, 0.5 mmol), 1-(4-nitrophenyl)prop-2-en-1-one (2n, 354.0
mg, 2 mmol) were used. The mixture was stirred for 4 h. Yield: 165.8
1
mg (88%). White solid; H NMR (300 MHz, CDCl3) δ 7.90 (d, J =
6.7 Hz, 2H), 7.44 (d, J = 6.7 Hz, 2H), 3.83 (s, 6H), 3.17 (t, J = 5.7 Hz,
2H), 2.61 (t, J = 5.7 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ −67.0
(s); 13C NMR (100 MHz, CDCl3) δ 196.3, 165.2, 150.4, 140.7, 129.0,
123.9, 123.3 (q, J = 288.9 Hz), 62.4 (q, J = 26.0 Hz), 53.7, 34.3, 29.6;
IR (KBr) ν 3059.8, 2952.0, 2922.1, 1739.2, 1676.2, 1626.1, 1468.0,
1278.5, 1181.6, 1123.3, 863.9, 748.1; MS (EI) m/z 377 [M]+; HRMS
(EI-TOF-MS) calcd for C15H14NF3O7 [M] 377.0722, found 377.0724.
Dimethyl 2-(3-(4-Chlorophenyl)-3-oxopropyl)-2-
(trifluoromethyl)malonate (3o). XPhos (9.5 mg, 0.05 mmol),
DMF (1 mL), methyl dimethyl 2-(trifluoromethyl)malonate (1b, 100
mg, 0.5 mmol), 1-(4-chlorophenyl)prop-2-en-1-one (2o, 332.0 mg, 2
mmol) were used. The mixture was stirred 4 h. Yield: 164.9 mg (90%).
White solid; mp 81.5 °C; 1H NMR (300 MHz, CDCl3) δ 7.87 (d, J =
8.5 Hz, 2H), 7.42 (d, J = 8.5 Hz, 2H), 3.82 (s, 6H), 3.14 (t, J = 7.8 Hz,
2H), 2.59 (t, J = 7.8 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ −67.0
(s); 13C NMR (100 MHz, CDCl3) δ 196.5, 165.3, 139.8, 134.7, 129.4,
129.0, 123.2 (q, J = 270.0 Hz), 62.5 (q, J = 26.0 Hz), 53.6, 33.6, 25.0;
IR (KBr) ν 2946.0, 2916.1, 1733.2, 1682.2, 1586.3, 1439.4, 1256.6,
1178.6, 1088.7; MS (ESI) m/z 367.0 (M + 1)+; HRMS (ESI-FTICR-
MS) calcd for C15H15ClF3O5 [M + 1]+ 367.0555, found 367.0558.
Dimethyl 2-(3-(4-Methoxyphenyl)-3-oxopropyl)-2-
(trifluoromethyl)malonate (3p). XPhos (23.8 mg, 0.05 mmol),
DMF (1 mL), methyl dimethyl 2-(trifluoromethyl)malonate (1b,
100.0 mg, 0.5 mmol), 1-(4-methoxyphenyl)prop-2-en-1-one (2p,
324.0 mg, 2 mmol) were used. The mixture was stirred for 4 h.
5-Oxo-5-(2-thienyl)-2,2-bis(trifluoromethyl)pentanoic Acid
Methyl Ester (3k). XPhos (9.5 mg, 0.02 mmol), DMF (0.4 mL),
methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate (1a, 42.0 mg, 0.2
mmol), 1-(thiophen-2-yl)prop-2-en-1-one (2k, 82.8 mg, 0.6 mmol)
were used. The mixture was stirred for 1 h. Yield: 50.1 mg (72%).
Colorless oil; 1H NMR (300 MHz, CDCl3) δ 7.73 (m, 1H), 7.67 (m,
1H), 7.15 (t, J = 4.2 Hz, 1H) 3.92 (s, 3H), 3.08 (t, J = 7.8 Hz, 2H),
1
Yield: 85.1 mg (47%). White solid; H NMR (300 MHz, CDCl3) δ
7.93 (d, J = 6.6 Hz, 2H), 6.93 (d, J = 6.6 Hz, 2H), 3.86 (s, 3H), 3.83
(s, 6H), 3.12 (t, J = 6 Hz, 2H), 2.61 (t, J = 6 Hz, 2H); 19F NMR (282
MHz, CDCl3) δ −67.1 (s); 13C NMR (100 MHz, CDCl3) δ 196.2,
165.2, 163.6, 130.2, 129.4, 123.4 (q, J = 287.0 Hz), 113.7, 62.6 (q, J =
E
dx.doi.org/10.1021/jo402212j | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
26.0 Hz), 55.4, 53.5, 33.2, 25.2; IR (KBr) ν 2959.3, 2952.8, 1748.4,
1680.1, 1602.0, 1511.8, 1421.1, 1260.3, 1173.5, 1112.3, 1027.5; MS
(ESI) m/z 363.0 (M + 1)+; HRMS (ESI-FTICR-MS) calcd for
C16H17F3O6Na [M + Na]+ 385.0869, found 385.0880.
CDCl3) δ −67.1 (s); 13C NMR (100 MHz, CDCl3) δ 170.5, 165.2,
150.5, 129.4, 125.9, 122.5 (q, J = 286.5 Hz), 121.4, 62.3 (q, J = 26.1
Hz), 53.6, 29.6, 25.7; IR (KBr) ν 3498.0, 3045.7, 2962.6, 2359.8,
1762.7, 1594.2, 1493.8, 1274.2, 1239.7, 1165.0, 1069.3; MS (ESI) m/z
371 [M + Na]+; HRMS (ESI-FTICR-MS) calcd for C15H15F3O6Na
[M + Na]+ 371.0718, found 371.0718.
1-Methyl 5-Phenyl 2,2-Bis(trifluoromethyl)pentanedioate
(3x). Tris(4-methoxyphenyl)phosphine (7.0 mg, 0.02 mmol), DMF
(0.4 mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate (1a,
42.0 mg, 0.2 mmol), phenyl acrylate (2p, 88.8 mg, 0.6 mmol) were
used. The mixture was stirred for 1 h. Yield: 59.4 mg (83%). Colorless
oil; 1H NMR (300 MHz, CDCl3) δ 7.39 (t, J = 7.6 Hz, 2H), 7.26 (t, J
= 7.6 Hz, 1H), 7.09 (d, J = 7.6 Hz, 2H), 3.93 (s, 3H), 2.77 (t, J = 7.6
Hz, 2H), 2.63 (t, J = 7.6 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ
−62.3 (s); 13C NMR(100 MHz, CDCl3) δ 169.7, 162.5, 150.4, 129.5,
126.1, 122.5(q, J = 286.5 Hz), 121.4, 60.4 (m), 54.2, 29.0, 23.5; IR
(KBr) ν 3045.7; 2962.6; 2359.8; 1762.7; 1594.2; 1493.8; 1452.4;
1239.7; 1150.1; 1069.3; 967.6; 811.3; 755.1; 689.4; MS (ESI) m/z 381
[M + Na]+; HRMS (ESI-FTICR-MS) calcd for C14H12F6O4Na [M +
Na]+ 381.0532, found 381.0530.
Procedure of Hydrolysis. LiOH (72.0 mg, 3 mmol) was added to
a solution of 3a (342.0 mg, 1 mmol) in 9 mL of methanol and 3 mL of
water. The solution was stirred at room temperature for 16 h. Diluted
HCl aqueous solution was added to the reaction mixture. After that,
the mixture was extracted with EtOAc. The extract was washed with
brine, dried over Na2SO4, and then concentrated in vacuo. The residue
was purified by flash column chromatography on silica gel to yield the
desired product. Yield: 302.0 mg (92%).
5-Oxo-5-phenyl-2,2-bis(trifluoromethyl)pentanoic Acid (4).
Yellow solid; mp 114.1 °C; 1H NMR (300 MHz, CDCl3) δ 7.95 (d, J
= 7.5 Hz, 2H), 7.60 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 2H), 3.20
(t, J = 8.4 Hz, 2H), 2.65 (t, J = 8.4 Hz, 2H); 19F NMR (282 MHz,
CDCl3) δ −66.2; 13C NMR (100 MHz, CDCl3) δ 197.9, 165.5, 136.0,
133.8, 128.8, 128.1, 122.5 (q, J = 282.0 Hz), 60.4 (m), 32.9, 22.9. IR
(KBr) ν 3430.8, 3066.8, 2925.4, 1750.6, 1655.2, 1599.9, 1451.4,
1252.4, 1185.3, 1062.4, 1006.1, 747.6, 703.4; MS (ESI) m/z 351 [M +
Na]+; HRMS (ESI-FTICR-MS) calcd for C13H10F6O3Na [M + Na]+
351.0426, found 351.0436.
Dimethyl 2-(3-Oxobutyl)-2-(trifluoromethyl)malonate
(3q).6a Tris(4-methoxyphenyl)phosphine (17.6 mg, 0.05 mmol),
DMF (1 mL), methyl dimethyl 2-(trifluoromethyl)malonate (1b,
100.0 mg, 0.5 mmol), but-3-en-2-one (2q, 140.0 mg, 2 mmol) were
used. The mixture was stirred for 4 h. Yield: 120.2 mg (89%).
Dimethyl 2-(3-Oxopentyl)-2-(trifluoromethyl)malonate (3r).
Tris(4-methoxyphenyl)phosphine (35.2 mg, 0.1 mmol), DMF (1 mL),
methyl dimethyl 2-(trifluoromethyl)malonate (1b, 100.0 mg, 0.5
mmol), pent-1-en-3-one (2r, 168.0 mg, 2 mmol) were used. The
1
mixture was stirred for 4 h. Yield: 75.2 mg (53%).Colorless oil; H
NMR (300 MHz, CDCl3) δ 3.78 (s, 6H), 2.57 (t, J = 6.3 Hz, 2H),
2.42−2.35 (m, 4H), 1.02 (t, J = 7.5 Hz, 3H); 19F NMR (282 MHz,
CDCl3) δ −67.2 (s); 13C NMR (100 MHz, CDCl3) δ 208.8, 165.3,
123.3 (q, J = 278 Hz), 62.4 (q, J = 24 Hz), 53.5, 37.0, 35.8, 24.5, 7.7;
IR (KBr) ν 2958.0, 1745.2, 1712.2, 1433.4, 1283.5, 1076.7, 1028.7; MS
(ESI) m/z 285.0 (M + 1)+; HRMS (ESI-FTICR-MS) calcd for
C11H15F3O5Na [M + Na]+ 307.0764, found 307.0773.
Dimethyl 2-(3-Oxooctyl)-2-(trifluoromethyl)malonate (3s).
Tris(4-methoxyphenyl)phosphine (35.2 mg, 0.1 mmol), DMF (1
mL), methyl dimethyl 2-(trifluoromethyl)malonate (1b, 100.0 mg, 0.5
mmol), oct-1-en-3-one (2s, 252.0 mg, 2 mmol) were used. The
1
mixture was stirred for 4 h. Yield: 83.1 mg (51%). Colorless oil; H
NMR (300 MHz, CDCl3) δ 3.82 (s, 6H), 2.61(t, J = 8.1 Hz, 2H), 2.43
(t, J = 8.4 Hz, 2H), 2.40 (t, J = 7.5 Hz, 2H), 0.91−0.83 (m, 9H); 19F
NMR (282 MHz, CDCl3) δ −67.2 (s); IR (KBr) ν 2959.3, 2856.2,
1748.2, 1715.2, 1437.4, 1284.2, 1047.7, 804.0; MS (ESI) m/z 327.1
(M + 1)+; HRMS (ESI-FTICR-MS) calcd for C14H21F3O5Na [M +
Na]+ 349.1233, found 349.1227.
5-Oxo-2,2-bis(trifluoromethyl)hexanoic Acid Methyl Ester
(3t).6g Tris(4-methoxyphenyl)phosphine (7.0 mg, 0.02 mmol), DMF
(0.4 mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate (1a,
42.0 mg, 0.2 mmol), but-3-en-2-one (2q, 42.0 mg, 0.6 mmol) were
used. The mixture was stirred for 1 h. Yield: 52.1 mg (93%).
5-Oxo-2,2-bis(trifluoromethyl)heptanoic Acid Methyl Ester
(3u). Tris(4-methoxyphenyl)phosphine (14.1 mg, 0.04 mmol), DMF
(0.4 mL), methyl methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate
(1a, 42.0 mg, 0.2 mmol), pent-1-en-3-one (2r, 50.4 mg, 0.6 mmol)
were used. The mixture was stirred for 1 h. Yield: 42.9 mg (73%).
Colorless oil; 1H NMR (300 MHz, CDCl3) δ 3.90 (s, 3H), 2.59 (t, J =
7.2 Hz, 2H), 2.46 (m, 4H), 1.08 (t, J = 7.2 Hz, 3H); 19F NMR (282
MHz, CDCl3) δ −66.1 (s); 13C NMR (100 MHz, CDCl3) δ 208.0,
162.6, 122.6 (q, J = 286.6 Hz), 60.4 (m), 53.9, 36.3, 35.8, 22.3, 7.6; IR
(KBr) ν 2982.7, 2913.6, 1761.0, 1452.8, 1235.9, 1093.1, 1026.8; MS
(ESI) m/z 317 [M + Na]+; HRMS (ESI-FTICR-MS) calcd for
C10H12F6O3Na [M + Na]+ 317.0583, found 317.0597.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H NMR, 13C NMR and 19F NMR spectroscopies for
all new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: yxj@ecust.edu.cn.
*E-mail: murasyt@pearl.ocn.ne.jp.
*E-mail: chenqy@sioc.ac.cn.
*E-mail: yguo@sioc.ac.cn.
■
5-Oxo-2,2-bis(trifluoromethyl)nonanoic Acid Methyl Ester
(3v). Tris(4-methoxyphenyl)phosphine (14.1 mg, 0.04 mmol), DMF
(0.4 mL), methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate (1a,
42.0 mg, 0.2 mmol), oct-1-en-3-one (2s, 75.6 mg, 0.6 mmol) were
uesd. The mixture was stirred for 1 h. Yield: 45.7 mg (68%). Colorless
Notes
1
The authors declare no competing financial interest.
oil; H NMR (300 MHz, CDCl3) δ 3.89 (s, 3H), 2.57 (t, J = 5.4 Hz,
2H), 2.46 (m, 4H), 1.53−1.64 (m, 2H), 1.36−1.24 (m, 4H), 0.89 (t, J
= 6.9 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ −66.8 (s); 13C NMR
(100 MHz, CDCl3) δ 207.8, 162.7, 122.6 (q, J = 284.3 Hz), 60.4 (m),
54.0, 42.7, 36.7, 31.2, 23.4, 22.3, 22.2, 13.8; IR (KBr) ν 2961.1, 2875.1,
1760.5, 1455.0, 1296.7, 1045.6; MS (ESI) m/z 359 [M + Na]+; HRMS
(ESI-FTICR-MS) calcd for C13H18F6O3Na [M + Na]+ 359.1052,
found 359.1061.
ACKNOWLEDGMENTS
■
This work was supported by National Basic Research Program
of China (973 Program) (No. 2012CB821600), National
Natural Science Foundation of China (No. 21032006,
21172241) and Shanghai Science and Technology Commission
(11ZR1445700).
1-Methyl 5-Phenyl 2-Methoxycarbonyl-2-trifluoromethyl-
pentanedioate (3w). Tris(4-methoxyphenyl)phosphine (7.0 mg,
0.02 mmol), DMF (0.4 mL), methyl dimethyl 2-(trifluoromethyl)-
malonate (1b, 40.0 mg, 0.2 mmol), phenyl acrylate (2p, 88.8 mg, 0.6
mmol) were used. The mixture was stirred for 1 h. Yield: 52.9 mg
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