α-Fluoroalkylation of carbonyl compounds mediated by a highly reactive alkyl-rhodium complex

Article abstract of DOI:10.1016/j.jfluchem.2009.10.012

Treatment of silyl enol ethers of various carbonyl compounds with Et₂Zn and fluoroalkyl halides (R_f-X) in the presence of RhCl(PPh₃)₃ in DME gave the corresponding α-R_f carbonyl compounds. A highly reactive alkyl-rhodium complex which was derived from RhCl(PPh₃)₃ and Et₂Zn must be crucial in this reaction by accelerating the reaction rate and improving the yields dramatically. This reaction overcomes difficulties on the synthesis of α-R_f carbonyl compounds due to inverse polarization of R_f-X.

Full text of DOI:10.1016/j.jfluchem.2009.10.012

Journal of Fluorine Chemistry 131 (2010) 86–90
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
a
-Fluoroalkylation of carbonyl compounds mediated by a highly reactive
alkyl-rhodium complex
Kazuyuki Sato, Satoshi Yamazoe, Yukiko Akashi, Tetsuya Hamano, Arisa Miyamoto, Shuhei Sugiyama,
*
Atsushi Tarui, Masaaki Omote, Itsumaro Kumadaki, Akira Ando
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
Treatment of silyl enol ethers of various carbonyl compounds with Et2Zn and fluoroalkyl halides (Rf–X) in
Received 17 September 2009
Received in revised form 28 October 2009
Accepted 28 October 2009
Available online 5 November 2009
the presence of RhCl(PPh3)3 in DME gave the corresponding a-Rf carbonyl compounds. A highly reactive
alkyl-rhodium complex which was derived from RhCl(PPh3)3 and Et2Zn must be crucial in this reaction
by accelerating the reaction rate and improving the yields dramatically. This reaction overcomes
difficulties on the synthesis of
a-Rf carbonyl compounds due to inverse polarization of Rf–X.
ß 2009 Elsevier B.V. All rights reserved.
Keywords:
a
-Fluoroalkylation
Rhodium
Silyl enol ether
a
-Position
1. Introduction
reactive alkyl-rhodium complex that was derived from
RhCl(PPh3)3 and Et2Zn (Scheme 1) [9]. The reaction smoothly
In the search for various medicinal candidates, a synthesis of
designed proteins and/or peptides has become an important
proceeded and gave various a-CF3 carbonyl compounds in good
yields. Thus, our reaction provided one of a breakthrough for the
synthesis of them.
project. Fluorinated amino acids, especially
a-fluoroalkylated
amino acids, are more stable than the corresponding non-
fluorinated counterparts, and often used for these purposes [1].
However the effective syntheses of the fluorine-containing
compounds, especially which have a fluoroalkyl (Rf) group at
In this paper, we would like to report a further expansion of the
scope of this reaction mediated by a highly reactive alkyl-rhodium
complex to the synthesis of
pounds.
a-fluoroalkylated carbonyl com-
the
development of their new synthetic methodology is highly desired
[2–5]. The reason of the difficulty of the synthesis of -Rf carbonyl
a-position of a carbonyl group, are limited, and the
2. Results and discussion
a
compounds is attributed that the polarization of fluoroalkyl
2.1. Synthesis of a-fluoroalkylated ketones
d
d
d
+
halides (Rf À–X +) is opposite to that of the alkyl halides (R
–
d
X
À), which makes it difficult to introduce Rf+ unit to enolates [6].
Based on the previous condition [9b], various Rf–X (1) and 1-
(trimethylsiloxy)cyclohexene as a model compound of the silyl
enol ethers were treated with Et2Zn in the presence of RhCl(PPh3)3.
The results are summarized in Table 1.
Although Mikami and co-workers have already reported
a-
trifluoromethylation of ketones by using Li, Ti, or Zn enolates
assisted by Et3B/O2, their applications were limited to aliphatic
ketones [7]. More recently, MacMillan and co-workers reported
fluoroalkylation of aldehydes via the enamines by using
photoredox catalyst under the visible light [8]. This methodology
is a very innovative reaction, but the reaction vessel was needed to
place near luminous source at under a cool bath.
a
a
-
As shown in entries 1–3, perfluoroalkyl iodides (1a–c) gave the
corresponding products in moderate to good yields, although a
mixture of 4a and 5a was obtained in entry 1. The latter was
assumed to be formed during the work-up. We confirmed this by
treating the mixture with alumina (pH = 9.0–11.0) overnight
before purification. As expected, the dehydrofluorination of 4a
occurred and only 5a was obtained. Since the ratio of 4a and 5a
varied depending on a slight differences in the work-up conditions,
here is only shown the yield of 5a after complete dehydrofluor-
ination. Interestingly, C10F21 group did not lead to the dehydro-
Recently, we reported an
a-trifluoromethylation of carbonyl
compounds via trimethylsilyl enol ethers mediated by a highly
* Corresponding author.
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.10.012

K. Sato et al. / Journal of Fluorine Chemistry 131 (2010) 86–90
87
Table 1
a-Fluoroalkylation of cyclohexanone via its silyl enol ether.
.
Entry
Rf–X
Temp. (8C)
Time (h)
Product
Yield (%)a
1
2
3
4
5
C4F9–1
0 to r.t.
24
2
5a
4b
4c
4d
4d
54 (66)b,c
77
C10F21–I
0
C6F5–CF2–I
EtOOCCF2–Br
EtOOCCF2–CI
0
23
5
60
0
70 (82)d
n.r.
0 to r.t.
24
a
Isolated yield.
b
c
19F NMR yield of the product (5a) calculated based on benzotrifluoride (BTF) as an internal standard.
A mixture of the products was treated with alumina overnight.
d
19F NMR yield calculated based on BTF as an internal standard.
rhodium complex (6), which was derived from RhCl(PPh3)3 and
Et2Zn, to form a Rh(III) complex (7) was followed by the
coordination onto the
p-bond of silyl enol ether (2). By subsequent
insertion of the CF3 unit into the olefin, another Rh(III) complex (9)
was formed, which suffered from the reductive elimination to give
the desired
lane (TMS–Et) or trimethylsilane (TMS–H) and ethylene.
We believe that this -fluoroalkylation must proceed through
a-CF3 product (3) along with loss of ethyltrimethylsi-
a
Scheme 1.
the same mechanism. The oxidative addition of Cl–CF2COOEt onto
the complex (6) would be difficult due to the hard C–Cl bond, and
this is the reason of non-reactivity of the Cl-ester, as shown in entry
5 in Table 1.
fluorination contrary to the case of C4F9 group (entry 2). It may be
attributed to the inflexibility of C10F21 group to form the rigid
structure. On the other hand, ethyl bromodifluoroacetate (1d) gave
the desired product (4d) in a good yield, while the reaction did not
proceed with ethyl chlorodifluoroacetate (1e) even if the
temperature was risen to room temperature (entries 4 and 5).
2.2. Synthesis of various
a
-fluoroalkylated carbonyl compounds
Next, we examined the several substrates for
a-fluoroalkyla-
We have also reported that the
a
-fluoroalkylation of ketones
tion, and the results are summarized in Table 2. The yields and the
reaction rates are well accorded with the order of electron density
proceeded by heating in 1,4-dioxane only in the presence of
RhCl(PPh3)3 using the corresponding silyl enol ethers [10].
However the yield of products was low and dehydrofluorination
also was observed in most cases because of the harsh condition in
the previous report.
On the other hand, the addition of Et2Zn improved the yield
considerably, and suppressed the dehydrofluorination. The addi-
tion effect of Et2Zn would be understood by our previous
of the
p-bond of the corresponding silyl enol ethers. Especially, the
N,O-silyl ketene acetal from N-methyl-N-phenylisobutyramide
reacted, though it has two methyl groups at the olefinic position
that might cause a steric hindrance. In addition, it might be another
reason of the low reactivity why there is less electron donation
from nitrogen owing to the distortion by steric repulsion between
TMS and amino groups. This result suggests that more electron rich
silyl enol ethers would become to easily coordinate to the complex
(7). Furthermore, it is understandable that the size of Rf–X also
affects the yield.
a-
trifluoromethylation mechanism as shown in Fig. 1 [9b]. Namely,
the oxidative addition of CF3–I onto the highly reactive ethyl-
On the other hand, the dehydrofluorinated product (5a) was
obtained in a considerable yield in the reaction of C4F9–I with 1-
(trimethylsiloxy)cyclohexene as mentioned above (entry 1 in
Table 1). This result would be attributed to the enhanced acidity of
a
-hydrogen between ketone and Rf group, and this dehydro-
fluorination was suppressed in -C4F9 ester (10a). This tendency
becomes prominent by changing the functional group, and -C4F9
thioester (12a) was obtained without dehydrofluorination.
Based on these results, we next tried to use the silyl enol ether
derived from an aldehyde. An effective -fluoroalkylation of
a
a
a
aldehydes has hardly ever reported, while most of them suffer
from cross-coupling reactions with sp2-halides [11], radical
reactions [12] or photochemical reaction [13]. The present
transformation will become more useful from the above results,
if the reactions would proceed with silyl enol ethers of aldehydes
to give
rates was confirmed as expected, while the higher acidity of the
hydrogen caused the dehydrofluorination of the products,
a-Rf aldehydes. As shown in Table 3, the increase of reaction
a
-
Fig. 1. Reaction mechanism of Rh-catalyzed
a-trifluoromethylation.
a-Rf

88
K. Sato et al. / Journal of Fluorine Chemistry 131 (2010) 86–90
Table 2
Various
a-fluoroalkylated carbonyl compounds.
.
Entry
Product
Time (h)
Yield (%)a
1
2
3
4
C4F9 (10a)
3
7
5
3
44b
32
C10F21 (10b)
CF2C6F5 (10c)
CF2COOEt (10d)
44
668
5
6
7
8
C4F9 (11a)
3
3
2
3
39
27
C
10F21 (11b)
CF2C6F5 (11c)
29
42c
CF2COOEt (11d)
9
10
11
12
C4F9 (12a)
3
5
2
3
34
21
0
0c
C
10F21 (12b)
CF2C6F5 (12c)
CF2COOEt (12d)
a
Isolated yield.
b
c
Dehydrofluorinated product (13a) was isolated in 14% as the by-product along with 10a.
BrCF2COOEt (1d) was used as the starting material.
Table 3
a
-Fluoroalkylation of aldehydes.
.
Entry
Rf–X
C4F9–I
Temp. (8C)
Time (h)
Product
Yield (%)a
1
2
3
4
0
0
0
0
1
1
2
1
14a
14b
14c
14d
51
38
24
0
C10F21–I
C6F5–CF2–I
EtOOCCF2–Br
a
Isolated yield.
aldehydes (14). Unfortunately, the yields were not improved
owing to the less stability and the higher reactivity, but we could
R-90H and JEOL-ECA-600SN spectrometers. Chemical shifts of 1H
NMR and 13C NMR are reported in ppm from tetramethylsilane
(TMS) as an internal standard. Chemical shifts of 19F NMR are
reported in ppm from benzotrifluoride (BTF) as an internal
standard. All data are reported as follows: chemical shifts, relative
integration value, multiplicity (s, singlet; d, doublet; t, triplet; q,
quartet; br, broad; m, multiplet), and coupling constants (Hz).
Mass spectra were obtained on JEOL JMS-700T spectrometers. IR
spectra were recorded on Hitachi 270-30 Infrared spectrophot-
ometer. Melting points were measured on Yanagimoto micro
melting point apparatus MP-S3 and uncorrected. Analytical gas–
liquid chromatography (GLC) was carried out on Hitachi 263-50
gas chromatograph (column; 5% SE-30 3 mm  2 m, carrier; N2 at
30 mL/min). Peak areas were calculated on Shimadzu C-R5A
Chromatopac.
confirm the formation of
3. Conclusions
a
-Rf aldehydes (Table 3).
We obtained various
a
-Rf carbonyl compounds which have
been difficult to synthesize, especially it is rare for the direct
fluoroalkylation of thioesters and aldehydes. Most results relevant
to this -fluoroalkylation supported the previous proposed
mechanism which was mediated by a highly reactive alkyl-
rhodium complex. Since the -fluoroalkylation reaction can be
a-
a
a
widely applicable to various silyl enol ethers of carbonyl
compounds, we expect that the reaction will play an important
role in medicinal and/or material fields.
The purity of products was certificated by 1H NMR, and then
HRMS was used as substitute for elemental analysis. 19F NMR
yields were calculated based on BTF as an internal standard.
Dimethoxyethane (DME) was distilled from CaH2 and stored over
4. Experimental
4.1. General information
˚
MS 4 A. All commercially available reagents were used without
further purification. All experiments were carried out under argon
atmosphere unless otherwise noted.
1H NMR and 13C NMR spectra were recorded on JNM-GX400
spectrometers. 19F NMR spectra were recorded on Hitachi FT-NMR

K. Sato et al. / Journal of Fluorine Chemistry 131 (2010) 86–90
89
4.2. General procedure
4.4.3. 3-Perfluorobenzylchroman-2-one (10c)
A colorless oil; 1H NMR (CDCl3)
: 3.39 (2H, m), 3.73 (1H, m),
7.05–7.33 (4H, m); 19F NMR (600 MHz, CDCl3)
: À23.6 (1F, dt,
d
To a solution of RhCl(PPh3)3 (2 mol%) and ketene silyl acetal (2,
1.0 mmol) in DME (5 mL) was added Rf–X (1, 1.5 mmol) at 0 8C.
Then 1.0 M Et2Zn in hexane (1 mL, 1.0 mmol) was slowly added,
and was stirred at the same temperature. The resulting mixture
was quenched with 10% HCl, and extracted with AcOEt. The organic
layer was washed with sat. NaCl and dried over MgSO4. The solvent
was removed in vacuo, then benzotrifluoride (BTF) was added in
the residue. The yield was calculated from the integration ratio of
the product and BTF on 19F NMR. After the calculation, the residue
was purified by column chromatography to give the corresponding
d
J = 15.5 Hz), À43.4 (1F, ddt, J = 38.0 Hz), À76.6 to À76.7 (2F, m),
À87.1 (1F, dt, J = 20.7 Hz), À97.8 to À97.9 (2F, m); MS m/z: 364
(M+); HRMS Calcd for C16H7O2F7: 364.033 (M+), Found: 364.033; IR
(neat) cmÀ1: 1760, 1332, 1258, 1234, 1162, 1094.
4.4.4. Ethyl difluoro-(2-oxochroman-3-yl)acetate (10d)
A colorless oil; 1H NMR (CDCl3)
d
: 1.38 (3H, t, J = 7.24 Hz), 3.21
(1H, dd, J = 6.2, 6.8 Hz), 3.32 (1H, t, J = 14.5 Hz), 3.74 (1H, m), 4.41
(2H, q, J = 7.1 Hz), 7.07–7.33 (4H, m); 13C NMR (100 MHz, CDCl3)
d
:
a
-fluoroalkylated carbonyl compound.
13.8, 22.6 (t, J = 4.4 Hz), 63.4, 116.8, 120.6, 125.1, 128.3, 128.6,
150.8, 162.6 (t, J = 30.0 Hz), 164.6, 164.7; 19F NMR (90 MHz, CDCl3)
4.3. Spectroscopic data of -Rf ketones
a
d
: À50.1 (2F, ddd, J = 19.4, 5.4, 4.6 Hz); MS m/z: 270 (M+); HRMS
Calcd for C13H12O4F2: 270.071 (M+), Found: 270.071; IR (neat)
cmÀ1: 1758, 1334, 1228, 1172, 1108.
4.3.1. 2-Octafluorobutylidenecyclohexanone (5a); as the E-Z mixture
A colorless oil; 1H NMR (CDCl3)
: 1.84–2.03 (4H, m), 2.56 (2H, t,
J = 6.7 Hz), 2.62–2.70 (2H, m); 19F NMR (600 MHz, CDCl3)
: À65.2
d
d
4.5. Spectroscopic data of a-Rf amides
(1.6F, m), À64.5 (0.2F, m), À63.6 (0.4F, m), À58.1 (0.8F, m), À52.1
(1.6F, m), À51.9 (0.4F, m), À18.0 (0.6F, m), À17.9 (2.4F, m); MS m/z:
296 (M+); HRMS Calcd for C10H8OF8: 296.045 (M+), Found:
296.045; IR (neat) cmÀ1: 1730, 1680, 1356, 1302, 1188.
4.5.1. 3,3,4,4,5,5,6,6,6-Nonafluoro-N,2,2-trimethyl-N-
phenylpropionamide (11a)
A colorless oil; 1H NMR (CDCl3)
d
: 1.20 (6H, s), 3.25 (3H, s), 7.17–
7.45 (5H, m); 19F NMR (600 MHz, CDCl3)
d
: À63.3 (2F, m), À59.4
4.3.2. 2-Henicosafluorodecylcyclohexanone (4b)
(2F, m), À54.7 (2F, m), À17.9 (3F, m); MS m/z: 395 (M+); HRMS
Calcd for C15H14ONF9: 395.093 (M+), Found: 395.093; IR (neat)
cmÀ1: 1650, 1596, 1494, 1480, 1236, 1124.
Colorless crystals; M.p. 73.5–74.0 8C; 1H NMR (CDCl3)
d
: 1.69–
2.09 (5H, m), 2.26 (1H, m), 2.49 (2H, m), 3.20 (1H, m); 19F NMR
(90 MHz, CDCl3)
À58.9 (8F, m), À57.2 (2F, m), À51.1 (1F, m), À49.4 (1F, m), À18.0
(3F, m); MS m/z: 616 (M+); HRMS Calcd for C16H9OF21: 616.032
(M+), Found: 616.031; IR (KBr) cmÀ1: 1724, 1216, 1154.
d
: À63.8 (2F, m), À59.9 (2F, m), À59.1 (2F, m),
4.5.2. 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-Henicosafluoro-
N,2,2-trimethyl-N-phenyl-propionamide (11b)
Colorless crystals; M.p. 80.0–81.0 8C; 1H NMR (CDCl3)
d
: 1.12
(6H, s), 3.25 (3H, s), 7.21–7.43 (5H, m); 19F NMR (600 MHz, CDCl3)
4.3.3. 2-Perfluorobenzylcyclohexanone (4c)
d
: À63.3 (2F, m), À59.9 to À60.0 (2F, m), À59.1 (2F, m), À58.7 to
A colorless oil; 1H NMR (CDCl3)
d
: 1.71–1.78 (2H, m), 1.91–2.12
(3H, m), 2.27–2.35 (1H, m), 2.39–2.48 (2H, m), 3.34 (1H, m); 19F
NMR (600 MHz, CDCl3)
À58.9 (8F, m), À53.7 (2F, m), À48.4 (2F, m), À18.0 (3F, m); MS m/z:
695 (M+); HRMS Calcd for C20H14ONF21: 695.074 (M+), Found:
695.074; IR (KBr) cmÀ1: 1656, 1592, 1238, 1143.
d
: À98.5 (2F, m), À88.5 (1F, m), À76.7 (2F,
m), À41.5 (1F, ddt, J = 36.2 Hz), À26.0 (1F, dt, J = 15.5 Hz); MS m/z:
314 (M+); HRMS Calcd for C13H9OF7: 314.054 (M+), Found:
314.055; IR (neat) cmÀ1: 1726, 1372, 1330, 1222, 1038.
4.5.3. 2-Perfluorobenzyl-N,2,2-trimethyl-N-phenylpropionamide
(11c)
Colorless crystals; M.p. 79.0–80.0 8C; 1H NMR (CDCl3)
d
: 1.12
4.3.4. Ethyl 2,2-difluoro-2-(2-oxocyclohexyl)acetate (4d)
(6H, s), 3.21 (3H, s), 7.27–7.43 (5H, m); 19F NMR (600 MHz, CDCl3)
A colorless oil; 1H NMR (CDCl3)
d
: 1.35 (3H, t, J = 7.2 Hz), 1.69
(2H, m), 1.86 (1H, m), 2.08 (2H, m), 2.35 (2H, m), 2.45 (1H, m), 3.33
(1H, m), 4.34 (2H, m); 13C NMR (100 MHz, CDCl3)
: 13.8, 23.9, 25.3
(m), 26.5, 41.6 (m), 54.4 (m), 62.7, 114.1 (m), 163.6 (m), 206.4 (m);
d
: À99.0 to À99.1 (2F, m), À88.5 (1F, m), À75.1 to À75.3 (2F, m),
À33.3 (2F, t, J = 31.0 Hz); MS m/z: 393 (M+); HRMS Calcd for
C18H14ONF7: 393.096 (M+), Found: 393.096; IR (KBr) cmÀ1: 1653,
1586, 1248, 1142.
d
19F NMR (90 MHz, CDCl3)
d
: À55.3 (1F, dd, J = 273.8, 19.4 Hz),
À46.2 (1F, dd, J = 273.8, 7.6 Hz); MS m/z: 220 (M+); HRMS Calcd for
4.5.4. Ethyl 2,2-difluoro-3,3-dimethyl-4-(N-methyl-N-phenyl)-4-
oxoacetate (11d)
C
10H14O3F2: 220.091 (M+), Found: 220.090; IR (neat) cmÀ1: 1778,
1760, 1720, 1318, 1222, 1140.
Colorless crystals; M.p. 81.0–82.0 8C; 1H NMR (CDCl3)
d
: 1.18
(6H, s), 1.39 (3H, t, J = 7.0 Hz), 3.21 (3H, s), 4.38 (2H, q, J = 7.0 Hz),
7.24–7.45 (5H, m); 13C NMR (100 MHz, CDCl3)
: 13.9, 21.5 (t,
4.4. Spectroscopic data of -Rf esters
a
d
J = 5.2 Hz), 41.2, 52.6 (dd, J = 22.6, 23.2 Hz), 62.2, 116.2 (t,
J = 255.5 Hz), 128.4, 128.8, 129.4, 143.2, 164.2 (t, J = 32.4 Hz),
4.4.1. 3-Perfluorobutylchroman-2-one (10a)
A colorless oil; 1H NMR (CDCl3)
: 2.80–3.30 (2H, m), 3.62 (1H,
m), 7.08–7.35 (5H, m); 19F NMR (600 MHz, CDCl3)
À57.9 (2F, m), À50.1 (2F, m), À18.1 (3F, m); MS m/z: 366 (M+);
HRMS Calcd for C13H7O2F9: 366.030 (M+), Found: 366.030; IR
(neat) cmÀ1: 1784, 1360, 1236.
d
172.5 (t, J = 3.3 Hz); 19F NMR (90 MHz, CDCl3)
d
: À50.2 (2F, s); MS
d
: À63.3 (2F, m),
m/z: 299 (M+); HRMS Calcd for C15H19O3NF2: 299.133 (M+), Found:
299.133; IR (KBr) cmÀ1: 1754, 1652, 1226.
4.6. Spectroscopic data of
a-Rf thioesters
4.4.2. 3-Perfluorodecylchroman-2-one (10b)
4.6.1. S-phenyl 3,3,4,4,5,5,6,6,6-nonafluoro-2-methylhexanethioate
(12a)
Colorless crystals; M.p. 118.0 8C; 1H NMR (CDCl3)
d
: 3.31 (2H, d,
J = 8.0 Hz), 3.62 (1H, m), 7.10–7.34 (4H, m); 19F NMR (600 MHz,
CDCl3)
Colorless crystals; M.p. 41.0 8C; 1H NMR (CDCl3)
d
: 1.53 (3H, d,
d
: À63.3 (2F, m), À59.9 (2F, m), À59.1 (2F, m), À58.8 (8F, m),
J = 7.0 Hz), 3.56 (1H, m), 7.41–7.45 (5H, m); 19F NMR (600 MHz,
À57.5 (2F, m), À51.2 (1F, m), À48.6 (1F, m), À18.0 (3F, m); MS m/z:
666 (M+); HRMS Calcd for C19H7O2F21: 666.011 (M+), Found:
666.011; IR (KBr) cmÀ1: 1730, 1346, 1208, 1154, 1108.
CDCl3)
d
: À63.2 (2F, m), À58.6 (2F, m), À52.2 (2F, m), À18.2 (3F, m);
MS m/z: 384 (M+); HRMS Calcd for C13H9OF9S: 384.022 (M+),
Found: 384.022; IR (KBr) cmÀ1: 1693, 1392, 1221.

90
K. Sato et al. / Journal of Fluorine Chemistry 131 (2010) 86–90
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henicosafluoro-2-methyldodecanethioate (12b)
[1] (a) V.P. Kukhar’, V.A. Soloshonok (Eds.), Fluorine-containing Amino Acids: Synth-
esis and Properties, John Wiley & Sons, Chichester, 1995;
Colorless crystals; M.p. 68.0 8C; 1H NMR (CDCl3)
d
: 1.53 (3H, d,
J = 7.2 Hz), 3.56 (1H, m), 7.23–7.52 (5H, m); 19F NMR (600 MHz,
CDCl3)
(b) N.C. Yoder, K. Kumar, Chem. Soc. Rev. 31 (2002) 335–341;
(c) J.-P. Be´gue´, D. Bonnet-Delpon, Bioorganic and Medicinal Chemistry of
Fluorine, John Wiley & Sons, New Jersey, 2008.
d
: À63.3 (2F, m), À59.9 to À60.0 (2F, m), À59.2 (2F, m),
À58.7 to À58.9 (8F, m), À55.0 (2F, m), À48.8 (2F, m), À18.0 (3F, m);
MS m/z: 684 (M+); HRMS Calcd for C19H9OF21S: 684.004 (M+),
Found: 684.004; IR (KBr) cmÀ1: 1696, 1394, 1238, 1138.
[2] For the trifluoromethylation using an electrophilic trifluoromethylating reagents:
(a) T. Umemoto, S. Ishihara, J. Am. Chem. Soc. 115 (1993) 2156–2164;
(b) T. Umemoto, Chem. Rev. 96 (1996) 1757–1777 (and references therein);
(c) J.-A. Ma, D. Cahard, J. Org. Chem. 68 (2003) 8726–8729.
[3] For the trifluoromethylation of silyl and germyl enolates of esters and ketones:
(a) K. Miura, M. Taniguchi, K. Nozaki, K. Oshima, K. Utimoto, Tetrahedron Lett. 31
(1990) 6391–6394;
4.7. Spectroscopic data of
a-Rf aldehydes
(b) K. Miura, Y. Takeyama, K. Oshima, K. Utimoto, Bull. Chem. Soc. Jpn. 64 (1991)
1542–1553.
[4] For the trifluoromethylation of lithium enolate of imides:
(a) K. Iseki, T. Nagai, Y. Kobayashi, Tetrahedron Lett. 34 (1993) 2169–2170;
(b) K. Iseki, T. Nagai, Y. Kobayashi, Tetrahedron: Asymmetry 5 (1994) 961–974.
[5] For the trifluoromethylation of enamines:
4.7.1. 2-(1,2,2,3,3,4,4,4-Octafluorobutylidene)dodecanal (14a); as the
E–Z mixture
A colorless oil; 1H NMR (CDCl3)
d
: 0.89 (3H, t, J = 7.1 Hz), 1.27–
1.47 (16H, m), 2.30 (0.5H, m), 2.45 (1.5H, m), 9.98 (0.75H, m), 10.22
(0.25H, m); 19F NMR (600 MHz, CDCl3)
d
: À64.7 to À64.4 (2F, m),
`
(a) D. Cantacuzene, R. Dorme, Tetrahedron Lett. 25 (1975) 2031–2034;
À53.5 (0.2F, m), À49.5 to À49.4 (2F, m), À44.0 (0.8F, m), À17.7 (3F,
m); MS m/z: 382 (M+); HRMS Calcd for C16H22OF8: 382.154 (M+),
Found: 382.154; IR (neat) cmÀ1: 2924, 1694, 1228, 1122, 964, 736.
(b) D. Cantacuze`ne, C. Wakselman, R. Dorme, J. Chem. Soc., Perkin Trans. 1 (1977)
1365–1371;
(c) T. Kitazume, N. Ishikawa, J. Am. Chem. Soc. 107 (1985) 5186–5191;
(d) C. Semisch, P. Margaretha, J. Fluorine Chem. 30 (1986) 471–475.
[6] (a) J.E. Huheey, J. Phys. Chem. 69 (1965) 3284–3291;
(b) M. Yoshida, N. Kamigata, J. Fluorine Chem. 49 (1990) 1–20.
[7] (a) Y. Itoh, K. Mikami, Org. Lett. 7 (2005) 649–651;
(b) Y. Itoh, K. Mikami, Org. Lett. 7 (2005) 4883–4885;
(c) Y. Itoh, K. Mikami, Tetrahedron 62 (2006) 7199–7203;
(d) K. Mikami, Y. Tomita, Y. Ichikawa, K. Amikura, Y. Itoh, Org. Lett. 8 (2006)
4671–4673;
(e) Y. Itoh, K.N. Houk, K. Mikami, J. Org. Chem. 71 (2006) 8918–8925.
[8] D.A. Nagib, M.E. Scott, D.W.C. MacMillan, J. Am. Chem. Soc. 131 (2009) 10875–
10877.
[9] (a) K. Sato, T. Yuki, A. Tarui, M. Omote, I. Kumadaki, A. Ando, Tetrahedron Lett. 49
(2008) 3558–3561;
4.7.2. 2-(1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-
Icosafluorodecylidene)dodecanal (14b); as the E–Z mixture
Colorless crystals; M.p. 46.0 8C; 1H NMR (CDCl3)
d
: 0.88 (3H, t,
J = 6.5 Hz), 1.27–1.44 (16H, m), 2.31 (0.3H, m), 2.45 (1.7H, m), 9.99
(0.85H, m), 10.22 (0.15H, m); 19F NMR (600 MHz, CDCl3)
d
: À63.4
to À63.3 (2F, m), À60.1 (2F, m), À59.9 (2F, m), À59.1-À59.9 (8F, m),
À48.4-À48.3 (2F, m), À43.7-À44.6 (1F, m), À18.0 (3F, t, J = 9.7 Hz);
MS m/z: 682 (M+); HRMS Calcd for C22H22OF20: 682.135 (M+),
Found: 682.135; IR (KBr) cmÀ1: 2932, 1694, 1221, 1184.
(b) K. Sato, T. Yuki, R. Yamaguchi, T. Hamano, A. Tarui, M. Omote, I. Kumadaki, A.
Ando, J. Org. Chem. 74 (2009) 3815–3819.
[10] K. Sato, M. Higashinagata, T. Yuki, A. Tarui, M. Omote, I. Kumadaki, A. Ando, J.
Fluorine Chem. 129 (2008) 51–55.
[11] (a) J.M. Paratian, E. Labbe, S. Sibille, J.J. Perichon, Organomet. Chem. 489 (1995)
137–143;
(b) N. Kamigata, K. Udodaira, T. Shimizu, Phosphorus Sulfur Silicon Relat. Elem.
129 (1997) 155–168;
(c) I. Nowak, M.J. Robins, J. Org. Chem. 72 (2007) 2678–2681.
[12] S. Tews, R. Miethchen, H. Reinke, Synthesis (2003) 707–716;
(b) A. Wegert, R. Miethchen, M. Hein, H. Reinke, Synthesis (2005) 1850–1858.
[13] M. Mitani, H. Sakata, H. Tabei, Bull. Chem. Soc. Jpn. 75 (2002) 1807–1814.
4.7.3. 2-(1-Fluoro-1-pentafluorophenyl)ethylidenedodecanal (14c);
as the E–Z mixture
A colorless oil; 1H NMR (CDCl3)
d
: 0.88 (3H, t, J = 7.1 Hz), 1.21–
1.51 (16H, m), 2.41–2.45 (2H, m), 10.00 (0.6H, m), 10.22 (0.4H, m);
19F NMR (600 MHz, CDCl3)
d
: À93.4 (2F, m), À84.1 (1F, m), À73.9 to
À73.8 (2F, m), À16.9 to À16.8 (1F, m); MS m/z: 380 (M+); HRMS
Calcd for C19H22OF6: 380.157 (M+), Found: 380.157; IR (neat)
cmÀ1: 2928, 2860, 1694, 1652, 1500, 1186.