Catalytic fluorination of 1,3-dicarbonyl compounds using iodoarene catalysts

Article abstract of DOI:10.1016/j.tetlet.2013.08.129

Catalytic fluorination of 1,3-dicarbonyl compounds with aqueous hydrofluoric acid proceeded efficiently with the aid of iodoarene catalysts in the presence of m-CPBA as a terminal oxidant. o-Iodotoluene, o-iodoanisole, and o-ethyliodobenzene showed a high

Full text of DOI:10.1016/j.tetlet.2013.08.129

Tetrahedron Letters 54 (2013) 6118–6120
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Tetrahedron Letters
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Catalytic fluorination of 1,3-dicarbonyl compounds using iodoarene
catalysts
⇑
Tsugio Kitamura , Kazutaka Muta, Satoshi Kuriki
Department of Chemistry and Applied Chemistry, Graduate School of Science and Engineering, Saga University, Honjo-machi, Saga 840-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Catalytic fluorination of 1,3-dicarbonyl compounds with aqueous hydrofluoric acid proceeded efficiently
with the aid of iodoarene catalysts in the presence of m-CPBA as a terminal oxidant. o-Iodotoluene,
o-iodoanisole, and o-ethyliodobenzene showed a high catalytic efficiency to give 2-fluoro-1,3-dicarbonyl
compounds in good yields.
Received 18 July 2013
Revised 27 August 2013
Accepted 30 August 2013
Available online 7 September 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Iodoarene catalysis
Fluorination
Hydrofluoric acid
1
,3-Dicarbonyl compounds
Recently hypervalent iodine compounds have been used widely
Table 1
a
in organic synthesis because they have synthetically useful advan-
tages such as mild oxidation ability and the chemical behaviors
similar to transition metals.1 In addition, due to the superleaving
Catalytic fluorination of 1a with a HF reagent
O
O
2
O
O
20 mol% PhI
ability of hypervalent iodine, nucleophilic substitution occurs eas-
+
HF reagent
Ph
OEt
ily under mild conditions. This unique behavior has been demon-
Ph
OEt
m-CPBA, solvent
-functionalization of carbonyl compounds.1b In the
F
strated in
a
o
4
0 C, 24 h
1a
2a
fluorination reaction of carbonyl compounds, p-(difluoroiodo)tolu-
ene was shown to be an efficient fluorinating reagent. Hara et al.
reported that p-(difluoroiodo)toluene could be applied to the fluo-
Yieldb (%)
Entry
HF reagent (mmol)
Solvent (mL)
3
rination of b-ketoesters, b-ketoamides and b-diketones. Recently,
1
2
3
4
5
6
55% HF (10 mmol)
55% HF (5 mmol)
DCM (2 mL)
DCM (2 mL)
DCM (2 mL)
DCM (4 mL)
DCE (4 mL)
DCE (5 mL)
DCE (4 mL)
DCE (4 mL)
DCE (4 mL)
DCE (4 mL)
DCE (4 mL)
DCE (4 mL)
DCE (4 mL)
51
55
45
57
72
58
34
64
52
17
56
69
78
we reported that a convenient fluorination reaction of 1,3-dicar-
bonyl compounds without p-(difluoroiodo)toluene.4 This method
involves direct use of commercially available hydrofluoric acid
and iodosylbenzene (PhIO) and does not require synthesis of p-
55% HF (20 mmol)
55% HF (10 mmol)
55% HF (10 mmol)
55% HF (10 mmol)
55% HF (10 mmol)
55% HF (10 mmol)
55% HF (10 mmol)
TEAꢀ3HF (10 mmol)
TEAꢀ5HF (10 mmol)
TEAꢀ5HF (20 mmol)
HFꢀpyridine (10 mmol)
(
difluoroiodo)toluene or (difluoroiodo)benzene. However, this
c
7
method still remains drawbacks, that is, it requires synthesis of
iodosylbenzene or p-iodosyltoluene and needs a stoichiometric
amount of iodosylarenes. Iodosylarenes are reasonably stable but
cause a slight decomposition during long term storage. In the case
of large-scale synthesis, such drawbacks may cause a serious prob-
lem. In the fluorination using hydrofluoric acid/PhIO reagent, PhIO
was reduced to iodobenzene via (difluoroiodo)benzene. If the
d
8
e
9
10
11
12
13
a
Conditions: 1a (1 mmol), a HF reagent, m-CPBA (1.5 mmol), PhI (0.2 mmol), a
solvent, 40 °C, 24 h.
5
resulting PhI can be re-oxidized to PhIO in situ, it can participate
b
Yields were determined by 1H NMR using the integral of doublet methine
in the fluorination again. Namely, it is considered that PhI can
serve as a catalyst for fluorination. However, to the best of our
knowledge, there are no reports that fluorination proceeds
proton of 2a.
c
m-CPBA (0.5 mmol) was used.
d
e
m-CPBA (1 mmol) was used.
m-CPBA (2 mmol) was used.
⇑
Corresponding author. Tel.: +81 952 28 8550; fax: +81 952 28 8548.
E-mail address: kitamura@cc.saga-u.ac.jp (T. Kitamura).
0
040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.08.129

T. Kitamura et al. / Tetrahedron Letters 54 (2013) 6118–6120
6119
Table 2
roiodobenzene and p-diiodobenzene also acted as good catalysts to
give 2a in 70% and 74% yields, respectively (Table 2, entries 9 and
a
Iodoarene-catalyzed fluorination of 1a
1
0).
2
0 mol% ArI
O
O
O
O
55% aq. HF
Ph
OEt
Ph
OEt
m-CPBA, DCE
F
2a
o
Table 3
4
0 C, 24 h
a
1a
Iodoarene-catalyzed fluorination of 1,3-dicarbonyl compounds 1
Entry
Iodoarene
Yieldb (%)
20 mol% ArI
O
O
O
O
55% aq. HF
1
2
3
4
5
6
7
8
9
1
1
PhI
79
83
85
80
15
83
88
85
70
74
35
R1
R2
p-Iodotoluene
o-Iodotoluene
Iodomesitylene
p-Iodoanisole
m-Iodoanisole
o-Iodoanisole
o-Ethyliodobenzene
p-Chloroiodobenzene
p-Diiodobenzene
p-Iodonitrobenzene
R1
R2
m-CPBA, DCE
F
2
o
40 C
1
Entry ArI
Time
(h)
Product
Yieldb
(%)
O
F
O
0
1
I
OEt
a
1
24
24
82
75
Conditions: 1a (1 mmol), 55% aqueous HF (10 mmol), m-CPBA (1.5 mmol), ArI
0.2 mmol), DCE (4 mL), 40 °C, 24 h.
Isolated yields by column chromatography on silica gel.
F
(
O N
2
b
2
b
F
F
O
O
2c
F
efficiently with iodobenzene catalysis. Here, we wish to report the
first example of catalytic fluorination of 1,3-dicarbonyl compounds
using iodoarene catalysts.
To explore the catalytic fluorination using iodoarenes as catalyst,
we first optimized the reaction conditions in the fluorination reac-
tion of ethyl benzoylacetate (1a) as the model substrate. Since we
succeeded previously in the stoichiometric fluorination of 1,3-
dicarbonyl compounds by aqueous HF with the aid of PhIO, the
reaction conditions similar to the stoichiometric ones were
adopted. When the reaction of 1a (1 mmol) with 55% aqueous HF
OEt
2
PhI
F
2
c
3
4
I
24
1
2c
78
74
4
PhI
O
O
2d
(
10 equiv HF) was conducted in the presence of PhI (20 mol %) as
catalyst and m-CPBA (1.5 equiv) as oxidant in dichloromethane
DCM). The reaction at 40 °C for 24 h in DCM (2 mL) gave ethyl
-fluorobenzoylacetate (2a) in 51% yield (Table 1, entry 1).
OEt
PhI
F
(
2
2
d
Decreasing or increasing the amount of HF from 10 equiv HF re-
sulted in a similar yield of 2a (Table 1, entries 2 and 3). Using
5
6
1
1
2d
79
79
I
I
4
mL of DCM slightly increased the yield to 57% (Table 1, entry 4).
O
O
O
2e
The reaction in dichloroethane (DCE) improved the yield to give
the best result (72% yield) (Table 1, entry 5) but increasing the
amount of DCE to 5 mL decreased the yield to 58% (Table 1, entry
OEt
F
6
). By examining the amount of m-CPBA (0.5–2.0 equiv), the best
amount of m-CPBA was found to be 1.5 equiv (Table 1, entries 5,
–9). Then, we examined other HF sources such as TEAꢀ3HF,
O
2f
7
I
Ph
Ph
7
24
44
TEAꢀ5HF and HFꢀpyridine complexes (Table 1, entries 10–13). The
fluorination using TEAꢀ5HF (20 equiv) and HFꢀpyridine (10 equiv)
gave 2a in 69% and 78% yields, respectively. Although HFꢀamine
complexes are also good HF sources, these complexes are much
more expensive than aqueous HF. We decided that the method
using HFꢀamine complexes was not suitable for large-scale synthe-
sis. Therefore, we continued to examine the catalytic fluorination
with aqueous HF.
F
2f
OMe
8
9
24
2f
50
70
I
OMe
24 (rt)c
2f
I
Using the above optimized conditions, several iodoarenes were
screened to check the catalytic efficiency. The results obtained
from the fluorination of 1a are given in Table 2. Compared with
PhI (Table 2, entry 1), p-iodotoluene, o-iodotoluene, iodomesityl-
ene, m-iodoanisole, o-iodoanisole and o-ethyliodobenzene served
as good catalysts (Table 2, entries 2–4, 6–8). These catalysts gave
O
O
2g
I
Ph
1
0
1
24
24
46
62
F
2
g
OMe
I
2
a in 80–88% yields. However, the presence of strong electron-
withdrawing (NO ) and electron-donating (MeO) substituents at
the para position decreased the catalytic efficiency to afford 2a in
5 and 35% yields, respectively (Table 2, entries 5 and 11). p-Chlo-
1
2g
2
(
continued on next page)
1

6
120
T. Kitamura et al. / Tetrahedron Letters 54 (2013) 6118–6120
Table 3 (continued)
and 2i in 56 and 58% yields, respectively (Table 3, entries 10 and
11).
A proposed mechanism for the iodoarene-catalyzed fluorination
Entry ArI
Time
h)
Product
Yieldb
(%)
(
is outlined in Scheme 1. First, an iodoarene is oxidized by m-CPBA
O
O
O
2h
to an iodosylarene which may exist as its hydrate due to the pres-
7
1
1
2
3
I
I
2
2
56
58
ence of water. The iodosylarene is readily converted to a (difluo-
NMe2
2i
8
roiodo)arene
by
reaction
with
HF.
The
resulting
F
(
difluoroiodo)arene then reacts with the enols of 1,3-dicarbonyl
O
compounds 1 to give 2-fluorinated 1,3-dicarbonyl compounds 2,
with re-generation of the iodoarene catalyst.
NEt2
F
In summary, we have demonstrated an iodoarene-catalyzed
fluorination of 1,3-dicarbonyl compounds using aqueous HF as a
cheap HF source and m-CPBA as a terminal oxidant. High catalytic
efficiency of the iodoarene was observed in the cases of o-iodotol-
uene, o-iodoanisole and o-ethyliodobenzene. The catalytic fluori-
nation reduces the drawbacks caused by the stoichiometric
reaction with iodosylarenes. As compared with other expensive
HF sauces, use of aqueous HF has a merit in cost performance,
and it is also suitable for large-scale synthesis.
a
Conditions: 1 (1 mmol), 55% aqueous HF (10 mmol), m-CPBA (1.5 mmol), ArI
(
0.2 mmol), DCE (4 mL), 40 °C.
b
Isolated yields by column chromatography on silica gel.
c
At room temperature.
2
m-CPBA, H O
O
O
Acknowledgment
HF + R1
R2
ArI
m-CBA
This work was partly supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science
and Technology of Japan (25410048).
F
2
ArIO (or ArIO-H O)
2
References and notes
OH
O
1.
For recent reviews on hypervalent iodine compounds, see (a) Zhdankin, V. V. J.
Org. Chem. 2011, 76, 1185–1197; (b) Merritt, E. A.; Olofsson, B. Synthesis 2011,
2HF
R1
R2
ArIF
2
517–538; (c) Brand, J. P.; González, D. F.; Nicolai, S.; Waser, J. Chem. Commun.
2011, 102–115; (d) Satam, V.; Harad, A.; Rajule, R.; Pati, H. Tetrahedron 2010, 66,
7659–7706; (e) Uyanik, M.; Ishihara, K. Chem. Commun. 2009, 2086–2099; (f)
H O
Zhdankin, V. V. ARKIVOC 2009, i, 1–62; (g) Zhdankin, V. V.; Stang, P. J. Chem. Rev.
2008, 108, 5299–5358.
(a) Wiberg, K. B.; Pratt, W. E.; Matturo, M. G. J. Org. Chem. 1982, 47, 2720–2722;
(b) Okuyama, T.; Takino, T.; Sueda, T.; Ochiai, M. J. Am. Chem. Soc. 1995, 117,
2
O
O
2
3
.
.
R1
R2
3
360–3367.
(a) Hara, S.; Sekiguchi, M.; Ohmori, A.; Fukuhara, T.; Yoneda, N. Chem. Commun.
996, 1899–1900; (b) Yoshida, M.; Fujikawa, K.; Sato, S.; Hara, S. ARKIVOC 2003,
1
1
Scheme 1. A proposed mechanism.
vi, 36–42.
4
5
.
.
Kitamura, T.; Kuriki, S.; Morshed, M. H.; Hori, Y. Org. Lett. 2011, 13, 2392–2394.
For reviews on a catalytic cycle of iodoarenes, see (a) Richardson, R. D.; Wirth, T.
Angew. Chem., Int. Ed. 2006, 45, 4402–4404; (b) Ochiai, M.; Miyamoto, K. Eur. J.
Org. Chem. 2008, 4229–4239; (c) Dohi, T.; Kita, Y. Chem. Commun. 2009, 2073–
Table 3 demonstrates the scope of 1,3-dicarbonyl compounds in
6
the iodoarene-catalyzed fluorination reaction. In addition to 1a,
2
085.
0
other b-ketoesters such as ethyl 3-(4 -nitrophenyl)-3-oxopropio-
nate (1b), ethyl 3-oxo-3-(2 ,3 ,4 ,5 -tetrafluorophenyl)propionate
1c), ethyl 3-oxohexanoate (1d) and ethyl 3-oxoheptanoate (1e)
6. General procedure for catalytic fluorination of 2: In a PFA test tube were added ArI
(0.2 mmol), 55% aqueous HF (0.64 mL, 10 mmol HF), m-CPBA (1.5 mmol) and
DCE (4 mL). After stirring for 15 min at room temperature, 1 (1 mmol) was
added and then the mixture was stirred at 40 °C for the time given in Table 3.
0
0
0
0
(
were fluorinated by using o-iodotoluene or iodobenzene as catalyst
to give products 2b–2e in high yields (74–82%) (Table 3, entries
After neutralizing the reaction mixture with aqueous NaHCO
extracted with CH Cl
(6 mL ꢁ 3). The combined organic layer was washed with
saturated NaCl and dried over anhydrous Na SO . After evaporation of the
solvent, the product was isolated by column chromatography on silica gel with
EtOAc/hexane. All products 2 were identified on the basis of the spectra of the
authentic samples or the reported data.4
(a) Ochiai, M.; Miyamoto, K.; Shiro, M.; Ozawa, T.; Yamaguchi, K. J. Am. Chem.
Soc. 2003, 125, 13006–13007; (b) Ochiai, M.; Miyamoto, K.; Yokota, Y.; Suefuji,
T.; Shiro, M. Angew. Chem., Int. Ed. 2005, 44, 75–78.
(a) Sawaguchi, M.; Ayuba, S.; Hara, S. Synthesis 2002, 1802–1803; (b) Arrica, M.
A.; Wirth, T. Eur. J. Org. Chem. 2005, 395–403.
3
the product was
2
2
2
4
1
–6). In the case of dibenzoylmethane (1f), the catalytic fluorina-
tion with o-iodotoluene resulted in a moderate yield of product
f (Table 3, entry 7). Use of o-iodoanisole as catalyst slightly im-
2
7
8
.
.
proved the yield of 2f (Table 3, entry 8). In addition, lowering the
reaction temperature to room temperature increased the yield of
2
f to 70% (Table 3, entry 9). Similarly, the fluorination of 1-phe-
nyl-1,3-butanedione (1g), o-iodoanisole afforded a better yield of
product 2g than o-iodotoluene. The fluorination of b-ketoamides
1
h and 1i was catalyzed by o-iodotoluene to give products 2h