Chromium-mediated fluoroalkenylation reactions of 1,1-dibromo-1- fluoroalkane and 1-bromo-1-fluoroalkene derivatives

Article abstract of DOI:10.1016/j.jfluchem.2005.05.003

CrCl₂- and NiCl₂-mediated coupling reactions of E/Z mixture of 1-bromo-1-fluoroalkenes with aldehydes proceeded in a high stereoselectivity to give the corresponding (Z)-2-fluoroallylic alcohol derivatives. On the other hand, in the

Full text of DOI:10.1016/j.jfluchem.2005.05.003

Journal of Fluorine Chemistry 126 (2005) 1166–1173
www.elsevier.com/locate/fluor
Chromium-mediated fluoroalkenylation reactions of
1,1-dibromo-1-fluoroalkane and 1-bromo-1-fluoroalkene derivatives
*
Akio Saito, Muga Nakagawa, Takeo Taguchi
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan
Received 16 March 2005; received in revised form 9 May 2005; accepted 9 May 2005
Available online 23 June 2005
Abstract
CrCl2- and NiCl2-mediated coupling reactions of E/Z mixture of 1-bromo-1-fluoroalkenes with aldehydes proceeded in a high
stereoselectivity to give the corresponding (Z)-2-fluoroallylic alcohol derivatives. On the other hand, in the reaction of 1,1-dibromo-1-
fluoroalkane with CrCl2, (Z)-fluoroalkene derivative was formed via a-elimination reaction of the chromium carbenoid intermediate
accompanying the concomitant 1,2-shift of b-hydrogen.
# 2005 Elsevier B.V. All rights reserved.
Keywords: Chromium chloride; Fluoroalkenylation; 1-Bromo-1-fluoroalkene; 1,1-Dibromo-1-fluoroalkane; 2-Fluoroallylic alcohol
1. Introduction
alkenes in palladium-catalyzed coupling reactions [10] are
providing highly useful positions.
Fluorinated olefins are an important class of compounds in
the field of medicinal chemistry and material science, for
example in medicinal chemistry area as potential enzyme
inhibitors [1,2] or as an ideal mimic of amide bond [3–5].
Therefore, development of new and efficient synthetic
methods for fluorinated olefins has been extensively investi-
gated. The synthetic methods for fluorinated olefins can be
classified into two types, which involve carbon–fluorine bond
forming reactions and the use of the fluorinated compounds as
building blocks. In the former case, fluorination of alkenyl
anion with electrophilic fluorinating reagent, such as N-
fluorosulfonamide [6] or fluoroolefin formation by the react-
ion of carbonyl compounds with diethylaminosulfur
trifluoride (DAST) [7] are known, while there remains
several problems in the stereoselectivity and the generality of
these reactions. As typical building blocks for fluorinated
olefin synthesis, fluorophosphonoacetate in the Horner–
Emmons reaction [8], fluorosilylacetate in the Peterson
olefination [9] and 1-fluoro-1-sulfonyl- or 1-fluoro-1-stannyl-
It would be expected that like non-fluorinated vinyl metal
chemistry [11], if fluorovinyl metal species were readily
generated by hydrometalation or carbometalation reaction
with fluoroacetylene derivatives, such reactive organome-
tallics should open convenient accesses to a variety type of
fluorinated olefins. However, it is known that fluoroacety-
lenes oligomerize very easily [12], that is, fluoroacetylenes
are too unstable to handle as synthetic intermediates
(Scheme 1).
Therefore, development of an efficient method for the
stereo- and chemo-selective generation of reactive fluor-
ovinyl metal species should be challenging subject. Among
such studies, Burton et al. have reported the kinetic
separation of the (E)- and (Z)-isomers of 1-bromo-1-
fluoroalkenes using Pd-catalyzed carbonylation and hydro-
genolysis reactions, in which the (E)-isomer shows
remarkably higher reactivity than the (Z)-isomer [13].
Related to this, very recently, Pannecoucke and co-workers
reported the stereoselective dehydrobromination of 1-
bromo-1-fluoroalkenes with DBU or LiHMDS obtaining
the (E)-isomer unchanged [14].
* Corresponding author. Tel.: +81 426 76 3257; fax: +81 426 76 3257.
E-mail address: taguchi@ps.toyaku.ac.jp (T. Taguchi).
0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.05.003

A. Saito et al. / Journal of Fluorine Chemistry 126 (2005) 1166–1173
1167
Scheme 1.
Accumulated synthetically useful methods for the
preparation of alkenylated compounds employing chro-
mium chemistry [15] prompted us to examine the generation
of fluoroalkenyl chromium species from 1,1-dihalo-1-
fluoroalkane or 1-bromo-1-fluoroalkene. Falck et al. demon-
strated that 1,1,1-trichloroalkane 1 reacts with chromium(II)
chloride to generate (E)-chloroalkenyl chromium(III)
species 3 stereoselectively via gem-bischromium(III) car-
benoid intermediate 2 and this chloroalkenyl chromium
species 3 can serve in carbon–carbon bond forming reactions
such as addition to aldehyde and Pd-catalyzed arylation
reaction [16] (Scheme 2). As one of the most useful
chromium-mediated reactions, a highly chemo-selective
addition reaction of alkenylchromium(III) generated from
alkenyl iodide and CrCl2/NiCl2 with aldehyde, so-called
Nozaki–Hiyama–Kishi (N–H–K) reaction, has been well
documented with many applications to the key steps in the
total synthesis of structurally complicated natural products
[15,17].
Scheme 3.
temperature promoted the reaction giving rise to (Z)-
fluoroalkene 6 in 16% yield after 20 h (entry 2). In DMF
reaction proceeded smoothly consuming 5 within 6 h to give
fluoroalkene 6 in 75% yield with complete Z-selectivity after
aqueous work-up (entry 3). Furthermore, it was found that
treatment of the reaction mixture obtained under the same
conditions with D2O or benzaldehyde instead of aqueous
work-up resulted in the formation of fluoroalkene 6 as a sole
product, and any deuterium incorporation or fluoroalk-
enylation of aldehyde was not observed (entries 4–6).
Under the Barbier’s conditions, namely when a mixture
of 5, benzaldehyde, CrCl2 and Mn powder in DMF was
stirred at room temperature, we obtained the fluoroallyl
alcohol 7db in only 12% yield along with the isolation of 6
in 39% yield, still as a major product (Scheme 4).
Contrary to the hydrocarbon chemistry area, however,
when we started the chromium chemistry, there had been no
report on the reaction of 1,1-dihalo-1-fluoroalkane or 1-
bromo-1-fluoroalkene with CrCl2 [18], while very recently,
Pannecoucke et al. reported the stereoselective fluoroalk-
enylation of aldehydes employing N–H–K reaction of 1-
bromo-1-fluoroalkene [19]. In this paper, we report our
collective results obtained from the reactions of 1,1-
dibromo-1-fluoroalkane and 1-bromo-1-fluoroalkene deri-
vatives with CrCl2, in particular, the former shows a
different reactivity as compared with that of trichloroalkanes
and the latter provides Z-selective formation of 1-substituted
2-fluoroallylic alcohols using the E/Z mixture (Scheme 3).
Possible reaction pathway is illustrated in Scheme 5.
From these results and the efficient fluoroalkenylation of
aldehyde with 1-bromo-1-fluoroalkene mediated by CrCl2/
NiCl2 in DMF (vide infra), it would be likely that the
formation of fluoroalkenyl chromium species 11 is not the
major reaction pathway in the reaction of dibromofluor-
oalkane 5 with CrCl2 and Mn powder in DMF. On the other
hand, the 1,2-shift of b-hydrogen to divalent carbon
resulting in the formation of an alkene is well known
reaction via carbene and carbenoid intermediate [20].
Likewise, the reaction pathway to the major product
fluoroalkene 6 from dibromofluoride 5 possibly involves
the generation of chromium carbenoid intermediate 9 as the
first step, and then a-elimination of bromine accompanying
the concomitant 1,2-shift of b-hydrogen prior to the second
reaction of the carbenoid intermediate 9 with CrCl2 to
generate bischromium intermediate 10 (Scheme 5).
Mechanistic detail is the future subject.
2. Results and discussion
Initially, reaction of TBDPS ether of 3,3-dibromo-3-
fluoropropanol 5 with CrCl2 was conducted under various
conditions to see the possibility for the generation of
fluoroalkenyl chromium species, similar to trichloro
derivative (Table 1). Dibromofluoro compound 5 did not
react with CrCl2 in THF at room temperature (entry 1), while
a combination of CrCl2 and Mn powder in THF at the same
Scheme 2.

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A. Saito et al. / Journal of Fluorine Chemistry 126 (2005) 1166–1173
Scheme 4.
Scheme 5.
Since it was difficult to achieve chromium-mediated
Z = 47:53) with 3-phenylpropanal gave the adduct 7ba in
75% yield, and with benzaldehyde the product 7bb was
obtained in 70% yield (entries 3, 4). In these cases, a high Z
selectivity of the isolated fluoroallyl alcohol derivative was
observed, 7ba; Z/E = 94:6 and 7bb; Z/E = 92:8, respec-
tively. Under the similar conditions, the homoallyl ether
derivative 8c reacted with 3-phenylpropanal and benzalde-
hyde to give the corresponding adduct 7ca in 70% yield (Z/
E = 93:7) and 7cb in 73% yield (Z/E = 95:5), respectively
(entries 5, 6). In the case of the allyl ether derivative 8d,
while a longer reaction time was required, highly Z selective
formation of the adducts 7da and 7db was also observed (Z/
E > 95:5) (entries 7,8).
fluoroalkenylation of aldehyde using 1,1-dibromo-1-fluor-
oalkane, we next examined the N–H–K reaction using a E/Z
mixture of 1-bromo-1-fluoroalkene. According to the
reported procedure [21], 1-bromo-1-fluoroalkenes 8a–8d
were prepared as an almost 1:1 E/Z mixture, which was used
chromium-mediated reaction with aldehyde. Results are
summarized in Table 2. When a mixture of the 1-bromo-1-
fluorostyrene 8a (E/Z = 45:55, 4 equiv), 3-phenylpropanal (1
equiv), CrCl2 (8 equiv) and a catalytic amount of NiCl2
(8 mol %) in DMF was stirred at room temperature for 4 h,
the fluoroallyl alcohol 7aa was isolated in 74% yield as a
single (Z)-isomer (entry 1). Similarly, with benzaldehyde the
adduct 7ab consisting of only (Z)-isomer was obtained in
62% yield (entry 2). The alkyl group substituted substrate 8b
showed lower reactivity than styrene derivative 8a, requiring
much more NiCl2 for the reaction to proceed smoothly.
Thus, on using 80 mol% NiCl2, the reaction of 8b (E/
To see the difference in reactivity due to the olefin
geometry, we carried out the reaction of (Z)-isomer of
bromofluoroalkene (Z)-8d with 2 equiv of benzaldehyde
(Scheme 6). Reaction proceeded rather sluggishly to give the
(E)-isomer of alkenylated product (E)-7db in 10% yield
Table 1
Reaction of dibromofluoroalkane 5 with CrCl
Entry
CrCl2 (equiv)
Mn (equiv)
Solvent
Time (h)
E+
6 yield (%)a
1
2
3
4
4.8
2
0
4
4
4
4
4
THF
12
20
6
H2O
No reaction
THF
H2O
16
2
DMF
DMF
DMF–d7
DMF
H2O
75
2
6
D2O
73b
66b
60c
5
6
a
2
6
H2O
2
6
PhCHO
Isolated yield.
b
c
6-D was not detected.
2-Fluoroallylic alcohol 7db was not detected.

A. Saito et al. / Journal of Fluorine Chemistry 126 (2005) 1166–1173
1169
Table 2
Synthesis of 2-fluoroallyl alcohol derivatives 7
Entry
8 (E/Z)
R2CHO
Methoda
Time (h)
7
Yieldb (%)
Z/Ec
1
2
A
A
4
4
7aa
7ab
74
62
100:0
100:0
3
4
B
B
4
4
7ba
7bb
75
70
94:6
92:8
5
6
B
B
4
4
7ca
7cb
70
73
93:7
95:5
7
8
B
B
12
12
7da
7db
64
60
>95:5
>95:5
a
Method A: 8 mol% of NiCl2, 8 equiv of CrCl2 and 4 equiv of 8 were employed in DMF (0.03 M); method B: 8 mol% of NiCl2, 8 equiv of CrCl2 and 4 equiv of
8 were employed in DMF (0.06 M).
b
Isolated yield based on the aldehyde.
Z/E ratio was determined by 300 MHz 1H NMR.
c
along with the recovery of (Z)-8d in 4% yield, but (Z)-isomer
of alkenylated product (Z)-7db was not detected. Besides,
these compounds, formation of homocoupling products of
8d seemed to make this reaction rather complicated [17c,d].
Similar reaction using E/Z mixture (ratio 44:56) gave (Z)-
7db in 89% yield based on the starting (E)-isomer of the
bromide (E)-8d, and (E)-7db in 11% yield based on (Z)-8d
along with the recovery of (Z)-8d in 11%. From these
results, (E)-isomer of the bromide 8 shows highly efficient
reactivity with CrCl2/NiCl2 to form (E)-fluroalkenyl
chromium species, which reacts with aldehyde to give the
(Z)-fluoroallylic alchohol. On the other hand, compared with
the (E)-isomer, (Z)-isomer reacts with CrCl2/NiCl2 much
more slowly to form the (Z)-alkenylchromium species
stereospecifically leading to (E)-fluoroallylic alchohol
although yield is quite low. Therefore, when the reaction
is conducted using excess amount of bromofluoroalkene 8
relative to aldehyde, highly Z-selective fluoroalkenylation
reaction can be achieved.
In summary, CrCl2–NiCl2-mediated reaction of an E/Z
mixture of 1-bromo-1-fluoroalkene with aldehyde provided
a highly Z-selective alkenylation product. Furthermore, the
reaction of 1,1-dibromo-1-fluoroalkane with CrCl2 was
found to give (Z)-fluoroalkene derivative via a-elimination
reaction of the chromium carbenoid intermediate accom-
panying the concomitant 1,2-shift of b-hydrogen.
3. Experimental details
General: CrCl2, NiCl2 and Mn are available commer-
cially. All reactions were carried out under argon atmo-
1
sphere. H and 13C NMR spectra were taken on a Bruker
dpx400 spectrometer, and chemical shifts were reported in
Scheme 6.

1170
A. Saito et al. / Journal of Fluorine Chemistry 126 (2005) 1166–1173
1
2858, 1472, 1428, 1112, 740, 702. H NMR (400 MHz,
parts per million (ppm) using CHCl3 (7.26 ppm) in CDCl3
1
for H NMR, and CDCl3 (77.01 ppm) for 13C NMR as an
CDCl3) d; 1.06 (9H, s), 4.37 (2H, ddd, J = 6.6, 2.2, 1.5 Hz),
5.03 (1H, dtd, J = 42.2, 6.6, 4.8 Hz), 5.40 (1H, ddt, J = 84.0,
4.8, 1.5 Hz), 7.33–7.47 (6H, m), 7.61–7.73 (4H, m). 13C
NMR (100.6 MHz, CDCl3) d; 19.2, 26.8, 56.3 (d,
J = 7.6 Hz), 111.1 (d, J = 3.0 Hz), 127.7, 129.7, 133.6,
135.6, 147.7 (d, J = 260.4 Hz). 19F NMR (376.5 MHz,
CDCl3) d; À64.3 (1F, ddt, J = 84.0, 42.2, 2.2 Hz). EI–MS m/
z: 257 (M+–C4H9). HRMS calcd for C15H14FOSi: 257.0798
(M+–C4H9). Found: 257.0805.
internal standard, respectively. 19F NMR spectra were taken
on a Bruker dpx400 spectrometer, and chemical shifts were
reported in parts per million using benzotrifluoride as a
standard. Infrared (IR) spectra were recorded on a JASCO
FT/IR-620 infrared spectrophotometer. Mass spectra (MS)
were obtained on a VG Auto Spec. Medium pressure liquid
chromatography (MPLC) was performed using prepacked
column (silica-gel, 50 mm) with RI detector.
(Z)-4-{ [(1,1-Dimethylethyl)(diphenyl)silyl]oxy}-2-fluoro
-1-phenyl-2-buten-1-ol (7db): Colorless oil. IR (neat)
n cmÀ1; 3398, 3070, 2931, 2858, 1472, 1428, 1111, 1060,
741, 702. 1H NMR (400 MHz, CDCl3) d; 1.07 (9H, s), 2.16
(1H, br. s), 4.39 (2H, d, J = 6.6 Hz), 5.14 (1H, dd, J = 11.1,
4.4 Hz), 5.21 (1H, dt, J = 36.6, 6.6 Hz), 7.34–7.46 (11H, m),
7.67–7.70 (4H, m). 13C NMR (100.6 MHz, CDCl3) d; 19.1,
26.8, 57.1 (d, J = 6.8 Hz), 72.4 (d, J = 32.0 Hz), 107.2 (d,
J = 11.0 Hz), 126.7, 127.7, 128.4, 128.6, 129.6, 133.6,
135.6, 139.1, 158.7 (d, J = 260.4 Hz). 19F NMR
(376.5 MHz, CDCl3) fd; À55.9 (1F, dd, J = 36.6,
11.1 Hz). EI–MS m/z: 285 (M+–C10H15). HRMS calcd for
C16H16FO2Si: 285.0747 (M+–C10H15). Found: 285.0756.
Anal. Calcd for C26H29FO2Si: C, 74.25; H, 6.95. Found: C,
73.90; H, 7.03.
3.1. Preparation of (1,1-dimethylethyl)(diphenyl)silyl
3,3-dibromo-3-fluoropropyl ether (5)
Under an argon atmosphere, to a solution of LiBH4
(230 mg, 10.6 mmol) in Et2O (6 mL), ethyl 3,3-dibromo-3-
fluoropropionate [22] (2.7 g, 9.7 mmol) in Et2O (4 mL) and
trimethyl borate (200 mL, 1.8 mmol) were added at 0 8C.
After being stirred at the same temperature for 2 h and then
at room temperature for 5 h, addition of NH4Cl aq. followed
by extractive work-up gave 3,3-dibromo-3-fluoropropanol,
which was used without purification. A mixture of this
alcohol, tert-butyldiphenylchlorosilane (1.5 mL, 5.8 mmol)
and imidazole (550 mg, 8.1 mmol) in THF (6 mL) was
stirred at room temperature for 5 h. Addition of H2O
followed by extractive work-up and purification by column
chromatograpy (hexane/AcOEt = 100:1) gave the product 5
(2.5 g, 5.2 mmol, 54% yield).
3.3. General procedure for preparation of 1-bromo-1-
fluoroalkene: preparation of 1-[(E)- and (Z)-2-bromo-2-
fluoroethenyl]benzene (8a)
(1,1-Dimethylethyl)(diphenyl)silyl 3,3-dibromo-3-fluoro-
propyl ether (5): Colorless oil. IR (neat) n cmÀ1; 3071, 2931,
2858, 1472, 1428, 1113, 823, 739, 702. 1H NMR (400 MHz,
CDCl3) d; 1.09 (9H, s), 3.04 (2H, dt, J = 15.8, 6.7 Hz), 4.00
(2H, t, J = 6.7 Hz), 7.40–7.48 (6H, m), 7.69–7.72 (4H, m).
13C NMR (100.6 MHz, CDCl3) d; 19.1, 26.8, 54.8 (d,
J = 18.0 Hz), 61.0 (d, J = 2.9 Hz), 93.0 (d, J = 319.7 Hz),
127.8, 129.9, 133.1, 135.6. 19F NMR (376.5 MHz, CDCl3) d;
19.1 (1F, t, J = 15.8 Hz). EI–MS m/z: 291 (M+–C6H11BrF).
HRMS calcd for C13H12BrOSi: 290.9841 (M+–C6H11BrF),
Found: 290.9814. Anal. Calcd for C19H23Br2FOSi: C, 48.12;
H, 4.89. Found: C, 48.39; H, 4.91.
Under an argon atmosphere, to a suspension of Zn (1.2 g,
18.4 mmol) and triphenylphosphine (3.1 g, 11.8 mmol) in
THF (30 mL), a solution of benzaldehyde (0.6 mL,
5.9 mmol) and tribromofluoromethane (4.8 g, 17.7 mmol)
in THF (10 mL) was added at room temperature. After being
refluxed for 2 h, usual work-up and purification by column
chromatography (hexane/Et2O = 100:1) gave the product 8a
(1.1 g, 5.3 mmol, 89% yield, E/Z = 45:55).
1-[(E)- and (Z)-2-bromo-2-fluoroethenyl]benzene (8a):
1H and 19F NMR spectra of this compound was identical
with those reported by Burton and co-workers [21].
1-[(E)- and (Z)-4-bromo-4-fluoro-3-butenyl]benzene
(8b): 1H and 19F NMR spectra of this compound was
identical with those reported by Hiyama and co-workers
[23].
3.2. Reaction of 1,1-dibromo-1-fluoroalkane with CrCl2
Underanargonatmosphere,toamixtureofCrCl2 (94.0 mg,
0.77 mmol) and Mn (55.0 mg, 1.0 mmol) in DMF (3 mL)
sonicated for 10 min, was added a solution of 5 (120 mg,
0.25 mmol) and benzaldehyde (50 mL, 0.49 mmol) in DMF
(2 mL). After being stirred at room temperature for 14 h,
additionofH2Ofollowedbyextractivework-upandseparation
by column chromatography gave a fraction containing 6
(hexane/AcOEt = 50:1) and allylic alcohol 7db (12.4 mg,
0.03 mmol, 12%, hexane/AcOEt = 6:1). The former was
further separated by MPLC (hexane/AcOEt = 50:1, flow rate
7.0 mL/min) to give 6 (31.2 mg, 0.1 mmol, 39% yield).
(1,1-Dimethylethyl)(diphenyl)silyl (Z)-3-fluoro-2-prope-
nyl ether (6): Colorless oil. IR (neat) n cmÀ1; 3071, 2931,
(E)- and (Z)-4-bromo-4-fluoro-3-butenyl (1,1-dimethy-
lethyl)(diphenyl)silyl ether (8c): Colorless oil. IR (neat)
n cmÀ1; 3071, 2931, 2858, 1472, 1428, 1112, 1024, 822,
740, 702. 1H NMR (400 MHz, CDCl3) d; 1.09 (9H, s), 2.30
(Z–2H, dt, J = 7.4, 6.6 Hz), 2.38 (E–2H, dt, J = 7.7, 6.4 Hz),
3.69–3.76 (2H, m), 5.14 (E–1H, dt, J = 31.3, 7.7 Hz), 5.60
(Z–1H, dt, J = 13.4, 7.4 Hz), 7.40–7.49 (6H, m), 7.68–7.77
(4H, m). 13C NMR (100.6 MHz, CDCl3) d; 19.2, 26.8, 29.2,
31.1, 62.3, 62.4, 107.1 (d, J = 16.5 Hz), 109.6 (d,
J = 12.4 Hz), 127.7, 129.7, 132.4 (d, J = 316.1 Hz), 133.6,
135.6, 136.0 (d, J = 317.9 Hz). 19F NMR (376.5 MHz,

A. Saito et al. / Journal of Fluorine Chemistry 126 (2005) 1166–1173
1171
CDCl3) d; À7.5 (Z–1F, d, J = 13.4 Hz), À12.0 (E–1F, d,
J = 31.3 Hz). EI–MS m/z: 349 (M+–C4H9). HRMS calcd for
C16H15BrFOSi: 349.0060 (M+–C4H9). Found: 349.0054.
(E)- and (Z)-3-bromo-3-fluoro-2-propenyl (1,1-dimethy-
lethyl)(diphenyl)silyl ether (8d): Colorless oil. IR (neat)
n cmÀ1; 3071, 2958, 2857, 1472, 1428, 1113, 1070, 822,
740, 702. 1H NMR (400 MHz, CDCl3) d; 1.09 (9H, s), 4.24
(Z–2H, dd, J = 6.8, 2.2 Hz), 4.28 (E–2H, dd, J = 6.9,
2.7 Hz), 5.30 (E–1H, dd, J = 30.6, 6.9 Hz), 5.74 (Z–1H,
dd, J = 12.3, 6.8 Hz), 7.35–7.53 (6H, m), 7.62–7.78 (4H, m).
13C NMR (100.6 MHz, CDCl3) d; 19.1, 26.8, 57.9 (E, d,
J = 3.3 Hz), 61.0 (Z, d, J = 7.3 Hz), 109.8 (Z, d,
J = 14.7 Hz), 112.4 (E, d, J = 10.7 Hz), 127.8, 129.8,
133.2 (E), 133.2 (Z), 133.4 (E, d, J = 322.5 Hz), 135.5
(E), 135.6 (Z), 136.2 (Z, d, J = 318.6 Hz). 19F NMR
(376.5 MHz, CDCl3) d; À6.6 (Z–1F, dd, J = 12.3, 2.2 Hz),
À8.8 (E–1F, dd, J = 30.6, 2.7 Hz). EI–MS m/z: 335 (M+–
C4H9). HRMS calcd for C15H13BrFOSi: 334.9903 (M+–
C4H9). Found: 334.9908. Anal. Calcd for C19H22BrFOSi: C,
58.01; H, 5.64. Found: C, 58.18; H, 5.73.
J = 4.3 Hz), 31.4, 35.3, 35.4, 70.1 (d, J = 30.3 Hz), 105.9 (d,
J = 13.9 Hz), 126.0, 126.0, 128.3, 128.4, 141.3, 159.5 (d,
J = 257.4 Hz). 19F NMR (376.5 MHz, CDCl3) d; À61.5 (1F,
dd, J = 37.5, 16.6 Hz). EI–MS m/z: 284 (M+). HRMS calcd
for C19H21FO: 284.1576 (M+). Found: 284.1565. Anal.
Calcd for C19H21FO: C, 80.25; H, 7.44. Found: C, 79.98; H,
7.49.
(Z)-2-Fluoro-1,5-diphenyl-2-penten-1-ol (7bb): Color-
less oil. IR (neat) n cmÀ1; 3389, 3028, 2926, 2859, 1496,
1453, 1024, 748, 700. 1H NMR (400 MHz, CDCl3) d; 2.26
(1H, br. s), 2.48 (2H, dt, J = 7.5, 7.5 Hz), 2.73 (2H, t,
J = 7.5 Hz), 4.95 (1H, dt, J = 36.9, 7.5 Hz), 5.17 (1H, d,
J = 12.7 Hz), 7.19–7.25 (3H, m), 7.28–7.39 (7H, m). 13C
NMR (100.6 MHz, CDCl3) d; 25.1 (d, J = 4.0 Hz), 35.3,
72.7 (d, J = 32.0 Hz), 106.7 (d, J = 13.3 Hz), 126.0, 126.6,
128.2, 128.3, 128.4, 128.5, 139.5, 141.3, 158.8 (d,
J = 256.5 Hz). 19F NMR (376.5 MHz, CDCl3) d; À59.4
(1F, dd, J = 36.9, 12.7 Hz). EI–MS m/z: 256 (M+). HRMS
calcd for C17H17FO: 256.1263 (M+). Found: 256.1256.
(Z)-7-{[( 1,1-Dimethylethyl)(diphenyl)silyl]oxy}-4-fluoro
-1-phenyl-4-hepten-3-ol (7ca): Colorless oil. IR (neat)
n cmÀ1; 3388, 3070, 2930, 2858, 1472, 1428, 1111, 740,
701. 1H NMR (400 MHz, CDCl3) d; 1.09 (9H, s), 1.91–2.09
(2H, m), 2.40 (2H, dt, J = 7.4, 6.4 Hz), 2.66–2.85 (2H, m),
3.73 (2H, t, J = 6.4 Hz), 4.07 (1H, ddd, J = 15.8, 9.4,
6.2 Hz), 4.92 (1H, dt, J = 37.8, 7.4 Hz), 7.18–7.26 (3H, m),
7.28–7.33 (2H, m), 7.37–7.47 (6H, m), 7.69–7.71 (4H, m).
13C NMR (100.6 MHz, CDCl3) d; 19.6, 27.3, 27.4 (d,
J = 3.9 Hz), 32.0, 35.8, 63.5, 70.5 (d, J = 30.2 Hz), 103.8 (d,
J = 13.7 Hz), 126.4, 128.1, 128.9, 128.9, 130.0, 134.3,
136.0, 141.8, 160.6 (d, J = 257.5 Hz). 19F NMR
(376.5 MHz, CDCl3) d; À61.9 (1F, dd, J = 37.8, 15.8 Hz).
EI–MS m/z: 230 (M+–C16H21F). HRMS calcd for
C13H14O2Si: 230.0763 (M+–C16H21F). Found: 230.0780.
Anal. Calcd for C29H35FO2Si: C, 75.28; H, 7.62. Found: C,
75.38; H, 7.66.
3.4. General procedure for CrCl2/NiCl2-mediated
reaction of 1-bromo-1-fluoroalkene
with aldehyde
Under an argon atmosphere, to a mixture of CrCl2
(185 mg, 1.5 mmol) and NiCl2 (2.0 mg, 15 mmol) in DMF
(4 mL) sonicated for 10 min, was added a solution of 8a
(120 mg, 0.25 mmol) and 3-phenylpropanal (50 mL,
0.49 mmol) in DMF (2 mL). After being stirred at room
temperature for 4 h, addition of H2O followed by extractive
work-up and purification by column chromatography
(hexane/AcOEt = 5:1) gave the product 7aa (35.4 mg,
0.14 mmol, 74% yield).
(Z)-2-Fluoro-1,5-diphenyl-1-penten-3-ol (7aa): Color-
less oil. IR (neat) n cmÀ1; 3365, 3027, 2926, 1495, 1451,
1
1032, 752, 695. H NMR (400 MHz, CDCl3) d; 2.02–2.18
(Z)-5-{ [(1,1-Dimethylethyl)(diphenyl)silyl]oxy}-2-fluoro
-1-phenyl-2-penten-1-ol (7cb): Colorless oil. IR (neat)
n cmÀ1; 3397, 3070, 2930, 2858, 1472, 1428, 1111, 739,
702. 1H NMR (400 MHz, CDCl3) d; 1.06 (9H, s), 2.20 (1H,
br. s), 2.40 (2H, dt, J = 7.4, 6.4 Hz), 3.71 (2H, t, J = 6.4 Hz),
5.00 (1H, dt, J = 37.3, 7.4 Hz), 5.21 (1H, dd, J = 12.3,
3.5 Hz), 7.33–7.47 (11H, m), 7.66–7.71 (4H, m). 13C NMR
(100.6 MHz, CDCl3) d; 19.2, 26.8, 27.0 (d, J = 3.7 Hz), 63.0,
72.8 (d, J = 31.7 Hz), 104.5 (d, J = 13.3 Hz), 126.7, 127.6,
128.3, 128.5, 129.6, 133.8, 135.6, 139.5, 159.5 (d,
J = 257.0 Hz). 19F NMR (376.5 MHz, CDCl3) d; À58.7
(1F, dd, J = 37.3, 12.3 Hz). EI–MS m/z: 299 (M+–C10H15).
HRMS calcd for C17H18FO2Si: 299.0904 (M+–C10H15).
Found: 299.0893. Anal. Calcd for C27H31FO2Si: C, 74.61;
H, 7.19. Found: C, 74.37; H, 7.33.
(2H, m), 2.72–2.86 (2H, m), 4.24 (1H, ddd, J = 15.2, 7.2,
6.2 Hz), 5.78 (1H, d, J = 39.6 Hz), 7.20–7.37 (8H, m), 7.49–
7.53 (2H, m). 13C NMR (100.6 MHz, CDCl3) d; 31.5, 35.5,
70.6 (d, J = 30.1 Hz), 106.5 (d, J = 6.7 Hz), 126.0, 127.4,
128.5, 128.7, 128.7, 132.7, 141.2, 160.1 (d, J = 269.7 Hz).
19F NMR (376.5 MHz, CDCl3) d; À55.2 (1F, dd, J = 39.6,
15.2 Hz). EI–MS m/z: 256 (M+). HRMS calcd for
C17H17FO: 256.1263 (M+). Found: 256.1252. Anal. Calcd
for C17H17FO: C, 79.66; H, 6.69. Found: C, 79.27; H, 6.94.
1
(Z)-2-Fluoro-1,3-diphenyl-2-propen-1-ol (7ab): H and
19F NMR spectra of this compound was identical with those
reported by Hiyama et al [24].
(Z)-4-Fluoro-1,7-diphenyl-4-hepten-3-ol (7ba): Color-
less oil. IR (neat) n cmÀ1; 3377, 3027, 2925, 2858, 1496,
1
1454, 1030, 748, 699. H NMR (400 MHz, CDCl3) d; 1.86
(Z)-6-{ [(1,1-Dimethylethyl)(diphenyl)silyl]oxy}-4-fluoro
-1-phenyl-4-hexen-3-ol (7da): Colorless oil. IR (neat)
n cmÀ1; 3388, 3070, 2931, 2858, 1471, 1428, 1111, 1065,
740, 701. 1H NMR (400 MHz, CDCl3) d; 1.08 (9H, s), 1.72
(1H, br. s), 1.87–2.01 (2H, m), 2.64–2.81 (2H, m), 4.04 (1H,
(1H, br. s), 1.91–2.05 (2H, m), 2.47 (2H, dt, J = 7.5, 7.5 Hz),
2.59–2.78 (4H, m), 4.06 (1H, ddd, J = 16.6, 7.3, 6.5 Hz),
4.85 (1H, dt, J = 37.5, 7.5 Hz), 7.15–7.26 (6H, m), 7.29–
7.33 (4H, m). 13C NMR (100.6 MHz, CDCl3) d; 24.9 (d,

1172
A. Saito et al. / Journal of Fluorine Chemistry 126 (2005) 1166–1173
[10] (a) J.R. McCarthy, E.W. Huber, T.-B. Le, F. Mark Laskovics, D.
Mattews, Tetrahedron 52 (1996) 45–58;
ddd, J = 14.3, 7.1, 7.1 Hz), 4.38 (2H, d, J = 6.6 Hz), 5.09
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(2H, m), 7.38–7.45 (6H, m), 7.69–7.72 (4H, m). 13C NMR
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