Nickel-Catalyzed Hydroalkenylation of Alkynes through C-F Bond Activation: Synthesis of 2-Fluoro-1,3-dienes

Article abstract of DOI:10.1055/s-0036-1588842

2-Fluoro-1,3-dienes were synthesized through nickel-catalyzed coupling reactions between β,β-difluorostyrenes and alkynes in the presence of ZrF ₄ as co-catalyst and a hydride source derived from triethylborane and lithium isopropoxide. Mechanistic studies revealed that the carbon-fluorine bond was cleaved by β-fluorine elimination from intermediary nickelacyclopentenes generated through oxidative cyclization of the two substrates.

Full text of DOI:10.1055/s-0036-1588842

SYNTHESIS
0
0
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9
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8
8
1
1
4
3
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2
1
0
X
©
Georg Thieme Verlag Stuttgart · New York
2017, 49, A–G
special topic
A
en
Synthesis
Y. Watabe et al.
Special Topic
Nickel-Catalyzed Hydroalkenylation of Alkynes through C–F Bond
Activation: Synthesis of 2-Fluoro-1,3-dienes
Yota Watabe
Ar
F
F
Ar
NiII
Li
Ar
F
F
Kohei Kanazawa
Takeshi Fujita
Junji Ichikawa*
cat. Ni0
Et3B Oi-Pr
H
H
F
R
β-Fluorine
H
+
cat. ZrF4
Elimination
R
R
0
0
0
0
0-
0
0
1
6-
4
9
8
3-
2
6
X
R
R
R
Division of Chemistry, Faculty of Pure and Applied Sciences,
University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan
junji@chem.tsukuba.ac.jp
Published as part of the Special Topic Advanced Strategies in
Synthesis with Nickel
Received: 24.03.2017
Accepted after revision: 02.05.2017
Published online: 12.06.2017
ceeds from intermediary nickelacyclopentenes A to gener-
ate vinylnickels, providing 1,1-difluoro-1,4-dienes through
transmetalation with triethylsilane. As the next challenge,
we explored the synthesis of fluorinated 1,3-dienes
through nickel-catalyzed hydroalkenylation of alkynes with
DOI: 10.1055/s-0036-1588842; Art ID: ss-2017-c0187-st
Abstract 2-Fluoro-1,3-dienes were synthesized through nickel-cata-
lyzed coupling reactions between β,β-difluorostyrenes and alkynes in
the presence of ZrF as co-catalyst and a hydride source derived from
1,1-difluoro-1-alkenes. However, in the case of the nickel-
4
catalyzed reaction of 1,1-difluoroethylene with alkynes,
α,α-difluorinated nickelacycloheptadienes were generated
from one 1,1-difluoroethylene with two alkynes through
triethylborane and lithium isopropoxide. Mechanistic studies revealed
that the carbon–fluorine bond was cleaved by β-fluorine elimination
from intermediary nickelacyclopentenes generated through oxidative
cyclization of the two substrates.
11
oxidative cyclization and insertion (Scheme 2). Subse-
quent α-fluorine elimination afforded fluoroarenes. In con-
trast, we hypothesized that the reaction of β,β-difluorosty-
renes 1 might be controlled by coordination of the arene
Key words C–F bond activation, nickel, hydroalkenylation, β-fluorine
elimination, oxidative cyclization, 1,3-dienes, fluorine, alkynes
Conjugated dienes, often found in naturally occurring
(
a) Our previous work
1
compounds, are used as key substrates in various organic
H
2
F3C
R3
cat. Ni0
Et3SiH
F2C
transformations such as cycloaddition and polymeriza-
R2
+
3
tion. Thus, methods for their synthesis have been exten-
R1
R2
R1
R3
4
sively studied for decades. Among them, transition-metal-
F
5
catalyzed hydroalkenylation of alkynes is a straightfor-
NiII
R1
F3C
R3
R2
ward method for regio- and stereoselective synthesis of un-
symmetrical 1,3-dienes. Conventional methods for forma-
tion of 1,3-dienes through hydroalkenylation are classified
into three major categories according to the reaction mech-
anism: (a) through insertion of alkynes into alkenyl transi-
F2C
R2
NiII
β-Fluorine elimination
R1
R3
A
(b) This work
6
F
H
tion-metal species, (b) though insertion of alkynes into
F
R3
cat. Ni0
H– source
+
Ar
R2
7
transition-metal hydrides, or (c) through oxidative cycliza-
Ar
F
F
R2
R3
tion of alkynes and alkenes followed by β-hydrogen elimi-
1
2
3
8
nation from metalacycropentenes. Although the method
(
c) is considered to use highly atom-economical protocols,
the alkenes employed in oxidative cyclization are limited to
α,β-unsaturated carbonyl compounds in most cases.
F
F
F
NiII
Ar
R3
Ar
β-Fluorine elimination
R2
NiII
Recently, we reported nickel-catalyzed hydroallylation
of alkynes with 2-trifluoromethyl-1-alkenes through oxi-
dative cyclization and exocyclic β-fluorine elimination
R2
R3
B
Scheme 1 Nickel-catalyzed (a) hydroallylation or (b) hydroalkenylation
of alkynes through oxidative cyclization and β-fluorine elimination
9
10
(
Scheme 1a). In this reaction, β-fluorine elimination pro-
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

B
Synthesis
Y. Watabe et al.
Special Topic
moieties to the nickel center, generating β,β-difluorinated
nickelacyclopentenes B through oxidative cyclization of one
molecule each of 1 and alkyne 2 with Ni(0) (Scheme 1b).12
sult of screening extra additives, a catalytic amount of
ZrF414 was found to improve the yield to 59% (entry 6). Ad-
ditionally, the yield of 3aa was drastically increased to 89%
by lowering the reaction temperature to room temperature
(entry 7).
Subsequent endocyclic β-fluorine elimination from
would produce 2-fluoro-1,3-dienes 3.
B
With the optimal conditions established, the scope of
the reaction with respect to β,β-difluorostyrenes 1 and
alkynes 2 was investigated (Table 2). When simple β,β-di-
fluorostyrene (1b) was employed, the corresponding 2-flu-
oro-1,3-diene 3ba was obtained in 77% yield. β,β-Difluoro-
styrene 1c, bearing an electron-donating substituent (i-Pr),
successfully underwent hydroalkenylation to afford the cor-
responding 2-fluoro-1,3-diene 3ca in 62% yield. The reac-
tion of chlorine-bearing β,β-difluorostyrene 1d also provid-
ed 3da in 84% yield without C–Cl bond cleavage. The
hydroalkenylation of 2a with 1-(2,2-difluoro-ethenyl)naph-
thalene (1e) proceeded smoothly to afford 3ea in 86% yield.
Heterocycle-containing 1,3-dienes 3fa and 3ga were ob-
tained by reaction with 2-(2,2-difluoroethenyl)benzofuran
F
F
R
cat. Ni0
H
R
R
R
+
F
R
R
F
F
NiII
F
F
NiII
H
R
R
H
α-Fluorine elimination
R
R
R
R
R
R
Scheme 2 Nickel-catalyzed [2+2+2] cyclization through oxidative cy-
clization of 1,1-difluoroethylene with alkynes and α-fluorine elimina-
tion
(
1f) and -benzothiophene (1g), respectively. In addition to
We sought suitable conditions for the synthesis of 2-flu-
orohepta-1,3-diene 3aa by using β,β-difluorostyrene 1a
and 4-octyne (2a) as model substrates (Table 1). Initially, we
adopted the Ni(cod) /PCy catalyst system, which was effec-
symmetrical alkynes such as 2a and 2b, unsymmetrical
alkynes 2c and 2d participated in the hydroalkenylation to
afford the corresponding 2-fluoro-1,3-dienes 3ac and 3ad
with strict regioselectivities.12 Furthermore, hydrodienyla-
2
3
tive in defluorinative coupling between fluoroalkenes and
9,11,13
alkynes.
No product was obtained without a hydride
Table 2 Ni-Catalyzed Synthesis of 2-Fluoro-1,3-dienes 3a
source (entry 1). Whereas ZnEt , Et SiH, and Et B were not
2
3
3
effective hydride sources (entries 2–4), the combination of
Ni(cod)2 (10 mol%)
PCy3 (10 mol%)
ZrF4 (10 mol%)
Et B and i-PrOLi afforded 3aa in 46% yield as the sole prod-
3
F
H
F
R3
uct, without formation of fluoroarenes (entry 5). As the re-
R1
R1
+
R3
R2
3
Et B (1.5 equiv)
F
R2
i-PrOLi (1.5 equiv)
toluene, RT
3
Table 1 Optimization of Reaction Conditions for Ni-Catalyzed Hy-
droalkenylation
1
2
a
(2.0 equiv)
R
Ni(cod)2 (10 mol%)
PCy3 (10 mol%)
hydride source
F
H
3aa (R = Ph), 89% (24 h)
3ba (R = H), 77% (11 h)
3ca (R = i-Pr), 62% (18 h)
3da (R = Cl), 84% (20 h)
F
H
F
Pr
Pr
Ar
+
Ar
Pr
Pr
F
Pr
toluene, conditions
Pr
aa
3
1a
2a
F
H
F
H
H
H
Ar = C6H4(p-Ph) (2.0 equiv)
Pr
O
Pr
Et
Pr
Entry Hydride source (equiv)
Temp. (°C) Time (h) Yield (%)b
Pr
3
3
ea 86% (20 h)
3
fa 77% (10 h)
1
2
3
4
5
6
–
40
40
40
40
40
40
r.t.
12
12
16
10
12
N.D.c
N.D.
N.D.
N.D.
46
Ph
F
Et
Et
Et
Et
Et
Et
2
3
3
3
3
3
Zn (1.0)
SiH (1.0)
B (1.5)
F
H
S
Pr
Et
Pr
3
ab 80% (17 h)
ga 85% (12 h)
d
B + i-PrOLi (1.5)
Ph
Ph
F
H
F
B + i-PrOLi (1.5) + ZrF
B + i-PrOLi (1.5) + ZrF
4
4
(0.1)
(0.1)
3.5
24
59
7
89 (89)
i-Pr
Ph
Me
Me
a
Reaction conditions: Ni(cod)
2
(0.025 mmol), PCy
3
(0.025 mmol), 1a (0.25
b
b
3
ac 64% (12 h)
3ad 33% (15 h)
mmol), 2a (0.50 mmol), toluene (2.0 mL).
b
19
a
Yield was determined by F NMR spectroscopy using PhCF as internal
3
Reaction conditions: Ni(cod) (0.025 mmol), PCy (0.025 mmol), ZrF
(0.025 mmol), 1 (0.25 mmol), 2 (0.50 mmol), Et B (0.38 mmol), i-PrOLi
(0.38 mmol), toluene (2.0 mL).
Single regioisomer.
2
3
4
standard. Yield of isolated product given in parentheses.
3
c
N.D. = Not detected.
i-PrOLi was generated in situ from i-PrOH and n-BuLi.
d
b
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

C
Synthesis
Y. Watabe et al.
Special Topic
tion of 2a with 1,1-difluorobuta-1,3-diene 1h also proceed-
ed to give 3-fluorinated 1,3,5-triene 3ha in 62% yield
alkyne 2a ([2a] ), and Ni catalyst ([Ni] ) (Figure 1). On the
basis of these experiments, linear correlations of
0
0
(Scheme 3).
(Δ[3ea]/Δt)t=0 with [1e] and [2a] were obtained (Figure 1a
0
0
and 1c). In addition, linear fitting of the corresponding log–
log plots with slopes of 1.01 and 1.08 exhibited first-order
dependence of (Δ[3ea]/Δt)t=0 on [1e] and [2a] , respectively
(Figure 1b and 1d). Thus, both 1e and 2a were shown to be
involved in the rate-limiting initial step. Furthermore,
when a similar analysis was performed on the dependency
Ph
F
Ni(cod)2 (10 mol%)
PCy3 (10 mol%)
ZrF4 (10 mol%)
Ph
0
0
F
F
H
1
+
h
Pr
Pr
Et3B (1.5 equiv)
i-PrOLi (1.5 equiv)
toluene, 40 °C, 12 h
Pr
Pr
2.0 equiv)
3ha 62%
of (Δ[3ea]/Δt)t=0 on [Ni] , first-order dependence (slope of
2
a
0
(
0.910) was confirmed (Figure 1e and 1f). These results indi-
0
cate that oxidative cyclization of 1e and 2a with Ni is in-
Scheme 3 Hydrodienylation of alkyne 2a with difluorodiene 1h
volved in the rate-limiting initial step as path (I).
For hydroalkenylation of alkynes 2 with difluorosty-
renes 1, there are two possible reaction pathways initiated
by different elementary steps that involve 1 (Scheme 4).
Path (I) starts with oxidative cyclization of 1 and 2 with the
Ni catalyst, inducing regioselective formation of β,β-difluo-
rinated nickelacyclopentenes B with the help of coordina-
tion of the aryl groups to the Ni center (Scheme 4). Subse-
quent β-fluorine elimination from B generates vinylnickels
C. Thus, 2-fluoro-1,3-dienes 3 are obtained through trans-
metalation of C with borate generated from Et B and i-PrO-
3
Li. In path (II), vinylnickel intermediates B′ are initially
formed by oxidative addition of a vinylic C–F bond of 1 to
0
Ni (Scheme 4). Subsequent insertion of 2 to B′ affords the
common intermediates C.
F
Ar
F
1
path (I)
path (II)
R
Figure 1 (a) Initial reaction rate versus [1e] and (b) the corresponding
0
Oxidative
cyclization
Oxidative
addition
Ni0
F
Ni0
log–log plot. Reaction conditions: Ni(cod) (0.025 mmol), PCy (0.025
2
3
R
2
mmol), ZrF (0.025 mmol), 1e (0.25–0.60 mmol), 2a (0.50 mmol), Et B
4
3
F
F
(0.38 mmol), i-PrOLi (0.38 mmol), toluene (2.0 mL), RT, 10 min. (c) Ini-
Ar
R
Ar
tial reaction rate versus [2a] and (d) the corresponding log–log plot.
0
NiII
NiII
Reaction conditions: Ni(cod) (0.025 mmol), PCy (0.025 mmol), ZrF
2
3
4
F
R
(0.025 mmol), 1e (0.25 mmol), 2a (0.12–0.50 mmol), Et B (0.38
3
mmol), i-PrOLi (0.38 mmol), toluene (2.0 mL), RT, 10 min. (e) Initial re-
B
B'
R
action rate versus [Ni] and (f) the corresponding log–log plot. Reaction
0
β-Fluorine
elimination
Alkyne
insertion
conditions: Ni(cod) (0.0050–0.05 mmol), PCy (0.0050–0.050 mmol),
2
3
R
1
e (0.50 mmol), 2a (1.0 mmol), Et B (0.75 mmol), i-PrOLi (0.75 mmol),
2
3
toluene (2.0 mL), RT, 10 min.
F
F
NiII
H–
F
H
Ar
Ar
To clarify which hydrogen of the borate formed from tri-
ethylborane and lithium isopropoxide was installed as a hy-
dride source in the 2-fluoro-1,3-dienes 3, a deuterium-la-
R
R
R
R
C
3
beling experiment was conducted using i-PrOLi-d (Scheme
7
Scheme 4 Possible reaction pathways (I) and (II)
5). Nickel-catalyzed hydroalkenylation of 2a with 1a in the
presence of the borate generated from Et B and i-PrOLi-d
3
7
To determine the initial steps of the reaction pathway,
we examined the dependency in the initial formation rate
of 2-fluoro-1,3-diene 3ea [(Δ[3ea]/Δt)t=0] based on chang-
ing the initial concentrations of difluorostyrene 1e ([1e]0),
gave a 64:36 mixture of deuterated 2-fluoro-1,3-diene 3aa-
d and non-deuterated diene 3aa. This result indicates that
both an ethyl group on boron and an isopropyl group on ox-
ygen serve as the hydride source.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

D
Synthesis
Y. Watabe et al.
Special Topic
1H, 13C, and 19F NMR spectra were recorded with a Bruker Avance 500
or a JEOL ECS-400 spectrometer. Chemical shift values are given in
F
Ar
Ni(cod)2 (10 mol%)
PCy3 (10 mol%)
ZrF4 (10 mol%)
F
1
ppm relative to internal Me Si (for H NMR: δ = 0.00 ppm), CDCl (for
4
3
1
a
F
D (H)
Pr
13
19
C NMR: δ = 77.0 ppm), and C F (for F NMR: δ = 0.00 ppm). IR spec-
6
6
+
Ar
tra were recorded with a Horiba FT-300S spectrometer by the attenu-
ated total reflectance (ATR) method. Mass spectra were measured
with a JEOL JMS-T100GCV or a JMS-T100CS spectrometer. Elemental
analyses were carried out at the Elemental Analysis Laboratory, Divi-
sion of Chemistry, Faculty of Pure and Applied Sciences, University of
Tsukuba. Melting points were measured with a Yanaco micro melting
point apparatus, and are uncorrected. Column chromatography was
performed on silica gel (Silica Gel 60N, Kanto Chemical Co., Inc., 63–
Pr
Et3B (1.5 equiv)
CD3)2CDOLi (1.5 equiv)
toluene, RT, 12 h
(
Pr
Pr
2a
3aa–d 93%
(D/H = 64/36)
(
2.0 equiv)
Scheme 5 Deuterium-labeling experiments
On the basis of the aforementioned experiments, we
propose the following reaction mechanism (Scheme 6).
This reaction is initiated by regioselective oxidative cycliza-
210 μm). All the reactions were conducted under argon or nitrogen.
Diethyl ether (Et O), tetrahydrofuran (THF), and toluene were puri-
2
fied with a solvent-purification system (GlassContour) equipped with
columns of activated alumina and supported-copper catalyst (Q-5)
0
tion of difluoroalkene 1 and alkyne 2 with Ni to generate
the intermediary β,β-difluorinated nickelacyclopentenes B.
β-Fluorine elimination proceeds from B to generate vinyl-
nickel fluorides C. Replacement of the fluorine on the nickel
in C with an isopropoxy group or an ethyl group is accom-
plished through transmetalation with the borate, derived
before use. Benzene was dried over CaCl for one day, then distilled
2
from CaCl , and stored over activated 4 Å molecular sieves. i-PrOH
2
was distilled from CaH prior to use. Difluorostyrenes 1a, 1b and 1d–
2
16
17
h
and 1-phenyl-1-propyne (2d) were prepared according to re-
ported procedures. Unless otherwise noted, materials were obtained
from commercial sources and used directly without further purifica-
tion.
from Et B and i-PrOLi. Subsequent β-hydrogen elimination
3
induces the formation of vinylnickel hydrides D along with
acetone or ethylene. Finally, reductive elimination from D
affords 1,3-dienes 3 to regenerate nickel(0).
1-(2,2-Difluoroethenyl)-4-isopropylbenzene (1c)
To an N-methylpyrrolidone (20 mL) solution of (triphenylphospho-
nio)difluoroacetate (7.06 g, 19.8 mmol) was added 4-isopropylbenz-
aldehyde (1.48 g, 10.0 mmol). After stirring at 80 °C for 11 h, the reac-
tion was quenched with brine. Organic materials were extracted with
ether three times. The combined extracts were washed with brine
and dried over anhydrous Na SO . After the solvent was removed un-
F
R
Ar
+
F
R
1
2
2
4
F
der reduced pressure, the residue was purified by silica gel column
chromatography (hexane) to give difluorostyrene 1c.
F
F
H
Oxidative
cyclization
Ni0
Ar
R
Ar
R
NiII
Yield: 1.29 g (71%); colorless oil.
R
3
R
IR (neat): 2962, 1730, 1516, 1466, 1421, 1348, 1248, 1165, 1055, 937,
B
–1
8
41, 544 cm .
Reductive
elimination
β-Fluorine
elimination
1
H NMR (CDCl , 500 MHz): δ = 1.24 (d, J = 6.9 Hz, 6 H), 2.88 (sept, J =
3
6.9 Hz, 1 H), 5.22 (dd, JH–F = 26.5, 3.8 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 2 H),
7
.25 (d, J = 8.2 Hz, 2 H).
H
13
F
C NMR (CDCl , 126 MHz): δ = 23.9, 33.8, 81.9 (dd, J = 29, 14 Hz),
F
NiII
3
C–F
F
NiII
126.7, 127.6 (dd, JC–F = 6, 4 Hz), 127.8 (dd, JC–F = 6, 6 Hz), 147.8, 156.2
Ar
R
Ar
Ligand
exchange
(dd, JC–F = 298, 288 Hz).
R
R
19
R
F NMR (CDCl , 471 MHz): δ = 77.6 (dd, J = 34 Hz, JF–H = 4 Hz, 1 F),
3 F–F
D
C
79.7 (dd, JF–F = 34 Hz, JF–H = 26 Hz, 1 F).
+
HRMS (EI): m/z [M] calcd for C11H12F2: 182.0907; found: 182.0904.
O
BFEt3
Li
i-PrO
BEt2F
i-PrO
Li
BEt3
+
or
+
Anal. Calcd for C11H12F2: C, 72.51; H, 6.64. Found: C, 72.37; H, 6.88.
Li
Scheme 6 Proposed catalytic cycle
4-[(1Z,3E)-2-Fluoro-3-propylhepta-1,3-dien-1-yl]-1,1′-biphenyl
(3aa); Typical Procedure
In summary, we have developed a method for the syn-
thesis of 2-fluoro-1,3-dienes through nickel-catalyzed hy-
droalkenylation of alkynes 2 with β,β-difluorostyrenes 1
and a borate. The vinylic C–F bonds of 1 are readily cleaved
through β-fluorine elimination under mild conditions. The
monofluorinated 1,3-dienes obtained above are expected
to serve as components of bioactive compounds in pharma-
ceuticals and monomers for functional polymers.
Typical procedure for the synthesis of fluoro-1,3-dienes 3 in a nickel-
catalyzed reaction. In an argon-purged 50 mL test tube equipped with
a PTFE cap (EYELA, PPS25-TC) were placed i-PrOH (29 μL, 0.38 mmol)
and toluene (1.0 mL). To the mixture was slowly added n-BuLi (1.57 M
in hexane, 0.24 mL, 0.38 mmol) at 0 °C. After stirring at 0 °C for 10
min, Et B (1.0 M in hexane, 0.38 mL, 0.38 mmol) was added to the re-
15
3
action mixture at the same temperature. The reaction mixture was
warmed to r.t., and was stirred for another 30 min. To the reaction
mixture were added β,β-difluorostyrene (1a; 54 mg, 0.25 mmol), 4-
octyne (2a; 55 mg, 0.50 mmol), Ni(cod) (6.9 mg, 0.025 mmol), PCy3
2
(7.0 mg, 0.025 mmol), ZrF4 (4.1 mg, 0.025 mmol), and toluene (1.0
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

E
Synthesis
Y. Watabe et al.
Special Topic
1
mL). After stirring at r.t. for 24 h, the reaction mixture was filtered
through a pad of silica gel (EtOAc). The filtrate was concentrated un-
der reduced pressure and the residue was purified by silica gel col-
umn chromatography (hexane/EtOAc, 20:1) to give 2-fluoro-1,3-di-
ene 3aa.
H NMR (CDCl , 500 MHz): δ = 0.95 (t, J = 7.4 Hz, 3 H), 0.96 (t, J =
3
7.4 Hz, 3 H), 1.24 (d, J = 6.9 Hz, 6 H), 1.43–1.55 (m, 4 H), 2.16 (td, J =
7.4, 7.4 Hz, 2 H), 2.25 (t, J = 7.4 Hz, 2 H), 2.88 (sept, J = 6.9 Hz, 1 H),
5.71 (d, JH–F = 40.7 Hz, 1 H), 6.04 (t, J = 7.4 Hz, 1 H), 7.18 (d, J = 8.2 Hz,
2 H), 7.47 (d, J = 8.2 Hz, 2 H).
1
3
Yield: 69 mg (89%); white solid; mp 90.6–92.2 °C.
C NMR (CDCl , 126 MHz): δ = 14.0, 14.1, 22.4, 22.8, 23.9, 29.0 (d,
3
IR (neat): 2958, 2929, 2871, 1639, 1487, 856, 839, 760, 723, 694 cm–1
J
8
C–F = 3 Hz), 30.3, 33.9, 104.7 (d, JC–F = 12 Hz), 126.5, 128.8 (d, JC–F
Hz), 129.5 (d, JC–F = 9 Hz), 131.8 (d, JC–F = 19 Hz), 131.9, 147.5 (d,
JC–F = 2 Hz), 158.1 (d, JC–F = 259 Hz).
=
.
1
H NMR (CDCl , 500 MHz): δ = 0.97 (t, J = 7.4 Hz, 3 H), 0.99 (t, J =
3
7.4 Hz, 3 H), 1.45–1.57 (m, 4 H), 2.18 (td, J = 7.4, 7.4 Hz, 2 H), 2.28 (t,
1
9
F NMR (CDCl , 471 MHz): δ = 47.1 (d, J = 41 Hz).
J = 7.4 Hz, 2 H), 5.78 (d, JH–F = 40.4 Hz, 1 H), 6.09 (t, J = 7.4 Hz, 1 H),
3
F–H
+
7.33 (tt, J = 7.4, 1.4 Hz, 1 H), 7.43 (dd, J = 7.4, 7.4 Hz, 2 H), 7.57 (d, J =
HRMS (EI): m/z [M] calcd for C19H27F: 274.2097; found: 274.2096.
8.6 Hz, 2 H), 7.60–7.63 (m, 4 H).
13
C NMR (CDCl , 126 MHz): δ = 14.0, 14.2, 22.4, 22.7, 29.0 (d, J
=
1-Chloro-4-[(1Z,3E)-2-fluoro-3-propylhepta-1,3-dien-1-yl]-ben-
3
C–F
3
Hz), 30.3, 104.4 (d, JC–F = 11 Hz), 126.9, 127.1, 127.2, 128.8, 129.2 (d,
zene (3da)
JC–F = 8 Hz), 130.2 (d, JC–F = 9 Hz), 131.8 (d, JC–F = 19 Hz), 133.5 (d, JC–F
=
Compound 3da was synthesized according to the procedure de-
scribed for 3aa using i-PrOH (29 μL, 0.38 mmol), n-BuLi (0.24 mL, 0.38
2
Hz), 139.3 (d, JC–F = 2 Hz), 140.7, 158.8 (d, JC–F = 260 Hz).
1
9
mmol), Et B (0.38 mL, 0.38 mmol), 1d (44 mg, 0.25 mmol), 2a (55 mg,
F NMR (CDCl , 471 MHz): δ = 48.6 (d, J = 40 Hz).
3
3
F–H
0.50 mmol), Ni(cod)2 (6.9 mg, 0.025 mmol), PCy3 (7.0 mg, 0.025
+
HRMS (EI): m/z [M] calcd for C22H25F: 308.1940; found: 308.1943.
mmol), ZrF (4.1 mg, 0.025 mmol), and toluene (2.0 mL). The reaction
4
was conducted at r.t. for 20 h. Purification by silica gel column chro-
matography (hexane/EtOAc, 20:1) gave 3da.
[
(1Z,3E)-2-Fluoro-3-propylhepta-1,3-dien-1-yl]benzene (3ba)
Compound 3ba was synthesized according to the procedure de-
scribed for 3aa using i-PrOH (29 μL, 0.38 mmol), n-BuLi (0.24 mL, 0.38
Yield: 56 mg (84%); colorless oil.
IR (neat): 2958, 2871, 1641, 1491, 1456, 1092, 1012, 849, 748, 548,
mmol), Et B (0.38 mL, 0.38 mmol), 1b (35 mg, 0.25 mmol), 2a (56 mg,
3
–
1
5
11 cm .
0.51 mmol), Ni(cod)2 (7.0 mg, 0.025 mmol), PCy3 (7.0 mg, 0.025
1
mmol), ZrF (4.1 mg, 0.025 mmol), and toluene (2.0 mL). The reaction
H NMR (CDCl , 500 MHz): δ = 0.96 (t, J = 7.5 Hz, 3 H), 0.97 (t, J =
4
3
was conducted at r.t. for 11 h. Purification by silica gel column chro-
matography (hexane) gave 3ba.
7.5 Hz, 3 H), 1.43–1.54 (m, 4 H), 2.17 (td, J = 7.5, 7.5 Hz, 2 H), 2.25 (t,
J = 7.5 Hz, 2 H), 5.69 (d, JH–F = 39.9 Hz, 1 H), 6.08 (t, J = 7.5 Hz, 1 H),
7
.28 (d, J = 8.6 Hz, 2 H), 7.46 (d, J = 8.6 Hz, 2 H).
13C NMR (CDCl
, 126 MHz): δ = 13.9, 14.1, 22.4, 22.7, 28.9 (d, JC–F
Hz), 30.3, 103.7 (d, JC–F = 12 Hz), 128.6, 130.0 (d, JC–F = 8 Hz), 130.7
d, JC–F = 9 Hz), 131.6 (d, JC–F = 18 Hz), 132.2 (d, JC–F = 3 Hz), 132.9 (d, JC–
2 Hz), 158.9 (d, JC–F = 261 Hz).
Yield: 45 mg (77%); colorless oil.
IR (neat): 2958, 2871, 1639, 1456, 1377, 831, 748, 690 cm–1
=
.
3
3
(
1
H NMR (CDCl , 500 MHz): δ = 0.94 (t, J = 7.4 Hz, 3 H), 0.96 (t, J =
3
7
2
4
.4 Hz, 3 H), 1.46 (qt, J = 7.4, 7.4 Hz, 2 H), 1.51 (qt, J = 7.4, 7.4 Hz, 2 H),
.15 (td, J = 7.4, 7.4 Hz, 2 H), 2.25 (t, J = 7.4 Hz, 2 H), 5.73 (d, JH–F
0.4 Hz, 1 H), 6.07 (t, J = 7.4 Hz, 1 H), 7.17 (t, J = 7.5 Hz, 1 H), 7.30 (dd,
=
F
=
19
F NMR (CDCl , 471 MHz): δ = 48.7 (d, J = 40 Hz).
3
F–H
+
J = 7.5, 7.5 Hz, 2 H), 7.53 (d, J = 7.5 Hz, 2 H).
HRMS (EI): m/z [M] calcd for C16H20ClF: 266.1238; found: 266.1238.
13
C NMR (CDCl , 126 MHz): δ = 13.9, 14.1, 22.4, 22.7, 29.0 (d, J
=
3
C–F
3
(
Hz), 30.3, 104.8 (d, JC–F = 12 Hz), 126.7 (d, JC–F = 2 Hz), 128.4, 128.8
d, JC–F = 8 Hz), 130.0 (d, JC–F = 9 Hz), 131.7 (d, JC–F = 19 Hz), 134.3 (d,
JC–F = 2 Hz), 158.5 (d, JC–F = 260 Hz).
1-[(1Z,3E)-2-Fluoro-3-propylhepta-1,3-dien-1-yl]naphthalene
(3ea)
Compound 3ea was synthesized according to the procedure described
for 3aa using i-PrOH (29 μL, 0.38 mmol), n-BuLi (0.24 mL, 0.38 mmol),
19
F NMR (CDCl , 471 MHz): δ = 48.3 (d, J = 40 Hz).
3
F–H
Et B (0.38 mL, 0.38 mmol), 1e (47 mg, 0.25 mmol), 2a (55 mg, 0.50
+
3
HRMS (EI): m/z [M] calcd for C16H21F: 232.1627; found: 232.1628.
mmol), Ni(cod)2 (6.8 mg, 0.025 mmol), PCy3 (6.9 mg, 0.025 mmol),
ZrF4 (4.1 mg, 0.025 mmol), and toluene (2.0 mL). The reaction was
conducted at r.t. for 20 h. Purification by silica gel column chromatog-
raphy (hexane/EtOAc, 50:1) gave 3ea.
Anal. Calcd for C16H21F: C, 82.71; H, 9.11. Found: C, 82.33; H, 9.14.
1
-[(1Z,3E)-2-Fluoro-3-propylhepta-1,3-dien-1-yl]-4-isopropylben-
zene (3ca)
Yield: 60 mg (86%); colorless oil.
Compound 3ca was synthesized according to the procedure described
for 3aa using i-PrOH (29 μL, 0.38 mmol), n-BuLi (0.24 mL, 0.38 mmol),
IR (neat): 2958, 2871, 1637, 1508, 1458, 1394, 1381, 1103, 899, 795,
–1
773, 731 cm
.
Et B (0.38 mL, 0.38 mmol), 1c (46 mg, 0.25 mmol), 2a (55 mg, 0.50
3
1
H NMR (CDCl , 500 MHz): δ = 0.98 (t, J = 7.4 Hz, 3 H), 1.04 (t, J =
mmol), Ni(cod)2 (6.9 mg, 0.025 mmol), PCy3 (7.0 mg, 0.025 mmol),
ZrF4 (4.2 mg, 0.025 mmol), and toluene (2.0 mL). The reaction was
conducted at r.t. for 18 h. Purification by silica gel column chromatog-
raphy (hexane) gave 3ca.
3
7
.4 Hz, 3 H), 1.49 (qt, J = 7.4, 7.4 Hz, 2 H), 1.64 (qt, J = 7.4, 7.4 Hz, 2 H),
.20 (td, J = 7.4, 7.4 Hz, 2 H), 2.39 (t, J = 7.4 Hz, 2 H), 6.13 (t, J = 7.4 Hz,
H), 6.40 (d, JH–F = 37.8 Hz, 1 H), 7.45–7.52 (m, 3 H), 7.74 (d, J =
.9 Hz, 1 H), 7.81 (d, J = 7.9 Hz, 1 H), 7.83 (d, J = 7.9 Hz, 1 H), 8.00 (d,
2
1
7
Yield: 42 mg (62%); colorless oil.
J = 7.9 Hz, 1 H).
IR (neat): 2958, 2871, 1643, 1510, 1458, 1419, 1379, 1055, 1018, 964,
13
C NMR (CDCl , 126 MHz): δ = 14.0, 14.2, 22.6, 22.7, 29.2 (d, J
Hz), 30.3, 101.3 (d, JC–F = 14 Hz), 124.0, 125.52, 125.53, 125.9, 127.31
=
3
C–F
–1
895, 854, 561 cm .
3
(d, JC–F = 6 Hz), 127.34, 128.6, 130.3 (d, JC–F = 6 Hz), 130.4 (d, JC–F
=
9
Hz), 131.5, 131.7 (d, JC–F = 19 Hz), 133.7, 158.9 (d, JC–F = 259 Hz).
F NMR (CDCl , 471 MHz): δ = 46.7 (d, J = 38 Hz).
19
3
F–H
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

F
Synthesis
Y. Watabe et al.
Special Topic
+
HRMS (EI): m/z [M] calcd for C20H23F: 282.1784; found: 282.1784.
Yield: 56 mg (80%); colorless solid; mp 64.3–65.9 °C.
IR (neat): 2972, 2937, 1722, 1689, 1489, 1458, 1279, 1115, 1076,
1009, 764, 698, 667 cm .
–1
2
-[(1Z,3E)-2-Fluoro-3-propylhepta-1,3-dien-1-yl]benzofuran (3fa)
Compound 3fa was synthesized according to the procedure described
for 3aa using i-PrOH (29 μL, 0.38 mmol), n-BuLi (0.24 mL, 0.38 mmol),
1
H NMR (CDCl , 500 MHz): δ = 1.07 (t, J = 7.5 Hz, 3 H), 1.11 (t, J =
3
7
.5 Hz, 3 H), 2.21 (qd, J = 7.5, 7.5 Hz, 2 H), 2.31 (q, J = 7.5 Hz, 2 H), 5.79
(d, JH–F = 40.4 Hz, 1 H), 6.04 (t, J = 7.5 Hz, 1 H), 7.33 (t, J = 7.6 Hz, 1 H),
7.43 (dd, J = 7.6, 7.6 Hz, 2 H), 7.54–7.63 (m, 6 H).
Et B (0.38 mL, 0.38 mmol), 1f (45 mg, 0.25 mmol), 2a (54 mg, 0.49
3
mmol), Ni(cod)2 (6.9 mg, 0.025 mmol), PCy3 (6.9 mg, 0.025 mmol),
ZrF4 (4.1 mg, 0.025 mmol), and toluene (2.0 mL). The reaction was
conducted at r.t. for 10 h. Purification by silica gel column chromatog-
raphy (hexane/EtOAc, 20:1) gave 3fa.
13
C NMR (CDCl , 126 MHz): δ = 13.9, 14.1, 20.1 (d, J = 4 Hz), 21.3,
3
C–F
1
1
04.4 (d, JC–F = 12 Hz), 126.9, 127.1, 127.2, 128.8, 129.2 (d, JC–F = 8 Hz),
31.1 (d, JC–F = 9 Hz), 132.9 (d, JC–F = 19 Hz), 133.5 (d, JC–F = 2 Hz), 139.3
Yield: 53 mg (77%); colorless oil.
(d, JC–F = 2 Hz), 140.7, 158.4 (d, JC–F = 260 Hz).
IR (neat): 2960, 2931, 2873, 1641, 1558, 1450, 1259, 1169, 1099,
19
F NMR (CDCl , 471 MHz): δ = 48.0 (d, J = 40 Hz).
3
F–H
–1
1011, 978, 812, 739 cm .
+
HRMS (EI): m/z [M] calcd for C20H21F: 280.1627; found: 280.1628.
1
H NMR (CDCl , 500 MHz): δ = 0.93 (t, J = 7.5 Hz, 3 H), 0.95 (t, J =
3
7
.5 Hz, 3 H), 1.42–1.53 (m, 4 H), 2.16 (td, J = 7.5, 7.5 Hz, 2 H), 2.23 (t,
4
-[(1Z,3E)-2-Fluoro-3,5-dimethylhexa-1,3-dien-1-yl]-1,1′-biphe-
J = 7.5 Hz, 2 H), 5.91 (d, JH–F = 38.7 Hz, 1 H), 6.13 (t, J = 7.5 Hz, 1 H),
nyl (3ac)
6.91 (s, 1 H), 7.15–7.22 (m, 2 H), 7.39 (d, J = 7.6 Hz, 1 H), 7.51 (d, J =
Compound 3ac was synthesized according to the procedure described
for 3aa using i-PrOH (29 μL, 0.38 mmol), n-BuLi (0.24 mL, 0.38 mmol),
Et B (0.38 mL, 0.38 mmol), 1a (55 mg, 0.25 mmol), 4-methyl-2-pen-
7.6 Hz, 1 H).
13
C NMR (CDCl , 126 MHz): δ = 13.9, 14.1, 22.4, 22.6, 28.8 (d, J
=
3
C–F
3
4 Hz), 30.4, 95.4 (d, JC–F = 14 Hz), 105.7 (d, JC–F = 13 Hz), 110.7, 120.7,
122.8, 124.0, 129.4, 130.9 (d, JC–F = 17 Hz), 131.8 (d, JC–F = 8 Hz), 151.6,
153.9, 159.8 (d, JC–F = 263 Hz).
tyne (2c, 41 mg, 0.50 mmol), Ni(cod) (6.9 mg, 0.025 mmol), PCy (6.9
2
3
mg, 0.025 mmol), ZrF4 (4.1 mg, 0.025 mmol), and toluene (2.0 mL).
The reaction was conducted at r.t. for 12 h. Purification by silica gel
column chromatography (hexane/EtOAc, 20:1) gave 3ac.
19
F NMR (CDCl , 471 MHz): δ = 55.4 (d, J = 39 Hz).
3
F–H
+
HRMS (EI): m/z [M] calcd for C18H21FO: 272.1576; found: 272.1576.
-[(1Z,3E)-2-Fluoro-3-propylhepta-1,3-dien-1-yl]benzo[b]thio-
Yield: 45 mg (64%); colorless solid; mp 112.9–114.3 °C.
IR (neat): 2960, 2866, 1641, 1489, 1410, 1362, 1323, 1138, 1059, 995,
–1
2
860, 760, 719, 688 cm .
phene (3ga)
1
H NMR (CDCl , 500 MHz): δ = 1.04 (d, J = 6.6 Hz, 6 H), 1.88 (s, 3 H),
3
Compound 3ga was synthesized according to the procedure de-
scribed for 3aa using i-PrOH (29 μL, 0.38 mmol), n-BuLi (0.24 mL, 0.38
2
.69 (d sept, J = 9.5, 6.6 Hz, 1 H), 5.75 (d, JH–F = 40.1 Hz, 1 H), 5.94 (d,
J = 9.5 Hz, 1 H), 7.33 (t, J = 7.4 Hz, 1 H), 7.43 (dd, J = 7.8, 7.8 Hz, 2 H),
7.56–7.58 (m, 2 H), 7.60–7.62 (m, 4 H).
mmol), Et B (0.38 mL, 0.38 mmol), 1g (48 mg, 0.25 mmol), 2a (55 mg,
3
0.50 mmol), Ni(cod)2 (7.0 mg, 0.025 mmol), PCy3 (7.0 mg, 0.025
13
C NMR (CDCl , 126 MHz): δ = 12.6 (d, J = 4 Hz), 22.8, 27.6, 104.7
3
C–F
mmol), ZrF (4.1 mg, 0.025 mmol), and toluene (2.0 mL). The reaction
4
(d, JC–F = 11 Hz), 124.7 (d, JC–F = 20 Hz), 126.9, 127.1, 127.2, 128.8,
was conducted at r.t. for 12 h. Purification by silica gel column chro-
matography (hexane/EtOAc, 20:1) gave 3ga.
1
29.2 (d, JC–F = 8 Hz), 133.4 (d, JC–F = 2 Hz), 136.9 (d, JC–F = 8 Hz), 139.3
(d, JC–F = 2 Hz), 140.7, 159.2 (d, JC–F = 260 Hz).
Yield: 60 mg (85%); colorless solid; mp 50.6–51.2 °C.
19
F NMR (CDCl , 471 MHz): δ = 47.1 (d, J = 40 Hz).
3
F–H
IR (neat): 3049, 2956, 2870, 1633, 1456, 1311, 1230, 845, 742,
+
HRMS (EI): m/z [M] calcd for C20H21F: 280.1627; found: 280.1628.
-[(1Z,3E)-2-Fluoro-3-methyl-4-phenylbuta-1,3-dien-1-yl]-1,1′-
–
1
5
77 cm .
1
H NMR (CDCl , 500 MHz): δ = 0.96 (t, J = 7.5 Hz, 3 H), 0.98 (t, J =
3
4
7.5 Hz, 3 H), 1.44–1.56 (m, 4 H), 2.18 (td, J = 7.5, 7.5 Hz, 2 H), 2.26 (t,
biphenyl (3ad)
J = 7.5 Hz, 2 H), 6.12 (d, JH–F = 38.9 Hz, 1 H), 6.14 (t, J = 7.5 Hz, 1 H),
Compound 3ad was synthesized according to the procedure de-
scribed for 3aa using i-PrOH (29 μL, 0.38 mmol), n-BuLi (0.24 mL, 0.38
mmol), Et B (0.38 mL, 0.38 mmol), 1a (55 mg, 0.25 mmol), 1-phenyl-
7.23–7.32 (m, 3 H), 7.69 (d, J = 7.6 Hz, 1 H), 7.78 (d, J = 7.6 Hz, 1 H).
13
C NMR (CDCl , 126 MHz): δ = 13.9, 14.1, 22.4, 22.7, 28.8 (d, J
=
3
C–F
3
3
Hz), 30.4, 99.9 (d, JC–F = 15 Hz), 121.9, 122.9 (d, JC–F = 4 Hz), 123.0 (d,
1-propyne (2d, 58 mg, 0.50 mmol), Ni(cod)2
(6.9 mg, 0.025 mmol),
JC–F = 1 Hz), 124.1, 124.2, 130.8 (d, JC–F = 17 Hz), 131.3 (d, JC–F = 8 Hz),
PCy3 (6.9 mg, 0.025 mmol), ZrF4 (4.2 mg, 0.025 mmol), and toluene
(2.0 mL). The reaction was conducted at r.t. for 15 h. Purification by
silica gel column chromatography (hexane/EtOAc, 20:1) gave 3ad.
37.2 (d, JC–F = 4 Hz), 139.4, 140.3 (d, JC–F = 9 Hz), 158.6 (d, JC–F
1 =
261 Hz).
19
F NMR (CDCl , 471 MHz): δ = 51.3 (d, J = 39 Hz).
3
F–H
Yield: 26 mg (33%); colorless solid; mp 149.9–150.2 °C.
Anal. Calcd for C18H21FS: C, 74.96; H, 7.34. Found: C, 74.64; H, 7.25.
IR (neat): 3028, 2970, 1489, 1441, 1219, 1068, 856, 771, 698 cm–1
.
1
H NMR (CDCl , 500 MHz): δ = 2.12 (s, 3 H), 5.98 (d, J
= 39.8 Hz,
3
H–F
4
-[(1Z,3E)-3-Ethyl-2-fluorohexa-1,3-dien-1-yl]-1,1′-biphenyl (3ab)
1
7
H), 7.13 (s, 1 H), 7.25–7.29 (m, 1 H), 7.36–7.39 (m, 5 H), 7.45 (dd, J =
.4, 7.4 Hz, 2 H), 7.62 (dd, J = 9.4, 9.4 Hz, 4 H), 7.68 (d, J = 8.0 Hz, 2 H).
Compound 3ab was synthesized according to the procedure de-
scribed for 3aa using i-PrOH (29 μL, 0.38 mmol), n-BuLi (0.24 mL, 0.38
mmol), Et B (0.38 mL, 0.38 mmol), 1a (54 mg, 0.25 mmol), 3-hexyne
13
C NMR (CDCl , 126 MHz): δ = 14.1 (d, J = 3 Hz), 106.8 (d, JC–F
=
3
C–F
3
11 Hz), 126.9, 127.1, 127.2, 127.3, 127.7 (d, JC–F = 10 Hz), 128.2, 128.4
(
2b; 41 mg, 0.50 mmol), Ni(cod) (7.0 mg, 0.025 mmol), PCy (6.9 mg,
2
3
(d, JC–F = 19 Hz), 128.8, 129.44 (d, JC–F = 8 Hz), 129.45, 133.1, 137.1,
0.025 mmol), ZrF4 (4.1 mg, 0.025 mmol), and toluene (2.0 mL). The
139.8, 140.6, 159.2 (d, JC–F = 260 Hz).
reaction was conducted at r.t. for 17 h. Purification by silica gel col-
umn chromatography (hexane/EtOAc, 20:1) gave 3ab.
19
F NMR (CDCl , 471 MHz): δ = 48.1 (d, J = 40 Hz).
3
F–H
+
HRMS (EI): m/z [M] calcd for C23H19F: 314.1471; found: 314.1474.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

G
Synthesis
Y. Watabe et al.
Special Topic
[
(1E,3Z,5E)-4-Fluoro-5-propylnona-1,3,5-trien-1-yl]benzene (3ha)
Mohan, S.; Wang, C.; Hattori, H. Acc. Chem. Res. 2008, 41, 1474.
(
2
d) De Paolis, M.; Chataigner, I.; Maddaluno, J. Top. Curr. Chem.
012, 327, 87.
Compound 3ha was synthesized according to the procedure de-
scribed for 3aa using i-PrOH (29 μL, 0.38 mmol), n-BuLi (0.24 mL, 0.38
(
(
(
5) For reviews on hydroalkenylation of alkenes, see: (a) RajanBabu,
mmol), Et B (0.38 mL, 0.38 mmol), 1h (42 mg, 0.25 mmol), 2a (55 mg,
3
T. V. Synlett 2009, 853. (b) Hilt, G. Eur. J. Org. Chem. 2012, 4441.
0.50 mmol), Ni(cod)2 (6.9 mg, 0.025 mmol), PCy3 (7.0 mg, 0.025
(c) Greenhalgh, M. D.; Jones, A. S.; Thomas, S. P. ChemCatChem
mmol), ZrF (4.2 mg, 0.025 mmol), and toluene (2.0 mL). The reaction
4
2
015, 7, 190.
was conducted at 40 °C for 12 h. Purification by silica gel column
chromatography (hexane/EtOAc, 50:1) gave 3ha.
6) (a) Arcadi, A.; Bernocchi, E.; Burini, A.; Cacchi, S.; Marinelli, F.;
Pietroni, B. Tetrahedron Lett. 1989, 30, 3465. (b) Uno, T.;
Wakayanagi, S.; Sonoda, Y.; Yamamoto, K. Synlett 2003, 1997.
Yield: 40 mg (62%); colorless oil.
IR (neat): 2958, 2871, 1624, 1595, 1495, 1454, 1377, 1309, 1113,
(c) Wu, J.; Yoshikai, N. Angew. Chem. Int. Ed. 2016, 55, 336.
–1
1
072, 964, 860, 746, 690 cm .
7) (a) Tsukada, N.; Setoguchi, H.; Mitsuboshi, T.; Inoue, Y. Chem.
Lett. 2006, 35, 1164. (b) Tekavec, T. N.; Louie, J. Tetrahedron
2008, 64, 6870. (c) Schabel, T.; Plietker, B. Chem. Eur. J. 2013, 19,
6938.
1
H NMR (CDCl , 500 MHz): δ = 0.95 (t, J = 7.8 Hz, 3 H), 0.96 (t, J =
3
7.8 Hz, 3 H), 1.42–1.52 (m, 4 H), 2.15 (td, J = 7.6, 7.6 Hz, 2 H), 2.20 (t,
J = 7.9 Hz, 2 H), 5.71 (dd, JH–F = 35.3, 10.9 Hz, 1 H), 6.02 (t, J = 7.6 Hz,
1
H), 6.55 (d, J = 15.8 Hz, 1 H), 7.15 (dd, J = 15.8, 10.9 Hz, 1 H), 7.21 (t,
(8) (a) Mitsudo, T.; Zhang, S.-W.; Nagao, M.; Watanabe, Y. J. Chem.
Soc., Chem. Commun. 1991, 598. (b) Hratchian, H. P.;
Chowdhury, S. K.; Gutiérrez-García, V. M.; Amarasinghe, K. K.
D.; Heeg, M. J.; Schlegel, H. B.; Montgomery, J. Organometallics
J = 7.5 Hz, 1 H), 7.31 (dd, J = 7.5, 7.5 Hz, 2 H), 7.43 (d, J = 7.5 Hz, 2 H).
13
C NMR (CDCl , 126 MHz): δ = 14.0, 14.2, 22.5, 22.7, 28.8 (d, J
=
3
C–F
4
1
Hz), 30.3, 106.1 (d, JC–F = 15 Hz), 121.7 (d, JC–F = 7 Hz), 126.3, 127.3,
28.6, 130.1 (d, JC–F = 8 Hz), 130.9 (d, JC–F = 3 Hz), 131.1, 137.6, 158.5
2004, 23, 4636. (c) Shibata, Y.; Hirano, M.; Tanaka, K. Org. Lett.
2008, 10, 2829. (d) Mannathan, S.; Cheng, C.-H. Chem. Commun.
2010, 1923. (e) Horie, H.; Koyama, I.; Kurahashi, T.; Matsubara,
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19
F NMR (CDCl , 471 MHz): δ = 45.1 (d, J = 35 Hz).
3
F–H
S. Chem. Commun. 2011, 2658.
+
HRMS (EI): m/z [M] calcd for C18H23F: 258.1784; found: 258.1784.
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Funding Information
12340. (c) Thornbury, R. T.; Toste, F. D. Angew. Chem. Int. Ed.
This work was financially supported by JSPS KAKENHI Grant No.
JP16H01002 (J.I.) for Precisely Designed Catalysts with Customized
Scaffolding, and JSPS KAKENHI Grant No. JP16K20939 (T.F.) for a
Grant-in-Aid for Young Scientists (B). We acknowledge Kanto Denka
2016, 55, 11629. (d) Doi, R.; Ohashi, M.; Ogoshi, S. Angew. Chem.
Int. Ed. 2016, 55, 341. (e) Ahrens, T.; Teltewskoi, M.; Ahrens, M.;
Braun, T.; Laubenstein, R. Dalton Trans. 2016, 17495. (f) Liu, Y.;
Zhou, Y.; Zhao, Y.; Qu, J. Org. Lett. 2017, 19, 946. (g) Wang, C.-Q.;
Ye, L.; Feng, C.; Loh, T.-P. J. Am. Chem. Soc. 2017, 139, 1762.
Kogyo Co., Ltd., for a generous gift of ethyl bromodifluoroacetate.
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(h) Wu, J.-Q.; Zhang, S.-S.; Gao, H.; Qi, Z.; Zhou, C.-J.; Ji, W.-W.;
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G