Ammonium bromides/KF catalyzed trifluoromethylation of carbonyl compounds with (trifluoromethyl)trimethylsilane and its application in the enantioselective trifluoromethylation reaction

Article abstract of DOI:10.1016/j.tet.2007.05.024

The trifluoromethylation of aldehydes and ketones is a potentially powerful method to introduce the CF₃ moiety into organic molecules. In general, the trifluoromethylation reaction has been performed by treatment of Me₃SiCF₃

Full text of DOI:10.1016/j.tet.2007.05.024

Tetrahedron 63 (2007) 8521–8528
Ammonium bromides/KF catalyzed trifluoromethylation of
carbonyl compounds with (trifluoromethyl)trimethylsilane and its
application in the enantioselective trifluoromethylation reaction
*
Satoshi Mizuta, Norio Shibata, Motoki Hibino, Shinichi Nagano,
*
Shuichi Nakamura and Takeshi Toru
Department of Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso,
Showa-ku, Nagoya 466-8555, Japan
Received 17 March 2007; revised 19 April 2007; accepted 7 May 2007
Available online 22 May 2007
Abstract—The trifluoromethylation of aldehydes and ketones is a potentially powerful method to introduce the CF3 moiety into organic mol-
ecules. In general, the trifluoromethylation reaction has been performed by treatment of Me3SiCF3 under initiation by TBAF, TBAT, TMAF as
well as CsF. However, these commercially available fluorides are rather expensive and moisture sensitive. Potassium fluoride (KF) is an in-
expensive and commonly used fluoride source and can be also used as an initiator for the trifluoromethylation, but the method suffers from the
significant limitation that only DMF is available as a solvent. Therefore, novel methods are highly desirable for laboratory-scale as well as
large-scale preparations. Here we wish to report a convenient procedure where a KF/TBAB combination acts as a catalyst for trifluoromethyl-
ation of aldehydes, ketones, and imides in a variety of organic solvents to provide trimethylsilyl-protected a-trifluoromethyl alcohols in good
to high yields. Application of the method in the enantioselective trifluoromethylation is also discussed.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
systems for this process. Following the initial report, a num-
ber of fluoride reagents5–9 such as tetrabutylammonium tri-
phenyldifluorosilicate (TBAT),5,7 tetramethylammonium
fluoride (TMAF),5,7 tris(dimethylamino)sulfonium difluoro-
trimethylsilicate (TASF)7 as well as cesium fluoride (CsF)8
have been successively reported to catalyze the trifluoro-
methylation with Me3SiCF3. On the other hand, trifluoro-
methylation catalyzed by other nucleophilic catalysts9a,10c
including Lewis bases10a,b such as trimethylamine
N-oxide,10d N-heterocyclic carbene,10e molecular sieves,10f
LiOAc,10g–i AcONBu4,10g–i phosphate salts,10j and
The synthesis of trifluoromethyl-containing organic com-
pounds has attracted significant interest in the fields of phar-
maceuticals, agrochemical chemistry, and material science
since these compounds possess unique properties.1 The con-
struction of a-trifluoromethyl alcohol units exemplified by
CF3C(OH)RR0 is particularly important as they frequently
are a constituent of biologically active molecules.2 Among
various methodologies available for the preparation of
a-trifluoromethyl alcohols, the nucleophilic trifluoromethyl-
ation reaction using Ruppert’s reagent ((trifluoromethyl)-
trimethylsilane, Me3SiCF3) is the most direct method for
introducing a CF3 unit in synthetically useful carbonyl com-
pounds.3 The Me3SiCF3 was first prepared by Ruppert
et al.,4 and in 1989, Prakash et al. found tetrabutylammo-
nium fluoride (TBAF) to be an effective catalyst for the tri-
fluoromethylation reaction of carbonyl compounds with
Me3SiCF3.5 The Me3SiCF3 is now becoming popular as
the Ruppert–Prakash reagent6 and considerable efforts
have been devoted to the development of efficient catalytic
10j
K2CO3 has made significant progress in recent years.
Our group has recently begun a program with the nucleo-
philic trifluoromethylation reaction. Tri-tert-butyl phos-
phine, as well as triphenylphosphine oxide catalyzed
trifluoromethylation of
a variety of carbonyls with
Me3SiCF3,11a and remote sulfinyl group-induced diastereo-
selective trifluoromethylation of aldehydes catalyzed by
TMAF11b have been reported. Lewis acids such as TiF4,
Ti(O-i-Pr)4, and Cu(OAc)2/1,2-bis(diphenylphosphino)-
ethane were also found to be able to promote the catalytic
trifluoromethylation of aldehydes.11c Although the catalytic
systems mentioned above for trifluoromethylation were ex-
amined by many research groups including us, the early fluo-
ride anion catalysis, especially TBAF, is still very important
because of its ability to promote transformations over a wide
Keywords: Trifluoromethylation; Enantioselective; Ammonium bromide;
Potassium fluoride; Cinchona alkaloid.
* Corresponding authors. Tel.: +81 527357543; fax: +81 527355442;
e-mail addresses: nozshiba@nitech.ac.jp; toru@nitech.ac.jp
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.024

8522
S. Mizuta et al. / Tetrahedron 63 (2007) 8521–8528
Table 1. Trifluoromethylation of 1a with Me3SiCF3
range of substrates with high chemical yields. Despite of its
good solubility and reactivity, it is relatively expensive and
very moisture sensitive. Potassium fluoride (KF) is an inex-
pensive and commonly used fluoride source and can also be
used as an initiator for trifluoromethylation,9 but the method
suffers from the significant limitation that only DMF is
available as a solvent. Although a KF/MeCN system with
or without 18-crown-6 is reported to catalyze the trifluoro-
methylation of carbonyls, the method is limited to fluoro
ketones and excess amount of KF is required.9b Therefore,
novel methods are highly desirable for laboratory-scale as
well as large-scale preparations. In the course of our research
program for the development of novel methodologies in
fluorine chemistry,12 we wish to report a convenient proce-
dure where a KF/TBAB combination (TBAB: tetrabutylam-
monium bromide) acts as a catalyst for trifluoromethylation
of aldehydes, ketones, and imides in a variety of organic sol-
vents to provide trimethylsilyl-protected a-trifluoromethyl
alcohols in good to high yields (Scheme 1).13 Application
of this method to the enantioselective trifluoromethylation
is also discussed.
O
OSiMe3
CF3
Me3SiCF3 (2.0 equiv.)
KF (10 mol%)
H
ammonium salt (10 mol%)
solvent, temp.
2a
Time (h) Yielda (%)
1a
Run Solvent Ammonium salt Temp
1
2
3
4
DMF
—
—
—
—
—
ꢀ20 ꢁC
0.5
12
12
12
12
82
Toluene
CH2Cl2
MeCN
THF
rt
Trace
Trace
Trace
12
rt
rt
rt
5
6
7
8
9
Toluene TBAB
CH2Cl2 TBAB
ꢀ20 ꢁC
ꢀ20 ꢁC
ꢀ20 ꢁC
ꢀ20 ꢁC
ꢀ20 ꢁC
ꢀ20 ꢁC
0 ꢁC
0.5
89
89
87
0.5
0.5
0.5
2
2
2
2
1
6
MeCN
THF
TBAB
TBAB
82
10
11
12
13
14
15
16
17
18
19
20
21
22
Toluene TBAC
THF TBAC
Toluene TEAB
THF TEAB
Toluene TEAC
THF TEAC
Toluene TMAB
THF TMAB
Toluene TMAC
THF TMAC
Toluene CTMAB
THF CTMAB
Toluene TBAB
80b
83b
92
0 ꢁC
82
87
81
ꢀ20 ꢁC
0 ꢁC
ꢀ20 ꢁC 12
ꢀ20 ꢁC 12
Trace
Trace
77
0 ꢁC
0.5
1
0.5
0.5
ꢀ20 ꢁC
ꢀ20 ꢁC
ꢀ20 ꢁC
rt
63
81
90
O
Me3SiCF3 (2.0 equiv.)
Me3SiO CF3
R'
KF/ ammonium bromide
(10 mol%), toluene
R
R
R'
12
Tracec
Scheme 1.
Determined by 19F NMR with standard material, benzotrifluoride.
A mixture of 2a and its desilylated 2a (OH form).
The reaction was carried out in the absence of KF.
a
b
c
2. Results and discussion
bromide (TMAB, runs 16 and 17). The reaction did not pro-
ceed in the absence of KF (run 22).
2.1. Trifluoromethylation of aldehydes, ketones,
and imides
We next applied these conditions to the trifluoromethylation
of a number of aldehydes (1b–j), ketones (3a–c), and imides
(3d,e) to assess the potential scope and limitations of the
method. The results are summarized in Tables 2 and 3.
Aryl aldehydes such as benzaldehyde (entries 1 and 2),
1-naphthaldehyde (entries 3 and 4), and p- or o-methoxy-
benzaldehyde (entry 5–8) reacted in high yields (84–99%).
As we mentioned in Section 1, a catalytic amount of KF acts
a good trigger for the trifluoromethylation of aldehyde 1a
with Me3SiCF3 in DMF at ꢀ20 ꢁC for 30 min (Table 1,
run 1). However, the reaction of 1a with Me3SiCF3 failed
to provide the adduct 2a in toluene, MeCN, or CH2Cl2 at
room temperature (runs 2–4). When we attempted the
same reaction in THF, the reaction was not complete at
room temperature even after 12 h. Only 2a was obtained in
12% yield (run 5). Incidentally, KF combined with quater-
nary ammonium salts have been shown as efficient fluorinat-
ing agents;14 however, none have been reported to be used in
the trifluoromethylation of carbonyls with Me3SiCF3. We
therefore decided to add TBAB as a co-catalyst in all the
cases. Reaction of 1a with Me3SiCF3 in the presence of
catalytic amounts of KF and TBAB in toluene, MeCN,
CH2Cl2, or THF at ꢀ20 ꢁC gave 2a in high yields within
30 min, confirming our expectations. We next examined
the effect of a variety of commercially available ammonium
salts as additives for the KF-catalyzed trifluoromethylation
reaction of 1a with Me3SiCF3. The results collected in Table
1 refer to a representative variety of quaternary ammonium
salts. Not surprisingly, the reaction is not limited to TBAB.
Ammonium salts such as tetrabutylammonium chloride
(TBAC), tetraethylammonium bromide (TEAB), tetraethyl-
ammonium chloride (TEAC), tetramethylammonium chlo-
ride (TMAC), and cetyl tetramethylammonium bromide
(CTMAB) were equally effective as initiators when com-
bined with KF, affording the CF3 adduct 2a in high yields
(runs 10–21), except for the cases of tetramethylammonium
Table 2. KF/TBAB catalyzed trifluoromethylation of 1 with Me3SiCF3
O
Me3SiCF3 (2.0 equiv.)
Me3SiO CF3
KF/ TBAB (10 mol%)
solvent, temp. time
R
H
R
H
1b—j
2b—j
Entry 1
R
Solvent Temp (ꢁC) Time (h) Yielda (%)
1
2
3
4
5
6
7
8
1b Ph
1b Ph
Toluene rt
THF
Toluene 0
THF
Toluene ꢀ20
THF
Toluene ꢀ20
THF rt
Toluene ꢀ20
THF
ꢀ20
Toluene ꢀ20
THF
ꢀ20
Toluene ꢀ20
THF rt
0.5
0.5
1
0.5
0.5
0.5
0.5
1
0.5
1
1
0.5
0.5
6
0.5
0.5
0.5
91
94
99
90
88
92
84
85
88
99
96
88
90
94
94
98
79
0
1c 1-Naphthyl
1c 1-Naphthyl
1d p-MeOC6H4–
1d p-MeOC6H4–
1e o-MeOC6H4–
1e o-MeOC6H4–
1f p-BrC6H4–
1f p-BrC6H4–
1g p-NO2C6H4–
1g p-NO2C6H4–
1h o-NO2C6H4–
1h o-NO2C6H4–
0
0
9
10
11
12
13
14
15
16
17
1i PhCH]CH-(E) Toluene 0
1j n-Heptyl
1j n-Heptyl
Toluene rt
THF
ꢀ20
a
Isolated yield.

S. Mizuta et al. / Tetrahedron 63 (2007) 8521–8528
8523
Table 3. KF/TBAB catalyzed trifluoromethylation of 3 with Me3SiCF3
that TBAB might be acting as some kind of phase transfer
catalyst, which can help solubilize KF.15 Although the reac-
tive species has not been ascertained yet, the catalytic system
using KF/ammonium bromide in toluene represents an at-
tractive method for the trifluoromethylation of a range of
carbonyl compounds. Compared to TBAF, the ammonium
bromides and chlorides such as TBAB and TBAC are stable
to moisture and are inexpensive.
O
Me3SiO
R
CF3
R'
Me3SiCF3 (2.0 equiv.)
KF/ TBAB (10 mol%)
toluene, rt, time
R
R'
4a—e
3a—e
Entry
1
3
Time
(h)
4
Yielda
(%)
O
F3C OSiMe3
Me
0.5
0.5
2
89
2.3. Enantioselective trifluoromethylation
4a
Me
3a
Asymmetric nucleophilic trifluoromethylation of carbonyl
compounds represents an effective approach for the syn-
thesis of optically active trifluoromethylated alcohols,16
important synthons for the preparation of drugs such as
Befloxatone2a and Efavirenz.2b Chiral trifluoromethylated
alcohols are also attracting much attention in the field of
material sciences, especially the development of novel liquid
crystals17 (Fig. 1).
O
F3C
OSiMe3
2
3
90
48
4b
3b
O
F3C OSiMe3
F3C
3c
4c
O
OSiMe3
4
N
24
N
86
3d
4d
Among the methods available to prepare these chiral syn-
thons,18 enantioselective catalysis is particularly important
due to the accessibility of both enantiomers, and the ease
with which small variations in the product can be introduced.
However, chiral auxiliary-based stereoselective trifluorome-
thylation is still the most widely applied approach19 and
enantioselective catalysis is still a challenge.20 Enantioselec-
tive trifluoromethylation using Me3SiCF3 was first examined
by Iseki et al. in 1994.20a Chiral ammonium fluorides derived
from cinchona alkaloids catalyzed the trifluoromethylation
reaction of aldehydes to furnish the corresponding trifluoro-
methylated alcohols with low to moderate enantioselectiv-
ities up to 51% ee. After the initial report, considerable
efforts were devoted to the development of an efficient cat-
alytic system for the nucleophilic enantioselective trifluoro-
methylation reaction,20 but the observed enantioselectivity
has not improved except for one example reported by Pfizer
research group.20c Their report suggests the enantioselectiv-
ity of the reaction is highly substrate dependent and the high
enantioselectivity could be achieved by a thorough screen-
ing of chiral ammonium fluorides. However, this protocol
is not an acceptable solution to this issue due to the trouble-
some preparation and purification of highly hygroscopic an-
hydrous ammonium fluorides from the corresponding chiral
ammonium salts.21 We therefore decided to extend our KF/
ammonium bromide strategy to the enantioselective trifluoro-
methylation reaction.22 Activation of KF with readily acces-
sible chiral ammonium bromide derived from cinchona
Ph
Ph
O
O
O
F3C
OSiMe3
N
24b
77c
3e
c
5
N
4e
t
t
CO2 Bu
CO2 Bu
O
O
a
Isolated yield.
Reaction was carried out at 40 ꢁC.
Mixture of 4e and its OH form.
b
c
Entries 9–12 further demonstrated that the present conditions
tolerated functional groups on the aromatics such as bromo
and nitro groups. Selective 1,2-addition was observed in
the reaction of cinnamyl aldehyde (1i) with Me3SiCF3 to
furnish the trimethylsilyl ether ofallyl alcohol 2i in high yield
(94%, entry 15). The reactions involving enolizable alde-
hydes posed some additional challenges due to the possibility
of proton abstraction by the hard fluoride anion. As shown in
entries 16 and 17, the enolizable n-octyl aldehyde (1j) was
nicely converted to the corresponding a-trifluoromethyl
alcohol 2j in high yields under the KF/TBAB combination.
Ketones (3a–c) and imides (3d,e) also reacted nicely under
the conditions described above in good to high yields (Table
3), but the trifluoromethylation of imides (3d,e) was rela-
tively slow (entries 4 and 5), and the cyclohexanone (3c)
shown in entry 3 afforded CF3 adduct in moderate yield
(48%, entry 3).
OMe
2.2. Reactive species
O
F3C
N
OH
Cl
The KF/TBAB combination has proven effective for the tri-
fluoromethylation of carbonyl compounds and the results are
similar to those observed by TBAF catalyst. In order to dis-
cuss a reactive species in the reaction, we investigated the
NMR study of the combination. The 19F NMR gave the
broad signal at ꢀ113 ppm (ꢀ105 ppm to ꢀ120 ppm) for
TBAF monohydrate in toluene-d8, whereas KF/TBAB in tol-
uene-d8 did not give any signal. These results show that in
situ generation of TBAF from the KF/TBAB combination
could be ruled out under this condition. Therefore, it appears
O
O
F3C
O
N
H
O
Efavirenz
Befloxatone
N
N
O
O
n-C12H25-O
O
CF3
C6H13
O
liquid crystal
Figure 1.

8524
S. Mizuta et al. / Tetrahedron 63 (2007) 8521–8528
alkaloids may allow for the rapid determination of suitable
catalysts for a number of substrates in the enantioselective
trifluoromethylation.
optimized conditions described above. A better result was
obtained when the 1a was treated with Me3SiCF3 in the pres-
ence of the KF/5b combination. The optically active 2a was
produced in 81% yield with 26% ee (entry 2). The better se-
lectivity of this catalyst might result from the CF3 substituent
on the aromatic ring. The cinchonium bromides, which have
CF3 groups on their aromatic moiety, were screened under
the same conditions. The cinchonium bromides were easily
prepared from cinchonine by quaternization using commer-
cially available CF3-substituted benzyl bromides in reflux-
ing THF overnight. We found that the ee of 2a was
slightly improved to 40% ee when the reaction of 1a with
Me3SiCF3 was carried out using the KF/5g combination at
room temperature for 18 h (entry 7). Interestingly, in the
presence of KF/ammonium chloride 5h, the trifluoromethyl-
ation of 1a smoothly proceeded to completion in only 3.5 h
to give 2a in 90% yield, albeit at slightly lower enantioselec-
tivity (entry 8, 36% ee). Finally, the enantioselective trifluoro-
methylation was also attempted using commercially
available organocatalysts, N-spiro C2-symmetric chiral
ammonium bromide 623 and TaDiAS diiodide 724 in the
presence of KF; however, the enantioselectivity was not im-
proved and more through optimization of the conditions for
each catalyst is required (runs 9–11).
In screening the cinchona alkaloid, the reaction of 2-naph-
thaldehyde (1a) with Me3SiCF3 was examined as a model
reaction (Table 4). First, commercially available cinchonium
bromides, 5a and 5b, were used in this reaction under the
Table 4. KF/chiral ammonium halides catalyzed enantioselective trifluoro-
methylation of 1a with Me3SiCF3
OH
O
1) Me3SiCF3 (2.0 equiv.)
CF3
KF (5 mol%)/ 5—7 (10 mol%)
H
*
toluene, temp (°C), time (h)
2) HCl aq
1a
(R)-2a (OH form)
F3C
5a: Ar=
N
CF3
5e: Ar=
Ar
HO
H
H
CF3
5b: Ar=
5c: Ar=
5d: Ar=
Br
F3C
CF3
N
5f: Ar=
5a—g
CF3
CF3
3. Conclusion
CF3
F3C
N
5g: Ar=
In conclusion, we have developed a general synthetic strat-
egy for the trifluoromethylation of carbonyl compounds
based on the ammonium bromide/KF combination. Our
approach does not require polar solvents especially DMF.
This represents an advantage of ammonium bromide/KF
combination because DMF solvent is often a major draw-
back when we attempt at extension of this chemistry to
asymmetric transformations. Compared to TBAF, the am-
monium bromides and chlorides are stable to moisture.
The catalytic system using KF/TBAB in toluene is inexpen-
sive and represents an attractive method for the trifluorome-
thylation of a range of carbonyl compounds. The usefulness
of the methodology was demonstrated by enantioselective
trifluoromethylation to provide the enantiomerically rich tri-
fluoromethylated alcohols, which constitute key structural
components of important drugs. Since chiral ammonium
bromides can be easily prepared without the use of typical
anion-exchange resins, highly hygroscopic anhydrous
chiral ammonium fluorides, which require troublesome
preparations and purifications would no longer be prerequi-
site. Utilizing the ubiquitous readily available chiral ammo-
nium bromides,25 this catalytic system offers a convenient
straightforward route to various chiral CF3-contaning
organic molecules.
HO
H
CF3
H
CF3
Cl
N
OMe
5h
OMe
F
F
Br
F
F
N
t
Bu
O
Me
Me
N
2I
Me
O
N
F
F
OMe
MeO
7
6
Run Ammonium salt Temp Time (h) Yielda (%) eeb (%)
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
5g
5h
6
rt
0
10
2
67
81
67
44
58
34
54
90
76
9
10
26
19
19
31
28
40
36
ꢁC
rt
rt
rt
rt
rt
0
24
24
16
48
18
ꢁC
3.5
4. Experimental
4.1. General
9
rt
15
12
48
2e
10c
11
6
7
rtd
rt
11e
2
47
a
Isolated yield.
Determined by HPLC analysis using CHIRALCEL OJ-H.
The reaction was carried out in THF.
All reactions were performed in oven- and flame-dried glass-
ware under a positive pressure of nitrogen. All of the reac-
tions were monitored by thin-layer chromatography (TLC)
carried out on 0.25 mm Merck silica-gel plate (60F-254).
The TLC plates were visualized with UV light and 7%
b
c
d
The reaction was started at ꢀ78 ꢁC, then the reaction temperature was
allowed to warm to rt over 2 h.
(S)-2a was obtained.
e

S. Mizuta et al. / Tetrahedron 63 (2007) 8521–8528
8525
phosphomolybdic acid in ethanol/heat or p-anisaldehyde
in ethanol/heat. Column chromatography was carried out
on a column packed with silica gel 60N spherical neutral
size 63–210 mm. 1H NMR (200 MHz) and 19F NMR
(188 MHz) spectra for solutions in CDCl3 were recorded
on a Varian Gemini-200. Chemical shifts (d) are expressed
in parts per million downfield from internal tetramethylsi-
lane for 1H NMR and CFCl3 for 19F NMR. Infrared spectra
were recorded on a JASCO FT/IR-200 spectrometer. Mass
spectra (EI) were taken on a SHIMADZU GC-MS-
QP5050A. Mass spectra (ESI) were taken on a SHIMADZU
LCMS-2010EV. HPLC analyses were performed on
a JASCO PU-2080 Plus or SHIMADZU LC-2010A HT
using 4.5ꢂ259 mm Daicel CHIRALCEL OJ-H. Optical
rotations were measured on a HORIBA SEPA-300.
KF (1.8 mg, 0.032 mmol) in THF (1 mL) gave 2d (81.5 mg,
92%) as a colorless oil. H NMR (CDCl3) d 0.11 (s, 9H),
1
3.81 (s, 3H), 4.85 (q, J¼6.6 Hz, 1H), 6.88 (dt, J¼2.6,
9.0 Hz, 2H), 7.34 (d, J¼8.2 Hz, 2H); 19F NMR (CDCl3)
d ꢀ78.8 (d, J¼6.0 Hz, 3F); IR (neat) 2960, 2840, 1614,
1516, 1466, 1368, 1254, 1172, 1131, 1036, 882, 845, 754,
682, 623, 587, 527 cmꢀ1; MS (EI, m/z) 278 (M+).
4.1.5. Trimethyl[2,2,2-trifluoro-1-(2-methoxyphenyl)-
ethoxy]silane (2e).20c Using the typical procedure, reaction
of 1e (38.9 mL, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.63 mmol), catalyzed TBAB (10.3 mg, 0.032 mmol), and
KF (1.8 mg, 0.032 mmol) in THF (1 mL) gave 2e
(75.7 mg, 85%) as a colorless oil. 1H NMR (CDCl3) d 0.08
(s, 9H), 3.84 (s, 3H), 5.53 (q, J¼6.6 Hz, 1H), 6.87 (d,
J¼8.4 Hz, 1H), 6.98 (dt, J¼1.8, 7.4 Hz, 1H), 7.31 (dt,
J¼1.8, 8.4 Hz, 1H), 7.56 (d, J¼7.6 Hz, 1H); 19F NMR
(CDCl3) d ꢀ78.3 (d, J¼6.6 Hz, 3F); IR (neat) 2961, 2843,
1605, 1592, 1494, 1467, 1442, 1378, 1250, 1173, 1134,
1090, 1050, 1030, 885, 847, 756, 685, 628 cmꢀ1; MS
(ESI, m/z) 301.0 (M+Na+).
4.1.1. Typical procedure for the trifluoromethylation:
trimethyl[2,2,2-trifluoro-1-(2-naphthalenyl)ethoxy]-
silane (2a).10j To a mixture of 1a (50.0 mg, 0.32 mmol),
TBAB (10.3 mg, 0.032 mmol), and KF (1.8 mg,
0.032 mmol) in toluene (1.0 mL) was added Me3SiCF3
(94.6 mL, 0.63 mmol) at ꢀ20 ꢁC. After 30 min, the reaction
was quenched with water, and the aqueous layer was ex-
tracted with ethyl acetate (2ꢂ5 mL). The combined organic
extracts were washed with brine, dried over MgSO4, and
concentrated under reduced pressure. The crude product
was purified by column chromatography on silica gel (n-
hexane). Product 2a was obtained in 89% yield, as a white
4.1.6. [1-(4-Bromophenyl)-2,2,2-trifluoroethoxy]tri-
methylsilane (2f).10j Using the typical procedure, reaction
of 1f (59.2 mg, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.63 mmol), catalyzed TBAB (10.3 mg, 0.032 mmol), and
KF (1.8 mg, 0.032 mmol) in THF (1 mL) gave 2f
(112.5 mg, 99%) as a colorless oil. 1H NMR (CDCl3)
d 0.12 (s, 9H), 4.86 (q, J¼6.6 Hz, 1H), 7.31 (d, J¼8.4 Hz,
2H), 7.50 (d, J¼8.4 Hz, 2H); 19F NMR (CDCl3) d ꢀ78.8 (d,
J¼6.0 Hz, 3F); IR (neat) 2960, 2900, 1594, 1489, 1407,
1367, 1257, 1173, 1135, 1012, 880, 846, 755, 725, 667,
622 cmꢀ1; MS (EI, m/z) 328 (M++1), 326 (M+ꢀ1).
1
solid. H NMR (CDCl3) d 0.14 (s, 9H), 5.07 (q, J¼6.4 Hz,
1H), 7.47–7.58 (m, 3H), 7.82–7.88 (m, 4H); 19F NMR
(CDCl3) d ꢀ78.2 (d, J¼6.0 Hz, 3F); IR (KBr) 3066, 2958,
2927, 2856, 1363, 1262, 1177, 1128, 969, 900, 853, 818,
748, 697, 575, 548 cmꢀ1; MS (EI, m/z) 298 (M+). Although
the reaction can also be performed using a catalytic amount
of TBAC, a mixture of 2a and desilylated 2a was obtained.
4.1.7. Trimethyl[2,2,2-trifluoro-1-(4-nitrophenyl)eth-
oxy]silane (2g).10j Using the typical procedure, reaction
of 1g (48.4 mg, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.63 mmol), catalyzed TBAB (10.3 mg, 0.032 mmol), and
KF (1.8 mg, 0.032 mmol) in toluene (1 mL) gave 2g
(89.7 mg, 96%) as a colorless oil. 1H NMR (CDCl3) d 0.15
(s, 9H), 5.01 (q, J¼6.4 Hz, 1H), 7.64 (d, J¼9.0 Hz, 2H), 8.24
(dt, J¼2.4, 8.8 Hz, 2H); 19F NMR (CDCl3) d ꢀ78.2 (d,
J¼6.0 Hz, 3F); IR (neat) 2961, 2900, 1528, 1351, 1269,
4.1.2. Trimethyl(2,2,2-trifluoro-1-phenylethoxy)silane
(2b).10j Using the typical procedure, reaction of 1b
(32.5 mL, 0.32 mmol) with Me3SiCF3 (94.6 mL, 0.63 mmol),
catalyzed TBAB (10.3 mg, 0.032 mmol), and KF (1.8 mg,
0.032 mmol) in THF (1 mL) gave 2b (113.4 mg, 94%) as
1
a colorless oil. H NMR (CDCl3) d 0.11 (s, 9H), 4.90 (q,
J¼6.6 Hz, 1H), 7.34–7.50 (m, 5H); 19F NMR (CDCl3)
d ꢀ78.5 (d, J¼6.0 Hz, 3F); IR (neat) 3069, 3036, 2961,
2898, 1497, 1456, 1369, 1271, 1172, 1133, 1031, 882,
756, 701, 634, 552 cmꢀ1; MS (EI, m/z) 248 (M+).
1176, 1138, 1016, 879, 848, 753, 710, 623, 554, 533 cmꢀ1
;
MS (EI, m/z) 293 (M+).
4.1.8. Trimethyl[2,2,2-trifluoro-1-(2-nitrophenyl)eth-
oxy]silane (2h).11a Using the typical procedure, reaction
of 1h (48.4 mg, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.63 mmol), catalyzed TBAB (10.3 mg, 0.032 mmol), and
KF (1.8 mg, 0.032 mmol) in THF (1 mL) gave 2h
(88.2 mg, 94%) as a colorless oil. 1H NMR (CDCl3) d 0.17
(s, 9H), 6.12 (q, J¼6.0 Hz, 1H), 7.53 (dt, J¼1.4, 8.8 Hz,
1H), 7.68 (dt, J¼1.4, 7.8 Hz, 1H), 7.93 (d, J¼1.2 Hz, 2H),
7.97 (d, J¼1.2 Hz, 1H); 19F NMR (CDCl3) d ꢀ78.2 (d,
J¼5.0 Hz, 3F); IR (neat) 2962, 1682, 1536, 1353, 1258,
1176, 1137, 884, 849, 788, 748, 714, 673, 627 cmꢀ1; MS
(EI, m/z) 293 (M+).
4.1.3. Trimethyl[2,2,2-trifluoro-1-(1-naphthalenyl)eth-
oxy]silane (2c).10f Using the typical procedure, reaction of 1c
(43.5 mL, 0.32 mmol) with Me3SiCF3 (94.6 mL, 0.63 mmol),
catalyzed TBAB (10.3 mg, 0.032 mmol), and KF (1.8 mg,
0.032 mmol) in toluene (1 mL) gave 2c (75.5 mg, 99%) as
1
a white solid. H NMR (CDCl3) d 0.10 (s, 9H), 5.74 (q,
J¼6.2 Hz, 1H), 7.46–7.62 (m, 3H), 7.79–7.89 (m, 3H), 8.08
(d, J¼8.0 Hz, 1H); 19F NMR (CDCl3) d ꢀ77.4 (d, J¼6.0 Hz,
3F); IR (KBr) 3066, 2962, 1599, 1514, 1354, 1272, 1172,
1131, 1008, 875, 850, 798, 776, 751, 696, 633, 536,
442 cmꢀ1; MS (EI, m/z) 298 (M+).
4.1.4. Trimethyl[2,2,2-trifluoro-1-(4-methoxyphenyl)-
ethoxy]silane (2d).10j Using the typical procedure, reaction
of 1d (38.9 mL, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.63 mmol), catalyzed TBAB (10.3 mg, 0.032 mmol), and
4.1.9. Trimethyl[[(2E)-3-phenyl-1-(trifluoromethyl)-2-
propenyl]oxy]silane (2i).10j Using the typical procedure, re-
action of 1i (40.3 mL, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.63 mmol), catalyzed TBAB (10.3 mg, 0.032 mmol), and

8526
S. Mizuta et al. / Tetrahedron 63 (2007) 8521–8528
KF (1.8 mg, 0.032 mmol) in toluene (1 mL) gave 2i
(124.3 mg, 94%) as a colorless oil. 1H NMR (CDCl3)
d 0.20 (s, 9H), 4.55 (quint, J¼6.4 Hz, 1H), 6.17 (dd,
J¼6.4, 16.0 Hz, 1H), 6.74 (d, J¼16.0 Hz, 1H) 7.24–7.50
(m, 5H); 19F NMR (CDCl3) d ꢀ78.7 (d, J¼7.0 Hz, 3F); IR
(neat) 3030, 2961, 1373, 1271, 1132, 970, 893, 847, 749,
694 cmꢀ1; MS (EI, m/z) 274 (M+).
1H); 19F NMR (CDCl3) d ꢀ79.3 (s, 3F); IR (KBr) 3065,
3035, 2965, 2925, 1715, 1381, 1307, 1258, 1192, 1120,
1084, 987, 965, 952, 895, 875, 849, 726, 705 cmꢀ1; MS
(ESI, m/z) 306.0 (MꢀꢀTMS).
4.1.15. (3-Oxo-1-trifluoromethyl-1-trimethylsilanyloxy-
1,3-dihydro-isoindol-2-yl)-acetic acid tert-butyl ester
(4e) and (1-hydroxy-3-oxo-1-trifluoromethyl-1,3-dihy-
dro-isoindol-2-yl)-acetic acid tert-butyl ester (4e, OH
form).11a Using the typical procedure, reaction of 3e
(83.6 mg, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.64 mmol), catalyzed TBAB (10.3 mg, 0.032 mmol), and
KF (1.8 mg, 0.032 mmol) in toluene (1 mL) gave 4e
(87.3 mg, 68%) as a colorless oil and its OH form
4.1.10. Trimethyl(1-trifluoromethyloctyloxy)silane
(2j).11a Using the typical procedure, reaction of 1j
(51.8 mL, 0.33 mmol) with Me3SiCF3 (97.8 mL, 0.66 mmol),
catalyzed TBAB (10.7 mg, 0.033 mmol), and KF (1.9 mg,
0.033 mmol) in toluene (1 mL) gave 2j (88.3 mg, 98%) as
a colorless oil. 1H NMR (CDCl3) d 0.16 (s, 9H), 0.89
(t, J¼6.8 Hz, 3H), 1.28 (br s, 9H), 1.54–1.70 (m, 2H),
3.78–3.98 (m, 1H); 19F NMR (CDCl3) d ꢀ78.8 (d,
J¼6.6 Hz, 3F); IR (neat) 2957, 2928, 2859, 1467, 1392,
1281, 1254, 1166, 1146, 844, 754, 722, 689 cmꢀ1; MS (EI,
m/z) 270 (M+).
1
(10.0 mg, 9.4%) as a white solid. Compound 4e: H NMR
(CDCl3) d ꢀ0.08 (s, 9H), 1.47 (s, 9H), 3.98 (d, J¼17.4 Hz,
1H), 4.24 (d, J¼17.2 Hz, 1H), 7.57–7.70 (m, 3H), 7.83–
7.94 (m, 1H); 19F NMR (CDCl3) d ꢀ80.1 (s, 3F); IR (neat)
2979, 1757, 1731, 1470, 1414, 1372, 1298, 1256, 1228,
1176, 1068, 981, 892, 876, 849, 744, 721; MS (EI, m/z)
330 (M+ꢀTMS). Compound 4e (OH form): 1H NMR
(CDCl3) d 1.49 (s, 9H), 4.06 (d, J¼18.0 Hz, 1H), 4.76 (d,
J¼18.0 Hz, 1H), 5.18 (br s, OH), 7.60–7.8 (m, 4H); 19F
NMR (CDCl3) d ꢀ79.3 (s, 3F); IR (KBr) 3118, 2981,
2930, 1756, 1712, 1697, 1475, 1423, 1370, 1272, 1228,
1171, 1080, 968, 946, 853, 768, 744, 735, 695, 625, 582,
556; MS (EI, m/z) 332 (M++1).
4.1.11. Trimethyl(2,2,2-trifluoro-1-methyl-1-phenyl-
ethoxy)silane (4a).10j Using the typical procedure, reaction
of 3a (37.3 mL, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.63 mmol), TBAB (10.3 mg, 0.032 mmol), and KF
(1.8 mg, 0.032 mmol) in toluene (1 mL) gave 4a (150.0 mg,
1
89%) as a colorless oil. H NMR (CDCl3) d 0.14 (s, 9H),
1.82 (s, 3H), 7.30–7.45 (m, 3H), 7.57–7.60 (m, 2H); 19F
NMR (CDCl3) d ꢀ81.7 (s, 3F); IR (neat) 2961, 1449, 1381,
1297, 1255, 1172, 1105, 1073, 995, 864, 845, 759, 698,
653 cmꢀ1; MS (EI, m/z) 262 (M+).
4.1.16. Enantioselective trifluoromethylation of 1a: (R)-
1-(20-naphthyl)-2,2,2-trifluoroethanol (2a).11b A mixture
of N-(3,5-bistrifluoromethyl)benzyl cinchonium bromide
(19.3 mg, 0.032 mmol) and KF (0.93 mg, 0.016 mmol) in
toluene (1.0 mL) was stirred at room temperature for 1 h
under N2 atmosphere. After addition of 1a (50.0 mg,
0.32 mmol), reaction mixture was cooled to 0 ꢁC. And
then Me3SiCF3 (95 mL, 0.64 mmol) was added and reaction
temperature was gradually increased to room temperature
over 1 h. After stirring for 18 h, the reaction was quenched
with water, and to the mixture was added 1 M HCl aqueous
solution (1 mL) and THF (1 mL), and stirred for 1 h. The
aqueous layer was extracted with ethyl acetate (2ꢂ5 mL).
The combined organic extracts were washed with brine,
dried over MgSO4, and concentrated under reduced pres-
sure. The crude product was purified by column chromato-
graphy on silica gel (EtOAc/n-hexane¼90:10). Product
(R)-2a was obtained in 54% yield, 40% ee as a white solid.
1H NMR (CDCl3) d 2.59 (br d, OH), 5.11–5.29 (m, 1H),
7.51–7.59 (m, 3H), 7.85–7.95 (m, 4H); 19F NMR (CDCl3)
d ꢀ78.1 (d, J¼7.0 Hz, 3F). The ee of the product was deter-
mined by HPLC using a Daicel Chiralcel OJ-H column (n-
hexane/i-PrOH¼90:10, flow rate 1.0 mL/min, l¼254 nm,
tR¼16.1 min, tS¼24.9 min); [a]2D5 ꢀ13.5 (c 0.36, CHCl3,
40% ee). The absolute configuration of 2a was assigned
to (R) by the relative retention times of the (R/S)-isomers
reported in the literature.11b
4.1.12. 9-(Trifluoromethyl)-9H-fluoren-9-yl trimethyl-
silyl ether (4b).26 Using the typical procedure, reaction of
3b (57.5 mg, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.63 mmol), catalyzed TBAB (10.3 mg, 0.032 mmol), and
KF (1.8 mg, 0.032 mmol) in toluene (1 mL) gave 4b
(92.9 mg, 90%) as a white solid. 1H NMR (CDCl3)
d ꢀ0.27 (s, 9H), 7.31 (dt, J¼1.2, 7.6 Hz, 2H), 7.74 (dt,
J¼1.4, 7.6 Hz, 2H), 7.60–7.69 (m, 4H); 19F NMR (CDCl3)
d ꢀ80.0 (s, 3F); IR (neat) 3068, 2965, 1964, 1925, 1608,
1451, 1409, 1306, 1253, 1181, 1118, 1082, 970, 943, 925,
889, 868, 843, 761, 739 cmꢀ1; MS (ESI, m/z) 271.1
(M+Na+ꢀTMS).
4.1.13. Trimethyl(1-trifluoromethylcyclohexyloxy)silane
(4c).5a Using the typical procedure, reaction of cyclohexa-
none 3c (33.1 mL, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.63 mmol), catalyzed TBAB (10.3 mg, 0.032 mmol), and
KF (1.8 mg, 0.032 mmol) in toluene (1 mL) gave 4c
(36.6 mg, 48%) as a colorless oil. 1H NMR (CDCl3) d 0.16
(s, 9H), 1.08–1.90 (m, 10H); 19F NMR (CDCl3) d ꢀ82.7
(s, 3F); IR (KBr) 2943, 2865, 1453, 1362, 1310, 1285,
1253, 1158, 1089, 1037, 899, 845, 757, 644; MS (EI, m/z)
240 (M+).
4.1.14. 2-Benzyl-3-hydroxy-3-trifluoromethyl-2,3-dihy-
dro-isoindol-1-one (4d).11a Using the typical procedure, re-
action of 3d (76.0 mg, 0.32 mmol) with Me3SiCF3 (94.6 mL,
0.63 mmol), catalyzed TBAB (10.3 mg, 0.032 mmol), and
KF (1.8 mg, 0.032 mmol) in toluene (1 mL) gave 4d
(104.6 mg, 86%) as a white solid. 1H NMR (CDCl3) d
0.12 (s, 9H), 4.55 (d, J¼15.8 Hz, 1H), 4.88 (d, J¼15.4 Hz,
1H), 7.22–7.37 (m, 5H), 7.56–7.70 (m, 3H), 7.84–7.94 (m,
4.1.17. N-3,5-Bis(trifluoromethylbenzyl)cinchonium bro-
mide (5g). A solution of cinchonine (200 mg, 0.68 mmol)
and
2,5-bis(trifluoromethylbenzyl)bromide
(150 mL,
1.08 mmol) in THF (20 mL) was refluxed under N2 atmo-
sphere. After 12 h, the reaction mixture was concentrated
under reduced pressure and recrystallized from ether/
CH2Cl2 to give 5g (347 mg, 85%) as a white solid.

S. Mizuta et al. / Tetrahedron 63 (2007) 8521–8528
8527
1H NMR (CDCl3) d 0.60–0.95 (m, 1H), 1.40–1.95 (m, 3H),
2.09 (t, J¼10.8 Hz, 1H), 2.34 (q, J¼7.4 Hz, 1H), 2.55 (q,
J¼10.4 Hz, 1H), 3.05 (t, J¼10.8 Hz,1H), 4.00–4.20 (m,
2H), 4.57 (t, J¼10.4 Hz, 1H), 5.16–5.29 (m, 2H), 5.61 (d,
J¼12.2 Hz, 1H), 5.74–5.91 (m, 1H), 6.51 (s, 2H), 6.66
(d, J¼11.8 Hz, 1H), 6.98 (quint, J¼7.2 Hz, 2H), 7.53 (d,
J¼8.2 Hz, 1H), 7.78–7.81 (m, 2H), 8.20–8.30 (br s, 3H),
8.80 (d, J¼4.4 Hz, 1H); 19F NMR (CDCl3) d ꢀ62.8 (s,
6F); IR (KBr) 3216, 1592, 1510, 1459, 1373, 1279, 1180,
1135, 1002, 920, 906, 775, 711, 683 cmꢀ1; MS (ESI, m/z)
522.2 (M+–Br); [a]D25 +102.9 (c 1.0, CHCl3).
2001, 77; (f) Prakash, G. K. S.; Mandal, M.; Schweizer, S.;
Petasis, N. A.; Olah, G. A. J. Org. Chem. 2002, 67, 3718; (g)
ꢀ
Mloston, G.; Prakash, G. K. S.; Olah, G. A.; Heimgartner, H.
Helv. Chim. Acta 2002, 85, 1644.
6. (a) Thayer, A. Chem. Eng. News 2006, 84, 15.
7. (a) Benayoud, F.; Abouabdellah, A.; Richard, C.; Bonnet-
ꢀ
ꢀ
Delpon, D.; Begue, J. P.; Levasseur, D.; Boutaud, O.;
Schuber, F. Tetrahedron Lett. 2000, 41, 6367; (b) Ahvazi,
B. C.; Argyropoulos, D. S. J. Fluorine Chem. 1996, 78, 195;
€
(c) Sevenard, D. V.; Kirsch, P.; Roschenthaler, G. V.;
Movchun, V. N.; Kolomeitsev, A. A. Synlett 2001, 379; (d)
Movchun, V. N.; Kolomeitsev, A. A.; Yagupolskii, Y. L.
J. Fluorine Chem. 1995, 70, 255.
8. (a) Singh, R. P.; Kirchmeier, R. L.; Shreeve, J. M. Org. Lett.
1999, 1, 1047; (b) Singh, R. P.; Cao, G.; Kirchmeier, R. L.;
Shreeve, J. M. J. Org. Chem. 1999, 64, 2873; (c) Singh, R. P.;
Shreeve, J. M. J. Org. Chem. 2000, 65, 3241; (d) Petrov,
V. A. Tetrahedron Lett. 2000, 41, 6959; (e) Kim, J.; Shreeve,
J. M. Org. Biomol. Chem. 2004, 2, 2728; (f) Hoffmann-
Acknowledgements
This research was supported in part by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan and by Japan Science
& Technology (JST) Agency. We also thank TOSOH
F-TECH Inc. for a gift of Me3SiCF3.
€
Roder, A.; Seiler, P.; Diederich, F. Org. Biomol. Chem. 2004,
2, 2267.
9. (a) Stahly, G. P.; Bell, D. R. J. Org. Chem. 1989, 54, 2873; (b)
Kotun, S. P.; Anderson, J. D. O.; DesMateau, D. D. J. Org.
Chem. 1992, 57, 1124; (c) Anderson, J. D.; Pennington,
W. T.; DesMarteau, D. D. Inorg. Chem. 1993, 32, 5079; (d)
Chen, G. C.; Chen, L. S.; Eapen, K. C.; Ward, W. E.
J. Fluorine Chem. 1994, 69, 61; (e) Allen, A. D.; Fujio, M.;
Mohammed, N.; Tidwell, T. T.; Tsuji, Y. J. Org. Chem. 1997,
62, 246; (f) Ishizaki, M.; Hoshino, O. Tetrahedron 2000, 56,
8813; (g) Borkin, D.; Loska, R.; Makosza, M. Pol. J. Chem.
2005, 79, 1187.
10. (a) Hagiwara, T.; Mochizuki, H.; Fuchikami, T. Synlett 1997,
587; (b) Hagiwara, T.; Kobayashi, T.; Fuchikami, T. Nippon
Kagaku Kaishi 1997, 869; (c) Nelson, D. W.; Owens, J.;
Hiraldo, D. J. Org. Chem. 2001, 66, 2572; (d) Prakash,
G. K. S.; Mandal, M.; Panja, C.; Mathew, T.; Olah, G. A.
J. Fluorine Chem. 2003, 123, 61; (e) Song, J. J.; Tan, Z.;
Reeves, J. T.; Gallou, F.; Yee, N. K.; Senanayake, C. H. Org.
Lett. 2005, 7, 2193; (f) Iwanami, K.; Oriyama, T. Synlett
2006, 112; (g) Kawano, Y.; Fujisawa, H.; Mukaiyama, T.
Chem. Lett. 2005, 34, 422; (h) Mukaiyama, T.; Kawano, Y.;
Fujisawa, H. Chem. Lett. 2005, 34, 88; (i) Kawano, Y.;
Kaneko, N.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 2006, 79,
1133; (j) Prakash, G. K. S.; Panja, C.; Vaghoo, H.;
Surampudi, V.; Kultyshev, R.; Mandal, M.; Rasul, G.;
Mathew, T.; Olar, G. A. J. Org. Chem. 2006, 71, 6806.
11. (a) Mizuta, S.; Shibata, N.; Sato, T.; Fujimoto, H.; Nakamura,
S.; Toru, T. Synlett 2006, 267; (b) Sugimoto, H.; Nakamura, S.;
Shibata, Y.; Shibata, N.; Toru, T. Tetrahedron Lett. 2006, 47,
1337; (c) Mizuta, S.; Shibata, N.; Ogawa, S.; Fujimoto, H.;
Nakamura, S.; Toru, T. Chem. Commun. 2006, 2575.
Supplementary data
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.05.024.
References and notes
1. (a) Kirsch, P. Modern Fluoroorganic Chemistry; Wiley-VCH:
Weinheim, Germany, 2004; (b) Chambers, R. D. Fluorine in
Organic Chemistry; Blackwell: Oxford, 2004.
2. (a) Rabasseda, X.; Sorbera, L. A.; Castan˜er, J. Drugs Future
1999, 24, 1057; (b) Adkins, J. C.; Noble, S. Drugs 1998,
56, 1055; (c) Choudhury-Mukherjee, I.; Schenck, H. A.;
Cechova, S.; Pajewski, T. N.; Kapur, J.; Ellena, J.; Cafiso,
D. S.; Brown, M. L. J. Med. Chem. 2003, 46, 2494; (d)
Cheng, J. F.; Huang, Y.; Penuliar, R.; Nishimoto, M.; Liu, L.;
Arrhenius, T.; Yang, G.; O’Leary, E.; Barbosa, M.; Barr, R.;
Dyck, J. R. B.; Lopaschuk, G. D.; Nadzan, A. M. J. Med.
Chem. 2006, 49, 4055; (e) Barker, M.; Clackers, M.; Copley,
R.; Demaine, A.; Humphreys, D.; Inglis, G. G. A.; Johnston,
M. J.; Jones, H. T.; Haase, M. V.; House, D.; Loiseau, R.;
Nisbet, L.; Pacquet, F.; Skone, P. A.; Shanahan, S. E.; Tape,
D.; Vinader, V. M.; Washington, M.; Uings, I.; Upton, R.;
McLay, I. M.; Macdonald, S. J. F. J. Med. Chem. 2006, 49,
4216.
3. (a) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97, 757;
(b) Singh, R. P.; Shreeve, J. M. Tetrahedron 2000, 56, 7613; (c)
Prakash, G. K. S.; Mandal, M. J. Fluorine Chem. 2001, 112,
123; (d) Langlois, B. R.; Billard, T.; Roussel, S. J. Fluorine
Chem. 2005, 126, 173; (e) Lin, P.; Jiang, J. Tetrahedron 2000,
56, 3635.
12. (a) Shibata, N.; Suzuki, E.; Takeuchi, Y. J. Am. Chem. Soc.
2000, 122, 10728; (b) Shibata, N.; Tarui, T.; Doi, Y.; Kirk,
K. L. Angew. Chem., Int. Ed. 2001, 40, 4461; (c) Shibata, N.;
Suzuki, E.; Asahi, T.; Shiro, M. J. Am. Chem. Soc. 2001,
123, 7001; (d) Shibata, N. Farumashia 2003, 39, 666; (e)
Shibata, N.; Ishimaru, T.; Suzuki, E.; Kirk, K. L. J. Org.
Chem. 2003, 68, 2494; (f) Shibata, N.; Ishimaru, T.; Nagai,
T.; Kohno, J.; Toru, T. Synlett 2004, 1703; (g) Shibata, N.;
Ishimaru, T.; Nakamura, M.; Toru, T. Synlett 2004, 2509; (h)
Shibata, N.; Kohno, J.; Takai, K.; Ishimaru, T.; Nakamura,
S.; Toru, T.; Kanemasa, S. Angew. Chem., Int. Ed. 2005, 44,
4204; (i) Fukuzumi, T.; Shibata, N.; Sugiura, M.; Nakamura, S.;
4. Ruppert, I.; Schlich, K.; Volbach, W. Tetrahedron Lett. 1984,
25, 2195.
5. (a) Prakash, G. K. S.; Krishnamurti, R.; Olah, G. A. J. Am.
Chem. Soc. 1989, 111, 393; (b) Ramaiah, R.; Prakash,
G. K. S. Synlett 1991, 643; (c) Prakash, G. K. S.; Mandal,
M.; Schweizer, S.; Petasis, N. A.; Olah, G. A. Org. Lett.
2000, 2, 3173; (d) Prakash, G. K. S.; Tongco, E. C.; Mathew,
T.; Vankar, Y. D.; Olah, G. A. J. Fluorine Chem. 2000, 101,
199; (e) Prakash, G. K. S.; Mandal, M.; Olah, G. A. Synlett

8528
S. Mizuta et al. / Tetrahedron 63 (2007) 8521–8528
Toru, T. J. Fluorine Chem. 2006, 127, 548; (j) Fukuzumi, T.;
Chem. Commun. 1994, 599; (e) Munier, P.; Giudicelli, M.-B.;
Picq, D.; Anker, D. J. Carbohydr. Chem. 1994, 13, 1225; (f)
Johnson, C. R.; Bhumralkar, D. R. Nucleosides Nucleotides
1995, 14, 185; (g) Lavaire, S.; Plantier-Royon, R.; Portella,
C. J. Carbohydr. Chem. 1996, 15, 361; (h) Munier, P.;
Giudicelli, M.-B.; Picq, D.; Anker, D. J. Carbohydr. Chem.
1996, 15, 739; (i) Lavaire, S.; Plantier-Royon, R.; Portella,
C. Tetrahedron: Asymmetry 1998, 9, 213; (j) Kozak, J.;
Johnson, C. R. Nucleosides Nucleotides 1998, 17, 2221; (k)
Prakash, G. K. S.; Mandal, M.; Olah, G. A. Angew. Chem.,
Int. Ed. 2001, 40, 589; (l) Li, N. S.; Tang, X. Q.; Piccirilli,
J. A. Org. Lett. 2001, 3, 1025; (m) Prakash, G. K. S.;
Mandal, M.; Olah, G. A. Org. Lett. 2001, 3, 2847; (n)
Prakash, G. K. S.; Mandal, M. J. Am. Chem. Soc. 2002, 124,
6538; (o) Qiu, X.-I.; Qing, F.-I. J. Org. Chem. 2002, 67,
Shibata, N.; Sugiura, M.; Yasui, H.; Nakamura, S.; Toru, T.
Angew. Chem., Int. Ed. 2006, 45, 4973; (k) Shibata, N.;
Fujimoto, H.; Mizuta, S.; Ogawa, S.; Ishiuchi, Y.; Nakamura,
S.; Toru, T. Synlett 2006, 3484; (l) Shibata, N. Yuki Gosei
Kagaku Kyokaishi 2006, 64, 14; (m) Shibata, N.; Ishimaru, T.;
Nakamura, S.; Toru, T. J. Fluorine Chem. 2007, 128, 469.
13. Preliminary results of this work were reported briefly. (a)
Hibino, M.; Nagano, S.; Shibata, N., Toru, T. The 28th
Fluorine Conference of Japan, Yokohama, November 2004;
Abstract, 1P-33; (b) Shibata, N.; Toru, T. Jpn. Kokai Tokkyo
Koho 2005, JP 2005306769.
ꢀ
14. (a) Ma˛kosza, M.; Fedorynski, M. Arkivoc 2006, 7; (b)
Mazkosza, M.; Fedorynski, M. Phase Transfer Catalysis in
Interfacial Catalysis; Volkov, A. G., Ed.; Marcel Dekker:
New York, NY, 2003; p 159; (c) Misra, S. N.; Ghosh, P. K.;
Gohil, M. S.; Jethva, A. D.; Ramachandraiah, G. Main Group
Metal Chem. 2003, 26, 13; (d) Mazkosza, M.; Fedorynski,
M. Adv. Catal. 1987, 35, 375; (e) Dehmlov, E. V.; Dehmlov,
S. S. Phase Transfer Catalysis, 3rd ed.; Chemie: Weinheim,
1993; (f) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase-
Transfer Catalysis: Fundamentals, Applications and
Industrial Perspectives; Chapman & Hall: New York, NY,
1994; (g) Wilkinson, J. A. Chem. Rev. 1992, 92, 505.
€
7162; (p) Eilitz, U.; Bottcher, C.; Hennig, L.; Burger, K.;
Haas, A.; Goeckel, S.; Sieler, J. J. Heterocycl. Chem. 2003,
40, 329; (q) Kawano, Y.; Mukaiyama, T. Chem. Lett. 2005,
34, 894; (r) Kawano, Y.; Kaneko, N.; Mukaiyama, T. Chem.
Lett. 2006, 35, 304; (s) Pedrosa, R.; Sayalero, S.; Vicente,
M.; Maestro, A. J. Org. Chem. 2006, 71, 2177; (t) Song, J. J.;
Tan, Z.; Xu, J.; Reeves, J. T.; Yee, N. K.; Ramdas, R.;
Gallou, F.; Kuzmich, K.; DeLattre, L.; Lee, H.; Feng, X.;
Senanayake, C. H. J. Org. Chem. 2007, 72, 292; (u)
Massicot, F.; Monnier-Benoit, N.; Deka, N.; Plantier-Royon,
R.; Portella, C. J. Org. Chem. 2007, 72, 1174.
15. Sasson reported that treatment of R4NBr with KF generates
R4NF in protic solvents. This difference might be in part due
to solvent effects. Dermeik, S.; Sasson, Y. J. Org. Chem.
1989, 54, 4827.
20. (a) Iseki, K.; Nagai, T.; Kobayashi, Y. Tetrahedron Lett. 1994,
35, 3137; (b) Kuroki, Y.; Iseki, K. Tetrahedron Lett. 1999, 40,
ꢀ
16. Billard, T.; Langlois, B. R. Eur. J. Org. Chem. 2007, 891.
17. (a) Inui, S.; Kawano, S.; Saito, M.; Iwane, H.; Takanishi, Y.;
Hiraoka, K.; Ouchi, Y.; Takezoe, H.; Fukuda, A. Jpn. J. Appl.
Phys. 1990, 29, L987; (b) Hiraoka, K.; Ouchi, Y.; Takezoe,
H.; Fukuda, A.; Inui, S.; Kawano, S.; Saito, M.; Iwane, H.;
Itoh, K. Mol. Cryst. Liq. Cryst. 1991, 199, 197; (c)
Shibahara, S.; Yamamoto, J.; Takanishi, Y.; Ishikawa, K.;
Takezoe, H. J. Phys. Soc. Jpn. 2002, 71, 802; (d) Kusumoto,
T.; Hiyama, T. Enantiocontrolled Synthesis of Fluoroorganic
Compounds; Soloshonok, V. A., Ed.; John Wiley & Sons:
Chichester, UK, 1999; pp 536–556.
18. (a) Enantiocontrolled Synthesis of Fluoro-Organic
Compounds; Soloshonok, V. A., Ed.; Wiley: Chichester, UK,
1999; (b) Ma, J.-A.; Cahard, D. Chem. Rev. 2004, 104, 6119;
(c) Umemoto, T. Chem. Rev. 1996, 96, 1757.
19. (a) Munier, P.; Picq, D.; Anker, D. Tetrahedron Lett. 1993, 34,
8241; (b) Wang, Z.; Ruan, B. J. Fluorine Chem. 1994, 69, 1; (c)
Schmit, C. Synlett 1994, 241; (d) Kozikowski, A. P.; Ognyanov,
V. I.; Fauq, A. H.; Wilcox, R. A.; Nahorski, S. R. J. Chem. Soc.,
8231; (c) Caron, S.; Do, N. M.; Arpin, P.; Larivee, A. Synthesis
2003, 1693; (d) Hagiwara, T.; Kobayashi, T.; Fuchikami, T.
Main Group Chem. 1997, 2, 13; (e) Iseki, K.; Kobayashi, Y.
Rev. Heteroat. Chem. 1995, 12, 211; (f) Roussel, S.; Billard,
T.; Langlois, B. R.; Saint-James, L. Chem.—Eur. J. 2005,
11, 939.
21. (a) Ando, A.; Miura, T.; Tatematsu, T.; Shioiri, T. Tetrahedron
Lett. 1993, 34, 1507; (b) Shioiri, T.; Bohsako, A.; Ando, A.
Heterocycles 1996, 42, 93; (c) Horikawa, M.; Busch-
Petersen, J.; Corey, E. J. Tetrahedron Lett. 1999, 40, 3843.
22. In situ-generation of chiral ammonium fluorides from am-
monium sulfate is examined for the reaction of aldehydes
with silyl enol ethers: Ooi, T.; Doda, K.; Maruoka, K.
Org. Lett. 2001, 3, 1273.
23. Maruoka, K.; Ooi, T. Chem. Rev. 2003, 103, 3013.
24. Shibuguchi, T.; Fukuta, Y.; Akachi, Y.; Sekine, A.; Ohshima,
T.; Shibasaki, M. Tetrahedron Lett. 2002, 43, 9539.
25. O’Donnell, M. J. Acc. Chem. Res. 2004, 37, 506.
26. Billard, T.; Bruns, S.; Langlois, B. R. Org. Lett. 2000, 2, 2101.