Synthesis and functionalization of (Z)-1,2-difluoro-1-tri-n-butylstannyl-1,4-pentadiene

Article abstract of DOI:10.1016/j.jfluchem.2014.12.006

The Zn reagent prepared from (E)-1,2-difluoro-1-iodo-2-triethylsilylethene followed by reaction with allyl bromide gave (Z)-1,2-difluoro-1-triethylsilyl-1,4-pentadiene. Further reaction of (Z)-1,2-difluoro-1-triethylsilyl-1,4-pentadiene with KF, n-Bu₃SnCl, in DMF at 70 °C gave (Z)-1,2-difluoro-1-tri-n-butylstannyl-1,4-pentadiene. Coupling of (Z)-1,2-difluoro-1-tri-n-butylstannyl-1,4-pentadiene with substituted aryl iodides under Stille-Libeskind (Pd(PPh₃)₄/Cu(I)I) conditions gave the arylated product. Similar coupling of perfluorovinyl iodides stereospecifically gave the corresponding trienes. Hydroboration/oxidation with 9-BBN and H₂O₂ of (Z)-1,2-difluoro-1-tri-n-butylstannyl-1,4-pentadiene gave (Z)-4,5-difluoro-5-tri-n-butylstannyl-4-penten-1-ol. Additional couplings of (Z)-4,5-difluoro-5-tri-n-butylstannyl-4-penten-1-ol with substituted aryl iodides under Stille-Libeskind conditions gave the corresponding difunctionalized molecule.

Full text of DOI:10.1016/j.jfluchem.2014.12.006

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Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis and functionalization of (Z)-1,2-difluoro-1-tri-n-
butylstannyl-1,4-pentadiene§
*
Sandra Lukaszewski-Rose, Donald J. Burton
Department of Chemistry, The University of Iowa, Iowa City, IA 52242, USA
A R T I C L E I N F O
A B S T R A C T
Article history:
The Zn reagent prepared from (E)-1,2-difluoro-1-iodo-2-triethylsilylethene followed by reaction
with allyl bromide gave (Z)-1,2-difluoro-1-triethylsilyl-1,4-pentadiene. Further reaction of (Z)-1,2-
difluoro-1-triethylsilyl-1,4-pentadiene with KF, n-Bu3SnCl, in DMF at 70 8C gave (Z)-1,2-difluoro-1-tri-n-
butylstannyl-1,4-pentadiene. Coupling of (Z)-1,2-difluoro-1-tri-n-butylstannyl-1,4-pentadiene with
substituted aryl iodides under Stille–Libeskind (Pd(PPh3)4/Cu(I)I) conditions gave the arylated product.
Similar coupling of perfluorovinyl iodides stereospecifically gave the corresponding trienes. Hydro-
boration/oxidation with 9-BBN and H2O2 of (Z)-1,2-difluoro-1-tri-n-butylstannyl-1,4-pentadiene
gave (Z)-4,5-difluoro-5-tri-n-butylstannyl-4-penten-1-ol. Additional couplings of (Z)-4,5-difluoro-5-
tri-n-butylstannyl-4-penten-1-ol with substituted aryl iodides under Stille–Libeskind conditions gave
the corresponding difunctionalized molecule.
Received 22 October 2014
Received in revised form 16 December 2014
Accepted 17 December 2014
Available online xxx
´
Dedicated to Professor Veronique
Gouverneur.
Keywords:
(E)-1,2-Difluoro-1-(aryl)-1,4-pentadiene
(E,E)-4,5,6,7,8,8,8-Heptafluoro-1,4,6-
octatriene
ß 2014 Elsevier B.V. All rights reserved.
(Z)-4,5-Difluoro-5-tri-n-butylstannyl-4-
penten-1-ol
(E)-4,5-Difluoro-5-(aryl)-4-penten-1-ol
1. Introduction
carbanions. The stability of the carbanions is tertiary
(ꢀC(CF3)3) > secondary (ꢀCF(CF3)2) > primary (ꢀCF2RF)). In con-
Recently, we have reported the synthesis of (E)- and (Z)-2-
chloro-1,2-difluoro-1-iodoethene and (E)- and (Z)-2-bromo-1,2-
difluoro-1-iodoethene [1]. Subsequently we developed the stereo-
specific synthesis of (E)- and (Z)-1-chloro-1,2-difluorostryenes
from (E)- and (Z)-2-chloro-1,2-difluoro-1-iodoethene [2]. The
selectivity and the formation of the styrenes depended on the
difference in reactivity of the two halogens. It occurred to us that
another system would also potentially exhibit selectivity depend-
ing on the reactivity of two functional groups. For example, 1,1,2-
trifluoro-1,4-pentadiene (CF255CFCH2CH55CH2) has two olefinic
bonds with significant reactivity differences. The trifluorovinyl
group reacts readily with nucleophiles whereas the vinyl group
(CH55CH2) reacts readily with electrophiles. Hexafluoropropene
reacts with Fꢀ and water to add HF via a carbanion intermediate
(Eq. (1)) [3]. The regiochemistry of the Fꢀ induced reactions with
fluoroolefins can be predicted by the stability of the intermediate
trast to the fluoroolefin the allyl group of 1,1,2-trifluoro-1,4-
pentadiene will react selectively with electrophiles to generate
the more stable carbocation (38 > 28 > 18).
Stannanes are useful intermediates in Pd(0) cross-coupling
reactions. Pedersen utilized (Z)-1-tri-n-butylstannyl-1,2,3,4,4-
pentafluoro-1,3-butadiene to develop the stereospecific prepara-
tion of (E)-1-aryl-F-1,3-butadienes (Eq. (2)) [4]. Liu and Burton
utilized a bis-stannane to achieve the high yield synthesis of
symmetrical stilbenes (Eq. (3)) [5]. Wesolowski and coworkers
developed an approach to (Z)-1,2-difluorostilbenes (Eq. (4)) [6].
ð1Þ
§
Abstracted in part from Sandra Lukaszewski-Rose thesis, University of Iowa,
2000.
(2)
*
Corresponding author. Tel.: +1 319 335 1363; fax: +1 319 335 1270.
E-mail addresses: donald-burton@uiowa.edu, mburton105@gmail.com
(D.J. Burton).
http://dx.doi.org/10.1016/j.jfluchem.2014.12.006
0022-1139/ß 2014 Elsevier B.V. All rights reserved.
Please cite this article in press as: S. Lukaszewski-Rose, D.J. Burton, J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/
j.jfluchem.2014.12.006

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unfortunately, significant amounts of the reduced product
(E)-CH255CHCH2CF55CFH were obtained (Eq. (9)).
ð3Þ
ð4Þ
ð7Þ
ð8Þ
2. Results and discussion
1,1,2-Trifluoro-1,4-pentadiene reacts with simple nucleophiles
to undergo addition and elimination reactions. However, we were
more interested in aryl or vinyl derivatives, so we needed a
substituent in place of vinyl fluorine to allow for the stereospecific
introduction of aryl or vinyl groups. We have previously shown
that fluorinated vinyl silanes can be stereospecifically converted to
vinyl stannanes [7]. Therefore we attempted to prepare (Z)-1,2-
difluoro-1-triethylsilyl-1,4-pentadiene (1). We investigated two
pathways to attain 1. The first method utilized (E)-1,2-difluoro-1-
iodo-2-triethylsilylethene as the precursor to produce 1 in 62%
yield (Eq. (5)). The second method utilized 1,2-difluoro-1-
triethylsilylethene to produce 1 in 75% yield (Eq. (6)).
(9)
2.1. Palladium catalyzed cross-coupling of 2 with aryl iodides and
fluorinated vinyl iodides
When 2 was reacted with aryl iodides, Pd(PPh3)4, and Cu(I)I [8]
at room temperature good yields of the aryl coupled products
were obtained (Table 1). Similarly, when 1-iodo-perfluoroalkenes
were used as substrates good yields of the coupled products were
obtained (Table 2).
When 2 was coupled with an aryl iodide, the major by-product
was tri-n-butylstannyliodide which needed to be removed from
the final product in the workup. Washing with aqueous KF did not
completely remove this by-product and when the n-Bu3SnI/cross-
coupled product mixture was purified by column chromatography,
the n-Bu3SnI streaked throughout the column and contaminated
the final product. During the workup, Cu(OAc)2 or Co(OAc)2 was
added and stirred with the reaction mixture to convert the n-
Bu3SnI to n-Bu3SnOAc, which remained on the column when
elution was performed with hexanes. However, the Cu(OAc)2 also
homo-coupled any remaining 2 to (E,E)-H2C55CHCH2CF55CFCF55
CFCH2CH55CH2 [9]. The homo-coupled product was detected in
small amounts in the reaction mixture of some of the cross-
coupled products before workup. This homo-coupled product
has a similar retention time to the cross-coupled product and is
difficult to remove from the purified cross-coupled product. When
Co(OAc)2 was used to remove n-Bu3SnI, it did not homo-couple
2. Therefore, if any 2 remained in the reaction mixture, it was best
to use Co(OAc)2 in the workup.
(5)
(6)
1 can be converted to (Z)-1,2-difluoro-1-tri-n-butylstannyl-1,4-
pentadiene (2) with KF, n-Bu3SnCl, and DMF at 70 8C (Eq. (7)).
Although
2 was formed, the reaction times depended on
concentration of 1 in DMF. When the concentration was kept
between 0.60 M and 0.77 M, the reaction was completed overnight
at 65–70 8C. When the concentration was approximately 1.0 M, the
reaction took 72–96 h for completion at 65–70 8C. Burton reported
that n-Bu3SnOSn(n-Bu)3 and catalytic KF gives a higher yield of
the stannane than the reaction that required stoichiometric KF
[7]. However, this method was not employed in this case due
to the high boiling point of the Et3SiOSiEt3 by-product, which
would cause difficulty in purification.
Table 1
Reaction of 2 with aryl iodides, Pd(PPh3)4, and Cu(I)I in DMF.
The thermal stability of 2 was determined by heating 2 in
an NMR tubes with DMF and
a,a,a-trifluorotoluene standard.
2 showed good thermal stability at the range of temperatures
needed for the coupling reactions with only slight decomposition
at 85–90 8C. Therefore, 2 can be used in Stille coupling reactions to
introduce aryl and vinyl groups.
An alternative route to coupled products would utilize the zinc
reagent from (Z)-1,2-difluoro-1-iodo-1,4-pentadiene (3), which
can be readily prepared from 1 or 2 (Eq. (8)). When this iodide
was reacted with Zn in DMF, (Z)-CH255CHCH2CF55CFZnI and,
X
T (8C)
Time (h)
Yielda
m-(I)-CF3
4
RT
RT
RT
RT
RT
65
12
12
82%
74%
65%
64%
67%
31%
m-NO2
-H 6
5
12
p-CH3
7
12
p-OMe 8
96
o-CF3
9
240
a
Isolated yield.
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j.jfluchem.2014.12.006

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3
Table 2
Table 3
Reaction of 2 with fluorinated vinyl iodides, Pd(PPh3)4, and Cu(I)I in DMF.
Reaction of 12 with aryl iodides, Pd(PPh3)4, and Cu(I)I in DMF.
Iodide
T (8C)
Time (h)
Yielda
X
T (8C)
Time (h)
Yielda
IFC5CF2 10
RT
RT
12
12
75%
54%
m-CF3 14
m-NO2 15
-H 16
RT
RT
RT
RT
RT
12
12
36
36
36
62%
52%
71%
60%
73%
(Z)-IFC5CFCF3 11
a
Isolated yield.
p-CH3 17
p-OMe 18
2.2. Functionalization of the vinyl group (H2C55CH–)
a
Isolated yield.
For functionalization of the vinyl group, we needed a method
that did not cause isomerization and was regiospecific for the
terminal methylene group. Our reagent of choice was 9-BBN
(9-borabicyclo[3.3.1]nonane), which adds to the terminal carbon
of a 1-alkene with a selectivity of 99.9% [10]. Oxidation with
hydrogen peroxide and hydroxide base cleanly gives the alcohols.
Organoboranes with a tri-n-butyltin functionality have been
prepared previously and there are also reports where the tri-n-
butyltin group survives the oxidation step (Eq. (10)) [11]. We
cannot predict what effect the difluorovinyl group that is attached
to the tri-n-butyltin will have on the hydroboration/oxidation.
However, when 2 was treated with 1.5 equivalents of 9-BBN
followed by 3 M sodium hydroxide and 30% hydrogen peroxide,
65% of the stannyl alcohol 12 was isolated (Eq. (11)). When 1 was
reacted under the same conditions 74% of the silyl alcohol 13
was obtained (Eq. (12)). However, when the silyl alcohol 13 was
treated with KF, n-Bu3SnCl, and DMF at 55 8C we got a mixture of
six products (Eq. (13)); this method was investigated no further.
allows for the bromine to be displaced by other nucleophiles to
elaborate the carbon chain.
(14)
ð15Þ
ð16Þ
ð17Þ
(10)
ð11Þ
3. Experimental
ð12Þ
ð13Þ
3.1. General experimental procedures
Routine 19F NMR spectra were recorded on a JEOL FX90Q
Spectrometer (83.81 MHz) and high-resolution data was obtained
on a Bruker AC-300 Spectrometer (282.41 MHz). Chemical shifts
have been reported in ppm relative to internal CFCl3. Spectra of
reaction mixtures were obtained in the 7Li external lock mode.
Quantitativedeterminations werecarried out byintegration relative
to internal benzotrifluoride. Routine 1H NMR (300.17 MHz) spectra
and high-resolution data were generally obtained on a Bruker
AC-300 Spectrometer. Unless noted otherwise, CDCl3 was used as
the NMR lock solvent. Chemical shifts have been reported in ppm
relative to internal TMS. High-resolution {1H} 13C NMR spectra were
recorded on a Bruker AC-300 Spectrometer (75.48 MHz). Chemical
shifts have been reported in ppm relative to internal TMS. High-
resolution mass spectra were obtained by the University of Iowa
Our initial intention was to functionalize the n-Bu3Sn- group of
2 followed by hydroboration/oxidation of the H2C55CH– group.
However, we needed to reverse the two processes to accomplish
our overall goal of functionalizing both groups (Table 3).
When 12 was treated with neat I2 we successfully created a
difunctionalized molecule synthon 19 that would be amenable for
further derivatization (Eq. (14)). Protection of the alcohol was
accomplished with acetic anhydride (Eq. (15)). Further conversion
of the alcohol group was carried out with dibromotriphenylpho-
sphorane (Eqs. (16) and (17)). The brominated product potentially
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High Resolution Mass Spectrometry Facility. Analytical GLPC were
performed on a Hewlett–Packard Model 5890 equipped with a
thermal conductivity detector and 3393A integrator. The column
was packed with 5% OV-101 on chromo-sorb P. All boiling points
were determined during fractional distillation using a partial
immersion thermometer and are uncorrected. THF was dried by
distillation from sodium benzophenone ketyl at ambient pressure.
1.3 Hz), 3.2 ppm (ddddd, 2H, 3JHF = 22.6 Hz, 3JHH = 6.2 Hz,
4
4
3
4JHF = 6.2 Hz, JHH = 1.5 Hz, JHH = 1.5 Hz), 1.0 ppm (t, 9H, JHH
=
3
7.8 Hz), 0.7 ppm (q, 6H, JHH = 8.0 Hz); 13C NMR (CDCl3):
1
2
163.74 ppm (dd, JCF = 238.9 Hz, JCF = 42.1 Hz), 154.70 ppm (dd,
1JCF = 258.4 Hz, JCF = 74.3 Hz), 131.79 ppm (dd, JCF = 2.4 Hz,
2
3
4JCF = 1.8 Hz), 117.9 ppm (s), 31.35 ppm (dd, JCF = 26.0 Hz, JCF
=
2
3
3
4
3.3 Hz), 7.11 ppm (s), 2.48 ppm (dd, JCF = 1.3 Hz, JCF = 1.3 Hz);
GC–MS, m/z (relative intensity): 218 (M+, 15.60), 105 (87.86), 95
(85.70), 77 (100.00), 67 (73.04), 65 (80.03); HRMS: C11H20F2Si
(calculated: 218.1302, observed: 218.1314).
˚
4 A molecular sieves (Fisher) were activated by heating under
vacuum (300 8C at 0.5 mm Hg) overnight. DMF was dried overnight
over CaH2 and then distilled at reduced pressure. Pd(PPh3)4 was
prepared by Coulson’s procedure [12]. Potassium fluoride was dried
by azeotropic distillation with benzene solvent and a Dean–Stark
apparatus. Residual benzene was removed under reduced pressure.
Silica gel was purchasedfrom EM Science (silica gel 60, particle sized
3.3. Preparation of (Z)-1,2-difluoro-1-triethylsilyl-1,4-pentadiene
(Z)-CH255CHCH2CF55CFSiEt3 (1) from (Z)-1,2-difluoro-1-
triethylsilylethene, (Z)-HFC55CFSiEt3
0.063–0.200
mm, 70–230 Mesh, ASTM). CuI (Aldrich) was purified
according to Kauffman and Fang’s procedure [13]. Allyl bromide
was distilled under N2 at atmospheric pressure. (E)-IFC55CFSiEt3
was prepared by Davis et al.’s method [14]. (Z)-HFC55CFSiEt3 was
also prepared via a method developed by Davis et al. [14]. IFC55CF2
was prepared by a method developed by Heinze and Burton [15].
Additionally, (Z)-IFC55CFCF3 was synthesized via a method pub-
lished by Heinze et al. [16]. ZnI2 was prepared by published methods
[17]. Cu(OAc)2 was prepared by Blumenthal and Burton’s method
[9]. Bromotrifluoroethylene (Halocarbon), 9-BBN (Aldrich), ClSnBu3
(Aldrich), any lithium reagents (Aldrich), trithethylsilyl chloride
(Farchan), substituted aryl iodides, Br2, PPh3, and chlorotrifluor-
oethylene were obtained from commercial sources and used
without further purification.
A 250 mL three-necked, round bottomed flask equipped with
a water condenser, nitrogen gas inlet, internal low temperature
thermometer, Teflon coated magnetic stir bar, and a rubber septum
port was charged with 60 mL of dry THF and 30 mL of anhydrous
diethyl ether. Next, (Z)-1,2-difluoro-1-triethylsilylethene (17.80 g,
100.0 mmol) was added via syringe and the reaction mixture was
cooled to ꢀ100 8C using a pentane/liquid N2 bath. Then, a solution
of n-BuLi in hexanes (48.0 mL, 120 mmol, 2.5 M) was slowly added
via syringe maintaining the temperature below ꢀ90 8C. After the
addition was complete, the reaction mixture was stirred an
additional 20 min at ꢀ100 8C. A solution of ZnI2 [17] (41.47 g,
130.0 mmol) in THF was slowly added via syringe maintaining the
temperature below ꢀ90 8C. The solution was cooled to ꢀ100 8C,
then warmed to room temperature overnight. To form the coupled
product, the reaction mixture was cooled to 0 8C and allyl bromide
(18.15 g, 150.0 mmol) was added via syringe. Cu(I)Br (5 mol%) was
added in one portion to the flask after the allyl bromide addition
had been completed. The reaction mixture was stirred at 0–5 8C for
1 h, warmed to room temperature, and stirred for an additional
30 min at room temperature. Ether (100 mL) and water (100 mL)
were added to the reaction mixture and then the solution was
vacuum filtered to remove any solids. The filtered solids were
rinsed with 15 mL ether. The filtrate was added to a separatory
funnel and washed with ether (2ꢁ 100 mL); the combined ether
layers were washed with water (2ꢁ 50 mL). The organic layer was
dried over MgSO4, filtered, and concentrated by simple distillation.
The crude product was purified by fractional distillation on a 6 cm
Vigreux column to give 1 (16.42 g, 75% isolated yield, purity by 1H
NMR = 92%): bp 86–88 8C/15 mmHg. The spectroscopic data are
identical to the data reported in Section 3.2.
3.2. Preparation of (Z)-1,2-difluoro-1-triethylsilyl-1,4-pentadiene,
(Z)-H2C55CHCH2CF55CFSiEt3 (1) from (E)-1,2-difluoro-1-iodo-2-
triethylsilylethene, (E)-IFC55CFSiEt3
A 250 mL three-necked, round bottomed flask equipped with a
water condenser, nitrogen gas inlet, Teflon coated magnetic stir
bar, internal thermometer, and a rubber septum port was charged
with zinc (5.50 g, 84.6 mmol), activated according to Knochel and
Normant’s method [18]. Then 70 mL of anhydrous DMF was added
to the flask. Next, (E)-1,2-difluoro-1-iodo-2-triethylsilylethene
(20.70 g, 67.70 mmol) was slowly added to the stirred mixture via
syringe so as not to exceed 50 8C. After 1 h, the 19F NMR spectrum
of the reaction mixture showed that all the (E)-IFC55CFSiEt3 had
been converted to the zinc reagent. (76% 19F NMR yield); 19F NMR
(DMF) ꢀ153 ppm (d, 1F) ꢀ173 ppm, (d, 1F). A clean 250 mL two
necked, round bottomed flask equipped with a water condenser,
nitrogen gas inlet, Teflon coated magnetic stir bar, and a rubber
septum port was charged via syringe with the solution of the
zinc reagent. Next, allyl bromide (9.40 mL, 108 mmol) was slowly
added via syringe. Cu(I)Br (3–5 mol%) was added in one portion to
the flask after the allyl bromide addition had been completed. An
exotherm resulted. The reaction mixture was stirred for 1 h until it
returned to room temperature. 1 was isolated by the slow addition
of 100 mL of a saturated aqueous solution of NaHCO3 (foams) to
the flask. Then ether (100 mL) was added and the solution was
vacuum filtered to remove any solids. The filtrate was added to a
separatory funnel and washed with ether (2ꢁ 50 mL), and the
combined ether layers washed with water (2ꢁ 25 mL). The organic
layer was dried over MgSO4, filtered, and the solvent was removed
by rotary evaporation. The crude product was purified by fractional
distillation on a 6 cm Vigreux column to give 1 (9.10 g, 62% isolated
yield, purity by 1H NMR = 92%): bp 86–888/15 mmHg; 19F NMR
3.4. Preparation of (Z)-1,2-difluoro-1-tri-n-butylstannyl-1,4-
pentadiene, (Z)-H2C55CHCH2CF55CFSnBu3-n (2)
A 250 mL two-necked, round bottomed flask equipped with a
water condenser, nitrogen gas inlet, Teflon coated magnetic stir
bar, and a rubber septum port was charged with anhydrous KF
(5.19 g, 89.4 mmol), 100 mL of dry DMF, 1 (14.30 g, 65.60 mmol),
and ClSnBu3-n (24.60 g, 75.69 mmol). The reaction mixture was
stirred at 70 8C overnight. The reaction mixture was extracted with
ether (2ꢁ 100 mL) and the combined ether layers were washed
with water (2ꢁ 100 mL). The organic layer was dried over MgSO4,
filtered, and the solvent was removed by rotary evaporation. The
crude product was purified by silica gel column chromatography
using hexanes as eluent to give 2 (20.90 g, 81% isolated yield, Rf
(hexanes) = 0.50, purity by GLPC analysis = 98%): bp 88–90 8C/
1 mm Hg; small satellite peaks due to couplings to natural
abundances of 7.68% 117Sn and 8.58% 119Sn isotopomers
where excluded for clarity; 19F NMR (CDCl3): ꢀ148.7 ppm
3
3
(CDCl3): ꢀ145.8 ppm (dt, 1F, JFF = 124.8 Hz, JFH = 21.9 Hz),
3
4
ꢀ172 ppm (dt, 1F, JFF = 124.8 Hz, JFH = 6.4 Hz); 1H NMR (CDCl3):
3
3
3
5.8 ppm (ddt, 1H, JHH = 17.0 Hz, JHH = 10.4 Hz, JHH = 6.2 Hz),
5.2 ppm (ddt, 1H, JHH = 17.2 Hz, JHH = 0.8 Hz, JHH = 0.7 Hz),
5.1 ppm (ddt, 1H, 3JHH = 10.1 Hz, 2JHH = 1.5 Hz, 4JHH
3
2
4
3
3
˙
(dt, 1F, JFF = 116.7 Hz, JFH = 21 8 Hz), ꢀ164.7 ppm (dt, 1F,
4
=
3JFF = 117.2 Hz, JFH = 6.4 Hz); 1H NMR (CDCl3): 5.8 ppm (ddt, 1H,
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5
3
3
3JHH = 17.0 Hz, JHH = 10.2 Hz, JHH = 6.3 Hz), 5.2 ppm (ddt, 1H,
and 5 mL of extra DMF for 2 h. Alternately, dry KF (0.58 g,
9.9 mmol) was added to the reaction flask and the mixture was
stirred overnight. The reaction mixture was then poured over
water (25 mL) in a separatory funnel and extracted with ether (3ꢁ
25 mL). The combined ether layers were washed with water (2ꢁ
25 mL). The organic layer was dried over MgSO4, filtered, and the
solvent was removed by rotary evaporation. The crude product
was purified by silica gel column chromatography using hexanes
as eluent to give 4 (2.90 g, 82% isolated yield, Rf (hexanes) = 0.36,
purity by GLPC analysis = 98%): 19F NMR (CDCl3) ꢀ63.4 ppm (s, 3F),
2
4
3JHH = 17.1 Hz, JHH = 1.5 Hz, JHH = 1.5 Hz), 5.1 ppm (ddt, 1H,
2
4
3JHH = 10.0 Hz, JHH = 1.4 Hz, JHH = 1.3 Hz), 3.2 ppm (ddddd, 2H,
3JHF = 22.0 Hz,
3JHH = 6.1 Hz,
4JHF = 6.1 Hz,
3
4JHH = 1.5 Hz,
4JHH = 1.5 Hz), 1.5 ppm (pent, 6H, JHH = 7.5 Hz), 1.3 ppm (sext,
6H, 3JHH = 7.2 Hz), 1.1 ppm (m, 6H), 0.9 ppm (t, 9H, 3JHH = 7.3 Hz);
13C NMR (CDCl3): 162.80 ppm (dd, JCF = 228.5 Hz, JCF = 34.1 Hz),
1
2
1
2
159.07 ppm (dd, JCF = 296.3 Hz, JCF = 96.9 Hz), 132.22 ppm (dd,
3JCF = 2.6 Hz, JCF = 1.2 Hz), 117.18 ppm (s), 30.97 ppm (dd,
4
3
2JCF = 28.0 Hz, JCF = 3.5 Hz), 28.85 ppm (s), 27.14 ppm (s),
2
4
3
3
13.66 ppm (s), 9.89 ppm (dd, JCF = 2.4 Hz, JCF = 1.9 Hz); GC–MS,
m/z (relative intensity): 335 (M+–C4H9, 26.74), 253 (100.00), 252
(59.29), 251 (99.65), 250 (61.02), 249 (99.76), 177 (89.61), 175
(74.26), 139 (63.53), 57 (69.84); HRMS: C13H23F2118Sn (M+–C4H9)
(calculated: 335.0784, observed: 335.0790).
ꢀ143.3 ppm (dt, 1F, JFF = 122.6 Hz, JFH = 23.9 Hz), ꢀ159.8 ppm
3 4
(dt, 1F, JFF = 123.7 Hz, JFH = 4.6 Hz); 19F{H} NMR (CDCl3):
ꢀ63.4 ppm (s, 3F), ꢀ143.3 ppm (d, 1F, 3JFF = 122.9 Hz),
3
ꢀ159.8 ppm (d, 1F, JFF = 123.4); 1H NMR (CDCl3): 7.9 ppm (s,
1H), 7.8 ppm (d, 1H, 3JHH = 7.9 Hz), 7.6 ppm (dd, 1H, 3JHH = 9.0 Hz,
3
3JHH = 7.8 Hz), 7.5 ppm (d, 1H, JHH = 7.7 Hz), 5.9 ppm (ddt, 1H,
3
3
3.5. Thermal stability of 2
3JHH = 17.0 Hz, JHH = 10.2 Hz, JHH = 6.4 Hz), 5.3 ppm (dm, 1H,
3JHH = 17.1 Hz), 5.2 ppm (dd, 1H, JHH = 10.1 Hz, JHH = 1.3 Hz),
3
2
3
3
4
The thermal stability was determined by heating 2 in an NMR
tube with DMF and
3.3 ppm (ddddd, 2H, JHF = 23.3 Hz, JHH = 6.5 Hz, JHH = 5.3 Hz,
4
a
,
a,
a
-trifluorotoluene standard. The mixture
4JHH = 1.4 Hz, JHH = 1.3 Hz); 13C NMR (CDCl3): 151.51 ppm (dd,
in the NMR tube was heated and the 19F NMR spectrum was taken
at varying time and temperature intervals. The ratio of 2 to the
standard was recorded. At 25 8C, 2 showed no decomposition. At
65–70 8C, 2 showed no significant decomposition after 48 h. After 2
was held at 85–90 8C for 3 h, a small peak grew in the 19F NMR
spectra. Since most of the Pd(0) coupling reactions can be
conducted at room temperature to 70 8C, 2 was considered a
useful synthon for the stereospecific introduction of aryl groups.
1JCF = 251.6 Hz, JCF = 55.9 Hz), 146.00 ppm (dd, JCF = 225.2 Hz,
2
1
2JCF = 43.3 Hz), 131.11 ppm (qd, JCF = 32.0 Hz, JCF = 2.7 Hz),
2
4
3
4
130.96 ppm (dd, JCF = 1.9 Hz, JCF = 1.8 Hz), 130.64 ppm (dd,
2JCF = 25.8 Hz, 3JCF = 6.6 Hz), 129.03 ppm (d, 4JCF = 2.0 Hz),
3
4
128.35 ppm (ddm, JCF = 8.5 Hz, JCF = 1.4 Hz), 125.16 ppm (m),
1
124.04 ppm (q, JCF = 272.3 Hz), 122.11 ppm (m), 118.43 ppm (s),
32.13 ppm (d, 2JCF = 22.8 Hz); GC–MS, m/z (relative intensity): 248
(M+, 100.00), 213 (62.76), 201 (62.15), 179 (85.05), 177 (57.02) 164
(92.70), 159 (70.96), 151 (98.55); HRMS: C12H9F5 (calculated:
248.0624, observed: 248.0620).
3.6. Preparation of (Z)-1,2-difluoro-1-iodo-1,4-pentadiene, (Z)-
CH255CHCH2CF55CFI (3)
3.8. Preparation of (E)-1,2-difluoro-1-(meta-nitrophenyl)-1,4-
pentadiene, (E)-CH255CHCH2CF55CFC6H4NO2-m (5)
A 50 mL two-necked, round bottomed flask equipped with a
nitrogen gas inlet, Teflon coated magnetic stir bar, and a rubber
septum port was charged with iodine (1.36 g, 5.34 mmol). Next, 2
(2.10 g, 5.34 mmol) was slowly added to maintain the temperature
of the reaction mixture below 50 8C. The reaction mixture was flash
distilled after a color change from dark brown to clear. Flash
distillation removed 3 from the tri-n-butyltin iodide (1.16 g, 94%
isolated yield, purity by 1H NMR = 99%); 19F NMR (CDCl3):
Similar to the procedure described in Section 3.7. 1-Iodo-3-
nitrobenzene (1.58 g 6.40 mmol) was reacted with 2 (3.00 g,
7.60 mmol), Pd(PPh3)4 (0.37 g, 3–5 mol%), Cu(I)I (0.61 g,
3.2 mmol), and 8 mL of dry DMF. The reaction mixture was stirred
12 h at room temperature. After standard workup, the crude
product was purified by silica gel column chromatography using a
mixture of 88% hexanes and 12% EtOAc as eluent to give 5 (1.06 g,
74%, Rf (88% hexanes, 12% EtOAc) 0.46, purity by 1H NMR = 99%):
19F NMR (CDCl3): ꢀ141.4 ppm (dt, 1F, 3JFF = 124.1 Hz,
3
4
ꢀ127.2 ppm (dt, 1F, JFF = 141.6 Hz, JFH = 5.3 Hz), ꢀ130.0 ppm
3
3
(dt, 1F, JFF = 142.1 Hz, JFH = 21.1 Hz); 19F{H} NMR (CDCl3):
ꢀ127.2 ppm (d, 1F, 3JFF = 140.9 Hz), ꢀ130.0 ppm (d, 1F
3JFF = 141.5 Hz); 1H NMR (CDCl3): 5.8 ppm (ddt, 1H, 3JHH = 17.0 Hz,
3
4
3JFH = 22.9 Hz), ꢀ160.0 ppm (dt, 1F, JFF = 124.0 Hz, JFH = 5.5 Hz);
3JHH = 10.3 Hz, JHH = 6.3 Hz), 5.2 ppm (dm, 1H, JHH = 17.1 Hz),
1H NMR (CDCl3): 8.5 ppm (dd, 1H, JHF = 2.0 Hz, JHF = 2.0 Hz),
3
3
4
5
3
2
4
3
4
5.2 ppm (ddt, 1H, JHH = 10.1 Hz, JHH = 1.3 Hz, JHH = 1.3 Hz),
8.2 ppm (dd, 1H, JHH = 8.2 Hz, JHF = 2.2 Hz), 7.9 ppm (d, 1H,
3
3
4
3
3
3.3 ppm (ddddd, 2H, JHF = 21.1 Hz, JHH = 6.5 Hz, JHF = 5.7 Hz,
3JHH = 8.0 Hz), 7.6 ppm (dd, 1H, JHH = 8.1 Hz, JHH = 8.0 Hz),
4
3
3
3
4JHH = 1.4 Hz, JHH = 1.4 Hz); 13C NMR (CDCl3): 155.01 ppm (dd,
5.9 ppm (ddt, 1H, JHH = 17.0 Hz, JHH = 10.1 Hz, JHH = 6.4 Hz),
2
3
3
3
1JCF = 244.2 Hz, JCF = 41.9 Hz), 130.31 ppm (dd, JCF = 3.4 Hz,
5.3 ppm (dm, 1H, JHH = 17.1 Hz), 5.2 ppm (dd, 1H, JHH = 10.0 Hz,
4JCF = 2.2 Hz), 118.62 ppm (s), 96.94 ppm (dd, JCF = 308.7 Hz,
2JHH = 1.3 Hz), 3.4 ppm (ddddd, 2H, JHF = 23.4 Hz, JHH = 6.5 Hz,
1
3
3
2JCF = 66.1 Hz), 31.73 ppm (d, 2JCF = 23.9 Hz); GC–MS, m/z (relative
intensity): 230 (M+, 29.0), 103 (46.0), 74 (64.0), 59 (100.00); HRMS:
C5H5F2I (calculated: 229.9404, observed: 229.9395).
4JHF = 6.5 Hz, JHH = 1.3 Hz); 13C NMR (CDCl3): 152.24 ppm (dd,
4
1JCF = 253.5 Hz, 2JCF = 54.7 Hz), 145.11 ppm (dd, 1JCF = 226.1 Hz, 2JCF
42.7 Hz), 148.44 ppm (s), 131.37 ppm (dd, 2JCF = 25.7 Hz,
3JCF = 6.4 Hz), 130.72 ppm (dd, 3JCF = 9.5 Hz, 4JCF = 6.9 Hz),
3
4
3.7. Preparation of (E)-1,2-difluoro-1-(meta-trifluoromethylphenyl)-
1,4-pentadiene, (E)-CH255CHCH2CF55CFC6H4CF3-m (4)
130.58 ppm (dd, JCF = 3.42 Hz, JCF = 3.42 Hz), 129.57 ppm (d,
5JCF = 1.9 Hz), 123.10 ppm (d, JCF = 2.7 Hz), 120.11 ppm (dd,
4
3JCF = 9.8 Hz, 4JCF = 8.1 Hz), 118.69 ppm (s), 32.11 ppm (d,
2JCF = 23.3 Hz); GC–MS, m/z (relative intensity): 225 (M+, 52.76),
177 (50.10), 164 (84.97), 151 (100.00), 133 (63.18); HRMS:
General procedure: A 25 mL two-necked, round bottomed flask
equipped with a water condenser, nitrogen gas inlet, Teflon coated
magnetic stir bar, and a rubber septum port was charged with
Pd(PPh3)4 (0.48 g, 3–5 mol%), Cu(I)I (0.87 g, 4.6 mmol), and 10 mL
of dry DMF. Next, 3-iodobenzotrifluorine (2.28 g, 8.30 mmol) was
added to the solution via syringe. Then, 2 (3.93 g, 9.22 mmol) was
slowly added to this solution by syringe. The reaction mixture
was stirred 12 h at room temperature. To remove the ISnBu3-n, the
reaction mixture was stirred with Cu(OAc)2 (3.36 g, 18.4 mmol)
C11H9F2NO2 (calculated: 225.0601, observed: 225.0604).
3.9. Preparation of (E)-1,2-difluoro-1-phenyl-1,4-pentadiene, (E)-
CH255CHCH2CF55CFC6H5 (6)
Similar to the procedure described in Section 3.7. Iodobenzene
(0.65 g, 3.2 mmol) was reacted with
2 (1.50 g, 3.80 mmol),
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j.jfluchem.2014.12.006

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3
Pd(PPh3)4 (0.18 g, 3–5 mol%), Cu(I)I (0.31 g, 1.6 mmol), and 4 mL of
dry DMF. The reaction mixture was stirred 12 h at room
temperature. After standard workup, the crude product was
purified by silica gel column chromatography using hexanes as
eluent to give 6 (0.37 g, 65% isolated yield, Rf (hexanes) = 0.38,
purity by 19F NMR = 92%): 19F NMR (CDCl3): ꢀ146.0 ppm (dt, 1F,
3JFF = 122.8 Hz, 3JFH = 23.3 Hz), ꢀ159.0 ppm (dt, 1F, 3JFF = 122.8 Hz,
3JHH = 6.3 Hz), 5.2 ppm (dm, 1H, JHH = 17.1 Hz), 5.1 ppm (dd, 1H,
3JHH = 9.9 Hz, JHH = 1.2 Hz), 3.7 ppm (s, 3H), 3.2 ppm (ddddd, 2H,
2
3JHF = 23.2 Hz,
3JHH = 5.1 Hz,
4JHF = 5.1 Hz,
4JHH = 1.4 Hz,
4JHH = 1.4 Hz); 13C NMR (CDCl3): 158.55 (d, JCF = 2.6 Hz), 147.80
5
1
2
1
(dd, JCF = 245.2 Hz, JCF = 56.7 Hz), 145.97 (dd, JCF = 224.0 Hz,
2JCF = 43.9 Hz), 130.66 (dd, JCF = 2.3 Hz, JCF = 2.3 Hz), 125.74 (dd,
3
4
3JCF = 7.3 Hz, 4JCF = 7.3 Hz), 121.31 (dd, 2JCF = 25.8 Hz, 3JCF = 6.2 Hz),
3
4
4JFH = 5.9 Hz); 1H NMR (CDCl3): 7.6 ppm (ddd, 2H, JHH 7.2 Hz,
116.70 (s), 112.76 (d, JCF = 1.9 Hz), 54.21 (s), 30.93 (d,
4JFH = 1.6 Hz, JHF = 1.1 Hz), 7.4 ppm (dddd, 2H, JHH = 8.3 Hz,
2JCF = 24.0 Hz). GC–MS, m/z (relative intensity): 210 (M+,
100.00); HRMS: C12H12F2O (calculated: 210.0856, observed:
210.0857).
5
3
5
6
3JHH = 7.1 Hz, JHF = 1.2 Hz, JHF = 0.8 Hz), 7.3 ppm (m, 1H),
3
3
3
5.9 ppm (ddt, 1H, JHH = 16.6 Hz, JHH = 10.2 Hz, JHH = 6.4 Hz),
5.3 ppm (dm, 1H, 3JHH = 17.1 Hz), 5.2 ppm (ddt, 1H, 3JHH = 10.0 Hz,
4
3
2JHH = 1.5 Hz, JHH = 1.3 Hz), 3.3 ppm (ddddd, 2H, JHF = 23.1 Hz,
3.12. Preparation of (E)-1,2-difluoro-1-(ortho-
trifluoromethylphenyl)-1,4-pentadiene, (E)-
CH255CHCH2CF55CFC6H4CF3-o (9)
3JHH = 6.4, JHF = 5.3 Hz, JHH = 1.5 Hz, JHH = 1.5 Hz); 13C NMR
4
4
4
(CDCl3): 150.14 ppm (dd, 1JCF = 248.6 Hz, 2JCF = 57.2 Hz),
1
2
146.92 ppm (dd, JCF = 224.4 Hz, JCF = 43.1 Hz), 131.42 ppm (dd,
3JCF = 2.5 Hz, 4JCF = 1.6 Hz), 129.74 ppm (dd, 2JCF = 25.4 Hz,
3JCF = 6.1 Hz), 128.44 ppm (dd, 3JCF = 10.9 Hz, 4JCF = 2.7 Hz),
125.28 ppm (d, JCF = 7.4 Hz), 125.16 ppm (d, JCF = 7.8 Hz),
117.95 ppm (s), 32.06 ppm (d, 2JCF = 23.9 Hz); GC–MS, m/z (relative
intensity): 180 (M+, 81.27), 165 (100.00), 133 (68.99); HRMS:
Similar to the procedure described in Section 3.7. 2-Iodobenzo-
trifluoride (0.44 g, 1.6 mmol) was reacted with
2 (0.77 g,
2.0 mmol), Pd(PPh3)4 (0.09 g, 3–5 mmol%), Cu(I)I (0.15 g,
0.78 mmol), and 2 mL of dry DMF. The reaction mixture was
stirred 240 h at 65 8C. After standard workup, the crude product
was purified by silica gel column chromatography using hexanes
as eluent to give 9 (0.15 g, 31% isolated yield, Rf (hexanes) = 0.38,
purity by 1H NMR = 99%); 19F NMR (CDCl3): ꢀ61.5 ppm (dd, 3F,
C
11H10F2 (calculated: 180.0751, observed: 180.0776).
3.10. Preparation of (E)-1,2-difluoro-1-(para-tolyl)-1,4-pentadiene,
(E)-CH255CHCH2CF55CFC6H4CH3-p (7)
6
3
5JFF = 12.1 Hz, JFF = 2.2 Hz), ꢀ141.4 ppm (dqt, 1F, JFF = 133.8 Hz,
4
3
5JFF = 12.7 Hz, JFH = 6.5 Hz), ꢀ146.5 ppm (dt, 1F, JFF = 134.2 Hz,
3JFH = 22.1 Hz); 19F{H} NMR (CDCl3): ꢀ61.5 ppm (dd, 3F,
Similar to the procedure described in Section 3.7. 4-Iodotoluene
(1.28 g, 5.90 mmol) was reacted with 2 (2.77 g, 7.05 mmol),
Pd(PPh3)4 (0.34 g, 3–5 mol%), Cu(I)I (0.50 g, 2.9 mmol), and 8 mL
of dry DMF. The reaction mixture was stirred 12 h at room
temperature. After standard workup, the crude product was
purified by silica gel column chromatography using hexanes as
eluent to give 7 (0.70 g, 64% isolated yield, Rf (hexanes) = 0.40,
purity by 1H NMR = 94%); 19F NMR (CDCl3): ꢀ147.0 ppm (dt, 1F,
3JFF = 122.7 Hz, 3JFH = 23.4 Hz), ꢀ158.7 ppm (dt, 1F, 3JFF = 122.7 Hz,
6
3
5JFF = 12.3 Hz, JFF = 2.2 Hz), ꢀ141.4 ppm (dq, 1F, JFF = 133.4 Hz,
5JFF = 12.2 Hz), ꢀ146.5 ppm (dq, 1F, JFF = 132.9 Hz, JFF = 3.1 Hz);
3
6
1H NMR (CDCl3): 7.8 ppm (d, 1H, JHH = 7.2 Hz), 7.6 ppm (m, 3H),
3
3
3
3
5.9 ppm (ddt, 1H, JHH = 16.8 Hz, JHH = 10.3 Hz, JHH = 6.3 Hz),
5.3 ppm (dm, 1H, 3JHH = 17.1 Hz), 5.2 ppm (dm, 1H, 3JHH = 10.1 Hz),
3.3 ppm (ddd, 2H, JHF = 22.5 Hz, JHH = 5.2 Hz, JHF = 5.2 Hz); 13C
3
3
4
1
2
NMR (CDCl3): 149.83 ppm (dd, JCF = 243.2 Hz, JCF = 52.9 Hz),
1
2
145.52 ppm (dd, JCF = 233.9 Hz, JCF = 49.9 Hz), 132.17 ppm (dd,
3
4
4JFH = 4.8 Hz); 1H NMR (CDCl3): 7.5 ppm (dd, 2H, JHH = 8.4 Hz,
3JCF = 4.6 Hz, JCF = 3.1 Hz), 131.71 ppm (s), 130.96 ppm (dd,
3
5
4JHF = 1.8 Hz), 7.2 ppm (dd, 2H, JHH = 8.0 Hz, JHF = 0.6 Hz),
3JCF = 2.3 Hz, 4JCF = 2.0 Hz), 130.14 ppm, (d, 4JCF = 2.0 Hz),
3
3
3
2
3
5.9 ppm (ddt, 1H, JHH = 17.0 Hz, JHH = 10.1 Hz, JHH = 6.4 Hz),
5.3 ppm (dm, 1H, 3JHH = 17.1 Hz), 5.2 ppm (ddt, 1H, 3JHH = 10.0 Hz,
129.53 ppm (q, JCF = 31.4 Hz), 126.71 ppm (qd, JCF = 5.0 Hz,
4JCF = 1.6 Hz), 127.18 ppm (dm, JCF = 24.8 Hz), 123.56 ppm (q,
2
2JHH = 1.4 Hz, JHH = 1.4 Hz), 3.3 ppm (ddddd, 2H, JHF = 23.3 Hz,
1JCF = 274.1 Hz), 118.17 ppm (s), 31.28 ppm (d, 2JCF = 23.7 Hz); GC–
MS, m/z (relative intensity): 248 (M+, 42.00), 179 (78.42), 164
(76.44), 159 (69.96), 151 (100.00); HRMS: C12H9F5 (calculated:
248.0624, observed: 248.0616).
4
3
3JHH = 6.4 Hz, 4JHF = 5.3 Hz, 4JHH = 1.4 Hz, 4JHH = 1.4 Hz), 2.4 ppm (s,
3H); 13C NMR (CDCl3): 149.66 ppm, (dd, JCF = 246.7 Hz,
1
2JCF = 56.8 Hz), 147.24 ppm (dd, JCF = 225.3 Hz, JCF = 43.5 Hz),
1
2
5
3
138.62 ppm (d, JCF = 2.2 Hz), 131.70 ppm (dd, JCF = 1.5 Hz,
4JCF = 1.5 Hz), 129.18 ppm (d, JCF = 2.5 Hz), 127.03 ppm (dd,
3.13. Preparation of (E)-1,1,2,3,4-pentafluoro-1,3,6-heptatriene, (E)-
CH255CHCH2CF55CFCF55CF2 (10)
4
2JCF = 25.2 Hz, 3JCF = 6.0 Hz), 125.27 ppm (dd, 3JCF = 8.2 Hz,
4JCF = 7.2 Hz), 117.94 ppm (s), 32.14 ppm (d, JCF = 23.5 Hz),
2
21.42 ppm (s); GC–MS, m/z (relative intensity): 194 (M+, 100.00,
179 (82.75), 164 (56.75); HRMS: C12H12F2 (calculated: 194.0907,
observed: 194.0914).
A 50 mL two-necked, round bottomed flask equipped with a
water condenser, nitrogen gas inlet, Teflon coated magnetic stir
bar, and a rubber septum port was charged with Pd(PPh3)4 (0.62 g,
3–5 mol%), Cu(I)I (1.00 g, 5.40 mmol), and 13 mL of dry DMF. Next,
trifluoroiodoethene (2.26 g, 10.8 mmol) was added to the solution.
Then, 2 (5.13 g, 13.0 mmol) was slowly added to this solution by
syringe. The reaction mixture was stirred 12 h at room tempera-
ture. The product was flash distilled from the reaction mixture. The
crude product was purified by fractional distillation on a 6 cm
Vigreuxcolumn to give 10 (1.49 g, 75% isolated yield, purity by 1H
NMR = 98%): bp 78–80 8C; 19F NMR (CDCl3): ꢀ96.0 ppm (dddd, 1F,
3.11. Preparation of (E)-1,2-difluoro-1-(para-methoxyphenyl)-1,4-
pentadiene, (E)-CH255CHCH2CF55CFC6H4OCH3-p (8)
Similar to the procedure described in Section 3.7. 4-Iodoanisole
(0.74 g, 3.2 mmol) was reacted with
2 (1.50 g, 3.80 mmol),
Pd(PPh3)4 (0.18 g, 3–5 mol%), Cu(I)I (0.31 g, 1.6 mmol), and 4 mL
of dry DMF. The reaction mixture was stirred 96 h at room
temperature. After standard workup, the crude product was
purified by silica gel column chromatography using a mixture of
88% hexanes and 12% EtOAc as eluent to give 8 (0.44 g, 67% isolated
yield, Rf (88% hexanes, 12% EtOAc) = 0.50, purity by 1H NMR = 99%);
19F NMR (CDCl3): ꢀ148.8 ppm (dt, 1F, 3JFF = 123.5 Hz,
2JFF = 52.5 Hz,
3JFF = 29.6 Hz,
4JFF = 5.0 Hz,
5JFF = 5.0 Hz),
ꢀ108.6 ppm (dddd, 1F, 3JFF = 116.4 Hz, 2JFF = 52.3 Hz, 5JFF = 17.6 Hz,
3
3
4JFF = 12.6 Hz), ꢀ134.8 ppm (dtddd, 1F, JFF = 134.3 Hz, JFH
=
5
4
5
22.6 Hz, JFF = 17.0 Hz, JFF = 10.5 Hz, JFF = 5.1 Hz), ꢀ164.5 ppm
3
3
4
4
(dddtd, 1F, JFF = 134.9 Hz, JFF = 32.6 Hz, JFF = 12.6 Hz, JFH
=
3
4
4
3
3JFH = 22.7 Hz), ꢀ158.2 ppm (dt, 1F, JFF = 123.7 Hz, JFH = 5.3 Hz);
4.7 Hz, JFF = 3.6 Hz), ꢀ181.2 ppm (ddddt, 1F, JFF = 116.4 Hz,
1H NMR (CDCl3): 7.5 ppm (d, 2H, JHH = 9.1 Hz), 6.8 ppm (d, 2H,
3JFF = 32.2 Hz, JFF = 30.0 Hz, JFF = 10.3 Hz, JFH = 3.0 Hz); 19F{H}
3 4 5
3
3
3
2
3
3JHH = 8.9 Hz), 5.8 ppm (ddt, 1H, JHH = 17.1 Hz, JHH = 10.3 Hz,
NMR (CDCl3): ꢀ96.0 ppm (dddd, 1F, JFF = 52.3 Hz, JFF = 29.6 Hz,
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j.jfluchem.2014.12.006

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5
3
4JFF = 4.1 Hz, JFF = 4.1 Hz), ꢀ108.6 ppm (dddd, 1F, JFF = 116.3 Hz,
was slowly added at room temperature. The reaction mixture was
stirred 16 h at room temperature. The oxidation was performed by
cooling the reaction mixture to 0 8C; then 3 M NaOH (1.6 mL,
5.0 mmol) and 30% H2O2 (2.80 g, 25.0 mmol) were slowly added
simultaneously via syringe. The reaction mixture was allowed to
warm to room temperature with stirring overnight. A saturated
aqueous solution of Na2CO3 (25 mL) was added to the reaction
mixture and the mixture was extracted with ether (3ꢁ 25 mL) in a
separatory funnel. Then the combined ether layers were washed
with water (3ꢁ 15 mL). The organic layer was dried over MgSO4,
filtered, and the solvent was removed by rotary evaporation. The
crude product was purified by silica gel column chromatography
using a mixture of 88% hexanes and 12% EtOAc as eluent to give 12
(1.29 g, 65% isolated yield, Rf (88% hexanes, 12% EtOAc) = 0.20,
purity by 1H NMR = 89%); 19F NMR (CDCl3): ꢀ149.0 ppm (dt, 1F,
3JFF = 117.0 Hz, 3JFH = 23.0 Hz), ꢀ165.1 ppm (dt, 1F, 3JFF = 116.4 Hz,
2JFF = 52.6 Hz, 5JFF = 18.1 Hz, 4JFF = 12.9 Hz), ꢀ134.8 ppm (dddd, 1F,
3JFF = 134.0 Hz, 5JFF
=
17.6 Hz, 4JFF = 11.1 Hz, 5JFF = 5.1 Hz),
ꢀ164.5 ppm (dddd, 1F 3JFF = 134.0 Hz, 3JFF = 32.4 Hz, 4JFF = 12.8 Hz,
4JFF = 3.4 Hz), ꢀ181.2 ppm (dddd, 1F, 3JFF = 116.3 Hz, 3JFF = 32.7 Hz,
3JFF = 29.6 Hz, JFF = 11.0 Hz); 1H NMR (CDCl3): 5.8 ppm (ddt, 1H,
4
3JHH = 17.1 Hz, JHH = 10.2 Hz, JHH = 6.3 Hz), 5.2 ppm (dm, 1H,
3
3
3JHH = 17.1 Hz), 5.2 ppm (dd, 1H, JHH = 10.0 Hz, JHH = 1.3 Hz),
3
2
3.2 ppm (dm, 2H, JHF = 22.2 Hz); 13C NMR (CDCl3): 155.48 ppm
3
1
2
(dddd, JCF = 294.0 Hz, JCF = 47.1 Hz, JCF = 6.7 Hz, JCF = 2.3 Hz),
153.54 ppm (dddd, JCF = 255.8 Hz, JCF = 49.8 Hz, JCF = 4.1 Hz,
JCF = 1.5 Hz), 151.70 ppm (dddd, JCF = 295.0 Hz, JCF = 47.6 Hz,
JCF = 6.7, JCF = 2.2 Hz), 136.27 ppm (dm, 1JCF = 207.9 Hz),
129.54 ppm (s), 118.96 ppm (s), 31.25 ppm (d, JCF = 22.4 Hz);
GC–MS, m/z (relative intensity): 184 (M+, 59.0), 115 (83.0), 84
(50.0), 75 (54.0), 69 (100.0); HRMS: C7H5F5 (calculated 184.0311,
observed 184.0312).
1
2
1
2
2
2
4JFH = 6.1 Hz, JFSn = 83.3 Hz satellite peaks); 1H NMR (CDCl3):
3
3
3.7 ppm (t, 2H, JHH = 6.4 Hz), 2.5 ppm (dtd, 2H, JHF = 22.8 Hz,
3JHH = 7.1 Hz, JHF = 6.5 Hz), 1.8 ppm (pent, 2H, JHH = 6.8 Hz),
4
3
3.14. Preparation of (E,E)-4,5,6,7,8,8,8-heptafluoro-1,4,6-octatriene,
(E,E)-CH255CHCH2CF55CFCF55CFCF3 (11)
3
1.5 ppm (m, 6H), 1.5 ppm (s), 1.3 ppm (sext, 6H, JHH = 6.7 Hz),
3
3
1.1 ppm (t, 6H, JHH = 7.9 Hz), 0.9 ppm, t, 9H, JHH = 7.2 Hz); 13C
1
2
NMR (CDCl3): 164.78 ppm (dd, JCF = 226.8 Hz, JCF = 35.1 Hz),
159.19 ppm (dd, 1JCF = 294.8 Hz, 2JCF = 98.1 Hz), 61.76 ppm
(s), 28.95 ppm (dd, 3JCF = 2.2 Hz, 4JCF = 2.2 Hz), 28.89 ppm
(s, JCSn = 10.7 Hz satellite peaks), 27.15 ppm (s, JCSn = 29.8 Hz
satellite peaks), 13.67 ppm (s), 22.72 ppm (dd, JCF = 27.3 Hz,
2JCF = 2.5 Hz), 9.90 ppm (dd, JCF = 1.8 Hz, JCF = 1.8 Hz, JCSn
A 50 mL two-necked, round bottomed flask equipped with a
water condenser, nitrogen gas inlet, Teflon coated magnetic stir bar
and a rubber septum port was charged with Pd(PPh3)4 (0.26 g, 3–5
mol%), Cu(I)I (0.43 g, 2.3 mmol), and 8 mL of dry DMF. Next, (Z)-
pentafluoro-1-iodo-1-propene (1.10 g, 4.50 mmol) was added to
the solution. Then, 2 (2.30 g, 5.80 mmol) was slowly added to this
solution by syringe. The reaction mixture was stirred 12 h at room
temperature. The product was flash distilled from the reaction
mixture. The crude product was purified by fractional distillation
on a 6 cm Vigreux column to give 11 (0.54 g, 54% isolated yield,
purity by 1H NMR = 98%): bp 43–44 8C/50 mm Hg; 19F NMR
(CDCl3): ꢀ68.4 ppm (dd, 3F, 4JFF = 20.7 Hz, 3JFF = 10.9 Hz),
ꢀ130.5 ppm (ddtd, 1F, 3JFF = 131.7 Hz, 5JFF = 29.8 Hz, 3JFH = 22.3 Hz,
3
2
2
3
4
1
=
172.0 Hz satellite peaks); GC–MS, m/z (relative intensity): 353
(M+–C4H9, 19.64), 253 (100.00), 251 (93.71), 249 (57.28); HRMS:
C
13H25F2O118Sn (M+–C4H9) (calculated: 353.0890, observed:
353.0888).
3.16. Preparation of (Z)-4,5-difluoro-5-triethsilyl-4-penten-1-ol,
(Z)-HOCH2CH2CH2CF55CFSiEt3 (13)
4JFF = 14.1 Hz), ꢀ153.0 ppm (ddqdt, 1F, JFF = 137.7 Hz, JFF
=
3
3
A 50 mL three-necked, round bottomed flask equipped with a
water condenser, nitrogen gas inlet, Teflon coated magnetic stir
bar, and a rubber septum port was charged with 0.5 M solution of
9-BBN in THF (13.8 mL, 6.90 mmol). Next, 1 (1.00 g, 4.59 mmol)
was slowly added at room temperature. The reaction was stirred
overnight. The oxidation was performed by cooling the reaction
mixture to 0 8C and adding 3 M NaOH (1.6 mL, 4.6 mmol) and 30%
H2O2 (2.80 g, 23.0 mmol) slowly and simultaneously via syringe.
The reaction mixture was allowed to warm to room temperature
with stirring overnight. A saturated aqueous solution of Na2CO3
(25 mL) was added to the reaction mixture and the mixture was
extracted with ether (3ꢁ 15 mL) in a separatory funnel. Then the
combined layers were washed with water (3ꢁ 15 mL). The organic
layer was dried over MgSO4, filtered, and the solvent was removed
by rotary evaporation. The crude product was purified by silica gel
column chromatography using a mixture of 88% hexanes and 12%
EtOAc as eluent to give 13 (0.80 g, 74% isolated yield, Rf (88%
hexanes, 12% (EtOAc) = 0.11, purity by 1H NMR = 97%); 19F NMR
4
4
5
32.0 Hz, JFF = 21.5 Hz, JFF = 13.6 Hz, JFH = 1.8 Hz), ꢀ158.7 ppm
(dddq,
1F,
3JFF = 138.9 Hz,
5JFF = 30.0 Hz,
4JFF = 13.4 Hz,
3JFF = 10.5 Hz), ꢀ169.4 ppm (dddtq, 1F, JFF = 131.7 Hz, JFF
=
3
3
32.8 Hz, JFF = 14.2 Hz, JFH = 7.3 Hz, JFF = 2.1 Hz); 19F{H} NMR
(CDCl3): ꢀ68.4 ppm (dd, 1F, 4JFF = 20.8 Hz, 3JFF = 10.9 Hz),
ꢀ130.5 ppm (ddd, 1F, 3JFF = 131.4 Hz, 5JFF = 29.9 Hz, 4JFF = 13.8 Hz),
ꢀ153.0 ppm (ddqd, 1F, 3JFF = 138.7 Hz, 3JFF = 32.0 Hz, 4JFF = 21.5 Hz,
4
4
5
4JFF = 13.6 Hz), ꢀ158.7 ppm (dddq, 1F, JFF = 137.7 Hz, JFF
=
3
5
4
3
30.0 Hz, JFF = 13.4 Hz, JFF = 10.5 Hz), ꢀ169.3 ppm (dddq, 1F,
3JFF = 131.8 Hz, JFF = 32.8 Hz, JFF = 14.2 Hz, JFF = 2.1 Hz); 1H
3
4
5
3
3
NMR (CDCl3): 5.8 ppm (ddt, 1H, JHH = 17.1 Hz, JHH = 10.2 Hz,
3JHH = 6.3 Hz), 5.2 ppm (dm, 1H, JHH = 17.1 Hz, JHH = 0.7 Hz),
5.2 ppm (dd, 1H, JHH = 10.0 Hz, JHH = 1.3 Hz), 3.2 ppm (dm, 2H,
3JHH = 22.2 Hz); 13C NMR (CDCl3): 155.62 ppm (dddd, JCF
263.1 Hz, JCF = 47.0 Hz, JCF = 3.6 Hz, JCF = 3.3 Hz), 142.42 ppm
(dddm, JCF = 254.3 Hz, JCF = 41.4 Hz, JCF = 28.5 Hz), 139.41 ppm
(dddm, JCF = 257.7 Hz, JCF = 41.1 Hz, JCF = 41.1 Hz), 136.13 ppm
(dddd, JCF = 229.9 Hz, JCF = 48.9 Hz, JCF = 26.8 Hz, JCF = 5.8 Hz),
129.07 ppm (s), 119.63 ppm (s), 118.41 ppm (qdd, 1JCF = 272.5 Hz,
2JCF = 35.3 Hz, 3JCF = 4.9 Hz), 31.63 ppm (d, 2JCF = 21.7 Hz); GC–MS,
m/z (relative intensity): 234 (M+, 2.7), 74 (95.7), 59 (100.0); HRMS:
C8H5F7 (calculated: 234.0279, observed: 234.0285).
3
3
3
3
1
=
2
3
4
1
2
3
1
2
2
1
2
2
3
3
3
(CDCl3): ꢀ146.0 ppm (dt, 1F, JFF = 125.5 Hz, JFH = 23.2 Hz),
ꢀ172.6 ppm (dt, 1F, 3JFF = 125.0 Hz, 4JFH = 6.2 Hz); 1H NMR (CDCl3):
3
3
3.7 ppm (t, 2H, JHH = 6.4 Hz), 2.5 ppm (dtd, 2H, JHF = 23.2 Hz,
3JHH = 7.3 Hz, JHF = 6.4 Hz), 1.9 ppm (s, 1H), 1.8 ppm (pent, 2H,
4
3JHH = 6.9 Hz), 1.0 ppm (t, 9H, JHH = 7.5 Hz), 0.7 ppm (q, 6H,
3
3JHH = 7.9 Hz); 13C NMR (CDCl3): 165.55 ppm (dd, JCF = 237.3 Hz,
1
2JCF = 41.7 Hz), 154.77 ppm (dd, JCF = 256.5 Hz, JCF = 76.2 Hz),
1
2
3.15. Preparation of (Z)-4,5-difluoro-5-tri-n-butylstannyl-4-penten-
1-ol (Z)-HOCH2CH2CH2CF55CFSnBu3-n (12)
3
61.63 ppm (s), 28.67 ppm (t, JCF = 1.8 Hz), 23.01 ppm (dd,
2JCF = 25.4 Hz, 3JCF = 2.1 Hz), 7.03 ppm (s), 2.36 ppm (dd,
3JCF = 2.0 Hz, JCF = 2.0 Hz); GC–MS, m/z (relative intensity): 207
4
A 50 mL three-necked, round bottomed flask equipped with a
water condenser, nitrogen gas inlet, Teflon coated magnetic stir
bar, and a rubber septum port was charged with a 0.5 M solution of
9-BBN in THF (15.0 mL, 7.50 mmol). Next, 2 (1.97 g, 5.01 mmol)
(M+–C2H5, 31.81), 105 (74.81), 95 (50.76), 93 (53.75), 77 (100.00);
HRMS: C9H17F2OSi (M+–C2H5) (calculated: 207.1017, observed:
207.1014).
Please cite this article in press as: S. Lukaszewski-Rose, D.J. Burton, J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/
j.jfluchem.2014.12.006

G Model
FLUOR-8483; No. of Pages 10
8
S. Lukaszewski-Rose, D.J. Burton / Journal of Fluorine Chemistry xxx (2015) xxx–xxx
3.17. Preparation of (E)-4,5-difluoro-5-(meta-
trifluoromethyphenyl)-4-penten-1-ol, (E)-HOCH2CH2CH2CF55
CFC6H4CF3-m (14)
3.19. Preparation of (E)-4,5-difluoro-5-phenyl-4-penten-1-ol,
(E)-HOCH2CH2CH2CF55CFC6H5 (16)
Similar to the procedure described in Section 3.17. 1-
Iodobenzene (0.45 g, 2.2 mmol), 12 (0.71 g, 1.7 mmol), Pd(PPh3)4
(0.13 g, 3–5 mol%), Cu(I)I (0.19 g, 1.1 mmol), and 5 mL of dry DMF.
The reaction mixture was stirred 36 h at room temperature. After
standard workup, the crude product was purified by silica gel
column chromatography using a mixture of 88% hexanes and 12%
EtOAc as eluent to give 16 (0.24 g, 71% isolated yield, Rf (88%
hexanes, 12% EtOAc) = 0.12, purity by 1H NMR = 99%); 19F NMR
General procedure: A 50 mL two-necked, round bottomed flask
equipped with a water condenser, nitrogen gas inlet, Teflon coated
magnetic stir bar, and a rubber septum port was charged with
Pd(PPh3)4 (0.15 g, 3–5 mol%), copper (I) iodide (0.19 g, 1.0 mmol),
5 mL of dry DMF, 3-iodobenzotrifluoride (0.72 g, 2.6 mmol), and 12
(1.00 g, 2.40 mmol). The reaction mixture was allowed to stir at
room temperature overnight. The reaction mixture was stirred
with Co(OAc)2 (0.86 g 4.8 mmol) and 3 mL of extra DMF for 2 h.
Then, the reaction mixture was poured over water (15 mL) in a
separatory funnel and extracted with ether (2ꢁ 15 mL). The
combined ether layers were washed with water (15 mL). The
organic layer was dried over MgSO4, filtered, and the solvent was
removed by rotary evaporation. The crude product was purified by
silica gel column chromatography using a mixture of 80% hexanes
and 20% EtOAc as eluent to give 14 (0.40 g, 62% isolated yield,
Rf (80% hexanes, 20% EtOAc) = 0.11, purity by 1H NMR = 99%);
19F NMR (CDCl3): ꢀ63.4 ppm (s, 3F), ꢀ143.6 ppm (dt, 1F,
3JFF = 122.8 Hz, 3JFH = 23.7 Hz), ꢀ160.0 ppm (dt, 1F, 3JFF = 122.8 Hz,
4JFH = 5.4 Hz); 1H NMR (CDCl3): 7.9 ppm (s, 1H), 7.8 ppm (d, 1H,
3
3
(CDCl3): ꢀ146.2 ppm (dt, 1F, JFF = 121.7 Hz, JFH = 23.9 Hz),
ꢀ159.2 ppm (dt, 1F, 3JFF = 122.6 Hz, 4JFH = 6.0 Hz); 1H NMR (CDCl3):
3
3
7.6 ppm (dm, 2H, JHH = 7.3 Hz), 7.4 ppm (t, 2H, JHH = 7.9 Hz),
3
7.3 ppm (m, 1H), 3.7 ppm (t, 2H, JHH = 6.4 Hz), 2.7 ppm (dtd, 2H,
3JHF = 23.7 Hz, JHH = 7.4 Hz, JHF = 5.7 Hz), 1.9 ppm (pent, 2H,
3JHH = 6.8 Hz), 1.6 ppm (s, 1H); 13C NMR (CDCl3): 151.99 ppm
(dd 1JCF = 247.6 Hz, 2JCF = 57.0 Hz), 147.04 ppm (dd, 1JCF = 224.8 Hz,
3
4
2JCF = 44.2 Hz), 129.78 ppm (dd, JCF = 25.2 Hz, JCF = 6.1 Hz),
2
3
128.43 ppm (d, JCF = 2.0 Hz), 128.37 ppm (d, JCF = 1.3 Hz),
3
4
125.15 ppm (dd, JCF = 9.3 Hz, JCF = 7.2 Hz), 61.80 ppm (s),
3
4
2
28.89 ppm (dd, JCF = 2.1 Hz, JCF = 1.9 Hz), 23.97 ppm (d, JCF
=
23.9 Hz); GC–MS, m/z (relative intensity): 198 (M+, 26.10), 165
(100.00), 133 (84.70); HRMS: C11H12F2O (calculated:198.0856,
observed 198.0850).
3
3JHH = 7.6 Hz), 7.6 ppm (d, 1H, JHH = 7.9 Hz), 7.5 ppm (dd, 1H,
3JHH = 7.8 Hz, 3JHH = 7.6 Hz), 3.8 ppm (t, 2H, 3JHH = 6.3 Hz), 2.7 ppm
(dtd, 2H, 3JHF = 23.7 Hz, 3JHH = 7.4 Hz, 4JHF = 5.6 Hz), 1.9 ppm (pent,
3
2H, JHH = 6.4 Hz), 1.7 ppm (s, 1H); 13C NMR (CDCl3): 153.32 ppm
3.20. Preparation of (E)-4,5-difluoro-5-(para-tolyl)-4-penten-1-ol,
(E)-HOCH2CH2CH2CF55CFC6H4CH3-p (17)
1
2
1
(dd, JCF = 250.3 Hz, JCF = 55.9 Hz), 145.94 ppm (dd, JCF
=
=
2
2
4
224.2 Hz, JCF = 43.5 Hz), 131.00 ppm (qd, JCF = 33.5 Hz, JCF
2.3 Hz),
128.98 ppm (d, JCF = 2.3 Hz), 128.22 ppm (dd, JCF = 8.6 Hz,
4JCF = 8.1 Hz), 125.00 ppm (m), 123.97 ppm (q, JCF = 272.0 Hz),
121.96 ppm (m), 61.74 ppm (s), 28.77 ppm (d, JCF = 1.9 Hz),
24.06 ppm (d, JCF = 24.3 Hz); GC–MS, m/z (relative intensity):
130.60 ppm
(dd,
2JCF = 25.7 Hz,
3JCF = 6.5 Hz),
Similar to the procedure described in Section 3.17. 4-
Iodotoluene (0.06 g, 0.3 mmol), 12 (0.10 g, 0.24 mmol), Pd(PPh3)4
(0.02 g (3–5 mol%), Cu(I)I (0.02 g, 0.1 mmol), and 1 mL of dry DMF.
The reaction mixture was stirred 36 h at room temperature. After
standard workup, the crude product was purified by silica gel
column chromatography using a mixture of 88% hexanes and 12%
EtOAc as eluent to give 17 (0.03 g, 60% isolated yield, Rf (88%
hexanes, 12% EtOAc) = 0.10, purity by 1H NMR = 85%); 19F NMR
4
3
1
3
2
266 (M+, 29.58), 248 (81.25), 233 (65.74), 213 (54.09), 201 (71.65),
179 (100.00), 164 (61.63), 151 (60.12); HRMS: C12H11F5O
(calculated: 266.0730, observed: 266.0729).
3
3
(CDCl3): ꢀ147.4 ppm (dt, 1F, JFF = 122.3 Hz, JFH = 23.2 Hz),
ꢀ159.1 ppm (dt, 1F, 3JFF = 122.3 Hz, 4JFH = 5.6 Hz); 1H NMR (CDCl3):
3
3
3.18. Preparation of (E)-4,5-difluoro-5-(meta-nitrophenyl)-4-
penten-1-ol, (E)-HOCH2CH2CH2CF55CFC6H4NO2-m (15)
7.5 ppm (d, 2H, JHH = 8.4 Hz), 7.2 ppm (d, 2H, JHH = 8.0 Hz),
3
3
3.7 ppm (m, 2H), 2.7 ppm (dtd, 2H, JHF = 23.7 Hz, JHH = 7.4 Hz,
4JHF = 5.6 Hz), 2.4 ppm (s, 3H), 1.9 ppm (pent, 2H, JHH = 6.9 Hz),
3
1.7 ppm (s, 1H); 13C NMR (CDCl3): 151.36 ppm (dd, 1JCF = 246.3 Hz,
Similar to the procedure described in Section 3.17. 1-Iodo-3-
nitrobenzene (0.55 g 2.2 mmol), 12 (0.82 g, 2.0 mmol), Pd(PPh3)4
(0.13 g, 3–5 mol%), Cu(I)I (0.19 g, 1.1 mmol), and 5 mL of dry DMF.
The reaction mixture was stirred 12 h at room temperature. After
standard workup, the crude product was purified by silica gel
column chromatography using a mixture of 88% hexanes and 12%
EtOAc as eluent to give 15 (0.25 g, 52% isolated yield, Rf (88%)
hexanes, 12% EtOAc) = 0.04, purity by 1H NMR = 97%); 19F NMR
2JCF = 56.7 Hz), 147.24 ppm (dd, JCF = 223.9 Hz, JCF = 43.9 Hz),
1
2
5
4
138.42 ppm (d, JCF = 2.3 Hz), 129.07 ppm (d, JCF = 1.63 Hz),
2
3
126.96 ppm (dd, JCF = 24.8 Hz, JCF = 6.2 Hz), 125.09 ppm (dd,
3JCF = 8.6 Hz, JCF = 7.1 Hz), 61.82 ppm (s), 28.93 ppm (dd, JCF
=
4
3
4
2
2.2 Hz, JCF = 1.6 Hz), 23.90 ppm (d, JCF = 24.0 Hz), 21.30 ppm (s);
GC–MS, m/z (relative intensity): 212 (M+, 39.61), 179 (100.00), 164
(56.91), 147 (72.09), 136 (62.63); HRMS: C12H14F2O (calculated:
212.1013, observed: 212.1015).
3
3
(CDCl3): ꢀ141.6 ppm (dt, 1F, JFF = 123.7 Hz, JFH = 23.3 Hz),
ꢀ160.0 ppm (dt, 1F, 3JFF = 123.2 Hz, 4JFH = 5.4 Hz); 1H NMR (CDCl3):
8.5 ppm (m, 1H), 8.2 ppm (dm, 1H, 3JHH = 8.3 Hz), 7.9 ppm (dm, 1H,
3.21. Preparation of (E)-4,5-difluoro-5-(para-methoxyphenyl)-4-
penten-1-ol, (E)-HOCH2CH2CH2CF55CFC6H4OCH3-p (18)
3
3
3JHH = 8.0 Hz), 7.6 ppm (dd, 1H, JHH = 8.1 Hz, JHH = 8.0 Hz),
3
3
3.8 ppm (t, 2H, JHH = 6.1 Hz), 2.7 ppm (ddt, 2H, JHF = 23.7 Hz,
4JHF = 7.5 Hz, JHH = 5.7 Hz), 1.9 ppm (pent, 2H, JHH = 7.3 Hz),
3
3
Similar to the procedure described in Section 3.17. 3-
Iodoanisole (0.93 g, 40 mmol), 12 (1.48 g, 3.60 mmol), Pd(PPh3)4
(0.23, 3–5 mol%), Cu(I)I (0.34 g, 1.8 mmol), and 6 mL of dry DMF.
The reaction mixture was stirred 36 h at room temperature. After
standard workup, the crude product was purified by silica gel
column chromatography using a mixture of 88% hexanes and 12%
EtOAc as eluent to give 18 (0.60 g, 73% isolated yield, Rf (88%
hexanes, 12% EtOAc) = 0.07, purity by 1H NMR = 99%); 19F NMR
1.7 ppm (s, 1H); 13C NMR (CDCl3): 154.17 ppm (dd, 1JCF = 252.0 Hz,
2JCF = 54.8 Hz), 145.17 ppm (dd, JCF = 224.81 Hz, JCF = 43.8 Hz),
1
2
2
3
148.38 ppm (s), 131.42 ppm (dd, JCF = 26.4 Hz, JCF = 6.5 Hz),
3
4
130.64 ppm (dd, JCF = 9.7 Hz, JCF = 6.7 Hz), 129.54 ppm (d,
JCF = 2.9 Hz), 122.95 ppm (d, JCF = 2.0 Hz), 120.02 ppm (dd,
3JCF = 10.7 Hz, JCF = 7.8 Hz), 61.67 ppm (s), 28.67 ppm (dd,
3JCF = 2.3 Hz, JCF = 2.3 Hz), 24.14 ppm (d, JCF = 23.4 Hz); GC–
MS, m/z (relative intensity): 243 (M+, 8.65), 164 (87.60), 151
(100.00); HRMS: C11H11F2NO3 (calculated: 243.07070, observed:
243.07074).
4
4
2
3
3
(CDCl3): ꢀ149.0 ppm (dt, 1F, JFF = 122.6 Hz, JFH = 23.9 Hz),
ꢀ158.4 ppm (dt, 1F, 3JFF = 122.8 Hz, 4JFH = 4.8 Hz); 1H NMR (CDCl3):
3
3
7.5 ppm (dm, 2H, JHH = 9.1 Hz), 6.9 ppm (dd, 2H, JHH = 9.1 Hz,
Please cite this article in press as: S. Lukaszewski-Rose, D.J. Burton, J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/
j.jfluchem.2014.12.006

G Model
FLUOR-8483; No. of Pages 10
S. Lukaszewski-Rose, D.J. Burton / Journal of Fluorine Chemistry xxx (2015) xxx–xxx
9
3
2
2
4JHF = 0.7 Hz), 3.8 ppm (s, 3H), 3.7 ppm (t, 2H, JHH = 6.4 Hz),
1JCF = 225.2 Hz, JCF = 42.8 Hz), 130.99 ppm (qd, JCF = 32.5 Hz,
3
3
4
2.7 ppm (dtd, 2H, JHF = 23.7 Hz, JHH = 7.3 Hz, JHF = 5.6 Hz),
4JCF = 2.3 Hz), 130.44 ppm (dd, 2JCF = 25.8 Hz, 3JCF = 6.0 Hz),
128.98 ppm (d, JCF = 2.8 Hz), 128.23 ppm (dd, JCF = 95 Hz,
4JCF = 7.7 Hz), 123.91 ppm (q, JCF = 272.2 Hz), 125.09 ppm (m),
122.00 ppm (m), 63.24 ppm (s), 24.94 ppm (s), 24.30 ppm
(d, 2JCF = 22.9 Hz), 20.89 ppm (s); GC–MS, m/z (relative intensity):
308 (M+, 0.29), 289 (7.97), 248 (82.62), 179 (100.00); HRMS:
C
14H13F5O2 (calculated: 308.0836, observed: 308.0854, (M+-F)
1.9 ppm (pent, 2H, JHH = 6.9 Hz), 2.4–1.5 ppm (s, 1H); 13C NMR
3
4
3
5
1
1
(CDCl3): 159.37 ppm (d, JCF = 2.5 Hz), 150.63 ppm (dd, JCF
245.0 Hz, JCF = 57.2 Hz), 146.94 ppm (dd, JCF = 223.9 Hz, JCF
=
=
2
1
2
3
4
45.4 Hz), 126.56 ppm (dd, JCF = 8.6 Hz, JCF = 7.2 Hz), 122.32 ppm
2
3
4
(dd, JCF = 25.6 Hz, JCF = 5.5 Hz), 113.68 ppm (d, JCF = 1.8 Hz),
3
61.57 ppm (s), 55.11 ppm (s), 28.83 ppm (dd, JCF = 2.0 Hz,
4JCF = 1.6 Hz), 23.74 ppm (d, JCF = 23.6 Hz); GC–MS, m/z (relative
calculated: 289.0852, observed: 289.0844).
2
intensity): 228 (M+, 59.45), 183 (l00,00), 152 (83.11), 139 (65.79);
HRMS: C12H14F2O2 (calculated: 228.0962, observed 228.0957).
3.24. Preparation of (E)-1,2-difluoro-1-(meta-
trifluoromethylphenyl)-5-bromo-1-pentene, (E)-
BrCH2CH2CH2CF55CFC6H4CF3-m (21)
3.22. Preparation of (Z)-4,5-difluoro-5-iodo-4-penten-1-ol,
(Z)-HOCH2CH2CH2CF55CFI (19)
A 15 mL two necked, round bottomed flask equipped with a
water condenser, nitrogen gas inlet, Teflon coated magnetic stir
bar, and a rubber septum port was charged with PPh3 (0.10 g,
0.40 mmol) and 14 (0.10 g 0.37 mmol). Next, 1 mL of DMF was
added and the mixture was stirred to dissolve the solids. Then, Br2
was added dropwise until the orange color persisted. The reaction
mixture was stirred overnight. The reaction mixture was added to
water (15 mL) in a separatory funnel and washed with ether (2ꢁ
20 mL). The combined ether layers were washed with water (2ꢁ
15 mL), dried over MgSO4, filtered and the solvent was removed by
rotary evaporation. The crude product was purified by silica gel
column chromatography using a mixture of 88% hexanes and 12%
EtOAc as eluent to give 21 (0.10 g, 83% isolated yield, Rf (88%
hexanes, 12% EtAcO) = 0.51, purity by 1H NMR = 97%); 19F NMR
A 50 mL two necked, round bottomed flask equipped with a
nitrogen gas inlet, Teflon coated magnetic stir bar, and a rubber
septum port was charged with of iodine (0.50 g, 2.0 mmol). Next,
12 (0.82 g, 2.0 mmol) was added. The solution turned dark very
slowly and was exothermic. Eventually, the reaction mixture
changed colors from a dark brown to clear. 19 did not flash distil,
so the mixture was added to ether (15 mL) and washed with
saturated aqueous KF (2ꢁ 15 mL) in a separatory funnel to remove
ISnBu3-n. The mixture was washed with water (1ꢁ 15 mL) and
dried over MgSO4, filtered, and the solvent was removed by rotary
evaporation. Since ISnBu3-n remained, 15 mL of DMF and Co(OAc)2
(0.36 g 4.0 mmol) was added and stirred for 1 h. The product
was added directly onto a silica gel column and eluted with
hexanes:EtOAc (80:20) to give 19 (0.31 g, 63% isolated yield, Rf
(80% hexanes, 20% EtOAc) = 0.12, purity by 1H NMR = 98%); 19F
3
(CDCl3): ꢀ63.4 ppm (s, 3F), ꢀ144.3 ppm (dt, 1F, JFF = 123.6 Hz,
3
4
3JFH = 23.4 Hz), ꢀ159.1 ppm (dt, JFF = 123.7 Hz, JFH = 5.3 Hz); 1H
3
4
3
NMR (CDCl3): ꢀ127.6 ppm (dt, 1F, JFF = 141.3 Hz, JFH = 5.7 Hz),
NMR (CDCl3): 7.9 ppm (s, 1H), 7.8 ppm (d, 1H, JHH = 7.8 Hz),
3
3
3
3
ꢀ130.4 ppm (dt, 1F, JFF = 141.3 Hz, JFH = 21.5 Hz); 1H NMR
7.6 ppm (d, 1H, JHH = 7.9 Hz), 7.6 ppm (dd, 1H, JHH = 7.8 Hz,
3
3
(CDCl3): 3.6 ppm (t, 2H, JHH = 6.2 Hz), 2.6 ppm (dtd, 2H,
3JHH = 7.6 Hz), 3.5 ppm (t, 2H, JHH = 6.7 Hz), 2.8 ppm (dtd, 2H,
3JHF = 21.5 Hz, JHH = 7.3 Hz, JHF = 6.0 Hz), 1.9 ppm (s, 1H), 1.7
3JHF = 23.2 Hz, JHH = 7.5 Hz, JHF = 5.4 Hz), 2.2 ppm (pent, 2H,
3
4
3
4
(pent, 2H, JHH = 6.8 Hz); 13C NMR (CDCl3): 155.83 ppm (dd,
3JHH = 6.9 Hz); 13C NMR (CDCl3): 152.17 ppm (dd, JCF = 250.4 Hz,
3
1
1JCF = 243.9 Hz, JCF = 40.6 Hz), 95.65 ppm (dd, JCF = 306.0 Hz,
2JCF = 55.6 Hz), 146.29 ppm (dd, JCF = 225.8 Hz, JCF = 43.6 Hz),
2
1
1
2
3
2
4
2JCF = 66.4 Hz), 60.31 ppm (s), 27.48 ppm (dd, JCF = 2.1 Hz,
131.04 ppm (qd, JCF = 32.6 Hz, JCF = 2.8 Hz), 130.38 ppm (dd,
2JCF = 25.7 Hz, 3JCF = 5.8 Hz), 129.02 ppm (d, 4JCF = 2.2 Hz),
4JCF = 2.1 Hz), 22.80 ppm (d, JCF = 23.9 Hz); GC–MS, m/z (relative
2
3
4
intensity): 248 (M+, 8.55), 230 (81.22), 103 (100.00), 83 (61.82);
HRMS: C5H7F2IO (calculated: 247.9510, observed: 247.9526).
128.29 ppm (dd, JCF = 8.6 Hz, JCF = 8.6 Hz), 125.20 ppm (m),
1
123.92 ppm (q, JCF = 272.1 Hz), 122.06 ppm (m), 32.05 ppm (s),
28.95 ppm (dd, JCF = 1.8 Hz, JCF = 1.8 Hz), 26.28 ppm (d, JCF
3
4
2
=
3.23. Preparation of (E)-4,5-difluoro-5-(meta-
trifluoromethyphenyl)-4-penten-1-acetate,
(E)-CH3C(O)OCH2CH2CH2CF55CFC6H4CF3-m (20)
23.9 Hz), GC–MS, m/z (relative intensity): 328 (M+, 68.47) 330
(M2+, 66.84), 221 (88.33), 201 (100.00), 151 (81.33); HRMS:
C12H1079BrF5 (calculated: 327.9886, observed: 327.9893).
A 15 mL two-necked, round bottomed flask equipped with a
water condenser, nitrogen gas inlet, Teflon coated magnetic stir
bar, and a rubber septum port was charged with 1.1 mL of pyridine,
14 (0.10 g, 0.38 mmol), and acetic anhydride (0.15 g, 1.5 mmol).
The reaction was stirred at room temperature for 5 h. Next, 5 mL of
water was added and the reaction was stirred overnight at room
temperature. The reaction mixture was added to ether (25 mL) in a
separatory funnel and washed with water (2ꢁ 15 mL). The organic
layer was dried over MgSO4, filtered and the solvent was removed
by rotary evaporation. The crude product was purified by silica gel
column chromatography using a mixture of 88% hexanes and 12%
EtOAc as eluent to give 20 (0.09 g, 77% isolated yield, Rf (88%
hexanes, 12% EtOAc) = 0.37, purity by 1H NMR = 99%); 19F NMR
3.25. (E)-1,2-Difluoro-1-(meta-nitrophenyl)-5-bromo-1-pentene,
(E)-BrCH2CH2CH2CF55CFC6H4NO2-m (22)
A 15 mL two-necked, round bottomed flask equipped with a
water condenser, nitrogen gas inlet, Teflon coated magnetic stir
bar, and a rubber septum port was charged with PPh3 (0.14 g,
0.54 mmol) and 15 (0.12 g, 0.50 mmol). Next, 1.5 mL of DMF was
added and the mixture was stirred to dissolve the solids. Then, Br2
was added dropwise until the orange color persisted. The reaction
mixture was stirred overnight at room temperature. The reaction
mixture was added to water (15 mL) in a separatory funnel and
washed with ether (2ꢁ 20 mL). The combined ether layers were
washed with water (2ꢁ 15 mL) dried over MgSO4, filtered and the
solvent was removed by rotary evaporation. The crude product
was purified by silica gel column chromatography using a mixture
of 88% hexanes and 12% EtOAc as eluent to give 22 (0.10 g, 67%
isolated yield, Rf (88% hexanes, 12% EtOAc) = 0.30, purity by 1H
NMR = 97%); 19F NMR (CDCl3): ꢀ142.4 ppm (dt, 1F, 3JFF = 123.2 Hz,
3
(CDCl3): ꢀ63.4 ppm (s, 3F), ꢀ144.3 ppm (dt, 1F, JFF =122.3 Hz,
3
4
3JFH = 24.0 Hz), ꢀ159.6 ppm (dt, 1F, JFF = 123.0 Hz, JFH = 5.4 Hz);
1H NMR (CDCl3): 7.9 ppm (s, 1H), 7.8 ppm (d, 1H, JHH = 7.7 Hz),
3
3
3
7.6 ppm (d, 1H, JHH = 7.8 Hz), 7.5 ppm (dd, 1H, JHH = 7.7 Hz,
3JHH = 7.6 Hz), 4.2 ppm (t, 2H, JHH = 6.3 Hz), 2.7 ppm (dtd, 2H,
3
3JHF = 23.2 Hz, 3JHH = 7.3 Hz, 4JHF = 5.6 Hz), 2.1 ppm (s, 3H), 2.0 ppm
3JFH = 22.8 Hz), ꢀ159.0 ppm (dt, 1F, JFF = 123.1 Hz, JFH = 5.6 Hz);
3
4
(pent, 2H, JHH = 7.3 Hz); 13C NMR (CDCl3): 171.06 ppm (s),
1H NMR (CDCl3): 8.5 ppm (dd, 1H, JHF = 2.0 Hz, JHF = 1.9 Hz),
8.2 ppm (ddd, 1H, JHH = 8.1 Hz, JHF = 2.3 Hz, JHF = 1.1 Hz),
3
3
4
1
2
3
5
6
152.60 ppm (dd, JCF = 250.1 Hz, JCF = 56.0 Hz), 146.04 ppm, dd,
Please cite this article in press as: S. Lukaszewski-Rose, D.J. Burton, J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/
j.jfluchem.2014.12.006

G Model
FLUOR-8483; No. of Pages 10
10
S. Lukaszewski-Rose, D.J. Burton / Journal of Fluorine Chemistry xxx (2015) xxx–xxx
3
3
4
7.9 ppm (ddd, 1H, JHH = 8.0 Hz, JHF = 1.5, JHF = 1.1 Hz), 7.6 ppm
(dd, 1H, 3JHH = 8.1 Hz, 3JHH = 8.0 Hz), 3.5 ppm (t, 2H, 3JHH = 6.6 Hz),
Stille–Liebeskind conditions gave the corresponding (E)-4,5-
difluoro-5-aryl-4-penten-1-ol (14–18). Reaction of (Z)-HOCH2
CH2CH2CF55CFSn(n-Bu)3 (12) with I2 (neat) gave (Z)-HOCH2CH2
CH2CF55CFI (19).
3
3
4
2.8 ppm (dtd, 2H, JHF = 23.2 Hz, JHH = 7.0 Hz, JHF = 5.6 Hz),
3
2.2 ppm (pent, 2H, JHH = 6.9 Hz); 13C NMR (CDCl3): 152.96 ppm
(dd, 1JCF = 251.4 Hz, 2JCF = 55.2 Hz), 145.57 ppm (dd, 1JCF = 226.3 Hz,
References
2JCF = 43.3 Hz), 148.42 ppm (s), 131.19 ppm (dd, JCF = 26.7 Hz,
2
3JCF = 7.0 Hz), 130.68 ppm (dd, 3JCF = 9.9 Hz, 4JCF = 7.7 Hz),
129.58 ppm (d, JCF = 2.1 Hz), 123.15 ppm (d, JCF = 1.7 Hz),
120.15 ppm (dd, 3JCF = 9.4 Hz, 4JCF = 7.6 Hz) 31.98 ppm (s),
[1] C. Lim, C.A. Wesolowski, D.J. Burton, J. Fluorine Chem. 159 (2014) 21–28.
[2] C. Lim, D.J. Burton, J. Fluorine Chem. 167 (2014) 61–73.
[3] For
a general survey of F-induced reactions with fluoroolefins: R.D.
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UK, 2004, pp. 185–191.
[4] S.D. Pedersen, D.J. Burton, J. Fluorine Chem. 155 (2013) 39–44.
[5] Q. Liu, D.J. Burton, Org. Lett. 4 (2002) 1483–1485.
[6] D.J. Burton, C.A. Wesolowski, Q. Liu, C.R. Davis, J. Fluorine Chem. 131 (2010)
989–995.
2
28.80 ppm (s), 26.31 ppm (d, JCF = 23.1 Hz), GC–MS, m/z (relative
intensity): 305 (M+, 43.11), 307 (M2+, 46.17), 198 (55.78), 152
(82.52), 151 (100.00); HRMS: C11H1079BrF2N02 (calculated:
304.9863, observed: 304.9855, (M2+
observed: 306.9834).
) calculated: 306.9843,
[7] L. Xue, L. Lu, S.D. Pederson, Q. Liu, R.M. Narske, D.J. Burton, J. Org. Chem. 62 (1997)
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131–134.
4. Conclusions
(Z)-H2C55CHCH2CF55CFSnBu3 (2) can be readily prepared from
1, KF, and ClSn(n-Bu)3 in DMF. 2 was coupled with substituted aryl
iodides under Stille–Liebeskind conditions to afford good yields to
the corresponding 1,2-difluoro-1-aryl-1,4-pentadiene (4–9). Both
electron withdrawing groups and electron releasing groups
worked equally well during the coupling procedure. Hydrobora-
tion/oxidation of 2 with 9-BBN in THF produced the corresponding
(Z)-HOCH2CH2CH2CF55CFSn(n-Bu)3 (12). Coupling of (Z)-HOCH2
CH2CH2CF55CFSn(n-Bu)3 (12) with substituted aryl iodides under
[17] D.J. Burton, T.D. Spawn, P.L. Heinze, A.R. Bailey, S. Shin-Ya, J. Fluorine Chem. 44
(1989) 167–174.
[18] P. Knochel, J.F. Normant, Tetrahedron Lett. 25 (1984) 1475–1478.
Please cite this article in press as: S. Lukaszewski-Rose, D.J. Burton, J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/
j.jfluchem.2014.12.006