Reductive modification of difluoromethylene moiety in pentafluoropropionyl group

Article abstract of DOI:10.1016/j.jfluchem.2007.12.003

The reductive Mg-promoted defluorinative-silylation of 2,2,3,3,3-pentafluoropropiophenone readily produces the α-trifluoromethyl enol silyl ether, which then react with electrophiles to give a variety of 2-substituted-3,3,3-trifluoropropiophenones in excellent yields. The same protocol is applicable for the preparation of enol silyl ether of 3,3,3-trifluoropropiophenone. Fluoride ion catalyzed 1,2-desilylative-defluorination of 2,3,3,3-tetrafluoro-2-trimethylsilyloxypropiophenone provided 3,3,3-trifluoro-1-phenyl-1,2-propanedione in a good yield.

Full text of DOI:10.1016/j.jfluchem.2007.12.003

Available online at www.sciencedirect.com
Journal of Fluorine Chemistry 129 (2008) 274–279
www.elsevier.com/locate/fluor
Reductive modification of difluoromethylene moiety in
pentafluoropropionyl group
*
Yutaka Nakamura , Yuu Ozeki, Kenji Uneyama
Department of Applied Chemistry, Faculty of Engineering, Okayama University, Okayama 700-8530, Japan
Received 6 November 2007; received in revised form 14 December 2007; accepted 15 December 2007
Available online 23 December 2007
Abstract
The reductive Mg-promoted defluorinative-silylation of 2,2,3,3,3-pentafluoropropiophenone readily produces the a-trifluoromethyl enol silyl
ether, which then react with electrophiles to give a variety of 2-substituted-3,3,3-trifluoropropiophenones in excellent yields. The same protocol is
applicable for the preparation of enol silyl ether of 3,3,3-trifluoropropiophenone. Fluoride ion catalyzed 1,2-desilylative-defluorination of 2,3,3,3-
tetrafluoro-2-trimethylsilyloxypropiophenone provided 3,3,3-trifluoro-1-phenyl-1,2-propanedione in a good yield.
# 2008 Elsevier B.V. All rights reserved.
Keywords: a-Trifluoromethyl enol silyl ethers; 2-Substituted-3,3,3-trifluoropropiophenones; Reductive-defluorination; Desilylative-defluorination; Magnesium
1. Introduction
opropiophenone is synthesized by Friedel-Crafts reaction of
benzene with 3,3,3-trifluoropropionic chloride, which is rather
expensive [21]. A three-steps synthesis of 3,3,3-trifluoropro-
piophenone via trifluoroacetylation of benzaldehyde dimethyl-
hydrazone is not practical due to the low total yield [26,6,7].
Mg(0)-promoted C–F bond activation method has found
useful for the transformation of trifluoromethyl ketones to 2,2-
difluoroenol silyl ethers, building-blocks feasible for CF2
compounds syntheses [27]. Herein, we describe a facile and
reliable preparation of a-trifluoromethyl enol silyl ethers 2 and
4, and their effective transformations to trifluoromethyl a-
diketone and 2-substituted-3,3,3-trifluoropropiophenones.
Development of general and efficient selective introduction
of a trifluoromethyl group into organic compounds has kept
high attentions in both academia and industry. This is because
many commercially available pharmaceuticals and agrochem-
icals owe their biological activity to the unique nature of
trifluoromethyl group [1–4]. a-CF3 carbonyl compounds can be
used as useful building blocks for attractive trifluoromethylated
compounds by the functionalization of a-position and
subsequent transformation of carbonyl groups [5–8]. However
there are many synthetic difficulty, such as easy defluorination
of the CF3CH2 anion species [9–12]. Mikami and Itoh have
reported a direct aldol reaction with in situ generated Ti-enolate
of a-CF3 ketones [13–15]. Recently, it was reported that the use
of metal enolates could avoid significant defluorination during
radical trifluoromethylation [15–20]. Most feasible way to
functionalize a-position of CF3-ketones is via a reaction of enol
silyl ethers [21–23], and in some cases, the related boron and
aluminum enolates [24,25]. However, there are only a few
reports which described the synthetic methods of a-CF3
carbonyl compounds, which required expensive starting
materials and gave low yields. For example, 3,3,3-trifluor-
2. Results and discussion
A series of the reductive transformations of 1–4 are shown in
Scheme 1. Tetrafluoro enol silyl ether 2 was prepared by the
Mg(0)-promoted defluorinative-silylation of 1 in an excellent
yield. Hydrolysis was then followed to afford 2,3,3,3-
tetrafluoropropiophenone 3 under acid catalysis. The second
Mg(0)-promoted defluorinative-silylation of 3 was proceeded
smoothly to afford 3,3,3-trifluoro enol silyl ether 4 in 90%
yield. The above described synthesis of 4 involves high
availability of 1, mild reaction conditions and an excellent total
yield in comparison with synthesis by O-silylation of the less
available 3,3,3-trifluoropropiophenone with Me3SiOTf [21].
* Corresponding author. Tel.: +81 86 455 5234; fax: +81 86 455 8769.
E-mail address: y-nakmr@kantodenka.co.jp (Y. Nakamura).
0022-1139/$ – see front matter # 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.12.003

Y. Nakamura et al. / Journal of Fluorine Chemistry 129 (2008) 274–279
275
Table 2
Products and yields in the reaction of 4 with NXS
Entry
NXS (eq.)
Yield (%)a
Scheme 1.
9
10
1
2
3
4
NBS (1.1)
NBS (2.1)
NCS (1.1)
NCS (2.1)
99 (97)
0
7
91
65
0
Interestingly, the relative stereochemistry of substituents
CF3 and OSiMe3 groups in both enol silyl ethers 2 and 4 is cis to
each other. This stereochemical preference may arise from the
intramolecular C–F. . .Si coordinative interaction as suggested
by Shi and co-workers [28].
21
99 (96)
Yields were analyzed by 19F NMR integration of products relative to C6F6 as
a
an internal standard. Yield in parentheses were isolated yields.
Transformations of 2 and 4 to a series of 2-substituted-
3,3,3-trifluoropropiophenones were examined. 2,3,3,3-Tetra-
fluoropropenyl silyl ether 2 reacts with m-chloroperbenzoic
acid (m-CPBA) in dichloromethane to afford the 2,3,3,3-
tetrafluoro-2-trimethylsiloxypropiophenone 6 (Scheme 2). It
is suggested that 6 is produced by migration of trimethylsilyl
group on ring opening of epoxide 5 initially formed in the
oxidation step [29,30]. Following fluoride ion promoted
desilylative-defluorination of 6 proceeded smoothly to
provide a valuable 1,2-diketone 7 by the use of catalytic
amount of fluoride ion (Scheme 3), which is recycled as
demonstrated by several 1,2- [31], 1,4- [32] and 1,6-
desilylative-defluorination reactions [33].
a-carbon of 2 is also possible. In the presence of Lewis acid, the
reaction of 2 with benzaldehyde dimethyl acetal gave 8d in
95% yield (Table 1).
Lewis acid catalyzed alkylation of 4 was already reported
[21]. Here, an interesting double chlorination is described. The
reaction of 4 with NBS provided a monobromide 9a exclusively
in quantitative yield. Meanwhile, the reaction of 4 with 1.1 eq.
of NCS provided a mixture of a monochloride 9b and a
dichloride 10b in favor of 9b. Addition of 2.1 eq. of NCS
provided only the dichloride 10b in 96% yield. It seems that a-
proton of 9b would be more acidic than 9a, meanwhile
dibromide 10a would be thermodynamically less stable than
monobromide 9a presumably due to the steric crowd at a,a-
dibromo-a-trifluoromethylated carbon of 10a (Table 2).
In conclusion, a variety of 2-substituted-3,3,3-trifluoropro-
piophenones were synthesized in high yields via reductive
Mg(0)-promoted defluorinative-silylation of easily available
2,2,3,3,3-pentafluoropropiophenone.
Moreover, the reaction of 2 with various electrophiles
afforded the 2-substituted-2,3,3,3-tetrafluoropropiophenones 8.
Thus, halogenation and sulfenylation proceeded smoothly
under the very mild conditions to give 2-chloro, 2-bromo and 2-
phenylthio-2,3,3,3-tetrafluoropropiophenones 8a–8c in excel-
lent yields, respectively. Carbon–carbon bond formation at the
Table 1
Products and yields of 8 in the reaction of 2 with electrophiles
a
Entry
Electrophile
Reaction conditions
Product, Yieldb (%)
1
2
3
4
NCS
DMF, rt, 1 h
Cl
8a, 97
8b, 99
8c, 91
8d, 95c
NBS
DMF, rt, 1 h
Br
PhSCl
DMF, rt, 1 h
PhS
PhCH(OMe)2
TMSOTf (1 eq.), CH2CI2, 0 8C, 4 h
PhCH(OMe)
a
Substituent E in products 8.
b
c
Isolated yields.
Diastereomer mixture. Diastereomeric ratio was determined by 1H NMR (65:35).

276
Y. Nakamura et al. / Journal of Fluorine Chemistry 129 (2008) 274–279
Scheme 2.
3. Experimental
pressure, and n-hexane was added. The resulting salt was
removed by filtration through completely dried Celite.
Evaporation of filtrate and distillation (0.5 mmHg, 50 8C)
provided a colorless oil of 2 (2.70 g, 97%) as a mixture of E/Z
isomers (90:10 by 19F NMR). IR (neat): 2968, 1680, 1378,
3.1. General
1H, 13C and 19F NMR spectra were recorded at 600, 150 and
564 MHz on a Varian UNITY INOVA 600 instrument,
respectively. The chemical shift were reported in d (ppm)
related to the CHCl3 (7.26 ppm) CDCl3 (77 ppm) and C6F6
(0 ppm). Coupling constants (J) were reported in hertz (Hz).
Infrared spectra were reported on a Hitachi 270-30 spectro-
meter. Only selected absorbance were reported (l in cmÀ1). MS
analyses were performed on a SHIMADZU GCMS-QP5050A.
Elemental analyses were performed on a Perkin-Elmer series II
CHNS/O Analyzer 2400. Melting points were determined on a
Yanako MP-S3 melting point measurement apparatus. All air-
or moisture-sensitive reactions were carried out under argon
atmosphere with freshly distilled solvents. THF was distilled
from sodium and benzophenone ketyl. DMF and Me3Si–Cl
were used after distillation over CaH2. CH2Cl2 was freshly
distilled from P2O5. m-CPBA was washed with phosphate
buffer and distilled water, then dried under reduced pressure.
The other reagents were used without further purification. Mg
turnings were purchased from nacalai tesque. Tetrabutylam-
monium triphenyldifluorosilicate (TBAT) was purchased from
Aldrich. Column chromatography was carried out on silica gel
(Merck, Silica gel 60).
1276, 1186, 862 cmÀ1 1H NMR (600 MHz, CDCl3): (E
;
isomer) d 0.09 (9H, s, Me3Si), 7.37–7.43 (3H, m), 7.52–7.54
(2H, m), (Z isomer) d 0.16 (9H, s, Me3Si), 7.37–7.43 (3H, m),
7.52–7.54 (2H, m); 13C NMR (150 MHz, CDCl3): (E isomer) d
0.06 (Me3Si), 120.4 (dq, J = 37, 270 Hz, CF3), 137.8 (dq,
J = 239, 37 Hz), 143.2 (dq, J = 30, 3 Hz), (Z isomer) d 0.25
(Me3Si), 120.5 (dq, J = 37, 270 Hz, CF3), 135.8 (dq, J = 240,
39 Hz), 142.5 (dq, J = 30, 3 Hz); 19F NMR (564 MHz, CDCl3):
(E isomer) d À4.6 (1F, q, J = 11 Hz), 96.1 (3F, d, J = 11 Hz,
CF3), (Z isomer) d 7.8 (1F, q, J = 13 Hz), 97.8 (3F, d, J = 13 Hz,
CF3); EI MS m/z (relative intensity): 278 [M]+ (15), 263 [M–
Me]+ (5), 186 [M À 92]+ (13), 177 [M À 101]+ (20), 139
[M À 139]+ (18), 105 [M À 173]+ (43), 77 [Ph]+ (100), 73
[Me3Si]+ (91); Anal. Calcd for C12H14F4OSi: C, 51.79; H, 5.07.
Found: C, 51.59; H, 5.13.
The stereochemistry of the compound 2 was determined by
19F NMR chemical shifts in reference to [34].
3.2.2. 2,3,3,3-Tetrafluoropropiophenone (3)
To the reaction mixture of 2 (3.7 g, 13.4 mmol) was added
3 M HCl at room temperature and then the mixture was stirred
for 5 h. The reaction mixture was poured into 5% NaHCO3 aq.
and the organic products were extracted with Et2O. The organic
layer was washed with brine, and dried over MgSO4. After
removal of the solvent, distillation (0.5 mmHg, 50 8C) provided
a pale yellow solid of 3 (2.6 g, 97% yield based on compound
1); mp = 35–36 8C; IR (neat): 1700, 1600, 1452, 1334, 1148,
3.2. Experimental procedures
3.2.1. 1-Phenyl-2,3,3,3-tetrafluoro-1-
trimethylsiloxypropene (2)
A suspension of Me3Si–Cl (5 mL, 40 mmol) in distilled THF
(40 mL) and Mg (turnings) (0.49 g, 20 mmol) was cooled down
at À10 8C under argon atmosphere. 2,2,3,3,3-Pentafluoropro-
piophenone 1 (2.24 g, 10 mmol) was added dropwise and then
the mixture was stirred for 20 min. Then, 1,4-dioxane (5 mL)
was added to the reaction mixture, and stirred for 5 min at
À10 8C. Residual magnesium and dioxane–MgCl2 salt were
separated by filtration through completely dried Celite. THF,
Me3Si–Cl and 1,4-dioxane were removed under reduced
860 cmÀ1 1H NMR (600 MHz, CDCl3) d 5.73 (1H, dq,
;
J = 46.8, 6.6 Hz, CHF), 7.52–7.55 (2H, m), 7.67–7.69 (1H, m),
8.00 (2H, d, J = 8.4 Hz); 13C NMR (150 MHz, CDCl3): d 87.7
(dq, J = 199, 33 Hz, CHF), 120.7 (dq, J = 26, 281 Hz, CF3),
128.9, 129.3, 129.4, 133.6, 134.9, 188.0 (d, J = 20 Hz, C O);
19F NMR (564 MHz, CDCl3): d À38.9 (1F, dq, J = 47, 12 Hz),
87.4 (3F, dd, J = 7, 12 Hz, CF3); EI MS m/z (relative intensity):
206 [M]+ (3), 105 [M–CHFCF3]+ (100), 77 [Ph]+ (89).
3.2.3. 1-Phenyl-3,3,3-trifluoro-1-trimethylsiloxypropene
(4)
A suspension of Me3Si–Cl (5 mL, 40 mmol) in distilled THF
(30 mL) and Mg (turnings) (0.49 g, 20 mmol) was cooled to
0 8C under argon atmosphere. A solution of compound 3
(2.06 g, 10 mmol) in distilled THF (10 mL) was added
dropwise and then the mixture was stirred for 1 h. After
Scheme 3.

Y. Nakamura et al. / Journal of Fluorine Chemistry 129 (2008) 274–279
277
evaporation of most of THF, n-hexane was added to the residue,
and the resulting salt was filtered. Evaporation of filtrate and
distillation (0.2 mmHg, 50 8C) provided a colorless oil of 4
(2.34 g, 90%) as a mixture of E/Z isomers (5:95 by 19F NMR).
J = 34 Hz), 121.5 (q, J = 286 Hz, CF3), 128.5, 128.7, 129.3,
130.2, 131.8, 135.2, 191.8; 19F NMR (564 MHz, CDCl3): d 80.5
(3F, s); EI MS m/z (relative intensity): 105 (100), 77 (98).
The spectral data were consistent with those reported [35].
IR (neat): 2972, 1654, 1366, 1190, 1110 cmÀ1 1H NMR
;
(600 MHz, CDCl3): (E isomer) d 0.19 (9H, s, Me3Si), 5.20 (1H,
q, J = 8.4 Hz), 7.36–7.42 (3H, m), 7.49–7.51 (2H, m), (Z
isomer) d 0.15 (9H, s, Me3Si), 5.35 (1H, q, J = 7.8 Hz), 7.36–
7.42 (3H, m), 7.49–7.51 (2H, m); 13C NMR (150 MHz,
CDCl3): (E isomer) d 0.28 (Me3Si), 99.2 (q, J = 33 Hz), 123.7
(q, J = 267 Hz, CF3), 126.7, 128.4, 130.0, 136.9, 159.6 (q,
J = 6 Hz), (Z isomer) d 0.09 (Me3Si), 99.8 (q, J = 35 Hz), 161.1
(q, J = 6 Hz); 19F NMR (564 MHz, CDCl3): (E isomer) d 108.5
(3F, d, J = 8 Hz), (Z isomer) d 104.9 (3F, d, J = 8 Hz); EI MS m/
z (relative intensity): 260 [M]+ (15), 245 [M–Me]+ (5), 181
[M À 79]+ (15), 149 [M À 111]+ (17), 105 [M À 155]+ (36), 77
[Ph]+ (100), 73 [Me3Si]+ (31).
3.2.5. 2-Chloro-2,3,3,3-tetrafluoropropiophenone (8a)
To a solution of NCS (400 mg, 3.03 mmol) in DMF (6 ml)
was added 2 (830 mg, 3.00 mmol) at room temperature under
an argon atmosphere. The reaction mixture was stirred for
additional 1 h. After removal of the solvent, purification of
crude product by chromatography on silica gel (n-hexane,
Rf = 0.60) afforded 8a (700 mg, 97%) as a colorless oil. IR
(neat): 3076, 1712, 1600, 1452, 1298, 1220, 690 cmÀ1; H
1
NMR (600 MHz, CDCl3): d 7.52–7.55 (2H, m), 7.68–7.71 (1H,
m), 8.12–8.14 (2H, m); 13C NMR (150 MHz, CDCl3): d 100.5
(dq, J = 270, 35 Hz), 119.7 (dq, J = 30, 284 Hz, CF3), 128.8,
128.9, 130.3, 130.4, 130.6–130.7 (m), 135.1, 183.9 (d,
J = 26 Hz); 19F NMR (564 MHz, CDCl3): d 31.1 (1F, q,
J = 6 Hz), 83.5 (3F, d, J = 6 Hz, CF3); EI MS m/z (relative
intensity): 135 [M–C( O)Ph]+ (1), 127 [M À 133]+ (4), 105
[C( O)Ph]+ (100), 77 [Ph]+ (92); Anal. Calcd for C9H5ClF4O:
C, 44.27; H, 2.09. Found: C, 44.17; H, 2.05.
The stereochemistry of the compound 4 was determined by
1H and 19F NMR chemical shifts in reference to [21]. Ref. [21]
reports that the synthesis of 4 by O-silylation of the 3,3,3-
trifluoropropiophenone with Me3SiOTf gives only Z isomer.
3.2.4. 3,3,3-Trifluoro-1-phenyl-1,2-propanedione, hydrate
(7)
3.2.6. 2-Bromo-2,3,3,3-tetrafluoropropiophenone (8b)
To a solution of NBS (550 mg, 3.03 mmol) in DMF (6 mL)
was added 2 (830 mg, 3.00 mmol) at room temperature under
argon atmosphere. The reaction mixture was stirred for
additional 1 h. After removal of the solvent, purification of
crude product by chromatography on silica gel (n-hexane,
Rf = 0.30) afforded 8b (850 mg, 99%) as a colorless oil. IR
(neat): 3076, 1704, 1600, 1494, 1296, 1222, 1190, 898,
838 cmÀ1; 1H NMR (600 MHz, CDCl3): d 7.52–7.55 (2H, m),
7.67–7.70 (1H, m), 8.14–8.16 (2H, m); 13C NMR (150 MHz,
CDCl3): d 93.9 (dq, J = 279, 34 Hz), 119.9 (dq, J = 30, 283 Hz,
CF3), 128.8, 128.9, 130.3, 130.4, 130.8–130.9 (m), 135.0, 184.6
(d, J = 25 Hz, C O); 19F NMR (564 MHz, CDCl3): d 27.1 (1F,
q, J = 8 Hz), 85.4 (3F, d, J = 8 Hz, CF3); EI MS m/z (relative
intensity): 127 [M À 157]+ (6), 105 [C( O)Ph]+ (100), 77 [Ph]+
(63); Anal. Calcd for C9H5BrF4O: C, 37.92; H, 1.77. Found: C,
37.78; H, 1.61.
To a solution of m-CPBA (2.6 g, 15 mmol) in distilled
CH2Cl2 (20 mL) was added 2 (1.4 g, 5 mmol) at room
temperature under an argon atmosphere. The reaction mixture
was stirred for 2.5 h. The precipitated m-chlorobenzoic acid
was removed by filtration. The organic layer was washed with
NaHCO3 solution and brine, and then dried over MgSO4. After
removal of the solvent, distillation (0.5 mmHg, 50 8C) provided
a yellow liquid of 6 (Yield by 19F NMR: 86%, GC purity: 88%).
Crude 6 was used for the next desilylative-defluorination
reaction.
Compound 6 was added to a mixture of TBAT (13 mg,
0.025 mmol) in distilled CH2Cl2 (10 mL), and then the
resulting mixture was stirred for additional 10 min at room
temperature. After removal of the solvent from the crude
reaction mixture, recrystallization (n-hexane/Et2O) afforded 7
in 72% yield based on compound 2 as a pale yellow powder.
3.2.4.1. 2,3,3,3-Tetrafluoro-2-trimethylsiloxypropiophenone
1
3.2.7. 2-Phenylthio-2,3,3,3-tetrafluoropropiophenone (8c)
To a solution of NCS (440 mg, 3.30 mmol) in distilled
CH2Cl2 (12 mL) was added PhSH (360 mg, 3.30 mmol) at
0 8C. After stirring at 0 8C for 1 h, to the yellow suspension was
added a solution of 2 (830 mg, 3.00 mmol) in distilled DMF
(6 mL) at room temperature under an argon atmosphere. The
reaction mixture was stirred for additional 1 h. The reaction was
quenched by the addition of water (10 mL). The aqueous layer
was extracted with n-hexane and the organic layer was dried
over MgSO4. After removal of the solvent, purification of crude
product by chromatography on silica gel (n-hexane, Rf = 0.55)
afforded 8c (850 mg, 91%) as a colorless oil. IR (neat): 3076,
(6). IR (neat): 2972, 1706, 1602, 1452, 1216, 862 cmÀ1; H
NMR (600 MHz, CDCl3): d 0.23 (9H, s, Me3Si), 7.48–7.50
(2H, m), 7.62–7.7.65 (1H, m), 8.12 (2H, d, J = 7.2 Hz); 13C
NMR (150 MHz, CDCl3): d 0.73 (Me3Si), 104.8 (dq, J = 238,
35 Hz), 119.9 (dq, J = 37, 287 Hz, CF3), 120.7, 128.5, 130.4,
132.6, 134.3, 188.8 (d, J = 29 Hz, C O); 19F NMR (564 MHz,
CDCl3): d 49.5 (1F, s), 80.6 (3F, d, J = 3 Hz, CF3); EI MS m/z
(relative intensity): 193 [M À 101]+ (1), 105 [C( O)Ph]+ (100),
77 [Ph]+ (84).
3.2.4.2. 3,3,3-Trifluoro-1-phenyl-1,2-propanedione, hydrate
(7). mp = 82–84 8C; IR (neat): 3424 (br), 1682, 1602, 1254,
1194, 1086 cmÀ1; 1H NMR (600 MHz, CDCl3): d 4.97 (2H, s,
OH), 7.49–.52 (2H, m), 7.66–7.69 (1H, m), 8.33 (2H, d,
J = 7.8 Hz); 13C NMR (150 MHz, CDCl3): d 93.9 (q,
1698, 1600, 1446, 1208, 1188, 838, 690 cmÀ1
(600 MHz, CDCl3): d 7.29–7.33 (2H, m), 7.38–7.42 (3H, m),
7.55–7.58 (1H, m), 7.60–7.61 (2H, m), 7.86–7.88 (2H, m); 13
NMR (150 MHz, CDCl3): d 103.9 (dq, J = 246, 31 Hz), 121.3
;
1H NMR
C

278
Y. Nakamura et al. / Journal of Fluorine Chemistry 129 (2008) 274–279
(dq, J = 33, 285Hz, CF3), 124.8, 128.2, 128.3, 129.3, 129.8,
129.9, 130.8, 133.9, 137.3, 189.2 (d, J = 26 Hz, C O); 19F
NMR (564 MHz, CDCl3): d 18.0 (1F, q, J = 11 Hz), 89.0 (3F, d,
J = 11 Hz, CF3); EI MS m/z (relative intensity): 314 [M]+ (0.4),
105 [C( O)Ph]+ (100), 77 [Ph]+ (34); Anal. Calcd for
C15H10F4OS: C, 57.32; H, 3.21. Found: C, 57.07; H, 3.18.
10b (370 mg, 96%) as a colorless oil. IR (neat): 3068, 1712,
1600, 1452, 1258, 1196, 864 cmÀ1 1H NMR (600 MHz,
;
CDCl3): d 7.51 (2H, t, J = 8.4 Hz), 7.64–7.67 (1H, m), 8.26–
8.28 (2H, m); 13C NMR (150 MHz, CDCl3): d 78.4 (q,
J = 31 Hz), 121.2 (q, J = 282 Hz, CF3), 128.5, 130.2 (q,
J = 2 Hz), 130.8, 134.5, 182.5 (d, J = 1 Hz, C O); 19F NMR
(564 MHz, CDCl3): d 86.8 (3F, s); EI MS m/z (relative
intensity): 105 [C( O)Ph]+ (100), 77 [Ph]+ (72); Anal. Calcd
for C9H5Cl2F3O: C, 42.05; H, 1.96. Found: C, 42.04; H, 1.93.
3.2.8. 2-Methoxyphenylmethyl-2,3,3,3-
tetrafluoropropiophenone (8d)
To a mixture of 2 (280 mg, 1.00 mmol) and benzaldehyde
dimethyl acetal (156 mg, 1.00 mmol) in distilled CH2Cl2
(2 mL) which was cooled to 0 8C under an argon atmosphere
was added Me3SiOTf (220 mg, 1.00 mmol). The resulting
mixture was stirred for an additional 4 h and then was poured
into 5% NaHCO3 aq. The organic products were extracted with
Et2O. The organic layer was washed with brine, and dried over
MgSO4. After removal of the solvent, purification of crude
product by chromatography on silica gel (n-hexane:Et2O = 5: 1,
Rf = 0.50) afforded 8d (300 mg, 95%) as a colorless oil.
Acknowledgements
This work was supported by the Ministry of Education,
Culture, Sports, Science and Technology of Japan (Grant-in-
Aid for Scientific Research (C), no. 17550104). We also thank
1
the SC-NMR Laboratory of Okayama University for the H,
13C and 19F NMR analyses.
References
1
Diastereomer mixture (65:35 by H NMR); IR (neat): 3072,
2944, 1696, 1602, 1450, 1208, 1098 cmÀ1
;
1H NMR
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(600 MHz, CDCl3): major d 3.17 (3H, s, OMe), 5.02 (1H, d,
J = 26.4 Hz), minor d3.34 (3H, s, OMe), 5.09 (1H, d,
J = 25.8 Hz); 13C NMR (150 MHz, CDCl3): major d 57.3,
82.7 (dd, J = 17, 1 Hz), 99.9 (dq, J = 216, 28 Hz), 120.8 (dq,
J = 28, 285 Hz, CF3), minor d 57.4, 89.9 (d, J = 11 Hz, 3F), 82.4
(dd, J = 17, 1 Hz), 100.1 (dq, J = 214, 29 Hz), 121.6 (dq,
J = 30, 286 Hz, CF3); 19F NMR (564 MHz, CDCl3): major d
À24.2 (1F, m), 89.3 (3F, d, J = 7 Hz, CF3), minor d À24.5 (1F,
m), 89.9 (3F, d, J = 11 Hz, CF3); EI MS m/z (relative intensity):
307 [M À 19]+ (1), 190 [M À 136]+ (6), 121 [CH(OMe)Ph]+
(100), 105 [C( O)Ph]+ (86), 77 [Ph]+ (39); Anal. Calcd for
C17H14F4O2: C, 62.58; H, 4.32. Found: C, 62.58; H, 4.31.
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To a solution of NBS (195 mg, 1.10 mmol) in DMF (4 mL)
was added 4 (260 mg, 1.00 mmol) at 60 8C under argon
atmosphere. The reaction mixture was stirred for additional 1 h.
After removal of the solvent, purification of crude product by
chromatography on silica gel (n-hexane, Rf = 0.30) afforded 9a
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3004, 1694, 1372, 1268, 1150, 1112 cmÀ1
;
1H NMR
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(600 MHz, CDCl3): d 5.45 (1H, q, J = 6.6 Hz), 7.53–7.56
(2H, m), 7.66–7.69 (1H, m), 7.97–7.99 (2H, m); 13C NMR
(150 MHz, CDCl3): d 39.9 (q, J = 32 Hz), 122.4 (q, J = 277 Hz,
CF3), 128.9, 129.1, 133.3, 134.7, 186.4 (C O); 19F NMR
(564 MHz, CDCl3): d 94.1 (3F, d, J = 6 Hz); EI MS m/z
(relative intensity): 105 [C( O)Ph]+ (100), 77 [Ph]+ (72); Anal.
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2.11.
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atmosphere. The reaction mixture was stirred at 60 8C for 1 h.
After removal of the solvent, purification of crude product by
chromatography on silica gel (n-hexane, Rf = 0.60) afforded
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