Fluorination of alcohols and diols with a novel fluorous deoxy-fluorination reagent

Article abstract of DOI:10.1016/j.jfluchem.2008.12.010

We prepared a novel fluorous deoxy-fluorination reagent N,N-diethyl-α,α-difluoro-[3,5-bis(1H,1H,2H,2H-perfluorodecyl)benzyl]amine (1b) from 3,5-diiodobenzoic acid (3b) via N,N-diethyl-3,5-bis(1H,1H,2H,2H-perfluorodecyl)benzamide (2b) in four steps and used it for the fluorination of alcohols and diols. After the fluorination reactions, the isolation of the products and recovery of 2b was performed by extraction with a fluorous/organic solvent system.

Full text of DOI:10.1016/j.jfluchem.2008.12.010

Journal of Fluorine Chemistry 130 (2009) 348–353
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Fluorination of alcohols and diols with a novel fluorous
deoxy-fluorination reagent
*
Tsukasa Furuya, Takashi Nomoto, Tsuyoshi Fukuhara, Shoji Hara
Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
A R T I C L E I N F O
A B S T R A C T
We prepared a novel fluorous deoxy-fluorination reagent N,N-diethyl-a,a-difluoro-[3,5-bis(1H,1H,2H,2H-
Article history:
Received 2 December 2008
Received in revised form 23 December 2008
Accepted 24 December 2008
Available online 31 December 2008
perfluorodecyl)benzyl]amine (1b) from 3,5-diiodobenzoic acid (3b) via N,N-diethyl-3,5-bis(1H,1H,2H,2H-
perfluorodecyl)benzamide (2b) in four steps and used it for the fluorination of alcohols and diols. After the
fluorination reactions, the isolation of the products and recovery of 2b was performed by extraction with a
fluorous/organic solvent system.
ß 2008 Elsevier B.V. All rights reserved.
Keywords:
Fluorous fluorination reagent
Deoxy-fluorination reaction
N,N-Diethyl-a,a-difluoro-[3,5-
bis(1H,1H,2H,2H-
perfluorodecyl)benzyl]amine
1. Introduction
products could be performed by simple extraction with a fluorous/
organic solvent system (Scheme 1).
Recently, fluorous chemistry using a fluorous/organic biphasic
system has been developing as an environmentally friendly
technology. The highly fluorinated compounds are selectively
soluble in fluorocarbon solvents and separable from other organic
compounds by simple extraction with a fluorous/organic biphasic
solvent systems. Many fluorous reagents having fluorous tags have
been prepared and successfully applied to organic synthesis [1].
The deoxy-fluorination reaction is a useful method for the selective
introduction of one or two fluorine atoms into molecules and many
deoxy-fluorination reagents such as DAST and deoxofluor have
been developed and used [2]. However, to our knowledge, no
recyclable fluorous deoxy-fluorination reagents have been
reported so far. Recently we reported the fluorination of alcohols
[3], aldehydes [4], diols [5], amino alcohols [6], and epoxides [7]
2. Result and discussion
2.1. Preparation of fluorous fluorination reagent 1b
We prepared
a fluorous deoxy-fluorination reagent, N,N-
diethyl- -difluoro-[3,5-bis(1H,1H,2H,2H-perfluorodecyl)benzy-
a,a
l]amine 1b, from 3,5-diiodobenzoic acid 3b [8] in four steps via
N,N-diethyl-3,5-diiodobenzamide 4b. Introduction of the fluorous
tags was performed by a Heck-type reaction of 4b with 1H,1H,2H-
perfluorodec-1-ene, followed by hydrogenation [9]. The resulting
N,N-diethyl-3,5-bis(1H,1H,2H,2H-perfluorodecyl)benzamide 2b
was converted to 1b by deoxychlorination with oxalyl chloride,
followed by a halogen-exchange reaction with Et3N–3HF [10]. The
fluorous fluorination reagent 1b is a moisture sensitive white solid
and can be kept in a TeflonTM PFA bottle with a tight screw cap
under inert atmosphere (Scheme 2).
using
a novel deoxy-fluorination reagent, N,N-diethyl-a,a-
difluoro-3-methylbenzylamine (DFMBA) 1a, which is prepared
from N,N-diethyl-3-methylbenzamide 2a and returns to 2a after
the fluorination reaction. Therefore, we planned to prepare the
fluorous deoxy-fluorination reagent, N,N-diethyl-a,a-difluoro-
2.2. Fluorination of alcohols with the fluorous deoxy-fluorination
reagent 1b and the separation of products and recovery of 2b by
extraction with a fluorous/organic solvent system
[3,5-bis(1H,1H,2H,2H-perfluorodecyl)benzyl]amine 1b, and apply
it to the fluorination of alcohols. After the fluorination reaction, 1b
will return to 2b, and the recovery of 2b as well as isolation of
Initially, we examined the fluorination ability of 1b by applying
it for the deoxy-fluorination of 1-dodecanol and butyl 5-hydro-
xypentanoate 6. The reactions were completed at 98 8C in 3 h, and
the corresponding fluorinated products, 1-fluorododecane and
* Corresponding author. Fax: +81 11 706 6556.
E-mail address: shara@eng.hokudai.ac.jp (S. Hara).
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.12.010

T. Furuya et al. / Journal of Fluorine Chemistry 130 (2009) 348–353
349
Table 1
Fluorination of alcohols with 1a or 1ba.
Alcohol
Fluorination reagent
Product
Yield (%)b
C12H25–OH
C12H25–OH
1a
1b
C12H25–F
C12H25–F
86c
88
BuOOCðCH2Þ4 ꢀ OH
BuOOCðCH2Þ4 ꢀ F
1b
87
6
7
a
1.2 equiv. of 1a or 1b to alcohol was used.
Isolation yield based on alcohol used.
Ref. [3].
Scheme 1.
b
c
Table 2
Fluorous organic liquid/liquid partition of amide (2b) and products.
Entry Solvent
Partition (fluorous organic)a
2b
C12H25–F
7
1
2
3
4
FC-77:hexane (2:1)
89:11
80:20
89:11
20:80
19:81
FC-77:toluene (2:1)
PFMC:toluene (2:1)
FC-77 + HFE-7100:CH3CN (5% H2O) (2:1)b >99:<1 38:62
<1:>99
<1:>99
<1:>99
3:97
a
Determined by GC.
b
FC-77:HFE-7100 = 1:1.
the solvent system of PFMC/toluene (2:1). The separated toluene
phase was washed with PFMC once and 1-fluorododecane was
obtained in a 75% yield (>99% purity) from the toluene phase. On
the other hand, GC analysis showed that the PFMC phase contains
2b, 1-fluorododecane and dodecyl 3,5-bis(1H,1H,2H,2H-perfluor-
odecyl)benzoate 8 in a ratio of 87:7:6 (Scheme 3) [11]. Benzoate 8
was generated by the hydrolysis of the intermediate derived from
1-dodecanol and 1b [3], and found only in the PFMC phase. The
recovered 2b and 8 can be converted to 1b.
In the reaction of 6 with 1b, the concentrated reaction mixture
was dissolved in the solvent system of FC-77 and HFE-7100/CH3CN
(5% H2O) (2:1). The separated organic layer was washed with a
mixture of FC-77 and HFE-7100. From the organic phase, 7 was
obtained in a 72% yield (>99% purity). In the fluorous phase, 2b, 7,
and 4-butoxycarbonylbutyl 3,5-bis(1H,1H,2H,2H-perfluorodecyl)-
benzoate 9 were present in a ratio of 95:2:3 (Scheme 4).
Thus, the fluorination of alcohols 3 and 6 can be achieved with
1b, and separation of the fluorinated product and recovery of 2b
and the ester (8 or 9) are possible by simple extraction with a
fluorous/organic solvent systems.
Scheme 2.
butyl 5-fluoropentanoate 7, were obtained in 88% and 87% yields,
respectively. These results indicated that the fluorination ability of
1b is comparable to that of DFMBA 1a [3], as shown in Table 1.
To separate the product and the amide 2b, their partition ratios
in various fluorous and organic solvent systems were examined
(Table 2). When FC-77 (a mixture of perfluoroalkanes and
pefluorocyclic ethers) was used as the fluorous solvent, an
appropriate organic solvent could not be found for their separa-
tions (entries 1 and 2). However, better results were obtained with
perfluoromethylcyclohexane (PFMC). When 2b and the product
were dissolved in a mixture of PFMC and toluene, the product came
to the toluene phase exclusively (>99%), and 2b was present in
PFMC phase selectively (89%) (entry 3). For the separation of 2b
and 7, the solvent system of FC-77 + HFE-7100 (nonafluorobutyl
methyl ether)/CH3CN (5% H2O) was superior to the PFMC/toluene
system. Thus, when 2b and 7 were dissolved in that solvent system,
2b came to the fluorous phase exclusively (>99%), and 7 was
predominantly present in the organic phase (97%) (entry 4).
After the reaction of 1-dodecanol with 1b, the solvent was
removed under reduced pressure and the residue was dissolved in
2.3. Fluorination of diols with 1b
Next, we applied 1b for the fluorination of 1,2-diols. In the
reaction of DFMBA with 1,2- or 1,3-diols, selective monofluorina-
Scheme 3.

350
T. Furuya et al. / Journal of Fluorine Chemistry 130 (2009) 348–353
Scheme 4.
Scheme 5.
Table 3
tion occurred and 3-methylbenzoates of the corresponding
fluorohydrins were formed [5]. The perfluoroalkylated benzoates
of fluorohydrins, generated by the reaction of 1b with 1,2-diols,
would be convertible to the corresponding fluorohydrins by
transesterification. The separation of the generated fluorohydrins
and recovery of the fluorous reagent would be possible by
extraction with a fluorous/organic solvent system (Scheme 5).
We performed the fluorination of ethylene glycol with
2.4 equiv. of 1b at 95 8C for 1 h and obtained 2-fluoroethyl 3,5-
bis(1H,1H,2H,2H-perfluorodecyl)benzoate 10 in an 84% yield. The
reactions of 1b with (1R,2R)-1,2-diphenyl-1,2-ethandiol and cis-
1,2-cyclododecanediol were more sluggish, and higher tempera-
tures (140 and 160 8C, respectively) were required. The resulting
perfluoroalkylated benzoates of the corresponding fluorohydrins
11 and 12 were obtained in 74% and 69% yields, respectively
(Table 3).
Fluorination of diols with 1ba.
Diol
Reaction cond.
Product
Yield (%)b
84
95 8C, 1 h
140 8C, 1 h
74
69
160 8C, 1 h
In order to prepare
a fluorohydrin, (1R,2S)-2-fluoro-1,2-
diphenylethanol, 11 was subjected to a transesterification reaction
after the reaction of 1b with (1R,2R)-1,2-diphenyl-1,2-ethandiol
without purification. The crude 11, butanol, and a distannoxane
catalyst [12] were dissolved in toluene and the mixture was stirred
a
The reactions were performed using 2.4 equiv. of 1b to diol without solvent. Ar
is 3,5-bis(1H,1H,2H,2H-perfluorodecyl)phenyl.
b
Isolation yield based on diol used.
Scheme 6.

T. Furuya et al. / Journal of Fluorine Chemistry 130 (2009) 348–353
351
under reflux. After the transesterification was completed, the
volatile portion was removed under reduced pressure. The residue
was dissolved in the solvent system of HFE-7100 and FC-77/CH3CN
(containing 5% H2O). From the organic phase, (1R,2S)-2-fluoro-1,2-
diphenyl-1-ethanol 13 was obtained in a 55% yield (>98% purity).
From the fluorous phase, 2b (60% based on 1b) and butyl 3,5-
bis(1H,1H,2H,2H-perfluorodecyl)benzoate (38% based on 1b) were
obtained (Scheme 6).
A mixture of 4b (0.215 g, 0.5 mmol), 1H,1H,2H-perfluorodec-1-
ene (0.49 g, 1.1 mmol), Pd(OAc)2 (5.6 mg, 0.025 mmol), Bu4NBr
(0.26 g, 0.8 mmol), and NaOAc (0.11 g, 1.3 mmol) in DMF (5 mL)
was stirred under N2 atmosphere at 115 8C for 4 days. After cooling
to room temperature, CH2Cl2 (30 mL) and water (30 mL) were
added to the reaction mixture. The separated organic phase was
washed with water (30 mL ꢁ 2), dried over MgSO4. Purification by
column chromatography (silica gel/CH2Cl2:ether = 10:1) gave
N,N-diethyl-3,5-bis(1H,2H-perfluorodec-1-enyl)benzamide
(300 mg, 0.28 mmol) in 56% yield: 5b; white solid; mp 68 8C. IR
(KBr): 2992, 1617, 1241, 1214, 1149, 979 cmꢀ1. 1H NMR
7.57 (s,
1H), 7.51 (s, 2H), 7.20 (d, J = 16.2 Hz, 2H), 6.29 (dt, J = 16.0, 11.8 Hz,
2H), 3.57 (brs, 2H), 3.28 (brs, 2H), 1.28 (brs, 3H), 1.15 (brs, 3H). 13
NMR 169.44, 139.10 (2C), 138.15 (t, J = 9.1 Hz, 2C), 134.75,
127.48, 126.58 (2C), 116.75 (t, J = 23.1 Hz, 2C), 43.41 (brs), 39.50
(brs), 14.25 (brs), 12.87 (brs) [13]. 19F NMR
6F), ꢀ112.01 (dt, J = 12.2, 12.2 Hz, 4F), ꢀ121.87 (m, 4F), ꢀ122.43
(m, 8F), ꢀ123.24 (m, 4F), ꢀ123.61 (m, 4F), ꢀ126.64 (m, 4F). HRMS
(EI): calcd. for C31H17NOF34Na ((M+Na)+): 1088.0675, found:
1088.0670.
5b
3. Conclusion
d
We prepared a novel fluorous deoxy-fluorination reagent,
N,N-diethyl-
a
,
a
-difluoro-[3,5-bis(1H,1H,2H,2H-perfluorodecyl)-
C
benzyl]amine 1b, and used it for the fluorination of alcohols and
diols. The fluorous deoxy-fluorination reagent 1b has comparable
fluorination ability to that of DFMBA, and alcohols can be
converted to the corresponding fluorinated products in good
yields. After the reaction, the fluorinated products can be isolated
in their pure forms by simple extraction with a fluorous/organic
solvent system. The amide 2b, generated from 1b after
fluorination, can be recovered from the fluorous phase of the
extract. The fluorous deoxy-fluorination reagent 1b was also
applied to the fluorination of 1,2-diols and the resulting
perfluoroalkylated benzoates of the fluorohydrins were con-
verted to the fluorohydrins by the transesterification reaction.
The isolation of the fluorohydrins and recovery of the fluorous
reagent was achieved by extraction with a fluorous/organic
solvent system.
d
d
ꢀ81.31 (t, J = 9.7 Hz,
A mixture of 5b (1.2 g, 1.10 mmol) and 10%-Pd/C (0.1983 g) in
AcOEt (45 mL) was subjected to a flask equipped with balloon (3 L)
filled with H2. The mixture was stirred at room temperature under
H2 atmosphere for 22 h. The catalyst was removed through celite
and washed with ether (20 mL ꢁ 2). The filtrate was concentrated
under reduced pressure to give pure N,N-diethyl-3,5-
bis(1H,1H,2H,2H-perfluorodecyl)benzamide 2b (1.2 g) in 99%
yield: 2b; white solid; mp 54 8C. IR (KBr): 2988, 1638, 1437,
1371, 1142, 872, 822, 664 cmꢀ1
2H), 3.23 (brs, 2H), 2.91–2.95 (m, 4H), 2.31–2.45 (m, 4H), 1.26 (brs,
3H), 1.11 (brs, 3H). 13C NMR
170.74, 140.15 (2C), 138.57, 129.06,
. d 7.10 (s, 3H), 3.55 (brs,
1H NMR
4. Experimental
d
4.1. General
124.54 (2C), 121.43–105.92 (complex signals of CF3 and CF2), 43.26
(brs), 39.29 (brs), 32.72 (t, J = 22.2 Hz, 2C), 26.33 (t, J = 4.2 Hz, 2C),
The melting points were measured with a Yanagimoto micro-
melting-point apparatus. The IR spectra were recorded using a
JASCO FT/IR-410. The 1H NMR (400 MHz) spectra, 19F NMR
(376 MHz) spectra, and 13C NMR (100 MHz) were recorded in
14.08 (brs), 12.79 (brs). 19F NMR
d
ꢀ81.31 (t, J = 10.4 Hz, 6F),
ꢀ115.02 (tt, J = 16.5, 14.6 Hz, 4F), ꢀ122.20 (m, 4F), ꢀ122.43 (m,
8F), ꢀ123.24 (m, 4F), ꢀ123.96 (m, 4F), ꢀ126.64 (m, 4F). HRMS (EI):
calcd. for
1092.0984.
C
31H21NOF34Na ((M+Na)+): 1092.0989, found:
CDCl3 on a JEOL JNM-A400II FT NMR and the chemical shift, d, is
referred to TMS (1H, 13C) and CFCl3 (19F), respectively. The EI-high-
resolution mass spectra were measured on a JEOL JMS-700TZ.
Optical rotation was measured with a Horiba High-Sensitive
Polarimeter. FC-77 was donated from Central Glass Co. Ltd. PFMC,
HFE-7100, and 1H,1H,2H-perfluorodec-1-ene were purchased
from Wako Pure Chemical Industries Ltd. 3,5-Diiodobenzoic acid
[8], Et3N–3HF [4], ClSnBu2OSnBu2Cl [12] were prepared according
to the literatures.
To a CH2Cl2 solution (30 mL) of 2b (15.9 g, 14.9 mmol) was
added oxalyl chloride (2.1 g, 16.4 mmol) at room temperature and
the mixture was stirred under reflux for 24 h. After cooling to 0 8C,
Et3N–3HF (1.85 g, 11.5 mmol) and Et3N (2.3 g, 23 mmol) were
added successively. The generated precipitate was separated by
filtration under N2 atmosphere and washed with hexane (30 mL).
The filtrate was concentrated under reduced pressure, and the
generated solid was separated by filtration under N2 atmosphere
again. The filtrate was concentrated under reduced pressure and
4.2. N,N-Diethyl-
a
,
a
-difluoro-[3,5-bis(1H,1H,2H,2H-
the distillation of the residue gave N,N-diethyl-a,a-difluoro-[3,5-
perfluorodecyl)benzyl]amine (1b)
bis(1H,1H,2H,2H-perfluorodecyl)benzyl]amine 1b (13.7 g) in 84%
yield (bp 200 8C/0.01 mmHg): 1b; white solid (moisture sensitive).
A mixture of 3,5-diiodobenzoic acid [8] (3.75 g, 10 mmol) and
thionyl chloride (14.3 g, 120 mmol) was stirred under reflux
overnight. Excess thionyl chloride was removed under reduced
pressure, and CH2Cl2 (10 mL) and Et2NH (3.65 g, 50 mmol) were
added at 0 8C successively. After stirring at 0 8C for 30 min, water
(50 mL) was added, and the product was extracted with ether
(50 mL ꢁ 4). The separated organic phase was washed with water
(30 mL ꢁ 2), dried over MgSO4, and concentrated under reduced
pressure. Purification by column chromatography (silica gel/
CH2Cl2) gave N,N-diethyl-3,5-diiodobenzamide 4b (3.22 g) in
75% yield: 4b; white solid; mp 68 8C. IR (KBr): 2967, 1619,
1H NMR
d
7.34 (d, J = 1.0 Hz, 2H), 7.14 (s, 1H), 2.93–2.97 (m, 4H),
2.87 (q, J = 7.1 Hz, 4H), 2.32–2.45 (m, 4H), 1.06 (t, J = 7.1 Hz, 6H).
19F NMR
d
ꢀ73.92 (s, 2F), ꢀ81.31 (s, 6F), ꢀ114.93 (s, 4F), ꢀ122.01
(s, 4F), ꢀ122.34 (s, 8F), ꢀ123.15 (s, 4F), ꢀ123.81 (s, 4F), ꢀ128.59 (s,
4F).
4.3. Fluorination of alcohols
4.3.1. 1-Fluorododecane
1-Dodecanol (186 mg, 1 mmol), 1b (1.34 g, 1.2 mmol), and
heptane (1 mL) were introduced into a reaction vessel made of
Teflon PFA with a tight screw cap, and the mixture was stirred at
98 8C for 3 h. After cooling to room temperature, the mixture was
concentrated under reduced pressure. The residue was dissolved in
a mixture of PFMC (10 mL) and toluene (5 mL), and separated
toluene phase was washed with PFMC (10 mL) twice. Concentra-
1538, 1279, 866 cmꢀ1
2H), 3.50 (brs, 2H), 3.23 (brs, 2H), 1.23 (brs, 3H), 1.12 (brs, 3H). 13
NMR 167.56, 145.67, 140.56, 134.31 (2C), 94.72 (2C), 43.32 (brs),
39.45 (brs), 14.13 (brs), 12.78 (brs). HRMS (EI): calcd. for
11H13I2NO (M+): 428.9087, found: 428.9078.
. d 8.08 (s, 1H), 7.66 (d, J = 1.3 Hz,
1H NMR
C
d
C

352
T. Furuya et al. / Journal of Fluorine Chemistry 130 (2009) 348–353
tion of toluene phase gave pure 1-fluorododecane (141 mg) in 75%
yield. On the other hand, GC analysis showed that the PFMC phase
contains 2b, 1-fluorododecane, and dodecyl 3,5-bis(1H,1H,2H,2H-
perfluorodecyl)benzoate 8 in a ratio of 87:7:6.
ꢀ126.69 (s, 4F), ꢀ187.70 (dd, J = 46.4, 17.7 Hz, 1F). HRMS (ESI):
calcd. for
1235.1018.
C
41H23O2F35Na ((M+Na)+): 1235.1033, found:
1-Fluorododecane [3b]; IR (neat): 2925, 2855, 1466, 1389, 1050,
4.4.3. trans-2-Fluorocyclododecyl 3,5-bis(1H,1H,2H,2H-
perfluorodecyl)benzoate (12)
1010 cmꢀ1
.
1H NMR
d
4.44 (dt, J = 47.3, 6.3 Hz, 2H), 1.74–1.64 (m,
2H), 1.39–1.26 (m, 18H), 0.88 (t, J = 6.7 Hz, 3H). 13C NMR
d
14.07,
White solid; mp 85.5–86 8C. IR (KBr): 1716, 1469, 1149 cmꢀ1
.
22.71, 25.19 (d, J = 5.0 Hz), 29.29, 29.39, 29.56, 29.60, 29.67, 29.69,
1H NMR
d
7.81 (s, 2H), 7.27 (s, 1H), 5.44–5.55 (m, 1H), 4.85 (ddt,
J = 48.6, 8.0, 4.3 Hz, 1H), 2.85–3.07 (m, 4H), 2.27–2.50 (m, 4H),
1.17–1.99 (m, 20H). 13C NMR
165.87, 140.08 (2C) 132.96, 131.46,
30.46 (d, J = 19.0 Hz), 31.96, 84.11 (d, J = 163.8 Hz). 19F NMR
ꢀ218.36 to ꢀ218.75 (1F, m).
d
d
127.99 (2C), 91.78 (d, J = 175.5 Hz), 72.97 (d, J = 17.0 Hz), 32.76 (t,
J = 22.3 Hz, 2C), 28.09 (d, J = 21.2 Hz), 27.31 (d, J = 5.0 Hz), 26.26 (t,
J = 3.5 Hz, 2C), 23.87, 23.78, 23.72, 23.68, 22.89, 22.82, 20.65, 20.44
4.3.2. Butyl 5-fluoropentanoate (7)
The reaction was carried out as in the case of 3.3.1 using butyl 5-
hydroxypentanoate 6 (174 mg, 1 mmol) instead of 1-dodecanol.
After the reaction, volatile part was removed under reduced
pressure, and the residue was dissolved in a mixture of FC-77
(10 mL), HFE-7100 (10 mL), and CH3CN (containing 5% H2O)
(10 mL). The separated CH3CN phase was concentrated under
reduced pressure to gave pure 7 (127 mg) in 72% yield. GC analysis
showed that the fluorous phase contained 2b, 7, and 5-
butoxycarbonylbutyl 3,5-bis(1H,1H,2H,2H-perfluorodecyl)benzo-
ate 9 in a ratio of 95:3:2.
(d, J = 3.5 Hz) [13]. 19F NMR
d
ꢀ81.34 (t, J = 9.7 Hz, 6F), ꢀ115.11
(quint, J = 15.3 Hz, 4F), ꢀ122.25 (s, 4F), ꢀ122.49 (s, 8F), ꢀ123.29 (s,
4F), ꢀ123.98 (s, 4F), ꢀ126.69 (s, 4F), ꢀ193.23 to ꢀ193.62 (m, 1F).
HRMS (ESI): calcd. for C39H33O2F35Na ((M+Na)+): 1221.1819,
found: 1221.1820.
4.4.4. (1R,2S)-2-Fluoro-1,2-diphenylethanol (13)
A mixture of 1b (1.337 g, 1.2 mmol) and (1R,2R)-1,2-diphenyl-
1,2-ethandiol (107 mg, 0.5 mmol) was stirred at 140 8C for 1 h. The
reaction mixture was cooled to room temperature and 5% aq NaOH
(20 mL) was added. The mixture was stirred for 30 min and HFE-
7100 (20 mL) was added. The separated aqueous layer was
extracted with HFE-7100 (10 mL ꢁ 2). The combined HFE-7100
layer was dried over MgSO4 and concentrated under reduced
pressure. The residue was dissolved in toluene (15 mL) with
butanol (1.113 g, 15 mmol) and ClSnBu2OSnBu2Cl (553 mg,
1 mmol), and the mixture was stirred under reflux for 8 days.
The mixture was cooled to 0 8C and solid part was removed by
filtration. The filtrate was concentrated under reduced pressure
and the residue was dissolved in a mixture of FC-77 (20 mL), HFE-
7100 (20 mL), and CH3CN (5% of H2O) (20 mL). The separated
CH3CN layer was washed with a mixture of FC-77 (20 mL) and HFE-
7100 (20 mL), once, and concentrated under reduced pressure to
give 13 (60 mg) in 55% yield. 19F NMR analysis of the fluorous layer
showed the formation of amide 2b (60%) and 8 (38%); 13; white
Butyl 5-fluoropentanoate
1172 cmꢀ1 1H NMR
4.46 (dt, J = 47.6, 5.6 Hz, 2H), 4.08 (t,
J = 6.6 Hz, 2H), 2.36 (t, J = 6.3 Hz, 2H), 1.80–1.71 (m, 4H), 1.65–1.56
(m, 2H), 1.43–1.33 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H). 13C NMR
13.58,
7 [3b], IR (neat): 2962, 1736,
.
d
d
19.04, 20.77 (d, J = 5.0 Hz), 29.69 (d, J = 19.9 Hz), 30.58, 33.64,
64.14, 83.47 (d, J = 165.4 Hz), 173.25. 19F NMR
ꢀ219.66 (m, 1F).
d
ꢀ219.25 to
4.4. Fluorination of diols
4.4.1. 2-Fluoroethyl 3,5-bis(1H,1H,2H,2H-perfluorodecyl)benzoate
(10)
Ethylene glycol (62 mg, 1 mmol) and 1b (2.674 g, 2.4 mmol)
were introduced into a reaction vessel made of TeflonTM PFA with a
tight screw cap and the mixture was stirred at 95 8C for 1 h. The
reaction mixture was poured into aqueous 5% NaOH (20 mL) and
separated aqueous layer was extracted with CH2Cl2 (20 mL ꢁ 3).
The combined organic layer was dried over MgSO4 and concen-
trated uder reduced pressure. Purification by column chromato-
graphy (silica gel/CH2Cl2–Et2O) gave 10 (890 mg) in 84% yield.
solid; mp 98 8C (lit. [14] 99 8C). ½a D22:1
ꢂ
¼ þ19:7 (c = 1.00, MeOH). IR
(KBr): 3578, 3033, 2880, 1452, 1050, 965, 706 cmꢀ1
.
1H NMR
d
7.19–7.39 (m, 10H), 5.52 (dd, J = 45.8, 5.6 Hz, 1H), 5.01 (ddd,
J = 12.1, 5.5, 4.0 Hz, 1H), 2.11 (d, J = 3.9 Hz 1H). 13C NMR
138.82
d
White solid; mp 62.5–63 8C. IR (KBr): 1725, 1454, 1203 cmꢀ1
NMR 7.82 (s, 2H), 7.30 (s, 1H), 4.76 (dt, J = 47.4, 3.7 Hz, 2H), 4.76
(dt, J = 28.8, 4.2 Hz, 2H), 2.94–3.02 (m, 4H), 2.31–2.48 (m, 4H). 13
NMR 165.94, 140.22 (2C), 133.34, 130.78, 128.03 (2C), 81.35 (d,
J = 170.6 Hz), 64.08 (d, J = 20.2 Hz), 32.73 (t, J = 22.7 Hz, 2C), 26.26
(t, J = 4.1 Hz, 2C) [13]. 19F NMR
.
1H
(d, J = 3.1 Hz), 135.95 (d, J = 19.9 Hz), 128.79 (d, J = 1.7 Hz), 128.25
(2C), 128.19 (2C), 127.00 (2C), 126.98 (2C), 126.78 (d, J = 7.2 Hz),
d
C
96.21 (J = 177.8 Hz), 76.31 (d, J = 27.2 Hz). 19F NMR
J = 45.8, 12.2 Hz, 1F).
d
ꢀ183.83 (dd,
d
d
ꢀ81.34 (t, J = 9.8 Hz, 6F), ꢀ115.10
References
(quint, J = 14.0 Hz, 4F), ꢀ122.25 (s, 4F), ꢀ122.50 (s, 8F), ꢀ123.30 (s,
4F), ꢀ123.99 (s, 4F), ꢀ126.70 (s, 4F), ꢀ225.03 (tt, J = 47.6, 28.7 Hz,
1F). HRMS (ESI): calcd. for C29H16O2F35 (M++H): 1061.0592, found:
1061.0609.
[1] (a) D.A. Curran, Angew. Chem. Int. Ed. 37 (1998) 1174–1196;
(b) A.P. Dobbs, M.R. Kimberley, J. Fluorine Chem. 118 (2002) 3–17;
(c) W. Zhang, Chem. Rev. 104 (2004) 253–25561;
(d) D.A. Curran, I.T. Horva´th, in: J.A. Gladysz (Ed.), Handbook of Fluorous Chem-
istry, Wiley-VCH, Weinheim, 2004.
[2] (a) C.-L.J. Wang, Fluorination by sulfur tetrafluoride, Organic Reactions, vol. 34,
Willey, New York, 1985, pp. 319–412;
4.4.2. (1R,2S)-2-Fluoro-1,2-diphenylethyl 3,5-bis(1H,1H,2H,2H-
perfluorodecyl)benzoate (11)
(b) M. Hudlicky, Fluorination with diethylaminosulfur trifluoride and related
aminofulorosulfuranes, Organic Reactions, vol. 35, Willey, New York, 1988, pp.
513–637;
White solid; mp 81–82 8C, ½a D21
ꢂ
¼ þ23:1 (c = 1.00, CHCl3). IR
(KBr): 1712, 1456, 1148 cmꢀ1 1H NMR
. d 7.88 (s, 2H), 7.15–7.35
(c) R.P. Singh, J.M. Shreeve, Synthesis (2002) 2561–2578.
[3] (a) S. Kobayashi, A. Yoneda, T. Fukuhara, S. Hara, Tetrahedron Lett. 45 (2004)
1287–1289;
(m, 11H), 6.29 (dd, J = 17.6, 4.0 Hz, 1H), 5.86 (dd, J = 46.2, 4.1 Hz,
1H), 2.90–3.01 (m, 4H), 2.29–2.39 (m, 4H). 13C NMR
164.86,
d
(b) S. Kobayashi, A. Yoneda, T. Fukuhara, S. Hara, Tetrahedron 60 (2004) 6923–
6930.
140.24 (2C), 135.41 (d, J = 20.2 Hz), 134.75 (d, J = 3.4 Hz), 133.34,
130.96, 128.85, 128.68, 128.24 (2C), 128.03 (2C), 128.00 (2C),
127.73 (2C), 126.55 (d, J = 7.3 Hz, 2C), 122.00–108.00 (complex
signals of CF3 and CF2), 94.51 (d, J = 180.3 Hz), 77.99 (d,
J = 25.7 Hz), 32.70 (t, J = 22.1 Hz, 2C), 26.26 (t, J = 3.9 Hz, 2C). 19F
[4] T. Furuya, T. Fukuhara, S. Hara, J. Fluorine Chem. 126 (2005) 721–725.
[5] A. Yoneda, T. Fukuhara, S. Hara, Chem. Commun. (2005) 3589–3590.
[6] T. Nomoto, T. Fukuhara, S. Hara, Synlett (2006) 1744–1746.
[7] H.-W. Yu, Y. Nakano, T. Fukuhara, S. Hara, J. Fluorine Chem. 126 (2005) 962–966.
[8] A. Endres, G. Maas, Tetrahedron 58 (2002) 3999–4005.
[9] (a) S. Darses, M. Pucheault, J.-P. Geneˆt, Eur. J. Org. Chem. (2001) 1121–1128;
(b) W. Chen, L. Xu, J. Xiao, Tetrahedron Lett. 42 (2001) 4257–4278.
NMR
d
ꢀ81.33 (t, J = 9.8 Hz, 6F), ꢀ115.06 (quint, J = 14.0 Hz, 4F),
ꢀ122.23 (s, 4F), ꢀ122.48 (s, 8F), ꢀ123.29 (s, 4F), ꢀ123.97 (s, 4F),

T. Furuya et al. / Journal of Fluorine Chemistry 130 (2009) 348–353
353
[10] T. Fukuhara, C. Hasegawa, S. Hara, Synthesis (2007) 1528–1534.
[11] From partition data in Table 2, contamination of fluorododecane in the fluorous
phase is not acceptable. In order to remove 2b from the organic phase completely
and to obtain the pure product, the separated organic phase was washed with
fluorous solvent again, and that extra operation must cause the contamination of
fluorododecane in fluorous phase.
[12] (a) J. Otera, T. Yano, A. Kawabata, H. Nozaki, Tetrahedron Lett. 27 (1986) 2383–
2389;
(b) A. Orita, K. Sakamoto, Y. Hamada, A. Mitsutome, J. Otera, Tetrahedron 55
(1999) 2899–2910.
[13] Signals due to carbons of the fluorocarbon chains were too weak to be assigned.
[14] S. Rozen, O. Lerman, J. Org. Chem. 45 (1980) 672–678.