2-Fluoro-3-phenyl-allyltrimethylsilane: A new fluorinated reagent for Hosomi-Sakurai reaction

Article abstract of DOI:10.1016/j.jfluchem.2010.03.005

2-Fluoro-3-phenyl-allyltrimethylsilane, prepared from β-fluorinated allylic acetate via a π-allylpalladium intermediate, reacted with various aldehydes and acetals in the presence of TiCl₄ to afford the corresponding homoallyl alcohols and homoallyl ethers, respectively, in good to moderate yields.

Full text of DOI:10.1016/j.jfluchem.2010.03.005

Journal of Fluorine Chemistry 131 (2010) 709–713
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
2-Fluoro-3-phenyl-allyltrimethylsilane: A new fluorinated reagent for
Hosomi–Sakurai reaction
*
Tsuyoshi Hayashi, Yoshinosuke Usuki , Hideo Iio
Department of Material Science, Osaka City University, Sugimoto, Sumiyoshi, Osaka 558-8585, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
2-Fluoro-3-phenyl-allyltrimethylsilane, prepared from
b-fluorinated allylic acetate via a p-allylpalla-
Received 9 February 2010
Received in revised form 11 March 2010
Accepted 13 March 2010
Available online 20 March 2010
dium intermediate, reacted with various aldehydes and acetals in the presence of TiCl4 to afford the
corresponding homoallyl alcohols and homoallyl ethers, respectively, in good to moderate yields.
ß 2010 Elsevier B.V. All rights reserved.
Keywords:
Hosomi–Sakurai reaction
b-Fluorinated allylsilane
Lewis acid-promoted allylation
1. Introduction
found that treatment of 2-fluoro-3-phenylprop-2-enyl acetate [9]
(E:Z = 45:1) with hexamethyl disilane (3 equiv.) in the presence
Allylation of carbonyl compounds using various allylic metals is
a well-established methodology for the stereoselective construc-
tion of C–C bonds to provide homoallylic alcohols [1]. Lewis acid-
promoted allylation of carbonyl compounds with allyltrimethyl-
silane is referred to as the Hosomi–Sakurai reaction [2]. Much
attention has been focused on syntheses and applications of
allylsilanes to synthetic reagents. However, a literature survey
revealed only a small number of reports on fluorine-containing
of 1 mol% of Pd(PPh3)4 at 160 8C in a sealed tube afforded 1
(E:Z = 1:10) in 75% yield (Scheme 1).
Attention was next directed to the Lewis acid-promoted
addition reaction of 1 to aldehydes. We first surveyed several
Lewis acids [SnCl4, TiCl4, BF3ꢀOEt2, Ti(OiPr)4] and a Brønsted acid
(CF3SO3H) in the reaction of 1 with benzaldehyde in dichlor-
omethane at ꢁ78 8C. The results are summarized in Table 1. In
the presence of 1.0 equiv. of either SnCl4 or Ti(OiPr)4, the
reaction did not yield the expected homoallyl alcohol. With
1.0 equiv. of TiCl4, the reaction occurred in 80% yield affording
the expected product 2a regioselectively as a single diaster-
eomer (entry 4). The dr of 2a was determined by 19F NMR
spectroscopy. The reaction presumably goes through an
open transition state [10] to afford the corresponding syn-
diastereomer, which was confirmed by X-ray crystallography
(Fig. 1).
We then investigated other aldehydes with 1 in the allylation
reaction under optimized conditions. The results are summarized
in Table 2. The reaction proceeded with both aromatic and
aliphatic aldehydes diastereoselectively to afford the correspond-
ing homoallyl alcohols in moderate to good yields. p-Nitroben-
zaldehyde was converted into 2d in 77% yield, however the dr was
decreased to 83:17 (entry 3). When the allylation was carried out
with p-methoxybenzaldehyde or 2-furylaldehyde, no desired
reaction occurred (not shown in Table 2). These results could be
explained by the electron-rich carbonyl group. While aliphatic
aldehydes had a slightly lower reactivity in comparison with
aromatic ones, these reactions were successfully performed with
high diastereoselectivity.
allylsilanes (
a
,
a
-difluoro [3],
g
,g
-difluoro-
b
-benzyloxy [4],
g,g-
difluoro- -carbamoyl [5] and
b
b
-trifluoromethyl [6]). b
-Fluoro-
allylsilane derivatives have not been reported, although they
would afford useful fluorinated homoallyl alcohol derivatives.
Furthermore, despite its electron-withdrawing inductive effect,
fluorine has
donation of its unshared electron pair to the vacant
the -carbon [7]. Since the former mesomeric effect is operative for
-sp2 carbons, carbocations are stabilized by
-fluorine. The
a
stabilizing effect on
a
-carbocations through
p
-orbital of
a
a
a
a
-
carbocation-stabilizing effect is well exemplified in biomimetic
polyene cyclization [8], where fluoroalkene moieties served as
terminators. Herein, we report the synthesis and reactivity of 2-
fluoro-3-phenyl-allyltrimethylsilane (1).
2. Results and discussion
We struggled to find milder and more efficient reaction
conditions for the preparation of 1. After several attempts, we
* Corresponding author. Tel.: +81 6 6605 2563; fax: +81 6 6605 2522.
E-mail address: usuki@sci.osaka-cu.ac.jp (Y. Usuki).
0022-1139/$ – see front matter ß 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2010.03.005

710
T. Hayashi et al. / Journal of Fluorine Chemistry 131 (2010) 709–713
Table 3
Allylation of dialkyl acetals with 1.
Scheme 1. Preparation of 2-fluoro-3-phenyl-allyltrimethylsilane 1.
R
R0
Product
Yield/%
dra
Table 1
1
2
3
PhCH2
BrCH2
Ph
Me
Et
3a
3b
3c
61
44
78
83:17
74:26
63:37
Allylation of benzaldehyde with 1.
Me
a
Diastereomeric ratio determined by 19F NMR.
Allylations of dialkyl acetals with 1 afforded the corresponding
homoallyl ethers 3 in moderate to good yields with moderate
diastereoselectivity as shown in Table 3. The reaction took place
Lewis acid
Temp.
Time/h
Yield/%
dra
1
2
3
4
5
SnCl4
ꢁ78 8C ! rt
ꢁ78 8C ! rt
ꢁ78 8C ! rt
ꢁ78 8C
24
5
0
0
–
regioselectively at the
previously reported results [11]. The relative configuration of the
product has not been assigned yet.
g-position of allylsilane 1 similar to the
Ti(OiPr)4
BF3ꢀOEt2
TiCl4
–
24
1
4
sdb
sdb
sdb
80
2
CF3SO3H
ꢁ78 8C ! rt
5
3. Conclusion
a
Diastereomeric ratio determined by 19F NMR.
b
Single diastereomer.
In summary, we have developed a new synthesis of
b-fluoro-
allylsilane derivative via a Pd-catalyzed process. This fluorine-
containing allylsilane reacts with various aldehydes and acetals to
provide the corresponding homoallyl alcohol derivatives in
moderate to good yields. Work to apply the present protocol in
fluorinated biomimetics is currently underway in our laboratory.
Table 2
Allylation of other aldehydes with 1.
4. Experimental
All air- and moisture-sensitive reactions were carried out in
flame-dried, argon-flushed, two-necked flasks sealed with rubber
septa, and the dry solvents and reagents were introduced using a
syringe. Tetrahydrofuran (THF) was fleshly distilled under an argon
atmosphere from sodium benzophenone ketyl. Dichloromethane
(CH2Cl2) was fleshly distilled from phosphoric pentaoxide (P2O5).
Flash column chromatography was carried out on a Kanto
R
Time/h
Product
Yield/%
dra
1
2
p-CH3C6H4
p-CF3C6H4
p-NO2C6H4
nPr
3
2b
2c
2d
2e
2f
40
54
77
58
58
44
72
52
66
36
sdb
sdb
1
3
1
83:17
sdb
4
1
5
Me
1.5
1.5
1.5
1
sdb
Chemical silica gel 60 N (spherical, neutral, 40–50
mm), and pre-
6
iPr
2g
2h
2i
sdb
coated Merck silica gel plates (Art5715 Kieselgel 60F254, 0.25 mm)
were used for thin-layer chromatography (TLC). Unless mentioned
otherwise, 1H, 13C and 19F nuclear magnetic resonance (NMR)
spectra were recorded in CDCl3 on a JEOL JNM-LA400, JEOL JNM-
LA300 or BRUKER AV-300. Chemical shifts of 19F NMR were given
7
BnOCH2
sdb
8
CH3(CH2)2CH(CH3)
PhCH(CH3)
nBuOC5O
83:17
sdb
sdb
9
1
2j
10
1
2k
Diastereomeric ratio determined by 19F NMR.
Single diastereomer.
a
b
by
d relative to that of an external trifluoroacetic acid (TFA). Mass
Fig. 1. X-ray structure of 2a.

T. Hayashi et al. / Journal of Fluorine Chemistry 131 (2010) 709–713
711
spectra were obtained on a JEOL JMS-700T or JEOL JMS-AX500
4.2.3. 2-Fluoro-3-phenyl-4-(4-trifluoromethyl-phenyl)-but-1-en-4-
spectrometer.
ol (2c)
1H NMR (300 MHz, CDCl3)
d
2.01 (d, 3JHH = 2.0 Hz, 1H), 3.63 (dd,
4.1. Trimethyl(2-fluoro-3-phenyl-2-propenyl)silane 1
3JHH = 8.3 Hz, 3JHF = 24.0 Hz, 1H), 4.22 (dd, 2JHH = 3.3 Hz,
3JHF = 50.0 Hz, 1H), 4.48 (dd, JHH = 3.3 Hz, JHF = 17.9 Hz, 1H),
2
3
3
2-Fluoro-3-phenylprop-2-enyl acetate (0.638 g, 3.29 mmol)
was placed in a Pyrex tube. After the atmosphere was replaced
with argon, tatrakis(triphenylphosphine)palladium (0.038 g,
0.033 mmol) and hexamethyl disilane (1.443 g, 2.0 mL,
9.86 mmol) were added. Then the tube was sealed and heated
at 160 8C for 3 h. After cooling to room temperature, the crude
product was purified by a flash column chromatography (hexane)
to give 1 (0.518 g, 2.48 mmol, yield 75%, E:Z = 1:10)
5.26 (dd, JHH = 2.0 Hz, 8.3 Hz, 1H), 7.32–7.38 (m, 5H), 7.48 (d,
3
3JHH = 8.0 Hz, 2H), 7.59 (d, JHH = 8.0 Hz, 2H); 13C NMR (100 MHz,
CDCl3)
C-1), 124.08 (q, JCF = 271.7 Hz), 125.18 (q, JCF = 4.1 Hz), 126.88,
d
57.91 (d, 2JCF = 23.9 Hz, C-3), 74.33, 93.21 (d, 2JCF = 19.0 Hz,
1
3
4
2
128.01, 128.88 (d, JCF = 1.6 Hz), 128.92, 130.09 (q, JCF = 32.2 Hz),
136.49, 145.39, 164.23 (d, 1JCF = 259.4 Hz, C-2); 19F NMR (283 MHz,
CDCl3)
d
ꢁ63.08 (s, 3F), -101.21 (ddd, 3JHF = 17.9, 24.0, 50.0 Hz, 1F).
MS (CI) m/z 293 [MꢁH2O+H]+; HRMS (CI) Calcd. for C17H13F4:
(Z)-1: 1H NMR (300 MHz, CDCl3)
d
0.10 (s, 9H), 1.78 (d,
293.0953, Found: 293.0952.
3JHF = 25.4 Hz, 2H), 5.27 (d, JHF = 39.8 Hz, 1H), 7.11–7.19 (m, 1H),
3
7.24–7.29 (m, 2H), 7.39–7.42 (m, 2H); 13C NMR (100 MHz, CDCl3)
d
4.2.4. 2-Fluoro-3-phenyl-4-(4-nitrophenyl)-but-1-en-4-ol (2d)
ꢁ1.55, 23.96 (d, 2JCF = 29.7 Hz, C-3), 103.84 (d, 2JCF = 10.7 Hz, C-1),
Major: 1H NMR (300 MHz, CDCl3)
d
2.07 (d, JHH = 2.9 Hz, 1H),
3
3
3
3
2
125.96, 127.81, 128.32, 134.64 (d, JCF = 2.5 Hz), 160.68 (d,
3.62 (dd, JHH = 8.2 Hz, JHF = 23.3 Hz, 1H), 4.23 (dd, JHH = 3.2 Hz,
3JHF = 50.0 Hz, 1H), 4.52 (dd, 2JHH = 3.2 Hz, 3JHF = 18.0 Hz, 1H), 5.17
(dd, 3JHH = 2.9, 8.2 Hz, 1H), 7.29–7.37 (m, 5H), 7.56 (d, 3JHH = 8.8 Hz,
1JCF = 262.7 Hz, C-2); 19F NMR (283 MHz, CDCl3)
d
ꢁ90.83 (dt,
3JHF = 39.8, 25.4 Hz). MS (CI) m/z 209 [M+H]+; HRMS (CI) Calcd. for
C
12H18FSi: 209.1162, Found: 209.1143.
2H), 8.19 (d, 3JHH = 8.8 Hz, 2H); 13C NMR (75.4 MHz, CDCl3)
d 57.94
(E)-1 (selected date): 1H NMR (300 MHz, CDCl3)
d
0.07 (s, 9H),
(d, JCF = 23.4 Hz, C-3), 73.54 (d, JCF = 0.9 Hz, C-4), 93.53 (d,
2JCF = 19.3 Hz, C-1), 123.42, 127.37, 128.17, 128.91 (d, 4JCF = 1.6 Hz,
2
3
1.97 (d, JHF = 28.0 Hz, 2H), 6.05 (d, JHF = 22.3 Hz, 1H); 13C NMR
3
3
(100 MHz, CDCl3)
d
ꢁ1.15, 20.12 (d, 2JCF = 32.2 Hz, C-3), 105.55 (d,
C-2), 129.00, 136.04, 147.57, 148.68, 164.00 (d, 1JCF = 259.9 Hz, C-
2JCF = 30.5 Hz, C-1); 19F NMR (283 MHz, CDCl3)
3JHF = 22.3, 28.0 Hz).
d
ꢁ86.33 (dt,
2); 19F NMR (283 MHz, CDCl3)
d
ꢁ101.23 (ddd, JHF = 18.0, 23.3,
3
50.0 Hz). MS (CI) m/z 288 [M+H]+; HRMS (CI) Calcd. for
C
16H15FNO3: 288.1036, Found: 288.1036.
4.2. Typical procedure for the reaction of aldehydes with 1
Minor (selected data): 1H NMR (300 MHz, CDCl3)
d 2.53 (d,
3JHH = 3.0 Hz, 1H), 4.65 (dd, JHH = 3.3 Hz, JHF = 49.9 Hz, 1H), 4.85
(dd, JHH = 3.3 Hz, JHF = 17.8 Hz, 1H), 5.17 (dd, JHH = 3.0, 9.2 Hz,
1H), 8.04 (d, 3JHH = 8.8 Hz, 2H); 13C NMR (75.4 MHz, CDCl3)
57.86
(d, JCF = 23.7 Hz, C-3), 74.21 (d, JCF = 2.9 Hz, C-4), 93.93 (d,
2JCF = 19.5 Hz, C-1), 123.18, 127.52, 127.80, 128.39 (d,
4JCF = 1.9 Hz), 128.72, 136.27, 147.38, 148.47, 164.07 (d,
1JCF = 261.7 Hz, C-2); 19F NMR (283 MHz, CDCl3)
3JHF = 17.8, 24.0, 50.0 Hz).
2
3
2
3
3
To a solution of benzaldehyde (0.17 mmol) in dry dichloro-
methane (0.28 mL) at ꢁ78 8C under an argon atmosphere was added
TiCl4 (1.0 M solution in dichloromethane; 0.17 mL, 0.17 mmol)
dropwise with a syringe. After stirring at this temperature for 5 min,
to the mixture was added dropwise a solution of 1 (0.035 g,
0.17 mmol) in dichloromethane (0.28 mL). The reaction mixture was
stirred for 1 h at ꢁ78 8C. The resulting mixture was quenched with
water (5 mL), and the aqueous layer was extracted with ether. The
combined organic layers were washed with sat aq NaHCO3, brine,
dried over anhydrous Na2SO4, and concentrated at reduced pressure.
The residue was purified by preparative thin-layer chromatography
to afford 2a in 80% yield as a single diastereomer.
d
2
3
d
ꢁ101.58 (ddd,
4.2.5. 2-Fluoro-3-phenyl-hept-1-en-4-ol (2e)
1H NMR (300 MHz, CDCl3) 0.93 (t, 3JHH = 7.0 Hz, 3H), 1.39–1.63
d
(m, 4H), 3.40 (dd, 3JHH = 7.3 Hz, 3JHF = 21.4 Hz, 1H), 4.12 (br t, 1H),
2
3
2
4.44 (dd, JHH = 3.1 Hz, JHF = 50.4 Hz, 1H), 4.65 (dd, JHH = 3.1 Hz,
3JHF = 18.1 Hz, 1H), 7.28–7.36 (m, 5H); 13C NMR (100 MHz, CDCl3)
d
2
4.2.1. 2-Fluoro-3,4-diphenyl-but-1-en-4-ol (2a)
13.95, 18.93, 37.05, 55.73 (d, JCF = 23.1 Hz, C-3), 71.19 (d,
1H NMR (300 MHz, CDCl3)
d
1.92 (s, 1H), 3.68 (dd, 3JHH = 8.4 Hz,
3JCF = 2.5 Hz, C-4), 92.26 (d, JCF = 19.8 Hz, C-1), 127.58, 128.75,
2
3JHF = 24.0 Hz, 1H), 4.22 (dd, 2JHH = 3.1 Hz, 3JHF = 50.0 Hz, 1H), 4.44
128.96, 137.46, 165.86 (d, 1JCF = 259.4 Hz, C-2); 19F NMR (283 MHz,
2
3
3
(dd, JHH = 3.1 Hz, JHF = 17.6 Hz, 1H), 5.19 (d, JHH = 8.4 Hz, 1H),
CDCl3)
d
ꢁ100.10 (ddd, 3JHF = 18.1, 21.4, 50.4 Hz). MS (CI) m/z 191
7.26–7.41 (m, 5H); 13C NMR (100 MHz, CDCl3)
d
57.85 (d,
[MꢁH2O+H]+; HRMS (CI) Calcd. for C13H16F: 191.1236, Found:
2JCF = 23.1 Hz, C-3), 74.44 (d, JCF = 1.6 Hz, C-4), 92.68 (d,
2JCF = 19.8 Hz, C-1), 126.54, 127.74, 127.99, 128.26, 128.76,
128.89 (d, 3JCF = 1.6 Hz), 137.13, 141.55, 164.76 (d, 1JCF = 260.2 Hz,
191.1239.
3
4.2.6. 2-Fluoro-3-phenyl-pent-1-en-4-ol (2f)
C-2); 19F NMR (283 MHz, CDCl3)
d
ꢁ100.82 (ddd, 3JHF = 17.6, 24.0,
1H NMR (300 MHz, CDCl3)
d
1.32 (d, 3JHH = 6.2 Hz, 3H), 1.50 (br
50.0 Hz). MS (CI) m/z 225 [MꢁH2O+H]+; HRMS (CI) Calcd. for
s, 1H), 3.33 (dd, JHH = 7.8 Hz, JHF = 22.9 Hz, 1H), 4.30 (dd,
3
3
2
3
C
16H14F: 225.1080, Found: 225.1077.
3JHH = 6.2, 7.8 Hz, 1H), 4.45 (dd, JHH = 3.1 Hz, JHF = 50.2 Hz, 1H),
2
3
4.64 (dd, JHH = 3.1 Hz, JHF = 18.0 Hz, 1H), 7.27–7.37 (m, 5H); 13C
NMR (100 MHz, CDCl3)
21.14, 57.35 (d, 2JCF = 23.1 Hz, C-3), 67.88
(d, JCF = 2.5 Hz, C-4), 92.20 (d, 2JCF = 19.8 Hz, C-1), 127.67, 128.80
4.2.2. 2-Fluoro-3-phenyl-4-p-tolyl-but-1-en-4-ol (2b)
1H NMR (300 MHz, CDCl3)
1.85 (s, 1H), 2.34 (s, 3H), 3.68 (dd,
3JHH = 8.6 Hz, 3JHF = 24.0 Hz, 1H), 4.23 (dd, 2JHH = 3.1 Hz,
d
3
d
3
1
(d, JCF = 1.6 Hz), 128.83, 137.47, 165.75 (d, JCF = 260.2 Hz, C-2);
2
3
3
3JHF = 50.0 Hz, 1H), 4.44 (dd, JHH = 3.1 Hz, JHF = 17.9 Hz, 1H),
19F NMR (283 MHz, CDCl3)
d
ꢁ100.55 (ddd, JHF = 18.0, 22.9,
3
3
5.15 (d, JHH = 8.6 Hz, 1H), 7.14 (d, JHH = 7.9 Hz, 2H), 7.25 (d,
3JHH = 7.9 Hz, 2H), 7.30–7.41 (m, 5H); 13C NMR (100 MHz, CDCl3)
21.17, 57.74 (d, JCF = 23.1 Hz, C-3), 74.33 (d, JCF = 1.6 Hz, C-4),
50.2 Hz). MS (EI) m/z 180 [M]+; HRMS (EI) Calcd. for C11H13FO:
d
180.0950, Found: 180.0952.
2
3
2
92.60 (d, JCF = 19.8 Hz, C-1), 126.48, 127.69, 128.74, 128.87 (d,
4.2.7. 2-Fluoro-5-methyl-3-phenyl-hex-1-en-4-ol (2g)
3JCF = 1.6 Hz), 128.97, 137.34, 137.67, 138.60, 164.89 (d,
1H NMR (300 MHz, CDCl3) 0.99 (d, 3JHH = 13.0 Hz, 3H), 1.01 (d,
d
1JCF = 260.2 Hz, C-2); 19F NMR (283 MHz, CDCl3)
d
ꢁ100.67 (ddd,
3JHH = 13.2 Hz, 3H), 1.36 (br s, 1H), 1.82–1.92 (m, 1H), 3.56 (dd,
3JHF = 17.9, 24.0, 50.0 Hz). MS (CI) m/z 239 [MꢁH2O+H]+; HRMS (CI)
3JHH = 7.9 Hz, JHF = 22.2 Hz, 1H), 3.91–3.96 (m, 1H), 4.41 (dd,
3
Calcd. for C17H16F: 239.1236, Found: 239.1237.
2JHH = 3.1 Hz, 3JHF = 50.4 Hz, 1H), 4.63 (dd, 2JHH = 3.1 Hz,

712
T. Hayashi et al. / Journal of Fluorine Chemistry 131 (2010) 709–713
3JHF = 18.0 Hz, 1H), 7.25–7.41 (m, 5H); 13C NMR (100 MHz, CDCl3)
15.61, 20.13, 30.40, 53.08 (d, JCF = 24.0 Hz, C-3), 75.69, 92.22 (d,
2JCF = 19.8 Hz, C-1), 127.54, 128.74, 129.01, 137.75, 166.00 (d,
d
50.8 Hz). MS (EI) m/z 248 [MꢁH2O]+; HRMS (EI) Calcd. for
2
C15H17FO2: 248.1213, Found: 248.1218.
1JCF = 260.2 Hz, C-2); 19F NMR (283 MHz, CDCl3)
d
ꢁ101.00 (ddd,
4.3. Typical procedure for the reaction of dialkylacetals with 1
To solution of phenylacetoaldehyde dimethyl acetal
3JHF = 18.0, 22.2, 50.4 Hz). MS (CI) m/z 191 [MꢁH2O+H]+; HRMS (CI)
Calcd. for C13H16F: 191.1236, Found: 191.1234.
a
(0.17 mmol) in dry dichloromethane (0.25 mL) at ꢁ78 8C under
an argon atmosphere was added TiCl4 (1.0 M solution in dichlor-
omethane; 0.17 mL, 0.17 mmol) dropwise with a syringe. After
stirring at this temperature for 5 min, to the mixture was added
dropwise a solution of 1 (0.035 g, 0.17 mmol) in dichloromethane
(0.28 mL). The reaction mixture was stirred for 1.5 h at ꢁ78 8C. The
resulting mixture was quenched withwater(5 mL), andthe aqueous
layer was extracted with ether (3ꢂ). The combined organic layers
were washed with sat aq NaHCO3, brine, dried over anhydrous
Na2SO4, and concentrated at reduced pressure. The residue was
purified by preparative thin-layer chromatography to afford 3a in
61% yield as a 83:17 mixture of diastereomers.
4.2.8. 5-Benzyloxy-2-fluoro-3-phenyl-pent-1-en-4-ol (2h)
3
1H NMR (300 MHz, CDCl3)
d
2.60 (d, JHH = 4.5 Hz, 1H), 3.22
3
2
3
(dd, JHH = 5.5 Hz, JHH = 9.7 Hz, 1H), 3.38 (dd, JHH = 2.8 Hz,
3
3
2JHH = 9.7 Hz, 1H), 3.62 (dd, JHH = 9.5 Hz, JHF = 24.2 Hz, 1H),
3
4.22 (ddd, JHH = 2.8, 5.5, 9.5 Hz, 1H), 4.39 (d,
2JHH = 11.7 Hz, 1H), 4.47 (dd, B of AB, JHH = 11.7 Hz, 1H), 4.54
A of AB,
2
2
3
2
(dd, JHH = 2.9 Hz, JHF = 50.0 Hz, 1H), 4.70 (dd, JHH = 2.9 Hz,
3JHF = 17.8 Hz, 1H), 7.24–7.35 (m, 10H); 13C NMR (100 MHz,
CDCl3)
d
52.45 (d, 2JCF = 24.7 Hz, C-3), 70.74 (d, 3JCF = 3.3 Hz, C-4),
2
71.47, 73.38, 92.38 (d, JCF = 19.8 Hz, C-1), 127.48, 127.74,
127.80, 128.13 (d, JCF = 1.6 Hz), 128.40, 128.74, 137.66,
137.97, 165.14 (d, JCF = 260.2 Hz, C-2); 19F NMR (283 MHz,
3
1
3
CDCl3)
d
ꢁ101.91 (ddd, JHF = 17.8, 24.2, 50.0 Hz). MS (EI) m/z
4.3.1. 2-Fluoro-4-methoxy-3,5-diphenylpent-1-ene (3a)
3
286 [M]+; HRMS (EI) Calcd. for C18H19FO2: 286.1369, Found:
286.1364.
Major: 1H NMR (300 MHz, CDCl3)
d
2.77 (dd, JHH = 7.1 Hz,
2JHH = 14.0 Hz, 1H), 2.84 (dd, 3JHH = 5.3 Hz, 2JHH = 14.0 Hz, 1H), 3.09
(s, 3H), 3.47 (dd, JHH = 6.6 Hz, JHF = 18.4 Hz, 1H), 3.90–3.96 (m,
1H), 4.31 (dd, JHH = 2.9 Hz, JHF = 50.6 Hz, 1H), 4.66 (dd,
2JHH = 2.9 Hz, JHF = 18.4 Hz, 1H), 7.18–7.39 (m, 10H); 13C NMR
38.85, 53.11 (d, JCF = 24.7 Hz, C-3), 59.01,
82.73, 92.63 (d, 2JCF = 19.8 Hz, C-1), 126.23, 127.17, 128.27, 128.29,
129.43, 129.49, 137.84 (d, JCF = 1.6 Hz), 138.68, 166.48 (d,
3
3
2
3
4.2.9. 2-Fluoro-5-methyl-3-phenyl-oct-1-en-4-ol (2i)
3
3
Major: 1H NMR (300 MHz, CDCl3)
d
0.91 (t, JHH = 6.8 Hz, 3H),
2
0.96 (d, 3JHH = 6.8 Hz, 3H), 1.21–1.55 (m, 5H), 1.81 (br s, 1H), 3.55
(100 MHz, CDCl3)
d
3
3
3
(dd, JHH = 9.3 Hz, JHF = 25.9 Hz, 1H), 4.08 (dt, JHH = 9.3, 2.9 Hz,
2
3
3
1H), 4.42 (dd, JHH = 2.9 Hz, JHF = 50.0 Hz, 1H), 4.61 (dd,
2JHH = 2.9 Hz, JHF = 18.0 Hz, 1H), 7.28–7.36 (m, 5H); 13C NMR
1JCF = 259.4 Hz, C-2); 19F NMR (283 MHz, CDCl3)
d
ꢁ100.11 (dt,
3
(100 MHz, CDCl3)
d 12.44, 14.20, 34.74, 36.66, 53.47 (d,
3JHF = 18.4, 50.6 Hz). MS (EI) m/z 270 [M]+; HRMS (EI) Calcd. for
2
2JCF = 23.1 Hz, C-3), 73.80 (C-4), 92.05 (d, JCF = 19.8 Hz, C-1),
C
18H19FO: 270.1420, Found: 270.1412.
127.57, 128.72, 128.84, 138.30, 165.69 (d, 1JCF = 260.2 Hz, C-2); 19
NMR (283 MHz, CDCl3)
MS (CI) m/z 237 [M+H]+; HRMS (CI) Calcd. for C15H22FO: 237.1654,
F
Minor (selected data): 1H NMR (300 MHz, CDCl3)
d 2.53 (dd,
d
ꢁ101.99 (ddd, 3JHF = 18.0, 25.9, 50.0 Hz).
3JHH = 7.5 Hz, 2JHH = 14.0 Hz, 1H), 2.78 (dd, 3JHH = 3.7 Hz,
2JHH = 14.0 Hz, 1H), 3.27 (s, 3H), 3.44 (dd, JHH = 8.6 Hz,
3
2
Found: 237.1660.
3JHF = 26.0 Hz, 1H), 3.85–3.92 (m, 1H), 4.47 (dd, JHH = 2.9 Hz,
Minor (selected data): 1H NMR (300 MHz, CDCl3)
d
3.98 (m, 1H),
3JHF = 50.2 Hz, 1H), 4.63 (dd, JHH = 2.9 Hz, JHF = 17.6 Hz, 1H),
2
3
2
3
2
4.40 (dd, JHH = 3.1 Hz, JHF = 50.6 Hz, 1H), 4.64 (dd, JHH = 3.1 Hz,
3JHF = 18.1 Hz, 1H); 13C NMR (100 MHz, CDCl3)
14.37, 16.84,
7.09–7.36 (m, 10H); 13C NMR (100 MHz, CDCl3)
d
38.30, 53.93 (d,
4
d
2JCF = 24.7 Hz, C-3), 58.94, 82.75 (d, JCF = 1.6 Hz, C-5), 92.09 (d,
20.27, 32.25, 35.24, 52.69 (d, 2JCF = 23.1 Hz, C-3), 75.75 (C-4), 92.35
2JCF = 20.6 Hz, C-1), 126.19, 127.37, 128.18, 128.46 (d,
(d, 2JCF = 19.8 Hz, C-1); 19F NMR (283 MHz, CDCl3)
3JHF = 18.1, 20.6, 50.6 Hz).
d
ꢁ100.66 (ddd,
3JCF = 1.6 Hz), 128.71, 129.55, 138.54; 19F NMR (283 MHz, CDCl3)
3
d
ꢁ102.21 (ddd, JHF = 17.6, 26.0, 50.2 Hz).
4.2.10. 3,5-Diphenyl-2-fluoro-hex-1-en-4-ol (2j)
4.3.2. 5-Bromo-4-ethoxy-2-fluoro-3-phenylpent-1-ene (3b)
1H NMR (300 MHz, CDCl3)
d
1.35 (d, 3JHH = 6.6 Hz, 3H), 1.52 (br
Major: 1H NMR (300 MHz, CDCl3)
d
1.07(t, 3JHH = 7.1 Hz, 3H), 3.34
3
3
3
2
3
s, 1H), 2.92 (quint, JHH = 6.6 Hz, 1H), 3.49 (dd, JHH = 6.6 Hz,
(dq, JHH = 7.1 Hz, JHH = 9.1 Hz, 1H), 3.35 (dd, JHH = 5.7 Hz,
2JHH = 11.0 Hz, 1H), 3.45 (dd, 3JHH = 5.1 Hz, 2JHH = 11.0 Hz, 1H), 3.63
3
3JHF = 19.8 Hz, 1H), 4.30 (t, JHH = 6.6 Hz, 1H), 4.42 (dd,
2JHH = 3.0 Hz, 3JHF = 50.6 Hz, 1H), 4.69 (dd, 2JHH = 3.0 Hz,
(dq, JHH = 7.1 Hz, JHH = 9.1 Hz, 1H), 3.82 (dd, JHH = 6.4 Hz,
3
2
3
3JHF = 19.8 Hz, 1H), 7.18–7.35 (m, 5H); 13C NMR (75.4 MHz, CDCl3)
3JHF = 18.4 Hz, 1H), 3.98–4.04 (m, 1H), 4.39 (dd, JHH = 3.1 Hz,
2
2
2
3
d
15.25, 42.50, 36.66, 52.50 (d, JCF = 24.0 Hz, C-3), 75.35 (d,
3JHF = 50.4 Hz, 1H), 4.69 (dd, JHH = 3.1 Hz, JHF = 18.4 Hz, 1H),
3JCF = 1.5 Hz, C-4), 92.47 (d, JCF = 19.8 Hz, C-1), 126.56, 127.53,
7.25–7.41 (m, 5H); 13C NMR (100 MHz, CDCl3)
51.75 (d, 2JCF = 24.7 Hz, C-3), 67.04, 78.65 (d, 3JCF = 1.6 Hz, C-4), 93.09
d 15.24, 33.37,
2
1
128.54, 128.57, 129.32, 137.20, 144.67, 166.19 (d, JCF = 260.4 Hz,
C-2); 19F NMR (282 MHz, CDCl3)
d
ꢁ100.70 (dt, JHF = 19.8,
(d, JCF = 19.0 Hz, C-1), 127.45, 128.32, 129.48 (d, JCF = 1.6 Hz),
3
2
4
50.6 Hz). MS (CI) m/z 253 [MꢁH2O+H]+; HRMS (CI) Calcd. for
136.51 (d, JCF = 1.6 Hz), 165.39 (d, JCF = 260.2 Hz, C-2); 19F NMR
3
1
C
18H18F: 253.1393, Found: 253.1396.
(283 MHz, CDCl3)
d
ꢁ100.89(dt, 3JHF = 18.4, 50.4 Hz). MS(EI)m/z286
[M]+;HRMS(EI)Calcd.forC13H1679BrFO:286.0369,Found:286.0370.
4.2.11. 4-Fluoro-2-hydroxy-3-phenyl-pent-4-enoic acid butyl ester
Minor (selected data): 1H NMR (300 MHz, CDCl3)
3JHH = 7.0 Hz, 3H), 3.03 (dd, 3JHH = 4.2 Hz, 2JHH = 11.1 Hz, 1H), 3.44
d 1.18 (t,
(2k)
1H NMR (300 MHz, CDCl3)
d
0.90 (t, 3JHH = 7.3 Hz, 3H), 1.24–1.36
(dd, JHH = 3.5 Hz, JHH = 11.1 Hz, 1H), 3.49 (dq, JHH = 7.0 Hz,
2JHH = 9.0 Hz, 1H), 3.66 (dd, JHH = 9.3 Hz, JHF = 25.7 Hz, 1H),
3
2
3
3
3
3
(m, 2H), 1.49–1.59 (m, 2H), 3.02 (d, JHH = 6.2 Hz, 1H), 3.96 (dd,
3JHH = 4.8 Hz, JHF = 14.0 Hz, 1H), 4.13 (t, JHH = 6.6 Hz, 2H), 4.39
3
3
3
2
3
3.68 (dq, JHH = 7.0 Hz, JHH = 9.0 Hz, 1H), 3.84 (dt, JHH = 3.8 Hz,
2
3
2
2
3
(dd, JHH = 3.1 Hz, JHF = 50.8 Hz, 1H), 4.77 (dd, JHH = 3.1 Hz,
3JHF = 18.5 Hz, 1H), 7.29–7.43 (m, 5H); 13C NMR (100 MHz, CDCl3)
3JHH = 9.3 Hz, 1H), 4.46 (dd, JHH = 2.9 Hz, JHF = 50.0 Hz, 1H), 4.58
(dd, 2JHH = 2.9 Hz, 3JHF = 17.2 Hz, 1H), 7.21–7.27 (m, 5H); 13C NMR
2
d
13.56, 18.93, 30.35, 52.46 (d, 2JCF = 25.6 Hz, C-3), 65.93, 71.96 (d,
(100 MHz, CDCl3)
d
15.27, 34.35, 52.81 (d, JCF = 24.0 Hz, C-3),
3JCF = 2.5 Hz, C-2), 93.97 (d, JCF = 18.1 Hz, C-5), 127.73, 128.61,
66.41, 78.09, 92.57 (d, 2JCF = 19.8 Hz, C-1), 127.71, 128.27, 128.89,
2
3
1
1
128.76, 136.87 (d, JCF = 2.5 Hz), 164.12 (d, JCF = 260.2 Hz, C-4),
173.33; 19F NMR (283 MHz, CDCl3)
164.58 (d, JCF = 261.0 Hz, C-2); 19F NMR (283 MHz, CDCl3)
d
3
d
ꢁ97.33 (ddd, 3JHF = 14.0, 18.5,
ꢁ102.95 (ddd, JHF = 17.2, 25.7, 50.0 Hz).

T. Hayashi et al. / Journal of Fluorine Chemistry 131 (2010) 709–713
713
Table 4
Crystal data and experimental details for 2a.
Appendix A. X-ray crystallographic study on 2a
Formula
C16H15FO
Formula weight
Temperature
Wavelength
Crystal system
Space group
242.28
The diffraction experiments were carried out at 150(2) K on a
150(2) K
Rigaku Mercury CCD area detector with graphite monochromated
˚
a (l = 0.71070 A) radiation. Crystal data and collection
˚
0.71070 A
Monoclinic
P21/n
Mo-K
details for 2a are summarized in Table 4. The structure was solved
by direct Methods (SIR97) [12] and refined on F2 by full-matrix
least-squares methods, using SHELXL-97 [13]. CCDC 768953
contains the supplementary crystallographic data for 2a. These
data can be obtained free of charge at http://www.ccdc.cam.ac.uk/
conts/retrieving.html or from Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge, CB12 1EZ, UK; fax: +44 1223
366 033, e-mail: deposit@ccdc.cam.ac.uk.
˚
Unit cell dimensions
a = 11.353(3) A
a
b
g
= 908
= 95.905(6)8
= 908
˚
b = 5.5834(13) A
˚
c = 20.232(5) A
3
˚
Cell volume
Z
1275.6(5) A
4
Density (calculated)
Absorption coefficient
F(0 0 0)
1.262 Mg mꢁ3
0.087 mmꢁ1
512
Crystal size
0.35 mm ꢂ 0.25 mm ꢂ 0.22 mm
Theta range for data collection 4.05–27.488
References
Reflections collected/unique
Data/restraints/parameters
Goodness of fit on F2
11,692/2886 [Rint = 0.0447]
2886/0/276
1.245
[1] (a) Y. Yamamoto, N. Asao, Chem. Rev. 93 (1993) 2207–2293;
(b) S.E. Denmark, J. Fu, Chem. Rev. 103 (2003) 2763–2794.
[2] (a) A. Hosomi, H. Sakurai, Tetrahedron Lett. 17 (1976) 1295–1298;
(b) A. Hosomi, Acc. Chem. Res. 21 (1988) 200–206.
[3] T. Hiyama, M. Obayashi, M. Sawahata, Tetrahedron Lett. 24 (1983) 4113–4116.
[4] Y. Usuki, O. Kobayashi, Y. Ohmura, H. Iio, ITE Lett. Batteries, New Technol. Med. 2
(2001) C12–C14.
[5] J. Lee, M. Tsukazaki, V. Snieckus, Tetrahedron Lett. 34 (1993) 415–418.
[6] T. Yamazaki, N. Ishikawa, Chem. Lett. 13 (1984) 521–524.
[7] (a) B.E. Smart, in: R.E. Banks, B.E. Smart, J.C. Tatlow (Eds.), Organofluorine
Chemistry, Principles and Commercial Applications, Plenum Press, New York,
1994, pp. 57–88;
R1 (I > 2
s
(I))
0.0873
wR2 (all data)
0.1716
ꢁ3
˚
Largest diff. peak and hole
0.316/ꢁ0.306 eA
4.3.3. 2-Fluoro-4-methoxy-3,4-diphenylbut-1-ene (3c)
Major: 1H NMR (300 MHz, CDCl3)
3.13 (s, 3H), 3.67 (dd,
d
3JHH = 8.5 Hz, 3JHF = 23.8 Hz, 1H), 4.16 (dd, 2JHH = 2.9 Hz,
3JHF = 50.0 Hz, 1H), 4.38 (dd, JHH = 2.9 Hz, JHF = 17.8 Hz, 1H), 4.69
2
3
(d, 3JHH = 8.5 Hz, 1H), 7.15–7.34(m, 10H);13CNMR (100 MHz, CDCl3)
(b) J. Ichikawa, in: V.A. Soloshonok, K. Mikami, T. Yamazaki, J.T. Welch, J. Honek
(Eds.), Current Fluoroorganic Chemistry. New Synthetic Directions, Technolo-
gies, Materials and Biological Applications, ACS Symposium Series 949, Oxford
University Press/American Chemical Society, Washington, DC, 2006 , pp. 155–
168.
d
56.84 (d, 2JCF = 24.0 Hz, C-3), 57.13, 83.39, 92.36 (d, 2JCF = 19.8 Hz,
C-1), 127.10, 127.30, 127.90, 128.16, 128.22, 128.78, 137.90, 139.69,
165.06(d, 1JCF = 260.2 Hz, C-2);19FNMR (283 MHz, CDCl3)
d
ꢁ104.11
3
(ddd, JHF = 17.8, 23.8, 50.0 Hz). MS (CI) m/z 225 [MꢁMeOH+H]+;
[8] (a) W.S. Johnson, G.W. Daub, T.A. Lyle, M. Niwa, J. Am. Chem. Soc. 102 (1980)
7800–7802;
HRMS (CI) Calcd. for C16H14F: 225.1080, Found: 225.1077.
Minor (selected data): 1H NMR (300 MHz, CDCl3)
d 3.26 (s, 3H),
(b) W.S. Johnson, T.A. Lyle, G.W. Daub, J. Org. Chem. 47 (1982) 161–163;
(c) P.V. Fish, W.S. Johnson, G.S. Jones, F.S. Tham, R.K. Kullnig, J. Org. Chem. 59
(1994) 6150–6152, and references therein.
3
3
3
3.68 (dd, JHH = 9.9 Hz, JHF = 24.8 Hz, 1H), 4.51 (d, JHH = 9.9 Hz,
1H), 4.53 (dd, JHH = 3.1 Hz, JHF = 50.2 Hz, 1H), 4.72 (dd,
2JHH = 3.1 Hz, JHF = 17.8 Hz, 1H), 7.04–7.16 (m, 10H); 13C NMR
(100 MHz, CDCl3)
3JCF = 3.3 Hz, C-4), 91.84 (d, JCF = 19.8 Hz, C-1), 127.02, 127.49,
127.72, 127.96, 128.22, 128.46 (d, JCF = 1.6 Hz), 137.74, 139.05,
165.49 (d, JCF = 261.0 Hz, C-2): 19F NMR (283 MHz, CDCl3)
2
3
[9] Y. Usuki, Y. Fukuda, H. Iio, ITE Lett. Batteries, New Technol. Med. 2 (2001) 237–
240;
(b) M. Engman, J.S. Diesen, A. Paptchikhine, P.G. Andersson, J. Am. Chem. Soc. 129
(2007) 4536–4537.
[10] (a) T. Hayashi, K. Kabeta, I. Hamachi, M. Kumada, Tetrahedron Lett. 24 (1983)
2865–2868;
(b) S.E. Denmark, E.J. Weber, Helv. Chim. Acta 66 (1983) 1655–1660.
[11] (a) H. Sakurai, K. Sasaki, A. Hosomi, Tetrahedron Lett. 22 (1981) 745–748;
(b) T. Mukaiyama, H. Nagaoka, M. Murakami, M. Ohshima, Chem. Lett. 14 (1985)
977–980.
3
2
d
56.82 (d, JCF = 24.0 Hz, C-3), 56.96, 84.11 (d,
2
3
1
d
3
ꢁ105.59 (ddd, JHF = 17.8, 24.8, 50.2 Hz).
[12] A. Altomare, M.C. Burla, M. Camalli, G.L. Cascarano, C. Giacovazzo, A. Gua-
gliardi, A.G.G. Moliterni, G. Polidori, R. Spagna, J. Appl. Cryst. 32 (1999) 115–
119.
Acknowledgements
We thank Dr. Tsuneaki Yamagata and Dr. Rika Tanaka for the X-
[13] G.M. Sheldrick, SHELX-97, Programs for Crystal Structure Analysis (Release
ray structure determination of 2a.
97-2), University of Go¨ttingen, Go¨ttingen, Germany, 1997 .