Novel biphasic reaction system of ferric chloride dissolved imidazolium hexafluorophosphate and benzotrifluoride: application to electron transfer reaction of cyclopropyl silyl ethers

Article abstract of DOI:10.1016/j.tet.2010.03.029

Ferric chloride (FeCl₃) promoted electron transfer oxidation of bicyclic cyclopropyl silyl ethers was performed in biphasic solution system of 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF₆) and benzotrifluoride (BTF). The resulting chloro-substituted ring-expanded cycloalkanones were treated with an appropriate base to produce substituted cyclic enones. These two-step reactions were successfully devised to proceed in a simpler manner in which the ordinary work-up operations for the former oxidation step, such as water-quench, extraction, and evaporation, were omitted; imidazole was found to be the most suitable base for the latter elimination step.

Full text of DOI:10.1016/j.tet.2010.03.029

Tetrahedron 66 (2010) 3447–3451
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Novel biphasic reaction system of ferric chloride dissolved imidazolium
hexafluorophosphate and benzotrifluoride: application to electron transfer
reaction of cyclopropyl silyl ethers
*
Hiroyuki Tsuchida, Eietsu Hasegawa
Department of Chemistry, Faculty of Science, Niigata University, Ikarashi-2 8050, Niigata 950-2181, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Ferric chloride (FeCl3) promoted electron transfer oxidation of bicyclic cyclopropyl silyl ethers was
performed in biphasic solution system of 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6)
and benzotrifluoride (BTF). The resulting chloro-substituted ring-expanded cycloalkanones were treated
with an appropriate base to produce substituted cyclic enones. These two-step reactions were
successfully devised to proceed in a simpler manner in which the ordinary work-up operations for the
former oxidation step, such as water-quench, extraction, and evaporation, were omitted; imidazole was
found to be the most suitable base for the latter elimination step.
Received 6 January 2010
Received in revised form 8 March 2010
Accepted 8 March 2010
Available online 16 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
several successful examples.8 In the course of these efforts, we
encountered an intriguing observation in which addition of
Development of practically convenient as well as environ-
mentally benign procedures to promote the transformation of
organic molecules should be appreciated not only for organic
synthesis but also for green sustainable chemistry.1 Among the
efforts to achieve this objective is the use of environmentally
benign reagents and solvents. Iron salts are recognized as one of
the least expensive and toxic reagents, and thus the use of iron salt
reagents is beneficial.2 Some imidazolium salts, known as room
temperature ionic liquids and environmentally benign solvents,
have been frequently used for organic synthesis.3 As suggested by
Ogawa and Curran, benzotrifluoride (PhCF3, BTF) is also known to
be an environmentally benign solvent, and thus BTF could replace
benzene and methylene chloride in several cases.4 On the other
hand, a procedure to promote the sequential chemical processes
with less experimental operations is also compatible with green
sustainable chemistry. For example, one-pot reaction that pro-
motes sequential processes in a single flask is one of the repre-
sentative examples.5
1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6)
to ferric chloride (FeCl3) in BTF significantly accelerated the
ring-expansion reaction of a bicyclic cyclopropyl silyl ether.8c
Upon addition of BmimPF6, solid FeCl3 dissolved in this ionic
liquid and the reaction proceeded under the liquid–liquid
biphasic condition.
In this paper, we would like to report the characteristic feature
of this novel biphasic reaction system of FeCl3 dissolved in
BmimPF6, which could be recognized as FeCl3–BmimPF6 hybrid
reagent, and BTF to promote electron transfer reaction of the title
substrates. Substrates and products together with representative
reagents and solvents investigated are shown in Chart 1.
O
O
OH
Me3SiO
R
R
Cl
R
Me
n
n
n
4
2
3
1
Electron transfer (ET) is a fundamental chemical process that
is operating in chemical as well as biological reduction and
oxidation reactions, and various ET based synthetic procedures
have been developed.6,7 Several years ago, we planned to develop
synthetically useful procedures that could promote the desired
ET reactions in a green sustainable manner, and have reported
a (n = 1, R = Me) , b (n = 0, R = Me), c (n = 2, R = Me),
d (n = 1, R = (CH2)2CH=CH2)
FeCl3
O
HO
nBu
Me
Me
Me
N
N
Me
PF6
(BmimPF6)
PhCF3
(BTF)
6a
5a
* Corresponding author. E-mail address: ehase@chem.sc.niigata-u.ac.jp.
Chart 1.
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.03.029

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H. Tsuchida, E. Hasegawa / Tetrahedron 66 (2010) 3447–3451
2. Results and discussion
These preliminary observations prompted us to further explore
the characteristics of this new reagent system of FeCl3 with
BmimPF6 in BTF. Our working hypothesis for the observation was
that the liquid–liquid biphasic system of FeCl3 dissolved in
BmimPF6 and BTF might provide better condition for an effective
contact between 1a and Fe(III) ion compared to the solid–liquid
biphasic system of FeCl3 and BTF. If so, the quantity of BmimPF6
might influence the reaction, which was examined at first. In these
experiments, instead of water-quench and Et2O extraction used for
the experiments in Table 1, separation of BTF layer followed by the
rinse of BmimPF6 layer with Et2O was performed (see Experimental
section).10 The results are summarized in Table 2. In all entries,
NaOAc treatment of crude 3a afforded 2a in various yields
depending on the quantity of BmimPF6 while trace amount of 6a
was also detected in certain case. Addition of some quantities of
BmimPF6 increased both the conversion of 1a and the yields of 2a
(entries 1–3), however further addition significantly decreased
them (entries 4 and 5).
In our earlier effort, we have found that ceric ammonium
nitrate, Ce(NH4)2(NO3)6 (CAN), was effective for oxidative ring-
opening reaction of certain bicyclic cyclopropanol derivatives as
shown below.9
O
O
O
OH
Nu
OH
R
OH
R
CAN
-HNu
R
Thus, silyl ether 1a was subjected to the reaction with CAN in
CH3CN, and desired ring-expanded enone 2a was obtained in
moderate yield as shown in Table 1 (entry 1).8e Then, we replaced
CH3CN by BTF, and found the reaction did not go to completion, and
only a trace amount of 2a was formed; deprotected cyclopropanol
5a was the major isolable product (entry 2). FeCl3 with pyridine in
DMF was also effective to obtain 2a in good yield after the treat-
Table 2
BmimPF6 quantity effect on the oxidation of 1a with FeCl3 and pyridine in BTFa
O
O
Me3SiO
ment of
b-chlorobenzosuberone 3a with a methanolic NaOAc
solution at reflux (entry 3).8e We were rather surprised to find that
toluene could be used for the reaction giving 2a in moderate yield
although FeCl3 appears to be insoluble in toluene (entry 4). On the
other hand, BTF was not as effective as above two solvents
(entry 5).8c However, addition of BmimPF6 to this reaction mixture
completely consumed 1a and gave 2a in the comparable yield to the
reaction conducted in DMF (entries 3 and 6).8c,e
1)
2)
Me
Cl
Me
Me
2a
1a
3a
1) FeCl3 / pyridine / BmimPF6 / BTF 2) NaOAc / MeOH
Entry
BmimPF6 (mL)
(equiv vs 1a)
Recovery of 1a (%)
Yield of 2a (%)
1b
2
3
4
0.00 (0.0)
0.10 (1.0)
0.23 (2.2)
0.50 (4.8)
1.00 (9.6)
67
0
0
31
44
15
50
62
29
23
Table 1
Reaction of 1a with oxidizing reagents (Ox)a
O
Me3SiO
5
Ox / additive
solvent
Me
a
Me
Substrate 1a (0.50 mmol), FeCl3 (2.2 equiv), pyridine (1.0 equiv), BTF (5.0 mL), at
room temperature for 1 h. Crude product mixture was heated with NaOAc
(5.0 equiv) in MeOH (5.0 mL) at 85 ꢀC for 2 h.
1a
2a
b
Same as the entry 5 of Table 1.
Entry
Ox
Additive
Solvent
Recovery of
Yield of
(equiv vs 1a)
1a (%)
2a (%)
The solubility of solid FeCl3 in BTF appears to be minimal since
BTF became only pale yellow upon addition of FeCl3. The oxidation
reaction of 1 in BTF was indeed inefficient without BmimPF6 (entry
5 in Table 1). On the other hand, addition of BmimPF6 to FeCl3
resulted in the formation of liquid phase containing FeCl3. Notably,
this brown colored liquid appears to be in part dissolved in BTF
because BTF phase clearly colored yellow by mixing these two
phases. Increasing the quantity of BmimPF6 decreased the
concentration of FeCl3, and therefore the reaction was gradually
decelerated by adding more quantity of BmimPF6 (entries 4 and 5 in
Table 2).
1
2
CANc
CANc
FeCl3
FeCl3
FeCl3
FeCl3
None
None
CH3CN
BTF
DMF
PhCH3
BTF
0
50
0
0
67
0
53
Traced
72
3b
4b
5b
6b
Pyridine (1.0)
Pyridine (1.0)
Pyridine (1.0)
Pyridine (1.0)
BmimPF6 (2.2)
59
15
BTF
68e
a
Substrate 1a (0.50 mmol), Ox (2.2 equiv), solvent (5.0–10.0 mL), at room tem-
perature for 1 h.
b
Crude product mixture was heated with NaOAc (5.0 equiv) in MeOH (2.0–
5.0 mL) at 85 ꢀC for 2 h.
c
Ce(NH4)2(NO3)6.
d
We next attempted to devise the simpler experimental opera-
tions, which are illustrated in Figure 1. If upper BTF layer of the
reaction mixture is transferred to another flask and subsequently
treated with appropriate base, requisite two-step transformations
Compound 5a was obtained (22%).
Compound 6a was obtained (12%).
e
BTF
BTF
products
substrate
work-up
and
base
isolation
treatment
desired
product
FeCl3
FeCl2
BTF
BmimPF6
BmimPF6
Figure 1.

H. Tsuchida, E. Hasegawa / Tetrahedron 66 (2010) 3447–3451
3449
could be achieved in simpler manner. For this purpose, we needed
to search for the base compatible with BTF. As shown in Table 3,
NaOAc, which is insoluble in BTF was not efficient (entry 1). Thus,
we examined BTF soluble amine bases. While pyridine was not
effective at all (entry 2), more basic Et3N promoted the reaction
(entry 5). Raising the reaction temperature and extending the
reaction time increased the yield of 2a (entry 6). Notably, imidazole
was effective to give 2a in the best yields (entries 3 and 4). On the
other hand, an attempt to optimize the reaction conditions using
strong base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was less
successful (entries 7 and 8). Consequently, imidazole was chosen
for the further experiments.
not significantly change the yield of 2a (compare entry 2 to 1).
However, the reaction in neat ionic liquid without BTF, resulted in
no formation of 2a (entry 3). Then, BTF was replaced with toluene
and cyclohexane. Mixing each solvent with BmimPF6 resulted in
the formation of biphasic solutions. When the reaction of 1a was
conducted under the formed biphasic conditions, the yields of 2a
were quite low in both cases (entries 4 and 5).11 These observations
clearly suggest that the use of proper quantity of BTF is essential
and BTF is certainly superior to toluene and cyclohexane for the
FeCl3 promoted biphasic reaction with BmimPF6.
We also examined the following experiments to further devise
the reaction procedure.12 First, the elimination reaction of 3a with
imidazole was conducted in biphasic solutions without a prior
separation of a BTF layer from a BmimPF6 layer. However, this
one-pot procedure resulted in the less formation of 2a (34%) than
that for the above described two-step procedure (see entry 3 in
Table 3). Secondly, we attempted to reuse the recovered BmimPF6
layer from the biphasic solutions after the reaction of 1a, and found
that 3a was indeed obtained, however, its yield was low (33%).
As described above, the new procedure in which FeCl3 promoted
oxidation in the biphasic solvent system of BmimPF6 and BTF
followed by imidazole treatment in BTF was found to be effective
for the transformation of 1a to 2a. Then, this procedure was applied
to other substrates such as 1b, 1c, and 1d (Scheme 1). In the
reactions of 1c and 1d, the corresponding ring-expanded enones 2c
and 2d were obtained in moderate yields. On the other hand, the
imidazole treatment was not necessary for the reaction of 1b to
obtain naphthol 4 in good yield.
Table 3
Base effect on the elimination of 3a derived from 1a in BTFa
O
O
Me3SiO
1)
2)
Me
Me
Cl
Me
2a
1a
3a
1) FeCl3 / pyridine / BmimPF6 / BTF 2) base / BTF
Entry
Base
pKa
Temp
(ꢀC)
Time
(h)
Yield of 2a
(%)
(conjugate acid)
1
2
3
4
5
6
7
8
NaOAc
Pyridine
Imidazole
Imidazole
Et3N
Et3N
DBU
DBU
4.75c
5.2c
85
85
85
120
85
120
85
rt
2
2
21
21
2
21
2
2
35
0b
6.95d
61
57
41b
56
22
0b
10.65e
14.3f
OH
Me3SiO
a
Substrate 1a (0.50 mmol), FeCl3 (2.2 equiv), pyridine (1.0 equiv), BmimPF6
(2.2 equiv), BTF (5.0 mL), at room temperature for 1 h. BTF layer containing crude
product mixture was treated with base (5.0 equiv) after additional BTF (2.0 mL) was
combined.
1)
1)
1)
Me
Me
Me
O
1b
4
b
Unreacted 3a was detected by 1H NMR.
Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456–463.
Hall, H. K, Jr. J. Am. Chem. Soc. 1957, 79, 5441–5444.
Bruice, T. C.; Schmir, G. L. J. Am. Chem. Soc. 1958, 80, 148–156.
73%
c
d
Me3SiO
e
Me
f
2)
2)
Leffek, K. T.; Pruszynski, P.; Thanapaalasingham, K. Can. J. Chem. 1989, 67,
590–595.
2c
1c
In order to determine the utility of BTF, screening of other sol-
vents was also performed. We chose toluene and cyclohexane,
which dissolve compounds such as 1a, 2a and 3a, and are insoluble
in BmimPF6. As shown in Table 4, less quantity of BTF (1.0 mL) did
51%
O
Me3SiO
Table 4
Solvent effect on the oxidation of 1a and the subsequent elimination of 3aa
2d
1d
52%
O
O
Me3SiO
1)
2)
1) FeCl3 / pyridine / BmimPF6 / BTF 2) imidazole / BTF
Me
Me
Cl
Me
Scheme 1.
2a
1a
3a
1) FeCl3 / pyridine / BmimPF6 / solvent 2) imidazole / solvent
On the basis of the related investigations,8a,c,e,f,13 plausible re-
action pathways are shown in Scheme 2. Single electron transfer
(SET) from the substrate 1 to FeCl3 to give the pair of radical cation
of 1 and chloride ion. Desilylation within the formed ion pair fol-
lows. Cyclopropoxy radical 7, that is a hypothetical intermediate,14
undergoes regioselective ring-opening to produce tertiary alkyl
radical 8 that is subsequently oxidized by another equivalent of
FeCl3 to give thermodynamically stable tertiary carbocation 9.
Addition of the simultaneously generated chloride ion to 9 gives the
chlorine adduct 3. Heating 3 with imidazole leads the elimination
of HCl giving enones 2. In the case of 1b, aromatization of the
expected enone 2b spontaneously occurred without imidazole to
give naphthol 4.
Entry
Solvent (mL)
Yield of 2a (%)
1b
2
3
4
BTF (5.0)
BTF (1.0)
Noc
61
60
0d
PhCH3 (5.0)
c-C6H12 (5.0)
14
Trace
5
a
Substrate 1a (0.50 mmol), FeCl3 (2.2 equiv), pyridine (1.0 equiv), BmimPF6
(2.2 equiv), at room temperature for 1 h. Organic layer containing crude product
mixture was heated at 85 ꢀC with imidazole (5.0 equiv) for 18–21 h after addition of
same solvent (2.0 mL).
b
Same as the entry 3 of Table 3.
BTF (2.0 mL) was used for the reaction with imidazole.
Compound 5a was obtained (7%).
c
d

3450
H. Tsuchida, E. Hasegawa / Tetrahedron 66 (2010) 3447–3451
O
Me3SiO
O
ClSiMe3
FeCl3
SET
R
R
1
Cl
R
internal-bond
cleavage
n
n
n
1
7
8
SET: single electron transfer
FeCl3
SET
O
O
O
OH
imidazole
n = 0
R
Cl
R
Cl
R
Me
n
n
n
4
2
HN
NH
Cl
9
3
Scheme 2.
3. Conclusion
was added to FeCl3 (178.4 mg, 1.10 mmol) and pyridine (0.040 mL,
0.50 mmol) in the presence or absence of BmimPF6 (0.23 mL,
1.10 mmol) in BTF (2 mL) under N2. The resulting mixture was
stirred under N2 at room temperature for 1 h. Then, it was extracted
with Et2O (30 mLꢁ3) after addition of water. The extract was
treated with water, satd aqueous Na2S2O3, satd aqueous NaHCO3,
satd aqueous NaCl, and dried over anhydrous MgSO4. The residue
obtained after concentration was subjected to TLC (CH2Cl2/
n-C6H14¼1/1) to give 3a. In the absence of BmimPF6, 82.7 mg of 1a
(0.34 mmol, 67%) was also recovered. Then, NaOAc (5.0 equiv vs
converted 1a) and MeOH (2–5 mL) were added to 3a. The mixture
was refluxed at 85 ꢀC for 2 h. After cooling, the mixture was con-
centrated, then water (30 mL) was added. The mixture was
extracted with Et2O (30 mLꢁ3). The extract was treated with water,
satd aqueous Na2S2O3, satd aqueous NaHCO3, satd aqueous NaCl,
and dried over anhydrous MgSO4. The residue obtained after con-
centration was subjected to TLC (CH2Cl2/n-C6H14¼1/1) to give 2a,
12.7 mg (0.074 mmol, 15%) or 58.5 mg (0.34 mmol, 68%) in the
absence or presence of BmimPF6, respectively.
We have developed a novel liquid–liquid biphasic reaction system
utilizing a combination of FeCl3 and BmimPF6 in BTF, which could
promote electron transfer reaction of bicyclic cyclopropyl silyl ethers
to give chloro-substituted ring-expanded cycloalkanones. Following
treatment of these compounds with an appropriate base finally pro-
duced substituted cyclic enones. Also noteworthy is that these two-
step reactions were successfully performed in BTF, which allowed
us to skip the ordinary work-up operations for the former oxidation
step, such as water-quench, extraction, and evaporation, and find
imidazole as the best suitable base for the latter elimination step.
FeCl3 isamongthe mostconvenientand leastexpensiveironreagents,
and can be used not only as oxidizing reagent15 but also as Lewis
acid.2,16 Therefore, our newly developed procedure must be also ap-
plicable to other reactions in which both FeCl3 and imidazolium salts
are used.17 Currently, related investigation isundergoing inour group.
4. Experimental section
4.1. General
4.2.3. BmimPF6 quantity effect on FeCl3 promoted reaction of 1a in
BTF. A BTF solution (3 mL) of 1a (123.2 mg, 0.50 mmol) was added
to FeCl3 (178.4 mg,1.10 mmol), pyridine (0.040 mL, 0.50 mmol), and
BmimPF6 (0.10–1.00 mL, 0.96–9.6 mmol) in BTF (2 mL) under N2.
The resulting mixture was stirred under N2 at room temperature for
1 h. Then, a BmimPF6 layer was rinsed with Et2O (2 mL) after
separation from a BTF layer. The residue obtained after concen-
tration of BTF and Et2O was subjected to TLC (CH2Cl2/n-C6H14¼1/1)
to give 1a and 3a. Then, 3a was subjected to NaOAc treatment
described above to give 2a.
NMR spectra were recorded in CDCl3 with Me4Si as an internal
standard at 200 MHz and 270 MHz for 1H NMR, and 50 MHz and
68 MHz for 13C NMR. Column chromatography was performed with
silica gel (Wakogel C-200). Preparative TLC was performed on
20 cmꢁ20 cm plates coated with silica gel (Wakogel B-5F). FeCl3
and Ce(NH4)2(NO3)6 were purchased and used for the reactions.
BTF, anhydrous DMF, and BmimPF6 were purchased and used
without distillation. MeCN was distilled over P2O5 and sub-
sequently distilled with K2CO3. Substrates 1a–d8c,13 were synthe-
sized according to literature procedures. Substrates and products
(2a,13 2c,13 2d,13 3a,13 4,8c 5a,8f and 6a13) are known compounds.
4.2.4. Base effect on the elimination of 3a derived from 1a in BTF. A
BTF solution (3 mL) of 1a (123.2 mg, 0.50 mmol) was added to FeCl3
(178.4 mg, 1.10 mmol), pyridine (0.040 mL, 0.50 mmol), and
BmimPF6 (0.23 mL, 1.1 mmol) in BTF (2 mL) under N2. The resulting
mixture was stirred under N2 at room temperature for 1 h. Then,
a BmimPF6 layer was rinsed with BTF (2 mL) after separation from
BTF layer. A base (2.5 mmol) was added to BTF solution, and the
mixture was stirred at room temperature w120 ꢀC for 2–21 h. After
cooling, the mixture was filtrated and concentrated. The residue
was subjected to TLC (CH2Cl2/n-C6H14¼1/1) to give 2a.
4.2. Reaction with oxidizing reagents
4.2.1. FeCl3 or Ce(NH4)2(NO3)6 promoted reaction of 1a in DMF or
MeCN. FeCl3 promoted reaction of 1a in DMF was previously
reported.8e An MeCN solution (6 mL) of 1a (123.2 mg, 0.50 mmol)
was added to Ce(NH4)2(NO3)6 (603.0 mg, 1.10 mmol) in MeCN
(4 mL) under N2. The resulting mixture was stirred under N2 at
room temperature for 1 h. Then, it was extracted with Et2O
(30 mLꢁ3) after addition of water. The extract was treated with
water, satd aqueous Na2S2O3, satd aqueous NaHCO3, satd aqueous
NaCl, and dried over anhydrous MgSO4. The residue obtained after
concentration was subjected to TLC (CH2Cl2/n-C6H14¼1/1, three
times) to give 2a (45.6 mg, 0.265 mmol, 53%).
4.2.5. Solvent effect on the oxidation of 1a and the subsequent
elimination of 3a. An appropriate solution (0.75 or 3.0 mL) of 1a
(123.2 mg, 0.50 mmol) was added to FeCl3 (178.4 mg, 1.10 mmol),
pyridine (0.040 mL, 0.50 mmol), and BmimPF6 (0.23 mL, 1.1 mmol)
in the same solvent (0.25 or 2.0 mL) under N2. In the case of neat
reaction (entry 3 in Table 4), 1a was dissolved in pyridine and then
the solution was added to FeCl3 and BmimPF6. The resulting mix-
ture was stirred under N2 at room temperature for 1 h. Then,
4.2.2. FeCl3 promoted reaction of 1a in the presence or absence of
BmimPF6 in BTF. A BTF solution (3 mL) of 1a (123.2 mg, 0.50 mmol)

H. Tsuchida, E. Hasegawa / Tetrahedron 66 (2010) 3447–3451
3451
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ration from the solvent layer. Imidazole (170.2 mg, 2.5 mmol) was
added to this solution, and the mixture was heated at 85 ꢀC for 18–
21 h. After cooling, the mixture was filtrated and concentrated. The
residue was subjected to TLC to give 2a.
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4.2.6. General procedure of FeCl3 promoted reaction of 1 and
sequential elimination of 3 in BTF. A BTF solution (3 mL) of 1a
(123.2 mg, 0.50 mmol) was added to FeCl3 (178.4 mg, 1.10 mmol),
pyridine (0.040 mL, 0.50 mmol), and BmimPF6 (0.23 mL, 1.1 mmol)
in BTF (2 mL) under N2. The resulting mixture was stirred under N2
at room temperature for 1 h. Then, a BmimPF6 layer was rinsed
with BTF (2 mL) after separation from BTF layer. Imidazole
(170.2 mg, 2.5 mmol) was added to BTF solution, and the mixture
was heated at 85 ꢀC for 21 h. After cooling, the mixture was filtrated
and concentrated. The residue was subjected to TLC to give 2a.
Same treatment of 1c and 1d gave 2c (0.253 mmol, 51%) or 2d
(0.258 mmol, 52%), respectively. In the case of 1b, 4 (57.6 mg,
0.364 mmol, 73%) was obtained without NaOAc treatment.
4.2.7. FeCl3 promoted reaction of 1a and sequential elimination of 3a
in biphasic solutions without separation of
a BTF layer from
a BmimPF6 layer. A BTF solution (3 mL) of 1a (123.2 mg, 0.50 mmol)
was added to FeCl3 (178.4 mg, 1.10 mmol), pyridine (0.040 mL,
0.50 mmol), and BmimPF6 (0.23 mL, 1.1 mmol) in BTF (2 mL) under
N2. The resulting mixture was stirred under N2 at room tempera-
ture for 1 h. Imidazole (170.2 mg, 2.5 mmol) was added, and the
biphasic solution mixture was heated at 85 ꢀC for 21 h. After
cooling, the mixture was filtrated by Celite and concentrated. The
residue was subjected to TLC (CH2Cl2/n-C6H14¼1/1, three times) to
give 2a (29.5 mg, 0.171 mmol, 34%).
4.2.8. The reaction of 1a with the recovered BmimPF6 after the
reaction of 1a. A BTF solution (5 mL) of 1a (123.2 mg, 0.50 mmol)
was added to the BmimPF6 layer that was separated from the BTF
layer after the reaction of 1a with FeCl3 (2.2 equiv). The resulting
mixture was stirred under N2 at room temperature for 1 h. Then,
BmimPF6 layer was rinsed with BTF (2 mL) after separation from
BTF layer. Imidazole (170.2 mg, 2.5 mmol) was added to BTF solu-
tion, and the mixture was heated at 85 ꢀC for 21 h. After cooling, the
mixture was filtrated and concentrated. The residue was subjected
to TLC (CH2Cl2/n-C6H14¼1/1, twice) to give 2a (28.2 mg,
0.164 mmol, 33%).
9. Iwaya, K.; Tamura, M.; Nakamura, M.; Hasegawa, E. Tetrahedron Lett. 2003, 44,
9317–9320.
10. Same experiments using toluene were conducted (comparable to entries 3, 4,
and 5 in Table 2). However, the reactions were not completed (contrastive to
entry 4 in Table 1). Results are as follows. The quantity of BmimPF6 (equiv): 2.2,
4.8, 9.6; the recovery of 1a (%): 68, 39, 52; the yield of 2a (%): 16, 26, 23,
respectively.
Acknowledgements
We thank Professor Hisahiro Hagiwara (Niigata University) for
his useful comments. We also thank Professor James M. Tanko
(Virginia Polytechnic Institute and State University, USA) for his
help to edit the manuscript. A Grant for Promotion of Niigata
University Research Projects is acknowledged.
11. The difference of the yield of 2a between the result reported in the note 10 and
that of entry 4 in Table 4 could be due to the difference of the solvent to rinse
BmimPF6 phase. While Et2O was used in the former experiment, toluene was
used in the latter. These observations also suggest that toluene would not be an
effective extraction solvent toward BmimPF6.
12. Although these devised procedures, that are more compatible with green
chemistry, do not reach the satisfactory level at this moment, the improvement
of them would be certainly the future subject to investigate. We thank two
reviewers who independently suggested us to conduct these experiments.
13. Hasegawa, E.; Yamaguchi, N.; Muraoka, H.; Tsuchida, H. Org. Lett. 2007, 9,
2811–2814.
14. (a) Ito, Y.; Fujii, S.; Saegusa, T. J. Org. Chem. 1976, 41, 2073–2074; (b) Iwasawa, N.;
Hayakawa, S.; Funahashi, M.; Isobe, K.; Narasaka, K. Bull. Chem. Soc. Jpn. 1993,
66, 819–827; (c) Booker-Milburn, K. I.; Thompson, D. F. J. Chem. Soc., Perkin
Trans. 1 1995, 2315–2321; (d) Jida, M.; Guillot, R.; Ollivier, J. Tetrahedron Lett.
2007, 48, 8765–8767.
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