Synthesis of precursors of gem-difluorodiols and amino alcohols using electrochemical and photochemical reactions

Article abstract of DOI:10.1055/s-2006-939079

Photo-initiated S-CF₂ bond cleavage of electrochemically prepared 4-[difluoro(phenylthio)methyl]-1,3-dioxolanone and 4- [difluoro(phenylthio)methyl]-1,3-oxazolidinone in the presence of olefins provided the corresponding radical addition products, while the photolysis in the presence of aromatics and heteroaromatics provided radical substitution products in moderate yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-939079

LETTER
1015
Synthesis of Precursors of gem-Difluorodiols and Amino Alcohols Using
Electrochemical and Photochemical Reactions
Synthesisof
P
a
recursors
o
t
gem-D
o
ifluorodiols
r
and
A
m
u
ino
A
lcohols Murakami, Toshio Fuchigami*
Department of Electronic Chemistry, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8502 Japan
Fax +81(45)9245406; E-mail: fuchi@echem.titech.ac.jp
Received 13 February 2006
O
O
O
Abstract: Photo-initiated S–CF2 bond cleavage of electrochemical-
ly prepared 4-[difluoro(phenylthio)methyl]-1,3-dioxolanone and 4-
[difluoro(phenylthio)methyl]-1,3-oxazolidinone in the presence of
olefins provided the corresponding radical addition products, while
the photolysis in the presence of aromatics and heteroaromatics
provided radical substitution products in moderate yields.
– 4e–, – 2H+
O
O
O
O
O
O
+
Et3N·3HF
DME
40 mA/cm2, 40 °C
SPh
SPh
SPh
F
F
F
3
1
2
48 F/mol
Key words: radical addition, radical aromatic substitution, photo-
trace
68%
reaction, difluoromethyl radical, sulfide
Scheme 1
presence of an electron-rich olefin, 2,3-dihydrofuran, as a
model olefin in CH2Cl2 using a 6-W low-pressure mercu-
ry-vapor lamp through a quartz filter until 2 was com-
pletely consumed. The results are summarized in Table 1.
As a kind of building block for constructing biologically
active compounds, organofluorine compounds hold high
promise for the pharmaceutical and agrochemical indus-
tries due to high electronegativity and the small van der
Waals radius of a fluorine atom.1 In particular, difluoro-
methylene compounds have attracted a great deal of inter-
est due to their being isosteric with an ether oxygen,2 and
synthesis of these compounds has thus become a subject
of investigation in organic chemistry. On the other hand,
fluorine-containing 1,2-diols are useful building blocks
for the preparation of valuable organofluorine compounds
and many papers have reported on the synthesis of 1,2-
diol analogues having a difluoromethylene group.3
Table 1 Photochemical Reaction of 2 with 2,3-Dihydrofuran
O
O
O
hν (λ >200 nm)
O
O
O
O
+
CH2Cl2
1 h
O
SPh
F
F
x equiv
F
F
4
2
Entry
X
Yield (%)a
38
Recently, electrochemical partial fluorination of organic
compounds has been shown to be a powerful method for
selective fluorination.4 Previously, we successfully car-
ried out anodic difluorination of 4-[(phenylthio)methyl]-
1,3-dioxolan-2-one (1) to provide the corresponding gem-
difluorinated product 2 in ca. 70% yield (Scheme 1).5
Since 2 has multiple functional groups, we expected that
2 can be converted to other useful organofluorine com-
pounds. Although metal6 and AIBN/organostannane-cat-
alyzed,7 and electrocatalytic8 radical addition of
difluorohalo esters and ketones across alkenes has been
studied intensively, photochemical radical addition has
been rarely reported.9
1
2
3
5
10
20
49
67 (58)b
a Determined by 19F NMR analyses. Isolated yield is shown in paren-
theses.
b Diastereomeric mixture.
In all cases, the expected radical addition took place and
the difluoromethylene group was introduced exclusively
to the 3-position of 2,3-dihydrofuran. The yield increased
with the amount of 2,3-dihydrofuran used, and the best
result was obtained by using 20 equivalents amounts of
2,3-dihydrofuran to 2 (run 3). Thus, we achieved photo-
induced cleavage of the S–CF2 bond followed by regio-
selective radical addition to 2,3-dihydrofuran. Next, we
extended this photoreaction to various substrates. The
results are shown in Table 2.
With this background in mind, we studied photolysis of 2
for generating the corresponding difluoromethyl radical,
which can be trapped with unsaturated compounds to
form new CF2-containing building blocks.
At first, we investigated the homolytic dissociation of the
S–CF2 bond of 2 using ultraviolet light in the presence of
olefins. The photolysis of 2 was carried out in the
Regardless of the molecular structures of olefins em-
ployed, the expected radical adducts 5–7 were formed in
moderate yields. Notably, the difluoromethylene group
was introduced to the terminal position of acyclic vinyl
ether and olefin exclusively (runs 2 and 4). Previously, we
SYNLETT 2006, No. 7, pp 1015–1020
0
3.
0
5.
2
0
0
6
Advanced online publication: 24.04.2006
DOI: 10.1055/s-2006-939079; Art ID: U01906ST
© Georg Thieme Verlag Stuttgart · New York

1016
S. Murakami, T. Fuchigami
LETTER
Fe2+
Fe3+
+
CHR1R2
CHR1R2
CHR1R2
+
– H+
CHR1R2
X
H
X
X
X
H
X = O, S
R1 = COOEt
R2 = H, Me
Scheme 2
PhSe SePh
(PhSe )
SePh
CF2R
hν
PhZ CF2R
CF R
2
+
– PhZ
step (b)
step (a)
– PhSe
H
CF2R
CF2R
A
B
O
O
O
2: Z = S; R =
N
O
Me
PhSe–
+
O
N
11: Z = S; R =
N
+
H
2': Z = Se; R = COOEt or P(O)(OEt)2
Scheme 3
found that photochemical reaction of a,a-difluoro-a-(phe- in moderate yields.13 This reaction seemed to involve
nylseleno)acetate with olefins always provided mixtures phenylselenyl transfer [Scheme 3, step (b)] followed by
of the corresponding saturated (radical adducts) and un- the elimination of a phenylselenol from the group transfer
saturated products (substituted products).10 In sharp con- adduct B once formed to provide aromatized products. In
trast, in these reactions, saturated radical adducts were this reaction, we found that the yields increased by the ad-
obtained exclusively and no unsaturated product was dition of diphenyl diselenide and 2,4,6-trimethylpyri-
formed. Lequex, Piettre and co-workers also reported dine.14 So, we tried to improve the yields of photolytic
homolytic cleavage of the S–CF2 bond of sulfanyldi- aromatic substitution using 2 by the addition of diphenyl
fluoromethylphosphonate using AIBN/n-Bu3SnH in the diselenide to form phenylselenyl group transfer adduct B
presence of various olefins and they always obtained and 2,4,6-trimethylpyridine to suppress the generation of
saturated adducts:11 The reaction with 2,3-dihydrofuran phenylselenol as a hydrogen atom source (Scheme 3).
provided the adduct to its 3-position exclusively in 47%
yield. In this case, a hydrogen atom source is n-Bu3SnH.
As expected, the yields increased twice for both benzene
and furan (runs 6 and 8) although much longer photoirra-
However, in our case, the hydrogen atom source has not
diation was required to complete the reaction. Thus, the
been specified at present.
yields increased appreciably, but they are still moderate
Next, photoreaction of 2 with aromatic compounds like because of considerable formation of unidentified by-
benzene and furan was carried out similarly. Interestingly, products detected by TLC.
aromatic substitution took place and the corresponding
Furthermore, we extended this photochemical reaction to
an oxazolidinone analogue having a difluoromethylene
unit in order to prepare precursors to difluorinated amino
alcohols. At first, we carried out anodic difluorination of
cross-coupling products 8 and 918 were obtained (runs 5
and 7). Notably, the substitution with the difluoromethyl
group at the a-position of furan proceeded regioselective-
ly to provide the corresponding product 9. However, the
4-[(phenylthio)methyl]-N-methyloxazolidinone (10) in
yields of 8 and 9 were low. Baciocchi et al. reported aro-
Et3N·3HF/DME–MeCN (1:1) to provide the correspond-
ing gem-difluorinated product 11 in moderate yield
(Scheme 4).
matic substitution with electrophilic carbon radicals gen-
erated by alkyl halides and triethylborane.12 Since the
radical addition step is reversible, an oxidizing reagent
like Fe3+ is necessary to shift the equilibrium to the right
side as shown in Scheme 2.
O
O
– 4e–, – 2H+
N
O
N
O
In the case of our aromatic substitution using 2, the cleav-
age of the aryl–CF2 bond of radical s-complex A probably
occurred similarly to Baciocchi’s case as shown in
Scheme 3 [step (a)]. On the other hand, we found recently
that the aromatic substitution of a,a-difluoroselenides 2¢
having ester and phosphonate groups under photoirra-
diation provided the corresponding substitution products
Et3N·3HF
SPh
SPh
DME–MeCN (1:1)
40 mA/cm2, 40 °C
16 F/mol
F
F
10
11
49%
Scheme 4
Synlett 2006, No. 7, 1015–1020 © Thieme Stuttgart · New York

LETTER
Synthesis of Precursors of gem-Difluorodiols and Amino Alcohols
1017
Table 2 Photoreaction of 2 with Various Olefins and Aromatics
Next, the photochemical reaction of 11 was carried out
similarly with cyclic and acyclic olefins, and aromatics.
The results are summarized in Table 3.
O
hν (λ >200 nm)
O
O
Product
+
Substrate
20 equiv
The expected radical addition and aromatic substitution
also took place and the corresponding products 12–1719
were obtained in moderate yields (runs 1–5, and 7). Nota-
bly, the corresponding regioselective addition and substi-
tution products were obtained similarly to the case of 1,3-
dioxolanone 2 (runs 1, 2, 4, and 7). Although the yields of
aromatic substitution were low, the yields were consider-
ably increased by the addition of diphenyl diselenide and
2,4,6-trimethylpyridine (runs 6 and 8).
Although heteroaryl-substituted difluoroketons,15,16
acetates,13 and phosphonate13 have been prepared, such
multifunctional difluoromethylene compounds have
never been prepared so far.
SPh
F
CH2Cl2
F
2
Run
1
Substrate
Time (h)
Product (%)a
O
1
2
2
2
4
8
4
8
O
O
O
O
F
4 67(58)
O
F
F
F
F
2
t-Bu
O
O
O
O
t-Bu
Table 3 Photoreaction of 11 with Various Olefins and
Aromatics17
F
5 45 (40)
O
O
3
hν (λ >200 nm)
O
F
N
+
Substrate
20 equiv
Product
O
O
SPh
F
CH2Cl2
11
F
6 43 (38)
O
Run
Substrate
Time (h) Product (%)a
4
4
O
1
2
3
4
5
2
2
2
2
4
O
O
O
O
O
F
4
N
F
7 48 (40)
O
F
F
F
F
12 66 (61)c
5
O
t-Bu
O
O
O
Ph
F
O
N
O
t-Bu
F
8 22 (20)
O
F
13 58 (52)
O
6b
O
O
Ph
F
O
N
F
8 46 (44)
O
F
14 66 (57)
O
7
O
O
O
O
O
4
O
N
4
F
9 24 (20)
O
F
F
15 50 (45)
O
8b
O
F
O
O
O
N
Ph
F
F
9 44 (41)
F
a Determined by 19F NMR analyses. Isolated yields are shown in
parentheses.
16 22 (19)
b In the presence of 1 equiv of PhSe–SePh and 5 equiv of 2,4,6-tri-
methylpyridine.
Synlett 2006, No. 7, 1015–1020 © Thieme Stuttgart · New York

1018
S. Murakami, T. Fuchigami
LETTER
Table 3 Photoreaction of 11 with Various Olefins and
References and Notes
Aromatics17 (continued)
(1) Hiyama, T. Organofluorine Compounds; Springer-Verlag:
Berlin, 2000.
O
(2) (a) Biomedicinal Aspects of Fluorine Chemistry; Filler, R.;
Kobayashi, Y., Eds.; Kodansya and Elsevier Biomedical:
Tokyo, 1982. (b) Tozer, M. J.; Herpin, T. F. Tetrahedron
1996, 52, 8619.
(3) (a) Audouard, C.; Gerry, A. J. F.; Kerouredan, E.; Miah, A.;
Percy, J. M.; Yang, H. Org. Lett. 2004, 6, 4269.
(b) Kornilov, A. M.; Sorochinsky, A. E.; Kukhar, V. P.
Tetrahedron: Asymmetry 1994, 5, 1015. (c) Hanazawa, Y.;
Inazawa, K.; Kon, A.; Aoki, H.; Kobayashi, Y. Tetrahedron
Lett. 1987, 28, 659.
(4) (a) Fuchigami, T.; Tajima, T. In Fluorine-Containing
Synthons, ACS Symposium Series 911; Soloshonok, V. A.,
Ed.; American Chemical Society: Washington, DC, 2005,
276. (b) Fuchigami, T. Organic Electrochemistry, 4th ed.;
Lund, H.; Hammerich, O., Eds.; Marcel Dekker: New York,
2001, Chap. 25. (c) Fuchigami, T. In Advances in Electron-
Transfer Chemistry, Vol. 6; Mariano, P. S., Ed.; JAI Press:
CT, 1999, 41.
hν (λ >200 nm)
O
F
N
+
Substrate
20 equiv
Product
SPh
F
CH2Cl2
11
Run
6b
Substrate
Time (h) Product (%)a
8
4
8
O
O
F
N
Ph
F
16 40 (37)
7
O
O
O
O
N
(5) Suzuki, K.; Ishii, H.; Fuchigami, T. Tetrahedron Lett. 2001,
42, 4861.
(6) (a) Kitagawa, O.; Miura, A.; Kobayashi, Y.; Taguchi, T.
Chem. Lett. 1990, 1011. (b) Yang, Z.-Y.; Burton, D. J. J.
Org. Chem. 1992, 57, 5144. (c) Qiu, Z.-M.; Burton, D. J. J.
Org. Chem. 1995, 60, 5570.
F
F
17 19 (16)
8b
O
O
O
O
N
(7) Roberts, J. L.; Borgese, J.; Chan, C.; Keith, D. D.; Wei, C.-
C. Heterocycles 1993, 35, 115.
F
F
(8) Médebielle, M. Tetrahedron Lett. 1995, 36, 2071.
(9) Qiu, Z.-M.; Burton, D. J. Tetrahedron Lett. 1994, 35, 1813.
(10) Murakami, S.; Ishii, H.; Fuchigami, T. J. Fluorine Chem.
2001, 42, 4861.
(11) Lequeux, T.; Lebouc, F.; Lopin, C.; Yang, H.; Gouhier, G.;
Piettre, S. R. Org. Lett. 2001, 3, 185.
17 43 (39)
a Determined by 19F NMR analyses. Isolated yields are shown in
parentheses.
b In the presence of 1 equiv of PhSe–SePh and 5 equiv of 2,4,6-tri-
methylpyridine.
c Diastereomeric mixture ca. 1:1.
(12) Baciocchi, E.; Muraglia, E. Tetrahedron Lett. 1993, 34,
5015.
(13) Murakami, S.; Kim, S.; Ishii, H.; Fuchigami, T. Synlett 2004,
815.
(14) Murakami, S.; Ishii, H.; Tajima, T.; Fuchigami, T.
Tetrahedron 2006, in press.
(15) Eto, H.; Kaneko, Y.; Sakamoto, T. Chem. Pharm. Bull.
2000, 48, 982.
(16) Uneyama, K.; Tanaka, H.; Kobayashi, S.; Shinoyama, M.;
Amii, H. Org. Lett. 2004, 6, 2733.
(17) Typical Procedure for Photochemical Reaction.
A solution of 2 or 11 (0.17 mmol) and olefin (3.40 mmol) in
CH2Cl2 (40 mL) or aromatic compounds (40 mL) without
any solvents was bubbled with Ar at r.t. for 0.5 h and then
photolyzed for 2 h or 4 h with 6-W low-pressure mercury-
vapor lamp. The reaction was conducted using a quartz
vessel inside the light source. After the photolysis, the
resulting solution was evaporated under vacuum and the
residue was purified by preparative thin-layer chromato-
graphy (MERCK Silica gel 60 GF254, 33% or 50% EtOAc in
hexane) and by HPLC (Develosil ODS-5, MeCN as eluent)
to provide pure products.
(18) (a) 4-[Difluoro-(3-tetrahydrofuryl)methyl]-1,3-dioxolan-
2-one (4): 1H NMR (270 MHz, CDCl3): d = 4.86–4.54 (m, 3
H), 4.02–3.74 (m, 4 H), 3.09–2.83 (m, 1 H), 2.20–1.89 (m, 2
H). 19F NMR (254 MHz, CDCl3): d = –41.91 to –44.34 (m,
2 F). MS: m/z = 207 [M+ – H], 189 [M+ – F], 87 [M+ – F2C –
C4H7O].
Finally, the deprotection of the carbonate group of 8 as a
model substrate was demonstrated (Scheme 5). Alkaline
hydrolysis of 8 readily proceeded to provide difluorinated
diol 8¢21 in good yield.
O
NaOH
OH
O
HO
O
MeOH–H2O
(3:1)
Ph
F
Ph
F
1 h
F
F
8' 78%
8
Scheme 5
In conclusion, we have successfully carried out the elec-
trochemical difluorination of 4-[(phenylthio)methyl]-N-
methyloxazolidinone similarly to the case of 4-[(phen-
ylthio)methyl]-1,3-dioxolanone.20 The photoinitiated S–
CF2 bond cleavage in the presence of various unsaturated
compounds such as olefins and aromatics provided regio-
selective addition and substitution products, respectively.
Moreover, the corresponding aromatic product was con-
verted to a difluoro diol in good yield. This method seems
to be highly useful for the preparation of various new CF2-
containing building blocks.
(b) 4-[(3-tert-Butoxy-1,1-difluoro)propyl]-1,3-dioxolan-
2-one (5): 1H NMR (270 MHz, CDCl3): d = 5.10–4.97 (m,
1 H), 4.59–4.48 (m, 2 H), 3.55 (t, 2 H, J = 5.8 Hz), 2.44–2.09
(m, 2 H), 1.19 (s, 9H). 13C NMR (67.8 MHz, CDCl3): d =
Synlett 2006, No. 7, 1015–1020 © Thieme Stuttgart · New York

LETTER
Synthesis of Precursors of gem-Difluorodiols and Amino Alcohols
1019
153.82, 120.56 (dd, J = 247.0, 243.1 Hz), 74.89 (dd,
J = 34.7, 26.3 Hz), 73.63, 64.26 (dd, J = 5.0, 2.8 Hz), 54.76
(t, J = 6.7 Hz), 34.54 (dd, J = 23.5, 22.9 Hz), 27.41. 19
NMR (254 MHz, CDCl3): d = –33.90 to –35.17 (m, 1 F),
–36.78 to –37.93 (m, 1 F). FAB-MS: m/z = 239 [M+ + H].
FAB–HRMS: m/z calcd for C10H17F2O4: 239.1095; found:
239.1091.
(c) 4-[(Cyclohexyl)difluoromethyl]-1,3-dioxolan-2-one
(6): 1H NMR (270 MHz, CDCl3): d = 4.92–4.78 (m, 1 H),
4.69–4.50 (m, 2 H), 2.01–1.74 (m, 6 H), 1.31–1.24 (m, 5 H).
13C NMR (67.8 MHz, CDCl3): d = 153.61, 121.25 (dd,
J = 249.8, 243.7 Hz), 72.36 (dd, J = 41.4, 28.5 Hz), 64.02
(dd, J = 5.6, 3.9 Hz), 40.80 (t, J = 21.8 Hz), 25.76 (dd,
J = 5.6, 2.8 Hz), 25.69, 25.46 (d, J = 1.1 Hz), 25.29, 24.04
(dd, J = 4.5, 3.9 Hz). 19F NMR (254 MHz, CDCl3): d =
–54.11 (ddd, 1 F, J = 303.3, 53.6, 3.7 Hz), –59.75 (ddd, 1 F,
J = 303.3, 55.5, 16.6 Hz). FAB-MS: m/z = 221 [M+ + H].
FAB–HRMS: m/z calcd for C10H15F2O3: 221.0989; found:
221.0986.
(c) 5-[(Cyclohexyl)difluoromethyl]-3-methyloxazol-
idinone (14): 1H NMR (270 MHz, CDCl3): d = 4.73–4.59
(m, 1 H), 3.74–3.58 (m, 2 H), 2.91 (s, 3 H), 2.14–1.62 (m, 6
H), 1.33–1.13 (m, 5 H). 13C NMR (67.8 MHz, CDCl3): d =
156.69, 121.84 (dd, J = 250.1, 244.3 Hz), 69.41 (dd,
J = 39.17, 29.1 Hz), 45.79 (dd, J = 5.3, 3.4 Hz), 40.66 (t,
J = 21.8 Hz), 30.94, 29.77, 25.95 (dd, J = 6.1, 2.8 Hz),
25.84, 25.43, 24.06 (dd, J = 5.0, 3.9 Hz). 19F NMR (254
MHz, CDCl3): d = –45.35 (ddd, 1 F, J = 258.9, 20.3, 3.7 Hz),
–46.72 (ddd, 1 F, J = 258.9, 18.5, 9.2 Hz). MS: m/z = 233
[M+], 100. HRMS: m/z calcd for C11H17F2NO2: 233.1227;
found: 233.1222.
F
(d) 5-(1,1-Difluorooctyl)-3-methyloxazolidinone (15):
1H NMR (270 MHz, CDCl3): d = 4.60–4.446 (m, 1 H), 3.71–
3.60 (m, 2 H), 2.91 (s, 3 H), 2.17–1.84 (m, 2 H), 1.58–1.46
(m, 2 H), 1.37–1.25 (m, 8 H), 0.89 (t, 3 H, J = 6.8 Hz).
13C NMR (67.8 MHz, CDCl3): d = 156.65, 121.36 (dd,
J = 248.2, 239.8 Hz), 71.22 (dd, J = 40.2, 27.9 Hz), 45.81
(dd, J = 4.5, 3.4 Hz), 33.07 (dd, J = 23.5, 22.9 Hz), 31.67,
30.94, 29.25, 29.03, 22.65, 21.36 (dd, J = 5.6, 2.8 Hz),
14.14. 19F NMR (254 MHz, CDCl3): d = –35.55 to –36.72
(m, 1 F), –40.22 to 41.43 (m, 1 F). MS: m/z = 249 [M+], 149,
100. HRMS: m/z calcd for C12H21F2NO2: 249.1540; found:
249.1539.
(e) 5-[Difluoro(phenyl)methyl]-3-methyloxazolidinone
(16): 1H NMR (270 MHz, CDCl3): d = 7.55–7.42 (m, 5 H),
4.85–4.73 (m, 1 H), 3.67 (d, 2 H, J = 7.4 Hz), 2.82 (s, 3H).
13C NMR (67.8 MHz, CDCl3): d = 156.45, 132.20 (dd,
J = 25.7, 25.2 Hz), 130.72 (t, J = 1.7 Hz), 128.51, 125.69 (t,
J = 6.1 Hz), 118.65 (dd, J = 248.7, 244.3 Hz), 72.93 (dd,
J = 39.13, 32.42 Hz), 46.32 (t, J = 3.35 Hz), 30.83. 19F NMR
(254 MHz, CDCl3): d –30.25 (dd, 1 F, J = 258.9, 5.5 Hz),
–38.53 (dd, 1 F, J = 258.9, 14.8 Hz). MS: m/z = 227 [M+].
HRMS: m/z calcd for C11H11F2NO2: 227.0758; found:
227.0748.
(f) 5-[Difluoro(2-furyl)methyl]-3-methyloxazolidinone
(17): 1H NMR (270 MHz, CDCl3): d = 7.52–7.49 (m, 1 H),
6.79–6.76 (m, 1 H), 6.48–6.45 (m, 1 H), 5.04–4.91 (m, 1 H),
3.73 (d, 2 H, J = 7.6 Hz), 2.89 (s, 3 H). 13C NMR (67.8 MHz,
CDCl3): d = 156.36, 144.31 (dd, J = 2.2, 1.7 Hz), 144.45 (dd,
J = 35.8, 33.0 Hz), 114.38 (dd, J = 243.7, 240.3 Hz), 111.78
(dd, J = 3.9, 2.8 Hz), 110.78 (t, J = 1.1 Hz), 71.22 (dd,
J = 36.3, 29.6 Hz), 45.97 (t, J = 3.4 Hz), 30.87. 19F NMR
(254 MHz, CDCl3): d = –28.77 (dd, 1 F, J = 277.4, 5.5 Hz),
–39.12 (dd, 1 F, J = 277.4, 12.9 Hz). MS: m/z = 217 [M+],
117, 100. HRMS: m/z calcd for C9H9F2NO3: 217.0550;
found: 217.0551.
(d) 4-(1,1-Difluorooctyl)-1,3-dioxolan-2-one (7): 1H NMR
(270 MHz, CDCl3): d = 4.80–4.51 (m, 3 H), 2.18–1.81 (m, 2
H), 1.60–1.48 (m, 2 H), 1.39–1.23 (m, 8 H), 0.89 (t, 3 H,
J = 7.1 Hz). 13C NMR (67.8 MHz, CDCl3): d = 153.49,
120.72 (dd, J = 249.3, 241.5 Hz), 74.16 (dd, J = 40.8, 27.9
Hz), 63.96 (dd, J = 5.0, 3.4 Hz), 33.11 (dd, J = 23.5, 22.4
Hz), 31.65, 29.18, 28.98, 22.65, 21.25 (dd, J = 5.6, 2.8 Hz),
14.41. 19F NMR (254 MHz, CDCl3): d = –35.57 to –36.76
(m, 1 F), –40.22 to –41.43 (m, 1 F). MS: m/z = 236 [M+],
149. HRMS: m/z calcd for C11H18F2O3: 236.1224; found:
236.1232.
(e) 4-[Difluoro(phenyl)methyl]-1,3-dioxlan-2-one (8):
1H NMR (270 MHz, CDCl3): d = 7.56–7.45 (m, 5 H), 5.04–
4.92 (m, 1 H), 4.68–4.43 (m, 2 H). 13C NMR (67.8 MHz,
CDCl3): d = 153.32, 131.36 (dd, J = 25.2, 24.6 Hz), 131.21
(dd, J = 2.2, 1.7 Hz), 128.83, 125.59 (t, J = 6.1 Hz), 118.15
(dd, J = 249.3, 244.3 Hz), 75.88 (dd, J = 39.7, 32.4 Hz),
64.21 (t, J = 3.3 Hz). 19F NMR (254 MHz, CDCl3): d =
–30.95 (dd, 1 F, J = 262.6, 5.5 Hz), –37.90 (dd, 1 F, J =
262.6, 12.9 Hz). MS: m/z = 214 [M+], 127. HRMS: m/z calcd
for C10H8F2O3: 214.0442; found: 214.0443.
(f) 4-[Difluoro(2-furyl)methyl]-1,3-dioxolan-2-one (9):
1H NMR (270 MHz, CDCl3): d = 7.55–7.54 (m, 1 H), 6.83–
6.81 (m, 1 H), 6.51–6.50 (m, 1 H), 5.23–5.11 (m, 1 H), 4.72–
4.56 (m, 2 H). 13C NMR (67.8 MHz, CDCl3): d = 153.24,
144.97 (dd, J = 2.2, 1.7 Hz), 143.58 (dd, J = 37.4, 33.0 Hz),
113.82 (dd, J = 243.7, 240.3 Hz), 112.33 (dd, J = 3.4, 2.8
Hz), 111.00 (t, J = 1.1 Hz), 74.21 (dd, J = 37.4, 29.6 Hz),
63.94 (t, J = 3.4 Hz). 19F NMR (254 MHz, CDCl3): d =
–28.80 (dd, 1 F, J = 280.0, 5.5 Hz), –38.17 (dd, 1 F,
J = 280.0, 11.1 Hz). MS: m/z = 204 [M+], 117. HRMS:
m/z calcd for C8H6F2O4: 204.0234; found: 204.0237.
(19) (a) 5-[Difluoro(3-tetrahydrofuryl)methyl]-3-methyl-
oxazolidinone (12): 1H NMR (270 MHz, CDCl3): d = 4.67–
4.44 (m, 1 H), 4.01–3.63 (m, 6 H), 3.18–2.92 (m, 4 H), 2.22–
1.87 (m, 2 H). 19F NMR (254 MHz, CDCl3): d = –43.16 (ddd,
1 F, J = 262.6, 18.5, 12.9 Hz), –44.43 (ddd, 1 F, J = 262.4,
20.2, 3.7 Hz). MS: m/z = 222 [M+ + H]. FAB–HRMS:
m/z calcd for C9H14F2NO3: 222.0942; found: 222.0945.
(b) 5-[(3-tert-Butoxy-1,1-difluoro)propyl]-3-methyl-
oxazol-idinone (13): 1H NMR (270 MHz, CDCl3): d = 4.81–
4.67 (m, 1 H), 3.64–3.54 (m, 4 H), 2.90 (s, 3 H), 2.44–2.06
(m, 2 H), 1.19 (s, 9 H). 13C NMR (67.8 MHz, CDCl3): d =
156.82, 121.00 (dd, J = 246.5, 244.3 Hz), 73.36, 71.69 (dd,
J = 34.1, 30.2 Hz), 54.91 (dd, J = 6.7, 6.1 Hz), 46.10 (dd,
J = 4.5, 3.4 Hz), 34.37 (dd, J = 23.5, 22.9 Hz), 30.95, 27.45.
19F NMR (254 MHz, CDCl3): d = –35.48 to –37.81 (m, 2 F).
FAB–MS: m/z 252 [M+ + H]. FAB-HRMS: m/z calcd for
C11H20F2NO3: 252.1411; found: 252.1407.
(20) Electrochemical Difluorination of 5-(Phenylthio)methyl-
3-methyloxazolidinone (10):
Constant current electrolysis (40 mA/cm–2) of 10 was carried
out at platinum electrodes (2 × 2 cm2) at 40 °C in DME–
MeCN (5 mL each) containing 0.3 M Et3N·3HF using
undivided cell. After electrolysis, the supporting electrolyte
was removed by silica gel short column chromatography.
The product 11 was isolated by silica gel column chromato-
graphy (EtOAc–hexane, 1:3).
5-[Difluoro(phenylthio)methyl]-3-methyloxazolidinone
(11): 1H NMR (270 MHz, CDCl3): d = 7.63–7.60 (m, 2 H),
7.49–7.35 (m, 3 H), 4.71–4.57 (m, 1 H), 3.74–3.61 (m, 2 H),
2.88 (s, 3 H). 13C NMR (67.8 MHz, CDCl3): d = 156.09,
138.46 (dd, J = 8.9, 0.6 Hz), 136.34, 130.23, 129.11, 126.41
(dd, J = 282.3, 280.6 Hz), 71.86 (dd, J = 31.9, 27.9 Hz),
46.48 (t, J = 2.8 Hz), 30.67. 19F NMR (254 MHz, CDCl3):
d = –11.22 (dd, 1 F, J = 218.2, 9.2 Hz), –12.91 (dd, 1 F,
J = 218.2, 9.2 Hz). MS: m/z = 259 [M+], 159, 77. HRMS:
m/z calcd for C11H11F2NO2S: 259.0479; found: 259.0485.
Synlett 2006, No. 7, 1015–1020 © Thieme Stuttgart · New York

1020
S. Murakami, T. Fuchigami
LETTER
(21) 3,3-Difluoro-3-phenylpropan-1,2-diol (8¢): 1H NMR (270
MHz, CDCl3): d = 7.55–7.45 (m, 5 H), 4.14–4.02 (m, 1 H),
3.78–3.64 (m, 2 H), 3.22–1.93 (br, 2 H). 13C NMR (67.8
MHz, CDCl3): d = 133.98 (t, J = 25.7 Hz), 130.23 (t, J = 1.7
Hz), 128.40, 125.50 (t, J = 6.7 Hz), 120.72 (t, J = 247.0 Hz),
74.23 (dd, J = 30.2, 29.1 Hz), 61.14 (t, J = 3.4 Hz). 19F NMR
(254 MHz, CDCl3): d = –29.62 (dd, 1 F, J = 253.4, 9.2 Hz),
–32.57 (dd, 1 F, J = 253.4, 12.9 Hz). MS: m/z = 188 [M+],
127, 77. HRMS: m/z calcd for C9H10F2O2: 188.0649; found:
188.0652.
Synlett 2006, No. 7, 1015–1020 © Thieme Stuttgart · New York