Fluorine-copper exchange reaction of α,β,γ,γ, γ-pentafluorocrotonates with organocuprates: Generation and cross-coupling reactions of β-metallated α,γ,γ,γ- tetrafluorocrotonates

Article abstract of DOI:10.1016/j.jfluchem.2013.01.031

Reaction of α,β,γ,γ,γ-pentafluorocrotonates with organocuprates derived from organomagnesium or zinc reagents in THF at -78 °C for 1 h took place smoothly to generate β-metallated intermediate, of which hydrolysis gave the β-reduction product in good yield. The fluorinated vinylcopper intermediate formed by fluorine-copper exchange was found to be stable at low temperature due to the strong electron-withdrawing effect of a CF₃ group, and was readily converted to various types of β-substituted products in good yields with high stereoselectivity by treating with electrophiles, such as iodine and allylic bromides.

Full text of DOI:10.1016/j.jfluchem.2013.01.031

Journal of Fluorine Chemistry 149 (2013) 95–103
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Fluorine–copper exchange reaction of
organocuprates: Generation and cross-coupling reactions of
-tetrafluorocrotonates
a
,
b
,
g
,
g
,
g
-pentafluorocrotonates with
b
-metallated
a,g,g,g
*
Shigeyuki Yamada, Toshio Takahashi, Tsutomu Konno, Takashi Ishihara
Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-0962, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
Reaction of
zinc reagents in THF at À78 8C for 1 h took place smoothly to generate
which hydrolysis gave the -reduction product in good yield. The fluorinated vinylcopper intermediate
formed by fluorine–copper exchange was found to be stable at low temperature due to the strong
electron-withdrawing effect of a CF3 group, and was readily converted to various types of -substituted
a
,
b
,
g
,
g
,
g
-pentafluorocrotonates with organocuprates derived from organomagnesium or
Received 21 December 2012
Received in revised form 28 January 2013
Accepted 29 January 2013
Available online 13 February 2013
b-metallated intermediate, of
b
b
products in good yields with high stereoselectivity by treating with electrophiles, such as iodine and
Keywords:
allylic bromides.
Fluorinated alkenes
Fluorine–copper exchange
Addition–elimination reaction
Organocuprates
ß 2013 Elsevier B.V. All rights reserved.
1. Introduction
reaction of a,b,g,g,g-pentafluorocrotonates with various organo-
cuprates derived from organomagnesium or zinc reagents in detail
(Scheme 2). In addition is also described the subsequent cross-
coupling reaction of the vinylcopper intermediates with various
electrophiles, leading to the efficient preparation of tetra-
substituted alkenes.
Selective C–F bond-cleavage reactions have become important
transformations as well as C–F bond-forming reactions in organic
chemistry [1]. Recently, C–C bond-forming reactions involving the
C–F bond-cleavage have been reported by several groups [2]. Out of
the C–F bond-cleavage reactions, addition–elimination reaction of
fluorinated alkenes is recognized as one of the most convenient
and powerful protocols for the transformation of a C–F bond to
other C–X bonds (X = C [3], O [4], S [5], N [6], etc.) (Scheme 1).
2. Results and discussion
2.1. Reaction of
a,b,g,g,g-pentafluorocrotonates with
Fluorine-substituted a,b-unsaturated carbonyl compounds are
organocuprates derived from Grignard reagents
highly promising substrates for the addition-elimination reactions
to afford various types of organofluorine compounds [7] as well as
fluorine-containing materials [8]. Among such compounds, we
recently reported that the reaction of some vinyl fluorides, such as
Initially, the reaction of a,b,g,g,g-pentafluorocrotonates 1 with
freshly prepared phenylmagnesium bromide (5a) in the absence or
presence of copper(I) salt was examined and the results are
summarized in Table 1. The starting crotonates 1 were prepared
from commercially available perfluorobutanoic acid in 3 steps with
a slight modification of the reported procedure [11], as described in
Section 4.
perfluorocyclopentene,
a,b,b-trifluoroacrylic ester, and a,b,b-
trifluorovinyl sulfone, with organometallic reagents proceeded
smoothly to give the corresponding addition–elimination products
with high stereoselectivity [9]. During the course of our continuous
studies, we found a synthetic strategy for 1,3,3,3-tetrafluoroprop-
1-en-2-ylcopper species involving fluorine–copper exchange reac-
Thus, the treatment of benzyl
a,b,g,g,g-pentafluorocrotonate
(1A) with 5a without any additive in THF at À78 8C for 1 h,
followed by hydrolysis, did not lead to any products (entry 1). As
shown in entries 2 and 3, CuBr and CuI were not the additive of
choice for the present reaction, the starting crotonate being
recovered in high yield. On the other hand, the use of CuCN was
tion of
a,b,g,g,g-pentafluoroprop-1-ene compounds bearing an
electron-withdrawing group with organocopper reagents [9,10]. In
this paper, we wish to describe this fluorine–copper exchange
somewhat effective, providing the
b-reduction product 2A in 34%
yield after hydrolysis (entry 4). Quite interestingly, any trace of the
* Corresponding author. Tel.: +81 75 724 7517; fax: +81 75 724 7580.
E-mail address: konno@chem.kit.ac.jp (T. Ishihara).
addition–elimination product 4Aa was not detected at all in this
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.01.031

96
S. Yamada et al. / Journal of Fluorine Chemistry 149 (2013) 95–103
Nucleophile
R1
R2
R3
R1
Nu
R2
R3
by treating a saturated aqueous NH4Cl solution, was carried out.
The results are tabulated in Table 2.
Aryl Grignard reagents bearing an electron-donating group, like
4-methoxy- (5b), 3-methoxy- (5c), and 4-methylphenylmagne-
sium bromide (5e), also took part well in the reaction to afford the
(Nu)
F
F
Scheme 1. C–F bond-cleavage involving addition–elimination reaction on
corresponding
b-reduction product 2A in 61–65% (50–56%
fluorinated alkenes.
isolated) yields (entries 2, 3, and 5). On the contrary, aryl Grignard
reagents having either a substituent at the 2-position on benzene
ring or an electron-withdrawing group, such as 2-methoxy- (5d) or
4-(trifluoromethyl)phenylmagnesium bromide (5f), were not
case [12]. Either prolonged reaction time (20 h) or raising reaction
temperature (À20 8C) did not cause any improvement on the yield
of 2A, while the formation of benzyl 4,4,4-trifluoro-2-butynoate
was observed (entries 5 and 6). Eventually, it was found that the
reaction of 1A with 2.2 equiv. of organocuprate, prepared from
CuCN (2.2 equiv.) and 5a (4.4 equiv.), in THF at À78 8C for 1 h
suitable nucleophiles, giving the
b-reduction product 2A in only
23% or 27% yield, respectively (entries 4 and 6). n-Butyl- (5 g) and
methylmagnesium bromide (5 h) reacted successfully with 1A to
produce 2A in 59% (40% isolated) and 60% (38% isolated) yields,
respectively (entries 7 and 8). Both secondary alkyl (5i) and vinyl
Grignard reagents (5j) were turned out to be unreactive, a large
amount of 1A being recovered (entries 9 and 10).
proceeded smoothly to give the corresponding
b-reduction
product 2A in 66% (50% isolated) yield as a sole stereoisomer,
together with benzyl -trifluoro- -phenylcrotonate (3Aa) in
g
,g
,
g
b
18% yield (entry 7). The use of hexamethylphosphoric triamide
(HMPA) or N,N-dimethylformamide (DMF) as an additive[13] did
not cause significant change in the yield of 2A (entries 8 and 9). The
reaction at higher temperature (À20 8C) gave 3Aa in 80% (79%
isolated) yield as a mixture of the E/Z isomers (E/Z = ca. 50/50)
(entry 10). Other fluorinated substrates 1B and 1C also underwent
Surprisingly, the use of allyl- (5k) or benzylmagnesium chloride
(5l) as a Grignard reagent resulted in the addition–elimination
product 4Ak or 4Al in 62% (Z/E = 68/32) or 51% (Z/E = 71/29) yield,
respectively (Scheme 3). In these cases, any trace of the
b-
reduction product 2A was not detected at all.
the similar reaction to yield the corresponding
b
-reduction
2.2. Reaction of
a,b,g,g,g-pentafluorocrotonates with organocuprate
product 2B or 2C in 64% (50% isolated) or 55% (42% isolated)
yield, respectively (entries 11 and 12).
derived from dialkylzinc
Subsequently, various Grignard reagents were applied to the
reaction with fluorinated crotonate 1A in order to verify the
generality of the Grignard reagent. Thus, the reaction of 1A with 2.2
equiv. of organocuprate, derived from CuCN (2.2 equiv.) and
Grignard reagent 5 (4.4 equiv.), in THF at À78 8C for 1 h, followed
Similarly, the reaction of the fluorinated crotonate 1A with
various organocuprates derived from organolithium or zinc
reagents was conducted. The reaction of 1A with 2.2 equiv. of
organocuprate, prepared from CuCN (2.2 equiv.) and phenyl-
lithium (4.4 equiv.), in THF at À78 8C for 1 h, followed by
F3C
F
F3C
F
F
F3C
RMgBr + CuCN
Electrophile
or
E
CO2R
F
CO2R
Cu
CO2R
R2Zn + CuCN
-78 °C
Vinylcopper
Intermediate
Scheme 2. Successive fluorine–copper exchange/cross-coupling reaction sequence.
Table 1
Cu(I)-mediated addition–elimination reaction of 1 with PhMgBr (5a) .
1) Cu(I) salt, PhMgBr (5a)
F3C
Ph
F
F3C
H
F
F3C
Ph
H
F3C
F
F
1) THF, temp, 1 h
2) sat. NH4Cl aq.
+
CO2R
CO2R
CO2R
CO2R
4a
1
2
3a
[E/Z= ~90/10]
[E/Z= ~50/50]
Entry
Substrate (R)
PhCH2 (1A)
Cu(I) salt/equiv.
Equiv. of PhMgBr (5a)
Temp. (8C)
Yielda (% of 2)
Yielda (% of 3a)
Recoverya(% of 1) [E/Z]
1
None
1.1
2.2
2.2
2.2
2.2
2.2
4.4
4.4
4.4
4.4
4.4
4.4
À78
À78
À78
À78
À78
À20
À78
À78
À78
À20
À78
À78
0
0
91
2
CuBr/1.1
Cul/1.1
0
0
0
87
3
0
76[78/20]
4
CuCN/1.1
CuCN/1.1
CuCN/1.1
CuCN/2.2
CuCN/2.2
CuCN/2.2
CuCN/2.2
CuCN/2.2
CuCN/2.2
34
0
64[80/20]
5b,c
6c
7
35
0
52[80/20]
5
0
35[60/40]
66(50)
56
18
22
2
0
8d
9e
10
11
12
8
63
17
0
0
80(79)
19
17
PhCH2CH2 (1B)
64(50)
55(42)
0
(Z)-PhCH5CHCH2 (1C)
0
a
Determined by 19F NMR. Values in parentheses are of isolated yields.
Carried out for 20 h.
b
c
Benzyl 4,4,4-trifluoro-2-butynoate was obtained in 4% (for entry 5) and 31% (for entry 6).
Hexamethylphosphoric triamide (HMPA) was used as an additive.
N,N-dimethylformamide (DMF) was used as an additive.
d
e

S. Yamada et al. / Journal of Fluorine Chemistry 149 (2013) 95–103
97
Table 2
Cu(I)-mediated addition–elimination reaction of 1A with various Grignard reagents .
1) CuCN (2.2 equiv.)
1) Grignard reagent (4.4 equiv.)/
F3C
H
F
F3C
R
H
F3C
F
F
1) THF, -78 °C, 1 h
2) sat. NH4Cl aq.
+
CO2Bn
CO2Bn
CO2Bn
1A
2A
3A
[E/Z= ~90/10]
[E/Z= ~50/50]
Entry
Grignard reagent (RMgBr)
Yielda (% of 2A)
Yielda (% of 3A)
Recoverya (% of 1A) [E/Z]
1
2
3
4
5
6
7
8
9
10
PhMgBr (5a)
66 (50)
61 (53)
62 (54)
23
18
25
23
0
0
4-MeOC6H4MgBr (5b)
3-MeOC6H4MgBr (5c)
2-MeOC6H4MgBr (5d)
4-MeC6H4MgBr (5e)
4-CF3C6H4MgBr (5f)
n-BuMgBr (5g)
Trace
Trace
73[90/10]
65 (54)
27
0
0
0
0
59 (40)
60 (38)
15
0
9
MeMgBr (5h)
0
10
s-BuMgBr (5i)
0
79[92/8]
78[88/12]
PhCH25CHMgBr (5j)
20
0
a
Determined by 19F NMR. Values in parentheses are of isolated yields.
Scheme 3. Cu(I)-mediated addition–elimination reaction of 1A with allyl- (5k) or benzylmagnesium chloride (5l).
hydrolysis, resulted in a complex mixture. The use of n-butylzinc
iodide as an organozinc reagent led to almost quantitative recovery
of 1A. However, it was found that organocuprate, derived from
CuBr and diethylzinc (7m), was somewhat more reactive, yielding
a small amount of the addition–elimination product 4Am along
with 81% recovery of 1A. Therefore, the reaction of 1A with
diethylzinc (7m)-derived organocuprate was investigated in
detail, and the results are shown in Table 3.
recovered (entry 1). Although various sorts of copper(I) salts, such
as CuBr, CuI, and CuCN, were examined, the addition–elimination
product 4Am as well as the reduction product 2A was not obtained
in good yield (entries 2–4). When 1A was treated with diethyl zinc
(7m) in the presence of CuCNÁ2LiCl [14] in THF at À78 8C for 1 h,
followed by hydrolysis, the b-reduction product 2A was produced
in 33% yield, along with the addition–elimination product 4Am
and homo-coupling product 6A [15] in 8% and 10% yields,
respectively (entry 5). The use of 2.2 equiv. of organocuprate,
prepared from CuCNÁ2LiCl (2.2 equiv.) and 7m (4.4 equiv.),
resulted in complete consumption of the starting material and
The reaction of benzyl
a,b,g,g,g-pentafluorocrotonate (1A)
with 1.1 equiv. of diethyl zinc (7m) in the absence of copper(I) salt
in THF at À78 8C for 1 h, followed by addition of an aqueous NH4Cl
solution, did not give any products, a large amount of 1A being
improvement on the yield of the
b-reduction product 2A (55%
Table 3
Cu(I)-mediated addition–elimination reaction of 1A with Et2Zn .
1) Cu(I)
F3C
F
1) Et2Zn (7m)
F3C
H
F
F3C
Et
F
BnO2C
F
F3C
F
F
1) THF, temp, 1 h
2) sat. NH4Cl aq.
+
+
CO2Bn
CO2Bn
CO2Bn
4Am
CF3
6A
CO2Bn
1A
2A
Entry
Cu(I) salt/equiv.
Equiv. of Et2Zn
Temp. (8C)
Yielda (% of 2A)
Yielda (% of 4Am)
Yielda (% of 6A)
Recoverya(% of 1A) [E/Z]
1
None
1.1
2.2
2.2
2.2
2.2
4.4
4.4
4.4
4.4
À78
À78
À78
À78
À78
À78
À78
À78
À20
0
0
11
12
8
0
0
91 [88/12]
2
CuBr/1.1
0
81 [90/10]
3
CuI/1.1
0
0
75 [90/10]
4
CuCN/1.1
Trace
33
55
54
55
37
0
83 [90/10]
5
CuCNꢀ2LiCl/1.1
CuCNꢀ2LiCl/2.2
CuCNꢀ2LiCl/2.2
CuCNꢀ2LiCl/2.2
CuCNꢀ2LiCl/2.2
8
10
20
20
14
8
40 [85/15]
6
7
0
0
0
0
7b
8c
9
16
7
20
a
b
c
Determined by 19F NMR.
With trimethylsilyl chloride (TMSCl) as an additive.
With hexamethylphosphoric triamide (HMPA) as an additive.

98
S. Yamada et al. / Journal of Fluorine Chemistry 149 (2013) 95–103
PhB(OH)2 (6.0 equiv)
CuCN•2LiCl
Pd(PPh3)4 (10 mol%)
Na2CO3 (3.0 equiv)
Me2Zn (7n)
2A + 4An + 6A
F3C
I
F
F3C
F
H2O (0.3 mL), EtOH (0.3 mL)
(34%) (24%) (14%)
C H ,
reflux, 12 h
6
6
CO2Bn
CO2Bn
CuCN•2LiCl
4Aq
F3C
F
F3C
F
i-Pr2Zn (7o)
4Aa
91%
39% isolated yield
CO2Bn
4Ao
F
CO2Bn
(isolated yield)
(88% NMR yield)
1A
CuCN•2LiCl
Scheme 5. Suzuki–Miyaura cross-coupling reaction of 4Aq with phenylboronic
Ph2Zn (7p)
acid.
No reaction
Quantitative recovery
of 1A
2.3. Cross-coupling reaction leading to fluorine-containing tetra-
substituted alkenes
Scheme 4. Cu(I)-mediated addition–elimination reaction of 1A with Me2Zn (7n), i-
Pr2Zn (7o) or Ph2Zn (7p).
Next we focused our interest on direct cross-coupling reaction
of the in situ-generated vinylcopper intermediate with various
electrophiles, leading to multi-substituted fluorine-containing
alkenes. The results are tabulated in Table 4.
Thus, on treating the fluorinated crotonate 1A with 2.2 equiv. of
diphenylcyanocuprate, prepared from CuCN (2.2 equiv.) and
phenylmagnesium bromide (5a, 4.4 equiv.), in THF at À78 8C for
1 h, followed by addition of I2 (5.0 equiv.) at the same temperature,
yield) (entry 6). As shown in entries 7 and 8, the addition of TMSCl
or HMPA as an additive [13] did not affect on the yield of 2A at all.
The reaction at higher temperature (À20 8C) led to a complex
mixture though the yield of the addition-elimination product 4Am
was slightly increased (entry 9).
In Scheme 4 are shown the results of the reaction of 1A with
some commercially available diorganozinc reagents, such as
dimethylzinc (7n), diisopropylzinc (7o), and diphenylzinc (7p),
under the conditions shown in entry 6 in Table 3.
benzyl a,g,g,g-tetrafluoro-b-iodocrotonate (4Aq) was obtained in
82% (79% isolated) yield as a mixture of the E/Z isomers (E/Z = 79/
21) (entry 1). Allyl bromide, methallyl bromide, and (E)-crotyl
bromide as an electrophile could also participate well in the
The reaction of 1A with organocuprate derived from CuCNꢀ2LiCl
and dimethylzinc (7n) yielded three types of products, i.e.
b
-
coupling reaction to give the corresponding b-substituted
reduction product 2A, addition–elimination product 4An, and
homo-coupling product 6A, in 34%, 24%, and 14% yields,
respectively. In sharp contrast, diisopropylzinc (7o) was quite
effective to form the addition–elimination product 4Ao exclusively
as a sole stereoisomer. Diphenylzinc (7p) was found to be much
less reactive, resulting in quantitative recovery of the starting
crotonate 1A.
products 4Ak, 4Ar, and 4As in 67% (42% isolated), 66% (62%
isolated), and 65% (56% isolated) yields, respectively (entries 2–4).
In the case of other electrophiles, like propargyl bromide, benzyl
bromide, and trimethylsilyl chloride, only b-reduction product 2A
was observed in 43%, 59%, and 41% yields, respectively.
Subsequently, we attempted further transformation of the
above-obtained
benzyl
a,g,g,g-tetrafluoro-b-iodocrotonate
Table 4
Direct cross-coupling reaction with various electrophiles .
1) CuCN (2.2 equiv)
1) PhMgBr (5a, 4.4 equiv)
F3C
F
F
F3C
F
1) THF, -78 °C, 1 h
2) Electrophile (E+, 5.0 equiv)
CO2Bn
E
CO2Bn
2) THF, -78 °C, 1 h
1A
4A
3) sat. NH4Cl aq.
(E/Z= ~90/10)
Entry
1
Electrophile
l2
Product
Yielda (% of 4A) [E/Z]
82 (79)
[79/21]
F3C
I
F
4Aq
CO2Bn
F
2
3
67 (42)
[0/100]
F3C
Br
Br
4Ak
CO2Bn
66 (62)
[18/82]
F3C
F
4Ar
CO2Bn
F
4
Br
65 (58)
[0/100]
F3C
4As
CO2Bn
a
Determined by 19F NMR. Values in parentheses are of isolated yields.

S. Yamada et al. / Journal of Fluorine Chemistry 149 (2013) 95–103
99
2 R-M + CuCN
F
F
OBn
O
F
F3C
F3C
F
F
R2CuCN•M
M = Mg or Zn
F3C
R
OBn
2
M
Cu
R
CO2Bn
R
F
O
Cu
-78 °C
M
R
Reductive
Elimination
F
F3C
F
F3C
E+
F3C
F
R2Cu
CO2Bn
Int-A
E
CO2Bn
R
CO2Bn
RCuCN
R-R
-20 °C
F3C
H
R2CuCN•M
2
F3C
CO2Bn
-20 °C
R
CO2Bn
Scheme 6. A possible reaction mechanism for the fluorine–copper exchange and subsequent cross-coupling reaction.
(4Aq), as shown in Scheme 5. Thus, the reaction of 4Aq with
phenylboronic acid in the presence of 10 mol% of Pd(PPh3)4,
3.0 equiv. of Na2CO3, and 0.3 mL each of H2O and EtOH in benzene
at reflux temperature for 12 h took place efficiently to lead to
efficiently to generate
hydrolysis gave the -reduction product in good yield. Treatment
of the organocopper intermediate with various electrophiles gave
the corresponding -substituted products in good yields. b-
b-metallated intermediate, of which
b
b
a
,
g
,
g
,
g
-tetrafluoro-
b
-phenylcrotonate 4Aa in 88% NMR yield [16].
Iodinated product was nicely subjected to the Suzuki–Miyaura
cross-coupling reaction, leading to the corresponding tetra-
substituted fluorinated crotonate in good yield. The present
copper–fluorine exchange and subsequent cross-coupling reac-
tion would become a powerful method to prepare various types of
organofluorine compounds.
2.4. Reaction mechanism
A
possible mechanism for the fluorine–copper exchange
reaction of
a,b,g,g,g-pentafluorocrotonates with organocopper
reagent and subsequent cross-coupling reaction with electrophiles
can be proposed as follows (Scheme 6).
4. Experimental
Thus, the in situ-generated organocuprate derived from CuCN
and organomagnesium or zinc reagent (R-M) may coordinate with
an olefinic double bond of the fluorinated crotonate, followed by
interaction between metal (magnesium or zinc) and the carbonyl
4.1. General experimental procedures
1H and 13C NMR spectra were measured with a Bruker DRX-500
(500.13 MHz for 1H and 125.75 MHz for 13C) spectrometer in a
chloroform-d (CDCl3) solution with tetramethylsilane as an
internal reference. A JEOL JNM-AL400 (376.05 MHz) was used to
measure 19F NMR spectra in CDCl3 using trichlorofluoromethane
(CFCl3) as an internal standard. Infrared spectra (IR) were
oxygen atom, to form a
p-complex [17]. Subsequent oxidative
addition of the copper species leads to an enolate-like intermedi-
ate, which will be in a rigid conformation owing to dual interaction
of metal with copper and with fluorine atom [18]. Then, the
elimination of metal fluoride takes place to form vinylcopper
intermediate Int-A, which is stabilized due to the strong electron-
withdrawing effect of a CF3 group [19] and is not susceptible to the
reductive elimination at À78 8C [20]. By treatment with various
electrophiles, the vinylcopper intermediate Int-A is converted to
determined in
a liquid film or KBr disk method with an
AVATAR-370DTGS spectrometer (Thermo ELECTRON) or an FT/
IR-4100 (JASCO). High resolution mass spectra were taken with a
JEOL JMS-700MS spectrometer. Elemental analyses were con-
ducted with a Yanaco CHN CORDER MT-5 instrument.
the corresponding
b-substituted product, along with the forma-
tion of homo-coupling product (R-R). On the other hand, addition–
elimination product can be formed with a reductive elimination of
RCuCN from Int-A, which depends on the nature of substituents on
copper center. Although it is still unclear, it is supposed that
migratory ability of the substituent from copper center to double
bond is one of the most important factors. On raising the reaction
temperature from À78 8C to À20 8C, the elimination of Cu-F in Int-
A proceeds to yield the corresponding alkynoate, which may
undergo the Michael addition reaction of an excess amount of
4.1.1. Materials
All chemicals were of reagent grade, and if necessary, were
purified in the usual manner prior to use. Anhydrous tetrahydro-
furan (THF) and diethyl ether were purchased from Wako
chemicals. Thin layer chromatography (TLC) was done with Merck
25 aluminum sheets (silica gel 60 F254). Column chromatography
was carried out with Wakogel C-200. All reactions were carried out
under an argon atmosphere.
organocuprate to afford b-substituted g,g,g-trifluorocrotonates as
a mixture of the E/Z isomers.
4.2. General procedure for the preparation of
pentafluorocrotonate
a,b,g,g,g-
3. Conclusion
The starting materials, a,b,g,g,g-pentafluorocrotonates 1 were
In conclusion, we have found that the fluorine–copper
exchange reaction of -pentafluorocrotonate with orga-
nomagnesium or zinc-derived organocuprates took place
prepared from easily available perfluorobutanoic acid in 3 steps
with a slight modification of the reported procedure, as follows: In
a two-necked round-bottomed flask, equipped with a stirrer bar, a
a,b,g,g,g

100
S. Yamada et al. / Journal of Fluorine Chemistry 149 (2013) 95–103
rubber septum, and an inlet tube for Ar, was placed 20 mmol of
P(OEt)3 [11]. After cooling the flask by immersing in an ice-
methanol bath, 10 mmol of freshly prepared perfluorobutanoic
acid chloride [11a] was added dropwise to the pre-cooled solution
via a syringe, followed by continuous stirring at room temperature
for 2 h. To the reaction mixture was slowly added 50 mL of water
via a syringe at 0 8C. The resultant solution was subjected to
extraction with Et2O (50 mL, 3 times) and the ethereal extracts
were washed with 5% aqueous NaHCO3 solution, dried over
anhydrous Na2SO4, and concentrated under reduced pressure. The
residue was chromatographed on silica gel (hexane/AcOEt = 1/1) to
give pure (Z)-diethyl 1-(diethylphosphono)-1-perfluorobutenyl
phosphate as viscous oil.
(dq, J = 139.1, 21.8 Hz, 1F), À150.99 (dq, J = 139.1, 9.8 Hz, 1F),
À68.88 (dd, J = 21.8, 9.8 Hz, 3F); 13C NMR (CDCl3)
d 67.4, 118.1
(qdd, J = 275.0, 35.3, 3.8 Hz), 120.8, 126.8, 128.5, 128.7, 136.3,
136.6, 141.5 (ddq, J = 230.4, 32.9, 2.4 Hz), 145.1 (ddq, J = 273.7,
40.9, 40.9 Hz), 157.3 (dd, J = 30.2, 6.2 Hz); Z-1C: 1H NMR (CDCl3)
d
4.98 (dd, J = 6.9, 0.9 Hz, 2H), 6.29 (dt, J = 15.9, 6.9 Hz, 1H), 6.75 (d,
J = 15.9 Hz, 1H), 7.27 – 7.37 (m, 3H), 7.39 – 7.44 (m, 2H); 19F NMR
(CDCl3)
d
À136.8 to À136.5 (m, 1F), À136.4 to À136.1 (m, 1F),
À65.65 (dd, J = 9.4, 9.4 Hz, 3F); IR (neat)
n 3029, 2957, 1749, 1701,
1495, 1371, 1270, 1222, 1162, 966 cmÀ1; HRMS (FAB) Calcd for
(M+) C13H9F5O2: 292.0523, Found 292.0530.
4.3. Typical procedure for the reaction of 1A with PhMgBr in the
presence of CuCN
4.2.1. (Z)-Diethyl 1-(diethylphosphono)-1-perfluorobutenyl
phosphate
A 30 mL two-necked round-bottomed flask, equipped with a
magnetic stirrer bar, a rubber septum, and an inlet tube for Ar, was
charged with a suspension of CuCN (0.42 mmol, 0.037 g) in THF
(1.0 mL). To this solution was slowly added a 1.0 M solution of
PhMgBr (0.84 mmol, 0.84 mL) in THF via a syringe at À78 8C. The
whole was warmed up to À20 8C and stirred for 15 min. To the
Yield: 77% (oil); 1H NMR (CDCl3)
4.22 (m, 8H); 19F NMR (CDCl3)
d 1.25 – 1.31 (m, 12H), 4.14 –
d
À137.45 to À137.32 (m, 1F),
À119.55 to À119.45 (m, 2F), À84.05 to À83.95 (m, 3F); 31P NMR
(CDCl3, H3PO4)
1P); IR (neat)
d
2.07 (d, J = 10.2 Hz, 1P), À7.22 (dd, J = 10.2, 2.4 Hz,
n
3412, 2990, 1764, 1481, 1363, 1274, 1216, 1149,
1031, 870 cmÀ1; HRMS (FAB) calcd for (M + H) C12H21F6O7P2:
453.0667, Found: 453.0678.
resulting solution was added benzyl a,b,g,g,g-pentafluorocroto-
nate (1A, 0.19 mmol, 0.050 g) in THF(2.0 mL) via a syringe at À78 8C.
After being stirred for 1 h, the reaction mixture was poured into an
ice-cooled saturated aqueous NH4Cl solution (30 mL), followed by
extraction with Et2O (30 mL each, 3 times). The organic layers were
dried over anhydrous Na2SO4, filtered and concentrated with a
rotary evaporator. Column chromatography of the residue using
The vinyl phosphate (5.0 mmol, 2.26 g) prepared was treated
with a suspension of CsF (5.5 mmol, 0.84 g) and alcohol (7.5 mmol)
in CH2Cl2 (10 mL) at 0 8C. After stirring at room temperature for 2 h,
the whole was poured into ice-cooled water (30 mL), followed by
extraction with Et2O (30 mL each, 3 times). The organic layers
combined were dried over anhydrous Na2SO4, filtered and
concentrated with a rotary evaporator under reduced pressure.
Column chromatography of the residue using hexane/benzene (5/
hexane/benzene (5/1) yielded pure benzyl (Z)-a,g,g,g-tetrafluor-
ocrotonate (2A, 0.09 mmol, 0.025 g).
1) gave pure product,
mixture of the E/Z isomers (E/Z = ꢁ90/10).
a
,
b
,
g
,
g
,
g
-pentafluorocrotonate (1) as a
4.3.1. Benzyl (Z)-
a
,
g
,
g
,
g
-tetrafluorocrotonate (2A)
5.33 (s, 2H), 6.28 (dq, J = 28.1,
Yield: 50% (oil); 1H NMR (CDCl3)
d
7.5 Hz, 1H), 7.35 – 7.41 (m, 5H); 19F NMR (CDCl3)
d
À111.08 (dq,
4.2.2. Benzyl
a,
b,
g
,g
,g
-pentafluorocrotonate (1A)
J = 28.1, 17.3 Hz, 1F), À59.80 (dd, J = 17.3, 7.5 Hz, 3F); 13C NMR
Yield: 82% (oil); E-1A: 1H NMR (CDCl3)
5.37 (s, 2H), 7.35 – 7.42
(m, 5H); 19F NMR (CDCl3)
À153.84 (dq, J = 138.6, 18.8 Hz, 1F),
À150.63 (dq, J = 138.6, 6.6 Hz, 1F), À68.91 (dd, J = 18.8, 6.6 Hz, 3F);
13C NMR (CDCl3)
68.4, 118.2 (qdd, J = 274.8, 31.4, 4.0 Hz), 128.5,
d
(CDCl3) d 68.6, 106.9, (qd, J = 37.2, 5.6 Hz), 121.1 (q, J = 270.5 Hz),
d
128.7, 128.8, 129.0, 134.0, 158.5 (d, J = 34.1 Hz), 152.0 (dq,
J = 284.4, 5.0 Hz); IR (neat) 3038, 2963, 1753, 1697, 1458,
1365, 1283, 1178, 1073, 947 cmÀ1; HRMS (EI) Calcd for (M+)
11H8F4O2: 248.0460, Found 248.0458.
n
d
128.7, 128.9, 134.1, 141.6 (ddq, J = 230.0, 32.8, 2.4 Hz), 145.1 (ddd,
J = 273.2, 41.0, 41.0 Hz), 157.3 (dd, J = 30.4, 6.2 Hz); Z-1A: 1H NMR
C
(CDCl3)
d
5.34 (s, 2H), 7.35 – 7.42 (m, 5H); 19F NMR (CDCl3)
d
n
4.3.2. 2-Phenylethyl (Z)-
Yield: 50% (oil); 1H NMR (CDCl3)
(dq, J = 28.1, 7.5 Hz, 1H), 7.20 – 7.37 (m, 5H); 19F NMR (CDCl3)
À111.24 (dq, J = 28.1, 16.9 Hz, 1F), À59.80 (dd, J = 16.9, 7.5 Hz, 3F);
13C NMR (CDCl3)
3.7, 67.3, 106.7 (qd, J = 37.0, 5.6 Hz), 121.1 (q,
J = 270.5 Hz), 127.0, 128.7, 128.8, 1136.6, 152.0 (dq, J = 284.8,
a
,g
,g
,
g
-tetrafluorocrotonate (2B)
À136.0 to À137.0 (m, 2F), À65.67 (dd, J = 8.8, 8.8 Hz, 3F); IR (neat)
d
3.02 (t, J = 7.0 Hz, 2H), 6.20
3038, 2966, 1751, 1458, 1372, 1273, 1224, 1162, 960 cmÀ1; HRMS
(EI) Calcd for (M+) C11H7F5O2: 266.0366, Found 266.0356; Anal.
Calcd for C11H7F5O2: C, 49.64: H, 2.65. Found: C, 49.60; H, 2.75.
d
d
4.2.3. 2-Phenylethyl
Yield: 72% (oil); E-1B: 1H NMR (CDCl3)
4.55 (t, J = 6.9 Hz, 2H), 7.23 – 7.30 (m, 3H), 7.31 – 7.37 (m, 2H); 19
a
,
b
,
g
,
g
,
g
-pentafluorocrotonate (1B)
4.9 Hz), 158.6 (d, J = 33.9 Hz); IR (neat) n 3031, 2963, 1753, 1697,
d
3.05 (t, J = 6.9 Hz, 2H),
1498, 1396, 1368, 1287, 1183, 1141, 1076, 910 cmÀ1; HRMS (EI)
Calcd for (M+) C12H10F4O2: 262.0617, Found 262.0608.
F
NMR (CDCl3)
d
À153.70 (dq, J = 139.1, 22.1 Hz, 1F), À151.16 (dq,
J = 139.1, 9.8 Hz, 1F), À68.88 (dd, J = 22.1, 9.8 Hz, 3F); 13C NMR
4.3.3. (Z)-3-Phenyl-2-propen-1-yl (Z)-
a
,g
,
g
,g
-tetrafluorocrotonate
(CDCl3)
d
34.7, 67.4, 118.1 (qdd, J = 274.9, 34.9, 3.6 Hz), 126.9,
(2C)
128.7, 128.9, 136.7, 141.5 (ddq, J = 262.8, 33.1, 2.4 Hz), 145.0 (ddq,
J = 273.6, 41.0, 41.0 Hz), 157.4 (dd, J = 30.7, 6.2 Hz); Z-1B: 1H NMR
Yield: 42% (oil); 1H NMR (CDCl3)
d 4.95 (dd, J = 6.8, 1.0 Hz, 2H),
6.30 (dq, J = 28.1, 7.5 Hz, 1H), 6.30 (dt, J = 15.8, 6.8 Hz, 1H), 6.74 (d,
J = 15.8 Hz, 1H), 7.25 – 7.38 (m, 3H), 7.39 – 7.43 (m, 2H); 19F NMR
(CDCl3)
(m, 3H), 7.31 – 7.37 (m, 2H); 19F NMR (CDCl3)
(m, 1F), À136.4 to À136.1 (m, 1F), À65.67 (dd, J = 9.4, 9.4 Hz, 3F); IR
d
3.03 (t, J = 6.5 Hz, 2H), 4.53 (t, J = 6.5 Hz, 2H), 7.23 – 7.30
d
À137.1 to À136.7
(CDCl3)
7.5 Hz, 3F); IR (neat)
1276, 1138, 1073, 967 cmÀ1
13H10F4O2: 274.0617, Found 274.0615.
d
À111.17 (dq, J = 28.1, 16.9 Hz, 1F), À59.79 (dd, J = 16.9,
3030, 2957, 1752, 1696, 1496, 1449, 1365,
HRMS (FAB) Calcd for (M+)
n
(neat)
n
3031, 2964, 1750, 1702, 1605, 1498, 1375, 1276, 1227,
;
1163, 984 cmÀ1; HRMS (FAB) Calcd for (M + H) C12H10F5O2:
281.0602, Found 281.0594.
C
4.3.4. Benzyl
g,g,g-trifluorobutynoate
4.2.4. 3-Phenyl-2-propen-1-yl
Yield: 70% (oil); E-1C: 1H NMR (CDCl3)
2H), 6.31 (dt, J = 15.8, 6.6 Hz, 1H), 6.76 (d, J = 15.8 Hz, 1H), 7.27 –
7.37 (m, 3H), 7.39 – 7.44 (m, 2H); 19F NMR (CDCl3)
À153.61
a
,
b
,
g
,
g
,
g
-pentafluorocrotonate (1C)
Oil; 1H NMR (CDCl3) 5.29 (s, 2H), 7.35 – 7.43 (m, 5H); 19F NMR
d
d
5.00 (dd, J = 6.6, 0.8 Hz,
(CDCl3)
d
À52.69 (s, 3F); 13C NMR (CDCl3)
d 69.0, 70.4 (q,
J = 54.9 Hz), 75.3 (q, J = 6.5 Hz), 113.3 (q, J = 260.3 Hz), 128.8,
d
128.81, 129.1, 133.6, 150.6 (q, J = 1.3 Hz); IR (neat) n 3037, 2965,

S. Yamada et al. / Journal of Fluorine Chemistry 149 (2013) 95–103
101
1732, 1608, 1457, 1376, 1270, 1163, 1094, 999 cmÀ1; HRMS (EI)
Calcd for (M+) C11H7F3O2: 228.0398, Found 228.0393.
charged with a solution of CuCN (0.037 g, 0.42 mmol) and LiCl
(0.035 g, 0.84 mmol) in THF (1.0 mL). To the solution was slowly
added a 1.0 M toluene solution of i-Pr2Zn (0.84 mL, 0.84 mmol) at
À78 8C. The resulting mixture was stirred at À20 8C for 15 min, and
then was re-cooled to À78 8C. To the whole was added dropwise a
4.4. Typical procedure for the preparation of benzyl
-phenylcrotonate (3Aa)
g,g,g-trifluoro-
b
solution of benzyl
a,b,g,g,g-pentafluorocrotonate (1A, 0.050 g,
A 30 mL two-necked round-bottomed flask equipped with a
0.2 mmol) in THF (2.0 mL) at À78 8C. After being stirred at À78 8C
for 1 h, the reaction mixture was poured into an ice-cooled
saturated aqueous NH4Cl solution (30 mL). The resultant mixture
was extracted with Et2O (30 mL, 3 times) and the organic layers
were dried over anhydrous Na2SO4, filtered, and concentrated in
vacuo with rotary evaporator. Column chromatography of the
magnetic stirrer bar, a rubber septum, and an inlet tube for Ar was
charged with a suspension of CuCN (0.037 g, 0.42 mmol) in THF
(1.0 mL) solution. To the solution was slowly added a 0.84 M
solution of PhMgBr (1.0 mL, 0.84 mmol) in THF via a syringe at
À78 8C. The whole was warmed up to À20 8C and stirred for
15 min. To the resulting solution was added benzyl
a
,b
,g
,
g
,g
-
residue using hexane/benzene (5/1) gave benzyl (Z)-a,g,g,g-
pentafluorocrotonate (1A, 0.050 g, 0.2 mmol) via a syringe at
À78 8C. After stirring at À20 8C for 1 h, the reaction mixture was
poured into an ice-cooled saturated aqueous NH4Cl solution
(30 mL), followed by extraction with Et2O (30 mL, 3 times). The
organic layers were dried over anhydrous Na2SO4, filtered and
concentrated under reduced pressure with a rotary evaporator.
Column chromatography of the residue using hexane/benzene (2/
tetrafluoro-
product.
b-isopropylcrotonate (4Ao, 0.050 g, 91%) as a pure
4.6.1. Benzyl (Z)-
a
,g
,
g,
g
-tetrafluoro-b-isopropylcrotonate (4Ao)
Yield: 91% (oil); 1H NMR (CDCl3)
d
1.21 (d, J = 7.6 Hz, 6H), 3.65 –
3.80 (m, 1H), 5.30 (s, 2H), 7.33 – 7.45 (m, 5H); 19F NMR (CDCl3)
d
À111.47 (q, J = 21.8 Hz, 1F), À58.09 (d, J = 21.8 Hz, 3F); 13C NMR
1) yielded pure benzyl
g
,g
,
g
-trifluoro-
b
-phenylcrotonate (3Aa,
(CDCl3) d 20.0, 26.0, 68.0, 123.3 (qd, J = 277.7, 2.5 Hz), 127.4 (qd,
0.046 g, 76%) as an E/Z mixture.
J = 27.3, 3.3 Hz), 128.4, 128.7, 128.8, 134.4, 148.2 (dq, J = 279.3,
3.3 Hz), 159.7 (d, J = 33.9 Hz); IR (neat)
n 3069, 3037, 2947, 2944,
4.4.1. Benzyl
Yield: 76% (oil); (E)-3Aa: 1H NMR (CDCl3)
2H), 7.35 – 7.45 (m, 10H); 19F NMR (CDCl3)
À60.52 (s, 3F); (Z)-3Aa:
1H NMR (CDCl3)
5.02 (s, 2H), 6.65 (q, J = 1.2 Hz, 2H), 7.35 – 7.45 (m,
10H); 19F NMR (CDCl3)
g
,
g
,
g
-trifluoro-
b
-phenylcrotonate (3Aa)
2885, 1739, 1656, 1457, 1381, 1254, 1139, 1032 cmÀ1; HRMS (EI)
Calcd for (M+) C14H14F4O2: 290.0930, Found 290.0936.
d
5.27 (s, 2H), 6.37 (s,
d
d
4.6.2. Benzyl (Z)-
NMR Yield: 7% (oil); 1H NMR (CDCl3)
2.63 (q, J = 7.6 Hz, 2H), 5.31 (s, 2H), 7.35 – 7.41 (m, 5H); 19F NMR
b
-ethyl-
a
,
g
,
g
,
g
-tetrafluorocrotonate (4Am)
d
À68.03 (s, 3F); IR (neat)
n
3065, 3036, 1736,
d
1.14 (t, J = 7.6 Hz, 3H),
1656, 1448, 1364, 1284, 1170, 1128, 1003, 949 cmÀ1; HRMS (FAB)
Calcd for (M+H) C17H14F3O2: 307.0947, Found 307.0951.
(CDCl3)
(neat)
d
À113.41 (q, J = 19.6 Hz, 1F), À62.51 (d, J = 19.6 Hz, 3F); IR
n
3037, 2962, 2875, 1740, 1671, 1456, 1383, 1348, 1246,
4.5. Typical procedure for the reaction of 1A with PhCH2 MgCl in the
presence of CuCN
1136, 1081 cmÀ1; HRMS (EI) Calcd for (M+) C13H12F4O2: 276.0773,
Found 276.0785.
A 30 mL two-necked round-bottomed flask, equipped with a
magnetic stirrer bar, a rubber septum, and an inlet tube for Ar, was
charged with a suspension of CuCN (0.42 mmol, 0.037 g) in THF
(1.0 mL). To this solution was slowly added a 1.0 M solution of
PhCH2MgCl (0.84 mmol, 0.84 mL) in THF via a syringe at À78 8C.
The whole was warmed up to À20 8C and stirred for 15 min. To the
4.6.3. Dibenzyl (1Z, 3Z)-1,4-difluoro-2,3-bis(trifluoromethyl)-1,3-
butadiene-1,4-dicarboxylate (6A)
NMR Yield: 20% (oil); 1H NMR (CDCl3)
d 5.15 (d, J = 11.6 Hz, 2H),
5.27 (d, J = 11.6 Hz, 2H), 7.28 – 7.38 (m, 10H); 19F NMR (CDCl3)
d
À101.45 (q, J = 17.3 Hz, 2F), À61.07 (d, J = 17.3 Hz, 6F); 13C NMR
(CDCl3)
d 69.0, 111.4 – 112.9 (m), 120.6 (qd, J = 276.8, 4.2 Hz),
resulting solution was added benzyl
a
,b
,
g,
g
,g
-pentafluorocroto-
128.8, 128.9, 129.2, 133.5, 151.6 (dq, J = 289.3, 2.5 Hz), 157.6 (d,
nate (1A, 0.19 mmol, 0.050 g) in THF (2.0 mL) via a syringe at
À78 8C. After being stirred for 1 h, the reaction mixture was poured
into an ace-cooled saturated aqueous NH4Cl solution (30 mL),
followed by extraction with Et2O (30 mL each, 3 times). The
organic layers were dried over anhydrous Na2SO4, filtered and
concentrated with a rotary evaporator. Column chromatography of
J = 33.0 Hz); IR (neat) n 3037, 2964, 1750, 1655, 1458, 1333, 1261,
1215, 1160, 954 cmÀ1; HRMS (FAB) Calcd for (M+H) C22H15F8O4:
495.0843, Found 495.0815.
4.7. Typical procedure for the preparation of benzyl
tetrafluoro- -iodocrotonate (4Aq)
a,g,g,g-
b
the residue using hexane/benzene (5/1) yielded pure benzyl
benzyl- -tetrafluorocrotonate (4Al, 0.07 mmol, 0.023 g) as
an E/Z mixture.
b-
a
,
g
,g
,
g
A 30 mL two-necked round-bottomed flask, equipped with a
magnetic stirrer bar, a rubber septum, and an inlet tube for Ar, was
charged with a suspension of CuCN (0.037 g, 0.42 mmol) in THF
(1.0 mL). To the solution was slowly added a 0.84 M solution of
PhMgBr (1.0 mL, 0.84 mmol) in THF via a syringe at À78 8C. The
whole was warmed up to À20 8C and stirred for 15 min. To the
4.5.1. Benzyl
b
-benzyl-
a
,
g
,
g
,
g
-tetrafluorocrotonate (4Al)
4.03 (s, 2H), 5.32 (s,
Yield: 36% (oil); (Z)-4Al: 1H NMR (CDCl3)
d
2H), 7.15 – 7.40 (m, 10H); 19F NMR (CDCl3)
d
À110.33 (q,
J = 19.5 Hz, 1F), À61.33 (d, J = 19.5 Hz, 3F); (Z)-4Al: 1H NMR (CDCl3)
resulting solution was added dropwise benzyl a,b,g,g,g-penta-
d
3.70 (d, J = 4.0 Hz, 2H), 5.31 (s, 2H), 7.15 – 7.40 (m, 10H); 19F NMR
fluorocrotonate (1A, 0.050 g, 0.2 mmol) in THF (2.0 mL) via a
syringe at À78 8C. After being stirred at the same temperature for
1 h, the mixture was treated with iodine (0.241 g, 0.95 mmol) in
THF (2.0 mL) at À78 8C. After stirring at À78 8C for 1 h, the reaction
mixture was poured into an ice-cooled saturated aqueous NH4Cl
solution (30 mL), followed by extraction with Et2O (30 mL, 3
times). The organic layers were dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure with rotary
evaporator. Column chromatography of the residue using hexane/
(CDCl3)
(neat)
d
À109.8 to À109.7 (m, 1F), À59.10 (d, J = 9.8 Hz, 3F); IR
n
3066, 2962, 1742, 1686, 1497, 1455, 1347, 1264, 1184,
1077, 996 cmÀ1; HRMS (FAB) Calcd for (M+Na) C18H14F4O2Na:
361.0828, Found 361.0822.
4.6. Typical procedure for the preparation of benzyl
tetrafluoro- -isopropylcrotonate (4Ao)
a,g,g,g-
b
A 30 mL two-necked round-bottomed flask equipped with a
magnetic stirrer bar, a rubber septum, and an inlet tube for Ar was
benzene (2/1) yielded pure benzyl
tonate (4Aq, 0.058 g, 79%) as a sole product.
a,g,g,g-tetrafluoro-b-iodocro-

102
S. Yamada et al. / Journal of Fluorine Chemistry 149 (2013) 95–103
4.7.1. Benzyl (E)-
a
,
g
,
g
,
g
-tetrafluoro-
b
d
-iodocrotonate (4Aq)
5.35 (s, 2H), 7.35 – 7.50 (m,
À80.78 (q, J = 24.4 Hz, 1F), À58.25 (d,
J = 24.4 Hz, 3F); 13C NMR (CDCl3)
68.8, 74.0 (qd, J = 30.7, 11.6 Hz),
120.9 (q, J = 274.9 Hz), 128.7, 128.7, 129.0, 133.9, 150.9 (dq,
J = 294.1, 2.8 Hz), 158.5 (d, J = 33.6 Hz); IR (neat) 3069, 2962,
J = 24.4 Hz, 3F); IR (neat)
n
3035, 2960, 1736, 1498, 1364, 1284,
HRMS (FAB) Calcd for (M+)
Yield: 79% (oil); 1H NMR (CDCl3)
1260, 1172, 1133, 1004 cmÀ1
;
5H); 19F NMR (CDCl3)
d
C17H12F4O2: 324.0773, Found 324.0777.
d
References
n
[1] H. Amii, K. Uneyama, Chem. Rev. 109 (2009) 2119–2183.
[2] (a) For selective reports on the C-F bond cleavage of aryl fluorides using nickel
catalyst, see: J.W. Dankwardt, J. Organomet. Chem. 690 (2005) 932–938;
(b) N. Yoshikai, H. Mashima, E. Nakamura, J. Am. Chem. Soc. 127 (2005) 17978–
17979;
1743, 1627, 1498, 1312, 1237, 1187, 1147, 956 cmÀ1; HRMS (FAB)
Calcd for (M+) C11H7F4IO2: 373.9427, Found 373.9438; Anal. Calcd
for C11H7F4IO2: C, 35.32: H, 1.89, Found: C, 35.50: H, 1.92.
(c) K. Lamm, M. Stollenz, M. Meier, H. Go¨rls, D. Walther, J. Organomet. Chem. 681
(2003) 24–36;
(d) F. Mongin, L. Mojovic, B. Guillamet, F. Tre´court, G. Que´guiner, J. Org. Chem. 67
(2002) 8991–8994;
(e) T. Braun, R.N. Perutz, M.I. Sladek, Chem. Commun. (2001) 2254–2255;
(f) V.P.W. Bo¨hm, C.W.K. Gsto¨ttmayr, T. Weskamp, W.A. Herrmann, Angew. Chem.
Int. Ed. 40 (2001) 3387–3389;
(g) For selective reports on the C-F bond cleavage of aryl fluorides using palladi-
um catalyst, see: Y.M. Kim, S. Yu, J. Am, Chem. Soc. 125 (2003) 1696–1697;
(h) R. Wilhelm, D.A. Widdowson, J. Chem. Soc., Perkin Trans. 1 (2000) 3808–3813;
(i) For a report on the C-F bond cleavage of aryl fluorides using copper catalyst,
see: T.J. Korn, M.A. Schade, S. Wirth, P. Knochel, Org. Lett. 8 (2006) 725–728;
(j) For selective reports on the C-F bond cleavage of alkyl fluorides using transi-
tion metal catalyst, see: K. Fuchibe, T. Kaneko, K. Mori, T. Akiyama, Angew. Chem.
Int. Ed. 48 (2009) 8070–8073;
4.7.2. Benzyl (Z)-
b
-allyl-
a
,
g
,
g
,
g
-tetrafluorocrotonate (4Ak)
3.39 (dd, J = 2.5, 1.5 Hz, 2H),
Yield: 42% (oil); 1H NMR (CDCl3)
d
5.12 (dd, J = 10.0, 1.5 Hz, 1H), 5.14 (dd, J = 16.5, 1.5 Hz, 1H), 5.31 (s,
2H), 5.78 (dq, J = 16.5, 10.0 Hz, 1H), 7.34 – 7.44 (m, 5H); 19F NMR
(CDCl3)
d
À111.38 (q, J = 19.6 Hz, 1F), À62.10 (d, J = 19.6 Hz, 3F);
29.2 (q, J = 1.6 Hz), 68.1, 117.9, 121.4 (qd,
13C NMR (CDCl3)
d
J = 30.5, 5.8 Hz), 122.6 (q, J = 260.2 Hz), 128.5, 128.7, 128.9, 132.2
(d, J = 3.6 Hz), 134.3, 148.9 (dq, J = 281.4, 3.8 Hz), 159.3 (d,
J = 32.9 Hz); IR (neat)
1274, 1186, 1143, 1097, 968 cmÀ1; HRMS (EI) Calcd for (M+)
14H12F4O2: 288.0773, Found 288.0760.
n 3070, 2961, 1739, 1672, 1499, 1348,
C
(k) J. Terao, N. Kambe, Bull. Chem. Soc. Jpn. 79 (2006) 663–672;
(l) J. Terao, H. Watabe, N. Kambe, J. Am. Chem. Soc. 127 (2005) 3656–3657;
(m) J. Terao, S.A. Begum, A. Oda, N. Kambe, Synlett (2005) 1783–1786;
(n) J. Terao, H. Todo, H. Watanabe, A. Ikumi, N. Kambe, Angew. Chem. Int. Ed. 43
(2004) 6180–6182;
(o) J. Terao, A. Ikumi, H. Kuniyasu, N. Kambe, J. Am. Chem. Soc. 125 (2003)
5646–5647;
(p) For C-F bond cleavage of alkenyl fluorides using low-valent zirconocenes, see:
M. Fujiwara, J. Ichikawa, T. Okauchi, T. Minami, Tetrahedron Lett. 40 (1999)
7261–7265.
4.7.3. Benzyl (Z)-
Yield: 62% (oil); 1H NMR (CDCl3)
4.71 (brs, 1H), 4.86 (brs, 1H), 5.30 (s, 2H), 7.25 – 7.45 (m, 5H); 19
NMR (CDCl3)
À110.29 (q, J = 19.5 Hz, 1F), À62.25 (d, J = 19.5 Hz,
3F); 13C NMR (CDCl3)
22.5, 32.6 (q, J = 3.8 Hz), 68.1, 112.1, 121.4
a
,
g
,
g
,
g
-tetrafluoro-
b
d
-methayllylcrotonate (4Ar)
1.73 (s, 3H), 3.35 (brs, 2H),
F
d
d
(qd, J = 29.6, 5.7 Hz), 122.5 (q, J = 276.8 Hz), 128.5, 128.7, 128.8,
134.2, 130.4 (d, J = 3.5 Hz), 149.5 (dq, J = 279.4, 2.8 Hz), 159.3 (d,
[3] (a) G. Landelle, P.A. Champagne, X. Barbeau, J.F. Paquin, Org. Lett. 11 (2009) 681–684;
(b) F. Babudri, A. Cardone, L. De Cola, G.M. Farinola, G.S. Kottas, C. Martinelli, F. Naso,
Synthesis (2008) 1583–1588;
(c) J. Ichikawa, K. Sakoda, Y. Wada, Chem. Lett. (2002) 282–283;
(d) V.A. Petrov, C.G. Krespan, J. Fluorine Chem. 102 (2000) 199–204;
(e) X.-H. Huang, P.Y. He, G.Q. Shi., J. Org. Chem. 65 (2000) 627–629.
[4] (a) H. Ueki, T. Chiba, T. Yamazaki, T. Kitazume, Tetrahedron 61 (2005)
11141–11147;
J = 33.9 Hz); IR (neat)
n 3037, 2975, 1740, 1670, 1456, 1347, 1277,
1220, 1143, 1120, 969 cmÀ1; HRMS (EI) Calcd for (M+) C15H14F4O2:
302.0930, Found 302.0920.
4.7.4. Benzyl (Z)-
Yield: 58% (oil); 1H NMR (CDCl3)
(d, J = 6.2 Hz, 2H), 5.31 (s, 2H), 5.37 (dt, J = 16.0, 6.2 Hz, 1H), 5.56
b
-crotyl-
a
,g
,
g
,g
-tetrafluorocrotonate (4As)
d
1.65 (d, J = 6.4 Hz, 3H), 3.31
(b) J. Ichikawa, Y. Wada, M. Fujiwara, K. Sakoda, Synthesis (2002) 1917–1936;
(c) K.W. Chi, H.A. Kim, G.G. Furin, E.L. Zhuzhgov, N. Protzuk, J. Fluorine Chem. 110
(2001) 11–20;
(d) Y. Wada, J. Ichikawa, T. Katsume, T. Nohiro, T. Okauchi, T. Minami, Bull. Chem.
Soc. Jpn. 74 (2001) 971–977;
(dq, J = 16.0, 6.2 Hz, 1H), 7.35 – 7.45 (m, 5H); 19F NMR (CDCl3)
d
À112.42 (q, J = 18.8 Hz, 1F), À61.99 (d, J = 18.8 Hz, 3F); 13C NMR
(CDCl3)
d 17.8, 28.1 (q, J = 9.4 Hz), 68.0, 122.2 (qd, J = 29.6 Hz,
(e) J. Ichikawa, M. Fujiwara, Y. Wada, T. Okauchi, T. Minami, Chem. Commun.
(2000) 1887–1888;
4.9 Hz), 122.7 (q, J = 274.9 Hz), 124.6 (d, J = 3.6 Hz), 128.5, 128.7,
128.8, 129.0, 134.3, 148.4 (dq, J = 272.1 Hz, 3.6 Hz), 159.4 (d,
(f) P.L. Coe, J. Burdon, I.B. Haslock, J. Fluorine Chem. 102 (2000) 43–50.
[5] (a) A.V. Shastin, V.G. Nenajdenko, V.M. Muzalevskiy, E.S. Balenkova, R. Froehlich,
G. Haufe, Tetrahedron 64 (2008) 9725–9732;
J = 33.9 Hz); IR (neat)
n 3035, 2965, 1740, 1672, 1456, 1348, 1266,
1210, 1143, 1122, 1099, 967 cmÀ1; HRMS (EI) Calcd for (M+)
C15H14F4O2: 302.0930, Found 302.0935.
(b) J. Ichikawa, R. Nadano, T. Mori, Y. Wada, Org. Synth. 83 (2006) 111–120;
(c) C.M. Timperley, M.J. Waters, J.A. Greenall, J. Fluorine Chem. 127 (2006)
249–256;
(d) C.M. Timperley, J. Fluorine Chem. 125 (2004) 685–693.
[6] (a) H. Wojtzowicz-Rajchel, H. Koroniak, A. Katrusiak, Eur. J. Org. Chem. (2008)
368–376;
4.8. Typical procedure for Pd(0)-catalyzed Suzuki–Miyaura cross-
coupling of (E)-4Aq with PhB(OH)2
(b) J. Ichikawa, Y. Wada, H. Kuroki, J. Mihara, R. Nadano, Org. Biomol. Chem. 5
(2007) 3956–3962;
A 30 mL two-necked round-bottomed flask, equipped with a
magnetic stirrer bar, a rubber septum, and an inlet tube for Ar, was
charged with a suspension of 10 mol% of Pd(PPh3)4 and benzyl (E)-
(c) H. Wojtowicz-Rajchel, M. Migas, H. Koroniak, J. Org. Chem 71 (2006)
8842–8846;
(d) H. Koroniak, J. Walkowiak, K. Grys, A. Rajchel, A. Alty, R. Du Boisson, J. Fluorine
Chem. 127 (2006) 1245–1251;
(e) J. Ichikawa, K. Sakoda, H. Moriyama, Y. Wada, Synthesis (2006) 1590–1598;
(f) V.V. Rudyuk, D.V. Fedyuk, L.M. Yagupolskii, J. Fluorine Chem 125 (2004)
1465–1471;
(g) N.K. Park, B.T. Kim, S.S. Moon, S.L. Jeon, I.H. Jeong, Tetrahedron 60 (2004)
7943–7949;
a,g,g,g-tetrafluoro-b-iodocrotonate (4Aq, 0.050 g, 0.13 mmol) in
benzene (3.0 mL). To the suspension were added Na2CO3 (0.042 g,
0.40 mmol), PhB(OH)2 (0.097 g, 0.80 mmol), 0.30 mL each of H2O
and EtOH, and the whole was stirred at reflux temperature for 12 h.
The reaction mixture was poured into an ice-cooled saturated
aqueous NH4Cl solution (30 mL), followed by extraction with Et2O
(30 mL, 3 times each). The organic layers were dried over
anhydrous Na2SO4, filtered, and concentrated in vacuo. Column
chromatography of the residue using hexane/benzene (2/1)
(h) J. Ichikawa, Y. Wada, H. Miyazaki, T. Mori, H. Kuroki, Org. Lett 5 (2003)
1455–1458.
[7] (a) For Diels-Alder reaction with dienes, see F. Chanteau, M. Essers, R. Plantier-
Royon, G. Haufe, C. Portella, Tetrahedron Lett. 43 (2002) 1677–1680;
(b) T. Umemoto, Y. Kuriu, S.I. Nakayama, O. Miyano, Tetrahedron Lett. 23 (1982)
1471–1474;
(c) For Michael-type addition reaction with organocopper reagents, see K. Sano,
T. Fukuhara, S. Hara, J. Fluorine Chem. 139 (2009) 708–713;
(d) J. Ichikawa, N. Yokota, M. Kobayashi, T. Minami, Synlett (1993) 186–188;
(e) For the synthesis of fluorine-containing heterocyclic compounds, see J.T. Liu,
H.J. Lu, Chin. J. Chem, 20 (2002) 1330–1333;
(f) J.T. Liu, H.J. Lu, J. Fluorine Chem 111 (2001) 207–212;
(g) J. Ichikawa, M. Kobayashi, Y. Noda, N. Yokota, K. Amano, T. Minami, J. Org.
Chem 61 (1996) 2763–2769;
yielded pure benzyl (Z)-
(4Aa, 0.016 g, 39%) as a pure compound.
a,g,g,g-tetrafluoro-b-phenylcrotonate
4.8.1. Benzyl (Z)-
Yield: 39% (oil); 1H NMR (CDCl3)
10H); 19F NMR (CDCl3)
À108.66 (q, J = 24.4 Hz, 1F), À60.98 (d,
a
,g
,g
,
g-tetrafluoro-
b
-phenylcrotonate (4Aa)
d
5.03 (s, 2H), 7.30 – 7.45 (m,
d

S. Yamada et al. / Journal of Fluorine Chemistry 149 (2013) 95–103
103
(h) T. Ishihara, Y. Yamasaki, T. Ando, Tetrahedron Lett. 27 (1986) 2879–2880;
(i) D.C. England, J.S. Piecara, J. Fluorine Chem. 28 (1985) 417–423.
[8] (a) For selected reports on applications of organofluorine compounds, see: J.P.
Be´gue´, D. Bonnet-Delpon, J. Fluorine Chem. 127 (2006) 992–1012;
(b) C. Isanbor, D. O’Hagen, J. Fluorine Chem. 127 (2006) 303–319;
(c) K. Morimoto, M. Irie, Chem. Commun. (2005) 3895–3905;
(d) R. Miethchen, J. Fluorine Chem. 125 (2004) 895–901.
[15] The formation of the homo-coupling product could be explained by a competitive
reductive elimination step of the divinylcuprate formed after transmetallation.
The similar results were reported in the following paper, see: J. Thibonnet, A.
Ducheˆne, J.L. Parrain, M. Abarbri, J. Org. Chem, 69 (2004) 4262–4264.
[16] Suzuki-Miyaura cross-coupling was conducted according to reported procedure
with a similar substrate, see: T. Konno, T. Takehana, J. Chae, T. Ishihara, H.
Yamanaka, J. Org. Chem. 69 (2004) 2188–2190.
[9] (a) For the reaction of perfluorocyclopentene, see: S. Yamada, E. Ishii, T. Konno, T.
Ishihara, Tetrahedron, 64 (2008) 4215–4223;
[17] (a) For related reports on p-complex between transition metal and polyfluori-
nated alkenes, see: T. Braun, D. Noveski, B. Neumann, H.G. Stammler, Angew.
Chem. Int. Ed. 41 (2002) 2745–2748;
(b) S. Yamada, E. Ishii, T. Konno, T. Ishihara, Org. Biomol. Chem. 5 (2007) 1442–1449;
(c) S. Yamada, T. Konno, T. Ishihara, H. Yamanaka, J. Fluorine Chem. 126 (2005)
125–133;
(b) M. Fujiwara, J. Ichikawa, T. Okauchi, T. Minami, Tetrahedron Lett. 40 (1999)
7261–7265;
(d) For the reaction of a,b,b-trifluoroacrylic ester, see: S. Yamada, M. Noma, K. Hondo,
T. Konno, T. Ishihara, J. Org. Chem. 73 (2008) 522–528;
(e) S. Yamada, M. Noma, T. Konno, T. Ishihara, H. Yamanaka, Org. Lett. 8 (2006)
843–845;
(c) A.R. Siedle, R.A. Newmark, Organomet. 8 (1989) 1442–1450.
[18] (a) For related reports on the interaction between metal and fluorine atom, see: T.
Yamazaki, J. Synth. Org. Chem. Jpn. 62 (2004) 911–918;
(b) T. Ishihara, J. Synth Org. Chem. Jpn. 57 (1999) 313–322;
(c) T. Ooi, K. Furuta, K. Maruoka, Chem. Lett. (1998) 817–818;
(d) T. Ooi, N. Kagoshima, D. Uraguchi, K. Maruoka, Tetrahedron Lett. 39 (1998)
7105–7108;
(e) T. Ooi, N. Kagoshima, K. Maruoka, J. Am. Chem. Soc. 119 (1997) 5754–5755;
(f) T. Ooi, D. Uraguchi, N. Kagoshima, K. Maruoka, Tetrahedron Lett. 38 (1997)
5679–5682;
(g) T. Yamazaki, T. Kitazume, J. Synth. Org. Chem. Jpn. 54 (1996) 665–674;
(h) T. Yamazaki, N. Shinohara, T. Kitazume, S. Sato, J. Org. Chem. 60 (1995)
8140–8141;
(f) For the reaction of a,b,b-trifluorovinyl sulfone, see: S. Yamada, K. Shimoji, T.
Takahashi, T. Konno, T. Ishihara, Chem. Asian J. 5 (2010) 1846–1853.
[10] S. Yamada, T. Takahashi, T. Konno, T. Ishihara, Chem. Commun. (2007) 3679–3681.
[11] (a) T. Ishihara, T. Maekawa, Y. Yamasaki, T. Ando, J. Fluorine Chem. 34 (1987)
323–335;
(b) T. Ishihara, Y. Yamasaki, T. Ando, Tetrahedron Lett. 27 (1986) 2879–2880.
[12] We revealed that the addition-elimination products were formed as a sole
product when a,b,b-trifluoroacrylate was treated with Grignard reagents in
the presence of Cu(I) salt, see: refs. [9d] and [9e].
[13] It was expected that the reductive elimination of R-CuX was promoted by the
addition of Lewis base like HMPA, DMF and TMSCl.
(i) T. Hanamoto, T. Fuchikami, J. Org. Chem. 55 (1990) 4969–4971.
[19] (a) T. Yamazaki, N. Shinohara, T. Kitazume, S. Sato, J. Fluorine Chem. 97 (1999)
91–96;
(b) T. Yamazaki, H. Umetani, T. Kitazume, Israel J. Chem. 39 (1999) 193–205;
(c) T. Yamazaki, H. Umetani, T. Kitazume, Tetrahedron Lett. 38 (1997) 6705–6708.
[20] The addition-elimination product observed in some cases might be formed due to
the high migration abilities of electron-rich aryl and alkyl groups.
[14] (a) For related reports on the preparation of organocopper reagents by the
treatment of organozinc reagents with CuCNꢀ2LiCl, see: M.J. Rozema, S.
AchyuthaRao, P. Knochel, J. Org. Chem. 57 (1992) 1956–1958;
(b) S. AchyuthaRao, P. Knochel, J. Am. Chem. Soc. 113 (1991) 5735–5741;
(c) P. Knochel, M.C.P. Yeh, S.C. Berk, J. Talbert, J. Org. Chem. 53 (1988) 2390–2392.