Stereoselective synthesis of (Z)-β-fluoro-α, β -unsaturated esters from (Z)-2-fluoro-1-alkenyliodonium salts

Article abstract of DOI:10.1016/j.jfluchem.2003.11.025

(Z)-β-Fluoro-α,β-unsaturated esters were stereoselectively synthesized from (Z)-2-fluoro-1-alkenyliodonium salts by the Pd-catalyzed methoxycarbonylation reaction. The reaction proceeded at room temperature and various functional groups on the substrate c

Full text of DOI:10.1016/j.jfluchem.2003.11.025

Journal of Fluorine Chemistry 125 (2004) 527–529
Stereoselective synthesis of (Z)-b-fluoro-a,b-unsaturated esters
from (Z)-2-fluoro-1-alkenyliodonium salts
Masanori Yoshida, Ayumu Komata, Shoji Hara*
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Received 12 October 2003; accepted 17 November 2003
Abstract
(Z)-b-Fluoro-a,b-unsaturated esters were stereoselectively synthesized from (Z)-2-fluoro-1-alkenyliodonium salts by the Pd-catalyzed
methoxycarbonylation reaction. The reaction proceeded at room temperature and various functional groups on the substrate can tolerate the
reaction conditions.
# 2004 Elsevier B.V. All rights reserved.
Keywords: (Z)-2-fluoro-1-alkenyliodonium salts; (Z)-b-fluoro-a,b-unsaturated esters; Methoxycarbonylation reaction; Pd catalyst
1. Introduction
2. Results and discussion
a-Fluoro-a,b-unsaturated esters have been used as build-
ing blocks or key intermediates for the synthesis of the
fluorinated analogs of natural compounds having a fluorine
atom on their double bonds because they can be stereo-
selectively prepared by the Horner–Wadsworth–Emmons
reaction using ethyl 2-fluorodiethylphosphonoacetate [1–8].
On the other hand, only few methods had been reported
for the stereoselective synthesis of b-fluoro-a,b-unsaturated
esters [9]. Recently, we reported the stereoselective synth-
esis of (E)-isomer of b-fluoro-a,b-unsaturated esters by
methoxycarbonylation of (E)-2-fluoro-1-alkenyliodonium
salts obtained from 1-alkynes and iodotoluene difluoride
[10,11]. However, the stereoselective synthesis of the (Z)-
isomer of b-fluoro-a,b-unsaturated esters still remained
undeveloped. Quite recently, we found that (Z)-2-fluoro-1-
alkenyliodonium salts (1) can be stereoselectively prepared
from 1-alkynyl(phenyl)iodonium salts [12]. We now report
here the stereoselective synthesis of the (Z)-isomer of
b-fluoro-a,b-unsaturated esters (2) from the (Z)-2-fluoro-
1-alkenyliodonium salts (1) (Eq. (1)).
The methoxycarbonylation reaction of (Z)-2-fluoro-1-
dodecenyl(phenyl)iodonium tetrafluoroborate (1a) was car-
ried out using PdCl2 as a catalyst and Et3N as base which
were used in the reaction of (E)-isomers [11]. The reaction
was completed in 2 h at room temperature and the desired
methyl (Z)-2-fluoro-2-tridecenoate (2a) could be obtained
in 70% yield based on 1a with high stereoselectivity
(Z > 98%). The yield of 2a could be slightly improved
(73%) by the use of NaHCO3 instead of Et3N, but applica-
tion of other Pd catalyst could not improve the results. The
stereochemistry of the double bond in 2a was determined
from NMR. A coupling constant value between F and H at C
2 is 31.1 Hz in 2a which is larger than that of (E)-isomer
(J ¼ 19:1 Hz) [9] and support that F and H are in trans-
relationship on double bond [9]. Under the reaction condi-
tions, functional groups such as an ester, ketone, chloride
remained unchanged and various (Z)-b-fluoro-a,b-unsatu-
rated esters could be synthesized in good yields as shown in
Table 1.
3. Conclusion
(1)
We succeeded to synthesize (Z)-b-fluoro-a,b-unsaturated
esters (2) stereoselectively by the Pd catalyzed methoxy-
carbonylation reaction of the (Z)-2-fluoro-1-alkenyliodo-
nium salts (1). As we previously succeeded in the
stereoselective synthesis of (E)-b-fluoro-a,b-unsaturated
* Corresponding author. Tel./fax: þ81-11-706-6556.
E-mail address: hara@org-mc.eng.hokudai.ac.jp (S. Hara).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2003.11.025

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M. Yoshida et al. / Journal of Fluorine Chemistry 125 (2004) 527–529
Table 1
Stereoselective synthesis of (Z)-b-fluoro-a,b-unsaturated esters from (Z)-2-fluoro-1-alkenyliodonium saltsa
Entry
1
1
Reaction time (h)
Product
Yield (%)b
73
2
2
2
70
3
4
5
0.5
2
64
67
66
2
6
2
68
a The reaction was carried out as shown in Section 4.
b Isolated yields based on alkyne used.
esters, now both (E)- and (Z)-isomers of b-fluoro-a,b-unsa-
turated esters can be stereoselectively prepared.
times. The combined organic phase was dried over MgSO4
and concentrated under reduced pressure. The crude product
was purified by recrystallization from CH2Cl2-hexane and
dried in vacuo to give 1a in 84% yield (200 mg, 0.42 mmol):
mp 27–28 8C. IR (KBr): n 3061, 3048, 2956 cmÀ1. 1H NMR
d 0.88 (t, 3H, J ¼ 7:3 Hz), 1.19–1.31 (m, 14H), 1.52–1.60
4. Experimental
3
4.1. General methods
(m, 2H), 2.57 (dt, 2H, JHÀF ¼ 17:3, J ¼ 7:6 Hz), 6.52 (d,
1H, 3JHÀFðolefinÞ ¼ 33:2 Hz), 7.45–8.02 (m, 5H). 19F NMR d
3
À63.90 (d, JHÀFðolefinÞ ¼ 33:2 Hz). 13C NMR d 14.11,
The IR spectra were recorded using a JASCO FT/IR-410.
1
The H-NMR (400 MHz), 19F-NMR (376 MHz) and 13C-
22.67, 25.48, 28.69, 29.03, 29.26, 29.35, 29.47, 31.86,
2
2
NMR (100 MHz) spectra were recorded in CDCl3 on a JEOL
JNM-A400II FT NMR and the chemical shifts, d, are referred
to TMS (1H, 13C) and CFCl3 (19F). The EI or FAB low- and
high-resolution mass spectra was measured on a JEOL
JMS-700TZ, JMS-FAB mate or JMS-HX110. The elemental
microanalysis was done using a Yanagimoto CHN Corder
MT-5. Hydrofluoric acid of 46% in water was purchased from
Wako Chemical Co., Inc., and diluted to 20% with distilled
water. The 1-alkynyl(phenyl)iodonium tetrafluoroborates 1
were prepared from the corresponding alkynes [13].
32.26 (d, JCÀF ¼ 23:2 Hz), 74.20 (d, JCÀF ¼ 21:5 Hz),
111.40, 132.28 (2C), 132.64, 135.27 (2C), 174.19 (d,
1JCÀF ¼ 280:0 Hz). Anal. calcd. for C18H27BF5I; C,
45.41; H, 5.72. Found: C, 45.48; H, 5.85.
4.2.1. Synthesis of methyl (Z)-3-fluoro-2-tridecenoate (2a)
In a flask fitted with a balloon (3 l) were placed PdCl2
(1.8 mg, 0.01 mmol), NaHCO3 (42 mg, 0.5 mmol) and
MeOH (4 ml). After the complete replacement of the atmo-
sphere in the flask with CO, the balloon was filled with CO.
Then a solution of 1a (238 mg, 0.5 mmol) in MeOH (1 ml)
was added. After stirring for 2 h at room temperature, the
reaction mixture was poured into 15% aq. NH4Cl (15 ml),
and extracted with diethyl ether (10 ml) three times. The
combined organic phase was dried over MgSO4, and con-
centrated under reduced pressure. Purification by column
chromatography (silica gel/hexane-diethyl ether) gave 2a
in 73% yield (89 mg, Z/E > 98/2). IR: (neat) n 2926,
4.2. Preparation of (Z)-2-fluoro-1-
dodecenyl(phenyl)iodonium tetrafluoroborate (1a)
In a TeflonTM PFA vessel were placed 1-dodecynyl(phe-
nyl)iodonium tetrafluoroborate (228 mg, 0.5 mmol) [13], a
20% hydrofluoric acid (500 mg, 5 mmol), and CHCl3 (2 ml)
and the mixture was vigorously stirred for 6 h at 60 8C. The
reaction mixture was poured into a 5% aqueous solution of
NaBF4 (20 ml) and extracted with CH2Cl2 (10 ml) four
1735, 1685, 1217 cmÀ1
.
7:1 Hz), 1.21–1.37 (m, 14H), 1.52–1.59 (m, 2H), 2.26 (dt,
1H NMR d 0.88 (t, 3H, J ¼

M. Yoshida et al. / Journal of Fluorine Chemistry 125 (2004) 527–529
529
3
2H, JHÀF ¼ 17:3, J ¼ 7:6 Hz), 3.72 (s, 3H), 5.18 (d, 1H,
4H), 2.19–2.27 (m, 4H), 3.69 (s, 3H), 4.92–5.02 (m, 1H),
3
3JHÀFðolefinÞ ¼ 33:1 Hz); 19F NMR d À79.53 (dt, 1F,
5.15 (d, 1H, JHÀFðolefinÞ ¼ 33:2 Hz). 19F NMR d À79.60
3JHÀF ¼ 17:3, JHÀFðolefinÞ ¼ 33:1 Hz). 13C NMR d 14.11,
( dt, JHÀF ¼ 17:7, JHÀFðolefinÞ ¼ 33:2 Hz). 13C NMR d
3
3
3
22.68, 25.54, 28.80, 29.21, 29.29, 29.42, 29.53, 31.88, 32.98
2
21.82 (2C), 24.92, 25.49, 28.68, 28.97 (2C), 29.00, 32.92
2
2
(d, JCÀF ¼ 24:1 Hz), 51.33, 98.38 (d, JCÀF ¼ 6:0 Hz),
(d, JCÀF ¼ 23:9 Hz), 34.63, 51.28, 67.32, 98.39 (d,
1
1
164.30, 172.40 (d, JCÀF ¼ 281:1 Hz). HRMS (EI): calc.
2JCÀF ¼ 5:7 Hz), 164.24, 172.28 (d, JCÀF ¼ 286:6 Hz),
for C13H22FO (Mþ-OMe): 213.1655. Found: 213.1648.
173.32. HRMS (EI): calc. for C16H27FO4: 302.1893. Found:
302.1878.
4.2.2. Methyl (Z)-4-cyclohexyl-3-fluoro-2-propenoate (2b)
Yield 64% (Z/E > 98/2). IR: (neat) n 1726, 1662,
4.2.6. Methyl (Z)-3-fluoro-13,13-dimethyl-12-oxo-2-
tetradecenoate (2f)
1166 cmÀ1 1H NMR d 3.80 (s, 3H), 5.92 (d, 1H,
.
3JHÀFðolefinÞ ¼ 33:4 Hz), 7.42–7.68 (m, 5H). 19F NMR d
Yield 68% (Z/E > 98/2). IR: (neat) n 2932, 1734, 1704,
À96.25 (d, JHÀFðolefinÞ ¼ 33:4 Hz). 13C NMR d 51.59,
1685, 1219 cmÀ1. H NMR d 1.10 (s, 9H), 1.20–1.32 (m,
3
1
2
3
3
96.75 (d, JCÀF ¼ 7:4 Hz), 125.61 (d, 2C, JCÀF
¼
8H), 1.47–1.56 (m, 4H), 2.23 (dt, 2H JHÀF ¼ 17:3,
2
8:2 Hz), 128.86 (2C), 130.51 (d, JCÀF ¼ 25:6 Hz),
J ¼ 7:8 Hz), 2.43 (t, 2H, J ¼ 7:3 Hz), 3.69 (s, 3H), 5.15
1
3
131.55, 164.48, 166.41 (d, JCÀF ¼ 277:6 Hz). HRMS
(d, 1H, JHÀFðolefinÞ ¼ 33:4 Hz). 19F NMR d À79.59 (dt,
3
(EI): calc. for C10H9FO2: 180.0586. Found: 180.0586.
3JHÀF ¼ 17:3, JHÀFðolefinÞ ¼ 33:4 Hz). 13C NMR d 23.82,
25.50, 26.38 (3C), 28.70, 29.02, 29.18, 29.26, 32.92 (d,
2JCÀF ¼ 23:9 Hz), 36.34, 44.06, 51.28, 98.39 (d,
4.2.3. Methyl (Z)-3-fluoro-3-phenylpropenoate (2c)
Yield 70% (Z/E > 98/2). IR: (neat) n 2926, 1732, 1683,
1
2JCÀF ¼ 4:9 Hz), 164.24, 172.33 (d, JCÀF ¼ 283:3 Hz),
1218 cmÀ1. H NMR d 0.91–1.00 (m, 2H), 1.09–1.31 (m,
216.04. HRMS (EI): calc. for C17H29FO3: 300.2101. Found:
300.2109.
1
3
3H), 1.59–1.77 (m, 6H), 2.14 (dd, 2H, JHÀF ¼ 20:9,
3
J ¼ 7:1 Hz), 3.72 (s, 3H), 5.16 (d, 1H, JHÀFðolefinÞ
¼
3
32:9 Hz). 19F NMR
d
À78.63 (dt, JHÀF ¼ 20:9,
3JHÀFðolefinÞ ¼ 32:9 Hz). 13C NMR d 25.93 (2C), 26.09,
References
2
32.82 (2C), 34.87, 40.85 (d, JCÀF ¼ 23:1 Hz), 51.27,
2
1
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99.45 (d, JCÀF ¼ 5:7 Hz), 164.18, 171.26 (d, JCÀF
¼
286:6 Hz). HRMS (EI): calc. for C11H17FO2: 200.1213.
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1
3
2H), 1.73–1.80 (m, 2H), 2.27 (dt, 2H, JHÀF ¼ 17:3,
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3
(d, 1H, JHÀFðolefinÞ ¼ 33:1 Hz). 19F NMR d À79.61 (dt,
[6] J. Kvicala, J. Plocar, R. Vlasakova, O. Paleta, A. Pelter, Syn. Lett.
´
´
3
3JHÀF ¼ 17:3, JHÀFðolefinÞ ¼ 33:1 Hz). 13C NMR d 25.50,
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26.79, 28.70, 28.76, 29.05, 29.19, 32.57, 32.93 (d,
2JCÀF ¼ 23:1 Hz), 45.10, 51.30, 98.42 (d, 2JCÀF ¼ 4:9 Hz),
1
164.24, 172.29 (d, JCÀF ¼ 285:8 Hz). HRMS (FAB): calc.
for C13H23ClFO2 (Mþ þ H): 265.1371. Found: 265.1390.
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´
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undecenoate (2e)
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Tetrahedron Lett. 40 (1999) 7815–7818.
Yield 66% (Z/E > 98/2). IR: (neat) n 2933, 1731, 1684,
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