SelectfluorTMon a PolyHIPE Material as Regenerative and Reusable Polymer-Supported Electrophilic Fluorinating Agent

Article abstract of DOI:10.1002/adsc.201601312

The first recyclable polymer-supported electrophilic fluorinating agent was prepared by reaction of molecular fluorine with the triethylenediamine motif that is grafted onto a poly(4-vinylbenzyl chloride-co-divinylbenzene) polyHIPE material. The resulting

Full text of DOI:10.1002/adsc.201601312

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DOI: 10.1002/adsc.201601312
SelectfluorTM on a PolyHIPE Material as Regenerative and
Reusable Polymer-Supported Electrophilic Fluorinating Agent
Kosuke Kawada,a,e,* Koji Okano,a Jernej Iskra,b,* Peter Krajnc,c
and Dominique Cahardd,*
a
Tosoh F-Tech, Inc. 4988, Kaisei-Cho, Shunan, 746-0006 Yamaguchi, Japan
Jozef Stefan Institute. Jamova cesta 39, 1000 Ljubljana, Slovenia
b
E-mail: jernej.iskra@ijs.si
c
University of Maribor, Faculty of Chemistry and Chemical Engineering, PolyOrgLab. Smetanova 17, 2000 Maribor,
Slovenia
d
UMR 6014 CNRS COBRA, Normandie Univ, INSA Rouen, UNIROUEN. 76821 Mont Saint Aignan, France
Fax : (+33)-2-3145-2959; phone (+33)-2-3552-2466; e-mail: dominique.cahard@univ-rouen.fr
Current address: Bio-Fine Chemicals Dept, Life Sciences Division, Mitsubishi Corporation, Marunouchi Park Bldg., 6-1,
e
Marunouchi 2-chome, Chiyoda-ku, 100-8086 Tokyo, Japan
Fax : (+81)-3–3210-5447; phone (+81)-3-3210-3053; e-mail: kosuke.kawada@mitsubishicorp.com
Received: November 28, 2016; Revised: December 6, 2016; Published online: && &&, 0000
Supporting information for this article can be found under: http://dx.doi.org/10.1002/adsc.201601312.
Abstract: The first recyclable polymer-supported
electrophilic fluorinating agent was prepared by re-
action of molecular fluorine with the triethylenedia-
mine motif that is grafted onto a poly(4-vinylbenzyl
chloride-co-divinylbenzene) polyHIPE material.
The resulting polymeric SelectfluorTM-type reagent
demonstrated high efficiency in the fluorination of
naphthol in the course of repeated sequences of flu-
orination and regeneration. It also reacted with the
enol form and the sodium enolate of 1,3-dicarbonyl
compounds.
sources of positive fluorine were designed featuring
the O–F moiety (fluoroxyperfluoroalkanes RfOF, per-
fluoroacyl hypofluorites RfCOOF, and sulfonyl hypo-
fluorites RfSO2OF) but their explosive nature caused
their rapid phase-out.[3] Thereafter, N–F reagents
emerged as safer and shelf-stable reagents for electro-
philic fluorinations.[4] A wide range of fluorinating
powers together with commercial availability secured
a widespread use of this class of reagents. Representa-
tive reagents include NFSI (N-fluorobenzenesulfon-
AHCTUNGTRENNUNG
imide), N-fluoropyridinium salts and SelectfluorTM
{1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]oc-
tane bis(tetrafluoroborate) or F-TEDA-BF4; TEDA=
triethylenediamine}. These reagents have been contin-
uously employed in a wide variety of fluorination re-
actions; however, they suffer from poor atom-econo-
my because of their high molecular weight for the
transfer of 19F and no effort was made to recover and
regenerate either the benzenesulfonimide, the pyri-
Keywords: fluorination; green chemistry; high inter-
nal phase emulsion (HIPE) templating; molecular
fluorine; supported reagents
The synthesis of selectively fluorinated new chemical dine moiety or the TEDA residue of the correspond-
entities is an important challenge in organic chemistry ing reagents. In a previous work on enantioselective
that receives an ever-growing attention due to the electrophilic fluorination by means of quinine-based
wide potential applications in the life science fields [N–F]+ reagents conducted in ionic liquids, the Cin-
and materials science. Indeed, the chemical position- chona alkaloid as well as the solvent were recycled.[5]
ing of a fluorine atom, which possesses a strong elec- With a view to ensuring minimization of waste gener-
tron-withdrawing ability and a relatively small size, ation toward a greener chemistry, we envisaged the
often leads to stunning changes in the physical, chem- preparation, applications, and the regeneration of de
ical and biological properties of fluorinated com- novo polymeric architectures as support for electro-
pounds when compared with their non-fluorinated an- philic fluorinating agents. In the context of green
alogues.[1] From a synthetic point of view, the direct chemistry, polymer-supported reagents offer attractive
and selective electrophilic fluorination of organic and practical approaches for the clean and efficient
compounds was made possible thanks to a collection synthesis of organic compounds.[6] Polymeric electro-
of various fluorinating agents.[2–4] In the early stages, philic fluorinating agents are extremely rare. In 1986,
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zyl chloride (VBC) and divinylbenzene (DVB) in
ratio of VBC/DVB=93:7 by utilizing the high inter-
nal phase emulsion (HIPE) templating approach,[10a]
which enables the preparation of monolithic polymer
supports with interconnected, multi-level porosity
thus avoiding the diffusion limitations that are usually
problematic with gel-type polymer supports. Poly-
HIPE supports based on VBC have already been
shown as suitable carriers of reagents and catalysts.[10]
Our styrene/DVB-based polyHIPE material was pow-
dered and further functionalized by nucleophilic dis-
Figure 1. Structures of Banksꢁ and Umemotoꢁs polymeric
fluorinating agents.
Banksꢁ group reported polymeric analogues of N-fluo- placement of chloride by triethylenediamine to afford
roperfluoropiperidines (Figure 1, left).[7] The LaMar the polyHIPE-TEDA 1 (Scheme 1), which was titrat-
fluorination process was applied on cross-linked ed by anion exchange with a 0.02M sodium hydroxide
poly(4-vinylpyridine) and two other similar entities to solution for measuring the loading of TEDA units at
yield perfluoropolymers. However, the fluorination of 1.24 mmolgÀ1.
sodium malonates and 1-(N-morpholinyl)cyclohexene
by these polymers did not proceed in more than 23%
yield and the recycling was not addressed. In 1998,
Umemoto et al. synthesized poly(N-fluoropyridinium)
salts that have increased effective fluorine content
(Figure 1, right) but only the dimeric ones were stud-
ied and demonstrated high fluorination capacity.[8]
Herein, we describe the preparation of the first poly-
meric F-TEDA reagent, its successful application in
the fluorination of naphthols, the enol form of diben-
zoylmethane, and the sodium enolate of ethyl 3-oxo-
3-phenylpropanoate as well as its regeneration and
reuse.
Possessing a high electrophilic power, SelectfluorTM
is one of the most employed fluorinating agents. With
the aim to mimic SelectfluorTM, we designed a poly-
meric analogue by grafting the triethylenediamine
motif onto a polymer (Figure 2). We reasoned that
Scheme 1. Synthesis of polyHIPE F-TEDA.
a suitable polymeric support for an electrophilic fluo-
rinating agent would have appropriate porosity to fa-
From this polyHIPE-TEDA, four synthetic routes
cilitate efficient contact with molecular fluorine.[9] We were considered for the preparation of the corre-
prepared the highly porous polymer from 4-vinylben- sponding polyHIPE F-TEDA 3 by means of molecu-
lar fluorine: (i) fluorination of 1 and subsequent
anion metathesis, (ii) fluorination of a mixture of
1 and the metal salt of an acid, (iii) fluorination of
a preformed ammonium hydrogen salt 2, (iv) fluorina-
tion of an ammonium-Lewis acid complex.[11] We
opted for the procedure (iii) in which the anion ex-
change is done prior to the fluorination in order to
avoid possible oxidation of chloride anions by F2. Fur-
thermore, this procedure allows the control of the
counteranion and titration of the intermediate ammo-
nium hydrogen salts 2a–c. The polyHIPE-TEDA was
treated under ultrasound irradiation with a Brønsted
acid that include triflic acid, tetrafluoroboric acid so-
lution 48 wt% in water, and trifluoroacetic acid in
order to produce the bis-ammonium salts polyHIPE
H-TEDA 2a–c (Scheme 1). At this stage, titration
with a 0.01M sodium hydroxide solution was conduct-
ed to determine the loading of protonated TEDA
units, i.e., the number of available nitrogen sites for
Figure 2. Structure of polyHIPE F-TEDA (chemical compo-
sition and schematic representation).
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Table 1. Synthesis and titration of polyHIPE H-TEDA 2a–c.
Synthesis[a]
Titration by 0.01M NaOH[b]
Amount of
1 [mg]
Brønsted
acid
Amount of
product 2 [mg]
Amount of
2 [mg]
NaOH
[mL]
Loading of H-TEDA
[mmol/g]
1000
500
500
TfOH
HBF4
CF3CO2H
1670 (2a)
603 (2b)
552 (2c)
34.1 (2a)
29.1 (2b)
27.6 (2c)
5.74
6.48
5.84
0.84
1.11
1.06
[a]
Typical reaction conditions for 2a: 1 (1.00 g, 1.24 mmol of TEDA unit), acetonitrile (50 mL), ultrasonic irradiation, room
temperature, 30 min, triflic acid (1.36 g, 9.07 mmol).
See the Supporting Information for full details.
[b]
fluorination (Table 1). The loading of functional sites cules and it allows a direct comparison of the reactivi-
in the polyHIPE H-TEDA was calculated to be in the ty of our supported reagent versus that of non-sup-
range 0.84–1.11 mmolgÀ1. Finally, the fluorination was ported fluorinating agents.[13] To a suspension of the
performed by flowing 5% F2 in N2 into the teflon re- polyHIPE F-TEDA 3a in acetonitrile (stoichiometric
actor containing the polyHIPE H-TEDA.[12] We no- amount and 2.2 equivalents), 2-naphthol was added at
ticed that the fluorination gave better results when it room temperature and the reaction was monitored by
was conducted in the presence of a catalytic amount gas chromatography (Table 3, entries 1–10). As ex-
of free TEDA. Indeed, the active fluorine content of pected, two fluorinated products were obtained by
the polymer declined by nearly 70% when the fluori- fluorination at the position 1 only: 1-fluoro-2-naph-
nation was achieved without additional free TEDA. thol
Because F2 gas itself is almost insoluble in acetoni- (Scheme 2, top).
trile, it is therefore rather difficult to have the F2 gas With one equivalent of fluorinating agent, the reac-
5
and 1,1-difluoro-2(1H)-naphthalenone
6
in close contact with the polymer. We believe that tion did not go to completion and the monofluorinat-
TEDA can assist the fluorination of polyHIPE ed product 5 was predominant in a 5/6 ratio of 5.1:1
through reaction with F2 generating an F2 adduct with and an overall yield of 73.6% whereas with 2.2 equiv-
TEDA that is readily soluble in acetonitrile. TEDA alents of 3a the difluorinated product 6 became the
may work as an effective carrier of F2 gas within the major one with a 5/6 ratio of 1:4.3 and an overall
insoluble polymer. Next, the oxidation ability of the yield of 90.6%. These results are in line with those
polyHIPE F-TEDA 3a–c was determined by iodomet- obtained using SelectfluorTM. Next, the fluorinating
ric titration. The active fluorine content was calculat- power of polyHIPE F-TEDA-OTf 3a was compared
ed to be 0.52, 0.80, and 0.63 mmolgÀ1 for the triflate, with those of SelectfluorTM, N-fluoro-2,6-dichloropyri-
the tetrafluoroborate and the trifluoroacetate, respec- dinium tetrafluoroborate (FP-B800) and N-fluoropyri-
tively (Table 2). These values are to be compared dinium triflate (FP-T500). Our polymeric reagent
with SelectfluorTM reagent that has a fluorine loading showed slightly weaker activity than SelectfluorTM
of 2.82 mmolgÀ1. To test the general robustness of the and FP-B800, but a much stronger reactivity than FP-
fluorination, we demonstrated on eight batches that T500 (Table 3, entries 5–23). This is a very encourag-
the optimized fluorination conditions consistently pro- ing result for further application of the polyHIPE F-
vided the polyHIPE F-TEDA with similar active fluo- TEDA reagents. For example, the regioisomeric 1-
rine contents.
naphthol 7 was fluorinated at the positions 2 and 4 in
As a model reaction to evaluate the fluorinating a ratio 10.1:1 and a yield of 79.2% (Scheme 2). In ad-
power of the polyHIPE F-TEDA 3a–c, we examined dition to aromatic substrates, the methylene active di-
the fluorination of 2-naphthol 4 because it is a relevant benzoylmethane 10 reacted smoothly via its enol form
structural unit found in many biologically active mole- with the polymer 3a to give the mono- and difluori-
Table 2. Synthesis and iodometry of polyHIPE F-TEDA 3a–c.
Synthesis[a]
Amount of TEDA
[mg]
Iodometric titration[b]
Amount of 2
[mg]
Amount of product 3
[mg]
Amount of 3
[mg]
Na2S2O3
[mL]
Active fluorine
[mmol/g]
252 (2a)
202 (2b)
226 (2c)
5.6
5.0
5.4
242 (3a)
205 (3b)
220 (3c)
30.5 (3a)
28.7 (3b)
32.3 (3c)
1.58
2.30
2.24
0.52
0.80
0.63
[a]
Typical reaction conditions for 3a: 2a (252 mg, 0.212 mmol of TEDA units), TEDA (5.6 mg), acetonitrile (50 mL), ultra-
sonic irradiation, then À208C, 5% F2/N2 (2,12 mmol at 10 mL/min).
[b]
See the Supporting Information for full details.
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Table 3. Fluorination of 2-naphthol 4. Comparison of the re-
activity of polyHIPE F-TEDA-OTf 3a with SelectfluorTM
,
FP-B800 and FP-T500.
Fluorination of 2-naphthol 4 with 3a [1 equiv.][a]
Entry Time [h] 4 [%] 5 [%] 6 [%] Yield [%][b]
1
2
3
4
0
2
6
24
100
0
0
0
43.8
40.0
36.7
47.5
50.9
53.0
8.7
9.1
10.3
64.9
69.1
73.6
Fluorination of 2-naphthol 4 with 3a [2.2 equiv.]
5
6
7
8
9
10
0
2
3
6
24
48
100
3.9
0
0
0
0
0
0
38.2
35.1
25.9
20.2
18.8
57.9
64.9
74.1
79.8
81,2
77.0
82.5
87.1
89.9
90.6
0
Fluorination of 2-naphthol 4 with SelectfluorTM [2.2 equiv.]
11
12
13
14
15
0
0.5
1
2
4
100
0
0
0
0
0
0
0
46.7
28.4
13.8
7.8
53.3
71.6
86.2
92.2
76.7
85.8
93.1
96.1
Fluorination of 2-naphthol 4 with FP-B800 [2.2 equiv.]
16
17
18
19
20
21
0
0.5
1
2
4
100
2.5
0
0
0
0
0
0
Scheme 2. Fluorination of 2-naphthol 4, 1-naphthol 7, diben-
zoylmethane 10, sodium enolate of ethyl 3-oxo-3-phenylpro-
panoate 13.
60.2
42.3
26.6
11.2
6.5
37.3
57.7
73.4
88.8
93.5
67.4
78.9
86.7
94.4
96.7
no polymeric fluorinating agent was recycled. For
cost-effective industrial fluorination and to better ac-
count for environmental concerns, we herein report
the first regeneration and reuse of the polymer-sup-
ported electrophilic fluorinating agent polyHIPE F-
TEDA. After the reaction with 2-naphthol, the poly-
HIPE H-TEDA 2a2–c2 were recovered by simple fil-
tration and washing, and then resubmitted to the fluo-
rination step by means of F2 to give a “second genera-
tion” of polyHIPE F-TEDA 3a2–c2. The regeneration
proceeded very well providing polymers with similar
6
0
Fluorination of 2-naphthol 4 with FP-T500 [2.2 equiv.]
22
23
0
48
100
100
0
0
0
0
0
0
[a]
[b]
Reaction conditions: 3a (200 mg, 0.104 mmol of active
fluorine), 4 (14.4 mg, 0.1 mmol), acetonitrile (5 mL),
room temperature, 0–24 h.
Yields were determined by gas chromatography.
nated products 11 and 12 in a ratio 5.3:1 in 70.9% or even slightly increased active fluorine contents;
yield (Scheme 2). More efficiently and selectively, the this trend was confirmed in a second regeneration
sodium enolate of ethyl 3-oxo-3-phenylpropanoate re- giving rise to a “third generation” of polymer 3a3
acted with the polymer 3a to give the monofluorinat- (Table 4). Subsequently, the fluorinating powers of
ed b-keto ester 14 in 92.5% yield (Scheme 2).
polyHIPE F-TEDA 3a2 and 3a3 were assessed in the
The fluorination of 2-naphthol was next performed fluorination of a stoichiometric amount of 2-naphthol
with polyHÀIPE F-TEDA À3b and 3c featuring counter- for comparison with data obtained with polyHIPE F-
anions BF4 and CF3CO2 for assessment of their ef- TEDA 3a (Table 5 versus Table 3, entries 1–4).
fectiveness. We observed a decreased efficiency with
Interestingly, the reactivity of the regenerated poly-
overall reaction yields of 60% and 18% for 3b and 3c, HIPE F-TEDA 3a2 was improved compared to the
respectively. Therefore, although we regenerated the original polymeric fluorinating agent 3a; indeed, the
polyHIPE F-TEDA 3a–c, the recycling studies were overall yield 5+6 increased from 73.6 to 88.3%, prob-
conducted only with the most efficient polyHIPE F- ably as the result of an increased fluorine content of
TEDA-OTf 3a. Apart from one case in the literature the regenerated polymer. The regeneration/reuse se-
of reuse of the dimeric N,N’-difluoro-2,2’-bipyridinium quence was repeated one more time affording the
bis(tetrafluoroborate) (MEC-31) by Adachi et al.,[13d] third generation polyHIPE F-TEDA-OTf 3a3 and
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Table 4. “Second and third generations” of polyHIPE F-TEDA 3 from recovered materials.
Synthesis[a]
Amount of
TEDA [mg]
Iodometric titration[b]
Recovered
2 [mg]
Amount of
product 3 [mg]
Amount of
3 [mg]
Na2S2O3
[mL]
Active fluorine
[mmol/g][c]
146 (2a2)
122 (2b2)
125 (2c2)
213 (2a3)
4.1
3.4
3.1
4.5
128 (3a2)
112 (3b2)
118 (3c2)
199 (3a3)
30.4 (3a2)
29.0 (3b2)
28.6 (3c2)
33.2 (3a3)
1.60
2.38
1.78
1.92
0.53 (0.52)
0.82 (0.80)
0.62 (0.63)
0.58 (0.53)
[a]
See the Supporting Information for full details.
See the Supporting Information for full details.
Values in parentheses refer to active fluorine contents measured for the preceding fluorination.
[b]
[c]
Table 5. Fluorination of 2-naphthol by means of regenerated
polyHIPE F-TEDA-OTf 3a2 and 3a3.
and has the potential to reduce manufacturing costs
in fluorination reactions in batch. This is particularly
true on a large scale in the industry while small scale
fluorinations in research laboratories may prefer flow
mode reactions on regenerable cartridges. Further de-
velopments of the block column–flow technique ap-
proach and applications with other substrates are on-
going in our laboratories.
Fluorination of 2-naphthol 4 with 3a2[a]
Entry
Time [h]
4 [%]
5 [%]
6 [%]
Yield [%][b]
1
2
3
4
0
1
6
24
100
0
0
0
45.2
30.0
28.4
45.7
57.3
54.9
9.1
12.7
16.7
63.9
82.7
88.3
Fluorination of 2-naphthol with 3a3[c]
Experimental Section
5
6
7
8
0
1
6
24
100
0
0
0
43.0
33.9
30.8
33.7
47.4
51.1
23.3
18.7
18.1
80.3
84.8
87.3
General Information
1H (400 MHz), 13C (100.6 MHz) and 19F (376 MHz) NMR
spectra were recorded on a Bruker AVANCE II 400. Chem-
[a]
Reaction conditions: 3a2 (320.8 mg, 0.17 mmol of active
fluorine), 4 (24.5 mg, 0.17 mmol), acetonitrile (8.5 mL),
room temperature, 0–24 h.
Yields were determined by gas chromatography.
Reaction conditions: 3a3 (163.8 mg, 0.095 mmol of active
fluorine), 4 (13.7 mg, 0.095 mmol), acetonitrile (4.8 mL),
room temperature, 0–24 h.
1
ical shifts in H NMR spectra are reported in parts per mil-
lion from TMS resonance as the internal standard. Chemical
shifts in 19F NMR spectra are reported in parts per million
from C6F6 or CF3CH2OH resonance as the internal standard.
The conversion and ratio of the products 4–14 were deter-
mined by gas chromatography on a SHIMAZU GC-2014.
Unless otherwise noted, all solvents and reagents were pur-
chased from commercial sources and were used without fur-
ther purification. CAUTION: Molecular fluorine F2, neat or
diluted in N2, is a highly oxidizing and toxic gas that re-
quires appropriate precautions for its safe handling.
[b]
[c]
a constant efficiency in the fluorination of 2-naphthol
in a high overall yield for 5+6 of 87.3% (Table 5, en-
tries 5–8).
In conclusion, a joint research effort by academic
laboratories and Tosoh F-Tech chemical company al-
lowed us to investigate the first high-potential poly-
mer-supported electrophilic fluorinating agent. The
TEDA motif that is found in SelectfluorTM was anch-
ored on a polyHIPE architecture and the polyHIPE
Synthesis of polyHIPE TEDA 1
A 100 mL aqueous phase, consisting of K2S2O8 (0.11 g,
0.41 mmol) in deionized water (100 mL), was added drop-
wise with continuous stirring at 300 rpm to an oil phase, con-
sisting of 4-vinylbenzyl chloride (11.62 g, 76 mmol), divinyl-
F-TEDA reagent was prepared by fluorination with benzene (0.79 g, 1.9 mmol), and the surfactant sorbitan mon-
ooleate (Span 80; 2.20 g). The emulsion was stirred for an-
other 30 min after addition of the aqueous phase, then trans-
ferred to a mold for curing (24 h at 608C). The resulting
polyHIPE was purified by Soxhlet extraction (deionized
water and acetone, both for 24 h) then dried under vacuum
for 24 h. Next, 1 g of powdered VBC/DVB polyHIPE
(5.5 mmol of chlorine) was suspended in 4 mL of dichloro-
methane and 680 mg of 1,4-diazabicyclo[2.2.2]octane
(TEDA) were added (1.1 times excess with regards to chlor-
omethyl groups). The mixture was stirred using a magnetic
molecular fluorine. The relatively high active fluorine
content of the polyHIPE F-TEDA did impart a high
reactivity in the fluorination of the test substrates 1-
and 2-naphthol as well as dibenzoylmethane and ethyl
3-oxo-3-phenylpropanoate. Importantly, the material
has high mechanical strength and we have demon-
strated the regeneration and the reuse of the fluori-
nating agent as initially planned in our requirement
specification. We now have in hand a reagent with un-
matched recycling performance that minimizes wastes stirrer at 408C for 24 hours, filtered, washed with dichloro-
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methane and 2-propanol and further purified via Sohxlet ex-
traction with 2-propanol for 24 hours and air dried.
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Zhou, J. Wang, Z. Gu, S. Wang, W. Zhu, J. L. AceÇa,
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116, 422–518.
Synthesis of polyHIPE H-TEDA-OTf 2a
1.00 g of 1 (1.24 mmol of TEDA unit) was suspended in
50 mL of acetonitrile under ultrasonic irradiation at room
temperature for 30 min. To this suspension, 1.36 g of triflic
acid (9.07 mmol) was added and the mixture was left at
room temperature under ultrasonic irradiation for additional
30 minutes. Then, 2a was collected by filtration under re-
duced pressure, and washed with 50 mL of acetonitrile 3
times to give 2a; yield: 1.67 g.
[2] C. N. Neumann, T. Ritter, Angew. Chem. 2015, 127,
3261–3267; Angew. Chem. Int. Ed. 2015, 54, 3216–3221.
[3] S. Rozen, Chem. Rev. 1996, 96, 1717–1736.
[4] a) J. Baudoux, D. Cahard, in: Organic Reactions, Vol.
69, John Wiley & Sons, Inc., Hoboken, NJ, 2007;
pp 347–672; b) C.-L. Zhu, M. Maeno, F.-G. Zhang, T.
Shigehiro, T. Kagawa, K. Kawada, N. Shibata, J.-A.
Ma, D. Cahard, Eur. J. Org. Chem. 2013, 6501–6505;
c) F. Wang, J. Li, Q. Hu, X. Yang, X.-Y. Wu, H. He,
Eur. J. Org. Chem. 2014, 3607–3613; d) R. Pereira, J.
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Synthesis of polyHIPE F-TEDA-OTf 3a
252 mg of 2a (0.212 mmol of TEDA unit) and 23.5 mol% of
TEDA (5.6 mg) were suspended in 50 mL of acetonitrile,
under ultrasonication at room temperature for 30 min under
10 mLminÀ1 N2 flow conditions. This suspension was cooled
to À208C and 10 equivalents of F2 gas diluted to 5% con-
centration by N2 gas were introduced at
a rate of
10 mLminÀ1 into the suspension under vigorous stirring.
Then, only N2 gas was continuously bubbled for 30 min and
the temperature of the reaction mixture was raised to room
temperature. Product 3a was collected by filtration under re-
duced pressure and washed with 10 mL of acetonitrile for 5
times and dried to give 3a; yield: 242 mg.
Procedure for the Fluorination of 2-Naphthol by
polyHIPE F-TEDA-OTf 3a
[7] R. E. Banks, E. Tsiliopoulos, J. Fluorine Chem. 1986,
34, 281–285.
The polyHIPE F-TEDA-OTf 3a (200 mg, 0.104 mmol of
active fluorine) was suspended in 5 mL of acetonitrile and
2-naphthol (14.4 mg, 0.1 mmol) was added and the mixture
stirred for 24 h at room temperature with monitoring of the
conversion by gas chromatography. On completion of the re-
action, the polymer was filtered out and washed twice with
5 mL of acetonitrile to give recovered 2a; yield: 197 mg.
The acetonitrile layers were combined and concentrated
under vacuum to give a crude mixture of 1-fluoro-2-naph-
[8] T. Umemoto, M. Nagayoshi, K. Adachi, G. Tomizawa,
J. Org. Chem. 1998, 63, 3379–3385.
[9] Initial attempts to use commercially available Merri-
field resins failed to produce a donor of electrophilic
fluorine, which justifies the design of polyHIPE materi-
als.
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2012, 33, 1731–1746; b) P. Krajnc, J. F. Brown, N. R. Ca-
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Krajnc, N. R. Cameron, Ind. Eng. Chem. Res. 2005, 44,
8565–8572; d) P. Krajnc, N. Leber, J. F. Brown, N. R.
Cameron, React. Funct. Polym. 2006, 66, 81–91; e) S.
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2009, 47, 6726–6734; f) I. Pulko, J. Wall, P. Krajnc,
N. R. Cameron, Chem. Eur. J. 2010, 16, 2350–2354.
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K. Tomita, Bull. Chem. Soc. Jpn. 1991, 64, 1081–1092.
[12] Molecular fluorine F2, neat or diluted in N2, is a highly
oxidizing and toxic gas that requires appropriate pre-
cautions for its safe handling. See fluorination appara-
tus in the Supporting Information.
[13] a) T. Umemoto, M. Nagayoshi, Bull. Chem. Soc. Jpn.
1996, 69, 2287–2295; b) R. E. Banks, M. K. Besheesh,
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Trans. 1 1996, 2069–2076; c) S. Stavber, M. Zupan, Syn-
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173–183; e) G. Stavber, M. Zupan, M. Jereb, S. Stavber,
Org. Lett. 2004, 6, 4973–4976; f) M. R. P. Heravi, J. Flu-
orine Chem. 2008, 129, 217–221.
thol
5 and 1,1-difluoro-1,2-dihydronaphthalen-2-one 6;
yield: 14.7 mg. The fluorination yield was measured to be
72% by 19F NMR with trifluoroethanol as internal standard.
From this mixture, 6.8 mg of 5 and 2.7 mg of 6 were isolated
as pure products by HPLC separation.
1-Fluoro-2-naphthol (5): 1H NMR (acetone-d6): d=8.87
(d, J=1.6 Hz, 1H), 7.94 (d, J=8.4 Hz, 1H), 7.85 (d, J=
8.4 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.53 (t, J=7.2 Hz,
1H), 7.38 (t, J=7.2 Hz, 1H), 7.28 (t, J=8.8 Hz, 1H);
19F NMR (acetone-d6): d=À152.8 (d, J=7.5 Hz, 1F).
1
1,1-Difluoro-2(1H)-naphthalenone (6): H NMR (acetone-
d6): d=7.87 (d, J=6.8 Hz, 1H), 7.78 (d, J=10.0 Hz, 1H),
7.70–7.62 (m, 3H), 6.29 (dt, J=10.0, 2.6 Hz, 1H); 19F NMR
(acetone-d6): d=À101.18 (s, 2F).
References
[1] a) V. Bizet, T. Besset, J.-A. Ma, D. Cahard, Curr. Top.
Med. Chem. 2014, 14, 901–940; b) D. Cahard, V. Bizet,
Chem. Soc. Rev. 2014, 43, 135–147; c) E. P. Gillis, K. J.
Eastman, M. D. Hill, D. J. Donnelly, N. A. Meanwell, J.
Adv. Synth. Catal. 0000, 000, 0 – 0
6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
SelectfluorTM on a PolyHIPE Material as Regenerative and
Reusable Polymer-Supported Electrophilic Fluorinating
Agent
7
Adv. Synth. Catal. 2016, 358, 1 – 7
Kosuke Kawada,* Koji Okano, Jernej Iskra,* Peter Krajnc,
Dominique Cahard*
Adv. Synth. Catal. 0000, 000, 0 – 0
7
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!