Facile nucleophilic fluorination by synergistic effect between polymer-supported ionic liquid catalyst and tert-alcohol reaction media system

Article abstract of DOI:10.1016/j.tet.2008.02.094

A highly efficient method was developed for nucleophilic fluorination using an alkali metal fluoride through the synergistic effect of the polymer-supported ionic liquid (PSIL) as a catalyst and tert-alcohol as an alternative reaction media. This PSIL/tert-alcohol system not only enhances the reactivity of alkali metal fluorides and reduces the formation of by-products but also allows the use of a polymer-supported catalyst protocol. As an example, the nucleophilic fluorinations of the model compound, 2-(3-bromopropoxy)naphthalene, with CsF using only tert-amyl alcohol as solvent (for 2 h reaction time), 0.5 equiv of PS[hmim][BF₄] in CH₃CN (for 12 h reaction time), and 0.5 equiv of PS[hmim][BF₄] in tert-amyl alcohol (which is a PSIL/tert-alcohol system for the synergistic effect; for 2 h reaction time) provided 18, 40, and 84% yield, respectively. The characteristics of the nucleophilic fluorination reactions of some halo- and alkanesulfonyloxyalkane systems to the corresponding fluoroalkanes using various alkali metal fluorides are also reported.

Full text of DOI:10.1016/j.tet.2008.02.094

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 4209e4214
www.elsevier.com/locate/tet
Facile nucleophilic fluorination by synergistic effect between
polymer-supported ionic liquid catalyst and tert-alcohol
reaction media system
a,*
a
Dong Wook Kim , Hwan-Jeong Jeong , Seok Tae Lim ,
a
a
b,
Myung-Hee Sohn , Dae Yoon Chi *
a
Department of Nuclear Medicine, Research Institute of Clinical Medicine, Chonbuk National University School of Medicine,
Jeonju, Jeonbuk 561-712, Republic of Korea
b
Department of Chemistry, Inha University, 253 Yonghyundong Namgu, Inchon 402-751, Republic of Korea
Received 30 January 2008; received in revised form 27 February 2008; accepted 27 February 2008
Available online 4 March 2008
Abstract
A highly efficient method was developed for nucleophilic fluorination using an alkali metal fluoride through the synergistic effect of the
polymer-supported ionic liquid (PSIL) as a catalyst and tert-alcohol as an alternative reaction media. This PSIL/tert-alcohol system not only
enhances the reactivity of alkali metal fluorides and reduces the formation of by-products but also allows the use of a polymer-supported catalyst
protocol. As an example, the nucleophilic fluorinations of the model compound, 2-(3-bromopropoxy)naphthalene, with CsF using only tert-amyl
alcohol as solvent (for 2 h reaction time), 0.5 equiv of PS[hmim][BF ] in CH CN (for 12 h reaction time), and 0.5 equiv of PS[hmim][BF ] in
4
3
4
tert-amyl alcohol (which is a PSIL/tert-alcohol system for the synergistic effect; for 2 h reaction time) provided 18, 40, and 84% yield,
respectively. The characteristics of the nucleophilic fluorination reactions of some halo- and alkanesulfonyloxyalkane systems to the correspond-
ing fluoroalkanes using various alkali metal fluorides are also reported.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: tert-Alcohol; Ionic liquid; Polymer-supported ionic liquid; Nucleophilic substitution; Fluorination; Alkali metal fluoride
1
proceed and leads to the development of a number of phase-
,3
1
. Introduction
4
transfer protocols, such as crown ether derivatives and quater-
5
nary ammonium fluorides over the past several decades to
Nucleophilic fluorination using alkali metal fluorides, which
are traditional fluoride sources, is an important synthetic trans-
1
formation because low fluorinated compounds play a crucial
role in the life sciences including molecular imaging area using
1
[
tomography (PET). However, the limited solubility and low
nucleophilicity of alkali metal fluorides in organic solvents gen-
erally require vigorous reaction conditions for this reaction to
overcome the drawbacks of the low solubility and nucleophilic-
ity of the alkali metal fluorides in polar aprotic media such as
acetonitrile and dimethylformamide (DMF), which are gener-
ally known to be good solvents for nucleophilic displacement
8
F]-labeled radiopharmaceuticals for positron emission
2
3
reactions including fluorination. However, despite their good
solubility and reactivity, ‘naked’ fluoride generated from these
phase-transfer protocols can cause elimination and hydroxyl-
ation reactions as side reactions on account of their strong basic-
5
,6
ity in the fluorination.
Although the immobilization of catalysts or reagents on
polymeric supports is an attractive protocol for both chemical
processes and eco-friendly alternatives on account of their
easy handling, easy recycling, and unique microenvironment,
*
Corresponding authors. Tel.: þ82 63 250 2396; fax: þ82 63 255 1172
(
D.W.K.); tel.: þ82 32 860 7686; fax: þ82 32 867 5604 (D.Y.C.).
E-mail addresses: kimdw@chonbuk.ac.kr (D.W. Kim), dychi@inha.ac.kr
D.Y. Chi).
(
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.02.094

4210
D.W. Kim et al. / Tetrahedron 64 (2008) 4209e4214
polymeric supported phase-transfer catalysts have relatively
low reactivity compared with the corresponding non-immobi-
liquid portion/g) in tert-amyl alcohol. Although fluorination
was carried out using a 0.5 equiv of PS[hmim][BF ] in aceto-
nitrile for 12 h at 80 C, 9% of the starting mesylate still
remained unreacted (entry 1). However, the same reaction
in tert-amyl alcohol was complete within 1 h, affording 2-
(3-fluoropropoxy)-naphthalene (2a) in very high yield (96%,
entry 2). Moreover, in entry 3, the use of only 0.25 equiv of
4
7
ꢀ
lized catalysts.
It was found that ionic liquid containing imidazolium and
8
their counter anions as alternative reaction media can enhance
the reactivity of alkali metal fluorides in the nucleophilic
9
fluorination remarkably. In particular, polystyrene-based
polymer-supported ionic liquids (PSILs) have shown still
highly efficient catalytic activity in the nucleophilic fluorina-
tion using cesium fluoride in polar aprotic solvents affording
many practical qualities such as the ease of purification, han-
dling, and recovery. Recently, we found that tertiary alco-
hols, as non-polar protic reaction media, play an important
role in the nucleophilic fluorination of alkane sulfonyl
substrates, such as alkyl mesylate using alkali metal fluorides
PS[hmim][BF ] accelerated the fluorination reaction rate to
4
afford the fluoroalkane 2a (96%) and suppressed the alkoxyl-
ation by tert-amyl alcohol solvent as a side reaction (only 2%
of ether 2b was detected by NMR) compared with the same
reaction in absence of any PSILs (entry 4) in tert-amyl alco-
hol. Entry 5 shows that an alternative PSIL, PS[hmim][OTf],
with a different anion has slightly lower catalytic activity in
1
0
providing product 2a (95%) than PS[hmim][BF ]. A compar-
4
(
particularly CsF), thereby enhancing the reactivity of alkali
metal fluorides and suppressing the formation of by-products
such as alkenes or alcohols) compared with conventional
ison of Table 1 entries 6 and 7 shows that the use of PSIL with
tert-alcohol reaction media significantly enhanced the reactiv-
ity of RbF due to the stronger ionic bond than CsF, and also
reduced ether formation reaction as a side reaction compared
with the same reaction in the absence of PSILs. In particular,
in the absence of PSIL, the fluorination reaction using KF,
which is an economical and traditional fluoride source but
has low reactivity, barely proceeded in tert-alcohol, providing
only trace amounts of the fluoroalkane 2a together with 7% of
the ether by-product 2b (entry 9). However, the fluorination
reaction in the presence of PSIL (0.5 equiv) with KF in tert-
alcohol was completed within 7 h, and produced the fluoroal-
kane 2a in good yield (91%, entry 8). In order to examine the
(
methods using polar aprotic solvents including the PSIL
system. However, this tert-alcohol reaction media system is
inefficient in the case of using the metal fluoride, which forms
a tight ion pair such as KF, and the use of a substrate with a
1
1
halide-leaving group, such as alkyl bromides and iodides.
This paper reports the synergistic effect of PSIL as a catalyst
and tert-alcohol as a non-polar protic solvent for nucleophilic
fluorination using alkali metal fluorides. This PSIL/tert-alcohol
system not only significantly enhances the reactivity of metal
fluorides and suppresses the formation of by-products but also
employs many practical merits of the polymer-supported cata-
lyst protocol itself (easy purification, recycle, and reuse) com-
pared with the conventional method including the use of
a tert-alcohol solvent or PSIL system only.
possibility of the reuse of PS[hmim][BF ], the fluorination was
4
carried out repeatedly under conditions given in entry 10 in
Table 1. PS[hmim][BF ] can be reused repeatedly (10 times)
4
without any loss of its catalytic activity; in each cycle, the
fluoro-product 2a was obtained in high yield (96e92%). In
entries 11 and 12, the use of conventional phase-transfer cata-
2
. Results and discussion
lyst and solvent (such as 18-crown-6 and CH CN) did not
3
show good performance in the fluorination when compared
with the use of PSIL/tert-alcohol system.
PSILs PS[hmim][X] (PS¼polymer support; hmim¼1-n-
hexyl-3-methylimidazolium cation; X¼BF , OTf) were used
Table 2 shows further characteristics of this fluorination
reaction with various halides or sulfonate substrates using
3 equivofCsF. Inentry1, thefluorinationof2-(3-bromopropoxy)-
naphthalene proceeded slowly in the tert-amyl alcohol solvent
system (Method A), converting only 18% of the starting bro-
4
as catalysts considering their catalytic activity and easy
production, and tert-amyl alcohol was used as the reaction
solvent considering its efficiency, boiling point, and cost, as
1
0,11
shown Figure 1.
ꢀ
Table 1 shows the nucleophilic fluorination reaction of
a model compound, 2-(3-methanesulfonyloxypropoxy)-naph-
thalene (1), with various alkali metal fluorides such as CsF,
mide to the corresponding fluoride 2a in 2 h at 90 C because
of no formation of H-bonds between the bromide leaving group
and tert-alcohol solvent, which do not accelerate the fluorination
1
reaction rate perfectly in the tert-alcohol system. In addition,
1
RbF, or KF in the presence of PS[hmim][BF ] (2.2 mmol ionic
4
liquid portion per gram) or PS[hmim][OTf] (2.1 mmol ionic
the same reaction with 0.5 equiv of PS[hmim][BF ] in CH CN
4
3
instead of tert-amyl alcohol (entry 2, Method B) after extended
reaction times (12 h) provided the fluoro-product in relatively
low yield (40%) due to the formation of the alkene by-product
(52%). These results should be compared with the fluorination
reaction using the PSIL/tert-alcohol system presumably due to
the synergistic effect (entry 3, Method C), which proceeded
quite selectively to completion within 2 h, providing the fluo-
rine-substituted product in high yield (84%), with a relatively
small amount of the alkene by-product (11%). Furthermore,
while the fluorination of 2-(3-chloropropyl)naphthalene to the
A
6'
1'
2
B
O
N
N
-
4
[X]
OH
5
4
X = BF4: PS[hmim][BF4]
X = OTf: PS[hmim][OTf]
tert-amyl alcohol
4
Figure 1. (A) Polymer-supported ionic liquids PS[hmim][BF ] and PS[hmi-
m][OTf]; hmim¼1-n-hexyl-3-methylimidazolium cation; PS¼polymer sup-
port. (B) Structure of tert-amyl alcohol.

D.W. Kim et al. / Tetrahedron 64 (2008) 4209e4214
4211
Table 1
a
4
Fluorinations of mesylate 1 with MF using PS[hmim][BF ] in tert-amyl alcohol
O
OMs
O
F
3
eq. MF
PS[hmim][BF4],
t-amylalcohol
+
ether 2b
1
2a
b
] mg (equiv )
ꢀ
c
Entry
PS[hmim][BF
4
MF
Temp ( C)
Time (h)
Yield of product (%)
d
1
2a
2b
d
1
2
3
4
5
6
227 (0.5) in CH
227 (0.5)
114 (0.25)
d
3
CN
CsF
CsF
CsF
CsF
CsF
RbF
RbF
80
80
12
1
9
89
96
96
93
95
97
76
91
d
e
d
d
d
d
d
13
d
90
d
91
53
2
e
80
80
1.5
6
2
e
5
e
3
PS[hmim][OTf] (0.5)
227 (0.5)
d
80
90
2.5
1.5
24
7
e
2
f
7
90
9
g
e
8
227 (0.5)
d
454 (1.0)
KF
100
100
80
4
f
g
e
9
KF
24
1
Trace
96
7
h
e
1
1
1
0
1
2
a
b
c
d
e
f
CsF
CsF
2
i
j
d in CH
3
CN
18-crown-6 (2.0) in CH
100
100
2
24
Trace
40
d
d
g
KF
3
CN
All reactions were carried out on a 1.0 mmol reaction scale of mesylate 1 using 3 mmol of CsF in 4.0 mL of solvent.
Tells the mole of ionic liquid portion, not PS[hmim][BF
Isolated yield.
4
].
2
-[3-(2-Methyl-2-butoxy)propoxy]naphthalene was obtained.
Determined by NMR spectroscopy.
Ref. 11.
g
h
i
KF of 5 equiv was used.
This PSIL was reused repeatedly.
Ref. 10a.
j
Ref. 9a.
Table 2
Fluorination of various alkyl halides and mesylates using CsF in the presence of PS[hmim][BF
a
4
] in tert-amyl alcohol
b
ꢀ
c
Yield (%)
Entry
Compound
Method
Temp ( C)
Time (h)
Comment
d
d
1
2
3
A
B
C
90
90
90
2
12
2
18
81% SM
52% Alkene
11% Alkene
O
Br
40
84
4
5
Cl
A
C
100
100
24
24
Trace
92
90% SM
Trace alkene
OMs
6
7
B
90
90
12
1
24
87
73% Alkene
9% Alkene
e
C
Br
8
9
C
C
80
80
0.5
1
96
97
N
N
O
OTs
O2N
OTf
O
O
1
0
C
80
0.5
93
O
O
a
All the reactions were carried out on a 1.0 mmol scale of substrate with 3.0 equiv of CsF, and an ether compound was detected in the all reaction using Method
C in approximately 2% yield.
b
4 3 4
Method A: in tert-amyl alcohol, B: with 0.5 equiv of PS[hmim][BF ] in CH CN, C: with 0.5 equiv of PS[hmim][BF ] in tert-amyl alcohol.
c
Isolated yield.
Yield determined by NMR.
d
e
4
0.25 equiv of PS[hmim][BF ] was used.

4212
D.W. Kim et al. / Tetrahedron 64 (2008) 4209e4214
corresponding fluoroalkane in tert-amyl alcohol (entry 4,
Method A) barely proceeded, the same reaction in the presence
of PSIL (Method C) proceeded smoothly within 24 h to afford
the fluoro-product in very high yield (entry 5). This suggests
that this PSIL/tert-alcohol protocol can be quite an attractive
method for the transformation of halides to fluorides. The
introduction of fluoride to alkanesulfonylethyl aromatic com-
pounds using phase-transfer protocol including PSIL was
difficult because elimination mainly occurs to give vinylic
aromatic systems. However, a comparison of entries 6 and 7
4. Experimental section
4.1. General
Unless otherwise noted all reagent and solvents were com-
mercially available. Reaction progress was followed by TLC
on 0.25 mm silica gel glass plates containing F-254 indicator.
Visualization on TLC was monitored by UV light. Flash chro-
1
matography was performed with 230e400 mesh silica gel. H
1
and C NMR spectra were recorded on a 400 or 600 MHz spec-
3
shows that the use of 0.25 equiv of PS[hmim][BF ] in a tert-
trometer, and chemical shifts were reported in d units (ppm)
4
1
3
19
alcohol solvent allowed the fluorination of 1-(2-mesyoxy-
ethyl)naphthalene to 1-(2-fluoroethyl)naphthalene to proceed
much faster with greater selectivity (Method C; 87% yield
with only 9% of elimination product in 1 h reaction time) than
relative to tetramethylsilane. Solid state C, and F NMR spec-
tra were also recorded on 600 MHz spectrometer at rt. Low-
and high-resolution electron impact (EI, 70 eV) spectra were
obtained. The preparation of PSILs, PS[hmim][BF ], and
4
with the use of PSIL in CH CN (Method B; only 24% yield
3
PS[hmim][BF ], as a catalyst was performed as described in
4
the literature, and the identity was confirmed by comparison
of NMR data.
1
0
with 73% elimination product after 12 h reaction time). A ben-
zylic fluoride was obtained in good yield through the fluorina-
tion of the corresponding bromide using PSIL in tert-amyl
alcohol (entry 8). Entries 9 and 10 show the fluorination of the
substrate containing many heteroatoms, which can only be
extracted from ionic liquids with great difficulty due to its
high solubility in liquid salts. The fluorination reaction of
4.2. Typical procedure in Table 1
CsF (454 mg, 3 mmol) was added to the mixture of mesylate
1 (280 mg, 1.0 mmol) and PS[hmim][BF ] (227 mg, 0.5 mmol)
4
1
4
-(3-tosyloxypropyl)-4-nitroimidazole to 1-(3-fluoropropyl)-
-nitroimidazole with PSIL in tert-amyl alcohol not only pro-
in tert-amyl alcohol (4.0 mL). The mixturewas stirred over 1.0 h
ꢀ
at 80 C. The reaction mixture was filtered and the flash column
ceeded in 97% yield but also allowed the fluoro-product to be
isolated and purified easily. As a final example, a fluorosugar
was also produced in high yield within 30 min through the
fluorination of the corresponding sugar triflate under the same
reaction conditions (entry 10).
chromatography (5% EtOAc/hexanes) of the filtrate afforded
196 mg (96%) of 2-(3-fluoropropoxy)naphthalene (2a) as a
colorless oil with trace amount of ether by-product, 2-[3-
(2-methyl-2-butoxy)propoxy]naphthalene (2b).
4
.2.1. 2-(3-Fluoropropoxy)naphthalene (2a)
1
H NMR (400 MHz, CDCl ) d 2.14e2.39 (m, 2H), 4.24
3
3
. Conclusion
(t, J¼6.2 Hz, 2H), 4.72 (dt, J¼46.8, 5.8 Hz, 2H), 7.16e7.22
1
m, 2H), 7.34e7.53 (m, 2H), 7.76e7.83 (m, 3H); C NMR
3
(
(100 MHz, CDCl3)
In summary, a highly efficient method was developed for
d
30.4 (d, J¼20.1 Hz), 63.6 (d,
the nucleophilic fluorination of some halo- and alkanesulfonyl-
oxyalkane systems to the corresponding fluoroalkanes using al-
kali metal fluoride by the synergistic effect between PSIL and
a tert-alcohol solvent. This PSIL/tert-alcohol system could (i)
significantly enhance the reactivity of the alkali metal
fluoride forming tight ion pairs such as potassium fluoride;
J¼5.3 Hz), 80.8 (d, J¼163.9 Hz), 106.8, 118.8, 123.6, 126.4,
126.7, 127.6, 129.1, 129.4, 134.6, 156.7; MS (EI) m/z 204
(M ); HRMS (EI) m/z calcd for C H FO (M ) 204.0950,
þ
þ
1
3 13
found 204.0932. Registry no. provided by the author:
398-53-8.
(
ii) remarkably enhance the reactivity of the halide leaving
4.2.2. 2-[3-(2-Methyl-2-butoxy)propoxy]naphthalene (2b)
1
group, consequently, accelerating the fluorination reaction
rate of the alkyl halide; and (iii) afford highly chemoselective
fluorination, thereby reducing the formation of elimination,
hydroxylation, and alkoxylation by-products compared with
the use of PSIL in polar aprotic solvents or a tert-alcohol
solvent without PSIL. Furthermore, because PSIL itself still
provides a number of practical uses such as the simple
purification of the product, easy reuse, and recovery of cat-
alyst in the reaction, this PSIL/tert-alcohol system might be
useful in various industrial chemical processes. Further stud-
ies on the applications of this PSIL/tert-alcohol system to
other reactions such as the rapid labeling of radiopharma-
ceuticals for molecular imaging with the short-lived,
positron-emitting radionuclide fluorine-18 are currently
underway.
H NMR (400 MHz, CDCl ) d 0.86 (t, J¼7.4 Hz, 3H), 1.14
3
(s, 6H), 1.51 (q, J¼7.5 Hz, 2H), 2.03e2.10 (m, 2H), 3.54 (t,
J¼6.2 Hz, 2H), 4.19 (t, J¼6.2 Hz, 2H), 7.14e7.16 (m, 2H),
1
3
7.30e7.45 (m, 2H), 7.72e7.77 (m, 3H);
(100 MHz, CDCl ) d 8.24, 25.03, 30.34, 32.67, 57.43, 64.96,
C NMR
3
74.73, 106.62, 118.98, 123.43, 126.24, 126.71, 127.60,
þ
128.87, 129.25, 134.61, 157.06; MS (EI) m/z 272 (M ), 185,
þ
144 (100); HRMS (EI) m/z calcd for C H O (M )
1
8 24 2
272.1776, found 272.1774.
4.2.3. 2-(3-Methanesulfonyloxypropoxy)naphthalene (1) as
a starting material in Table 1
1
H NMR (200 MHz, CDCl ) d 2.24e2.36 (m, 2H), 3.00 (s,
3
3H), 4.22 (t, J¼5.9 Hz, 2H), 4.50 (t, J¼6.1 Hz, 2H),
7.10e7.15 (m, 2H), 7.31e7.49 (m, 2H), 7.71e7.79 (m, 3H);

D.W. Kim et al. / Tetrahedron 64 (2008) 4209e4214
4213
1
3
þ
C NMR (100 MHz, CDCl ) d 29.0, 37.1, 63.0, 66.8, 106.5,
3
C H F (M ) 188.1001, found 188.1001. Registry no. pro-
13 13
1
18.6, 123.8, 126.4, 126.7, 127.6, 129.0, 129.5, 134.4, 156.3;
þ
þ
vided by the author: 561009-56-1.
MS (EI) m/z 280 (M ); HRMS (EI) m/z calcd for C H O S
(M ) 280.0769, found 280.0770. Registry no. provided by the
author: 463934-08-9.
1
4 16 4
4
.4.2. 1-(2-Fluoroethyl)naphthalene
1
H NMR (600 MHz, CDCl ) d 3.49 (dt, J¼13.7, 6.9 Hz, 2H),
3
4
.75 (dt, J¼47.4, 6.9 Hz, 2H), 7.37e7.54 (m, 4H), 7.75e8.02
4
4
.3. Starting material for Table 2
13
(
8
1
m, 3H); C NMR (150 MHz, CDCl ) d 33.8 (d, J¼20.1 Hz),
3
3.5 (d, J¼168.0 Hz), 123.3, 125.5, 125.6, 126.2, 127.1, 127.5,
.3.1. 2-(3-Bromopropoxy)naphthalene
28.9, 132.0, 132.8 (d, J¼8.5 Hz), 133.8; MS (EI) m/z 174
1
H NMR (400 MHz, CDCl ) d 2.36e2.43 (m, 2H), 3.67 (t,
3
þ
(M ), 141 (100). Anal. Calcd: C, 82.73; H, 6.36. Found: C,
J¼6.6 Hz, 2H), 4.23 (t, J¼5.6 Hz, 2H), 7.14e7.17 (m, 2H),
8
2
2.63; H, 6.34. Registry no. provided by the author: 693785-
5-0.
1
.34e7.49 (m, 2H), 7.74e7.80 (m, 3H); C NMR (100 MHz,
3
7
CDCl ) d 30.1, 32.2, 65.2, 106.6, 118.8, 123.7, 126.4, 126.7,
3
þ
1
27.6, 128.9, 129.4, 134.4, 156.5; MS (EI) m/z 264 (M ), 266
þ
79
þ
(M ); HRMS (EI) m/z calcd for C H O Br (M ) 264.0150,
found 264.0151. Registry no. provided by the author: 3245-62-3.
4.4.3. 1-Vinylnaphthalene
Compound 7 (14 mg, 9%) as a by-product in the above re-
1
action was obtained as a colorless oil. H NMR (600 MHz,
1
3 13
CDCl ) d 5.47 (dd, J¼10.7, 1.7 Hz, 1H), 5.79 (dd, J¼17.5,
4
.3.2. 2-(3-Chloropropyl)naphthalene
3
1
8
.8 Hz, 1H), 7.43e7.52 (m, 4H), 7.61e7.62 (m, 1H), 7.77e
H NMR (400 MHz, CDCl ) d 2.16e2.23 (m, 2H), 2.97 (t,
3
1
.85 (m, 2H), 8.10e8.12 (m, 1H); C NMR (150 MHz,
3
7
CDCl ) d 117.1, 123.6, 123.7, 125.6, 125.7, 126.0, 128.1,
J¼7.4 Hz, 2H), 3.58 (t, J¼6.4 Hz, 2H), 7.35e7.37 (m, 1H),
1
3
7
.44e7.51 (m, 2H), 7.67 (s, 1H), 7.80e7.85 (m, 3H);
NMR (100 MHz, CDCl ) d 32.8, 33.8, 44.2, 125.3, 126.0,
C
3
þ
þ
1
1
1
28.5, 131.1, 133.6, 134.4, 135.6; MS (EI) m/z 154 (M ),
53 (100), 76; HRMS (EI) m/z calcd for C H (M )
3
1
26.7, 127.1, 127.4, 127.6, 128.1, 132.1, 133.5, 138.1; MS
þ
12 10
54.0783, found 154.0784. Registry no. provided by the
(EI) m/z 204 (M ), 141 (100), 115. HRMS (EI) m/z calcd
for C H Cl (M ) 204.0706, found 204.0702. Registry no.
þ
author: 826e74-4.
1
3 13
provided by the author: 27650-58-4.
4
.4.4. 2-Fluoromethylnaphthalene
1
4
.3.3. 1-(2-Methanesulfonylethyl)naphthalene
H NMR (200 MHz, CDCl ) d 5.57 (d, J¼47.6 Hz, 2H),
3
1
1
7.50e7.58 (m, 3H), 7.87e7.93 (m, 4H); C NMR (50 MHz,
3
H NMR (400 MHz, CDCl ) d 2.79 (s, 3H), 3.55 (t,
3
J¼7.2 Hz, 2H), 4.54 (t, J¼7.2 Hz, 2H), 7.40e7.59 (m, 4H),
CDCl ) d 84.7 (d, J¼165.8 Hz), 124.9, 125.0, 126.4, 126.4,
3
1
.79e8.03 (m, 3H); C NMR (100 MHz, CDCl ) d 32.7,
3
7
3
1
3
126.6, 126.7, 127.7, 127.8, 128.0, 128.1, 128.4, 133.1,
133.4, 133.5, 133.8; MS (EI) m/z 160 (M ). Anal. Calcd: C,
þ
7.2, 69.6, 123.0, 125.5, 125.8, 126.5, 127.5, 127.9, 128.9,
þ
31.6, 132.0, 133.8; MS (EI) m/z 250 (M ); HRMS (EI) m/z
82.48; H, 5.66. Found: C, 82.45; H, 5.26. Registry no.
provided by the author: 55831-11-3.
þ
calcd for C H O S (M ) 250.0664, found 250.0700. Regis-
1
3
14
3
try no. provided by the author: 119744-43-3.
4
.4.5. 1-(3-Fluoropropyl)-4-nitroimidazole
4
.3.4. 1-(3-p-Toluenesulfonyloxypropyl)-4-nitroimidazole
1
1
H NMR (400 MHz, CDCl ) d 2.14e2.27 (m, 2H), 4.22 (t,
3
H NMR (400 MHz, CDCl ) d 2.17e2.23 (m, 2H), 2.46 (s,
3
J¼7.0 Hz, 2H), 4.45 (dt, J¼46.8, 5.4 Hz, 2H), 7.47 (d,
3
7
H), 4.02 (t, J¼5.6 Hz, 2H), 4.16 (t, J¼6.8 Hz, 2H),
1
3
1
3
J¼1.2 Hz, 1H), 7.83 (d, J¼1.6 Hz, 1H); C NMR (100 MHz,
.36e7.38 (m, 3H), 7.66 (s, 1H), 7.76 (d, J¼8.4 Hz, 2H);
C
CDCl ) d 31.1 (d, J¼19.7 Hz), 44.3 (d, J¼4.5 Hz), 79.7 (d,
3
NMR (100 MHz, CDCl ) d 21.4, 29.7, 44.1, 66.0, 119.5,
3
1
þ
J¼166.0 Hz), 119.5, 136.2, 148.0; MS (EI) m/z 173 (M ,
27.5, 129.9, 131.7, 136.1, 145.4, 147.7; MS (EI) m/z 325
þ
þ
100), 127, 61. HRMS (EI) m/z calcd for C
H
8
FN
O
(M )
6
3
2
(
(
M ), 324, 91 (100). HRMS (EI) m/z calcd for C H N O S
M ) 325.0732, found 325.0717. Registry no. provided by the
1
3 15 3 5
þ
173.0601, found 173.0633. Registry no. provided by the author:
75831-82-0.
6
author: 675831-81-9.
4
.4. Fluorination product for Table 2
4.5. Polymer-supported ionic liquids (PSIL)
4
.4.1. 2-(3-Fluoropropyl)naphthalene
4.5.1. Polystyrene-supported 1-n-hexyl-3-methylimid-
1
H NMR (400 MHz, CDCl ) d 2.07e2.20 (m, 2H), 2.95 (t,
3
azolium tetrafluoroborate, PS[hmim][BF ]
4
1
3
0
0
J¼7.6 Hz, 2H), 4.52 (dt, J¼47.6, 6.0 Hz, 2H), 7.37e7.39 (m,
C NMR (solid state) d 27e31 (C2 eC5 ), 37 (NeCH ),
3
1
3
0
1
H), 7.45e7.53 (m, 2H), 7.68 (s, 1H), 7.84e7.87 (m, 3H);
C
41 (aliphatic polystyrene skeleton), 50 (C1 ), 72 (O-benzylic
0
NMR (100 MHz, CDCl ) d 31.4 (d, J¼5.4 Hz), 31.9 (d,
carbon and C6 ), 128 (C4, C5, aromatic polystyrene skeleton),
3
1
9
J¼19.7 Hz), 83.0 (d, J¼163.7 Hz), 125.3, 126.0, 126.6,
137 (C2), 146 (aromatic polystyrene skeleton); F NMR
(solid state) d ꢁ148. Anal. N, 6.2 (2.2 mmol ionic liquid
portion/g); Cl, 0.1.
1
1
27.2, 127.4, 127.6, 128.0, 132.0, 133.6, 138.5; MS (EI) m/z
88 (M ), 141 (100), 115. HRMS (EI) m/z calcd for
þ

4214
D.W. Kim et al. / Tetrahedron 64 (2008) 4209e4214
4
.5.2. Polystyrene-supported 1-n-hexyl-3-methylimid-
4. (a) Gokel, G. W. Crown Ethers and Cryptands; Royal Society of
Chemistry: Cambridge, 1991; (b) Pedersen, C. J. J. Am. Chem. Soc.
1967, 89, 7017e7036.
azolium triflate, PS[hmim][OTf]
1
3
0
0
C NMR (solid state) d 27e31 (C2 eC5 ), 37 (NeCH ),
3
5
. (a) Dehmlow, E. V.; Dehmlow, S. S. Phase Transfer Catalysis, 3rd ed.;
VCH: New York, NY, 1993; (b) Dehmlow, E. V. Angew. Chem., Int. Ed.
Engl. 1977, 16, 493e505; (c) Cox, D. P.; Terpinski, J.; Lawrynowicz,
W. J. Org. Chem. 1984, 49, 3216e3219; (d) Sun, H.; DiMagno, S. G.
J. Am. Chem. Soc. 2005, 127, 2050e2051; (e) Sun, H.; DiMagno, S. G.
Angew. Chem., Int. Ed. 2006, 45, 2720e2725.
0
4
carbon and C6 ), 129 (C4, C5, aromatic polystyrene skeleton),
1
(solid state) d ꢁ77. Anal. N, 5.8 (2.1 mmol ionic liquid por-
tion/g); Cl, <0.2.
1 (aliphatic polystyrene skeleton), 52 (C1 ), 72 (O-benzylic
0
1
38 (C2), 147 (aromatic polystyrene skeleton); F NMR
9
6
7
. Pilcher, A. S.; Ammon, H. L.; DeShong, P. J. Am. Chem. Soc. 1995, 117,
5
166e5167.
. (a) Cinquini, M.; Colonna, S.; Molinari, H.; Montanari, F.; Tundo, P.
J. Chem. Soc., Chem. Commun. 1976, 394e396; (b) Molinari, H.;
Montanari, F.; Tundo, P. J. Chem. Soc., Chem. Commun. 1977,
Acknowledgements
This work was supported by the fund of Chonbuk National
University Hospital Research Institute of Clinical Medicine (to
D.W.K.), grant from the Atomic Energy Technology and
Development Program of KOSEF (2008-00285 to D.W.K),
and KOSEF grant funded by the Korea government (MOST,
6
39e641; (c) Regen, S. L.; Lee, D. P. J. Am. Chem. Soc. 1974, 96,
294e296; (d) Regen, S. L. J. Am. Chem. Soc. 1975, 97, 5956e5957.
. For recent reviews on ionic liquids, see: (a) Zhao, H.; Malhotra, S. V.
Aldrichimica Acta 2002, 35, 75e83; (b) Sheldon, R. Chem. Commun.
8
9
2
001, 2399e2407; (c) Wasserscheid, P.; Kein, W. Angew. Chem., Int.
Ed. 2000, 39, 3772e3789; (d) Welton, T. Chem. Rev. 1999, 99,
071e2083; (e) Tzschucke, C. C.; Markert, C.; Bannwarth, W.;
Roller, S.; Hebel, A.; Haag, R. Angew. Chem., Int. Ed. 2002, 41,
964e4000.
. (a) Kim, D. W.; Song, C. E.; Chi, D. Y. J. Am. Chem. Soc. 2002, 124,
0278e10279; (b) Kim, D. W.; Song, C. E.; Chi, D. Y. J. Org. Chem.
2
006-03770 to D.Y.C.).
2
3
References and notes
1
1
2
3
. For reviews on nucleophilic fluorination, see: (a) Gerstenberger, M. R. C.;
Haas, A. Angew. Chem., Int. Ed. Engl. 1981, 20, 647e667; (b) Mascaretti,
O. A. Aldrichimica Acta 1993, 26, 47e58.
2003, 68, 4281e4285; (c) Kim, D. W.; Choe, Y. S.; Chi, D. Y. Nucl.
Med. Biol. 2003, 30, 345e350.
10. (a) Kim, D. W.; Chi, D. Y. Angew. Chem., Int. Ed. 2004, 43, 483e485; (b)
Kim, D. W.; Hong, D. J.; Jang, K. S.; Song, C. E.; Chi, D. Y. Adv. Synth.
Catal. 2006, 348, 1719e1727.
11. Kim, D. W.; Ahn, D.-S.; Oh, Y.-H.; Lee, S.; Oh, S. J.; Lee, S. J.; Kim,
J. S.; Ryu, J.-S.; Moon, D. H.; Chi, D. Y. J. Am. Chem. Soc. 2006, 128,
16394e16397.
. See: (a) Special Issue: Fluorine in the Life Sciences, ChemBioChem 2004,
5, 557e726; (b) Phelps, M. E. Proc. Natl. Acad. Sci. U.S.A. 2000, 97,
9226e9233.
. See: Smith, M. D.; March, J. Advanced Organic Chemistry, 5th ed.;
Wiley-Interscience: New York, NY, 2001; pp 389e674.