Efficient synthesis of silylated 2,2-difluorostyrene derivatives through Suzuki-Miyaura cross-coupling of 2,2-difluoro-1-iodo-1-silylethenes

Article abstract of DOI:10.1039/c2ob27221k

We report a new synthetic sequence for the preparation of silylated 2,2-difluorostyrene derivatives. This new route has numerous advantages over the previous one including enhanced scope, higher yields, ease of purification, and significant reduction of the amount of desilylated side-products. An unexpected transformation of a silylated 2,2-difluorostyrene derivative is also presented.

Full text of DOI:10.1039/c2ob27221k

Organic &
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Efficient synthesis of silylated 2,2-difluorostyrene
derivatives through Suzuki–Miyaura cross-coupling of
2,2-difluoro-1-iodo-1-silylethenes†
Cite this: Org. Biomol. Chem., 2013, 11,
1367
Marc-Olivier Turcotte-Savard and Jean-François Paquin*
Received 14th November 2012,
Accepted 13th December 2012
We report a new synthetic sequence for the preparation of silylated 2,2-difluorostyrene derivatives. This
new route has numerous advantages over the previous one including enhanced scope, higher yields,
ease of purification, and significant reduction of the amount of desilylated side-products. An unexpected
transformation of a silylated 2,2-difluorostyrene derivative is also presented.
DOI: 10.1039/c2ob27221k
www.rsc.org/obc
Introduction
Monofluoroalkenes are a subset of fluoroorganic compounds1
that are of particular interest in medicinal chemistry. For
example, this motif can, among other things, be used as an
enol2 or an amide bond mimic.3 It is not therefore surprising
that a number of methods for their synthesis have been
described in the literature over the years.4
We have reported new methods for the preparation of tri-
and tetrasubstituted monofluoroalkenes (3),5 cis- and trans-
β-fluorostyrene (4) derivatives,6 and unsymmetrical 2,2-diaryl-
1-fluoroethenes (5)7 based on the addition/elimination reac-
tion of organolithium reagents to silylated 2,2-difluorostyrene
derivatives 1 or 2 (Fig. 1).8 The requisite silylated 2,2-
Scheme 1 Synthetic approaches to silylated 2,2-difluorostyrene derivatives.
difluorostyrene derivatives 1 or 2 were prepared in two steps as
shown in Scheme 1.9
First, the 1-iodo-2,2-difluorostyrenes (7) were prepared from
2,2,2-trifluoro-1-iodoethane following Burton’s procedure.10
Conversion of the vinyl iodides (7) to the vinyl silanes was per-
formed by in situ trapping of the vinyl lithium species (6)
obtained through iodine/lithium exchange.9a While a number
of silylated 2,2-difluorostyrene derivatives (1 or 2) could be pre-
pared, with low to good yields, using this route, on numerous
occasions, the final compounds could not be obtained or were
impure. More specifically, these limitations originated from
the somewhat narrow scope for the Negishi cross-coupling
(6 → 7), variable yield (due to LiF elimination on the inter-
mediate 6) and functional group incompatibility in the silyl
group introduction step, and reduction (i.e. compound 7 with
H instead of I) which proved to be challenging to separate in
certain cases while impossible to separate in others.
Fig. 1 Various monofluoroalkenes accessible from silylated 2,2-difluorostyrene
derivatives.
These fundamental limitations impeded us in the appli-
cation of our methodologies for the synthesis of more functio-
nalized monofluoroalkenes (i.e. 3–5) and compelled us to find
an alternative approach for the synthesis of silylated 2,2-
difluorostyrene derivatives. Accordingly, we wondered if using
a different sequence of events would allow us to circumvent
Canada Research Chair in Organic and Medicinal Chemistry, Department of
Chemistry, 1045 avenue de la Médecine, Université Laval, Québec, Canada.
E-mail: jean-francois.paquin@chm.ulaval.ca; Fax: +1-418-656-7916;
Tel: +1-418-656-2131 ext11430
†Electronic supplementary information (ESI) available: NMR spectra for all the
new compounds prepared. See DOI: 10.1039/c2ob27221k
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Table 1 Preparation of silylated 2,2-difluorostyrene
Scheme 2 Preparation of 2,2-difluoro-1-iodo-1-silylethenes 8–11.
Entry
Substrate
Product
Yielda (%)
1
2
3
4
8
9
10
11
1a
2a
12a
13a
58
91
68
57
the problems previously described. In this novel route, the
vinyl lithium species (6) would be intercepted with a chloro-
trialkylsilane11 or trialkylsilane triflate to provide 2,2-difluoro-
1-iodo-1-silylethenes. The latter would be used as a substrate
for Suzuki–Miyaura cross-coupling. Herein, we report the suc-
cessful development of this sequence. Improvements over the
previous method include enhanced scope, ease of purification,
and significant diminution in the amount of reduced
products.
a Isolated yield.
to behave equally well or slightly better in addition/elimination
reactions than 2,2-difluoro-1-iodo-1-trimethylsilylethene 8.5,7
We were pleased to find that employing standard Suzuki–
Miyaura cross-coupling, the reaction proceeded well with
various arylboronic acids without any sign of removal of the
silyl group, a concern owing to the basic conditions employed.
In terms of scope, good to excellent yields were obtained for a
wide range of arylboronic acids bearing various substituents at
the 3 or 4 position (Table 2). Notably, compounds 2d,e,j,k,l
would have been very difficult or impossible to prepare using
the previous route due to functional group incompatibility
with the use of n-BuLi in the silyl group introduction step.
While these conditions proved to be general for 3- and/or
4-substituted arylboronic acids, the ones bearing a substituent
at the 2 position behaved poorly. For instance, using 2-methoxy-
phenylboronic acid or 2-fluorophenylboronic acid provided
moderate NMR yields whereas when 2-chlorophenylboronic
acid was used, only trace amounts of the desired product were
observed. Also, in these cases, a significant amount of desily-
lated material (i.e. compounds 2n–p with H instead of TES)
was also observed in the crude NMR.
The limitations observed with the 2-substituted arylboronic
acids prompted us to evaluate alternative reaction conditions.
Of the ones screened, the condition reported by Buchwald
using an XPhos-based precatalyst provided interesting results
(Table 3).12,13 Indeed, moderate to good yields could be
obtained for a wide range of 2-substituted arylboronic acids
including the ones that did not proceed well with the original
Suzuki–Miyaura conditions (compare Table 3, entries 1–3 with
Table 2, entries 13–15).
Results and discussion
We initially examined the preparation of 2,2-difluoro-1-iodo-1-
silylethenes from 2,2,2-trifluoro-1-iodoethane (Scheme 2).
Thus, subjecting 2,2,2-trifluoro-1-iodoethane to 2.1 equiv. of
LDA in THF at −78 °C promoted an elimination followed by a
deprotonation generating the vinyl lithium intermediate 6 that
was trapped with an electrophilic trialkylsilane. Using chloro-
trimethylsilane, the desired 2,2-difluoro-1-iodo-1-silylethene
was obtained in 50% yield. The high volatility of 8 explains the
lower isolated yield since the NMR yield (determined by 19F
NMR using fluorobenzene as an internal standard) was over
90%. Using chlorotriethylsilane, compound 9 was obtained in
88% yield. Similarly, when tert-butyldimethylsilyl chloride and
triisopropylsilyl triflate were used, the corresponding 2,2-
difluoro-1-iodo-1-silylethenes 10 and 11 were obtained in 78%
and 80% yield respectively.
With these substrates in hand, we next investigated their
behavior in Suzuki–Miyaura cross-coupling using phenylboro-
nic acid (Table 1). With the trimethylsilyl substrate 8, the
product 1a was isolated in 58% yield (entry 1). Here again,
volatility of the product explains the moderate isolated yield.
On the other hand, compound 2a bearing a triethylsilyl was
obtained in an excellent 91% yield whereas coupling of com-
pound 10 gave 12a in 68% yield. Reaction of 11 under those
reaction conditions provided 13a in 57% yield. Notably, for
compounds 2a and 12a, the overall yields from CF2CH2I (80%
and 53% respectively) represent good improvement from the
ones obtained, also from CF2CH2I, using the previous
approach (57% and 37% respectively).5
The silylated 2,2-difluorostyrene derivatives prepared above
are useful building blocks since they can potentially be used
for the preparation of a wide range of monofluoroalkenes.5–7
Nevertheless, we also investigated additional transformations
and as such, we wondered if the silylated 2,2-difluorostyrene
derivatives (2) could be used as precursors for the synthesis of
2,2-difluorostyrenes through a protodesilylation reaction as
this transformation is known for similar compounds
We then decided to focus our effort on 2,2-difluoro-1-iodo-
1-triethylsilylethene 9 as, in addition to the overall good yield
obtained for its preparation, these substrates have been shown
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Table 2 Preparation of 1-triethylsilyl-2,2-difluorostyrene derivatives
Table 2 (Contd.)
Entry
12
Substrate
Product
Yielda (%)
93
Entry
1
Substrate
Product
Yielda (%)
80
13
14
15
45c
2
81
41c
3
4
92
89
Tracesc
5
95
98
68
95
89
79
85
a Isolated yield. b The reaction was performed using 3 mol% of Pd-
(PPh3)4. c NMR yield estimated by 19F NMR using fluorobenzene as an
internal standard.
6
(Scheme 3).6 In addition, 2,2-difluorostyrenes represent impor-
tant fluorinated building blocks in organic synthesis and
materials sciences.1,14,15 However, treating compound 2f with
TBAF in aqueous THF did not produce the expected 2,2-
difluorostyrene 15. Instead, compound 1616 was observed as
the major product (69% by NMR). It is worth noting that
(2,2,2-trifluoroethyl)arenes are valuable synthetic targets for
various applications in medicinal chemistry and materials
sciences.15a,17 Interestingly, using KF as the fluoride source in
the presence of 18-crown-6 completely reverses the selectivity
and a 66% NMR yield was observed for 15.9a At this point, the
exact mechanism leading to 16 and the reason for a complete
reversal in selectivity are unknown and will be the subject of
further investigations.15a Nonetheless, both reactions, after
additional optimization, would represent synthetically useful
modifications of silylated 2,2-difluorostyrene derivatives.
7
8b
9
10b
11
Conclusions
In conclusion, we have reported a new synthetic sequence for
the preparation of silylated 2,2-difluorostyrene derivatives.
This new route has numerous advantages over the previous
one including, in particular, an improved scope. In addition,
an unexpected transformation of a silylated 2,2-difluorostyrene
derivative into a (2,2,2-trifluoroethyl)arene was presented. The
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Table 3 Preparation of 1-triethylsilyl-2,2-difluorostyrene derivatives under
Buchwald’s conditions using 2-substituted arylboronic acids
Experimental
General
All reactions were carried out under an argon atmosphere with
dry solvents when anhydrous conditions were required. 1H,
13C, and 19F NMR spectra were recorded on an AGILENT DD2
500, a VARIAN Inova 400 or a BRUKER Avance 300 in CDCl3 at
ambient temperature using tetramethylsilane (1H NMR) or
residual CHCl3 (1H and 13C NMR) as the internal standard, or
CFCl3 (19F NMR) as the external standard. Infrared spectra
were recorded on a Nicolet MagnaIR 850 spectrometer. High-
resolution mass spectra were obtained on an LC/MS-TOF
Agilent 6210 using atmospheric pressure photoionization ioni-
zation (APPI) or electrospray ionization (ESI). Low-resolution
mass spectra were obtained on a ThermoFisher Scientific
Trace GC Ultra with an ITQ 900 Ion Trap mass spectrometer
using chemical ionization (CI) or electron impact (EI).18
Entry
1
Substrate
Product
Yielda (%)
73
2
3
4
5
73
75
83
84
(2,2-Difluoro-1-iodovinyl)trimethylsilane (8). To an oven-
dried, nitrogen flushed 25 mL round-bottom flask was added
successively dry, degassed diethyl ether (3 mL) and diisopropyl-
amine (1.65 mL, 11 mmol, 2.2 equiv.). The flask was cooled to
−78 °C, and n-butyllithium (4 mL of a 2.6 M in hexane,
10.5 mmol, 2.1 equiv.) was added dropwise. In an oven-dried,
nitrogen flushed 10 mL round-bottom flask were successively
added via a syringe: dry, degassed diethyl ether (3 mL), tri-
fluoroiodoethane (493 μL, 5.0 mmol, 1 equiv.) and chlorotri-
methylsilane (790 μL, 6.25 mmol, 1.25 equiv.). This 10 mL
round-bottom flask was cooled to −78 °C using a dry ice/
acetone bath. The content of the 10 mL round-bottom flask
was transferred to the 25 mL flask, maintained at −78 °C,
using a cannula and a nitrogen flow. The nitrogen pressure
was regulated to allow a dropwise addition of the LDA solu-
tion. The reaction mixture was then allowed to return to
room temperature over 14 h. The reaction mixture was
extracted using a solution of saturated sodium bicarbonate in
water (10 mL) diluted with an extra 15 mL of water. The
aqueous phase was extracted three times using pentane. The
combined organic layers were concentrated. The crude mixture
was filtered over a short (1.5 cm) plug of silica gel using four
portions of pentane (15 mL each). The filtrate was concen-
trated under reduced pressure (with extra care taken to avoid
reaching a vacuum stronger than 200 mbar) to give the
product (660 mg, 50%) as a colorless liquid. IR (neat) ν = 2961,
6
7
63
72
a Isolated yield.
1667, 1252, 1227, 1004, 869, 840, 756 cm−1
;
1H NMR
(400 MHz, CDCl3) δ = 0.19 (s, 9H); 13C NMR (100 MHz, CDCl3)
δ = 155.5 (dd, J = 299.6, 291.1 Hz), 43.7 (d, J = 45.5 Hz), −0.8;
19F NMR (376 MHz, CDCl3) δ = −51.9 (d, 1F, J = 22 Hz), −67.1
(d, 1F, J = 22 Hz); GC-MS (CI) m/z 262 (M+, 64%), 189 (68), 185
(55), 81 (50), 77 (66), 73 (88), 51 (100).
Scheme 3 Transformations of silylated 2,2-difluorostyrene derivative 2f.
General procedure for the preparation of (2,2-difluoro-1-
iodovinyl)trialkylsilanes 9–11
(2,2-Difluoro-1-iodovinyl)triethylsilane (9). To an oven-
dried, argon flushed, 50 mL round-bottom flask equipped with
a magnetic stirbar and covered with a rubber septum, was
added, via a syringe, diisopropylamine (3.22 mL, 21.7 mmol,
use of these newly accessible fluorinated building blocks in
various reactions is underway and will be reported in due
course.
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2.2 equiv.). Dry, degassed THF (10 mL) was then added via a covered with a rubber septum was added vinyl iodide (8)
syringe. The resulting solution was cooled to −78 °C in a dry (86.1 mg, 0.33 mmol, 1 equiv.). Phenylboronic acid (60.1 mg,
ice/acetone bath. n-Butyllithium (6.6 mL of a 3.1 M in hexane, 0.49 mmol, 1.5 equiv.), sodium carbonate (105 mg, 0.99 mmol,
20.7 mmol, 2.1 equiv.) was added dropwise, and the solution 3 equiv.) and Pd(PPh3)4 (3.7 mg, 0.0033 mmol, 1 mol%) were
was cooled back to −78 °C. Trifluoroiodoethane (1.00 mL, quickly weighed and added to the reaction flask. The flask was
9.84 mmol, 1 equiv.) was added dropwise, and the resulting stoppered with a septum, and submitted to 4 vacuum/argon
solution was stirred 5 minutes at −78 °C. Chlorotriethylsilane cycles while it was cooled in an ice/water bath. Toluene
(1.98 mL, 11.8 mmol, 1.2 equiv.) was added dropwise, and the (degassed under argon, 3 mL), 95% EtOH (degassed under
resulting mixture was allowed to warm back to room tempera- argon, 1 mL) and water (degassed under argon, 1 mL) were
ture over 12 h. The mixture was poured into an extraction added successively via a syringe. The reaction vessel was
funnel containing a cool HCl solution (10% in water, 25 mL). placed in an oil bath and warmed to 80 °C for 6 h. The reac-
The aqueous phase was extracted three times using small por- tion vessel was cooled down to room temperature, water
tions (25 mL) of diethyl ether. The combined organic layers (5 mL) was added, and the reaction mixture was extracted
were dried over magnesium sulfate and the solvents were evap- using three portions of Et2O (5 mL). The combined organic
orated. A pad of silica gel (approximately 2 cm in height) was extracts were dried over anhydrous MgSO4, filtered over a
pretreated with a solution of triethylamine in hexane (1 : 100) fritted glass funnel, and concentrated under reduced pressure.
and flushed with a portion of pentane. The crude reaction The crude material was purified via flash chromatography
mixture was then filtered over the short silica plug using 2 por- using 100% hexane as the eluent to give the desired product
tions of pentane (20 mL each) as the eluent. Pentane was evap- (40.4 mg, 58%) as a colorless oil. The spectroscopic data were
orated to give the product (2.64 g, 88%) as a faintly yellow identical as previously reported.5
liquid. IR (neat) ν = 2956, 2877, 1698, 1681, 1225, 1002, 845,
(2,2-Difluoro-1-phenylvinyl)triethylsilane (2a). According to
721 cm−1 1H NMR (400 MHz, CDCl3) δ = 0.97 (t, 9H, J = the general procedure on a 1.64 mmol scale of 9, heating the
;
7.9 Hz), 0.75 (q, 6H, J = 7.9 Hz); 13C NMR (100 MHz, CDCl3) δ = reaction vessel at 80 °C for 4 h, the desired product (380 mg,
156.2 (dd, J = 299.9, 291.0 Hz), 40.6 (d, J = 47.3 Hz), 7.0, 3.6; 91%) was isolated as a transparent oil via flash chromato-
19F NMR (376 MHz, CDCl3) δ = −50.4 (d, 1F, J = 22.2 Hz), −67.2 graphy using 100% hexane as the eluent. The spectroscopic
(d, 1F, J = 22.2 Hz); GC-MS (CI) m/z 304 (M+, 4%), 247 (100), data were identical as previously reported.5
219 (44), 203 (26).
tert-Butyl(2,2-difluoro-1-phenylvinyl)dimethylsilane
(12a).
tert-Butyl(2,2-difluoro-1-iodovinyl)dimethylsilane (10). Accord- According to the general procedure on a 0.33 mmol of 10,
ing to the general procedure on a 0.33 mmol scale of heating the reaction vessel at 80 °C for 14 h, the desired
1-iodo-2,2,2-trifluoroethane
chloride, the desired product (485 mg, 78%), a colorless oil, flash chromatography using 100% hexane as the eluent. IR
was isolated via flash chromatography using 100% hexane as (neat) ν = 2929, 2859, 1679, 1241, 1216, 1015, 808, 699 cm−1
the eluent. IR (neat) ν = 2930, 2859, 1660, 1464, 1228, 997, 837, 1H NMR (400 MHz, CDCl3) δ = 7.32 (t, 2H, J = 7.4 Hz), 7.23 (m,
774 cm−1 1H NMR (400 MHz, CDCl3) δ = 0.96 (s, 9H), 1H), 7.11 (br d, 2H, J = 7.2 Hz), 0.94 (s, 9H), 0.11 (d, 6H, J = 1.7
using
tert-butyldimethylsilyl product (57.0 mg, 68%) was isolated as a transparent oil via
;
;
0.27 (br d, 6H, J = 1.7 Hz); 13C NMR (100 MHz, CDCl3) Hz); 13C NMR (75 MHz, CDCl3) δ = 156.5 (dd, J = 306.6, 286.9
δ = 156.2 (dd, J = 300.0, 291.6 Hz), 39.8 (d, J = 45.5 Hz), Hz), 135.4 (dd, J = 10.1, 2.3 Hz), 129.6 (dd, J = 2.9, 1.5 Hz),
26.8, −3.8; 19F NMR (376 MHz, CDCl3) δ = −49.6 (d, 1F, 128.4, 126.5, 85.3 (dd, J = 33.5, 3.7 Hz), 27.0, 4.8; 19F NMR
J = 20.2 Hz), −64.3 (d, 1F, J = 20.2 Hz); GC-MS (EI) m/z 303 (376 MHz, CDCl3) δ = −69.2 (d, 1F, J = 25.4 Hz), −74.6 (d, 1F,
(M+, 4), 264 (7), 189 (C2F2I, 41) 79 (100).
(2,2-Difluoro-1-iodovinyl)triisopropylsilane (11). According
J = 25.4 Hz); GC-MS (EI) m/z 254 (M+, 5%), 115 (C6H15Si, 100).
(2,2-Difluoro-1-phenylvinyl)triisopropylsilane (13a). Accord-
to the general procedure on a 4.65 mmol scale of 1-iodo-2,2,2- ing to the general procedure on a 1.44 mmol scale of 11,
trifluoroethane using TIPS triflate, the desired product (1.28 g, heating the reaction vessel at 80 °C for 3 h, the desired
80%), a colorless oil, was isolated via flash chromatography product (303 mg, 57%) was isolated as a colorless oil via flash
using 100% hexane as the eluent. IR (neat) ν = 2945, 2867, chromatography using 100% hexane as the eluent. IR (neat)
1
1687, 1652, 1463, 1224, 985, 882 cm−1
;
1H NMR (400 MHz, ν = 2945, 2867, 1675, 1464, 1214, 995, 919, 755 cm−1; H NMR
CDCl3) δ = 1.39 (m, 3H), 1.11 (d, 18H, J = 7.5 Hz); 13C NMR (400 MHz, CDCl3) δ = 7.29 (t, 2H, J = 7.4 Hz), 7.21 (m, 1H), 7.14
(100 MHz, CDCl3) δ = 156.3 (dd, J = 299.0, 291.3 Hz), 38.9 (d, (br d, 1H, J = 7.2 Hz), 1.20 (m, 3H), 1.04 (br d, 18 H, J = 7.3
J = 47.3 Hz), 18.5, 12.4; 19F NMR (376 MHz, CDCl3) δ = −47.9 Hz); 13C NMR (100 MHz, CDCl3) δ = 156.4 (dd, J = 306.2, 286.4
(d, 1F, J = 21.0 Hz), −65.0 (d, 1F, J = 21.0 Hz); GC-MS (EI) m/z Hz), 135.3 (dd, J = 10.8, 2.4 Hz), 129.7 (dd, J = 2.8, 1.2 Hz),
345 (M+, 2%), 233 (24), 231 (28), 153 (19), 77 (100).
128.3, 126.5, 84.7 (dd, J = 34.9, 4.1 Hz), 18.7, 11.8; 19F NMR
(376 MHz, CDCl3) δ = −69.2 (d, 1F, J = 26.4 Hz), −73.8 (d, 1F,
J = 26.4 Hz); GC-MS (EI) m/z 296 (M+, 4%), 253 (39), 235 (23),
169 (30), 143 (77), 128 (60), 77 (100).
General procedure for the preparation of (2,2-difluoro-1-
arylvinyl)trialkylsilane via a traditional Suzuki–Miyaura type
cross-coupling reaction
(2,2-Difluoro-1-p-tolylvinyl)triethylsilane (2b). According to
(2,2-Difluoro-1-phenylvinyl)trimethylsilane (1a). To a 10 mL the general procedure on a 0.33 mmol scale of 9 using p-tolyl-
round-bottom flask equipped with a magnetic stirbar and boronic acid, heating at 80 °C for 17 h, the desired product
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(71.0 mg, 80%) was isolated as a transparent oil by flash
(1-(4-Chlorophenyl)-2,2-difluorovinyl)triethylsilane
(2f).
chromatography using 100% hexane as the eluent. IR (neat) ν According to the general procedure on a 3.3 mmol scale of 9
1
= 2955, 2876, 1681, 1510, 1215, 1002, 917, 812 cm−1; H NMR using 4-chlorophenylboronic acid, heating the reaction vessel
(400 MHz, CDCl3) δ = 7.11 (d, 2H, J = 8.0 Hz), 6.96 (d, 2H, J = at 80 °C for 14 h, the desired product (907 mg, 95%) was iso-
8.0 Hz), 2.32 (s, 3H), 0.93 (t, 9H, J = 7.9 Hz), 0.63 (q, 6H, J = lated as a transparent oil via flash chromatography using
7.9 Hz); 13C NMR (75 MHz, CDCl3) δ = 155.9 (dd, J = 305.6, 100% hexane as the eluent. IR (neat) ν = 2956, 2877, 1681,
286.7 Hz), 135.9, 131.7 (dd, J = 10.6, 2.2 Hz), 129.0, 128.9 (dd, 1489, 1216, 1091, 1013, 822 cm−1. 1H NMR (400 MHz, CDCl3) δ
J = 3.0, 1.4 Hz), 84.8 (dd, J = 34.4, 4.2 Hz), 21.1, 7.1, 3.3; = 7.32 (d, 2H, J = 8.3 Hz), 7.06 (d, 2H, J = 8.2 Hz), 0.97 (t, 9H, J
19F NMR (376 MHz, CDCl3) δ = −70.7 (d, 1F, J = 28.2 Hz), −78.1 = 7.9 Hz), 0.68 (q, 6H, J = 7.9 Hz); 13C NMR (100 MHz, CDCl3) δ
(d, 1F, J = 28.2 Hz); HRMS-APPI calcd for C15H22F2Si [M*]+ = 155.8 (dd, J = 307.9, 286.2 Hz), 133.3 (dd, J = 10.9, 2.1 Hz),
268.1453, found 268.1456.
132.4, 130.3 (m), 128.5, 84.3 (dd, J = 35.8, 4.7 Hz), 7.0, 3.2; 19F
(2,2-Difluoro-1-(4-methoxyphenyl)vinyl)triethylsilane
(2c). NMR (376 MHz, CDCl3) δ = −69.7 (d, 1F, J = 25.8 Hz), −77.1 (d,
According to the general procedure on a 0.33 mmol scale of 9 1F, J = 25.8 Hz); HRMS-APPI calcd for C14H19ClF2Si [M*]+
using 4-methoxyphenylboronic acid, heating the reaction 288.0907, found 288.0904.
vessel at 80 °C for 12 h, the desired product (75.3 mg, 81%)
(1-(3-Chlorophenyl)-2,2-difluorovinyl)triethylsilane
(2g).
was isolated as a transparent oil via flash chromatography According to the general procedure on a 0.33 mmol scale of 9
using hexane–Et2O (50 : 1) as the eluent. IR (neat) ν = 2955, using 3-chlorophenylboronic acid, heating the reaction vessel
2876, 1680, 1509, 1243, 1211, 1002, 827 cm−1 1H NMR at 80 °C for 4 h, the desired product (93.0 mg, 98%) was iso-
.
(300 MHz, CDCl3) δ = 6.99 (d, 2H, J = 8.7 Hz), 6.85 (d, 2H, J = lated via flash chromatography using 100% hexane as the
8.7 Hz), 3.78 (s, 3H), 0.93 (t, 9H, J = 7.8 Hz), 0.62 (q, 6H, J = eluent.5
7.9 Hz); 13C NMR (75 MHz, CDCl3) δ = 158.2, 156.0 (dd, J =
(2,2-Difluoro-1-(3-(trifluoromethyl)phenyl)vinyl)triethylsi-
305.6, 285.9 Hz), 130.0 (dd, J = 3.0, 1.4 Hz), 126.8 (dd, J = 10.8, lane (2h). According to the general procedure on a 0.33 mmol
2.0 Hz), 113.8, 84.4 (dd, J = 34.7, 4.3 Hz) 55.1, 7.1, 3.3; scale of 9 using 3-trifluoromethylphenylboronic acid, heating
19F NMR (376 MHz, CDCl3) δ = −70.8 (d, 1F, J = 28.3 Hz), −78.2 the reaction vessel at 80 °C for 6 h, the desired product
(d, 1F, J = 28.3 Hz); HRMS-APPI calcd for C15H22OF2Si [M*]+ (71.9 mg, 68%) was isolated as a transparent oil via flash
284.1402, found 284.1414.
4-(2,2-Difluoro-1-(triethylsilyl)vinyl)benzonitrile
chromatography using 100% hexane as the eluent. IR (neat) ν
(2d). = 2958, 2879, 1684, 1331, 1214, 1126, 1073, 801 cm−1. 1H NMR
According to the general procedure on a 0.33 mmol scale of 9 (300 MHz, CDCl3) δ = 7.46 (m, 2H), 7.33 (s, 1H), 7.26 (d, 1H, J =
using 4-cyanophenylboronic acid, heating the reaction vessel 7.8 Hz), 0.93 (t, 9H, J = 7.8 Hz), 0.64 (q, 6H, J = 7.9 Hz); 13C
at 80 °C for 17 h, the desired product (85.3 mg, 92%) was NMR (75 MHz, CDCl3) δ = 156.1 (dd, J = 308.4, 286.6 Hz), 135.9
isolated as a yellow oil via flash chromatography using (dd, J = 11.0, 2.2 Hz), 132.4 (m), 128.8, 128.6 (d, J = 61.2 Hz),
hexane–ethyl acetate (15 : 1) as the eluent. IR (neat) ν = 2956, 130.8 (d, J = 32.2 Hz), 125.8, 123.3 (q, J = 3.8 Hz), 84.7 (dd, J =
2877, 2229, 1680, 1219, 1003, 833, 721 cm−1
.
1H NMR 36.6, 5.0 Hz), 7.0, 3.2; 19F NMR (282 MHz, CDCl3) δ = −63.1 (s,
(400 MHz, CDCl3) δ = 7.61 (d, 2H, J = 8.4 Hz), 7.20 (d, 2H, J = 3F), −69.1 (d, 1F, J = 24.4 Hz), −76.6 (d, 1F, J = 24.4 Hz); GC-MS
8.5 Hz), 0.93 (t, 9H, J = 7.9 Hz), 0.64 (q, 6H, J = 7.9 Hz); (CI) m/z 321 ([M − H]+, 2%), 303 ([M − F]+, 100), 265 (10), 237
13C NMR (100 MHz, CDCl3) δ = 155.9 (dd, J = 309.0, 287.2 Hz), (21), 179 (36).
140.6 (dd, J = 11.0, 2.0 Hz), 132.4, 130.1 (dd, J = 2.8, 1.3 Hz),
(2,2-Difluoro-1-(3-nitrophenyl)vinyl)triethylsilane
(2i).
119.0, 110.6, 85.1 (dd, J = 36.8, 5.3 Hz) 7.3, 3.4; 19F NMR According to the general procedure on a 0.33 mmol scale of 9
(376 MHz, CDCl3) δ = −68.5 (d, 1F, J = 22.9 Hz), −75.9 (d, 1F, using 3-nitrophenylboronic acid and 3 mol% of Pd(PPh3)4,
J = 22.9 Hz); HRMS-ESI calcd for C15H19F2NSi [M]+ 279.1255, heating the reaction vessel at 80 °C for 17 h, the desired
found 279.1253.
product (93.5 mg, 95%) was isolated as a yellow oil via flash
4-(2,2-Difluoro-1-(triethylsilyl)vinyl)benzaldehyde
(2e). chromatography using hexane–ethyl acetate (10 : 1) as the
According to the general procedure on a 0.33 mmol scale of 9 eluent. IR (neat) ν = 2952, 2877, 1682, 1528, 1346, 1221, 1002,
using 4-formylphenylboronic acid, heating the reaction vessel 738 cm−1 1H NMR (400 MHz, CDCl3) δ = 8.13–8.10 (m, 1H),
.
at 80 °C for 19 h, the desired product (82.4 mg, 89%) was iso- 7.96 (m, 1H), 7.51 (t, 1H, J = 7.9 Hz), 7.43 (br d, 1H, J = 7.7 Hz),
lated as a transparent oil via flash chromatography using 0.95 (t, 9H, J = 7.9 Hz), 0.66 (q, 6H, J = 7.9 Hz); 13C NMR
hexane–ethyl acetate (10 : 1) as the eluent. IR (neat) ν = 2956, (400 MHz, CDCl3) δ = 156.1 (dd, J = 309.1, 287.3 Hz), 148.2,
2877, 1681, 1603, 1216, 1015, 917, 827 cm−1
.
1H NMR 136.8 (dd, J = 11.3, 2.1 Hz), 135.2 (dd, J = 2.8, 1.3 Hz), 123.8
(400 MHz, CDCl3) δ = 10.0 (s, 1H), 7.84 (d, 2H, J = 8.3 Hz), 7.26 (dd, J = 3.1, 1.4 Hz), 121.5, 84.8 (dd, J = 37.4, 5.4 Hz), 7.0, 3.2;
(d, 2H, J = 8.0 Hz), 0.94 (t, 9H, J = 7.9 Hz), 0.65 (q, 6H, J = 19F NMR (376 MHz, CDCl3) δ = −68.5 (d, 1F, J = 22.6 Hz), −75.9
7.9 Hz); 13C NMR (100 MHz, CDCl3) δ = 191.6, 155.5 (dd, J = (d, 1F, J = 22.6 Hz); HRMS-ESI calcd for C14H19F2NO2Si [M]+
308.6, 286.8 Hz), 149.9 (dd, J = 10.7, 2.0 Hz), 134.6, 129.7, 299.1153, found 299.1153.
129.6 (dd, J = 2.8, 1.4 Hz), 85.1 (dd, J = 36.2, 5.1 Hz), 7.0, 3.2;
1-(3-(2,2-Difluoro-1-(triethylsilyl)vinyl)phenyl)ethanone (2j).
19F NMR (376 MHz, CDCl3) δ = −68.9 (d, 1F, J = 23.4 Hz), −76.3 According to the general procedure on a 0.33 mmol scale of 9
(d, 1F, J = 23.4 Hz); HRMS-ESI calcd for C15H20F2OSi [M]+ using 3-acetylphenylboronic acid, heating the reaction vessel at
282.1252, found 282.1246.
80 °C for 19 h, the desired product (87.6 mg, 89%) was isolated
1372 | Org. Biomol. Chem., 2013, 11, 1367–1375
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as a transparent oil via flash chromatography using hexane– (d, 1F, J = 25.0 Hz); HRMS-APPI calcd for C12H18F2SSi [M*]+
ethyl acetate (10 : 1) as the eluent. IR (neat) ν = 2956, 2877, 260.0861, found 260.0866.
1682, 1279, 1203, 1002, 794, 721 cm−1 1H NMR (400 MHz,
.
General procedure for the preparation of (2,2-difluoro-1-
arylvinyl)trialkylsilane via a Suzuki–Miyaura type cross-
coupling reaction using Buchwald’s precatalyst (14)
CDCl3) δ = 7.83 (ddd, 1H, J = 7.8, 1.8, 1.2 Hz), 7.70–7.68 (m,
1H), 7.42 (t, 1H, J = 7.7 Hz), 7.30–7.27 (m, 1H), 2.60 (s, 3H),
0.94 (t, 9H, J = 7.9 Hz), 0.64 (q, 6H, J = 7.9 Hz); 13C NMR
(75 MHz, CDCl3) δ = 197.7, 155.9 (dd, J = 308.0, 286.2 Hz),
(2,2-Difluoro-1-(2-methoxyphenyl)vinyl)triethylsilane (2n). To
137.2, 135.4 (dd, J = 10.8, 2.2 Hz), 133.6 (dd, J = 2.9, 1.3 Hz), a 12 × 75 mm borosilicate test tube equipped with a
128.7 (dd, J = 3.0, 1.4 Hz), 128.5, 126.5, 84.7 (dd, J = 35.8, 4.9 magnetic stirbar and covered with a rubber septum was added
Hz), 26.5, 7.0, 3.2; 19F NMR (376 MHz, CDCl3) δ = −69.6 (d, 1F, vinyl iodide (9) (100 mg, 0.33 mmol, 1 equiv.), 2-methoxyphe-
J = 25.5 Hz), −77.0 (d, 1F, J = 25.5 Hz); HRMS-ESI calcd for nylboronic acid (74.9 mg, 0.49 mmol, 1.5 equiv.) and Buch-
C16H22F2OSi [M]+ 296.1408, found 296.1414.
wald’s precatalyst 1412 (7.8 mg, 0.0099 mmol, 3 mol%). The
3-(2,2-Difluoro-1-(triethylsilyl)vinyl)aniline (2k). According flask was stoppered with a septum, and submitted to 4
to the general procedure on a 0.33 mmol scale of 9 using vacuum/argon cycles. THF (degassed under argon, 0.66 mL)
3-aminophenylboronic acid monohydrate and 3 mol% of Pd- and a solution of K3PO4 in water (degassed under argon,
(PPh3)4, heating the reaction vessel at 80 °C for 6 h, the 0.5 M, 1.33 mL) are successively added via a syringe. The reaction
desired product (70.0 mg, 79%) was isolated as a brown oil via vessel was placed in an oil bath and warmed to 40 °C for 21 h.
flash chromatography using 100% CH2Cl2 as the eluent. IR The reaction vessel was cooled down to room temperature,
(neat) ν = 2955, 2876, 1684, 1601, 1220, 1003, 780, 720 cm−1
.
water (1 mL) was added, and the reaction mixture was
1H NMR (400 MHz, CDCl3) δ = 7.08 (t, 1H, J = 7.8 Hz), 6.55 (m, extracted using three portions of Et2O (1 mL). The combined
1H), 6.47 (d, 1H, J = 7.5 Hz), 3.64 (d, 2H), 0.93 (t, 9H, J = organic extracts were dried over anhydrous Na2SO4, filtered
7.9 Hz), 0.63 (q, 6H, J = 7.8 Hz); 13C NMR (100 MHz, CDCl3) δ = over a fritted glass funnel, which was carefully rinsed with a
155.6 (dd, J = 307.1, 285.1 Hz), 146.2, 135.8 (dd, J = 10.5, small portion of Et2O, and concentrated under reduced
2.12 Hz), 129.1, 119.4 (dd, J = 2.6, 1.0 Hz), 115.7, 113.3, 85.0 pressure. The crude material was purified via flash chromato-
(dd, J = 34.3, 4.6 Hz), 7.1, 3.2; 19F NMR (376 MHz, CDCl3) graphy using hexane–Et2O (40 : 1) as the eluent to give the
δ = −70.6 (d, 1F, J = 28.4 Hz), −78.4 (d, 1F, J = 28.4 Hz); desired product (69.1 mg, 73%) as a yellow oil. IR (neat) ν =
1
HRMS-ESI calcd for C14H21F2NSi [M]+ 269.1411, found 269.1421. 2954, 2876, 1687, 1492, 1253, 1116, 1004, 787 cm−1. H NMR
5-(2,2-Difluoro-1-(triethylsilyl)vinyl)-2-methoxybenzaldehyde
(500 MHz, CDCl3) δ = 7.21–7.19 (m, 1H), 7.00 (m, 1H), 6.89 (td,
(2l). According to the general procedure on a 0.33 mmol scale 1H, J = 7.4, 1.1 Hz), 6.84 (d, 1H, J = 8.4 Hz), 0.91 (t, 9H, J =
of 9 using 3-formyl-4-methoxyphenylboronic acid, heating the 7.9 Hz), 0.60 (q, 6H, J = 7.9 Hz); 13C NMR (400 MHz, CDCl3) δ =
reaction vessel at 80 °C for 19 h, the desired product (88.2 mg, 156.7, 154.7 (dd, J = 306.8, 284.3 Hz), 130.5 (dd, J = 2.7, 1.4
85%) was isolated as a yellow oil via flash chromatography Hz), 127.9, 123.6 (dd, J = 10.7, 1.9 Hz), 120.4, 110.4, 81.1 (dd,
using hexane–ethyl acetate (10 : 1) as the eluent. IR (neat) ν = J = 37.3, 4.2 Hz), 55.0, 7.1, 3.3; 19F NMR (470 MHz, CDCl3) δ =
1
2955, 2876, 1677, 1494, 1235, 1115, 1019, 721 cm−1. H NMR −70.2 (d, 1F, J = 27.9 Hz), −76.9 (d, 1F, J = 27.9 Hz); GC-MS (EI)
(400 MHz, CDCl3) δ = 10.50 (s, 1H), 7.55 (d, 1H, J = 2.4 Hz), m/z 284 (M+, 2%), 255 ([M − C2H5]+, 100), 240 (23), 197 (22),
7.27 (dd, J = 8.57, 2.4 Hz), 6.96 (d, 1H, J = 8.6 Hz), 3.93 (s, 3H), 128 (45), 115 (C6H15Si, 69), 89 (24).
0.93 (t, 9H, J = 7.9 Hz), 0.63 (q, 6H, J = 7.9 Hz); 13C NMR
(2,2-Difluoro-1-(2-fluorophenyl)vinyl)triethylsilane
(2o).
(75 MHz, CDCl3) δ = 189.4, 160.4, 156.1 (dd, J = 307.8, 286.3 According to the general procedure on a 0.33 mmol scale of 9
Hz), 136.4, 128.6 (dd, J = 3.1, 1.3 Hz), 127.2 (dd, J = 11.1, using 2-fluorophenylboronic acid, the desired product
2.2 Hz), 124.6, 111.7, 83.9 (dd, J = 36.0, 4.8 Hz), 55.6, 7.0, 3.2; (65.5 mg, 73%) was isolated as a transparent oil via flash
19F NMR (376 MHz, CDCl3) δ = −69.9 (d, 1F, J = 26.0 Hz), −77.1 chromatography using 100% hexane as the eluent. IR (neat) ν
1
(d, 1F, J = 26.0 Hz); HRMS-ESI calcd for C16H22F2O2Si = 2955, 2878, 1685, 1490, 1249, 1104, 1004, 809, 754 cm−1. H
[M]+ 312.1357, found 312.1361.
(2,2-Difluoro-1-(thiophen-3-yl)vinyl)triethylsilane
NMR (500 MHz, CDCl3) δ = 7.27–7.20 (m, 1H), 7.13–7.05 (m,
(2m). 3H), 0.97 (t, 9H, J = 7.9 Hz), 0.68 (q, 6H, J = 7.9 Hz); 13C NMR
According to the general procedure on a 0.33 mmol scale of 9 (125 MHz, CDCl3) δ = 159.8 (d, J = 244.6 Hz), 155.3 (dd, J =
using 3-thienylboronic acid, heating the reaction vessel at 307.8, 286.0 Hz), 131.2, 128.4 (d, J = 7.8 Hz), 123.9 (d, J =
80 °C for 6 h, the desired product (79.3 mg, 93%) was isolated 3.7 Hz), 122.3 (ddd, J = 16.9, 11.0, 2.0 Hz), 115.5 (d, J = 22.3 Hz),
as a transparent oil via flash chromatography using 100% 78.9 (dd, J = 39.1, 4.1 Hz), 7.0, 3.2; 19F NMR (470 MHz, CDCl3)
hexane as the eluent. IR (neat) ν = 2955, 2876, 1681, 1237, δ = −67.5 (dd, 1F, J = 22.6, 4.3 Hz), −75.4 (d, 1F, J = 22.6 Hz),
1
1002, 847, 786, 720 cm−1. H NMR (300 MHz, CDCl3) δ = 7.27 −113.7 (m, 1F); GC-MS (EI) m/z 243 ([M − C2H5]+, 9%), 187
(dd, 1H, J = 4.9, 3.0 Hz), 6.94 (dd, 1H, J = 3.0, 1.3 Hz), 6.87 (d, (10), 185 (17), 128 (100), 115 (C6H15Si, 19), 75 (28).
1H, J = 4.9 Hz), 0.93 (t, 9H, J = 7.8 Hz), 0.65 (q, 6H, J = 7.9 Hz);
(1-(2-Chlorophenyl)-2,2-difluorovinyl)triethylsilane
(2p).
13C NMR (125 MHz, CDCl3) δ = 155.8 (dd, J = 308.6, 285.7 Hz), According to the general procedure on a 0.33 mmol scale of 9
133.7 (dd, J = 10.9, 1.8 Hz), 128.6 (dd, J = 2.9, 1.6 Hz), 125.0, using 2-chlorophenylboronic acid, the desired product
121.7 (dd, J = 3.8, 1.6 Hz), 80.0 (dd, J = 37.3, 5.1 Hz), 7.1, 3.3; (71.2 mg, 75%) was isolated as a transparent oil via flash
19F NMR (282 MHz, CDCl3) δ = −68.6 (d, 1F, J = 25.0 Hz), −76.4 chromatography using 100% hexane as the eluent. IR (neat)
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ν = 2956, 2877, 1687, 1471, 1241, 1006, 925, 714 cm−1. 1H NMR ν = 2957, 2879, 1686, 1502, 1236, 1139, 970, 849 cm−1. 1H NMR
(500 MHz, CDCl3) δ = 7.39–7.37 (m, 1H), 7.21–7.15 (m, 2H), (500 MHz, CDCl3) δ = 7.04–6.99 (m, 1H), 6.86–6.79 (m, 2H),
7.08–7.06 (m, 1H), 0.93 (t, 9H, J = 7.9 Hz), 0.65 (m, 6H); 13C 0.93 (t, 9H, J = 7.9 Hz), 0.64 (q, 6H, J = 7.9 Hz); 13C NMR
NMR (100 MHz, CDCl3) δ = 155.1 (dd, J = 308.1, 286.1 Hz), (125 MHz, CDCl3) δ = 161.9 (dd, J = 248.0, 11.6 Hz), 159.7 (dd,
133.6 (dd, J = 11.5, 1.8 Hz), 130.8 (dd, J = 2.9, 1.3 Hz), 129.5, J = 248.0, 12.2 Hz), 155.5 (dd, J = 309.0, 286.5 Hz), 131.7 (m),
128.0, 126.5, 83.0 (dd, J = 38.7, 4.7 Hz), 7.1, 3.4; 19F NMR 118.2 (m), 111.1 (dd, J = 21.1, 3.6 Hz), 104.0 (t, J = 26.1 Hz),
(470 MHz, CDCl3) δ = −67.0 (d, 1F, J = 22.3 Hz), −76.7 (d, 1F, 78.2 (dd, J = 39.9, 5.2 Hz), 7.0, 3.2; 19F NMR (470 MHz, CDCl3)
J = 22.3 Hz); GC-MS (CI) m/z 269 ([M − F]+, 8), 259 (11), δ = −67.1 (dd, 1F, J = 21.4, 4.3 Hz), −74.9 (d, 1F, J = 21.4 Hz),
203 (21), 167 (24), 128 (100), 91 (13).
−109.3 (m, 1F), −112.1 (m, 1F); GC-MS (EI) m/z 260 ([M −
(2,2-Difluoro-1-o-tolylvinyl)triethylsilane (2q). According to C2H5]+, 9%), 156 (12), 146 (100), 127 (59), 99 (38), 75 (29).
the general procedure on a 0.33 mmol scale of 9 using o-tolyl-
Transformation of silylated 2,2-difluorostyrene derivative 2f
boronic acid, the desired product (83.1 mg, 88%) was isolated
as a transparent oil via flash chromatography using 100%
hexane as the eluent. IR (neat) ν = 2955, 2877, 1683, 1242, 1216,
1-Chloro-4-(2,2,2-trifluoroethyl)benzene (16). To 16
a
×
100 mm borosilicate test-tube equipped with a magnetic
stirbar and covered with a rubber septum were added substrate
2f (250 mg, 0.87 mmol, 1 equiv.), water (47 μL, 2.6 mmol, 3
equiv.) and THF (7.8 mL). The tube was covered with the
septum and TBAF (1.73 mL, 1 M solution in THF, 2 equiv.) was
added via a syringe. The reaction vessel was warmed to 40 °C
for 3 h. Water (20 mL) was added, and the reaction mixture
was extracted using three portions of Et2O (10 mL). The com-
bined organic phases were dried over sodium sulfate, filtered
and concentrated. Crude 19F NMR in CDCl3 indicated com-
plete conversion of 2f and the characteristic triplet at
−66.1 ppm for the CH2CF3 moiety as the only major signal
(69% by NMR). The crude material was purified via flash
chromatography using 100% hexane as the eluent to give the
desired product 16 (62.5 mg, 37%) as a colorless oil. IR (neat) ν
= 2925, 1496, 1361, 1249, 1134, 1077, 1018, 800 cm−1. 1H NMR
(400 MHz, CDCl3) δ = 7.32 (m, 2H), 7.22 (br d, 2H, J = 8.3 Hz),
3.32 (q, 2H, J = 10.7 Hz); 13C NMR (100 MHz, CDCl3) δ = 134.4,
131.6, 129.0, 128.7 (q, J = 3.0 Hz), 125.6 (q, J = 276.8 Hz), 39.8
(q, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3) δ = −66.1 (t, 3F, J =
10.7 Hz); GC-MS (EI) m/z 194 (M+, 36%), 127 (32), 125 (100), 99
(13), 89 (37), 63 (14).
1
1008, 920, 754 cm−1. H NMR (500 MHz, CDCl3) δ = 7.20–7.15
(m, 1H), 7.15–7.08 (m, 2H), 6.95 (m, 1H), 2.24 (s, 3H), 0.92 (t,
9H, J = 7.9 Hz), 0.63 (q, 6H, J = 8.0 Hz); 13C NMR (100 MHz,
CDCl3) δ = 154.4 (dd, J = 306.8, 285.8 Hz), 136.0, 133.0 (dd, J =
10.1, 2.0 Hz), 130.0, 129.2 (m), 126.7, 125.6, 83.4 (dd, J = 34.3,
3.5 Hz), 19.9, 7.1, 3.5; 19F NMR (470 MHz, CDCl3) δ = −68.3 (d,
1F, J = 27.1 Hz), −77.5 (d, 1F, J = 27.1 Hz); GC-MS (CI) m/z 297
([M + H]+, 3%), 249 ([M − F]+, 11), 183 (25), 143 (100), 117 (74).
(2,2-Difluoro-1-(naphthalen-1-yl)vinyl)triethylsilane
(2r).
According to the general procedure on a 0.33 mmol scale of 9
using naphthalene-1-boronic acid, the desired product
(85.1 mg, 84%) was isolated as a transparent oil via flash
chromatography using 100% hexane as the eluent. IR (neat)
1
ν = 2955, 2876, 1681, 1219, 1007, 913, 799, 773 cm−1. H NMR
(500 MHz, CDCl3) δ = 7.90 (d, 1H, J = 8.1 Hz), 7.84–7.81 (m,
1H), 7.73 (d, 1H, J = 8.2 Hz), 7.49–7.43 (m, 2H), 7.40 (dd, 1H, J
= 8.1, 7.1 Hz), 7.19–7.17 (m, 1H), 0.91 (t, 9H, J = 7.9 Hz), 0.62
(q, 6H, J = 7.7 Hz); 13C NMR (100 MHz, CDCl3) δ = 154.9 (dd, J
= 307.8, 286.5 Hz), 133.8, 132.0 (m), 128.4, 127.1, 126.4 (dd, J =
3.2, 1.2 Hz), 125.9, 125.8, 125.3, 125.2, 82.7 (dd, J = 35.3, 3.8
Hz), 7.2, 3.4; 19F NMR (470 MHz, CDCl3) δ = −66.9 (d, 1F, J =
24.8 Hz), −76.2 (d, 1F, J = 24.8 Hz); HRMS-APPI calcd for
C18H22F2Si [M*]+ 304.1459, found 304.1453.
1-Chloro-2-(2,2-difluorovinyl)benzene (15). To
a
16
×
100 mm borosilicate test-tube equipped with a magnetic
stirbar and covered with a rubber septum were added substrate
2f (150 mg, 0.52 mmol, 1 equiv.), KF (36.2 mg, 0.62 mmol, 1.2
equiv.), 18-crown-6 (165 mg, 0.62 mmol, 1.2 equiv.), and THF
(3.5 mL). The reaction mixture was stirred at room temperature
for 72 h. Water (10 mL) was added, and the reaction mixture
was extracted using three portions of Et2O (5 mL). The com-
bined organic phases were dried over sodium sulfate, filtered
and concentrated. Crude 19F NMR in CDCl3 using fluoroben-
zene as an internal standard indicates complete conversion of
(2,2-Difluoro-1-(thiophen-2-yl)vinyl)triethylsilane
(2s).
According to the general procedure on a 0.33 mmol scale of 9
using 1-thienylboronic acid, the desired product (54.4 mg,
63%) was isolated as a yellow oil via flash chromatography
using 100% hexane as the eluent. IR (neat) ν = 2955, 2876,
1676, 1226, 1002, 866, 834, 722 cm−1 1H NMR (500 MHz,
.
CDCl3) δ = 7.21 (dd, 1H, J = 5.2, 1.2 Hz), 6.96 (dd, 1H, J = 5.2,
3.5 Hz), 6.75 (dd, 1H, J = 3.5, 1.1 Hz), 0.94 (t, 9H, J = 7.9 Hz),
0.69 (q, 6H, J = 7.9 Hz); 13C NMR (125 MHz, CDCl3) δ = 156.3
(dd, J = 310.8, 287.6 Hz), 135.3 (dd, J = 12.5, 1.3 Hz), 126.8,
126.1 (dd, J = 3.1, 1.3 Hz), 124.6, 79.0 (dd, J = 40.4, 6.0 Hz), 7.1,
3.2; 19F NMR (470 MHz, CDCl3) δ = −65.7 (d, 1F, J = 18.1 Hz),
−74.1 (d, 1F, J = 18.1 Hz); HRMS-APPI calcd for C12H18F2SSi
[M*]+ 260.0861, found 2 600 864.
1
2f, and 66% of 15, along with traces of 16. H NMR (400 MHz,
CDCl3) δ = 7.30 (d, 2H, J = 8.7 Hz), 7.24 (d, 2H, J = 8.8 Hz), 5.23
(dd, 1H, J = 25.9, 3.6 Hz); 19F NMR (376 MHz, CDCl3) δ = −81.6
(dd, 1F, J = 25.9, 29.8 Hz), −84.0 (dd, 1F, J = 29.8, 3.7 Hz).19
(1-(2,4-Difluorophenyl)-2,2-difluorovinyl)triethylsilane (2t).
According to the general procedure on a 0.33 mmol scale of 9
using 2,4-difluorophenylboronic acid, the desired product
Acknowledgements
(69.2 mg, 72%) was isolated as a transparent oil via flash This work was supported by the Canada Research Chair
chromatography using 100% hexane as the eluent. IR (neat) Program, the Natural Sciences and Engineering Research
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Council of Canada, the Canada Foundation for Innovation, the
Fonds de recherche sur la nature et les technologies (FQRNT),
FQRNT Centre in Green Chemistry and Catalysis (CGCC),
FQRNT Research Network on Protein Function, Structure and
Engineering (PROTEO), and the Université Laval. We thank
Laetitia Angers and Grégoire Lassalle-Claux for some initial
experiments.
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13 XPhos
=
2-dicyclohexylphosphino-2′,4′,6′-triiso-
propylbiphenyl.
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18 HRMS analysis proved impossible to obtain for a number
of compounds, even after intensive optimization of various
parameters (concentration, solvent, ionisation mode, etc.).
For those compounds, LRMS data were obtained using
GCMS (either with CI or EI).
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