Electroreductive defluorination of trifluoromethyl ketones and trifluoroacetic acid derivatives

Article abstract of DOI:10.1021/jo990571d

Difluoroenol silyl ethers 5 and 6, difluoroketene silyl (O,O-, O,S-, and O,N-) acetals 9 and 21, and 2,2-difluoro-2-trimethylsilylacetates 10 were prepared by electroreductive defluorination of trifluoromethyl ketones and trifluoroacetic acid derivatives in an MeCN-TBAB-chlorotrialkylsilane system using a carbon rod as an anode and a lead plate as a cathode. TBAF- or KF- CuI-promoted α-alkylation of 10 with electrophiles such as aldehydes, ketones, imine, acylhalides, and alkylhalides provided α-alkylated-α,α- difluoroacetates in good to excellent yields.

Full text of DOI:10.1021/jo990571d

J . Org. Chem. 1999, 64, 6717-6723
6717
Electr or ed u ctive Deflu or in a tion of Tr iflu or om eth yl Keton es a n d
Tr iflu or oa cetic Acid Der iva tives
Kenji Uneyama,* Go Mizutani, Kazushige Maeda, and Tsuyoshi Kato
Department of Applied Chemistry, Faculty of Engineering, Okayama University,
Okayama 700-8530, J apan
Received March 31, 1999
Difluoroenol silyl ethers 5 and 6, difluoroketene silyl (O,O-, O,S-, and O,N-) acetals 9 and 21, and
2,2-difluoro-2-trimethylsilylacetates 10 were prepared by electroreductive defluorination of tri-
fluoromethyl ketones and trifluoroacetic acid derivatives in an MeCN-TBAB-chlorotrialkylsilane
system using a carbon rod as an anode and a lead plate as a cathode. TBAF- or KF-CuI-promoted
R-alkylation of 10 with electrophiles such as aldehydes, ketones, imine, acylhalides, and alkylhalides
provided R-alkylated-R,R-difluoroacetates in good to excellent yields.
In tr od u ction
pounds, and their synthetic utilization has been demon-
strated in fluorinated sugars and amino acids syntheses.8
Introduction of a difluoromethylene unit into organic
molecules is an important subject in current organofluo-
rine chemistry1 since recent works have revealed a wide
range of biologically interesting difluoromethylene com-
pounds such as anticancer agent gemcitabine,2 HIV-1
protease inhibitors,3 and phosphotyrosine (pTyr) mimet-
ics.4 For this reason, a variety of methods for the
preparation of functionalized difluoromethylene com-
pounds have been developed.5 Among them, CF2 building
blocks with an enol ether moiety6 and difluoroketene silyl
acetals7 are promising candidates for the difluoro com-
Constructions of difluoromethylene units are usually
achieved by the transformation of a ketonic carbonyl
group or its equivalent using fluorinating agents such
as DAST,9 NBS-HF-amine complexes,10 and the reac-
tion of difluorocarbenes11 and so on. However, the practi-
cal applicability of these approaches is often limited by
the requirement to deploy a carbonyl group at the
strategic position of suitably protected precursors, as well
as by the hazardous and reactive nature of most fluori-
nating agents. An attractive alternative approach is to
make use of readily accessible CF2-containing building
blocks. As an example, Reformatsky-type reactions of
halodifluoroacetates7,12 are widely used to synthesize the
difluoroketene silyl acetals. However, less availability of
halodifluoroacetates is one of the drawback in these
methods, so more reliable methods are strongly required.
The selective monodefluorination of easily available
trifluoromethyl compounds as starting materials is prom-
ising for this purpose.
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Frontiers of Fluorine Chemistry; American Chemical Society: Wash-
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skii, L. M., Eds. Organofluorine Compounds in Medicinal Chemistry
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Org. Chem. J pn. 1994, 52, 40. (j) Iseki, K.; Kobayashi, Y. Rev.
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Selective defluorinations from a trifluoromethyl group
such as base-catalyzed dehydrofluorination of a 2,2,2-
trifluoroethyl group,13 chemical6b and electrochemical14
reductive defluorination of trifluoromethylaromatics, SN2′-
type substitution of trifluoromethyl olefins15 and imines,16
and Brook-type rearrangement of trifluoroacetylsilanes17
(2) Chou, T. S.; Heath, P. C.; Patterson, L. E.; Poteet, L. M.; Lakin,
R. E.; Hunt, A. H. Synthesis 1992, 565.
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dron Lett. 1991, 32, 7255. (c) Mcharek, S.; Sibille, S.; Nedelec, J . Y. J .
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H. Tetrahedron Lett. 1992, 33, 337.
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H. Tetrahedron Lett. 1995, 36, 5003.
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T. Tetrahedron 1995, 51, 12217. (b) Shi, G.-Q.; Cai, W.-L. J . Org. Chem.
1995, 60, 6289. (c) Osipov, S. N.; Golubev, A. S.; Sewald, N.; Michel,
T.; Kolomiets, A. F.; Folkin, A. V.; Burger, K. J . Org. Chem. 1996, 61,
7521. (d) Xu, Y.; Dolbier, W. R., J r. J . Org. Chem. 1997, 62, 6503. (e)
Purrigton, S. T.; Sheu, K.-W. J . Fluorine Chem. 1993, 65, 165. (f)
Weigel, J . A. J . Org. Chem. 1997, 62, 6108. (g) Caddir, S.; Motherwell,
W. B.; Wilkinson, J . A. J . Chem. Soc., Chem. Commun. 1989, 881. (h)
Lee, J .; Tsukazaki, M.; Snieckus, V. Tetrahedron Lett. 1993, 34, 415.
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1988, 29, 1803. (b) Taguchi, T.; Kitagawa, O.; Suda, Y.; Ohkawa, S.;
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5291. (c) Iseki, K.; Kuroki, Y.; Asada, D.; Kobayashi, Y. Tetrahedron
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Lett. 1996, 37, 2045.
10.1021/jo990571d CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/07/1999

6718 J . Org. Chem., Vol. 64, No. 18, 1999
Uneyama et al.
of -20 to 30 °C (entries 3, 5, 6). A current density of
around 10 mA/cm2 or less was also effective (entries 3,
10, 11). Among the conditions examined, one of the
critical factors for the yield of 5a was the amount of
TMSCl (entries 1-4). More than 3 equiv of TMSCl to 4a
was essential to obtain 5a in a good yield. When only 1
equiv of TMSCl to 4a was used, 5a was not obtained
(entry 1). This result suggests that trapping of a fluoride
anion formed in situ from a trifluoromethyl group of 4a
was indispensable to prevent 5a from desilylation. In fact,
Me3SiF was observed in 19F NMR analysis of the crude
reaction mixture after electrolysis, and in the case of 1
equiv of TMSCl to 4a , the product 5a was desilylated in
situ and mostly transformed into the aldol condensation
product 7 (Scheme 2).
F igu r e 1.
Sch em e 1
This reaction can be applied to a variety of substituted
trifluoromethyl ketones 4 (Table 2). Trimethylsilyleno-
lates 523,24 were unstable for isolation in a pure form for
elemental analysis, and thus the yields of 5 were tenta-
tively analyzed by 19F NMR of two vinylic fluorines.
However, triethylsilylenolates 6 that were prepared
similarly were stable enough to be purified under silica
gel column chromatography and analyzed by spec-
troscopies and elemental analysis. Both aromatic and
aliphatic trifluoromethyl ketones provided 5 and 6 in
good yields. In the case of p-chlorophenyl compound 4c,
the chlorine atom on the aromatic ring was partially
replaced with a hydrogen atom under the reduction
conditions and a mixture of 5c (63%) and 5a (19%) was
obtained.25 Reactions of heteroaromatic compounds 4d -f
and active methylene compound 4j also gave the corre-
sponding difluoroenol silyl ethers.
Electr or ed u ctive Deflu or in a tion of Tr iflu or oa c-
eta tes 8. Difluoroenol silyl ethers 5 have been prepared
by Reformatsky reaction of halodifluoroketones7,12 and
Brook-type rearrangement of trifluoroacetylsilanes.17
Likewise, difluoroketene silyl acetals 9 have been pre-
pared by Reformatsky reaction of halodifluoroacetates
and have been employed in situ for Lewis acid catalyzed
aldol reaction with aldehydes. However, the reported
yields of 9 obtained by this method were not so good.
Asymmetric aldol condensation of the Reformatsky re-
agent is useful; however, the reported enantioselectivity
has been poor as a result of the unfavorable Lewis acid
catalysis by the coexisted zinc(II) salt. Recently, Iseki
succeeded in the isolation of pure 9a (R ) Et, 12% yield)
by the repeated filtration of the zinc(II) salt and reported
the first successful asymmetric Mukaiyama aldol reaction
of 9a by chiral Lewis acids.7c,26
have been widely studied. Most of these defluorinations
were achieved by 1,2-elimination-type reactions. Re-
cently, we have found the reaction of (N-aryl)trifluoro-
methylimines with diethylzinc provides N-aryl-N-ethyl-
â,â-difluoroenamines, which arise presumably via an
electron transfer from the zinc reagent to the imine.16
Taking into account the fact that an electron is a tiny
and strong nucleophile, we came up with an idea that
introduction of two electrons directly into the π-electron
system attached to a CF3 group would induce the pushing
out of one of the fluorine atoms of a trifluoromethyl
group,18,19 and the subsequent trapping of the anionic
intermediate with electrophiles on the π-system would
provide 3. The strategy of an electroreductive defluori-
nation is illustrated in Figure 1. The transformation of
1 to 2 has already been reported for the trifluoromethyl-
ated aromatics by Perichon’s group.14,18
In our previous communications,20,21 we reported the
one-pot syntheses of difluoroenol silyl ethers and â,â-
difluoroenamines by electroreductive defluorination of
trifluoromethyl ketones and imines, respectively. In this
paper, we describe details of the selective electroreductive
defluorination of trifluoromethyl ketones and trifluoro-
acetic acid derivatives, show the general applicability for
the syntheses of â,â-difluoroketene silyl (O,O-, O,S-, and
O,N-) acetals and 2,2-difluoro-2-trimethylsilyl acetates
(Scheme 1),22 and demonstrate the KF-CuI-promoted
selective R-alkylation of the acetates.
Resu lts a n d Discu ssion
E lect r or ed u ct ive Deflu or in a t ion of Tr iflu or o-
m eth yl Keton es 4. Electroreduction of trifluoromethyl
ketones 4 in the presence of TMSCl afforded difluoroenol
silyl ethers 5. Reaction conditions were surveyed using
a model compound (4a ), and the results are summarized
in Table 1. Combination of a lead cathode and n-Bu4NBr
as a supporting electrolyte gave a high yield of 5a .
Temperature did not affect the yield of 5a in the range
Thus, a new method for the preparation of metal salt
free difluoroketene silyl acetal or the alternative is
required. The base-catalyzed deprotonation and O-sily-
lation of difluoroacetate resulted in a mixture of the
(23) Acetal 5 was not stable enough to perform elemental analysis.
19F NMR (188 MHz) results follow. 5a : (CDCl3) δ 50.2 (d, J ) 68 Hz),
61.9 (d, J ) 68 Hz). 5b: (CDCl3) δ 48.3 (d, J ) 73 Hz), 59.9 (d, J ) 73
Hz). 5c: (C6D6) δ 48.3 (d, J ) 66 Hz), 59.9 (d, J ) 66 Hz). 5d : (CDCl3)
δ 51.8 (d, J ) 63 Hz), 59.7 (d, J ) 63 Hz). 5e: (C6D6) δ 53.4 (d, J ) 66
Hz), 60.0 (d, J ) 66 Hz). 5f: (C6D6) δ 56.2 (d, J ) 52 Hz), 66.3 (d, J )
52 Hz). 5g: (CDCl3) δ 41.7 (d, J ) 85 Hz), 55.6 (d, J ) 85 Hz). 5h :
(CDCl3) δ 51.8 (d, J ) 63 Hz), 59.7 (d, J ) 63 Hz). 5i: (CDCl3) δ 40.6
(d, J ) 91 Hz), 54.4 (d, J ) 91 Hz). 5j: (CDCl3) δ 43.4 (d, J ) 80 Hz),
57.2 (d, J ) 80 Hz).
(17) (a) J in, F.; J iang, B.; Xu, Y. Tetrahedron Lett. 1992, 33, 1221.
(b) Brigand, T.; Doussot, P.; Portella, C. J . Chem. Soc., Chem. Commun.
1994, 2117.
(18) Saboureau, C.; Troupel, M.; Sibille, S.; Perichon, J . J . Chem.
Soc., Chem. Commun. 1989, 1138.
(19) For the electroreduction of R,R,R-trifluoroacetophenone to ac-
etophenone, see: Stocker, J . H.; J enevein, R. M. J . Chem. Soc., Chem.
Commun. 1968, 934.
(20) Uneyama, K.; Maeda, K.; Kato, T.; Katagiri, T. Tetrahedron
Lett. 1998, 39, 3741.
(24) Ishihara, T.; Yamana, M.; Ando, T. Tetrahedron Lett. 1983, 24,
507.
(21) Uneyama, K.; Kato, T. Tetrahedron Lett. 1998, 39, 587.
(22) Uneyama, K.; Mizutani, G. J . Chem. Soc., Chem. Commun.
1999, 613.
(25) Volke, J ., Liska, F., Eds. Electrochemistry In Organic Synthesis;
Springer-Verlag: Berlin, 1994; pp 92-93.
(26) Iseki, K. Tetrahedron 1998, 54, 13887.

Electroreductive Defluorination
J . Org. Chem., Vol. 64, No. 18, 1999 6719
Ta ble 1. Electr or ed u ctive Deflu or in a tion of Tr iflu or om eth yl Keton e 4a
TMSCl
(mmol)
cathode
material
supporting
electrolyte
current density
(mA/cm2)
yield of 5a
entry
temp. (°C)
(%)a
1
2
3
4
5
6
7
8
9
0
0
0
1.0
2.0
3.0
5.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
Pb
Pb
Pb
Pb
Pb
Pb
Pb
C
n-Bu4NBr
n-Bu4NBr
n-Bu4NBr
n-Bu4NBr
n-Bu4NBr
n-Bu4NBr
LiClO4
n-Bu4NBr
n-Bu4NBr
n-Bu4NBr
n-Bu4NBr
15
15
15
15
15
15
15
15
15
4
0
53
80
63
81
80
39
77
65
78
71
0
-20
30
0
0
0
0
0
Pt
Pb
Pb
10
11
50
a
Yields were determined by 19F NMR analysis.
Sch em e 2
Sch em e 3
Ta ble 2. P r ep a r a tion of Diflu or oen ol Silyl Eth er s 5 a n d
6
However, under the reaction condition (0 °C, 4 equiv
of TMSCl) optimized for ketones 4, electroreduction of
8b afforded a mixture of tert-butyl difluoroketene silyl
acetal 9b (31%) and carbon silylated difluoroacetate 10b
(24%) (Scheme 3). Interestingly, the temperature was
found to be critical. The formation of 10 predominated
and no formation of 9 was observed at the higher
temperature (50 °C) in the presence of a large excess of
TMSCl [47% (65%), 58% (68%), and 62% (68%) for 9a ,28
9b, and 9c, respectively; yields in parentheses were
determined by 19F NMR].22 The silyl migration from
oxygen to carbon was observed at the higher tempera-
ture. In fact, a mixture of 9a and 10a (20:80) prepared
by the electrolysis of 8a at 0 °C was subjected to thermal
isomerization at 50 °C for 3 h, affording 10a 29 as a sole
product. Under this reaction condition the self-condensa-
tion product was not obtained, but less than 10% of the
acetals CF3CH(OTMS)OR,30 which might arise from the
simple reduction of the carbonyl group of 8, were ac-
companied in each case.
Recently, several types of compounds having an R,R-
difluoro-R-trimethylsilylmethyl group31 have been re-
ported and used as effective CF2 building blocks. The
present carbon-silylated difluoro compounds 10 are prom-
ising building blocks because they are easily available,
distillable, stable enough to be stored for a long time, and
highly reactive in the presence of a fluoride ion. To
(27) Stepanov, A. A.; Minyaeva, T. V.; Martynov, B. I. Tetrahedron
Lett. 1999, 40, 2203. Martynov, B. I.; Stepanov, A. A. cited in Nobel
Trends in Electroorganic Synthesis; Torii, S., Ed.; Springer-Verlag:
Tokyo, 1998; p 229.
(28) 9a and 9b were already reported.7c,29 9c: 19F NMR (188 MHz,
CDCl3) δ 50.2 (d, J ) 68 Hz), 61.9 (d, J ) 68 Hz). Acetals 9 were not
isolated as a result of their hydrolytic instability and were generated
in situ for subsequent reaction.
(29) Britton, T. C. J pn. Kokai Tokkyo Koho, J p 7-188260, 1994.
(30) Yields were determined by 19F NMR analysis. The structure of
CF3CH(OTMS)OC2H5 was determined by authentic sample. 19F NMR
(188 MHz, CDCl3) δ 78.7 (d, J ) 3 Hz); 1H NMR (200 MHz, CDCl3) δ
1.29 (t, 3 H, J ) 7.2 Hz), 4.14 (q, 2 H, J ) 7.2 Hz), 5.48-5.56 (m, 1 H).
(31) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 77, 7577 and
references therein.
Claisen product (CF3C(O)CF2CO2Et) and ethyl 2,2-di-
fluoro-2-trimethylsilyl acetate 10a.6f Meanwhile, Stepanov
et al. reported that electroreduction of 8a (R ) Et)
provided a mixture of the Claisen product and 10a with
the use of low equivalents of TMSCl.27

6720 J . Org. Chem., Vol. 64, No. 18, 1999
Uneyama et al.
Ta ble 3. Rea ction of n -Hexyl
r-Tr im eth ylsilyl-r,r-d iflu or oa ceta te (10c) w ith Va r iou s
Electr op h iles a n d Ha lid es
Ta ble 4. P r ep a r a tion of Diflu or ok eten e Silyl (O, S- a n d
O, N-) Aceta ls 21
R-alkylation of Reformatsky-type reagent with benzyl-
and crotylbromides was achieved only with iododifluoro-
acetate, and the reaction of bromo- and/or chlorodifluoro-
acetate was unsuccessful.34
E lect r or ed u ct ive Deflu or in a t ion of Tr iflu or o-
a ceta te Equ iva len ts, (O,S- a n d O,N-) Ester s 20. The
successful transformation of trifluoroacetates to 2,2-
difluoro-2-trimethylsilyl acetates prompted us to seek the
similar transformation of trifluoroacetamide and tri-
fluorothioacetate. Wigel reported the preparation of
difluoroketene silyl (O,S)-acetal by LDA-catalyzed silyl-
ation of difluoroethanethioate in the presence of TMSCl.6f
Preparation of the related compounds, CF2dC(SPh)2,6e
CF2dC(-S-CH2-CH2-S-),35 and CF2dC(NMe)26d,36 have
also been reported. All of these compounds have a unique
reactivity and have been utilized as building blocks for
bioactive compounds.
Interestingly, it was found that almost the same
electrolysis conditions as for trifluoromethyl ketones are
applicable for the preparation of ketene silyl (O,S-, and
O,N-) acetals. As demonstrated in Table 4, the electro-
chemical reaction of thioesters 20 (X ) SR) and amide
20 (X ) NPh2) afforded the corresponding difluoro ketene
silyl acetals in good yields.
Con clu sion
explore the reactivity of 2,2-difluoro-2-trimethylsilyl
acetates, 10c was subjected to the TBAF-catalyzed C-C
bond formation with electrophiles such as aldehydes,
ketones, acylhalides, imine, and alkylhalides and afforded
the desired alkylated products (Table 3). In entry 2,
reaction with cinnamaldehyde gave the 1,2-adduct se-
lectively. Taguchi’s group reported that the Lewis acid-
catalyzed reaction of ketene silyl acetal afforded a
mixture of 1,2- and 1,4-adducts.32 Meanwhile, Iseki’s
group reported that the Reformatsky reaction of halodi-
fluoroacetates afforded 1,2-adducts only.7c So, it can be
said that the reactivity of 2,2-difluoro-2-trimethylsilyl
acetates are closer to halodifluoroacetates than the
ketene silyl acetals. Reactions of 10c with acylhalides and
imine were also successful (entries 5-7). R-Alkylation of
10c in the presence of KF and CuI was successfully
achieved with allyl and benzylhalides. However, n-
butylbromide was not a good electrophile for this purpose.
Only n-butyliodide afforded the alkylated product in a
very poor yield.33 Most of the side product was a self-
condensation product (CF2HC(O)CF2CO2C6H13). The
In summary, a variety of difluoroenol ethers, difluoro-
ketene silyl (O,O-, O,S-, and O,N-) acetals, and 2,2-
difluoro-2-trimethylsilyl acetates were prepared elec-
troreductively from trifluoromethyl carbonyl compounds.
Alkylations of the 2,2-difluoro-2-trimethylsilyl acetates
with various electrophiles were successful. These CF2
building blocks are expected to be applied in the synthesis
of useful CF2 compounds. The present electrochemical
reaction is applicable to a useful preparation of the
various difluoromethylene compounds.
Exp er im en ta l Section
Gen er al P r ocedu r e. Acetonitrile, Et3N, TMSCl, and TESCl
were freshly distilled from CaH2. THF was distilled from Na
and benzophenone. Column chromatography was carried out
(33) Spectral data of n-hexyl 2,2-difluorohexanoate: 17% yield
(determined by 19F NMR analysis); 19F NMR (188 MHz, CDCl3) δ 55.9
(t, J ) 18 Hz); 1H NMR (200 MHz, CDCl3) δ 0.86 (m, 6 H), 1.33-1.53
(m, 10 H), 1.54-1.74 (m, 2 H), 1.93-2.17 (m, 2 H), 4.25 (t, 2 H, J )
6.9 Hz).
(34) Kitagawa, O.; Taguchi, T.; Kobayashi, Y. Chem. Lett. 1989, 389.
(35) Grimbert, Y.; Moradpour, T. A.; Dive, G.; Dehareng, D.; Lahil,
K. J . Org. Chem. 1993, 58, 4865.
(32) Kitagawa, O.; Hashimoto, A.; Kobayashi, Y.; Taguchi, T. Chem.
Lett. 1990, 1307.
(36) Xu, Y.; Dolbier, W. R., J r. J . Org. Chem. 1997, 62, 1576.

Electroreductive Defluorination
J . Org. Chem., Vol. 64, No. 18, 1999 6721
with E. Merck silica gel (Kieselgel 60, 230-400 mesh) and
J ) 85 Hz), 55.3 (d, 1 F, J ) 85 Hz); GC-MS m/z 298 (M+).
Anal. Calcd for C16H24F2OSi: C, 64.39; H, 8.11. Found: C,
64.09; H, 8.34.
1
alumina (about 300 mesh). The chemical shifts of H and 19F
NMR spectra are reported in δ ppm values relative to TMS
(0.00 ppm for 1H NMR) and C6F6 (0.0 ppm for 19F NMR) with
CDCl3, C6D6, and DMSO-d6 as solvents. NMR yields were
obtained with 19F NMR using 1,3-bistrifluoromethylbenzene
as an internal standard. Coupling constants (J ) are reported
in Hz.
2-Tr ieth ylsiloxy-1,1-d iflu or o-1-octen e (6h ). Colorless
1
oil: (147 mg, 53%); IR (neat) νmax 1768 (CdC) cm-1; H NMR
(200 MHz, CDCl3) δ 0.66 (q, 6 H, J ) 7.8 Hz), 0.88 (t, 3 H, J
) 6.7 Hz), 0.97 (t, 9 H, J ) 7.8 Hz), 1.28-1.48 (m, 8 H), 1.97-
2.09 (m, 2 H); 19F NMR (188 MHz, CDCl3) δ 40.6 (d, 1 F, J )
85 Hz), 54.6 (d, 1 F, J ) 85 Hz); GC-MS m/z 278 (M+). Anal.
Calcd for C14H28F2OSi: C, 60.39; H, 10.13. Found: C, 60.46;
H, 10.50.
Gen er a l P r oced u r e for Electr or ed u ctive Deflu or in a -
tion of Tr iflu or om eth yl Keton es, Tr iflu or oth ioa ceta tes,
a n d Tr iflu or om eth yla m id e in th e P r esen ce of Ch lor o-
tr ieth ylsila n e. The electroreductive defluorination of trifluo-
romethyl compounds 4 and 20 (1 mmol) was carried out by
using a Pb cathode (1 × 2 cm2) and a carbon anode in
anhydrous acetonitrile (7 + 7 mL) containing n-Bu4NBr (1.29
g, 4 mmol) and TESCl (452 mg, 3 mmol) in an H-type divided
cell. A constant current of 30 mA was passed at 0 °C under an
argon atmosphere until 4 and 20 were consumed (2 F/mol).
After the electrolysis, Et3N (303 mg, 3 mmol) was added. The
reaction mixture was concentrated in vacuo and chromato-
graphed quickly on silica gel pretreated with Et3N (hexane,
grade to 10% AcOEt/hexane) to give â,â-difluoroenol triethyl-
silyl ethers 6 and 21 as colorless oils.
1-Tr ieth ylsiloxy-2,2-d iflu or o-1-p h en yleth en e (6a ). Col-
orless oil: (227 mg, 84%); IR (neat) νmax 1730 (CdC) cm-1; 1H
NMR (200 MHz, CDCl3) δ 0.65 (q, 6 H, J ) 7.8 Hz), 0.94 (t, 9
H, J ) 7.8 Hz), 7.25-7.51 (m, 5 H); 19F NMR (188 MHz,CDCl3)
δ 49.3 (d, 1 F, J ) 69 Hz), 61.1 (d, 1 F, J ) 69 Hz); GC-MS
m/z 270 (M+). Anal. Calcd for C14H20F2OSi: C, 62.19; H, 7.46.
Found: C, 62.18; H, 7.08.
1-Cycloh exyl-1-tr ieth ylsiloxy-2,2-d iflu or oeth en e (6i).
Colorless oil: (152 mg, 55%); IR (neat) νmax 1758 (CdC) cm-1
;
1H NMR (200 MHz, CDCl3) δ 0.67 (q, 6 H, J ) 7.8 Hz), 0.98 (t,
9 H, J ) 7.8 Hz), 1.14-1.79 (m, 10 H), 2.04-2.21 (m, 1 H); 19
F
NMR (188 MHz, CDCl3) δ 40.1 (d, 1 F, J ) 91 Hz), 53.9 (d, 1
F, J ) 91 Hz); GC-MS m/z 276 (M+). Anal. Calcd for C14H26F2-
OSi: C, 60.83; H, 9.48. Found: C, 60.44; H, 9.66.
Eth yl 3-tr ieth ylsiloxy-4,4-diflu or o-3-bu ten oate (6j). Col-
orless oil: (118 mg, 42%); IR (neat) νmax 1748 (CdC) cm-1; 1H
NMR (200 MHz, CDCl3) δ 0.66 (q, 6 H, J ) 7.8 Hz), 0.95 (t, 9
H, J ) 7.8 Hz), 1.26 (t, 3 H, J ) 7.2 Hz), 3.06-3.09 (m, 2 H),
4.16 (q, 2 H, J ) 7.2 Hz); 19F NMR (188 MHz, CDCl3) δ 43.2
(d, 1 F, J ) 81 Hz), 57.0 (d, 1 F, J ) 81 Hz); GC-MS m/z 251
(M+ - Et). Anal. Calcd for C12H22F2O3Si: C, 51.40; H, 7.91.
Found: C, 51.13; H, 8.29.
2,2,4,4,4-P e n t a flu or o-3-h yd r oxy-1,3-d ip h e n yl-1-b u -
ta n on e (7). The electroreductive defluorination of trifluorom-
ethyl ketone 4a (174 mg, 1 mmol) was carried out by using a
Pb cathode (1 × 2 cm2) and a carbon anode in anhydrous
acetonitrile (7 + 7 mL) containing n-Bu4NBr (1.29 g, 4 mmol),
Et3N (101 mg, 1 mmol), and TMSCl (109 mg, 1 mmol) in an
H-type divided cell. A constant current of 30 mA (1.5 F/mol)
was passed at 0 °C under an argon atmosphere. The reaction
mixture was concentrated in vacuo and chromatographed on
silica gel (5% AcOEt/hexane as an eluent) to give 7. Colorless
1-Tr ie t h ylsiloxy-2,2-d iflu or o-1-(p -m e t h oxyp h e n yl)-
eth en e (6b). Colorless oil: (216 mg, 72%); IR (neat) νmax 1730
1
(CdC) cm-1; H NMR (200 MHz, CDCl3) δ 0.67 (q, 6 H, J )
7.3 Hz), 0.97 (t, 9 H, J ) 7.3 Hz), 3.83 (s, 3 H), 6.92 (d, 2 H, J
) 8.3 Hz), 7.43 (d, 2 H, J ) 8.3 Hz); 19F NMR (188 Mz, CDCl3)
δ 47.4 (d, 1 F, J ) 73 Hz), 59.3 (d, 1 F, J ) 73 Hz); GC-MS
m/z 300 (M+). Anal. Calcd for C15H22F2O2Si: C, 59.97; H, 7.38.
Found: C, 59.69; H, 7.77.
oil: (79 mg, 24%); IR (neat) νmax 3492 (OH), 1696 (CdO) cm-1
;
1H NMR (200 MHz, CDCl3) δ 4,86 (s, 1 H), 7.36-7.49 (m, 5
H), 7.60-7.72 (m, 3 H), 7.89-7.94 (m, 2 H); 19F NMR (188
MHz, CDCl3) δ 55.9 (q, 1 F, J ) 12 Hz), 56.2 (q, 1 F, J ) 9.7
Hz), 88.4 (t, 3 F, J ) 11 Hz). Anal. Calcd for C16H11F5O2: C,
58.19; H, 3.36. Found: C, 58.09; H, 3.57.
1-T r ie t h y ls ilo x y -2,2-d iflu o r o -1-(p -c h lo r o p h e n y l)-
eth en e (6c). Colorless oil: (149 mg, 49%); IR (neat) νmax 1730
1
(CdC) cm-1; H NMR (200 MHz, DMSO-d6) δ 0.63 (q, 6 H, J
) 7.3 Hz), 0.91 (t, 9 H, J ) 7.3 Hz), 7.48 (d, 2 H, J ) 8.9 Hz),
7.55 (d, 2 H, J ) 8.9 Hz); 19F NMR (188 MHz, CDCl3) δ 50.2
(d, 1 F, J ) 67 Hz), 62.0 (d, 1 F, J ) 67 Hz); GC-MS m/z 304
(M+). Anal. Calcd for C14H19ClF2OSi: C, 55.16; H, 6.28.
Found: C, 55.34; H, 6.32.
1-ter t-Bu t ylt h io-1-t r ie t h ylsiloxy-2,2-d iflu or oe t h e n e
(21a ). Following the general procedure, crude product was
purified using alumina column chromatography with hexane
as an eluent. Colorless oil: (152 mg, 54%); IR (neat) νmax 1714
1
2-(1-Tr ieth ylsiloxy-2,2-d iflu or oeth en yl)fu r a n (6d ). Col-
orless oil: (148 mg, 57%); IR (neat) νmax 1736 (CdC) cm-1; 1H
NMR (200 MHz, CDCl3) δ 0.71 (q, 6 H, J ) 8.1 Hz), 0.95 (t, 9
H, J ) 8.1 Hz), 6.39-6.40 (m, 1 H), 6.44-6.46 (m, 1 H), 7.43
(br. s, 1 H); 19F NMR (188 MHz, CDCl3) δ 51.5 (d, 1 F, J ) 64
Hz), 59.4 (d, 1 F, J ) 64 Hz); GC-MS m/z 260 (M+). Anal.
Calcd for C12H18F2O2Si: C, 55.36; H, 6.97. Found: C, 55.10;
H, 7.23.
(CdC) cm-1; H NMR (200 MHz, CDCl3) δ 0.72 (q, 6 H, J )
8.0 Hz), 0.98 (t, 9 H, J ) 8.1 Hz), 1.36 (s, 9 H); 19F NMR (188
MHz, CDCl3) δ 58.2 (d, 1 F, J ) 47 Hz), 70.0 (d, 1 F, J ) 47
Hz); GC-MS m/z 282 (M+). Anal. Calcd for C12H24F2OSSi: C,
51.03; H, 8.56. Found: C, 51.25; H, 8.74.
1-Tr ieth ylsiloxy-1-ph en ylth io-2,2-diflu or oeth en e (21b).
Colorless oil: (157 mg, 52%); IR (neat) νmax 1722 (CdC) cm-1
;
1H NMR (200 MHz, C6D6) δ 0.62 (q, 6 H, J ) 8.1 Hz), 0.92 (t,
9 H, J ) 8.1 Hz), 6.88-7.04 (m, 3 H) 7.30-7.34 (m, 2 H); 19F
NMR (188 MHz, C6D6) δ 56.5 (d, 1 F, J ) 49 Hz), 69.4 (d, 1 F,
J ) 49 Hz); GC-MS m/z 302 (M+). Anal. Calcd for C14H20F2-
OSSi: C, 55.60; H, 6.66. Found: C, 55.44; H, 6.39.
2-(1-Tr ieth ylsiloxy-2,2-d iflu or oeth en yl)th iop h en e (6e).
Colorless oil: (168 mg, 61%); IR (neat) νmax 1728 (CdC) cm-1
;
1H NMR (200 MHz, CDCl3) δ 0.65 (q, 6 H, J ) 8.1 Hz), 0.91 (t,
9 H, J ) 8.1 Hz), 6.93-6.98 (m, 1 H), 7.02-7.04 (m, 1 H), 7.19-
7.24 (m, 1 H); 19F NMR (188 MHz, CDCl3) δ 52.6 (d, 1 F, J )
66 Hz), 59.2 (d, 1 F, J ) 66 Hz); GC-MS m/z 276 (M+). Anal.
Calcd for C12H18F2OSSi: C, 52.14; H, 6.56. Found: C, 51.94;
H, 6.34.
N ,N -Dip h e n yl-1-t r ie t h ylsiloxy-2,2-d iflu or oe t h e n yl-
a m in e (21c). Colorless oil: (162 mg, 45%); IR (neat) νmax 1770
1
(CdC) cm-1; H NMR (200 MHz, CDCl3) δ 0.52 (q, 6 H, J )
7.5 Hz), 0.84 (t, 9 H, J ) 7.5 Hz), 6.98-7.12 (m, 6 H), 7.23-
7.32 (m, 4 H); 19F NMR (56.5 MHz, CDCl3) δ 44.4 (d, 1 F, J )
72 Hz), 52.3 (d, 1 F, J ) 72 Hz); GC-MS m/z 247 (M+ - SiEt3).
Anal. Calcd for C20H25F2NOSi: C, 66.45; H, 6.97; N, 3.87.
Found: C, 66.31; H, 7.22; N, 3.47.
2-(1-Tr iet h ylsiloxy-2,2-d iflu or oet h en yl)p yr id in e (6f).
Colorless oil: (157 mg, 58%); IR (neat) νmax 1724 (CdC) cm-1
;
1H NMR (200 MHz, CDCl3) δ 0.64 (q, 6 H, J ) 8.1 Hz), 0.89 (t,
9 H, J ) 8.0 Hz), 7.08-7.16 (m, 1 H), 7.40-7.46 (m, 1 H), 7.59-
7.67 (m, 1 H), 8.54-8.57 (m, 1 H); 19F NMR (188 MHz, CDCl3)
δ 54.3 (d, 1 F, J ) 54 Hz), 65.5 (d, 1 F, J ) 54 Hz); GC-MS
m/z 242 (M+ - Et). Anal. Calcd for C13H19F2NOSi: C, 57.54;
H, 7.06. Found: C, 57.34; H, 7.28.
Electr or ed u ctive Deflu or in a tion of Tr iflu or oa ceta te
8 in th e P r esen ce of TMSCl a n d Lew is Acid Ca ta lyzed
Mu k a iya m a Ald ol Rea ction of 9. The electroreductive
defluorination of trifluoroacetate 8 (1 mmol) was carried out
by using a Pb cathode (1 × 2 cm2) and a carbon anode in
anhydrous acetonitrile (7 + 7 mL) containing n-Bu4NBr (1.29
g, 4 mmol), Et3N (505 mg, 5 mmol), and TMSCl (545 mg, 5
mmol) in an H-type divided cell. A constant current of 30 mA
(2 F/mol) was passed at 0 °C under an argon atmosphere. After
2-Tr ieth ylsiloxy-1,1-d iflu or o-4-p h en ylbu ten e (6g). Col-
orless oil: (191 mg, 64%); IR (neat) νmax 1768 (CdC) cm-1; 1H
NMR (200 MHz, CDCl3) δ 0.70 (q, 6 H, J ) 7.8 Hz), 1.01 (t, 9
H, J ) 7.8 Hz), 2.30-2.41 (m, 2 H), 2.82 (t, 2 H, J ) 8.0 Hz),
7.18-7.34 (m, 5 H); 19F NMR (188 MHz, CDCl3) δ 41.4 (d, 1 F,

6722 J . Org. Chem., Vol. 64, No. 18, 1999
Uneyama et al.
the electrolysis, the product â,â-difluoroketene trimethylsilyl
acetals 9 were determined by 19F NMR, and 9 was extracted
with pentane from acetonitrile solution (2 mL × 5). To a
solution of benzaldehyde (106 mg, 1 mmol) and TiCl4 (1.0 mL
of a 1.0 M solution in CH2Cl2) in dry CH2Cl2 (2 mL) was added
the extracted pentane solution, and the mixture was stirred
at -78 °C under an argon atmosphere for 1.5 h. The reaction
mixture was allowed to warm to room temperature, stirred
for 5 h, and quenched with saturated aqueous NH4Cl. The
organic substrates were extracted with ether (4 mL × 5). The
organic layer was washed with water and brine, dried over
anhydrous MgSO4, concentrated in vacuo, and chromato-
graphed on silica gel (25% AcOEt/hexane) to give 11.
°C, the reaction mixture was filtered through a pad of Florisil
to remove salts. The filtrate was concentrated in vacuo.
Chromatography on silica gel (10% diethyl ether/hexane)
provided 11c (235 mg, 82%).
n -Hexyl 2,2-Diflu or o-3-h ydr oxy-3-piper on ylpr opan oate
(12). A solution of 10c (252 mg, 1 mmol), piperonal (450 mg,
3 mmol), KF (70 mg, 1.2 mmol), and CuI (285 mg, 1.5 mmol)
in DMF (1.5 mL) under an argon atmosphere was stirred for
8 h at 70 °C. The reaction mixture was filtered through a pad
of Florisil to remove salts. The filtrate was concentrated in
vacuo. Chromatography of the residue on silica gel provided
12. Colorless oil: (281 mg, 85%); IR (neat) νmax 1756 (CdO)
1
cm-1; H NMR (200 MHz, CDCl3) δ 0.89 (t, 3 H, J ) 5.5 Hz),
E t h yl
2,2-Diflu or o-3-h yd r oxy-3-p h en ylp r op a n oa t e
1.20-1.40 (m, 6 H), 1.59-1.75 (m, 2 H), 2.61-2.72 (br, 1 H),
4.24 (t, 2 H, J ) 5.8 Hz) 5.01-5.15 (m, 1 H), 5.99 (s, 2 H),
6.77-6.98 (m, 3 H); 19F NMR (188 MHz, CDCl3) δ 41.4 (dd, 2
F, J FH ) 15 Hz, J FF ) 259 Hz), 47.8 (dd, 2 F, J FH ) 8 Hz, J FF
) 259 Hz); GC-MS m/z 330 (M+). Anal. Calcd for C16H20F2O5:
C, 58.18; H, 6.10. Found: C, 58.12; H, 6.19.
(11a ).7c Colorless oil: (24 mg, 10%); IR (neat) 3475, 1762 (Cd
O) cm-1; H NMR (200 MHz, CDCl3) δ 1.26 (t, 3 H, J ) 7.2
1
Hz), 3.19 (br, 1 H), 4.27 (q, 2 H, J ) 7.2 Hz), 5.15 (ddd, 1 H,
J ) 5.4 Hz, J ) 8.5 Hz, J ) 15.2 Hz), 7.36-7.46 (m, 5 H); 19
F
)
NMR (188 MHz, CDCl3) δ 41.0 (dd, 2 F, J FH ) 15 Hz, J FF
261 Hz), 48.8 (dd, 2 F, J FH ) 8 Hz, J FF ) 261 Hz).
n -Hexyl 2,2-Diflu or o-3-h yd r oxy-5-p h en yl-4-p en ten oa te
(13). To a solution of 10c (252 mg, 1 mmol) and cinnamalde-
hyde (396 mg, 3 mmol) in THF (1.5 mL) at -78 °C was added
TBAF (1.0 mL of a 1.0 M solution in THF) dropwise. After the
mixture stirred for 1 h at -78 °C and 3 h at room temperature,
the usual workup procedure provided 13. Colorless oil: (237
mg, 76%); IR (neat) νmax 3476 (OH), 1764 (CdO) cm-1; 1H NMR
(200 MHz, CDCl3) δ 0.87 (t, 3 H, J ) 6.9 Hz), 1.25-1.34 (m, 6
H), 1.61-1.72 (m, 2 H), 2.41 (br, 1 H), 4.29 (t, 2 H, J ) 6.6
Hz), 4.63-4.82 (m, 1 H), 6.24 (dd, 1 H, J ) 6.6 Hz, J ) 15.8
Hz), 6.81 (d, J ) 15.8 Hz), 7.26-7.43 (m, 5 H); 19F NMR (188
MHz, CDCl3) δ 41.3 (dd, 2 F, J FH ) 13 Hz, J FF ) 263 Hz), 47.5
(dd, 2 F, J FH ) 8 Hz, J FF ) 263 Hz); GC-MS m/z 312 (M+).
Anal. Calcd for C17H22F2O3: C, 65.37; H, 7.10. Found: C, 65.06;
H, 7.41.
ter t-Bu tyl 2,2-Diflu or o-3-h yd r oxy-3-p h en ylp r op a n oa te
(11b). Colorless crystal: (69 mg, 27%); IR (neat) 3508, 1754
1
(CdO) cm-1; H NMR (200 MHz, CDCl3) δ 1.45 (s, 9 H), 2.72
(d, 1 H, J ) 5.4 Hz), 5.05-5.18 (m, 1 H), 7.35-7.46 (m, 5 H);
19F NMR (188 MHz, CDCl3) δ 42.9 (dd, 2 F, J FH ) 13 Hz, J FF
) 258 Hz), 47.6 (dd, 2 F, J FH ) 9 Hz, J FF ) 258 Hz); GC-MS
m/z 258 (M+). Anal. Calcd for C13H16F2O3: C, 60.46; H, 6.24.
Found: C, 60.29; H, 6.62.
n -Hexyl 2,2-Diflu or o-3-h yd r oxy-3-p h en ylp r op a n oa te
(11c). Colorless oil: (37 mg, 13%); IR (neat) 3532, 1760 (Cd
1
O) cm-1; H NMR (200 MHz, CDCl3) δ 0.89 (t, 3 H, J ) 6.8
Hz), 1.26-1.41 (m, 6 H), 1.58-1.68 (m, 2 H), 2.69 (d, 1 H, J )
5.4 Hz), 4.23 (t, 2 H, J ) 6.8 Hz), 5.16 (ddd, 1 H, J ) 5.4 Hz,
J ) 8.5 Hz, J ) 15.2 Hz), 7.36-7.46 (m, 5 H); 19F NMR (188
MHz, CDCl3) δ 41.6 (dd, 2 F, J FH ) 15 Hz, J FF ) 262 Hz), 47.8
(dd, 2 F, J FH ) 9 Hz, J FF ) 262 Hz); GC-MS m/z 286 (M+).
Anal. Calcd for C15H20F2O3: C, 62.92; H, 7.04. Found: C, 62.58;
H, 7.30.
n -Hexyl 2,2-Diflu or o-2-(1-h yd r oxycycloh exyl)a ceta te
(14). A solution of 10c (252 mg, 1 mmol), cyclohexanone (490
mg, 5 mmol), KF (70 mg, 1.2 mmol), and CuI (285 mg, 1.5
mmol) in DMF (1.5 mL) under an argon atmosphere was
stirred for 20 h at 60 °C; the usual workup procedure of the
mixture provided 14. Colorless oil: (256 mg, 92%); IR (neat)
P r ep a r a t ion of 2,2-Diflu or o-2-t r im et h ylsilyl Acet a t e
(10). The electroreductive defluorination of trifluoroacetate 8
(5 mmol) was carried out by using a Pb cathode (2 × 5 cm2)
and a carbon anode in anhydrous acetonitrile (60 mL) contain-
ing n-Bu4NBr (3.85 g, 12 mmol), Et3N (2.12 g, 21 mmol), and
TMSCl (2.17 g, 20 mmol) in an H-type divided cell. A constant
current of 80 mA (2 F/mol) was passed at 50 °C under an argon
atmosphere. After the electrolysis, the reaction mixture was
concentrated in vacuo, and the residue was distilled under
reduced pressure to give 10.
ν
max 3528 (OH), 1762 (CdO) cm-1; 1H NMR (200 MHz, CDCl3)
δ 0.89 (t, 3 H, J ) 5.9 Hz), 1.13-1.41 (m, 8 H), 1.54-1.74 (m,
10 H), 2.02 (br, 1 H), 4.27 (t, 2 H, J ) 6.7 Hz); 19F NMR (188
MHz, CDCl3) δ 41.9 (s, 2 F). Anal. Calcd for C14H24F2O3: C,
60.41; H, 8.69. Found: C, 60.28; H, 9.07.
n -Hexyl 3-(N-P h en yl)a m in o-2,2-d iflu or o-3-p h en ylp r o-
p a n oa te (15). A solution of 10c (252 mg, 1 mmol), imine (272
mg, 1.5 mmol), KF (70 mg, 1.2 mmol), and CuI (285 mg, 1.5
mmol) in DMF (1.5 mL) under an argon atmosphere was
stirred for 10 h at 70 °C; the usual workup procedure of the
mixture provided 15. Colorless oil: (299 mg, 83%); IR (neat)
Eth yl 2,2-Diflu or o-2-tr im eth ylsilyl Aceta te (10a ). Col-
orless oil: (461 mg, 47%); bp 40 °C/45 mmHg (Kugelrohr); IR
(neat) νmax 1756 (CdO) cm-1 1H NMR (200 MHz, CDCl3) δ
;
ν
max 3400 (NH), 1770 (CdO) cm-1; 1H NMR (200 MHz, CDCl3)
0.23 (s, 9 H), 1.34 (t, 3 H, J ) 7.2 Hz), 4.31 (q, 2 H, J ) 7.2
Hz); 19F NMR (188 MHz, CDCl3) δ 38.5 (s, 2 F); GC-MS m/z
196 (M+). Anal. Calcd for C7H14F2O2Si: C, 42.84; H, 7.19.
Found: C, 42.97; H, 7.45.
δ 0.79 (t, 3 H, J ) 6.9 Hz), 1.12-1.26 (m, 6 H), 1.45-1.57 (m,
2 H), 4.14 (t, 2 H, J ) 6.9 Hz), 4.94-5.11 (m, 1 H), 6.48-6.70
(m, 3 H), 7.00-7.09 (m, 2 H), 7.25-7.39 (m, 5 H); 19F NMR
(188 MHz, CDCl3) δ 42.4 (dd, 2 F, J FH ) 7 Hz, J FF ) 256 Hz),
52.6 (dd, 2 F, J FH ) 19 Hz, J FF ) 256 Hz). Anal. Calcd for
ter t-Bu tyl 2,2-Diflu or o-2-tr im eth ylsilyl Aceta te (10b).
Colorless oil: (650 mg, 58%); bp 50 °C/20 mmHg (Kugelrohr);
IR (neat) νmax 1760 (CdO) cm-1; 1H NMR (200 MHz, CDCl3) δ
0.22 (s, 9 H), 1.52 (s, 9 H); 19F NMR (188 MHz, CDCl3) δ 38.9
(s, 2 F); GC-MS m/z 224 (M+). Anal. Calcd for C9H18F2O2Si:
C, 48.19; H, 8.09. Found: C, 48.33; H, 8.01.
n -Hexyl 2,2-Diflu or o-2-tr im eth ylsilyl Aceta te (10c).
Colorless oil: (781 mg, 62%); bp 80 °C/2 mmHg (Kugelrohr);
IR (neat) νmax 1756 (CdO) cm-1; 1H NMR (200 MHz, CDCl3) δ
0.23 (s, 9 H), 0.89 (t, 3 H, J ) 6.6 Hz), 1.30-1.41 (m, 6 H),
1.62-1.72 (m, 2 H), 4.23 (t, 2 H, J ) 6.8 Hz); 19F NMR (188
MHz, CDCl3) δ 38.7 (s, 2 F); GC-MS m/z 152 (M+ - OC6H12),
73 (M+ - CF2CO2C6H13). Anal. Calcd for C11H22F2O2Si: C,
52.35; H, 8.79. Found: C, 52.04; H, 8.99.
C
21H25F2NO2: C, 69.79; H, 6.97; N, 3.88. Found: C, 69.69; H,
7.25; N, 3.99.
n -Hexyl 2,2-Diflu or o-3-oxo-3-p h en ylp r op a n oa te (16). A
solution of 10c (252 mg, 1 mmol) and benzoyl chloride (422
mg, 3 mmol), KF (70 mg, 1.2 mmol), and CuI (285 mg, 1.5
mmol) in DMF (1.5 mL) under an argon atmosphere was
stirred for 8 h at 60 °C; the usual workup procedure of the
mixture provided 16. Colorless oil: (170 mg, 60%); IR (neat)
ν
max 1776 (CdO) cm-1; 1H NMR (200 MHz, CDCl3) δ 0.79 (t, 3
H, J ) 6.8 Hz), 1.13-1.24 (m, 6 H), 1.55-1.62 (m, 2 H), 4.25
(t, 2 H, J ) 6.8 Hz), 7.19-7.62 (m, 3 H), 7.99-8.03 (m, 2 H);
19F NMR (188 MHz, CDCl3) δ 54.1 (S, 2 F); GC-MS m/z 355
(M+). Anal. Calcd for C15H18F2O3: C, 63.37; H, 6.38. Found:
C, 63.04; H, 6.63.
Gen er a l P r oced u r e for th e Rea ction of 2,2-Diflu or o-
2-tr im eth ylsilyl Aceta te w ith Electr op h ile. To a solution
of 10c (252 mg, 1 mmol) and benzaldehyde (3.18 mg, 3 mmol)
in THF (1.5 mL) at -78 °C was added TBAF (1.0 mL of a 1.0
M solution in THF) dropwise. After it stirred for 1 h at -78
Eth yl n -Hexyl 2,2-Diflu or om a lon a te (17). To a solution
of 10c (252 mg, 1 mmol) and ethylchloroformate (543 mg, 5
mmol) in THF (1.5 mL) at -45 °C was added TBAF (2.0 mL

Electroreductive Defluorination
J . Org. Chem., Vol. 64, No. 18, 1999 6723
of a 1.0 M solution in THF) dropwise. After stirred for 20 h at
-45 °C, the usual workup procedure of the mixture provided
17. Colorless oil: (113 mg, 45%); IR (neat) νmax 1784 (CdO)
n -Hexyl 2,2-Diflu or o-3-p h en ylp r op a n oa te (19). A solu-
tion of 10c (252 mg, 1 mmol), benzylbromide (380 mg, 3 mmol),
KF (70 mg, 1.2 mmol), and CuI (285 mg, 1.5 mmol) in DMF
(1.5 mL) under an argon atmosphere was stirred for 8 h at 70
°C; the usual workup procedure of the mixture provided 19.
1
cm-1; H NMR (200 MHz, CDCl3) δ 0.92 (t, 3 H, J ) 6.8 Hz),
1.26-1.40 (m, 9 H), 1.66-1.79 (m, 2 H), 4.29-4.42 (m, 4 H);
19F NMR (188 MHz, CDCl3) δ 49.6 (s, 2 F). Anal. Calcd for
C11H18F2O4: C, 52.38; H, 7.19. Found: C, 52.25; H, 7.36.
n -Hexyl 2,2-Diflu or o-4-p en ten oa te (18). A solution of 10c
(252 mg, 1 mmol), allyl chloride (383 mg, 5 mmol), KF (70 mg,
1.2 mmol), and CuI (285 mg, 1.5 mmol) in DMF (1.5 mL) under
an argon atmosphere was stirred for 5 h at 45 °C; the usual
workup procedure of the mixture provided 18. Colorless oil:
Colorless oil: (214 mg, 79%); IR (neat) νmax 1770 (CdO) cm-1
;
1H NMR (200 MHz, CDCl3) δ 0.89 (t, 3 H, J ) 6.8 Hz), 1.12-
1.41 (m, 6 H), 1.56-1.72 (m, 2 H), 3.38 (t, 2 H, J ) 16.4 Hz),
4.17 (t, 2 H, J ) 6.6 Hz) 7.21-7.34 (m, 5 H); 19F NMR (188
MHz, CDCl3) δ 57.2 (t, 2 F, J
) 17 Hz); GC-MS m/z 270
HF
(M+). Anal. Calcd for C15H20F2O2: C, 66.65; H, 7.46. Found:
C, 66.75; H, 7.24.
(187 mg, 85%); IR (neat) νmax 1774 (CdO), 1470 (CdC) cm-1
;
1H NMR (200 MHz, CDCl3) δ 0.89 (t, 3 H, J ) 6.6 Hz), 1.12-
1.46 (m, 6 H), 1.62-1.74 (m, 2 H), 2.74-2.94 (m, 2 H), 4.25 (t,
Ack n ow led gm en t. We are grateful to the Ministry
of Education, Science, Sports, and Culture for financial
support (09305058) and the SC-NMR Laboratory of
Okayama University for 19F NMR analysis.
2 H, J ) 6.7 Hz), 5.15-5.30 (m, 2 H), 5.68-5.89 (m, 1 H); 19
F
NMR (188 MHz, CDCl3) δ 56.3 (t, 2 F, J FH ) 15 Hz). Anal.
Calcd for C11H18F2O2: C, 59.98; H, 8.24. Found: C, 59.62; H,
8.15.
J O990571D