Condensation of the dianion of ethyl acetoacetate with perfluoroalkyl iodides. Application to the synthesis of 3-perfluoroalkylsalicylic acids

Article abstract of DOI:10.1007/s00706-013-0985-8

3-Perfluoroalkylsalicylic esters and acids were prepared based on the condensation of the dianion of ethyl acetoacetate with various perfluoroalkyl iodides. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-013-0985-8

Monatsh Chem (2013) 144:1057–1061
DOI 10.1007/s00706-013-0985-8
ORIGINAL PAPER
Condensation of the dianion of ethyl acetoacetate
with perfluoroalkyl iodides. Application to the synthesis
of 3-perfluoroalkylsalicylic acids
•
Constantin Mamat Peter Langer
Received: 11 December 2012 / Accepted: 27 March 2013 / Published online: 17 May 2013
Ó Springer-Verlag Wien 2013
Abstract 3-Perfluoroalkylsalicylic esters and acids were
prepared based on the condensation of the dianion of ethyl
acetoacetate with various perfluoroalkyl iodides.
demonstrated [20]. Haufe and coworkers reported the
synthesis of polyfluoroalkyl-containing pyrones, pyridines,
and pyrido [1,2-a]benzazoles from fluorinated b-alkoxye-
nones [21]. They also applied fluoroalkyl-substituted
enones as dienophiles in Diels–Alder reactions [22]. In
recent years, we developed a synthesis path to trifluoro-
methyl and perfluoroalkyl substituted arenes based on
cyclization reactions of (non-fluorinated) 1,3-bis(trimeth-
ylsilyloxy)-1,3-butadienes, masked 1,3-dicarbonyl dianions
(for a review of 1,3-bis(silyl enol ethers), see [23–25], for a
review of [3 ? 3] cyclizations of 1,3-bis(silyl enol ethers),
see: [26]), with trifluoromethyl and perfluoroalkyl substi-
tuted enones, respectively (for a review of the synthesis of
fluorinated molecules based on cyclization reactions of 1,3-
bis(silyl enol ethers), see [27]). We also reported cycliza-
tion reactions of 1-trifluoromethyl- and 1-perfluoroalkyl-
1,3-bis(trimethylsilyloxy)-1,3-butadienes derived from the
corresponding 1,3-diketones [28, 29]. Due to the low
nucleophilicity of these dienes, the cyclizations were
restricted to the use of highly electrophilic oxalyl chloride.
Herein, we report what are, to the best of our knowledge,
the first condensations of 1,3-dicarbonyl dianions with
perfluoroalkyl iodides to give novel perfluoroalkylated
b-ketoester. The latter were transformed to 1-methoxy-
4-perfluoroalkyl-1,3-bis(trimethylsilyloxy)-1,3-butadienes,
which are structurally new as they contain the perfluoro-
alkyl group at a different position as compared to our
previously reported 1-perfluoroalkyl-1,3-bis(trimethylsi-
lyloxy)-1,3-butadienes [29].
Keywords Dianions Á Condensation Á
Organofluorine compounds Á Arenes Á
Cyclizations Á Regioselectivity
Introduction
Perfluoroalkyl-substituted compounds are of considerable
importance in medicinal chemistry, as liquid crystals, and
as ligands and organocatalysts in fluorous biphase systems
[1–15]. Previously, (perfluoroalkyl)arenes have been pre-
pared by reaction of iodoarenes with (perfluoroalkyl)-
cuprates [16]. Portella et al. reported the synthesis of ortho-
perfluoroalkylphenones from hemifluorinated enones [17].
Perfluoroalkylated heterocycles have been prepared by
reactions of perfluoroketene dithioacetals, perfluorodi-
thiocarboxylic acid derivatives [18], and c-ketothioesters
[19]. In addition, the cyclocondensation of carboxylic
acid dianions with perfluoroketene dithioacetals has been
C. Mamat Á P. Langer (&)
¨
Institut fu¨r Chemie, Universitat Rostock, Albert Einstein Str. 3a,
18059 Rostock, Germany
e-mail: peter.langer@uni-rostock.de
C. Mamat
Institut fu¨r Radiopharmazeutische Krebsforschung,
Helmholtz-Zentrum Dresden-Rossendorf,
Bautzner Landstr.400, 01328 Dresden, Germany
Results and discussion
P. Langer
Leibniz-Institut fu¨r Katalyse an der Universitat Rostock e.V.,
The reaction of the dianion of ethyl acetoacetate (1),
generated by means of two equivalents of lithium
¨
Albert Einstein Str. 29a, 18059 Rostock, Germany
123

1058
C. Mamat, P. Langer
diisopropylamide (LDA), with 1-iodo-1H,1H,2H,2H-per-
fluoralkanes 2a–2d afforded the perfluoroalkylated b-
ketoesters 3a–3d (Scheme 1). The ethylene spacer of 2a–
2d was necessary because completely perfluorinated io-
dalkanes do not undergo nucleophilic displacement
reactions due to the electron withdrawing effect of fluorine
[30–32]. The silylation of 3a–3d produced mono-silylated
enol ethers 4a–4d, which were subsequently transformed to
dienes 5a–5d. The latter were directly subjected to the
TiCl4 mediated cyclization with 1,1,3,3-tetramethoxypro-
pane. While the cyclizations of dienes 5a–5c afforded the
desired salicylates 6a–6c, the employment of 5d, contain-
ing the longest perfluoroalkyl group, proved to be
unsuccessful due to its low solubility and precipitation in
CH2Cl2 at -78 °C. After aqueous workup, only unknown
by-products were isolated. Hydrolysis of 6b and 6c affor-
ded salicylic acids 7b and 7c, respectively (Table 1).
In conclusion, we have reported a new strategy for the
synthesis of 3-perfluoroalkylsalicylic esters and acids based
on the condensation of the perfluoroalkyl-functionalized
dianion of ethyl acetoacetate.
Table 1 Products and yields
3–7
n
3/%a
6/%a
7/%a
a
b
c
d
a
4
47
63
63
46
33
60
74
–
6
8
61
45
–
b
–
10
Yields of isolated products
b
Low solubility of the starting material
spectrometer. Mass spectrometric data (MS) were obtained
by electron impact ionization (EI, 70 eV). Chromato-
graphic separations were carried out with Merck silica gel
60 (63–200 mesh) and analytical TLC was made using
Merck silica gel 60 F254 sheets with visualization under
UV light (k = 254 nm). All cyclization reactions were
carried out in Schlenk tubes under an argon atmosphere
using dried solvents. The appropriate enol ethers were
prepared as described in the literature [23, 24].
General procedure for the synthesis of b-ketoesters
3a–3d
Experimental
A tetrahydrofuran (THF) solution of LDA was prepared by
addition of n-butyllithium (2.3 equiv., 2.5 M in n-hexane)
to a solution of diisopropylamine (2.3 equiv.) in THF. To
this solution we added ethyl acetoacetate (1 equiv.) at 0 °C.
The deep yellow, clear solution was stirred at 0 °C for 1 h.
We then added the alkyl halide (1 equiv.) at -78 °C. The
solution was allowed to rise to ambient temperature over
14 h and the solution was stirred at room temperature for
2 h. Hydrochloric acid (200 cm3, 10 %) was added to the
solution and the mixture was extracted with diethyl ether
(4 9 250 cm3). The combined organic layers were dried over
Na2SO4, filtered, and the solvent of the filtrate was removed in
vacuo. The residue was purified by chromatography (silica
gel, n-heptane/EtOAc = 20:1 ? 10:1) to give 3a–3d.
1H and 13C NMR spectra were measured in CDCl3 at 250,
300, and 500 MHz, respectively. Chemical shifts are
reported in parts per million using the solvent internal
1
standard (chloroform, 7.26 ppm for H and 77.0 ppm for
13C). Infrared spectra were recorded on
a FT-IR
Scheme 1
O
O
O
O
OEt
I
i
1
F2n+1Cn
OEt
OEt
+
F2n+1Cn
3a-d
ii
2a-d
Ethyl 7,7,8,8,9,9,10,10,10-nonafluoro-3-oxodecanoate
(3a, C12H13F9O3)
Me3SiO
O
iii
Me3SiO
OSiMe3
OEt
F2n+1Cn
Starting with 3.11 g of diisopropylamine (30.8 mmol),
12.3 cm3 of n-butyllithium (2.5 M, 30.8 mmol), 1.91 g of
ethyl acetoacetate (14.7 mmol), and 5.00 g of 1,1,1,2,2,
3,3,4,4-nonafluoro-6-iodohexane (13.4 mmol), 3a was iso-
lated after column chromatography as a colorless oil
(2.34 g, 47 %). Rf = 0.37 (n-heptane/EtOAc = 1:1); 1H
F2n+1Cn
4a-d
5a-d
OMeOMe
OMe
iv
MeO
OH
OH
O
O
3
F2n+1Cn
F2n+1Cn
v
NMR (250 MHz, CDCl3): d = 4.20 (q, 2H, J = 7.1 Hz,
OH
OEt
OCH2CH3), 3.44 (s, 2H, H-2), 2.69 (t, 2H, 3J = 6.7 Hz, H-
3
4), 1.84–2.25 (m, 4H, H-5, H-6), 1.28 (t, 3H, J = 7.1 Hz,
7a-d
6a-d
OCH2CH3) ppm; 13C NMR (63 MHz, CDCl3): d = 201.3
(C-3), 167.0 (C-1), 61.5 (OCH2CH3), 49.2 (C-2), 41.4 (C-
i: LDA, THF, -78 to 20 °C; ii: Me3SiCl, NEt3, n-pentane, 20 °C;
iii: 1) LDA, THF, -78 °C, 1 h, 2) Me3SiCl; iv: TiCl4, tetramethoxypropane,
CH2Cl2, -78 to 20 °C; v: NaOH, H2O, EtOH, 20 °C.
3
4), 29.6 (t, JC,F = 21.9 Hz, C-6), 14.3 (t, JC,F = 4.3 Hz,
4
123

Condensation of the dianion of ethyl acetoacetate with perfluoroalkyl iodides
1059
C-5), 13.9 (OCH2CH3) ppm; 19F NMR (235 MHz, CDCl3):
2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-henicosafluoro-12-iodo-
dodecane (7.42 mmol), 3d was isolated after column
chromatography as a colorless solid (2.33 g, 46 %). M.p.:
56 °C; Rf = 0.39 (n-heptane/EtOAc = 1:1); 1H NMR
(250 MHz, CDCl3): d = 4.20 (q, 2H, 3J = 7.2 Hz,
d = -81.0 (CF3), -114.6 (CH2CF2), -121.8, -124.4
ꢀ
(CF2), -126.1 (CF2CF3) ppm; IR (neat): m = 1,746
(COOEt), 1,720 (C=O) cm-1; MS (EI, 70 eV): m/z =
376 (M?), 330 (M?-OCH2CH3); HRMS (EI): calcd. for
C12H13F9O3 (M?) 376.0716, found 376.0709.
3
OCH2CH3), 3.44 (s, 2H, H-2), 2.69 (t, 2H, J = 6.7 Hz,
H-4), 1.84–2.25 (m, 4H, H-5, H-6), 1.28 (t, 3H, 3J =
7.2 Hz, OCH2CH3) ppm; 13C NMR (63 MHz, CDCl3):
d = 201.5 (C-3), 167.1 (C-1), 61.7 (OCH2CH3), 49.4
Ethyl 7,7,8,8,9,9,10,10,11,11,12,12,12-tridecafluoro-3-
oxododecanoate (3b, C14H13F13O3)
Starting with 2.46 g of diisopropylamine (24.3 mmol),
15.2 cm3 of n-butyllithium (1.6 M, 24.3 mmol), 1.37 g of
ethyl acetoacetate (10.5 mmol), and 5.00 g of 1,1,1,2,2,3,3,
4,4,5,5,6,6-tridecafluoro-8-iodooctane (10.5 mmol), 3b
was isolated after column chromatography as a colorless
oil (3.17 g, 63 %). Rf = 0.53 (n-heptane/EtOAc = 1:1);
1H NMR (250 MHz, CDCl3): d = 4.20 (q, 2H,
3J = 7.0 Hz, OCH2CH3), 3.44 (s, 2H, H-2), 2.69 (t, 2H,
3J = 6.7 Hz, H-4), 1.85–2.24 (m, 4H, H-5, H-6), 1.28 (t,
3H, 3J = 7.0 Hz, OCH2CH3) ppm; 13C NMR (63 MHz,
CDCl3):d = 201.5(C-3), 167.1(C-1),61.7(OCH2CH3),49.4
(C-2), 41.6 (C-4), 29.9 (t, 3JC,F = 22.3 Hz, C-6), 14.7 (C-5),
14.4 (OCH2CH3) ppm; 19F NMR (235 MHz, CDCl3): d =
-80.7 (CF3), -114.3 (CH2CF2), -121.8, -122.8, -123.4
3
(C-2), 41.6 (C-4), 29.9 (t, JC,F = 22.3 Hz, C-6), 14.5
(t, 3JC,F = 22.3 Hz, C-5), 14.1 (OCH2CH3) ppm; 19F NMR
(235 MHz, CDCl3): d = -80.5 (CF3), -114.2 (CH2CF2),
-121.4, -122.4, -123.2 (CF2), -125.8 (CF2CF3) ppm; IR
(Nujol): m = 1,744 (COOEt), 1,713 (C=O) cm-1; MS (EI,
ꢀ
70 eV): m/z = 676 (M?), 631 (M?-OEt); HRMS (EI):
calcd. for C18H13F21O3 (M?) 676.0524, found 676.0521.
General procedure for the synthesis of silyl enol ethers
4a–4d
To a pentane solution of b-ketoester 3a–3d (1.0 equiv.) we
added NEt3 (1.5 equiv.). After stirring for 1 h at 20 °C,
TMSCl (1.5 equiv.) was then added dropwise at 20 °C.
After stirring for 48 h, the precipitated salts were filtered
and the filtrate was concentrated in vacuo to give 4a–4d.
Due to their lability, the products were directly used
without purification and characterization for the next step.
ꢀ
(CF2), -126.0 (CF2CF3) ppm; IR (neat): m = 1,744 (COOEt),
1,719 (C=O)cm-1; MS (EI, 70 eV): m/z = 476 (M?), 431
(M?-OCH2CH3), 389 (M?-CH2C(O)OCH2CH3).
Ethyl 7,7,8,8,9,9,10,10,11,11,12,12,13,13,14,14,14-hepta-
decafluoro-3-oxotetradecanoate (3c, C16H13F17O3)
Starting with 2.03 g of diisopropylamine (20.0 mmol),
8.0 cm3 of n-butyllithium (1.6 M, 19.8 mmol), 1.13 g of
ethyl acetoacetate (8.71 mmol), and 5.00 g of 1,1,1,2,2,3,3,
General procedure for the synthesis of 1,3-bis(silyl enol
ethers) 5a–5d
4,4,5,5,6,6,7,7,8,8-heptadecafluoro-10-iododecane
(8.71
To a THF solution of LDA, prepared by addition of
n-butyllithium (1.5 equiv., 1.6 M in hexane) to a THF
solution of diisopropylamine (1.5 equiv.) at 0 °C and stir-
ring for 20 min, we added a THF solution of 4a–4d (1.0
equiv.) at -78 °C. After stirring for 1 h at -78 °C, we then
added TMSCl (1.5 equiv.). The solution was allowed to
rise to ambient temperature over 2 h and was then stirred
for 1 h at 20 °C. The solvent was removed in vacuo and n-
hexane was added to the residue. The precipitated lithium
chloride was removed by filtration under inert conditions
and the solvent of the filtrate was removed in vacuo to give
5a–5d. Due to their lability, the products were directly used
without purification and characterization for the next step.
mmol), 3c was isolated after column chromatography as a
colorless solid (3.17 g, 63 %). M.p.: 32.5 °C; Rf = 0.53 (n-
heptane/EtOAc); 1H NMR (250 MHz, CDCl3): d = 4.19 (q,
2H, 3J = 7.1 Hz, OCH2CH3), 3.43 (s, 2H, H-2), 2.69 (t, 2H,
3J = 6.7 Hz, H-4), 1.84–2.24 (m, 4H, H-5, H-6), 1.27 (t, 3H,
3J = 7.1 Hz, OCH2CH3) ppm; 13C NMR (63 MHz, CDCl3):
d = 201.5 (C-3), 167.1 (C-1), 61.7 (OCH2CH3), 49.4 (C-2),
3
41.6 (C-4), 29.9 (t, JC,F = 22.3 Hz, C-6), 14.5 (C-5), 14.1
(OCH2CH3) ppm; 19F NMR (235 MHz, CDCl3): d = -80.7
(CF3), -114.3 (CH2CF2), -121.8, -122.6, -123.3 (CF2),
ꢀ
-126.0 (CF2CF3) ppm; IR (neat): m = 1,742 (COOEt), 1,713
(C=O) cm-1; MS (EI, 70 eV): m/z = 576 (M?), 531 (M?-
OCH2CH3); HRMS (EI): calcd. for C16H13F17O3 (M?)
576.0588, found 576.0579.
General procedure for the synthesis of 6a–6d
Ethyl 7,7,8,8,9,9,10,10,11,11,12,12,13,13,14,14,15,15,16,
16,16-henicosafluoro 3-oxo-hexadecanoate
(3d, C18H13F21O3)
To a CH2Cl2 solution of 1,3-bis(silyl enol ether) 5a–5d (1
equiv.) and 1,1,3,3-tetramethoxypropane (1.03 equiv.) we
added TiCl4 (1 equiv.) at -78 °C under argon atmosphere.
The temperature of this mixture was allowed to rise to
20 °C over 14 h. Afterwards, we added aqueous HCl
solution (10 %, 10 cm3), separated out the organic layer,
Starting with 1.73 g of diisopropylamine (17.1 mmol),
6.83 cm3 of n-butyllithium (2.5 M, 17.1 mmol), 1.06 g
of ethyl acetoacetate (8.2 mmol), and 5.00 g of 1,1,1,2,
123

1060
C. Mamat, P. Langer
and extracted the residue with CH2Cl2 (3 9 10 cm3). The
combined organic layers were dried (Na2SO4), filtered and
the filtrate was concentrated in vacuo. The residue was
purified by column chromatography (silica gel, n-heptane/
EtOAc = 50:1 ? 20:1).
TiCl4 (1.38 mmol), we isolated 6c as a colorless solid
(627 mg, 74 %). M.p.: 57 °C; Rf = 0.85 (n-heptane/
1
EtOAc = 2:3); H NMR (250 MHz, CDCl3): d = 11.19
(s, 1H, OH), 7.78 (dd, 1H, J5,6 = 7.9 Hz, J4,6 = 1.7 Hz,
3
4
3
4
H-6), 7.34 (dd, 1H, J4,5 = 7.3 Hz, J4,6 = 1.4 Hz, H-4),
6.83 (dd, 1H, 3J4,5 = 7.3 Hz, 3J5,6 = 7.9 Hz, H-5), 4.41 (q,
2H, 3J = 7.0 Hz, OCH2CH3), 2.92–3.00 (m, 2H, H-1’),
2.30–2.55 (m, 2H, H-2’), 1.42 (t, 3H, 3J = 7.0 Hz,
OCH2CH3) ppm; 13C NMR (63 MHz, CDCl3): d = 170.6
(C=O), 160.0 (C-2), 136.0 (C-4), 128.8 (C-6), 127.7 (C-3),
118.9 (C-5), 112.7 (C-1), 61.6 (OCH2CH3), 30.6 (t,
Ethyl 3-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)salicylate
(6a, C15H13F9O3)
Starting with 0.14 cm3 of 1,1,3,3-tetramethoxypropane
(0.84 mmol), 312 mg of 5a (0.6 mmol), and 0.07 cm3 of
TiCl4 (0.6 mmol), 6a was isolated as a colorless oil
(81 mg, 33 %). Rf = 0.55 (n-heptane/EtOAc = 1:1); 1H
NMR (250 MHz, CDCl3): d = 11.18 (s, 1H, OH), 7.78
3
2JC,F = 22.9 Hz, C-2’), 21.8 (t, JC,F = 4.4 Hz, C-1’),
14.3 (OCH2CH3) ppm; 19F NMR (235 MHz, CDCl3):
d = -80.5 (CF3), -114.5 (CH2CF2), -121.7, -122.5,
-123.3, (CF2), -125.9 (CF2CF3) ppm; IR (Nujol):
3
4
(dd, 1H, J5,6 = 8.1 Hz, J4,6 = 1.6 Hz, H-6), 7.34 (dd,
3
4
1H, J4,5 = 7.5 Hz, J4,6 = 1.6 Hz, H-4), 6.83 (dd, 1H,
3J4,5 = 7.5 Hz, J5,6 = 8.1 Hz, H-5), 4.41 (q, 2H,
3
m = 3,199 (OH), 1,685 (C=O) cm-1; MS (70 eV):
ꢀ
3J = 7.3 Hz, OCH2CH3), 2.96 (dt, 2H, H-1’), 2.30–2.55
m/z = 612 (M?), 566 (M?-HOEt).
3
(m, 2H, H-2’), 1.42 (t, 3H, J = 7.3 Hz, OCH2CH3) ppm;
13C NMR (63 MHz, CDCl3): d = 170.6 (C=O), 160.0
(C-2), 136.0 (C-4), 128.8 (C-6), 127.6 (C-3), 118.9 (C-5),
3-(3,3,4,4,5,5,6,6,7,7,8,8,8-Tridecafluorooctyl)salicylic
acid (7b, C15H9F13O3)
2
112.5 (C-1), 61.7 (OCH2CH3), 30.5 (t, JC,F = 22.0 Hz,
A solution of 259 mg 6b (0.51 mmol) and 70 mg NaOH
(1.75 mmol) in 20 cm3 of EtOH were stirred under reflux
for 4–5 h. After cooling to room temperature, the solution
was acidified to pH 1 by addition of conc. hydrochloric
acid. We added 10 cm3 of water to the solution and
extracted the mixture using diethyl ether (3 9 20 cm3).
The combined organic layers were dried (Na2SO4), filtered,
and the filtrate was concentrated in vacuo. The residue was
purified by chromatography (silica gel, n-heptane/
EtOAc = 1:1) to give 7b as a colorless solid (150 mg,
61 %). M.p.: 120 °C; Rf = 0.2 (n-heptane/EtOAc = 2:3);
1H NMR (250 MHz, CDCl3): d = 10.72 (s, 1H, OH), 7.86
3
C-2’), 21.7 (t, JC,F = 4.4 Hz, C-1’), 14.3 (OCH2CH3)
ppm; 19F NMR (235 MHz, CDCl3): d = -80.8 (CF3),
-114.7 (CH2CF2), -124.3 (CF2), -125.8 (CF2CF3) ppm;
IR (neat): m = 3,139 (OH), 1,674 (C=O) cm-1; MS (EI,
ꢀ
70 eV): m/z = 412 (M?), 366 (M?-HOEt); HRMS (EI):
calcd. for C15H13F9O3 (M?) 412.07155, found 412.072366.
Ethyl 3-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)salicy-
late (6b, C17H13F13O3)
Starting with 130 mg of 1,1,3,3-tetramethoxypropane
(0.8 mmol), 390 mg of 5b (0.8 mmol), and 0.69 cm3 of
TiCl4 (6.3 mmol), we isolated 6b as a colorless solid
(245 mg, 60 %). M.p.: 41 °C; Rf = 0.8 (n-heptane/
3
4
(dd, 1H, J5,6 = 8.1 Hz, J4,6 = 1.7 Hz, H-6), 7.43 (dd,
3
4
1H, J4,5 = 7.3 Hz, J4,6 = 1.7 Hz, H-4), 6.90 (t, 1H,
3J4,5 = 7.3 Hz, 3J5,6 = 8.1 Hz, H-5), 2.92–3.03 (m, 2H, H-
1’), 2.31–2.56 (m, 2H, H-2’) ppm; 13C NMR (63 MHz,
CDCl3): d = 174.6 (C=O), 160.5 (C-2), 137.4 (C-4), 129.8
(C-6), 128.0 (C-3), 119.5 (C-5), 111.3 (C-1), 30.6 (t,
1
EtOAc = 2:3); H NMR (250 MHz, CDCl3): d = 11.19
3
4
(s, 1H, OH), 7.78 (dd, 1H, J5,6 = 8.0 Hz, J4,6 = 1.5 Hz,
3
4
H-6), 7.34 (dd, 1H, J4,5 = 7.3 Hz, J4,6 = 1.5 Hz, H-4),
6.83 (dd, 1H, 3J4,5 = 7.3 Hz, 3J5,6 = 8.0 Hz, H-5), 4.41 (q,
3
2H, J = 7.0 Hz, OCH2CH3), 2.96 (dt, 2H, H-1’), 2.30–
3
2JC,F = 22.3 Hz, C-2’), 21.7 (t, JC,F = 4.7 Hz, C-1’)
3
2.55 (m, 2H, H-2’), 1.42 (t, 3H, J = 7.0 Hz, OCH2CH3)
ppm; 19F NMR (235 MHz, CDCl3): d = -80.5 (CF3),
-114.5 (CH2CF2), -121.6, -122.6, -123.3 (CF2), -125.8
ppm; 13C NMR (63 MHz, CDCl3): d = 170.6 (C=O),
160.0 (C-2), 136.0 (C-4), 128.8 (C-6), 127.6 (C-3), 118.9
(C-5), 112.7 (C-1), 61.7 (OCH2CH3), 30.6 (t,
ꢀ
(CF2CF3) ppm; IR (Nujol): m = 3,200 (OH), 1,645 (C=O)
cm-1; MS (70 eV): m/z = 484 (M?), 466 (M?-H2O).
3
2JC,F = 21.7 Hz, C-2’), 21.7 (t, JC,F = 4.7 Hz, C-1’),
14.3 (OCH2CH3) ppm; 19F NMR (235 MHz, CDCl3):
d = -80.5 (CF3), -114.5 (CH2CF2), -121.6, -122.6,
-123.3 (CF2), -125.9 (CF2CF3) ppm; IR (Nujol):
3-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-Heptadecafluorode-
cyl)salicylic acid (7c, C15H9F17O3)
The synthesis was carried out following the procedure
given for the synthesis of 7b. Starting with 300 mg 6c
(0.49 mmol) and 70 mg NaOH (1.75 mmol) in 20 cm3 of
EtOH, we isolated 7c as a colorless solid (130 mg, 45 %).
M.p.: 138 °C; Rf = 0.1 (n-heptane/EtOAc = 2:3); 1H
NMR (250 MHz, CDCl3): d = 10.72 (s, 1H, OH), 7.72
m = 3,194 (OH), 1,679 (C=O) cm-1; MS (70 eV):
ꢀ
m/z = 512 (M?), 466 (M?-HOEt).
Ethyl 3-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecaflu-
orodecyl)salicylate (6c, C19H13F17O3)
3
3
Starting with 227 mg of 1,1,3,3-tetramethoxypropane
(1.38 mmol), 1.00 g of 5c (1.38 mmol), and 0.15 cm3 of
(d, 1H, J5,6 = 7.9 Hz, H-6), 7.26 (d, 1H, J4,5 = 7.5 Hz,
3
H-4), 6.75 (t, 1H, J4,5 = 7.5 Hz, J5,6 = 7.9 Hz, H-5),
3
123

Condensation of the dianion of ethyl acetoacetate with perfluoroalkyl iodides
1061
¨
11. Schwabisch D, Wille S, Hein M, Miethchen R (2004) Liq
Crystals 31:1143
2.80–2.93 (m, 2H, H-1’), 2.21–2.47 (m, 2H, H-2’) ppm;
13C NMR (63 MHz, CDCl3): d = 172.8 (C=O), 160.0 (C-
2), 135.7 (C-4), 129.4 (C-6), 127.1 (C-3), 118.7 (C-5), 30.5
12. Nicoletti M, Bremer M, Kirsch P, O’Hagan D (2007) Chem
Commun 47:5075
¨
13. Kirsch P, Hahn A, Frohlich R, Haufe G (2006) Eur J Org Chem
4819
14. Schneider S, Tzschucke CC, Bannwarth W (2005). In: Cornils B,
Herrmann WA, Horvath IT, Leitner W, Mecking S, Olivier-
Booubigou H, Vogt D (eds), Multiphase Homogeneous Catalysis.
Wiley-VCH, Weinheim, chapter 4.2, p 346
15. Clarke D, Ali MA, Clifford AA, Parratt A, Rose P, Schwinn D,
Bannwarth W, Rayner CM (2004) Curr Top Med Chem 7:729
16. Burton DJ, Yang Z (1992) Tetrahedron 48:189
17. Chanteau F, Plantier-Royon R, Haufe G, Portella C (2006) Tet-
rahedron 62:9049
2
(t, JC,F = 22.3 Hz, C-2’), 21.5 (C-1’) ppm; 19F NMR
(235 MHz, CDCl3): d = -80.8 (CF3), -114.7 (CH2CF2),
-121.8, -122.6, -123.4 (CF2), -126.1 (CF2CF3) ppm; IR
(Nujol): ꢀm = 3,169 (OH), 3,110 (OH), 1,666 (C=O) cm-1
;
MS (70 eV): m/z = 584 (M?), 566 (M?-H2O); HRMS
(EI): calcd. for C17H9F17O3 (M?) 584.0275, found
584.0260.
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123