Unexpected high regiocontrol in Heck reaction of fluorine-containing electron-deficient olefins-Highly regio- and stereoselective synthesis of β-fluoroalkyl-α-aryl-α,β-unsaturated ketones

Article abstract of DOI:10.1016/j.jfluchem.2009.07.002

Treatment of (E)-4,4,4-trifluoro-1-aryl-2-buten-1-one with various aryldiazonium salts in the presence of palladium catalyst gave the corresponding α-arylated Heck adducts with high regio- and stereoselectivity in good to high yields.

Full text of DOI:10.1016/j.jfluchem.2009.07.002

Journal of Fluorine Chemistry 130 (2009) 913–921
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Unexpected high regiocontrol in Heck reaction of fluorine-containing
electron-deficient olefins—Highly regio- and stereoselective synthesis
of
b-fluoroalkyl-a-aryl-a,b-unsaturated ketones
*
Tsutomu Konno , Shigeyuki Yamada, Akinori Tani, Masataka Nishida,
Tomotsugu Miyabe, Takashi Ishihara
Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
Treatment of (E)-4,4,4-trifluoro-1-aryl-2-buten-1-one with various aryldiazonium salts in the presence
Received 17 June 2009
Received in revised form 3 July 2009
Accepted 4 July 2009
of palladium catalyst gave the corresponding
stereoselectivity in good to high yields.
a
-arylated Heck adducts with high regio- and
ß 2009 Elsevier B.V. All rights reserved.
Available online 30 July 2009
Keywords:
Fluorine-containing alkenes
Heck reaction
Aryldiazonium salts
b
-Fluoroalkyl-
Regioselective
Stereoselective
a,b-unsaturated ketones
1. Introduction
b
-fluoroalkylated-
via a highly regio- and stereoselective Heck reaction of
fluoroalkylated- -unsaturated carbonyl compounds with var-
a-aryl-a,b-unsaturated carbonyl compounds
b-
Recently, considerable interest has been focused on organo-
fluorine compounds as pharmaceutical and agrochemical agents
because the fluorine atom often alters the physiochemical
properties of organic compounds, thereby modifying biological
activities [1a-h]. Consequently, the development of novel and
convenient methods for the preparation of fluorine-containing
materials has been becoming more and more important in fluorine
chemistry [2a-i].
Among various types of fluoroorganic molecules, alkenes 1
bearing a fluoroalkyl group (Rf) and an electron-withdrawing
group (EWG) (Fig. 1) have been well known as one of the most
valuable synthetic targets because they have wide utility as potent
synthetic blocks, particularly as Michael acceptors for conjugate
additions [3a-i], or dienophiles and dipolarophiles for cycloaddi-
tion reactions [4a-d]. In spite of such great utility, there have been
somewhat limited studies on the stereoselective synthesis of such
molecules, especially tri- or tetra-substituted alkenes thus far [5a-
l]. Herein is described a novel and convenient synthesis of
a,b
ious aryldiazonium salts [6a-d].
2. Results and discussion
Our initial studies were addressed to the Heck reaction of (E)-
4,4,4-trifluoro-1-phenyl-2-buten-1-one (2a) with phenyldiazo-
nium salt 3a (Scheme 1, Table 1, Ar = Ph). Thus, treatment of 2a
with 1.2 equiv. of 3a in the presence of 2.5 mol% of Pd2(dba)3ÁCHCl3
in THF at 40 8C for 2 h gave the corresponding a-arylated adduct 4a
in 4% yield, together with 90% of the starting material recovered
(entry 1). In this case, only Z isomer 4aZ was detected and neither E
isomer 4aE nor b-arylated product 6 was obtained [7]. As shown in
entries 2–5, various sorts of solvents, such as toluene, 1,4-dioxane,
ether, and methanol, did not lead to the satisfactory results (no
reaction or low regioselectivity), however, the use of ethanol
resulted in the formation of 9% of 4a as a sole product (entry 6).
Therefore, we next examined the reaction conditions in THF or
EtOH. As described in entries 7–10, the addition of various types of
phosphine ligands did not improve the yield in the reaction in THF.
On the other hand, the reaction at the reflux temperature of THF
afforded the Heck adducts 4aZ and 4aE in a ratio of 92:8 in 24%
* Corresponding author.
E-mail address: konno@chem.kit.ac.jp (T. Konno).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.07.002

914
T. Konno et al. / Journal of Fluorine Chemistry 130 (2009) 913–921
reaction to give the corresponding adducts in good yields. In these
cases, high Z stereoselection was observed. When the reaction was
carried out in THF at the reflux temperature, a slight decrease of the
yield as well as the stereoselectivity was detected (entries 4 and 6).
Very interestingly, the Heck reaction with ortho-tolyl (3d) or para-
anisyldiazonium salt (3e) in THF at the refluxing temperature took
place smoothly to afford the corresponding Heck adducts in 75 or
71% yield, respectively (entries 8 and 10), whereas the reactions in
EtOH at 40 8C resulted in very low yield of the products (entries 7
and 9). As indicated in entries 11–16, various halogen-substituted
aryldiazonium salts (3f, 3g, and 3h) were applied for the Heck
reaction successfully, giving the desired products in 62–74% yields
with high Z stereoselection, though ca. 10–20% of Michael adducts
Fig. 1. Fluoroalkylated alkenes.
combined yield (entry 11). Though the prolonged reaction time as
well as the use of 2.2 equiv. of 3a did not bring about a significant
change (entries 12 and 13), the reaction with 2.2 equiv. of 3a in the
presence of 20 mol% of palladium catalyst gave 4aZ and 4aE in 61%
yield (entry 14). Additionally, the reaction with 4.4 equiv. of 3a at
the reflux temperature caused a significant improvement of the
yield, 4aZ and 4aE being obtained in 79% yield in a ratio of 90:10
(entry 16).
We also investigated the reaction in EtOH as shown in entries
17–21. In sharp contrast to the reaction in THF, the ligand effect
was observed significantly. Thus, when P(o-Tol)3 was used, the
starting material was completely consumed and the corresponding
arylated adducts 4aZ and 4aE were obtained in 82% yield in a ratio
of 94:6 (entry 19), though the Michael adduct 5a was also given as
a byproduct. Additionally, bulky or bidentate ligands resulted in a
significant decrease of the yield (entries 20 and 21). With this best
reaction conditions (entries 16 and 19), we conducted the Heck
reaction with various types of aryldiazonium salts. The results are
summarized in Table 2.
5
were given as byproducts. However, aryldiazonium salt
substituted by more strongly electron-withdrawing group, such
as cyano (3i), ethoxycarbonyl (3j), and nitro groups (3k), on the
benzene ring, did not lead to the satisfactory results in the reaction
in EtOH at 40 8C, the starting substrate 2 being almost quantita-
tively recovered (entries 17, 19, and 21). Interestingly, the reaction
with CO2Et-substituted aryldiazonium salt in THF at the reflux
temperature gave the Heck adducts 4jZ and 4jE in 64% yield in a
ratio of 80:20 (entry 20). On the other hand, the reaction with the
CN- or NO2-substituted aryldiazonium salts in THF did not lead to a
dramatical change. (entries 18, 22 and 23). Additionally, 1-
naphthyldiazonium salt (3l) could not also be applied for the
present Heck reaction successfully (entries 24 and 25).
Next, our interest was directed toward the Heck reaction using
various types of fluorine-containing electron-deficient olefins as
shown in Table 3.
As shown in entries 3 and 5, para- and meta-substituted
aryldiazonium salts (3b and 3c) could participate well in the Heck
As described in entries 3, 4, 7, and 8, various enones having an
electron-donating group (MeO) or an electron-withdrawing group
Scheme 1.
Table 1
Investigation of the reaction conditions (Ar = Ph).
Entry
X/equiv.
Catalyst
Y/mol%
Solvent
Yielda/% of 4a
Ratioa (4aZ:4aE)
Yielda/% of 5a
Recoverya/% of 2a
1
2
3
4
5
6
1.2
1.2
1.2
1.2
1.2
1.2
[1/2][Pd2(dba)3ÁCHCl3]
[1/2][Pd2(dba)3ÁCHCl3]
[1/2][Pd2(dba)3ÁCHCl3]
[1/2][Pd2(dba)3ÁCHCl3]
[1/2][Pd2(dba)3ÁCHCl3]
[1/2][Pd2(dba)3ÁCHCl3]
5
5
5
5
5
5
THF
4
100:0
–
0
0
2
0
0
3
90
97
67
89
35
90
Toluene
1,4-Dioxane
Ether
0
10
0
80:20
–
MeOH
EtOH
10
9
80:20
100:0
7
8
1.2
1.2
1.2
1.2
1.2
1.2
2.2
2.2
3.3
4.4
[1/2][Pd2(dba)3ÁCHCl3] + 2PPh3
[1/2][Pd2(dba)3ÁCHCl3] + 2P(o-Tol)3
[1/2][Pd2(dba)3ÁCHCl3] + 2PCy3
[1/2][Pd2(dba)3ÁCHCl3] + dppe
[1/2][Pd2(dba)3ÁCHCl3]
5
5
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
0
–
0
0
Quant.
93
0
–
9
5
2
100:0
–
0
85
10
5
0
0
Quant.
59
11b
12b,c
13b
14b
15b
16b
5
24
28
8
92:8
75:25
88:12
82:18
83:17
90:10
4
[1/2][Pd2(dba)3ÁCHCl3]
5
9
71
[1/2][Pd2(dba)3ÁCHCl3]
5
2
90
[1/2][Pd2(dba)3ÁCHCl3]
20
20
20
61
63
79
12
12
11
17
[1/2][Pd2(dba)3ÁCHCl3]
22
[1/2][Pd2(dba)3ÁCHCl3]
2
17
18
19
20
21
2.2
2.2
2.2
2.2
2.2
[1/2][Pd2(dba)3ÁCHCl3]
20
20
20
20
20
EtOH
EtOH
EtOH
EtOH
EtOH
51
92:8
3
7
32
36
0
[1/2][Pd2(dba)3ÁCHCl3] + 2PPh3
[1/2][Pd2(dba)3ÁCHCl3] + 2P(o-Tol)3
[1/2][Pd2(dba)3ÁCHCl3] + 2PCy3
[1/2][Pd2(dba)3ÁCHCl3] + dppe
45
93:7
82 (69)
47
94:6
11
4
89:11
88:12
33
76
17
0
a
Determined by 19F NMR. Value in parentheses is of isolated yield.
Carried out at the reflux temperature.
Carried out for 12 h.
b
c

T. Konno et al. / Journal of Fluorine Chemistry 130 (2009) 913–921
915
Table 2
The Heck reaction with various types of aryldiazonium salts.
Entry
Diazonium salt
Methoda
Yieldb/% of 4
Ratiob (4Z:4E)
Yieldb/% of 5
1
2
A
B
82 (69)
79
94:6
11
11
90:10
3
4
A
B
57 (48)
35
93:7
10
9
86:14
5
6
A
B
73 (57)
48
95:5
9
88:12
10
7
8
A
B
9
44:56
48:52
0
6
75 (63)
9
A
B
5
100:0
92:8
4
10
71 (55)
17
11
12
A
B
74 (58)
69
89:11
80:20
15
13
13
14
A
B
67 (50)
68
89:11
79:21
10
19
15
16
A
B
65 (54)
62
88:12
79:21
12
19
17
18
A
B
0
0
–
–
0
Trace
19
20
A
B
28
86:16
80:20
6
64 (63)
15
21
22
23
A
B
C
11
38
41
100:0
69:31
73:27
0
11
10
24
25
A
B
23
36
88:17
58:42
0
9
a
Method A: 2, 2.2 equiv., EtOH, 40 8C, 2 h; Method B: 2, 4.4 equiv., THF, reflux, 2 h; Method C: 2, 4.4 equiv., THF, reflux, 10 h.
Determined by 19F NMR. Values in parentheses are of isolated yield.
b

916
T. Konno et al. / Journal of Fluorine Chemistry 130 (2009) 913–921
Table 3
The Heck reaction of various substrates with phenyldiazonium salt.
Entry
Substrate
Methoda
Product
Yieldb/% of 4
Ratioa (Z:E)
Yieldb/% of 5
Recoveryb/% of 2
1
2
R = Ph (a)
Ac
Bd
A
B
82 (69)
79
94:6
11
11
6
0
90:10
94:6
2
3
R = p-MeOC6H4 (m)
R = o-MeOC6H4 (n)
R = p-ClC6H4 (o)
R = 1-Naphthyl (p)
R = PhCH2CH2 (q)
R = c-Hex (r)
36
36
17
Trace
0
4
69 (55)
90 (86)
87
93:7
14
6
5
A
B
86:14
79:21
93:7
6
11
7
7
A
B
41
50
10
39
10
42
23
27
9
8
70 (62)
46
81:19
90:10
85:15
71:29
59:41
77:23
71:29
19
8
9
A
B
10
11
12
13
14
72 (48)
14
6
A
B
4
41
10
10
10
A
B
61
80 (68)
15
16
A
B
13
26
N.D.e
97:3
6
8
81
66
17
18
A
B
0
0
–
–
3
5
76
68
19
20
A
B
4
0
–
–
3
3
76
97
21
22
A
B
1
0
–
–
0
0
22
17
23
24
A
B
39
12
81:19
N.D.e
2
5
18
15
a
Method A: 3a, 2.4 equiv., EtOH, 40 8C, 2 h; Method B: 3a, 4.8 equiv., THF, reflux, 2 h.
Determined by 19F NMR. Values in parentheses are of isolated yield.
2.2 equiv. of PhN2BF4 was used.
b
c
d
e
4.4 equiv. of PhN2BF4 was used.
Not determined.
(Cl) on the benzene ring in 2 could participate nicely in the Heck
reaction to give the corresponding adducts 4m, 4o with high regio-
and stereoselectivity in good yields. In these cases, the reaction at
the reflux temperature in THF (Method B) gave better results in the
chemical yield as well as the stereoselectivity than the reaction at
40 8C in EtOH (Method A). Ortho substitution on the benzene ring
in 2 also led to satisfactory results on both Methods A and B, though
a slight decrease of the stereoselectivity was observed (entries 5
and 6). A naphthyl group was also found to be a good substituent
(entries 9 and 10), but the use of alkyl substituent as R resulted in a
significant decrease of the stereoselectivity (entries 11–14). In the
case of 2-phenylethyl substituent as R, the chemical yield was also
decreased significantly.
changing a fluoroalkyl group from a CF3 to CHF2 group caused a
significant decrease of the chemical yield (entries 23 and 24),
although the relatively high regioselectivity was obtained.
The reaction mechanism may be proposed as shown in
Scheme 2. Thus, the reaction presumably proceeds via (1) oxidative
addition of aryldiazonium salt
3 to Pd(0), leading to the
corresponding arylpalladium complex Int-A, (2) coordination of
the fluorine-containing electron-deficient olefin 2 to the metal
center of Int-A and subsequent insertion into the Ar–Pd bond to
form Int-B, not Int-C, (3) carbon–carbon bond rotation to produce
Int-D, and (4) reductive elimination to give tri-substituted alkene 4
and to regenerate Pd(0).
The high regioselectivity may be attributed to a bulkiness of a
CF3 group [12]. Generally, migration of an aryl group in the
insertion step of the alkene into the Ar–Pd bond favors the less
We also examined the reaction of other fluorine-containing
electron-deficient olefins as described in entries 15–22. Similar to
the precedent work [6c],
a
,
b
-unsaturated ester 2s did not react
substituted carbon with lower electron density, therefore b-
with phenyldiazonium salt smoothly, giving the corresponding
adduct 4s in very low yield, together with a large amount of the
starting ester [8]. Vinylphosphonate (2t) [9] and vinylsulfone (2u)
[10] were also found to be very less reactive, only the starting
olefins being recovered. In the case of nitroalkene (2v) [11a-b],
neither the starting material nor the desired Heck adduct was
detected, and the complex mixture was observed. Additionally,
arylation occurs in the Heck reaction of ethyl acrylate, acrylonitrile,
styrene, etc. In the present reaction, a COR group is a stronger
electron-withdrawing group than a CF3 group whereas a CF3 group
is much bulkier than a COR group. Thus,
a-arylation in this study
indicates that the steric hindrance of the substituent is a very
important factor for determining the regioselectivity, rather than
an electron-withdrawing effect.

T. Konno et al. / Journal of Fluorine Chemistry 130 (2009) 913–921
917
CDCl3 solution with internal CFCl3 too. CFCl3 was used (
d
F = 0) as an
internal standard for 19F NMR. Infrared spectra (IR) were recorded
on a Shimadzu FTIR-8200A (PC) spectrophotometer. Mass spectra
(MS) were taken on a JEOL JMS-700.
4.1.1. Materials
Anhydrous tetrahydrofuran (THF) was purchased from Wako
Pure Chemical Industries, Ltd. Ethanol was distilled from
magnesium. All chemicals were of reagent grade and, if necessary,
were purified in the usual manner prior to use. Thin layer
chromatography (TLC) was done with Merck silica gel 60F254 plates
and column chromatography was carried out with Wako gel C-200.
All aryldiazonium salts were prepared according to the literature
[13a-e].
4.2. Typical procedure for the preparation of 4,4,4-trifluoro-2-(4-
fluorophenyl)-1-phenyl-2-buten-1-one
Method A: To a solution of Pd2(dba)3ÁCHCl3 (10 mol%) and P(o-
Tol)3 (40 mol%) in EtOH was added (E)-4,4,4,-trifluoro-1-phenyl-2-
buten-1-one (2) (50 mg, 0.25 mmol) and 4-fluorophenyldiazo-
nium tetrafluoroborate (3f) (115 mg, 0.55 mmol) at room tem-
perature, and the resulting mixture was stirred at 40 8C for 2 h.
After cooling to room temperature, the mixture was poured into a
saturated aqueous NH4Cl solution, and the resulting mixture was
extracted three times with Et2O. The combined organic layers were
washed with a saturated solution of NaCl, dried over anhydrous
Na2SO4, filtered, and concentrated in vacuo. The residue was
purified by silica-gel column chromatography to give the
corresponding Heck adduct (4f) (43 mg, 0.45 mmol: Z/E = 89:11;
58% yield).
Method B: The reaction with 4.4 equiv. of the corresponding
diazonium salt in the presence of Pd2(dba)3ÁCHCl3 (10 mol%) in
THF at reflux temperature for 2 h was conducted. The workup was
the same as Method A.
Scheme 2. A plausible mechanism.
4.2.1. 4,4,4-Trifluoro-1,2-diphenyl-2-buten-1-one (4a)
IR (neat) 3063, 2930, 1678, 1597, 1580, 1496, 1449, 1354, 1279,
1219, 1134, 1015 cmÀ1
.
3. Conclusion
HRMS (FAB) calcd for (M+H) C16H12F3O 277.0841; found:
277.0853.
Z isomer: 1H NMR (CDCl3)
(m, 7H), 7.53–7.61 (m, 1H), 7.90–7.96 (m, 2H); 13C NMR (CDCl3)
= 115.67 (q, J = 34.9 Hz), 122.4 (q, J = 271.0 Hz), 126.6, 128.8,
129.2, 129.5, 130.3, 133.8, 134.2, 135.2, 149.6 (q, J = 5.4 Hz), 194.2;
19F NMR (CDCl3, CFCl3)
= À59.1 (d, J = 8.1 Hz, 3F).
E isomer: 1H NMR (CDCl3)
= 6.10 (q, J = 7.9 Hz, 1H), 7.35–7.50
(m, 7H), 7.53–7.61 (m, 1H), 7.90–7.96 (m, 2H); 19F NMR (CDCl3,
CFCl3)
= À57.3 (d, J = 7.9 Hz, 3F).
In summary, we have developed an easy access to a variety of
-fluoroalkylated- -aryl- -unsaturated carbonyl compounds
d = 6.22 (q, J = 8.1 Hz, 2H), 7.35–7.50
b
a
a,b
via a regio- and stereoselective Heck reaction with readily
available aryldiazonium salts. Various aryldiazonium salts bear-
ing an electron-donating group and halogens at the para, meta or
ortho position of the benzene ring could participate nicely in the
Heck reaction, the corresponding Z isomer being given preferen-
tially. On the other hand, aryldiazonium salts having an electron-
withdrawing group or bulky salts did not afford the satisfactory
results. Additionally, we also found that the electron-with-
drawing group (EWG) influenced largely on the efficacy of the
reaction.
d
d
d
d
4.2.2. 4,4,4-Trifluoro-2-(4-methylphenyl)-1-phenyl-2-buten-1-one
(4b)
IR (neat) 3069, 2924, 1679, 1513, 1450, 1353, 1286, 1220, 1128,
1015 cmÀ1
.
4. Experimental
HRMS (FAB) calcd for (M+H) C17H14F3O 291.0997; found:
291.1003.
Z isomer: M.p. 74–76 8C; 1H NMR (CDCl3)
d = 2.34 (s, 3H), 6.19
4.1. General methods
(q, J = 8.1 Hz, 1H), 7.18 (ABq, J = 8.2 Hz, 2H), 7.32 (ABq, J = 8.2 Hz,
2H), 7.43–7.60 (m, 1H), 7.90–7.96 (m, 2H); 13C NMR (CDCl3)
1H NMR spectra were measured with
a
Bruker DRX
(500.13 MHz) spectrometer in a chloroform-d (CDCl3) solution
with tetramethylsilane (Me4Si) as an internal reference. 13C NMR
spectra were recorded on a Bruker DRX (125.77 MHz). A JEOL JNM-
d
= 21.2, 114.6 (q, J = 35.1 Hz), 122.5 (q, J = 271.0 Hz), 126.5, 128.8,
129.48, 129.9, 133.8, 134.1, 135.3, 140.7, 149.5 (q, J = 5.0 Hz),
194.5; 19F NMR (CDCl3, CFCl3)
= À58.9 (d, J = 8.1 Hz, 3F).
E isomer: 1H NMR (CDCl3)
= 2.35 (s, 3H), 6.05 (q, J = 7.9 Hz, 1H),
d
EX90F (84.21 MHz, FT) or
a
JEOL JNM-AL400 (376.05 MHz)
d
spectrometer was used for determining 19F NMR yield with
internal C6F6. It was used for determining regioselectivity and
stereoselectivity and was used for taking 19F NMR spectra in a
7.18 (ABq, J = 8.2 Hz, 2H), 7.32 (ABq, J = 8.2 Hz, 2H), 7.43–7.60 (m,
1H), 7.90–7.96 (m, 2H); 19F NMR (CDCl3, CFCl3)
J = 7.9 Hz, 3F).
d
= À57.2 (d,

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T. Konno et al. / Journal of Fluorine Chemistry 130 (2009) 913–921
4.2.3. 4,4,4-Trifluoro-2-(3-methylphenyl)-1-phenyl-2-buten-1-one
(4c)
4.2.7. 2-(4-Chlorophenyl)-4,4,4-trifluoro-1-phenyl-2-buten-1-one
(4g)
IR (neat) 3062, 2924, 1681, 1597, 1450, 1347, 1288, 1264, 1231,
IR (neat) 3067, 2928, 1678, 1595, 1493, 1450, 1347, 1284, 1219,
1137, 1015 cmÀ1
.
1134, 1038 cmÀ1
.
HRMS (FAB) calcd for (M+H) C17H14F3O 291.0997; found:
291.0990.
Z isomer: 1H NMR (CDCl3)
7.19–7.28 (m, 4H), 7.42–7.48 (m, 2H), 7.55–7.60 (m, 1H), 7.91–7.96
(m, 2H); 13C NMR (CDCl3)
= 21.4, 115.5 (q, J = 34.8 Hz), 122.4 (q,
HRMS (FAB) calcd for (M+H) C16H11ClF3O 311.0451; found:
311.0451.
Z isomer: 1H NMR (CDCl3)
(m, 4H), 7.44–7.50 (m, 2H), 7.57–7.62 (m, 1H), 7.89–7.93 (m, 2H);
13C NMR (CDCl3)
= 116.1 (q, J = 35.3 Hz), 122.2 (q, J = 271.1 Hz),
d
= 2.34 (s, 3H), 6.20 (q, J = 8.1 Hz, 1H),
d = 6.17 (q, J = 7.9 Hz, 1H), 7.33–7.40
d
d
J = 270.9 Hz), 123.8, 127.1, 128.8, 129.1, 129.5, 131.1, 133.7, 134.1,
135.2, 139.1, 149.8 (q, J = 5.3 Hz), 194.3; 19F NMR (CDCl3, CFCl3)
128.0, 128.9, 129.48, 129.51, 130.0, 134.1, 134.4, 135.0, 136.6,
148.5 (q, J = 5.5 Hz), 193.9; 19F NMR (CDCl3, CFCl3)
J = 7.9 Hz, 3F).
d
= À59.2 (d,
d
= À59.1 (d, J = 8.1 Hz, 3F).
E isomer: 1H NMR (CDCl3)
d
= 2.34 (s, 3H), 6.06 (q, J = 7.9 Hz, 1H),
E isomer: 1H NMR (CDCl3)
d
= 6.13 (q, J = 7.8 Hz, 1H), 7.33–7.40
(m, 4H), 7.44–7.50 (m, 2H), 7.57–7.62 (m, 1H), 7.89–7.93 (m, 2H);
19F NMR (CDCl3, CFCl3)
= À57.4 (d, J = 7.8 Hz, 3F).
7.19–7.28 (m, 4H), 7.42–7.48 (m, 2H), 7.55–7.60 (m, 1H), 7.91–7.96
(m, 2H); 19F NMR (CDCl3, CFCl3)
= À57.8 (d, J = 7.9 Hz, 3F).
d
d
4.2.4. 4,4,4-Trifluoro-2-(2-methylphenyl)-1-phenyl-2-buten-1-one
(4d)
4.2.8. 2-(4-Bromophenyl)-4,4,4-trifluoro-1-phenyl-2-buten-1-one
(4h)
IR (neat) 3064, 2920, 1674, 1597, 1449, 1346, 1278, 1252, 1141,
IR (neat) 3066, 1678, 1596, 1489, 1345, 1285, 1138, 1074,
1012 cmÀ1
.
1012 cmÀ1
.
HRMS (FAB) calcd for (M+H) C17H14F3O 291.0997; found:
291.0987.
Z isomer: 1H NMR (CDCl3)
1H), 7.13–7.35 (m, 4H), 7.43–7.65 (m, 3H), 7.89–7.99 (m, 2H);
13C NMR (CDCl3)
= 20.4, 120.5 (q, J = 34.9 Hz), 122.0 (q,
HRMS (FAB) calcd for (M+H) C16H11BrF3O 354.9946; found:
354.9930.
Z isomer: 1H NMR (CDCl3)
(m, 2H), 7.43–7.55 (m, 4H), 7.58–7.62 (m, 1H), 7.89–7.92 (m, 2H);
13C NMR (CDCl3)
= 116.1 (q, J = 35.5 Hz), 122.6 (q, J = 271.1 Hz),
124.9, 128.2, 128.9, 129.5, 132.5, 134.1, 135.0, 148.6 (q, J = 5.1 Hz),
193.8; 19F NMR (CDCl3, CFCl3)
= À59.2 (d, J = 7.9 Hz, 3F).
E isomer: 1H NMR (CDCl3)
= 6.13 (q, J = 7.8 Hz, 1H), 7.28–7.32
(m, 2H), 7.43–7.55 (m, 4H), 7.58–7.62 (m, 1H), 7.89–7.92 (m, 2H);
19F NMR (CDCl3, CFCl3)
= À57.4 (d, J = 7.8 Hz, 3F).
d
= 2.51 (s, 3H), 5.98 (q, J = 8.0 Hz,
d = 6.21 (q, J = 7.9 Hz, 1H), 7.28–7.32
d
d
J = 271.2 Hz), 149.4 (q, J = 5.1 Hz), 193.7. The peak of aromatic
carbon could not be identified; 19F NMR (CDCl3, CFCl3)
(d, J = 8.0 Hz, 3F).
d
= À59.7
d
d
E isomer: 1H NMR (CDCl3)
d
= 2.28 (s, 3H), 6.38 (q, J = 7.6 Hz, 1H),
7.13–7.35 (m, 4H), 7.43–7.65 (m, 3H), 7.89–7.99 (m, 2H); 13C NMR
(CDCl3) = 20.1, 121.1 (q, J = 26.7 Hz), 122.3 (q, J = 272.9 Hz), 149.9
(q, J = 4.8 Hz), 194.1. The one signal of aromatic carbon could not be
identified; 19F NMR (CDCl3, CFCl3)
= À59.2 (d, J = 7.6 Hz, 3F).
d
d
4.2.9. 2-[4-(Ethoxycarbonyl)phenyl]-4,4,4-trifluoro-1-phenyl-2-
buten-1-one (4j)
IR (neat) 3066, 2984, 1719, 1679, 1450, 1350, 1280, 1140,
1020 cmÀ1
.
d
4.2.5. 4,4,4-Trifluoro-2-(4-methoxylphenyl)-1-phenyl-2-buten-1-
one (4e)
HRMS (FAB) calcd for (M+H) C19H16F3O3 349.1052; found:
349.1054.
Z isomer: 1H NMR (CDCl3)
IR (neat) 2936, 2840, 1678, 1605, 1514, 1450, 1354, 1279, 1253,
1134, 1016 cmÀ1
.
d = 1.37 (t, J = 7.1 Hz, 3H), 4.36 (q,
HRMS (FAB) calcd for (M+) C17H13F3O2 306.0868; found:
306.0877.
Z isomer: 1H NMR (CDCl3)
J = 7.1 Hz, 2H), 6.29 (q, J = 7.9 Hz, 1H), 7.43–7.53 (m, 4H), 7.56–7.61
(m, 1H), 7.86–7.93 (m, 2H), 8.01–8.08 (m, 2H); 13C NMR (CDCl3)
d
= 3.79 (s, 3H), 6.14 (q, J = 8.2 Hz, 1H),
d
= 14.2, 61.3, 117.3 (q, J = 35.1 Hz), 122.1 (q, J = 271.1 Hz), 126.6,
128.9, 129.5, 130.3, 132.0, 134.1, 134.4, 137.8, 148.8 (q, J = 4.9 Hz),
165.6, 193.6; 19F NMR (CDCl3, CFCl3)
= À58.0 (d, J = 7.9 Hz, 3F).
E isomer: 1H NMR (CDCl3)
= 1.38 (t, J = 7.1 Hz, 3H), 4.37 (q,
6.88 (ABq, J = 8.9 Hz, 2H), 7.37 (ABq, J = 8.9 Hz, 2H), 7.40–7.48 (m,
2H), 7.50–7.60 (m, 1H), 7.90–7.96 (m, 2H); 13C NMR (CDCl3)
d
d
= 55.3, 113.3 (q, J = 34.8 Hz), 122.6 (q, J = 270.6 Hz), 122.1, 128.8,
129.5, 130.0, 133.5, 135.3, 149.0 (q, J = 5.4 Hz), 194.7; 19F NMR
(CDCl3, CFCl3)
= À58.6 (d, J = 8.2 Hz, 3F).
E isomer: 1H NMR (CDCl3)
= 3.80 (s, 3H), 6.01 (q, J = 7.5 Hz, 1H),
d
J = 7.1 Hz, 2H), 6.18 (q, J = 7.9 Hz, 1H), 7.43–7.53 (m, 4H), 7.56–7.61
(m, 1H), 7.86–7.93 (m, 2H), 8.01–8.08 (m, 2H); 19F NMR (CDCl3,
d
d
CFCl3)
d
= À55.6 (d, J = 7.8 Hz, 3F).
6.88 (ABq, J = 8.9 Hz, 2H), 7.37 (ABq, J = 8.9 Hz, 2H), 7.40–7.48 (m,
2H), 7.50–7.60 (m, 1H), 7.90–7.96 (m, 2H); 19F NMR (CDCl3, CFCl3)
4.2.10. 4,4,4-Trifluoro-2-(4-nitrophenyl)-1-phenyl-2-buten-1-one
(4k)
IR (neat) 3080, 2940, 1680, 1598, 1521, 1450, 1349, 1278, 1140,
1017 cmÀ1
.
d
= À57.2 (d, J = 7.5 Hz, 3F).
4.2.6. 4,4,4-Trifluoro-2-(4-fluorophenyl)-1-phenyl-2-buten-1-one
(4f)
HRMS (FAB) calcd for (M+H) C16H11BrF3NO3 322.0692; found:
322.0700.
Z isomer: 1H NMR (CDCl3)
(m, 2H), 7.58–7.68 (m, 4H), 7.89–7.93 (m, 1H), 8.17–8.28 (m, 2H);
13C NMR (CDCl3)
= 118.6 (q, J = 39.7 Hz), 121.8 (q, J = 271.5 Hz),
124.4, 127.8, 129.1, 129.5, 130.0, 134.8, 139.8, 147.7 (q, J = 5.3 Hz),
148.7, 193.0; 19F NMR (CDCl3, CFCl3)
= À59.6 (d, J = 7.8 Hz, 3F).
E isomer: 1H NMR (CDCl3)
= 6.28 (q, J = 7.6 Hz, 1H), 7.45–7.54
(m, 2H), 7.58–7.68 (m, 4H), 7.89–7.93 (m, 1H), 8.17–8.28 (m, 2H);
19F NMR (CDCl3, CFCl3)
= À57.5 (d, J = 7.6 Hz, 3F).
IR (neat) 3069, 2929, 1677, 1599, 1510, 1450, 1350, 1135,
1016 cmÀ1
.
d = 6.34 (q, J = 7.8 Hz, 1H), 7.45–7.54
HRMS (FAB) calcd for (M+H) C16H11F4O 295.0747; found:
295.0745.
Z isomer: 1H NMR (CDCl3)
(m, 4H), 7.56–7.62 (m, 1H), 7.89–7.94 (m, 2H); 13C NMR (CDCl3)
= 115.6 (q, J = 36.8 Hz), 116.4 (d, J = 22.0 Hz), 122.3 (q,
d
d
= 6.17 (q, J = 8.0 Hz, 1H), 7.39–7.50
d
d
d
J = 270.6 Hz), 128.7 (d, J = 8.4 Hz), 128.9, 129.5, 130.0, 134.1,
134.3, 148.5 (q, J = 5.4 Hz), 194.1; 19F NMR (CDCl3, CFCl3)
(d, J = 8.0 Hz, 3F), À110.3 to À110.2 (m, 1F).
d
= À59.1
d
E isomer: 1H NMR (CDCl3)
d
= 6.13 (q, J = 7.8 Hz, 1H), 7.39–7.50
4.2.11. 4,4,4-Trifluoro-2-(1-naphthyl)-1-phenyl-2-buten-1-one (4l)
IR (neat) 3062, 2926, 1679, 1596, 1449, 1349, 1285, 1226, 1143,
1089, 990 cmÀ1
.
(m, 4H), 7.56–7.62 (m, 1H), 7.89–7.94 (m, 2H); 19F NMR (CDCl3,
CFCl3)
= À57.3 (d, J = 7.8 Hz, 3F), À111.9 to À111.8 (m, 1F).
d

T. Konno et al. / Journal of Fluorine Chemistry 130 (2009) 913–921
919
HRMS (FAB) calcd for (M+) C20H13F3O 326.0918; found:
326.0927.
Z isomer: 1H NMR (CDCl3)
(m, 3H), 7.48–7.58 (m, 3H), 7.63–7.68 (m, 1H), 7.83–7.89 (m, 2H),
7.98–8.03 (m, 2H), 8.42–8.47 (m, 1H); 19F NMR (CDCl3, CFCl3)
4.3.5. (E)-4,4,4-Trifluoro-1-(2-phenylethyl)-2-buten-1-one (2q)
IR (neat) 3029, 2958, 1714, 1661, 1497, 1303, 1266, 1128 cmÀ1
HRMS (EI) calcd for (M+) C12H11F3O 228.0762; found: 228.0757.
1H NMR (CDCl3)
= 2.97 (s, 4H), 6.58 (dq, J = 16.0, 7.5 Hz, 1H),
6.70 (dq, J = 16.0, 1.8 Hz, 1H), 7.14–7.25 (m, 3H), 7.27–7.37 (m,
2H); 13C NMR (CDCl3)
= 29.4, 43.4, 122.3 (q, J = 270.1 Hz), 126.4,
128.3, 128.6, 128.6 (q, J = 35.2 Hz), 134.0 (q, J = 5.5 Hz), 140.2,
197.1; 19F NMR (CDCl3)
= À65.8 (d, J = 7.5 Hz, 3F).
.
d
= 6.20 (q, J = 7.9 Hz, 1H), 7.39–7.46
d
d
= À59.7 (d, J = 7.9 Hz, 3F).
d
E isomer: 1H NMR (CDCl3)
d
= 6.56 (q, J = 7.9 Hz, 1H), 7.39–7.46
(m, 3H), 7.48–7.58 (m, 3H), 7.63–7.68 (m, 1H), 7.83–7.89 (m, 2H),
7.98–8.03 (m, 2H), 8.42–8.47 (m, 1H); 19F NMR (CDCl3, CFCl3)
d
d
= À58.9 (d, J = 7.6 Hz, 3F).
4.3.6. (E)-1-Cyclohexyl-4,4,4-trifluoro-2-buten-1-one (2r)
IR (neat) 2934, 2858, 1708, 1656, 1452, 1305, 1267, 1136 cmÀ1
.
4.3. Preparation of various
g
-trifluoromethylated
a
,b
-unsaturated
HRMS (EI) calcd for (M+) C10H13F3O 206.0918; found: 206.0915.
1H NMR (CDCl3)
d = 1.20–1.38 (m, 5H), 1.67–1.72 (m, 1H),
ketones 2
1.78–1.90 (m, 4H), 2.54 (tt, J = 14.3, 3.4 Hz, 1H), 6.47 (dq, J = 15.7,
6.5 Hz, 1H), 6.81 (dq, J = 15.7, 1.9 Hz, 1H); 13C NMR (CDCl3)
The
g-trifluoromethylated a,b-unsaturated ketones 2 were
prepared according to the previous literature method by three
steps [14a-b].
d
= 25.4, 25.7, 27.9, 50.0, 122.5 (q, J = 270.1 Hz), 128.4 (q,
J = 34.9 Hz), 132.9 (q, J = 5.5 Hz), 200.6; 19F NMR (CDCl3)
= À65.6 (d, J = 6.5 Hz, 3F).
d
4.3.1. (E)-4,4,4-Trifluoro-1-(4-methoxyphenyl)-2-buten-1-one (2m)
IR (KBr) 3058, 2941, 1682, 1600, 1511, 1423, 1308, 1265,
4.4. Typical procedure for Heck reaction of various g-
1172 cmÀ1
.
trifluoromethylated
a,b-unsaturated ketones with phenyldiazonium
HRMS (FAB) calcd for (M+) C11H9F3O2 230.0555; found:
230.0565.
M.p. 39–41 8C; 1H NMR (CDCl3)
J = 15.5, 7.1 Hz, 1H), 6.99 (ABq, J = 8.9 Hz, 2H), 7.53 (dq, J = 15.5,
2.0 Hz, 1H), 7.98 (ABq, J = 8.9 Hz, 2H); 13C NMR (CDCl3)
= 55.5,
tetrafluoroborate
d
= 3.90 (s, 3H), 6.73 (dq,
The Heck reactions were carried out using either Method A or
Method B, as mentioned above.
d
114.2, 122.7 (q, J = 270.1 Hz), 129.2, 129.4 (q, J = 35.1 Hz), 131.1 (q,
4.4.1. 4,4,4-Trifluoro-1-(4-methoxyphenyl)-2-phenyl-2-buten-1-one
J = 5.8 Hz), 131.2, 164.4, 186.1; 19F NMR (CDCl3)
J = 7.1 Hz, 3F).
d
= À65.5 (d,
(4m)
IR (neat) 3062, 2937, 1667, 1599, 1356, 1263, 1169, 1135 cmÀ1
.
HRMS (FAB) calcd for (M+H) C17H14F3O2 307.0947; found:
307.0951.
Z isomer: 1H NMR (CDCl3)
6.92 (ABq, J = 8.8 Hz, 2H), 7.34–7.47 (m, 5H), 7.92 (ABq, J = 8.8 Hz,
1H); 13C NMR (CDCl3)
= 55.4, 114.0, 115.2 (q, J = 34.7 Hz), 122.5
4.3.2. (E)-4,4,4-Trifluoro-1-(2-methoxyphenyl)-2-buten-1-one (2n)
IR (neat) 3089, 2943, 1679, 1646, 1487, 1271, 1165, 1127,
d = 3.83 (s, 3H), 6.20 (q, J = 8.0 Hz, 1H),
1016 cmÀ1
.
HRMS (FAB) calcd for (M+H) C11H10F3O2 231.0634; found:
231.0624.
1H NMR (CDCl3)
d
(q, J = 270.3 Hz), 126.6, 128.4, 129.1, 131.9, 132.5, 134.0, 149.9 (q,
d
= 3.90 (s, 3H), 6.65 (dq, J = 15.6, 7.5 Hz, 1H),
J = 5.8 Hz), 164.3, 192.7; 19F NMR (CDCl3)
d
= À59.1 (d, J = 8.0 Hz,
6.98 (d, J = 8.4 Hz, 1H), 7.03 (ddd, J = 7.7, 7.7, 0.8 Hz, 1H), 7.47 (dq,
J = 15.6, 2.1 Hz, 1H), 7.52 (ddd, J = 8.4, 7.7, 1.8 Hz, 1H), 7.70 (dd,
J = 7.7, 1.8 Hz, 1H); 13C NMR (CDCl3)
d = 55.5, 111.7, 121.0, 127.1 (q,
3F).
E isomer: 1H NMR (CDCl3)
d
= 3.84 (s, 3H), 6.04 (q, J = 7.6 Hz, 1H),
6.92 (ABq, J = 8.8 Hz, 2H), 7.34–7.47 (m, 5H), 7.92 (ABq, J = 8.8 Hz,
1H); 19F NMR (CDCl3)
= À57.1 (d, J = 7.11 Hz, 3F).
J = 34.8 Hz), 122.9 (q, J = 269.6 Hz), 126.9, 131.0, 134.8, 135.7 (q,
d
J = 5.8 Hz), 159.0, 189.5; 19F NMR (CDCl3)
3F).
d
= À65.3 (d, J = 7.5 Hz,
4.4.2. 4,4,4-Trifluoro-1-(2-methoxyphenyl)-2-phenyl-2-buten-1-one
(4n)
4.3.3. (E)-1-(4-Chlorophenyl)-4,4,4-trifluoro-2-buten-1-one (2o)
IR (neat) 3064, 2944, 1657, 1598, 1486, 1296, 1277, 1207,
IR (KBr) 3072, 2928, 1686, 1591, 1402, 1305, 1224, 1136,
1133 cmÀ1
.
1009 cmÀ1
.
HRMS (FAB) calcd for (M+H) C17H14F3O2 307.0947; found:
307.0950.
Z isomer: 1H NMR (CDCl3)
HRMS (EI) calcd for (M+) C10H6ClF3O 234.0059; found:
234.0065.
M.p. 46–48 8C. 1H NMR (CDCl3)
1H), 7.49 (dq, J = 16.0, 2.0 Hz, 1H), 7.51 (ABq, J = 8.0 Hz, 2H),
7.92 (ABq, J = 8.0 Hz, 2H); 13C NMR (CDCl3)
= 122.4
d
= 3.69 (s, 3H), 5.92 (q, J = 8.0 Hz, 1H),
d
= 6.83 (dq, J = 16.0, 7.5 Hz,
6.87 (d, J = 8.4 Hz, 1H), 7.02 (dd, J = 7.6, 7.6 Hz, 1H), 7.30–7.41 (m,
5H), 7.49 (ddd, J = 8.4, 8.4, 1.2 Hz, 1H), 8.01 (dd, J = 7.6, 1.2 Hz, 1H);
13C NMR (CDCl3)
d = 55.2, 112.1, 112.8 (q, J = 34.7 Hz), 120.7, 122.8
d
(q, J = 270.4 Hz), 129.4, 130.2, 130.5 (q, J = 5.5 Hz), 130.7 (q,
(q, J = 270.3 Hz), 124.9, 126.8, 128.8, 129.6, 131.5, 134.1, 135.7,
J = 37.5 Hz), 134.5, 140.8, 186.7; 19F NMR (CDCl3)
J = 7.5 Hz, 3F).
d
= À65.7 (d,
153.1 (q, J = 5.7 Hz), 159.9, 192.5; 19F NMR (CDCl3)
J = 8.0 Hz, 3F).
d
= À59.1 (d,
E isomer: 1H NMR (CDCl3)
d = 3.79 (s, 3H), 6.15 (q, J = 7.1 Hz, 1H),
4.3.4. (E)-4,4,4-Trifluoro-1-(1-naphthyl)-2-buten-1-one (2p)
aromatic proton could not be identified; 19F NMR (CDCl3)
(d, J = 7.1 Hz, 3F).
d
= À57.5
IR (neat) 3057, 1753, 1682, 1644, 1573, 1510, 1302, 1133 cmÀ1
.
HRMS (FAB) calcd for (M+) C14H9F3O 250.0605; found:
250.0597.
1H NMR (CDCl3)
4.4.3. 1-(4-Chlorophenyl)-4,4,4-trifluoro-2-phenyl-2-buten-1-one
(4o)
d
= 6.79 (dq, J = 15.7, 6.6 Hz, 1H), 7.42 (dq,
J = 15.7, 1.9 Hz, 1H), 7.45–7.52 (m, 1H), 7.55–7.59 (m, 1H), 7.60–
IR (neat) 3063, 2926, 1679, 1588, 1402, 1353, 1287, 1217,
7.68 (m, 1H), 7.79–7.88 (m, 1H), 7.89–7.94 (m, 1H), 8.00–8.03 (m,
1137 cmÀ1
.
1H), 8.56–8.61 (m, 1H); 13C NMR (CDCl3)
d
= 122.6 (q, J = 270.4 Hz),
HRMS (FAB) calcd for (M+H) C16H11ClF3O 311.0451; found:
311.0441.
Z isomer: 1H NMR (CDCl3)
(m, 7H), 7.87 (ABq, J = 8.6 Hz, 2H); 13C NMR (CDCl3)
124.2, 125.4, 126.8, 128.3, 128.6, 129.2, 130.1 (q, J = 35.2 Hz),
130.3, 130.9, 133.8, 133.8, 134.7 (q, J = 5.5 Hz), 191.1; 19F NMR
d
= 6.22 (q, J = 8.0 Hz, 1H), 7.35–7.45
= 115.9 (q,
(CDCl3)
d
= À65.4 (d, J = 6.6 Hz, 3F).
d

920
T. Konno et al. / Journal of Fluorine Chemistry 130 (2009) 913–921
(d) I. Ojima, J.R. McCarthy, J.T. Welch (Eds.), Biomedical Frontiers of Fluorine
Chemistry, American Chemical Society, Washington, DC, 1996;
(e) R.E. Banks, B.E. Smart, J.C. Tatlow (Eds.), Organofluorine Chemistry: Principals
and Commercial Applications, Plenum Press, New York, 1994;
(f) D. O’Hagen, H. Rzepa, Chem. Commun. (1997) 645–652;
(g) J. Mann, Chem. Soc. Rev. 16 (1987) 381–436;
(h) J.T. Welch, Tetrahedron 43 (1987) 3123–3197.
[2] For reviews, see:
J = 35.1 Hz), 122.3 (q, J = 271.1 Hz), 126.6, 129.29, 129.32, 130.3,
130.5, 130.8, 133.5, 133.6, 140.8, 149.2 (q, J = 5.4 Hz), 193.0; 19F
NMR (CDCl3)
d
= À59.1 (d, J = 8.0 Hz, 3F).
= 6.11 (q, J = 7.1 Hz, 1H), 7.35–7.45
E isomer: 1H NMR (CDCl3)
d
(m, 7H), 7.83 (ABq, J = 8.6 Hz, 2H); 19F NMR (CDCl3)
J = 7.1 Hz, 3F).
d
= À57.3 (d,
(a) R. Dave, B. Badet, P. Meffre, Amino Acids 24 (2003) 245–261;
(b) X.-L. Qiu, W.-D. Meng, F.-L. Qing, Tetrahedron 60 (2004) 6711–6745;
(c) K. Mikami, Y. Itoh, M. Yamanaka, Chem. Rev. 104 (2003) 1–16;
(d) J.H. van Steenis, A. van der Gen, J. Chem. Soc., Perkin Trans. 1 (2002) 2117–
2133;
(e) R.P. Singh, J.M. Shreeve, Tetrahedron 56 (2000) 7613–7632;
(f) S.D.R. Christie, J. Chem. Soc., Perkin Trans. 1 (1998) 1577–1588;
(g) I. Ojima, Chem. Rev. 88 (1988) 1011–1030;
4.4.4. 4,4,4-Trifluoro-1-(1-naphthyl)-2-phenyl-2-buten-1-one (4p)
IR (neat) 3060, 2932, 1666, 1509, 1447, 1344, 1287, 1134 cmÀ1
.
HRMS (FAB) calcd for (M+H) C20H14F3O 327.0997; found:
327.0992.
Z isomer: 1H NMR (CDCl3)
d
= 6.23 (q, J = 8.1 Hz, 1H), 7.33–7.40
(h) G.K.S. Prakash, A.K. Yudin, Chem. Rev. 97 (1997) 757–786;
(i) M.A. McClinton, D.A. McClinton, Tetrahedron 48 (1992) 6555–6666.
[3] (a) T. Konno, T. Tanaka, T. Miyabe, A. Morigaki, T. Ishihara, Tetrahedron Lett. 49
(2008) 2106–2110;
(m, 3H), 7.40–7.47 (m, 1H), 7.50–7.58 (m, 2H), 7.59–7.64 (m, 1H),
7.70–7.76 (m, 1H), 7.88–7.92 (m, 1H), 7.94–7.98 (m, 1H), 8.03–8.07
(m, 1H), 9.32–9.35 (m, 1H); 13C NMR (CDCl3)
d = 115.2 (q,
J = 34.9 Hz), 122.6 (q, J = 270.8 Hz), 124.3, 125.4, 126.1, 126.6,
126.9, 128.3, 128.6, 129.2, 129.3, 130.2, 130.9, 133.4, 134.2, 135.3,
(b) T. Yamazaki, N. Shinohara, T. Kitazume, S. Sato, J. Fluorine Chem. 97 (1999)
91–96;
(c) O. Klenz, R. Evers, R. Miethchen, M. Michalik, J. Fluorine Chem. 81 (1997) 205–
210;
(d) T. Konno, T. Yamazaki, T. Kitazume, Tetrahedron 52 (1996) 199–208;
(e) L. Antolini, A. Forni, I. Moretti, F. Prati, Tetrahedron: Asymmetry 7 (1996)
3309–3314;
(f) N. Shinohara, J. Haga, T. Yamazaki, T. Kitazume, S. Nakamura, J. Org. Chem. 60
(1995) 4363–4374;
150.9 (q, J = 5.5 Hz), 196.0; 19F NMR (CDCl3)
d
= À58.9 (d, J = 8.1 Hz,
3F).
E isomer: 1H NMR (CDCl3)
d = 6.28 (q, J = 7.1 Hz, 1H), 7.33–7.40
(m, 3H), 7.40–7.47 (m, 1H), 7.50–7.58 (m, 2H), 7.80–7.83 (m, 1H),
7.88–7.92 (m, 1H), 8.00–8.03 (m, 1H), 8.48–8.52 (m, 1H); 19F NMR
(g) T. Yamazaki, J. Haga, T. Kitazume, Chem. Lett. (1991) 2175–2178;
(h) T. Yamazaki, N. Ishikawa, J. Chem. Soc., Chem. Commun. (1987) 1340–
1342;
(i) P.F. Bevilacqua, D.D. Keith, J.L. Robert, J. Org. Chem. 49 (1984) 1430–
1434.
(CDCl3)
d
= À57.6 (d, J = 7.1 Hz, 3F).
4.4.5. 4,4,4-Trifluoro-1-(2-phenylethyl)-2-phenyl-2-buten-1-one
(4q)
The titled compound could not be separated as a sole compound
from Michael type adduct.
Z isomer: 1H NMR (CDCl3)
7.01–7.45 (m, 10H); 19F NMR (CDCl3)
E isomer: 1H NMR (CDCl3)
= 2.96 (s, 4H), 6.54 (q, J = 6.0 Hz, 1H),
7.01–7.45 (m, 10H); 19F NMR (CDCl3)
= À58.0 (d, J = 6.0 Hz, 3F).
[4] (a) M. Redon, Z. Janousek, H.G. Viehe, Tetrahedron 53 (1997) 6861–6872;
(b) K. Tanaka, T. Imase, S. Iwata, Bull. Chem. Soc. Jpn. 69 (1996) 2243–2248;
(c) D. Bonnet-Delpon, A. Chennoufi, M.H. Rock, Bull. Soc. Chim. Fr. 132 (1995)
402–405;
(d) Y. Hanzawa, M. Suzuki, Y. Kobayashi, T. Taguchi, Y. Iitaka, J. Org. Chem. 56
(1991) 1718–1725.
[5] Recently, several groups and we have reported the stereoselective syntheses of
fluoroalkylated alkenes. See:
d
= 2.95 (s, 4H), 5.86 (q, J = 8.0 Hz, 1H),
= À59.0 (d, J = 8.0 Hz, 3F).
d
d
d
(a) T. Konno, A. Morigaki, K. Ninomiya, T. Miyabe, T. Ishihara, Synthesis (2008)
564–572;
(b) T. Konno, J. Chae, T. Tanaka, T. Ishihara, H. Yamanaka, J. Fluorine Chem. 127
(2006) 36–43;
(c) T. Konno, T. Daitoh, A. Noiri, J. Chae, T. Ishihara, H. Yamanaka, Tetrahedron 61
(2005) 9391–9404;
(d) S. Radix-Large, S. Kucharski, B.R. Langlois, Synthesis (2004) 456–465;
(e) T. Konno, J. Chae, T. Tanaka, T. Ishihara, H. Yamanaka, Chem. Commun. (2004)
690–691;
4.4.6. 1-Cyclohexyl-4,4,4-trifluoro-2-phenyl-2-buten-1-one (4r)
IR (neat) 2934, 2856, 1704, 1649, 1449, 1348, 1278, 1133 cmÀ1
.
HRMS (FAB) calcd for (M+) C16H18F3O 283.1310; found:
283.1309.
Z isomer: 1H NMR (CDCl3)
1H), 1.70–1.74 (m, 2H), 1.81–1.88 (m, 2H), 2.45 (tt, J = 11.2, 3.6 Hz,
1H), 5.84 (q, J = 8.4 Hz, 1H), 7.31–7.46 (m, 5H); 13C NMR (CDCl3)
d
= 1.05–1.40 (m, 5H), 1.58–1.65 (m,
(f) T. Konno, T. Daitoh, A. Noiri, J. Chae, T. Ishihara, H. Yamanaka, Org. Lett. 6
(2004) 933–936;
d
= 25.61, 25.63, 28.1, 50.4, 115.0 (q, J = 35.5 Hz), 122.5 (q,
J = 270.3 Hz), 126.6, 129.2, 130.1, 133.8, 152.0 (q, J = 5.8 Hz),
207.0; 19F NMR (CDCl3)
= À59.1 (d, J = 8.4 Hz, 3F).
E isomer: 1H NMR (CDCl3)
= 6.40 (q, J = 8.0 Hz, 1H). The other
proton signal (cyclohexyl and phenyl protons) could not be
identified; 19F NMR (CDCl3)
= À57.7 (d, J = 8.0 Hz, 3F).
(g) T. Konno, T. Takehana, J. Chae, T. Ishihara, H. Yamanaka, J. Org. Chem. 69
(2004) 2188–2190;
(h) M. Shimizu, T. Fujimoto, X. Liu, H. Minezaki, T. Hata, T. Hiyama, Tetrahedron
59 (2003) 9811–9823;
(i) J. Chae, T. Konno, M. Kanda, T. Ishihara, H. Yamanaka, J. Fluorine Chem. 120
(2003) 185–193;
(j) M.P. Jennings, E.A. Cork, V. Ramachanfran, J. Org. Chem. 65 (2000) 8763–8766;
(k) R.-q. Pan, X.-x. Liu, M.Z. Deng, J. Fluorine Chem. 95 (1999) 167–170;
d
d
d
´
ˆ
(l) G. Prie, J. Thibonnet, M. Abarbri, A. Duchene, J. Parrain, Synlett (1998) 839–
4.4.7. Ethyl 4,4,4-trifluoro-2-phenyl-2-butenoate (4s)
Known compound. Z isomer: 1H NMR (CDCl3)
840;
(m) Y. Shen, S. Gao, J. Fluorine Chem. 76 (1996) 37–39.
d
= 1.35 (t,
[6] Several Heck reactions of fluorine-containing alkenes were reported, see:
(a) S. Darses, M. Pucheault, J.-P. Geneˆt, Eur. J. Org. Chem. (2001) 1121–1128;
(b) S. Peng, F.-L. Qing, Y. Guo, Synlett (1998) 859–860;
J = 7.10 Hz, 3H), 4.37 (q, J = 7.10 Hz, 2H), 6.02 (q, J = 7.90 Hz, 1H),
7.42 (s, 5H); 19F NMR (CDCl3)
= À60.3 (d, J = 7.90 Hz, 3F).
d
The Heck reaction of b-fluoroalkylated a,b-unsaturated carbonyl compounds
with aryl halide in the presence of palladium catalyst has been reported, however
neither the high regioselectivity nor the high yields have been achieved (<48%
yield, the regioselectivity = <29:71), see:
4.4.8. 4,4-Difluoro-1,2-diphenyl-2-buten-1-one (4w)
Z isomer: 1H NMR (CDCl3)
= 6.20 (dt, J = 6.79, 55.6 Hz, 1H),
d
(c) Y. Gong, K. Kato, H. Kimoto, J. Fluorine Chem. 105 (2000) 169–173;
6.26–6.40 (m, 1H), 7.30–7.36 (m, 1H), 7.50–7.54 (m, 1H), 7.60–7.65
Recently, we have disclosed
a preliminary finding on the Heck reaction of
(m, 1H), 7.96–7.98 (m, 1H); 19F NMR (CDCl3)
55.6 Hz, 2F).
d
= À110.1 (dd, J = 9.8,
fluorine-containing a,b-unsaturated ketones. See:
(d) T. Konno, S. Yamada, A. Tani, T. Miyabe, T. Ishihara, Synlett (2006) 3025–
E isomer: 1H NMR (CDCl3)
d
= 6.21 (dt, J = 6.79, 53.8 Hz, 1H); 19
F
3028.
[7] The stereochemistry was determined on the basis of the chemical shifts in 1H
NMR according to the literature. See Ref. [6c].
NMR (CDCl3)
d
= À109.4 (dd, J = 9.8, 53.8 Hz, 2F).
[8] Investigation of the reaction conditions for the Heck reaction of 2s with phenyl-
diazonium salt was investigated in detail, like the case of 2a. However, the
satisfactory results were not obtained at all.
References
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