Polyfluorination using IF5

Article abstract of DOI:10.1021/jo101672g

The polyfluorination of α-(arylthio)carbonyl compounds was achieved by a successive application of polyfluorination using IF₅, Friedel-Crafts arylation, and desulfurizing fluorination using IF₅. Three to six fluorine atoms were selec

Full text of DOI:10.1021/jo101672g

pubs.acs.org/joc
Polyfluorination Using IF5
Tadahito Fukuhara and Shoji Hara*
Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
shara@eng.hokudai.ac.jp
Received August 30, 2010
The polyfluorination of R-(arylthio)carbonyl compounds was achieved by a successive application of
polyfluorination using IF5, Friedel-Crafts arylation, and desulfurizing fluorination using IF5. Three
to six fluorine atoms were selectively introduced to the carbons located between the aromatic ring and
the carbonyl group.
Introduction
known for the introduction of multiple fluorine atoms to the
particular carbons of a molecule.4 Recently, the deoxyfluori-
nation reaction of R-diketones by SF4,2b DAST,2b or Deoxo-
fluor5 was used for introducing four fluorine atoms to the
adjacent carbons. However, the method is effective only
when the carbonyl group is attached to the aromatic ring;
otherwise, the yield is low. Previously, we found that in the
reaction of aryl alkyl sulfides with IF5, three to seven fluorine
atoms were introduced into the alkyl group of the sulfides.6
In the reaction, the arylthio group migrated on the alkyl
chain, and only the arylthio group attached carbons were
fluorinated. Therefore, we can selectively introduce multiple
fluorine atoms on the appropriate carbons by this reaction.
Quite recently, we have also found a desulfurizing difluori-
nation reaction of benzylic sulfides by IF5, where oxidative
fluorination and desulfurizing fluorination reactions occur
successively in the benzylic sulfides to yield gem-difluoro
compounds.7 On the basis of these two findings, we have
planned a new polyfluorination method to introduce multi-
ple fluorine atoms to the carbons located between the
carbonyl group and the aromatic ring.
Polyfluoro compounds are widely used in our lives as
plastics, paints, water-repellents, and so on.1 Polyfluoro
compounds containing 2-3 polyfluorinated carbons are
currently attracting attention as functional materials.2 They
are prepared by a “building block method,” where the avail-
able polyfluoro compounds are used for making the poly-
fluorinated part of the target molecules.2a,3 However, an
appropriate building block for the synthesis of a target
molecule is not always available, and a multistep synthesis
is often required to obtain the target molecule from the
available building block. If the selective introduction of the
multifluorine atoms to the particular carbons in the molecule
were possible, the partially polyfluorinated molecules could
be prepared more easily, and we would no longer need to look
for suitable building blocks. However, only a few methods are
(1) (a) Kirsh, P. In Modern Fluoroorganic Chemistry; Wiley-VCH;
Weinheim, 2004; p 203. (b) Hiyama, T. In Organofluorine Compounds;
Yamamoto, H., Ed.; Springer-Verlag: Heidelberg, 2000; p 212. (c) Anderson,
R. F.; Punderson, J. O. In Organofluorine Chemicals and Their Industrial
Applications; Banks, R. E., Ed.; Ellis Horwood LTD.: Chichester, 1979; p 235.
(2) (a) Kirsch, P.; Huber, F.; Lenges, M.; Taugerbeck, A. J. Fluorine
Chem. 2001, 112, 69. (b) Kirsch, P.; Bremer, M.; Huber, F.; Lannert, H.;
Ruhl, A.; Lieb, M.; Wallmichrath, T. J. Am. Chem. Soc. 2001, 123, 5414.
(c) Hird, M.; Goodby, J. W.; Lewis, R. A.; Toyne, K. J. Mol. Cryst. Liq.
Cryst. 2003, 401, 115.
(3) (a) Hiyama, T. In Organofluorine Compounds; Yamamoto, H., Ed.;
Springer-Verlag: Heidelberg, 2000; p 77. (b) In Fluorine-Containing Syn-
thons; Soloshonok, V. A., Ed.; American Chemical Society: Washington,
DC, 2005. (c) Uneyama, K. In Organofluorine Chemistry, Blackwell Publish-
ing: Oxford, 2006; Chapter 7, p 223.
In our plan, (R-arylthio)carbonyl compounds (2), which
are easily accessible from the corresponding carbonyl com-
pounds, are used as the starting material.8 By the reaction
with IF5, three (n = 2) or five (n = 3) fluorine atoms can be
introduced to 2, and the arylthio group can be migrated to
the terminal carbon to yield a polyfluorinated sulfide (3).6
An aryl group is introduced to the terminal carbon of 3 by a
(4) (a) Zupan, M.; Pollak, A. J. Org. Chem. 1974, 39, 2646. (b) Gregorcic,
A.; Zupan, M. J. Org. Chem. 1979, 44, 4120. (c) Mcewen, W. E.; Guzikowski,
A. P.; Wolf, A. P. J. Fluorine Chem. 1984, 25, 169. (d) Rozen, S.; Brand, M.
J. Org. Chem. 1986, 51, 222. (e) York, C.; Prakash, G. K. S.; Olah, G. A.
J. Org. Chem. 1994, 59, 6493. (f ) Gatenyo, J.; Rozen, S. J. Fluorine Chem.
2009, 130, 332.
(5) (a) Singh, R. P.; Majumder, U.; Shreeve, J. M. J. Org. Chem. 2001, 66,
6263. (b) Chang, Y.; Tewari, A.; Adi, A.-I.; Bae, C. Tetrahedron 2008, 64,
9837.
(6) Ayuba, S.; Fukhara, T.; Hara, S. Org. Lett. 2003, 5, 2873.
(7) Fukuhara, T.; Hara, S. Synlett 2009, 198.
(8) Trost, B. M. Chem. Rev. 1978, 78, 363.
DOI: 10.1021/jo101672g
r
Published on Web 10/11/2010
J. Org. Chem. 2010, 75, 7393–7399 7393
2010 American Chemical Society

Fukuhara and Hara
JOCArticle
SCHEME 1. Plan for Polyfluorination of 2
TABLE 2. Friedel-Crafts Arylation of Sulfide 3a
a
TABLE 1. Polyfluorination of Sulfides 2 Using IF5
a If otherwise not mentioned, CH2Cl2 was used as solvent. bIsolation
yield based on 2 used. cHexane was used as solvent. Ar = 4-chlorophenyl.
a If otherwise not mentioned, the reaction was carried out in an
aromatic compound (2 mL) at room temperature for 15 h using 1.5
equiv of SnCl4 to 3 (0.5 mmol). bIsolated yield based on 3. cThe reaction
was carried out in CH2Cl2 (3 mL) using 0.5 mmol of 3 and 1 g of
naphthalene. Ar0 = 4-chlorophenyl.
Friedel-Crafts reaction. As the terminal carbon of 3 is
substituted by an arylthio group that stabilizes the carboca-
tion, the aryl group must be introduced at the terminal car-
bon to yield benzylic sulfide (4).9 By the reaction of 4 with
IF5, oxidative fluorination and desulfurizing fluorination
can be successively induced to yield the target molecule 1
that contains four (n = 2) or six (n = 3) fluorine atoms bet-
ween the aryl group and the carbonyl group (Scheme 1).7
TABLE 3. Desulfurizing Difluorination of 4aa Using IF5
Results and Discussion
Ethyl 2-(4-chlorophenylthio)propionate (2a), 2-(4-chloro-
phenylthio)propiophenone (2b), and ethyl 2-(4-chlorophenyl-
thio)butanoate (2c) were used for the polyfluorination reac-
tion using IF5. In the reaction with 2a, migration of the
arylthio group to the terminal carbon and polyfluorination
took place to yield trifluorinated product (3a) in 96% yield.
Similarly, from 2b and 2c, trifluorinated product (3b) and
pentafluorinated product (3c) were obtained in 64% and 76%
yield, respectively (Table 1).
The aryl group was introduced to the terminal carbon of 3
by the Friedel-Crafts reaction using SnCl4 as Lewis acid.9
As expected, the arylation of 3a-c with various aromatic
compounds occurred selectively at the terminal carbon to
give the corresponding arylated sulfides (4aa-4cb) in a fairly
good yield (Table 2).
yield (%)a
entry
reagent
IF5 (1.5 equiv)
IF5/Et3N-3HF (1.5 equiv)
IF5/Et3N-3HF (1.5 equiv)
(i) IF5/Et3N-3HF (1.5 equiv) rt, 40 h
(ii) IF5 (0.8 equiv) rt, 24 h
condition
1aa
5aa 6aa
1
2
3
rt, 45 h
rt, 24 h
rt, 192 h
60
25
99
32
0
0
0
75
0
4
92 (92)
0
0
a 19F NMR yield based on 4aa, in parentheses, isolated yield. Ar0 =
4-chlorophenyl.
The desulfurizing difluorination of ethyl 2,2-difluoro-3-
phenyl-3-(4-chlorophenylthio)propionate (4aa) was per-
formed using IF5 at room temperature, and the desired
tetrafluoro product (1aa) was obtained in 60% yield with
an unexpected trifluoro product (5aa) (32% yield) (entry 1 in
Table 3). In our plan, ethyl 2,2,3-trifluoro-3-phenyl-3-(4-
chlorophenylthio)propionate (6aa) is initially formed by the
oxidative fluorination of 4aa; the subsequent substitution of
the arylthio group with the fluoride gives 1aa selectively.7
However, in fact, the substitution reaction of the arylthio
group with the fluoride took place from the beginning, and
the formation of 5aa competed with that of 6aa. To prevent
(9) For the Friedel-Crafts-type alkylation of aromatic compounds using
alkyl fluorides, see: (a) Olah, G. A.; Farooq, O.; Farnia, S. M. F.; Wu, A.
J. Org. Chem. 1990, 55, 1516. (b) Aoyama, M.; Hara, S. Tetrahedron 2009, 65,
3682. For the Friedel-Crafts-type alkylation using R-halosulfides, see:
(c) Tamura, Y.; Choi, H. D.; Shindo, H.; Ishibashi, H. Chem. Pharm. Bull.
1982, 30, 915. (d) Arai, K.; Ohara, Y.; Iizumi, T.; Takakuwa, Y. Tetrahedron
Lett. 1983, 24, 1531. (e) Uneyama, K.; Momota, M. Tetrahedron Lett. 1989,
30, 2265. (f ) Uneyama, K.; Momota, M.; Hayashida, K.; Itoh, T. J. Org.
Chem. 1990, 55, 5364.
7394 J. Org. Chem. Vol. 75, No. 21, 2010

Fukuhara and Hara
JOCArticle
the formation of 5aa, we used a less reactive reagent, IF5/
Et3N-3HF.10 In the reaction of 4aa with IF5/Et3N-3HF at
room temperature for 24 h, the formation of 1aa (25%) and
6aa (75%), and the absence of 5aa were confirmed from an
19F NMR analysis (entry 2). By the application of IF5/Et3N-
3HF, the formation of 5aa could be prevented as expected,
and the oxidative fluorination product 6aa was mainly
formed. When the reaction was continued under the condi-
tions for 192 h, 1aa was selectively formed in a quantitative
yield (entry 3). When IF5 was further added to the reaction
mixture of 6aa and IF5/Et3N-3HF, the substitution of the
arylthio group in 6aa with the fluoride could be accelerated,
and 1aa could be obtained in 92% yield in a short reaction
time (entry 4).
Similarly, from 3-(4-chlorophenylthio)-2,2-difluoro-1,3-
diphenylpropan-1-one (4b), the tetrafluoro product (1b)
was obtained in 84% yield by the reaction with IF5/Et3N-
3HF (Method A) (entry 5 in Table 4). However, in the
reaction of ethyl 3-(4-chlorophenylthio)-3-(2,5-dimethyl-
phenyl)-2,2-difluoropropanoate (4ab), which has an electron-
rich aromatic group, the substitution of the arylthio group
with the fluoride is fast and the trifluoro product (5ab) was
mainly formed even in the reaction with IF5/Et3N-3HF
(Method A). When IF5/2(Et3N-3HF) was used as the fluori-
nation reagent (Method B), ethyl 3-(2,5-dimethylphenyl)-
2,2,3,3-tetrafluoropropanoate (1ab) was obtained as the
main product (entry 2). On the other hand, the trifluoro
product 5ab can be selectively prepared by using IF5; 5ab
was obtainedin 94%yield(MethodC) (entry 3). Similarly, the
trifluoro product (5ac) could be selectively obtained from the
naphthyl-group-attached substrate (4ac) under the condition
of Method A (entry 4). In the reaction of tetrafluorinated
sulfides (4ca and 4cb) with IF5 (Methods D and C), the
pentafluoro products (5ca and 5cb) could be selectively ob-
tained in 88% and 84% yield, respectively (entries 6 and 7).
To obtain the hexafluoro product (1ca), 4ca was subjected
to the reaction with IF5/Et3N-3HF for 63 h, followed by IF5
for 45 h, and the expected product 1ca was obtained in 22%
yield (entry 1 in Table 5). However, the main product of the
reaction was unexpectedly a cyclic ether (a mixture of
stereoisomers, 6ca and 6ca0, 39% and 27%, respectively),11
which must be formed by the attack of the carbonyl oxygen
on the arylthio-group-substituted carbon in the desulfurizing
fluorination step, as shown in Scheme 2. We carried out the
reaction under various conditions to prevent the cyclization
reaction and succeeded in improving the yield of 1ca slightly
but failed to prevent the formation of the cyclic ethers 6ca
and 6ca0 (entries 2 and 3).
a
TABLE 4. Desulfurizing Fluorination of Sulfide 4 Using IF5
a If otherwise not mentioned, CH2Cl2 was used as solvent. bMethod A:
1.5 equiv of IF5/Et3N-3HF. Method B: 1.5 equiv of IF5/2(Et3N-3HF).
Method C: 0.8 equiv of IF5. Method D: 3equiv of IF5. Isolated yield
Next, we attempted to convert the cyclic ether 6ca and 6ca0
to 1ca. By the treatment of the cyclic ether with BF3 etherate,
the cleavage of the ether bond occurred and a ketone (7ca)
was obtained in 89% yield. From 7ca, the hexafluoro product
c
based on 4; in parentheses, 19FNMR yield. dHexane was used as solvent.
Ar0 = 4-chlorophenyl.
TABLE 5. Desulfurizing Difluorination of 4ca
yield (%)a
entry
1
reagent
solvent
CH2Cl2
condition
1ca
6ca
6ca0
(i) IF5/Et3N-3HF (3.0 equiv)
(ii) IF5 (0.8 equiv)
rt, 63 h
rt, 45 h
22
39
27
(i) IF5/Et3N-3HF (3.0 equiv)
(ii) IF5 (0.8 equiv)
IF5/Et3N-3HF (3.0 equiv)
rt, 63 h
40 °C, 45 h
rt, 168 h
2
3
hexane
CH2Cl2
39
30
36
39
25
28
a 19F NMR yield based on 4ca. Ar0 = 4-chlorophenyl.
J. Org. Chem. Vol. 75, No. 21, 2010 7395

Fukuhara and Hara
JOCArticle
SCHEME 2. Mechanism of the Formation of 1ca and 6ca (6ca0)
temperature. It should be carefully handled with Teflon equip-
ment in a bench hood.
IF5/Et3N-3HF {IF5/2(Et3N-3HF)}. From a cylinder, IF5 was
transferred through a Teflon tube into a Teflon bottle under an
N2 atmosphere. After measuring the amount of IF5 in the bottle,
a 1 (or 2) molar amount of Et3N-3HF was added at room
temperature. It should be carefully handled with Teflon equip-
ment in a bench hood.
Ethyl 3-(4-Chlorophenylthio)-2,2,3-trifluoropropanoate (3a).
In a Teflon reactor with a tight screw cap, IF5/5CH2Cl2 (730
mg, 1.13 mmol), 2a (127 mg, 0.52 mmol), and hexane (3 mL)
were introduced at 0 °C, and mixture was stirred at room tem-
perature for 24 h. The mixture was poured into water (10 mL),
neutralized with aq NaHCO3, and extracted with Et2O(20mLꢀ 3).
The combined organic layer was washed with aq Na2S2O3,
dried over MgSO4, and concentrated under reduced pressure.
Purification by column chromatography (silica gel/hexane-
EtOAc) gave 3a (149 mg) in 96% yield; IR (neat) 2987, 1779
(CdO), 1477, 1014 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.38 (t,
J = 7.3 Hz, 3H), 4.40 (q, J = 7.2 Hz, 2H), 5.97 (ddd, J = 50.8,
SCHEME 3
11.9, 10.0 Hz, 1H), 7.36 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.5 Hz,
2H); 19F NMR (376 MHz, CDCl3) δ -114.66 (ddd, JF-F
2
=
3
3
SCHEME 4
269.8 Hz, JF-F = 21.9 Hz, JF-H = 10.1 Hz, 1F), -115.72
(ddd, 2JF-F = 269.8 Hz, 3JF-F = 20.5 Hz, 3JF-H = 11.9 Hz,
=
1F), -167.49 (ddd, 2JF-H = 51.0 Hz, 3JF-F = 21.9 Hz, 3JF-F
20.8 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ 13.8, 63.8, 99.3
(ddd, 1JC-F = 232.1 Hz, 2JC-F = 29.5 Hz, 2JC-F = 28.0 Hz),
=
111.1 (td, 1JC-F = 259.9 Hz, 2JC-F =30.4 Hz), 128.6(d, 3JC-F
1.9 Hz), 129.6 (2C), 134.8 (d, 4JC-F = 1.9 Hz, 2C), 135.9, 161.3
2
(t, JC-F = 30.9 Hz); HRMS (EI) calcd for C11H10ClF3O2S,
298.0042, found 298.0038.
3-(4-Chlorophenylthio)-2,2,3-trifluoro-1-phenylpropan-1-one
(3b). In a Teflon reactor with a tight screw cap, IF5/5CH2Cl2
(1.16 g, 1.8 mmol), 2b (278 mg, 1.00 mmol), and CH2Cl2 (4 mL)
were introduced at 0 °C, and mixture was stirred at room
temperature for 20 h. The mixture was poured into water
(10 mL), neutralized with aq NaHCO3, and extracted with
Et2O (20 mL ꢀ 3). The combined organic layer was washed
with aq Na2S2O3, dried over MgSO4, and concentrated under
reduced pressure. Purification by column chromatography
(silica gel/hexane-EtOAc) gave 3b (212 mg) in 64% yield; IR
1ca was obtained in 42% yield by the reaction with DAST-
SbF3, although the cyclization to 6ca and 6ca0 competitively
occurred under the conditions (Scheme 3).
Consequently, 1ca was totally prepared in 62% yield from
4ca (Scheme 4).
Summary
(neat) 1701 (CdO), 1477, 1013 cm-1 1H NMR (400 MHz,
;
Polyfluoro compounds having three to six fluorine atoms
on the adjacent carbons located between the carbonyl and
the aryl group were selectively prepared by the successive
application of polyfluorination using IF5, Friedel-Crafts
arylation, and desulfurizing fluorination using IF5 to
2-(arylthio)carbonyl compounds. In the desulfurizing fluori-
nation step, one or two fluorine atoms were introduced to the
terminal carbon depending on the substituted aryl group or the
desulfurizing fluorination reagent.
CDCl3) δ 6.19 (ddd, J = 50.9, 11.9, 10.1 Hz, 1H), 7.35 (d, J =
8.6 Hz, 2H), 7.50-7.55 (m, 4H), 7.69 (t, J = 7.6 Hz, 1H), 8.09 (d,
J = 7.7 Hz, 2H); 19F NMR (376 MHz, CDCl3) δ -107.81 (ddd,
3
3
2JF-F = 292.8 Hz, JF-F = 21.5 Hz, JF-H = 10.1 Hz, 1F),
2
3
3
-109.66 (ddd, JF-F = 292.7 Hz, JF-F =19.4 Hz, JF-H
=
11.8 Hz, 1F), -166.90 (ddd, 2JF-H = 51.0 Hz, 3JF-F = 20.8 Hz,
3JF-F = 19.8 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ 99.7
(ddd, 1JC-F = 231.4 Hz, 2JC-F = 29.7 Hz, 2JC-F = 26.8 Hz),
114.0 (ddd, 1JC-F = 265.6 Hz, 1JC-F = 262.8 Hz, 2JC-F = 29.0
Hz), 128.8 (2C), 129.3 (d, 3JC-F = 1.7 Hz), 129.6 (2C), 130.0 (t,
4JC-F = 3.6 Hz, 2C), 131.7 (t, 3JC-F = 2.2 Hz), 134.6 (d, 4J =
Experimental Section
2
1.9 Hz, 2C), 134.8, 135.6, 187.3 (t, JC-F = 28.7 Hz); HRMS
General Methods. Et3N-3HF was purchased from a commer-
cial source. IF5 was supplied by Asahi Glass Co., Ltd. The
reaction using IF5 or DAST was perfoemed in a Teflon FEP
centrifuge tube with a tight screw cap.
IF5/5CH2Cl2. As IF5 is liquid of high hygroscopicity and low
viscosity, it was used as a solution of CH2Cl2. From a cylinder,
IF5 was transferred through a Teflon tube into a Teflon bottle
under an N2 atmosphere. After measuring the amount of IF5 in
the bottle, a 5 molar amount of CH2Cl2 was added at room
(EI) calcd for C15H10ClF3OS 330.0093, found, 330.0091.
Ethyl 4-(4-Chlorophenylthio)-2,2,3,3,4-pentafluorobutanoate
(3c)6. The reaction was performed as above using IF5/5CH2Cl2
(2.42 g, 3.74 mmol), 2c (257 mg, 0.99 mmol), and CH2Cl2 (4 mL)
at room temperature for 48 h. Purification by column chroma-
tography (silica gel/hexane-EtOAc) gave 3c (262 mg) in 76%
1
yield; IR (neat) 2987, 1776 (CdO), 1013 cm-1; H NMR (400
MHz, CDCl3) δ 1.38 (t, J = 7.1 Hz, 3H), 4.41 (q, J = 7.1 Hz,
2H), 5.98 (ddd, J = 50.3, 16.6, 5.1 Hz, 1H), 7.37 (d, J = 8.7 Hz,
2H), 7.52 (d, J = 8.7 Hz, 2H); 19F NMR (376 MHz, CDCl3)
δ -165.48 to -156.19 (m, 1F), -124.84 (ddd, 2JF-F = 279.5 Hz,
(10) Previously, IF5/Et3N-3HF was used for the oxidative fluorination
reaction of the sulfides; see: Ayuba, S.; Yoneda, N.; Fukuhara, T.; Hara, S.
Bull. Chem. Soc. Jpn. 2002, 75, 1597.
3JF-F = 17.1 Hz, 3JF-F = 17.1 Hz, 1F), -120.22 (ddd, 2JF-F
=
3
3
(11) The cyclic ethers (6ca and 6ca0) are separable by silica gel column
chromatography, but their stereochemical identification is difficult.
276.5 Hz, JF-F = 7.3 Hz, JF-F = 3.7 Hz, 1F), -119.38
2
3
(dd, JF-F = 276.5 Hz, JF-F = 8.5 Hz, 1F), -117.42 (ddm,
7396 J. Org. Chem. Vol. 75, No. 21, 2010

Fukuhara and Hara
JOCArticle
2JF-F = 279.8 Hz, 3JF-F = 21.2 Hz, 1F); 13C NMR (100 MHz,
CDCl3) δ 13.7, 64.3, 98.1 (ddd, 1JC1-F = 229.9 Hz, 2JC-F = 33.9
Hz, JC-F = 24.8 Hz), 108.5 (tt, JC-F = 265.1 Hz, JC-F =
IR (neat) 3063, 1703 (CdO), 1179, 1050 cm-1; H NMR (400
1
MHz, CDCl3) δ 4.87 (dd, J = 19.5 Hz, 12.4 Hz, 1H), 7.17-7.23
(m, 4H), 7.30-7.37 (m, 5H), 7.47 (t, J = 7.5 Hz, 1H), 7.62 (t, J =
7.3 Hz, 1H), 7.97 (d, J = 8.0 Hz, 2H); 19F NMR (376 MHz,
CDCl3) δ -97.51 (dd, 2JF-F = 279.1 Hz, 3JF-H = 12.6 Hz, 1F),
2
2
1
1
33.1 Hz), 112.7 (dddt, JC-F = 264.7 Hz, JC-F = 260.9 Hz,
2JC-F = 29.8 Hz, 2JC-F = 29.8 Hz), 128.2 (d, 3JC-F = 1.4 Hz),
=
129.8(2C), 135.2(d, 4JC-F = 1.4 Hz, 2C), 136.2, 159.5 (t, 2JC-F
-104.11 (dd, JF-F = 279.4 Hz, JF-H = 19.4 Hz, 1F); 13C
NMR (100 MHz, CDCl3) δ 56.9 (t, 2JC-F = 22.8 Hz), 117.7 (t,
1JC-F = 261.1 Hz), 128.5 (2C), 128.5 (2C), 128.6 (2C), 129.1
2
3
29.8 Hz); HRMS (EI) calcd for C12H10ClF5O2S 348.0010, found
348.0006.
Ethyl 3-(4-Chlorophenylthio)-2,2-difluoro-3-phenylpropano-
ate (4aa). Under N2 atmosphere, SnCl4 (195 mg, 0.75 mmol)
was added at room temperature to a mixture of 3a (149 mg, 0.50
mmol) and benzene (1 mL). After stirring at room temperature
for 15 h, the mixture was poured into water (10 mL), neutralized
with aq NaHCO3, and extracted with Et2O (20 mL ꢀ 3). The
combined organic layer was dried over MgSO4 and concen-
trated under reduced pressure. Purification by column chroma-
tography (silica gel/hexane-EtOAc) gave 4aa (164 mg) in 92%
yield; IR (neat) 2984, 1773 (CdO), 1476, 1095 cm-1; 1H NMR
(400 MHz, CDCl3) δ 1.20 (t, J = 7.2 Hz, 3H), 4.16-4.25 (m,
2H), 4.62 (dd, J = 17.2, 14.2 Hz, 1H), 7.20-7.32 (m, 9H); 19F
(2C), 129.7 (2C), 129.8 (t, 3JC-F = 2.9 Hz), 131.6, 132.6 (t, 3JC-F
=
2.2 Hz), 134.0 (d, 4JC-F = 1.9 Hz), 134.2, 134.5 (2C), 134.5, 189.2
(t, JC-F = 29.7 Hz); HRMS (EI) calcd for C21H15ClF2OS
388.0500, found 388.0500.
2
Ethyl 4-(4-Chlorophenylthio)-2,2,3,3-tetrafluoro-4-phenylbu-
tanoate (4ca). The reaction was performed as above using 3c
(550 mg, 1.58 mmol), benzene (5 mL), and SnCl4 (625 mg, 2.40
mmol) at room temperature for 15 h. Purification by column
chromatography (silica gel/hexane-EtOAc) gave 4ca (609 mg)
in 95% yield; IR (neat) 2986, 1773 (CdO), 1316, 1095 cm-1; 1H
NMR (400 MHz, CDCl3) δ 1.32 (t, J = 7.2 Hz, 3H), 4.27 (q, J =
7.2 Hz, 2H), 4.57 (dd, J = 19.0, 12.4 Hz, 1H), 7.20-7.33 (m,
=
2
9H); 19F NMR (376 MHz, CDCl3) δ -109.09 (dd, JF-F
2
NMR (376 MHz, CDCl3) δ -105.19 (dd, JF-F = 257.9 Hz,
274.0 Hz, 3JF-H = 12.6 Hz, 1F), -114.31 (dd, 2JF-F = 274.1
Hz, 3JF-H = 19.0 Hz, 1F), -117.45 (d, 2JF-F = 277.7 Hz, 1F),
3JF-H =14.0 Hz, 1F), -108.91 (dd, 2JF-F = 257.9 Hz, 3JF-H
17.2 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ13.7, 57.2 (t, 2JC-F
=
=
-118.28(d, JF-F = 277.7 Hz, 1F); 13C NMR (100 MHz,
2
23.5 Hz), 63.1, 114.6 (t, 1JC-F = 258.2 Hz), 128.6 (2C), 128.8,
2
129.2(2C), 129.5(t, 4JC-F =1.2 Hz, 2C), 131.3, 133.5 (d, 3JC-F
=
CDCl3) δ 13.5, 55.5 (t, JC-F = 23.0 Hz), 63.8, 106.3-119.2
2.9 Hz), 134.7, 134.8 (2C), 163.0 (t, 2JC-F = 32.6 Hz); HRMS
(EI) calcd for C17H15ClF2O2S 356.0449, found 356.0434.
Ethyl 3-(4-Chlorophenylthio)-3-(2,5-dimethylphenyl)-2,2-di-
fluoropropanoate (4ab). The reaction was performed as above
using 3a (596 mg, 2.00 mmol), p-xylene (4 mL), and SnCl4 (782
mg, 3.00 mmol) at room temperature for 15 h. Purification by
column chromatography (silica gel/hexane-EtOAc) gave 4ab
(714 mg) in 93% yield; IR (neat) 2982, 1775 (CdO), 1475, 1093,
1054 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.14 (t, J = 7.0 Hz,
3H), 2.23 (s, 3H), 2.27 (s, 3H), 4.12-4.18 (m, 2H), 4.92 (t, J =
16.0 Hz, 1H), 6.99-7.04 (m, 2H), 7.16-7.23 (m, 3H), 7.27-7.29
(m, 2C), 128.4 (2C), 128.7 (2C), 129.1 (2C), 129.39, 131.1, 133.4
(d, 3JC-F = 3.8 Hz), 134.8, 135.0 (2C), 159.9 (t, 2JC-F = 30.2
Hz); HRMS (EI) calcd for C18H15ClF4O2S 406.0417, found
406.0418.
Ethyl 4-(4-Chlorophenylthio)-4-(2,5-dimethylphenyl)-2,2,3,3-
tetrafluorobutanoate (4cb). The reaction was performed as
above using 3c (1.046 g, 3.00 mmol), p-xylene (6 mL), and SnCl4
(1.17 g, 4.49 mmol) at room temperature for 15 h. Purification
by column chromatography (silica gel/hexane-EtOAc) gave
4cb (1.28 g) in 98% yield; IR (neat) 2985, 1772(CdO), 1476,
1313 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.31 (t, J = 7.2 Hz,
3H), 2.17 (s, 3H), 2.28 (s, 3H), 4.22 (q, J = 7.2 Hz, 2H), 4.87 (dd,
J = 18.3, 13.6 Hz, 1H), 7.01 (s, 2H), 7.18-7.28 (m, 5H); 19F
(m, 2H); 19F NMR (376 MHz, CDCl3) δ -105.28 (dd, 2JF-F
=
258.2 Hz, 3JF-H = 14.4 Hz, 1F), -106.29 (dd, 2JF-F = 257.9
2
Hz, 3JF-H = 16.9 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ 13.5,
19.0, 20.8, 52.2 (t, JC-F = 21.6 Hz), 62.9, 115.0 (t, JC-F =
NMR (376 MHz, CDCl3) δ -108.12 (dd, JF-F = 273.0 Hz,
3JF-H = 13.3 Hz, 1F), -113.78 (dd, 2JF-F = 273.0 Hz, 3JF-H
=
2
1
18.3 Hz, 1F), -117.84 (d, 3JF-F = 38.1 Hz, 2F); 13C NMR (100
MHz, CDCl3) δ 13.5, 18.9, 20.6, 50.1 (t, 2JC-F = 22.5 Hz), 63.8,
106.3-119.6 (m, 2C), 129.0 (2C), 129.3, 129.9 (d, 3JC-F = 3.8
Hz), 130.3, 131.2, 131.5 (d, 4JC-F = 3.8 Hz), 133.1, 135.0, 135.5
257.5 Hz), 128.9 (2C), 129.2, 129.6, 130.2, 131.4, 131.6, 133.2,
134.7, 135.2 (2C), 135.8, 163.1 (t, 2JC-F = 32.6 Hz); HRMS (EI)
calcd for C19H19ClF2O2S 384.0762, found 384.0758.
Ethyl 3-(4-Chlorophenylthio)-2,2-difluoro-3-(naphthalen-1-yl)-
propanoate (4ac). Under N2 atmosphere, SnCl4 (197 mg, 0.76
mmol) was added at room temperature to a mixture of 3a (149 mg,
0.50 mmol) and naphthalene (1.0 g, 7.8 mmol) in CH2Cl2 (3 mL).
After stirring at room temperature for 15 h, the mixture was
poured into water (10 mL), neutralized with aq NaHCO3, and ex-
tracted with Et2O (20 mL ꢀ 3). The combined organic layer was
dried over MgSO4, and concentrated under reduced pressure.
Purification by column chromatography (silica gel/hexane-
EtOAc) gave 4ac (191 mg) in 94% yield; IR (neat) 2983, 1769
(CdO), 1314, 1050 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.00 (t,
J = 7.2 Hz, 3H), 4.04-4.10 (m, 2H), 5.60 (t, J = 15.2 Hz, 1H),
2
(2C), 135.8, 160.0 (t, JC-F = 30.4 Hz); HRMS (EI) calcd for
C20H19ClF4O2S 434.0730, found 434.0730.
Ethyl 2,2,3,3-Tetrafluoro-3-phenylpropanoate (1aa)12. To IF5/
Et3N-3HF (300 mg, 0.78 mmol) in a Teflon reactor with a tight
screw cap was added 4aa (178 mg, 0.50 mmol) in CH2Cl2 (3 mL)
at 0 °C. The mixture was stirred at room temperature for 40 h,
and the complete consumption of 4aa was confirmed by GC
analysis. Then, IF5/5CH2Cl2 (250 mg, 0.39 mmol) was added,
and the reaction mixture was stirred at room temperature for
another 24 h. The mixture was poured into water (10 mL), neu-
tralized with aq NaHCO3, and extracted with Et2O (20 mL ꢀ 3).
The combined organic layer was washed with aq Na2S2O3,
dried over MgSO4, and concentrated under reduced pressure.
Purification by column chromatography (silica gel/hexane-
EtOAc) gave 1a (115 mg) in 92% yield; IR (neat) 2989, 1777
7.15-7.24 (m, 4H), 7.40-7.60 (m, 4H), 7.82-8.00 (m, 3H); 19
F
2
NMR (376 MHz, CDCl3) δ -104.90 (dd, JF-F = 255.5 Hz,
3JF-H = 14.4 Hz, 1F), -105.77 (dd, 2JF-F = 255.5 Hz, 3JF-H
=
=
15.5 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ13.4, 51.0 (t, 2JC-F
1
(CdO), 1322, 1170 cm-1; H NMR (400 MHz, CDCl3) δ 1.35
1
24.0 Hz), 63.0, 115.1 (t, JC-F = 258.2 Hz), 122.3, 125.2, 125.9,
126.8, 127.6, 129.0 (2C), 129.1, 129.2, 129.3, 131.1, 131.2, 133.6,
134.8 (2C), 135.2, 163.1 (t, 2JC-F = 32.6 Hz); HRMS (EI) calcd for
C21H17ClF2O2S 406.0606, found 406.0604.
3-(4-Chlorophenylthio)-2,2-difluoro-1,3-diphenylpropan-1-one
(4b). The reaction was performed as above using 3b (165 mg,
0.50 mmol), benzene (2 mL), and SnCl4 (195 mg, 0.75 mmol) at
room temperature for 15 h. Purification by column chromatog-
raphy (silica gel/hexane-EtOAc) gave 4b (185 mg) in 95% yield;
(t, J = 7.2 Hz, 3H), 4.39 (q, J = 7.3 Hz, 2H), 7.47-7.59
=
3
(m, 5H); 19F NMR (376 MHz, CDCl3) δ -112.10 (t, JF-F
3
6.1 Hz, 2F), -119.44 (t, JF-F = 6.2 Hz, 2F); 13C NMR (100
MHz, CDCl3) δ 13.4, 63.6, 109.3 (tt, 1JC-F = 263.3 Hz, 2JC-F
39.5 Hz), 115.6 (tt, JC-F = 255.4 Hz, JC-F = 31.9 Hz),
=
1
2
3
126.6 (tt, JC-F = 6.5 Hz, JC-F =1.2 Hz, 2C), 128.4, 129.4
4
(12) Yang, Z.-Y. J. Fluorine Chem. 2004, 125, 763.
J. Org. Chem. Vol. 75, No. 21, 2010 7397

Fukuhara and Hara
JOCArticle
(376 MHz, CDCl3) δ -110.42 (t, 3JF-F = 12.9 Hz, 2F), -113.63
(t, 3JF-F = 12.2 Hz, 2F); 13C NMR (100 MHz, CDCl31) δ 112.1
2
(t, JC-F = 24.4 Hz), 131.5 (t, JC-F = 2.7 Hz, 2C), 160.2
4
2
(t, JC-F = 30.7 Hz); HRMS (EI) calcd for C11H10F4O2
250.0617, found 250.0616.
1
2
(tt, JC-F = 265.9 Hz, JC-F = 39.0 Hz), 116.1 (tt, JC-F
254.9 Hz, 2JC-F = 31.6 Hz), 126.8 (tt, 3JC-F = 6.5 Hz, 4JC-F
=
=
Ethyl 3-(2,5-Dimethylphenyl)-2,2,3,3-tetrafluoropropanoate
(1ab). The reaction was performed as above using IF5/2(Et3N-
3HF) (408 mg, 0.75 mmol) and 4ab (205 mg, 0.5 mmol) in
CH2Cl2 (4 mL) at room temperature for 144 h. From 19F NMR
analysis of the crude mixture, 5ab was found to be formed in
27% yield. Purification by column chromatography (silica gel/
hexane-EtOAc) gave 1ab (94 mg) in 74% yield; IR (neat) 2987,
1772(CdO), 1317 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.37 (t,
J = 7.2 Hz, 3H), 2.34 (s, 3H), 2.44 (t, J = 3.0 Hz, 3H), 4.40 (q,
J = 7.2 Hz, 2H), 7.14 (d, J = 7.9 Hz, 1H), 7.20 (d, J = 7.9 Hz,
1H), 7.28 (s, 1H); 19F NMR (376 MHz, CDCl3) δ -106.96 to
-106.96 (m, 2F), -108.51 to -108.57 (m, 2F); 13C NMR (100
MHz, CDCl3) δ 13.6, 19.80-20.0 (m), 20.5, 63.6, 111.0 (tt,
1.2 Hz, 2C), 128.4 (2C), 128.7, 129.8 (t, 2JC-F = 24.4 Hz), 130.3
(t, 4JC-F = 3.6 Hz, 2C), 131.4 (t, 4JC-F = 1.4 Hz, 2C), 132.5 (t,
3JC-F = 1.4 Hz), 134.8, 186.0 (t, 2JC-F = 26.3 Hz); HRMS (EI)
calcd for C15H10F4O 282.0668, found 282.0669.
Ethyl 2,2,3,3,4-Pentafluoro-4-phenylbutanoate (5ca). The re-
action was performed as above using IF5/5CH2Cl2 (1.01 g, 1.56
mmol) and 4ca (202 mg, 0.50 mmol) in hexane (3 mL) at 40 °C
for 72 h. Purification by column chromatography (silica gel/
hexane-EtOAc) gave 5ca (124 mg) in 88% yield; IR (neat) 2989,
1776 (CdO), 1316, 1170, 1142 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 1.38 (t, J = 7.2 Hz, 3H), 4.41 (q, J = 7.2 Hz, 2H),
5.80 (ddd, J = 44.3, 18.5, 3.8 Hz, 1H), 7.45 (s, 5H). 19F NMR
(376 MHz, CDCl3) δ -119.50 (dd, 2JF-F = 277.3 Hz, 3JF-F
=
1JC-F = 261.8, JC-F = 41.0 Hz), 117.2 (tt, JC-F = 254.7,
2
1
10.0 Hz, 1F), -121.06 (dt, 2JF-F = 276.9 Hz, 3JF-F = 5.4 Hz,
2JC-F = 33.2 Hz), 132.0 (t, 4JC-F = 1.5 Hz), 127.1 (t, 2JC-F
=
2
22.2 Hz), 128.6 (tt, 3JC-F = 7.1, 4JC-F = 1.4 Hz), 132.3, 134.7
(t, 3JC-F = 2.4 Hz), 135.3, 160.5 (t, 2JC-F = 30.5 Hz); HRMS
(EI) calcd for C13H14F4O2 278.09299, found 278.09305.
1F), -121.29 (dm, JF-F = 286.2 Hz, 1F), -128.77 (ddd,
2JF-F = 285.9 Hz, JF-F = 18.0 Hz, JF-F = 15.5 Hz, 1F),
3
3
-194.07 (dm, JF-H = 44.2 Hz, 1F); 13C NMR (100 MHz,
1
CDCl3) δ 13.4, 64.0, 88.5 (ddd, 1JC1-F = 184.0 Hz, 2JC-F =33.3
Hz, JC-F = 23.2 Hz), 109.0 (tt, JC-F = 264.7 Hz, JC-F =
Ethyl 3-(2,5-Dimethylphenyl)-2,2,3-trifluoropropanoate (5ab).
The reaction was performed as above using IF5/5CH2Cl2 (505
mg, 0.78 mmol) and 4ab (201 mg, 0.49 mmol) in CH2Cl2 (4 mL)
at room temperature for 24 h. Purification by column chroma-
tography (silica gel/hexane-EtOAc) gave 5ab(120 mg) in 94%
yield; IR (neat) 2986, 1777 (CdO), 1308, 1075 cm-1; 1H NMR
(400 MHz, CDCl3) δ 1.35 (t, J = 7.4 Hz, 3H), 2.34 (s, 6H), 4.38
(q, J = 7.2 Hz, 2H), 6.05 (ddd, J = 43.5, 17.3, 4.4 Hz, 1H),
7.09-7.15 (m, 2H), 7.30 (s, 1H); 19F NMR (376 MHz, CDCl3) δ
-113.63 (ddd, 2JF-F = 270.8 Hz, 3JF-F = 13.3 Hz, 3JF-H = 4.7
2
2
33.1 Hz), 110.1-116.2 (m), 127.7 (d, 3JC-F = 7.2 Hz, 2C), 128.5,
130.1 (d, 2JC-F = 20.6 Hz), 130.3 (d, 4JC-F = 1.9 Hz, 2C), 159.8
(t, JC-F = 29.7 Hz); HRMS (ESI) calcd for C12H11F5O2Na
305.0577, found 305.0580.
1
Ethyl 4-(2,5-Dimethylphenyl)-2,2,3,3,4-pentafluorobutanoate
(5cb). The reaction was performed as above using IF5/5CH2Cl2
(350 mg, 0.54 mmol) and 4cb (308 mg, 0.71 mmol) in CH2Cl2
(4 mL) at room temperature for 48 h. Purification by column
chromatography (silica gel/hexane-EtOAc) gave 5cb (185 mg)
in 84% yield; IR (neat) 2987, 1777 (CdO), 1316, 1172, 1101
cm-1; 1H NMR (400 MHz, CDCl3) δ 1.39 (t, J = 7.3 Hz, 3H),
2.31 (s, 3H), 2.35 (s, 3H), 4.42 (q, J = 7.3 Hz, 2H), 6.09 (dd, J =
44.1, 20.3 Hz, 1H), 7.09-7.16 (m, 2H), 7.32 (s, 1H); 19F NMR
2
3
Hz, 1F), -121.69 (ddd, JF-F = 271.9 Hz, JF-F = 15.7 Hz,
3JF-H = 15.7 Hz, 1F), -192.92 (dt, 2JF-H = 43.5 Hz, 3JF-F
14.4 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ 13.4, 18.3, 20.5,
63.2, 87.4 (ddd, 1JC-F = 180.1 Hz, 2JC-F = 32.6 Hz, 2JC-F
=
=
1
1
24.9 Hz), 112.4 (ddd, JC-F = 262.5 Hz, JC-F = 253.0 Hz,
=
(376 MHz, CDCl3) δ -120.36 (ddd, 2JF-F = 276.2 Hz, 3JF-F
=
2JC-F = 33.1 Hz), 128.2 (d, 4JC-F = 7.7 Hz), 128.6 (d, 3JC-F
19.2 Hz), 129.7 (d, JC-F = 26.8 Hz), 130.5 (d, JC-F = 12.9
10.4 Hz, 3JF-H = 2.9 Hz, 1F), -121.40 (dm, 2JF-F = 286.3 Hz,
2
3
2
3
Hz), 133.6 (d, 4JC-F = 3.8 Hz), 135.5, 162.3 (dd, 2JC-F = 32.6
Hz, JC-F = 29.0 Hz); HRMS (EI) calcd for C13H15F3O2
260.1024, found 260.1024.
1F), -121.91 (dt, JF-F = 276.2 Hz, JF-F = 5.4 Hz, 1F),
-129.69 (dddd, 2JF-F = 287.3 Hz, 3JF-F = 17.2 Hz, 3JF-F
15.8 Hz, 4JF-F = 1.8 Hz, 1F), -193.83 to -193.59 (m, 1F); 13
NMR (100 MHz, CDCl3) δ 13.5, 18.3 (d, 4JC-F = 3.4 Hz), 20.6,
63.9, 85.1 (ddd, 1JC-F = 181.6 Hz, 2JC-F = 34.7 Hz, 2JC-F
2
=
C
Ethyl 2,2,3-Trifluoro-3-(naphthalen-1-yl)propanoate (5ac).
The reaction was performed as above using IF5/Et3N-3HF
(540 mg, 1.41 mmol) and 4ac (380 mg, 0.94 mmol) in CH2Cl2
(4 mL) at 0 °C for 24 h. Purification by column chromatography
(silica gel/hexane-EtOAc) gave 5ac (225 mg) in 85% yield; IR
=
1
2
22.8 Hz), 109.1 (tt, JC-F = 264.4 Hz, JC-F = 33.8 Hz),
110.5-116.6 (m), (dddt, 1JC-F = 265.4 Hz, 1JC-F = 253.9 Hz,
2JC-F = 29.9 Hz, 2JC-F =29.5 Hz), 128.2 (d, 2JC-F = 11.5 Hz),
3
4
(neat) 2986, 1768 (CdO), 1306 cm-1 1H NMR (400 MHz,
;
128.3 (d, JC-F = 9.6 Hz), 130.5, 130.8 (d, JC-F = 1.9 Hz),
3
2
133.7 (d, JC-F = 5.3 Hz), 135.7, 159.9 (t, JC-F = 30.0 Hz);
HRMS (ESI) calcd for C14H15F5O2 310.0992, found 310.0997.
Ethyl 2,2,3,3,4,4-Hexafluoro-4-phenylbutanoate (1ca)13 and
2-Ethoxy-2,3,3,4,4,5-hexafluoro-5-phenyltetrahydrofuran (6ca and
6ca0). A mixture of IF5/Et3N-3HF (574 mg, 1.50 mmol) and 4ca
(203 mg, 0.50 mmol) in hexane (2 mL) was stirred at room
temperature for 63 h. Then, IF5/5CH2Cl2 (258 mg, 0.40 mmol)
was added, and the reaction mixture was stirred at 40 °C for 45 h.
After work-up operation, yields of 1ca (39%), 6ca (36%), and
6ca0 (25%) were determined by 19F NMR using fluorobenzene
as an internal standard. They can be isolated by column
chromatography (silica gel/hexane-EtOAc) but were used for
the next step without purification. 1ca: IR (neat) 2991, 1778
(CdO), 1320, 1181 cm-1, 1H NMR (400 MHz, CDCl3) δ 1.38 (t,
J = 7.2 Hz, 3H), 4.41 (q, J = 7.2 Hz, 2H), 7.48-7.59 (m, 5H),
19F NMR(376 MHz, CDCl3) δ -111.00 (t, 3JF-F = 10.1 Hz, 2F),
CDCl3) δ 1.31 (t, J = 7.2 Hz, 3H), 4.35 (q, J = 7.2 Hz, 2H), 6.63
(ddd, J = 43.3, 16.1, 5.1 Hz, 1H), 7.52-7.60 (m, 3H), 7.74 (d,
J = 7.2 Hz, 1H), 7.90-8.02 (m, 3H); 19F NMR (376 MHz,
CDCl3) δ -113.99 (ddd, 2JF-F = 269.4 Hz, 3JF-F = 12.2 Hz,
3JF-H = 5.0 Hz, 1F), -121.82 (dt, 2JF-F = 269.8 Hz, 3JF-F
=
15.8 Hz, 1F), -194.44 (ddd, 2JF-H = 43.1 Hz, 3JF-F = 15.4 Hz,
3JF-F = 12.9 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ 13.5,
=
63.4, 87.8 (ddd, 1JC-F =182.5 Hz, 2JC-F = 31.9 Hz, 2JC-F
1
1
25.9 Hz), 112.4 (ddd, JC-F = 263.5 Hz, JC-F = 263.5 Hz,
2JC-F = 32.8 Hz), 122.8, 124.8, 125.9, 126.3 (d, 2JC-F = 19.2
Hz), 126.6 (d, 3JC-F = 9.6 Hz), 126.8, 128.8, 130.7 (d, 4JC-F
1.9 Hz), 130.8 (d, JC-F = 3.1 Hz), 133.4, 162.3 (dd, JC-F
=
=
3
2
32.6 Hz, 2JC-F = 29.7 Hz); HRMS (EI) calcd for C15H13F3O2
282.0868, found 282.0866.
2,2,3,3-Tetrafluoro-1,3-diphenylpropan-1-one (1b). The reac-
tion was performed as above using IF5/Et3N-3HF (320 mg, 0.84
mmol) and 4b (198 mg, 0.51 mmol) in CH2Cl2 (3 mL) at room
temperature for 40 h. Purification by column chromatography
(silica gel/hexane-EtOAc) gave 1b (121 mg) in 84% yield; IR
3
3
-118.89 (tt, JF-F = 10.1 Hz, JF-F = 2.5 Hz, 2F), -124.27
3
(t, JF-F = 2.5 Hz, 2F), 13C NMR (100 MHz, CDCl3) δ 13.5,
64.2, 108.6 (ttt, JC-F = 266.8 Hz, JC-F = 32.1 Hz, 1.4 Hz),
1
2
(neat) 3068, 1701 (CdO), 1151 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 7.49-7.67 (m, 8H), 8.09 (d, J = 7.6 Hz, 2H); 19F NMR
7398 J. Org. Chem. Vol. 75, No. 21, 2010
(13) McLoughlin, V. C. R.; Thrower, J. Tetrahedron 1969, 25, 5921.

Fukuhara and Hara
JOCArticle
= 1.9 Hz), HRMS (EI); calcd for C12H10F6O2
111.6-105.5 (m, 2C), 115.9 (tt, 1JC-F = 255.8 Hz, 2JC-F = 31.9
Hz), 126.8 (tt, 3JC-F = 6.7 Hz, 4JC-F = 1.4 Hz, 2C), 128.5 (2C),
129.1 (t, JC-F = 24.4 Hz), 131.8 (t, JC-F = 1.9 Hz), 159.4
4
(d, 2C, J
C-F
300.0585, found 300.0585.
2
4
Ethyl 2,2,3,3-Tetrafluoro-4-oxo-4-phenylbutanoate (7ca). To
a CH2Cl2 solution (2 mL) of a crude mixture of 1ca, 6ca, and 6ca0
prepared above was added BF3 etherate (63 mg, 0.45 mmol) at
room temperature, and the reaction mixture was stirred at room
temperature for 24 h. The complete consumption of 6ca and 6ca0
was confirmed by GC, and the mixture was poured into water
(10 mL), neutralized by aq NaHCO3, and extracted with Et2O
(20 mL ꢀ 3). The combined organic layer was dried over MgSO4
and concentrated under reduced pressure. From 19F NMR anal-
ysis, 1ca was found to remain unchanged under the conditions, and
7ca was formed in 89% yield from 6ca and 6ca0. It can be isolated
by column chromatography (silica gel/hexane-AcOEt = 20:1).
2
(t, JC-F = 29.7 Hz); HRMS (ESI) calcd for C12H10F6O2
300.05850, found 300.05852; 6ca (a nonpolar isomer): IR
(neat) 2992, 1455, 1008 cm-1, H NMR (400 MHz, CDCl3) δ
1
1.38 (t, J = 7.2 Hz, 3H), 4.09-4.17 (m, 2H), 7.47-7.57 (m, 5H);
19F NMR (376 MHz, CDCl3) δ -83.14 to -83.21 (m, 1F),
-108.67 to -108.79 (m, 1F), -123.12 (dddd, 2J F-F = 252.2 Hz,
3J
= 11.1 Hz, J
= 8.6 Hz, J
= 2.5 Hz, 1F),
F-F
=
3
4
F-F
F-F
-125.55 (ddt, 2J F-F = 247.5 Hz, 3J F-F = 10.8 Hz, 3J F-F
2
7.6 Hz, 1F), -135.21 (dm, J
= 247.9 Hz, 1F), -136.02
F-F
(ddddd, 2J F-F = 251.8 Hz, 3J F-F = 12.9 Hz, 3J F-F = 11.1 Hz,
3J F-F = 6.8 Hz, 4J F-F = 1.4 Hz, 1F); 13C NMR (100 MHz,
CDCl3) δ 14.6, 61.8 (d, 3J C-F = 2.4 Hz), 110.1 (dddt, 1J C-F
=
7ca: IR (neat) 2989, 1780 (CdO), 1701 (CdO), 1317, 1104 cm-1
;
242.2 Hz, 2J C-F = 33.1 Hz, 2J C-F = 24.0 Hz, 3J C-F = 4.1 Hz),
110.7 (dddddd, 1J C-F = 279.3 Hz, 1J C-F = 269.0 Hz, 2J C-F
33.8 Hz, 2J C-F = 27.1 Hz, 2J C-F = 22.8 Hz, 3J C-F = 2.2 Hz),
1H NMR (400 MHz, CDCl3) δ 1.37 (t, J = 7.3 Hz, 3H), 4.42 (q,
J = 7.2 Hz, 2H), 7.53-7.57 (m, 2H), 7.69-7.73 (m, 1H), 8.09-
=
=
8.11 (m, 2H); 19F NMR (376 MHz, CDCl3) δ -113.68 (t, 3JF-F
112.4 (ddddd, 1J C-F = 282.2 Hz, 1J C-F = 260.1 Hz, 2J C-F
=
5.0 Hz, 2F), -121.05 (t, JF-F = 4.7 Hz, 2F); 13C NMR (100
3
2
36.9 Hz, J
2
= 25.9 Hz, J
= 21.8 Hz), 117.2 (dtdd,
C-F
=
MHz, CDCl3) δ 13.6, 63.8, 108.1 (tt, 1JC-F = 264.4 Hz, 2JC-F
28.8 Hz), 115.6 (tt, 1JC-F = 271.9 Hz, 2JC-F = 28.3 Hz), 129.0
=
C-F
1J C-F = 258.7 Hz, 2J C-F = 26.1 Hz, 3J C-F = 6.7 Hz, 3J C-F
1.0 Hz), 126.8 (dd, 3J C-F = 5.3 Hz, 4J C-F = 1.2 Hz, 2C), 128.7,
(2C), 130.1 (t, JC-F = 3.4 Hz, 2C), 130.9 (t, JC-F = 2.9 Hz),
2 2
4
3
2
129.0 (d, J
4
= 27.1 Hz), 131.5 (d, J
= 1.9 Hz, 2C),
C-F
135.5, 159.7 (t, JC-F = 29.7 Hz), 185.4 (t, JC-F = 27.8 Hz);
HRMS (ESI) calcd for C12H10F4O3Na 301.0458, found 301.0460.
A mixture of DAST (490 mg, 3.04 mmol) and SbF3 (110 mg,
0.62 mmol) in a Teflon reactor with a tight screw cap was stirred
at 0 °C for 10 min. Then, a CH2Cl2 solution (2 mL) of 7ca (107 mg,
0.39 mmol) was added, and the mixture was stirred at room
temperature for 48 h. The mixture was poured into water (10 mL),
neutralized with aq NaHCO3, and extracted with Et2O (20 mL ꢀ 3).
The yields of 1ca (42%),6ca (21%),and6ca0 (31%) were determined
by 19F NMR using fluorobenzene as an internal standard.
C-F
HRMS (EI); calcd for C12H10F6O2 300.0585, found 300.0583.
6ca0 (a polar isomer): IR (neat) 2992, 1455, 1195, 976 cm-1, 1H
NMR (400 MHz, CDCl3) δ 1.42 (t, J = 7.2 Hz, 3H), 4.15-4.22
(m, 2H), 7.47-7.57 (m, 5H), 19F NMR (376 MHz, CDCl3) δ
-83.81 to -83.83 (m, 1F), -110.44 (dt, 3J F-F = 13.6 Hz, 3J F-F
=
7.2 Hz, 1F), -122.84 (dm, 2J F-F = 245.0 Hz, 1F), -123.47 (dtt,
3
= 249.3 Hz, J
4
= 8.2 Hz, J
= 249.3 Hz, 1F), -133.69 (dm, J
2J
= 2.2 Hz, 1F),
F-F
F-F
F-F
2
2
-132.82 (dm, J
=
F-F
245.0 Hz, 1F); 13FC-FNMR (100 MHz, CDCl3) δ 14.8, 62.1 (d,
1
= 5.0 Hz), 110.1 (dddm, J
2
= 244.3 Hz, J
3J
=
C-F
C-F
C-F
32.6 Hz, 2J C-F = 25.2 Hz), 110.9 (dddddd, 1J C-F = 277.4 Hz,
=
Acknowledgment. We are grateful to Asahi Glass Co.,
Ltd. for their donation of IF5.
1J C-F = 273.3 Hz, 2J C-F = 33.1 Hz, 2J C-F = 25.9 Hz, 2J C-F
3
23.0 Hz, J
1
= 1.9 Hz), 112.2 (ddddd, J
= 281.0 Hz,
C-F
=
C-F
1J C-F = 261.6 Hz, 2J C1-F = 37.4 Hz, 2J C-F = 25.4 Hz, 2J C-F
Supporting Information Available: General experimental
methods and 1H and 13C NMR spectra of all new compounds.
This material is available free of charge via the Internet at http://
pubs.acs.org.
2
22.3 Hz), 117.2 (dtdt, J
= 270.0 Hz, J
= 27.1 Hz,
3J C-F = 6.0 Hz, 3J C-F = 1.2 Hz), 126.6 (dd, 3CJ-CF-F = 5.7 Hz,
C-F
4J C-F = 1.2 Hz, 2C), 128.7, 128.9 (d, 2J C-F = 26.1 Hz), 131.4
J. Org. Chem. Vol. 75, No. 21, 2010 7399