Regioselective Synthesis of α-Perfluoroalkylated Ketals via Double Michael Addition of Alcohols to Activated Alkynes

Article abstract of DOI:10.1055/s-0034-1380753

An efficient method was developed for the synthesis of alkyl 3,3-dialkoxy-3-(perfluoroalkyl)propanoates from ethyl 3-(perfluoroalkyl)propynoates and alcohols using a base-catalyzed double Michael addition reaction (which was accompanied by transesterification in the case of MeOH, EtOH, PrOH, and BuOH). This method provides easy access to the product α-perfluoroalkyl ketals with reasonable to good yields with total regioselectivity. This procedure does not require the use of expensive supplementary additives for the preparation of α-perfluoroalkyl ketals which are very sensitive to acidic conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0034-1380753

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 2635–2640
paper
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Synthesis
Regioselective Synthesis of α-Perfluoroalkylated Ketals via
Double Michael Addition of Alcohols to Activated Alkynes
RF
Ella Ndonga
RO
CO2Et
Guy Judicaela
Jean Luc Parrainb
Mohamed Abarbri*a
Na (10 mol%)
OR
RF
+
RF
CO2Et
ROH
or
CO2R
RO
RF = CF3, C2F5
a Laboratoire d’Infectiologie et Santé Publique (UMR 1282), Equipe Recherche
et Innovation en Chimie Médicinale, Faculté des Sciences, Parc de Grandmont,
37200 Tours, France
mohamed.abarbri@univ-tours.fr
b Aix Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397
Marseille, France
R = alkyl, propargyl, etc.
OR
13 examples (56–84%)
Received: 11.02.2015
Accepted after revision: 16.04.2015
Published online: 17.06.2015
conditions is still rare and the simplicity and the high-atom
economy of such hydroalkoxylations are highly desirable. In
this work, we wish to demonstrate that the introduction of
strong electron-withdrawing substituents (e.g., perfluoro-
alkyl) into an alkyne favors the double hydroalkoxylation
under basic conditions providing ketals. Moreover, and de-
spite numerous reports, the acid-catalyzed formation of α-
perfluoroalkyl ketals from the corresponding ketones is
somewhat difficult since the perfluoroalkyl group strongly
stabilizes the ketone hydrate and hemiacetal forms.11
To overcome the low reactivity of perfluoroketones un-
der acidic activation, the corresponding acetals were pre-
pared under basic conditions from halogeno alcohols.11a,12
Nevertheless, under these conditions, only the formation of
cyclic acetals was reported and more sophisticated meth-
ods using orthoformate,13 Mitsonobu’s conditions,14 or
phosphorus reagents15 are required to provide acyclic α-
perfluoroalkyl acetals.
We report here new direct access to α-perfluoroalkyl
ketals by double conjugate addition of alcohols to ethyl 3-
(perfluoroalkyl)propynoates using sodium metal as a cata-
lyst. To the best of our knowledge, there has been no report
of metal-catalyzed intermolecular hydroalkoxylation of
alkynes 1, and only a few reports in this field of the synthe-
sis of α-perfluoroalkyl ketals.16 Moreover, the incorporation
of a fluoroalkyl group in organic compounds plays an im-
portant role in the search for new active pharmaceutical
compounds.17 Indeed, the trifluoromethyl moiety is known
to influence metabolic stability, binding activity, and lipo-
philicity.18
DOI: 10.1055/s-0034-1380753; Art ID: ss-2015-z0103-op
Abstract An efficient method was developed for the synthesis of alkyl
3,3-dialkoxy-3-(perfluoroalkyl)propanoates from ethyl 3-(perfluoroal-
kyl)propynoates and alcohols using a base-catalyzed double Michael
addition reaction (which was accompanied by transesterification in the
case of MeOH, EtOH, PrOH, and BuOH). This method provides easy ac-
cess to the product α-perfluoroalkyl ketals with reasonable to good
yields with total regioselectivity. This procedure does not require the
use of expensive supplementary additives for the preparation of α-per-
fluoroalkyl ketals which are very sensitive to acidic conditions.
Key words hydroalkoxylation, Michael addition, fluorinated alkyne,
sodium catalyst, perfluorinated ketals
Hydroalkoxylation of alkynes by the addition of alcohols
is one of the most economical methods to access vinyl
ethers and ketals directly.1 Although extensive methods
have been developed for the intramolecular hydroalkoxyl-
ation of alkynes,2 few synthetic studies have been pub-
lished on the intermolecular hydroalkoxylation of alkynes.
In particular, such hydroalkoxylations were performed us-
ing different metal catalysts, such as rhodium,3 palladium,4
silver,5 iridium,6 platinum,7 and gold(I) complexes.8 In the
case of ethyl propynoate, Bertz et al.9 described the prepa-
ration of ethyl 3,3-diethoxypropanoate by copper(I) triflate
catalyzed addition of ethanol to ethyl propynoate where
the presence of the intermediate ethyl 3-ethoxyacrylate
was found to depend on the reaction conditions. The β-ke-
tal was obtained as the sole product when the reaction was
performed with copper(II) sulfate in refluxing ethanol. In
general, the reports have shown that the hydroalkoxylation
reaction of ethyl propynoate provided only vinyl enol
ethers that are sufficiently stable to avoid a second addition
of alcohol.10 Despite the work performed in this area, the
intermolecular addition of alcohols to alkynes under mild
The reaction of ethyl 4,4,4-trifluorobut-2-ynoate (1a)
with ethanol was selected to optimize the reaction condi-
tions of the double conjugate addition (Table 1). First, we
examined the use of a variety of metal catalysts [CuI,
AgOCOCF3, ZnCl2, CuCl2, AuCl3, Mg(OTf)2, and FeCl3] to pro-
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Table 1 Effects of the Catalyst on the Hydroalkoxylation of 1a
mote this hydroalkoxylation reaction, and in all cases these
reactions led exclusively to isomer mixtures of vinyl ether
3a without the formation of ketal 2a (entries 1–6, 9). Using
bases such as DABCO or Et3N also led to the same result (en-
tries 7 and 8). Upon optimization, we found that sodium
was the most effective catalyst. In fact, when the hy-
droalkoxylation of fluorinated alkyne 1a was performed
with excess ethanol using 10 mol% sodium at room tem-
perature for three hours, the double Michael addition gave
solely ketal 2a in 84% yield (entry 10). The formation of two
C–O bonds took place regioselectively at the β-position of
1a, and no ketal in the α-position of 1a was detected. Fur-
ther optimization of the conditions revealed that decreas-
ing the amount of sodium to 2 mol% under the same reac-
tion conditions was not efficient and gave the monoaddi-
tion product 3a (entry 11). When a stoichiometric amount
of sodium was used, no significant difference in yield of ke-
tal 2a was observed (compare entries 10 and 12).
F3C
CO2Et
OEt
3a
EtOH
F3C
CO2Et
catayst (10 mol%)
CF3
1a
EtO
CO2Et
OEt
2a
Entry
Catalyst (10 mol%) Product
Ratioa E/Z
Yield (%)
1
2
CuI
3a
3a
3a
3a
3a
3a
3a
3a
3a
2a
3a
2a
0:100
5:95
43:57
50:50
6:94
40:60
88:12
95:5
52:48
–
50
68
49
45
70
65
88
62
63
84
52
80
AgOCOCF3
ZnCl2
CuCl2
AuCl3
Mg(OTf)2
DABCO
Et3N
3
4
5
6
7
CF3
ROH
RO
8
RF
CO2Et
CO2Et (or R)
Na (10 mol%)
OR
9
FeCl3
Na
1
2a–m
1a RF = CF3
1b RF = C2F5
10
11b
12c
Na
63:27
–
Scheme 1 Hydroalkoxylation of 1
Na
a Determined by 1H NMR.
b Na (2 mol%) was used.
c A stoichiometric amount of Na was used.
The scope of this reaction was investigated using a vari-
ety of alcohols for the regioselective synthesis of ketals
(Scheme 1). The results are summarized in Table 2.
Table 2 Synthesis of Perfluoroalkylated Ketals 2a–m
Entry
1
RF
Alcohol
EtOH
Product
Yield (%)
84
CF3
EtO
MeO
PrO
BuO
CF3
CO2Et
2a
2b
OEt
CF3
2
3
4
CF3
CF3
CF3
MeOH
PrOH
73
71
62
CO2Me
CO2n-Pr
OMe
CF3
2c
PrO
CF3
BuOH
2d
CO2n-Bu
BuO
CF3
O
CO2Et
HO
5
CF3
2e
73
O
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Table 2 (continued)
Entry
RF
Alcohol
Product
Yield (%)
CF3
O
HO
6
CF3
2f
69
O
CO2Et
CF3
O
OH
CO2Et
CO2Et
O
7
8
CF3
CF3
2g
2h
68
56
HO
HO
CF3
O
OH
O
F3C
9
CF3
2i
2j
57
60
O
CO2Et
CO2Et
O
HO
OH
CF3
SH
10
CF3
S
HS
S
C2F5
OEt
EtO
11
12
C2F5
C2F5
EtOH
2k
2l
71
68
CO2Et
C2F5
MeO
MeOH
CO2Me
C2F5
OMe
O
CO2Et
HO
13
C2F5
2m
70
O
CF3
i-PrO
14
15
CF3
CF3
i-PrOH
2n
2o
0
0
CO2i-Pr
i-PrO
CF3
t-BuO
t-BuOH
CO2t-Bu
t-BuO
As shown in Table 2, sodium metal was found to cata-
lyze the double conjugate addition of a variety of alcohols
to ethyl 3-(perfluoroalkyl)propynoate 1 to produce the cor-
responding α-perfluoroalkyl ketals 2a–m. The reaction
proceeded smoothly with reasonable to good yields, and
was highly regioselective. A range of primary alcohols such
as methanol, ethanol, propanol, and butanol underwent
double Michael reactions, providing perfluoroalkylated 3,3-
dialkoxypropanoates 2a–d,k,l in 62–84% yields (entries 1–
4, 11, and 12); the alcohols were used as both reactant and
solvent, hence transesterification also took place. Moreover,
no traces of vinyl ethers resulting from monoaddition were
detected. The use of a stoichiometric amount of alcohol
does not prevent the transesterification, and leads to a mix-
ture of several products. The use of secondary and bulkier
alcohols in this reaction gave no product (entries 14 and
15). However, the use of a diol as substrate containing both
primary and secondary alcohol functions such as propane-
1,2-diol provided the double conjugate addition adduct 2i
as a mixture of diastereomers [57% yield in a ratio ca. 60:40
(entry 9)]. This result showed that the addition of the sec-
ond alkoxide was facilitated by the intramolecular process,
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certainly for entropic reasons. Propargyl alcohols also re-
acted effectively to provide good yields of the expected
products 2e,f,m (entries 5, 6, and 13) and, interestingly, no
transesterification was observed. Note that in the case of
propargyl alcohols, the use of 1,4-diazabicyclo[2.2.2]cy-
clooctane (DABCO) at 40 °C instead of sodium catalyst led
to the formation of fluorinated furans, as previously report-
ed.19 Propynoate 1a was directly converted into cyclic ketal
2g on treatment with one equivalent of ethane-1,2-diol
(entry 7). Moreover, the use of propane-1,3-diol readily
provided 1,3-dioxolane 2h in 56% yield (entry 8); the exten-
sion of this reaction to ethane-1,2-dithiol successfully gave
1,3-dithiolane 2j in 60% yield (entry 10).
In order to examine the influence of the fluoroalkyl
group under these conditions, ethanol was added to ethyl
but-2-ynoate and this provided vinyl ether 4 only in 40%
isolated yield, without the formation of the ketal (Scheme
2). This result shows the important role of the presence of
the fluorinated group in the formation of ketals, thus facili-
tating the double conjugate addition of the second alkoxide
to 1, providing the exclusive formation of ketals 2a–m.
nals. HRMS-ESI were run on a hybrid tandem quadrupole/time-of-
flight (Q-TOF) instrument, equipped with a pneumatically assisted
electrospray (Z-spray) ion source (Micromass, Manchester, U.K.) oper-
ated in positive mode.
α-Perfluoroalkyl Ketals 2a–m; General Procedure
To a 25-mL dry schlenk flask under argon was added alcohol (36.0
mmol, 20 equiv) followed by the careful introduction of Na (4 mg,
0.18 mmol, 10 mol%). After homogenization of the solution, 1a or 1b
(1.8 mmol, 1 equiv) was added via syringe. The mixture was stirred
overnight at r.t. The solvent was evaporated in vacuo and the crude
product was purified on neutral alumina (Et2O) to give the products
2a–m in good yields.
Ethyl 3,3-Diethoxy-4,4,4-trifluorobutanoate (2a)
Colorless oil; yield: 389 mg (84%).
1H NMR (300 MHz, CDCl3): δ = 4.12 (q, J = 6.0 Hz, 2 H), 3.82–3.77 (m, 2
H), 3.64–3.59 (m, 2 H), 2.80 (s, 2 H), 1.25 (t, J = 6.0 Hz, 3 H), 1.23 (t, J =
6.0 Hz, 6 H).
13C NMR (75 MHz, CDCl3): δ = 167.9, 120.7 (q, J = 288.8 Hz), 97.6 (q, J =
30.8 Hz), 61.0, 58.7 (2 C), 38.4, 15.0 (2 C), 14.0.
19F NMR (282 MHz, CDCl3): δ = –78.1.
HRMS (ESI): m/z [M + H]+ calcd for C10H18F3O4: 259.1157; found:
259.1153 (0.6 ppm).
CO2Et
OEt
Methyl 4,4,4-Trifluoro-3,3-dimethoxybutanoate (2b)
Colorless oil; yield: 260 mg (73%).
4 (40%)
Et-OH
CO2Et
Na (10 mol%)
EtO
CO2Et
OEt
1H NMR (300 MHz, CDCl3): δ = 3.70 (s, 3 H), 3.44 (s, 6 H), 2.82 (s, 2 H).
13C NMR (75 MHz, CDCl3): δ = 167.8, 124.0 (q, J = 289.5 Hz), 97.8 (q, J =
30.0 Hz), 52.2, 50.7 (2 C), 37.6.
Scheme 2 Hydroalkoxylation of ethyl but-2-ynoate
19F NMR (282 MHz, CDCl3): δ = –77.7.
HRMS (ESI): m/z [M + H]+ calcd for C7H12F3O4: 217.06877; found:
217.07082 (11.9 ppm).
Finally, we found that the perfluoroalkyl ketals 2a–m
are extremely unstable under mildly acidic conditions, such
as in the presence of silica gel, and they decompose to form
the vinyl ether, ethyl 4,4,4-trifluoro-3-oxobutanoate, the
starting material, and unidentified products. To avoid such
decomposition on silica gel, the obtained ketals were,
therefore, purified on a neutral alumina column.
In summary, we have developed an efficient, convenient
method for the regioselective double conjugate addition of
alcohols to ethyl 3-(perfluoroalkyl)propynoates to give easy
access to α-perfluorinated ketals. The processes reported
are operationally simple and atom-economical, and employ
mild reaction conditions. Extending the reaction conditions
to other substrates and the conversion of the double
Michael products into other potentially useful compounds
are underway in our laboratory.
Propyl 4,4,4-Trifluoro-3,3-dipropoxybutanoate (2c)
Yellow oil; yield: 351 mg (71%).
1H NMR (300 MHz, CDCl3): δ = 4.04 (t, J =6.0 Hz, 2 H), 3.71–3.66 (m, 2
H), 3.53–3.50 (m, 2 H), 2.83 (s, 2 H), 1.68–1.59 (m, 6 H), 0.95 (t, J = 6.0
Hz, 3 H), 0.92 (t, J = 6.0 Hz, 6 H).
13C NMR (75 MHz, CDCl3): δ = 167.7, 120.8 (q, J = 289.9 Hz), 97.4 (q, J =
30.0 Hz), 66.6, 64.6 (2 C), 38.4, 23.0 (2 C), 22.0, 10.7 (2 C), 10.5.
19F NMR (282 MHz, CDCl3): δ = –77.8.
HRMS (ESI): m/z [M + H]+ calcd for C13H24F3O4: 301.16267; found:
301.16510 (0.05 ppm).
Butyl 3,3-Dibutoxy-4,4,4-trifluorobutanoate (2d)
Yellow oil; yield: 345 mg (62%).
1H NMR (300 MHz, CDCl3): δ = 4.07 (t, J = 6.0 Hz, 2 H), 3.74–3.53 (m, 4
H), 2.81 (s, 2 H), 1.62–1.39 (m, 6 H), 1.38–1.33 (m, 6 H), 0.92 (t, J = 6.0
Hz, 9 H).
13C NMR (75 MHz, CDCl3): δ = 167.7, 120.8 (q, J = 289.9 Hz), 97.9 (q, J =
30.0 Hz), 64.9, 62.8 (2 C), 38.4, 31.3 (2 C), 30.6, 19.3 (2 C), 19.1, 13.9 (2
C), 13.7.
All reactions were carried out under argon atmosphere. Alcohols
were obtained from commercial sources and were used without fur-
ther purification. Et2O was dried and freshly distilled from Na/benzo-
phenone. Column chromatography was performed using Merck neu-
tral alumina (150 mesh).1H (300 MHz), 13C (75 MHz), and 19F (282
MHz) NMR spectra were obtained using a Bruker Avance 300 spec-
trometer relative to residual CHCl3 (δ = 7.26) or DMSO (δ = 2.50) sig-
19F NMR (282 MHz, CDCl3): δ –77.8.
HRMS (ESI): m/z [M + H]+ calcd for C16H30F3O4: 343.20962; found:
343.20910 (0.1 ppm).
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Ethyl 4,4,4-Trifluoro-3,3-bis(prop-2-ynyloxy)butanoate (2e)
1H NMR (300 MHz, CDCl3): δ (minor) = 4.34–4.28 (m, 1 H), 4.27–4.21
(m, 2 H), 4.18 (q, J = 6.0 Hz, 2 H), 2.90 (s, 2 H), 1.34 (d, J = 6.0 Hz, 3 H),
1.28 (t, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ (minor) = 167.2, 122.8 (q, J = 288.7 Hz),
104.4 (q, J = 32.2 Hz), 75.6, 73.5, 61.0, 37.3, 17. 6, 14.1.
Colorless oil; yield: 336 mg (73%).
1H NMR (300 MHz, CDCl3): δ = 4.59 (dd, J = 15.0, 3.0 Hz, 2 H), 4.38 (dd,
J = 15.0, 3.0 Hz, 2 H), 4.19 (q, J = 6.0 Hz, 2 H), 2.90 (s, 2 H), 2.48 (t, J =
3.0 Hz, 2 H), 1.27 (t, J = 6.0 Hz, 3 H).
19F NMR (282 MHz, CDCl3): δ (minor) = –83.6.
13C NMR (75 MHz, CDCl3): δ = 166.2, 122.0 (q, J = 290.2), 98.5 (q, J =
31.5), 78.3 (2 C), 75.4 (2 C), 61.5, 52.4 (2 C), 37.8, 13.6.
Ethyl 2-[2-(Trifluoromethyl)-1,3-dithiolan-2-yl]acetate (2j)
19F NMR (282 MHz, CDCl3): δ = –78.2.
Colorless oil; yield: 102 mg (60%).
1H NMR (300 MHz, CDCl3): δ = 4.18 (q, J = 7.5 Hz, 2 H), 3.40 (s, 4 H),
3.10 (s, 2 H), 1.25 (t, J = 7.5 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C12H14F3O4: 279.0840; found:
279.0840 (0.5 ppm).
Ethyl 4,4,4-Trifluoro-3,3-bis(pent-2-ynyloxy)butanoate (2f)
13C NMR (75 MHz, CDCl3): δ = 167.7, 126.5 (q, J = 277.0 Hz), 66.8 (q, J =
28.5 Hz), 61.0, 41.1, 40.2, 13.1.
19F NMR (282 MHz, CDCl3): δ = –73.6.
HRMS (ESI): m/z [M + H]+ calcd for C8H12F3O2S2: 261.30489; found:
261.02263 (0.39 ppm).
Colorless oil; yield: 308 mg (69%).
1H NMR (300 MHz, CDCl3): δ = 4.53 (dt, J = 15.0, 3.0 Hz, 2 H), 4.33 (dt,
J = 15.0, 3.0 Hz, 2 H), 4.15 (q, J = 6.0 Hz, 2 H), 2.88 (s 2 H), 2.27–2.17
(m, 4 H), 1.26 (t, J = 6.0 Hz, 3 H), 1.14 (t, J = 6.0 Hz, 6 H).
13C NMR (75 MHz, CDCl3): δ = 166.6, 122.1 (q, J = 281.2 Hz), 98.3 (q, J =
26.3 Hz), 88.6 (2 C), 74.1 (2 C), 61.2, 52.7 (2 C), 38.1, 14.0 (2 C), 12.5,
12.4 (2 C).
19F NMR (282 MHz, CDCl3): δ = –78.0.
HRMS (ESI): m/z [M + H]+ calcd for C16H22F3O4: 335.1470; found:
Ethyl 3,3-Diethoxy-4,4,5,5,5-pentafluoropentanoate (2k)
Golden oil; yield: 246 mg (71%).
1H NMR (300 MHz, CDCl3): δ = 4.14 (q, J = 7.2 Hz, 2 H), 3.84–3.59 (m, 4
H), 2.90 (s, 2 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.22 (t, J = 7.0 Hz, 6 H).
13C NMR (75 MHz, DMSO-d6): δ = 167.5, 118.8 (tq, J = 285.0, 34.5 Hz),
115.1 (qt, J = 268.5, 35.2 Hz), 98.6 (t, J = 22.5), 61.0, 59.4 (2 C), 38.1,
14.8, 13.9 (2 C).
335.1466 (0.4 ppm).
Ethyl 2-[2-(Trifluoromethyl)-1,3-dioxolan-2-yl]acetate (2g)
19F NMR (282 MHz, CDCl3): –79.7, –121.1.
Colorless oil; yield: 153 mg (68%).
1H NMR (300 MHz, CDCl3): δ = 4.22–4.17 (m, 4 H), 4.15 (q, J = 6.0 Hz, 2
H), 2.87 (s, 2 H), 1.25 (t, J = 6.0 Hz, 3 H).
HRMS (ESI) m/z [M + Na]+ calcd for C11H17F5O4Na: 331.09447; found:
331.09344 (–1.44427 ppm).
13C NMR (75 MHz, CDCl3): δ = 167.1, 120.8 (q, J = 288.0 Hz), 104.2 (q,
J = 30.1 Hz), 67.3 (2 C), 60.9, 37.0, 14.0.
19F NMR (282 MHz, CDCl3): δ = –83.5.
Methyl 4,4,5,5,5-Pentafluoro-3,3-dimethoxypentanoate (2l)
Yellow solid; yield: 185 mg (68%); mp 90–92 °C.
1H NMR (300 MHz, CDCl3): δ = 3.60 (s, 3 H), 3.40 (s, 6 H), 3.04 (s, 2 H).
HRMS (ESI): m/z [M + H]+ calcd for C8H12F3O4: 229.17369; found:
13C NMR (75 MHz, CDCl3): δ = 167.2, 118.3 (tq, J = 272.0, 33.2 Hz),
115.2 (qt, J = 286.0, 33.3 Hz), 98.9 (t, J = 22. 5 Hz), 51.6 (2 C), 51.0,
36.0.
229.06822 (0.02 ppm).
Ethyl 2-[2-(Trifluoromethyl)-1,3-dioxan-2-yl]acetate (2h)
19F NMR (282 MHz, CD3Cl): δ = –79.1, –120.1.
Colorless oil; yield: 124 mg (56%).
1H NMR (300 MHz, CDCl3): δ = 4.12 (q, J = 6.0 Hz, 2 H), 4.08–4.02 (m, 4
H), 2.77 (s, 2 H), 1.75–169 (m, 2 H), 1.22 (t, J = 6.0 Hz, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C8H11F5O4Na: 289.04752; found:
289.04674 (–0.78793 ppm).
13C NMR (75 MHz, CDCl3): δ = 167.3, 121.1 (q, J = 291.0), 94.5 (q, J =
30.5 Hz), 61.7 (2 C), 60.9, 38.4, 23.6, 14.1.
19F NMR (282 MHz, CDCl3): δ = –78.7.
Ethyl 4,4,5,5,5-Pentafluoro-3,3-bis(prop-2-ynyloxy)pentanoate
(2m)
Yellow oil; yield: 283 mg (70%).
HRMS (ESI): m/z [M + H]+ calcd for C9H14F3O4: 243.20027; found:
1H NMR (300 MHz, CDCl3): δ = 4.64 (dt, J = 15.0, 3.0 Hz, 2 H), 4.43 (dt,
J = 15, 3.0 Hz, 2 H), 4.18 (q, J = 6.0 Hz, 2 H), 2.99 (s, 2 H), 2.49 (t, J = 3.0
Hz, 2 H), 1.27 (t, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 166.6, 118.4 (tq, J = 288.7, 34.5 Hz),
114.6 (qt, J = 266.2, 36.5 Hz), 99.0 (t, J = 23.2 Hz), 78.3 (2 C), 75.4 (2 C),
61.3, 52.7 (2 C), 38.2, 13.8.
243.08374 (–0.54 ppm).
Ethyl 2-[4-Methyl-2-(trifluoromethyl)-1,3-dioxolan-2-yl]acetate
(2i)
Colorless oil; yield: 244 mg (57%); mixture of two diastereomer in a
ratio ca. 60:40.
HRMS (ESI): m/z [M + H]+ calcd for C9H14F3O4: 243.20027; found:
19F NMR (282 MHz, CDCl3): δ = –79.6, –121.7.
HRMS (ESI): m/z [M + Na]+ calcd for C13H13F5O4Na: 351.06317; found:
243.08374 (–0.54 ppm).
1H NMR (300 MHz, CDCl3): δ (major) = 4.56–4.52 (m, 1 H), 4.17 (q, J =
6.0 Hz, 2 H), 3.71–3.61 (m, 2 H), 2.86 (s, 2 H), 1.33 (d, J = 6.0 Hz, 3 H),
1.27 (t, J = 6.0 Hz, 3 H).
351.06221 (–1.17359 ppm).
Acknowledgment
13C NMR (75 MHz, CDCl3): δ (major) = 167.4, 122.6 (q, J = 287.2 Hz),
104.5 (q, J = 31.9 Hz), 75.7, 73.1, 61.0, 37.4, 17.4, 14.2.
19F NMR (282 MHz, CDCl3): δ (major) = –83.8.
We thank the ‘Département d’analyses Chimiques et Médicales’
(Tours, France) for chemical analyses.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2635–2640

2640
E. Ndong et al.
Paper
Synthesis
Supporting Information
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Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380753.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2635–2640