Efficient synthesis of benzofurans utilizing [3,3]-sigmatropic rearrangement triggered by N-trifluoroacetylation of oxime ethers: Short synthesis of natural 2-arylbenzofurans

Article abstract of DOI:10.1002/ejoc.200601001

A new synthetic method for the preparation of benzofurans has been developed. The key step of this method is the [3,3]-sigmatropic rearrangement of N-trifluoroacetyl-ene-hydroxylamines, which was triggered by acylation of oxime ethers. TFAA has been proved to be the best reagent to induce [3,3]-sigmatropic rearrangement for the synthesis of cyclic or acyclic dihydrobenzofurans. On the other hand, the TFAT-DMAP system is found to be the most effective for constructing various benzofurans. Synthetic utility of this reaction is demonstrated by the short synthesis of natural benzofurans without protection of the hydroxy group. The synthesis of Stemofuran A was accomplished via condensation of ketones with aryloxyamine and subsequent reaction with TFAT-DMAP in a four-step synthesis with 72% overall yield. Similarly, Eupomatenoid 6 and Coumestan were synthesized through the reaction of oxime ether with TFAT-DMAP. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200601001

FULL PAPER
DOI: 10.1002/ejoc.200601001
Efficient Synthesis of Benzofurans Utilizing [3,3]-Sigmatropic Rearrangement
Triggered by N-Trifluoroacetylation of Oxime Ethers: Short Synthesis of
Natural 2-Arylbenzofurans
Norihiko Takeda,[a] Okiko Miyata,[a] and Takeaki Naito*[a]
Keywords: Benzofuran / Sigmatropic rearrangement / Total synthesis / Trifluoroacetic anhydride / Trifluoroacetyl triflate
A new synthetic method for the preparation of benzofurans
has been developed. The key step of this method is the [3,3]-
sigmatropic rearrangement of N-trifluoroacetyl-ene-hydrox-
ylamines, which was triggered by acylation of oxime ethers.
TFAA has been proved to be the best reagent to induce [3,3]-
sigmatropic rearrangement for the synthesis of cyclic or
acyclic dihydrobenzofurans. On the other hand, the TFAT-
tion is demonstrated by the short synthesis of natural benzo-
furans without protection of the hydroxy group. The synthe-
sis of Stemofuran A was accomplished via condensation of
ketones with aryloxyamine and subsequent reaction with
TFAT-DMAP in a four-step synthesis with 72% overall yield.
Similarly, Eupomatenoid 6 and Coumestan were synthesized
through the reaction of oxime ether with TFAT-DMAP.
DMAP system is found to be the most effective for con- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
structing various benzofurans. Synthetic utility of this reac- Germany, 2007)
of our knowledge, there has been no report on reagent-con-
trolled synthesis of dihydrobenzofurans 3 and benzofurans
4 by highly efficient [3,3]-sigmatropic rearrangement under
Introduction
Benzofurans and dihydrobenzofuran (coumaran) have
attracted widespread interest in view of their presence in
mild conditions.
natural products, and their biological and pharmacological
activities.[1] The benzofuran nucleus is a central component
of a diverse class of heterocyclic natural and synthetic prod-
ucts that possess a broad range of biological activities.[2]
However, known synthetic methods of benzofuran utiliz-
ing [3,3]-sigmatropic rearrangement[3] exhibit some disad-
vantages: (i) acid catalysts, such as H2SO4 and HCl, and
high temperature are generally required for the successful
reaction, (ii) these harsh conditions cannot be applied to
acid-sensitive substrates, (iii) in most cases, the desired ben-
zofurans were obtained in only moderate yields, and (iv) a
Scheme 1. General reaction of the oxime ethers 1 with TFAA or
TFAT-DMAP.
synthetic method for dihydrobenzofurans has not yet been
well established.
From the background described above, we have recently
reported effective synthetic methods for the dihydrobenzo-
Results and Discussion
furans 3 and benzofurans 4 involving acylation, rearrange-
ment, and intramolecular cyclization reactions of the oxime
ethers 1 (Scheme 1).[4] In this paper, we describe the full
details of the synthesis of the dihydrobenzofurans 3 and
benzofurans 4 by optimizing reaction conditions. Further-
more, we have also applied a newly found efficient pro-
cedure to a short synthesis of natural products, namely Ste-
mofuran A,[5] Eupomatenoid 6[6] and Coumestan,[7] with-
out protection of the phenolic hydroxy group. To the best
Benzofuran and Dihydrobenzofuran Synthesis by [3,3]-
Sigmatropic Rearrangement of N-Trifluoroacetyl-ene-
hydroxylamines Generated in Situ
A series of requisite oxime ethers 7 were prepared by the
reaction of O-arylhydroxylamine 5 with the corresponding
ketones 6 in good to high yields (Table 1). Compound 5 was
prepared from commercially available arylboronic acid in
two steps according to the literature procedures.[8] The ox-
ime ethers 7Ie,7Je, and 7Ke carrying either an o-, m-, or a
p-nitro group were easily prepared from acetophenone ox-
ime and nitrofluorobenzenes 8A–C (Table 2).
[a] Kobe Pharmaceutical University,
4-19-1, Motoyamakita, Higashinada, Kobe 658-8558, Japan
Fax: +78-441-7554
E-mail: taknaito@kobepharma-u.ac.jp
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FULL PAPER
Table 1. Preparation of oxime ethers 7Aa–7He.
Entry
Substrate
R1
Ketone
R2
R3
Product[a]
% Yield
1
2
3
4
5
6
7
8
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5A
5B
5C
5D
5E
5F
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
6a
6b
6c
6d
6e
6f
6g
6h
6i
–(CH2)3–
7Aa
7Ab
7Ac
7Ad
7Ae
7Af
7Ag
7Ah
7Ai
98
91
89
79
86
91
91
98
–(CH2)4–
Me
H
H
H
H
H
H
Me
Me
Me
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Et
Me
Ph
p-BrC6H4
p-NO2C6H4
p-OHC6H4
p-OMeC6H4
Ph
p-BrC6H4
p-OHC6H4
p-OMeC6H4
m-BrC6H4
m-NO2C6H4
m-OHC6H4
m-OMeC6H4
o-BrC6H4
o-NO2C6H4
o-OHC6H4
o-OMeC6H4
Ph
9
96
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
6j
6k
6l
7Aj
90[b]
93[b]
96[b]
88[b]
97
7Ak
7Al
6m
6n
6o
6p
6q
6r
6s
6t
6u
6e
6e
6e
6e
6e
6e
6e
7Am
7An
7Ao
7Ap
7Aq
7Ar
7As
7At
7Au
7Be
7Ce
7De
7Ee
7Fe
91
90
H
H
H
H
93
89[c]
78[d]
84
H
95[b]
97
p-Br
p-Me
m-Br
m-Me
m-OMe
o-Br
o-Me
Ph
Ph
Ph
Ph
Ph
Ph
99
94
99
81
97
99
5G
5H
7Ge
7He
[a] 7Aa–7Ad were carried out in MeOH at room temperature (Entries 1–4). 7Ae–7He were carried out in EtOH and concd. aqueous HCl
(cat.) at room temperature (Entries 5–28). [b] E:Z = 10:1. [c] E:Z = 4:1. [d] Stereostructures of E and Z isomers (4.5:1) have not been
established.
Table 2. Preparation of oxime ethers 7Ie–Ke.
(TFAA) (1 equiv.) and Et3N (1.5 equiv.) in CH2Cl2 at 0 °C
gave the rearranged product 11Aa in 8% yield along with
the unreacted starting material 7Aa (Entry 1).
Upon treatment with trifluoroacetic acid (TFA), the phe-
nol 11Aa could be readily converted to the dihydrobenzofu-
ran 10Aa. This result suggests strongly that 11Aa could be
formed by acylation of the oxime ether 7Aa with TFAA
followed by [3,3]-sigmatropic rearrangement of the resulting
N-trifluoroacetyl-ene-hydroxylamine 9Aa. Additionally,
TFA was found to be essential for the cyclization reaction
of the rearranged product 11Aa as a possible intermediate.
Therefore, we expected that the reaction of the oxime ether
Entry
Substrate
R
Product
% Yield
1
2
3
8A
8B
8C
p-NO2
m-NO2
o-NO2
7Ie
97
87
90
7Je[a]
7Ke
[a] 8B and acetophenone oxime were mixed with tBuOK in DMF 7Aa with TFAA in the absence of a base would proceed to
and then the reaction mixture was heated at 80 °C.
afford the desired dihydrobenzofuran 10Aa. In fact, trifluo-
roacetylation, [3,3]-sigmatropic rearrangement, and cycliza-
tion of 7Aa proceeded smoothly in the presence of TFAA
Under the reaction conditions employed in our related (1 equiv.) without a base to afford the corresponding cis-
work involving a hydrazone system,[9] we first examined tri- dihydrobenzofuran 10Aa in excellent yield at even below
fluoroacetylation of the oxime ether 7Aa (Table 3). Treat- room temperature (Entry 2). In the reaction at room tem-
ment of the oxime ether 7Aa with trifluoroacetic anhydride perature, the desired 10Aa was formed after being stirred
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Short Synthesis of Natural 2-Arylbenzofurans
FULL PAPER
Table 3. Reaction of oxime ether 7Aa with acid anhydride.
Entry
Reagent (equiv.)
R
T/°C
t/h
% Yield 10Aa
[a]
1
2
3
4
5
6
7
8
TFAA (1), Et3N (1.5)
TFAA (1)
TFAA (1)
TFA (1)
TCAA (1)
Ac2O (1)
TFAT (1)
TFAT (1), Et3N (1.5)
TFAT (1), Et3N (5)
TFAT (2), Et3N (1)
TFAT (2), pyridine (1)
TFAT (2), pyridine (1), DMAP (0.1)
TFAT (2), DMAP (0.1)
TFAT (2), DMAP(1)
COCF3
COCF3
COCF3
H
COCCl3
COCH3
COCF3
COCF3
COCF3
COCF3
COCF3
COCF3
COCF3
COCF3
0
0
4
3
1
20
5
8
2
0.5
2
0.5
0.5
0.5
0.5
0.5
–
99
99
room temp.
room temp.
40
40
0
0
0
0
0
[b]
–
[c]
–
[d]
–
58 (9)[e]
24 (67)[e]
[d]
9
–
10
11
12
13
14
80
30 (39)[e]
84
0
0
0
69 (16)[e]
89
[a] 11Aa was obtained in 8% yield and 7Aa was recovered. [b] 10d was obtained in 16% yield. [c] 10b was obtained in 94% yield. [d]
7Aa was recovered. [e] Yields in parentheses are for the recovered 7Aa.
for 1 h (Entry 3). This is the first example of the formation ran 10Aa in 80% yield (Entry 10). Replacement of Et3N by
of dihydrobenzofuran 10Aa which was formed only by acyl- pyridine as a base led to lower chemical yield (30%) (Entry
ation conditions. The cis-dihydrobenzofuran 10Aa was un- 11). However, the yield of dihydrobenzofuran 10Aa was im-
ambiguously characterized by 1H NMR, 13C NMR, COSY, proved by the addition of a catalytic amount of DMAP
and NOESY spectroscopic analyses.
(Entry 12). Though the reaction with TFAT (1 equiv.) in
In order to check the possibility that TFA itself might the presence of DMAP (0.1 equiv.) as a base proceeded ef-
facilitate the [3,3]-sigmatropic rearrangement by proton- fectively to give 10Aa in moderate yield (Entry 13), reaction
ation at the nitrogen atom, we examined the reaction of with a combination of TFAT (2 equiv.) and DMAP
oxime ether 7Aa with only TFA and found that the 3a- (1 equiv.) gave the desired dihydrobenzofuran 10Aa in 89%
aminodihydrobenzofuran 10d was isolated in 16% yield yield (Entry 14). Thus, our reaction involving acylation,
(Entry 4). Therefore, it is apparent that the acylation reac- [3,3]-sigmatropic rearrangement, and cyclization was found
tion of 7Aa for the formation of acyl-ene-hydroxylamine is to be accelerated when oxime ether was acylated with a
the main and crucial step for [3,3]-sigmatropic rearrange- stronger reagent bearing an electron-withdrawing group
ment.
such as the trifluoroacetyl group. We choose TFAA in the
Next, we investigated systematically the acylation by formation of dihydrobenzofuran.
changing four types of acylating reagents. When trichlo-
In order to establish intermediary N-trifluoroacetyl-ene-
roacetic anhydride (TCAA) was used as an acylating rea- hydroxylamine 9Aa which would be possibly formed by
gent, the reaction proceeded in refluxing CH2Cl2 to give acylating oxime ether 7Aa, we examined acylation of O-
dihydrobenzofuran 10b in good yield (Entry 5). In contrast benzyl oxime ether 12[11] (Table 4). Oxime ether 12 was pre-
to TFAA and TCAA, Ac2O did not give satisfactory results, pared by condensation of cyclopentanone with O-benzylhy-
and the starting material was completely recovered (Entry droxylamine and then subjected to acylation with TFAA or
6). The reaction of 7Aa with trifluoroacetyl triflate TFAT in the presence of DMAP. The product was expected
(TFAT),[10] which is a stronger acylating reagent than N-trifluoroacetyl-ene-hydroxylamine 13 which was ob-
TFAA, gave 10Aa in lower 58% yield (Entry 7). However, tained in moderate to good yield (Entries 1 and 2). Thus,
treatment of 7Aa with a mixture of TFAT (1 equiv.) and formation of the intermediate 9Aa is proposed in our reac-
Et3N (1.5 equiv.) gave the dihydrobenzofuran 10Aa in 24% tion though the isolation was not achieved yet.
yield along with 67% yield of the starting material 7Aa (En-
We next investigated the reaction of the oxime ether 7Ab
try 8). The presence of excess Et3N retarded the reaction derived from cyclohexanone (Table 5). Reaction of 7Ab
(Entry 9). Reaction of 7Aa with TFAT (2 equiv.) and Et3N with TFAA at room temperature suffered from the compet-
(1 equiv.) proceeded smoothly to give the desired dihydrofu- ing formations of the dihydrobenzofuran 10Ab, the benzo-
Eur. J. Org. Chem. 2007, 1491–1509
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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N. Takeda, O. Miyata, T. Naito
FULL PAPER
Table 4. Reaction of oxime ether 12 with TFAA or TFAT-DMAP. TFA proceeded to give the desired 2,3-dihydrobenzofuran
15 in moderate yield. In order to determine the reaction
pathway, we investigated the conversion of the dihydroben-
zofuran 10Ab to the benzofuran 14Ab (Table 6). Through
extensive screening of the reaction conditions, we found
that treatment of the dihydrobenzofuran 10Ab with trifluo-
romethanesulfonic acid (TfOH) gave the benzofuran 14Ab
effectively as a result of elimination of the trifluoroacet-
Entry
Reagent (equiv.)
Base (equiv.)
% Yield
amido group, while the treatment with TFA required a
longer reaction time (Entries 1 and 2). Treatment of 10Ab
with either DMAP or its salt 16[13] resulted in the recovery
of the starting compound only (Entries 3 and 4). In the
reaction with TFAT, it was clearly indicated that the dihy-
drobenzofuran 10Ab was converted to the benzofuran 14Ab
by treatment with TfOH, which was unavoidably generated
as a byproduct in the trifluoroacetylation of the oxime ether
7Ab.
1
2
TFAA (1)
TFAT (2)
–
81
63
DMAP (1)
furan 14Ab, and the rearranged products 11Ab, 11ЈAb (En-
tries 1, 2). The ratio of benzofuran 14Ab to dihydrobenzo-
furan 10Ab obtained was found to be influenced by the
temperature used. Lower temperature (0 °C) favored the
formation of dihydrobenzofuran 10Ab. When the reaction
was carried out in dichloromethane with TFAA at 0 °C, the
From the above results, we can propose plausible reac-
desired dihydrobenzofuran 10Ab was obtained as the sole tion pathways to dihydrobenzofuran 10Ab and benzofuran
product (Entry 3). On the contrary, treatment of 7Ab with 14Ab (Scheme 2). First, acylation on the nitrogen atom of
TFAT and DMAP produced exclusively the benzofuran the oxime ether 1 leads to the formation of N-trifluoroace-
14Ab in 83% yield (Entry 4). When the reaction was carried tyl-ene-hydroxylamine 2, and then the [3,3]-sigmatropic re-
out in CH2Cl2 with TFAT (5 equiv.) and DMAP (3 equiv.) arrangement smoothly follows to form the acylimine 17.
as a base, a highest yield of 92% was achieved for benzofu- Formation of the dihydrobenzofuran 3 would proceed by
ran 14Ab (Entry 6). It is worthy to note that the selective intramolecular cyclization of 17. When TFAT was used as
synthesis of either dihydrobenzofuran 10Ab or benzofuran an acylating agent, the benzofuran 4 was formed through
14Ab was achieved only by changing the reaction condi- oxonium ion 18, which was generated by elimination of the
tions such as the TFAA or TFAT-DMAP system.
trifluoroacetamido group in the presence of TfOH. The
We examined the reductive deamination of the dihydro- overall pathway would be very similar to that of Fischer
benzofuran 10Ab for the synthesis of the 2,3-dihydrobenzo- indolization, which involves analogous three-step key reac-
furan (coumaran) 15.[12] Though reductive deamination of tions of hydrazones. However, it is generally difficult to iso-
10Ab with sodium cyanoborohydride in acetic acid did not late dihydrobenzofurans under Fischer indolization condi-
occur at all, the reaction of 10Ab with the same reagent in tions. To the best of our knowledge, there has been only
Table 5. Reaction of oxime ether 7Ab with TFAA or TFAT-DMAP.
Entry
Reagent (equiv.)
T/°C
t/h
% Yield
10Ab
14Ab
11Ab+11ЈAb[a]
1
2
3
4
5
6
TFAA (1)
TFAA (2)
TFAA (4)
TFAT (2), DMAP (1)
TFAT (5), DMAP (3)
TFAT (5), DMAP (3)
room temp.
room temp.
0
0
23
23
23
0.5
0.5
0.5
37
53
94
–
–
–
19
10
–
83
90
92
23
19
–
–
–
0
room temp.
–
[a] Combined yields of two regioisomers.
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Short Synthesis of Natural 2-Arylbenzofurans
FULL PAPER
Table 6. Conversion of 10Ab to 2,3-dihydrobenzofuran 15 and ben-
zofuran 14Ab.
In order to disclose the role of DMAP, we examined the
preparation of N-trifluoroacetylaniline[14] by acylation with
commercially available TFAT which gave the desired amide
in not quantitative yield but 63% yield. It suggests that
TFAT itself is not so pure and contains a small amount of
TFA and TfOH.
As shown in Entry 4 of Table 3, the reaction of 7Aa with
only TFA gave the dihydrobenzofuran 10d in 16% yield,
suggesting that the rearrangement step of the protonated
intermediate is less effective than that under acylating con-
ditions. Furthermore, reaction with commercially available
TFAT gave the dihydrobenzofuran 10Aa in 58% yield, but
the product yield increased to 89% when DMAP was added
(Entries 7 and 14).
Although the precise reason for the effect of DMAP on
the reaction with TFAT is unclear, DMAP would accelerate
the first acylation step. DMAP traps a small amount of
TFA and TfOH which are contaminated with commercially
available TFAT.[15] Thus, in the presence of DMAP (in the
absence of a proton source such as TFA and TfOH), the
acylation reaction of the oxime ether 1 (1Ǟ2) would effec-
tively proceed to effect the subsequent rearrangement step
(2Ǟ17) (Scheme 2).
To investigate the scope and limitations of the TFAA or
TFAT-DMAP system utilized for benzofuran synthesis, we
next tried to use a series of acyclic oxime ethers 7Ac,d as
substrate (Table 7). Reaction of oxime ether 7Ac,d with
TFAA gave the dihydrobenzofuran 10Ac,d in good yield
(Entries 2 and 4). On the contrary, the reaction with a com-
bination of TFAT and DMAP gave exclusively the benzofu-
ran 14Ac,d (Entries 3, 5 and 6). These results clearly dem-
onstrate the utility of [3,3]-sigmatropic rearrangement as a
novel method for the synthesis of complex benzofurans.
The remarkable result obtained in the reaction of oxime
ethers 7Aa–d prompted us to extend our procedure to the
synthesis of various types of 2-arylbenzofurans.
Entry
Reagent (equiv.)
t
% Yield 14Ab
1
2
3
4
TfOH (1)
TFA (1)
DMAP (1)
1 min
6 h
24 h
24 h
84
80
[a]
–
[a]
–
(2)
TFAT (5),
DMAP (3)
5
0.5 h
94
[a] 10Ab was recovered.
one paper pertaining to the isolation of dihydrobenzofurans
which were synthesized from the oxime ethers bearing α,αЈ-
disubstituted cyclopentane ring.[3h]
Table 7. Reaction of oxime ethers 7Ac,d with TFAA or TFAT-
DMAP.
Scheme 2. Possible reaction pathway.
The different structures of the two products in the reac-
tion with TFAT-DMAP (dihydrobenzofuran 10Aa from cy-
clopentanone oxime ether 7Aa and benzofuran 14Ab from
cyclohexanone oxime ether 7Ab) could be explained as fol-
lows. The benzofuran double bond is not readily accommo-
dated in a fused system such as 2,3-dihydro-1H-cyclopenta-
[b]benzofuran in which two rings are five-membered and
rather rigid. On the other hand, it is clear that no compar-
able difficulty exists in the elimination of the trifluoroacet-
amido group when a more flexible six-membered cyclohex-
ane ring is present.
Entry Substrate Reagent
(equiv.)
Solvent T/°C
t/h % Yield
10Ac,d 14Ac,d
1
2
3
7Ac
7Ac
7Ac
TFAA (6)
TFAA (6)
TFAT (5),
DMAP (3)
TFAA (6)
TFAT (5),
DMAP (3)
TFAT (5),
DMAP (3)
CH2Cl2 40
9
5
2
21
64
–
–
–
89
MeCN
CH2Cl2
80
0
4
5
7Ad
7Ad
MeCN
CH2Cl2
80
0
4
2
94
–
–
43
6
7Ad
CH2Cl2 room 0.5
temp.
–
65
Eur. J. Org. Chem. 2007, 1491–1509
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N. Takeda, O. Miyata, T. Naito
FULL PAPER
The Substituent Effect on the Benzene Ring of the
Arylimine Part; Synthesis of 2-Arylbenzofurans 14Ae–u
benzofuran 14Ah was directly obtained after chromatog-
raphy using silica gel (Entry 4). We succeeded in the isola-
tion of the p-trifluoroacetyloxybenzofuran 14Av by only
recrystallization (not chromatography) of the crude product
obtained from the oxime ether 7Ah (Entry 5). Unfortu-
nately, the reaction of 7Ai with the p-methoxy group af-
forded the desired benzofuran 14Ai (15%) along with the
starting material (12%) and the 3-trifluoroacetylbenzofuran
14ЈAi (21%) (Entry 6). Compound 14ЈAi would be formed
through trifluoroacetylation at the 3-position of the benzo-
furan 14Ai formed under the reaction conditions.
Oxime ethers bearing an additional carbon 7Aj–l under-
went effective reaction under the same reaction conditions
to afford the corresponding 2-aryl-3-methylbenzofurans
14Aj–l in excellent yields (Entries 7–9). However, the oxime
ether 7Am with the p-methoxy group gave the desired ben-
zofuran 14Am but in low yield though the reason is not
clear (Entry 10). Substituents at the m position had no
marked influence on the reaction, giving the expected ben-
zofurans 14An–q in excellent yields (Entries 11–14).
To test the scope of this novel method for the synthesis
of benzofurans, we next examined the substituent effects on
the aromatic ring in the reaction of the oxime ethers 7Ae–
u with the TFAT-DMAP system (Table 8).[16] Among ben-
zofurans, 2-arylbenzofurans are inhibitors of cell prolifera-
tion and platelet activating factor and some of them show
other interesting activities.[17] Thus, we started to investigate
the substituent effect of our reaction and its application to
the synthesis of 2-arylbenzofurans.
Treatment of the unsubstituted oxime ether 7Ae with
TFAT and DMAP gave the desired 2-phenylbenzofuran
14Ae quantitatively. We could not isolate the proposed in-
termediate 9Ae which underwent the [3,3]-sigmatropic re-
arrangement to afford the final benzofuran 14Ae (Entry 1).
Similarly, reaction of the oxime ether 7Af,g bearing an elec-
tron-withdrawing substituent such as a bromo or nitro
group at the p position proceeded smoothly to give the 2-
arylbenzofuran 14Af,g in good yields (Entries 2 and 3). To
The next substrates of choice were the oxime ethers 7Ar–
our delight, when the oxime ether 7Ah bearing a free hy- u with an ortho-substituted phenyl group. o-Bromo, o-hy-
droxy group was treated with TFAT-DMAP, the hydroxy- droxy, and o-methoxy-oxime ethers 7Ar,t,u were employed
Table 8. Reaction of oxime ethers 7Ae–u with TFAT-DMAP.
Entry
Substrate
R1
R2
t/h
Product
% Yield
1
2
3
4
5
6
7
8
7Ae
7Af
7Ag
7Ah
7Ah
7Ai
H
H
H
H
H
H
Me
Me
Me
Me
H
H
H
H
H
H
H
H
H
p-Br
p-NO2
p-OH
p-OH
p-OMe
H
1
1.5
5
2
2
2
2
2
2
2
2
5
2
1.5
2
2
2
2
14Ae
14Af
14Ag
14Ah
14Av
14Ai
14Aj
14Ak
14Al
14Am
14An
14Ao
14Ap
14Aq
14Ar
19As
14At
14Au
99
96
85 (9)[a]
84
92
15 (12)[a][b]
7Aj
82
91
86
7Ak
7Al
p-Br
9
p-OH
p-OMe
m-Br
m-NO2
m-OH
m-OMe
o-Br
o-NO2
o-OH
o-OMe
10
11
12
13
14
15
16
17
18
7Am
7An
7Ao
7Ap
7Aq
7Ar
7As
7At
7Au
26 (13)[a]
94
95
86
93
76
78[c]
82
80
[a] Yields in parentheses are for the recovered starting materials. [b] 14ЈAi was obtained in 21% yield. [c] 19As was obtained instead of
14As.
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Eur. J. Org. Chem. 2007, 1491–1509

Short Synthesis of Natural 2-Arylbenzofurans
FULL PAPER
under the same conditions to give the desired benzofurans lowers the reactivity of the intermediates A and B formed
14Ar,t,u in good yields (Entries 15, 17, and 18). When the from 7Ai and 7Am toward nucleophilic attack of the car-
o-nitro oxime ether 7At was treated with TFAT-DMAP, bonyl oxygen. In contrast, reaction of the oxime ether 7Au
benzofuran was not obtained, but the rearranged product bearing an o-methoxy group under the same conditions
19As was isolated (Entry 16).
gave the desired 2-arylbenzofuran 14Au in good yield. This
In the case of the oxime ether 7Ah with the hydroxy result would be explained as follows. Steric hindrance be-
group, acylation would proceed at both the arylimine part tween the o-methoxy group and the imine part would make
and the hydroxy group to form a diacylated ene-hydroxyl- the intermediate C nonplanar, and the resonance effect be-
amine, which then rearranged to afford the acylated 2-aryl- tween the benzene ring and the acyl imine part would there-
benzofuran 14Av. This labile benzofuran 14Av was readily fore not be very strong. Thus, the electrophilic reactivity of
hydrolyzed during column chromatography using silica gel the acyl imine part is not as low as that of the p-methoxy
to give the phenolic benzofuran 14Ah. Similarly, the oxime substrate.
ethers 7Al, 7Ap and 7At, all of which have the hydroxy
group, would give the desired 2-arylbenzofurans 14Al, 14Ap
and 14At via the corresponding diacylated intermediates.
As mentioned above, the series of reactions leading to
the formation of 2-arylbenzofurans proceeded smoothly ex-
cept for oxime ethers having a p-methoxy group (7Ai and
7Am) (Figure 1). The electron-donating methoxy group
The Effects of Substituents on the Phenoxy Ring; Synthesis
of 2-Phenylbenzofurans 14Be–Le Functionalized at the 4–7
Positions
In order to explore the wide generality of our benzofuran
synthesis, we have newly investigated the substituent effects
in [3,3]-sigmatropic rearrangement of O-aryl-ene-hydroxyl-
amines 9Be–Le, which were generated in situ by acylation
of the substituted oxime ethers 7Be–Le (Table 9). Treatment
of the oxime ethers 7Be, 7Ie, 7Ce carrying p-bromo, p-nitro,
p-methyl groups with TFAT-DMAP afforded, as expected,
the functionalized 2-phenylbenzofurans 14Be, 14Ie, 14Ce in
good to excellent yields (Entries 1–3). A similar trend was
observed in the reaction of the oxime ethers 7Ge, 7Ke, 7He
with the o-substituted group such as bromo, nitro, and
methyl groups. o-Bromo and o-methyl oxime ethers 7Ge
and 7He gave the corresponding 7-substituted 2-phenylben-
zofurans 14Ge and 14He in good yields though reaction
times are different (Entries 9 and 11). Reaction of the oxime
ether 7Ke having the o-nitro group proceeded to give a sepa-
Figure 1. Acylimines A, B, and C with a methoxy group as interme-
diates.
Table 9. Reaction of oxime ethers 7Be–Le with TFAT-DMAP.
Entry
Substrate
R1
t/h
Product
% Yield
Ratio[g] 14:14Ј
1
2
3
4
5
6
7
8
7Be
7Ie
7Ce
7De
7Je
7Ee
7Le[e]
7Fe
7Ge
7Ke
7He
p-Br
p-NO2
p-Me
2
22
2
3
22
2
2.5
3
22
22
4
14Be[a]
81
14Ie[a]
84
14Ce[a]
73[h]
92
m-Br
14De[b]+14ЈDe[c]
14Je[b]+14ЈJe[c]
14Ee[b]+14ЈEe[c]
14Le[b]+14ЈLe[c]
14Fe[b]+14ЈFe[c]
14Ge[d]
1:1
2:1
1:1.5
1:1.5
1:4
m-NO2
m-Me
m-OH
m-OMe
o-Br
o-NO2
o-Me
84
94
85
78
9
10
11
80
14Ke[d]
41[f]
89
14He[d]
[a] 14Be,Ie,Ce were 5-substituted benzofurans. [b] 14De,Je,Ee,Le,Fe were 4-substituted benzofurans. [c] 14ЈDe,Je,Ee,Le,Fe were 6-substi-
tuted benzofurans. [d] 14Ge,Ke,He were 7-substituted benzofurans. [e] 7Le was prepared by treatment of 7Fe with BBr3. [f] 19Ke was
obtained in 24% yield and 7Ke was recovered in 16% yield. [g] The ratios of regioisomers were determined by 1H NMR analysis. [h]
Reaction was carried out at 0 °C.
Eur. J. Org. Chem. 2007, 1491–1509
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1497

N. Takeda, O. Miyata, T. Naito
FULL PAPER
rable mixture of the 7-substituted 2-phenylbenzofurans prepared from 20, was condensed with dihydroxyacetophe-
14Ke and rearranged product 19Ke (Entry 10). Reaction of none to afford the oxime ether 21 in good yield. When the
oxime ether 7De, 7Je, 7Ee, 7Le, 7Fe bearing a bromo, nitro, oxime ether 21 was treated with TFAT in the presence of
methyl, hydroxy or methoxy group at the m position pro- DMAP at room temperature, the desired benzofuran was
ceeded smoothly to give the desired 2-phenylbenzofuran isolated in excellent yield and found to be identical with
14De, 14Je, 14Ee, 14Le, 14Fe and 14ЈDe, 14ЈJe, 14ЈEe, Stemofuran A (22) upon comparison of their spectroscopic
14ЈLe, 14ЈFe in good yields (Entries 4–8). The m-substituted data with those reported in the literature.[5] Thus, short syn-
oxime ethers 7De, 7Je, 7Ee, 7Le, 7Fe, however, gave two thesis of Stemofuran A (22) was accomplished in four steps
types of benzofurans with low regioselectivity in all cases.
with 72% overall yield.
Secondly, we chose Eupomatenoid 6 (26)[6] as our syn-
thetic target which has shown antifungal, insecticidal, and
antioxidant activities. Although Bach’s[19] and Steven-
son’s[20] groups synthesized Eupomatenoid 6, the syntheses
include many transformations involving protection and de-
protection of the hydroxy group. To introduce the (E)-pro-
penyl group of Eupomatenoid 6 at the last stage of our
synthesis, we constructed the benzofuran part as the first
step. Condensation of O-phenylhydroxylamine (5B) carry-
ing the p-bromo group with p-hydroxypropiophenone gave
the oxime ether 24 which was subjected to our reaction con-
ditions to afford the 5-bromobenzofuran 25 in 95% yield.
Finally, the benzofuran 25 was subjected to the Suzuki
coupling reaction with (E)-propenyl boronic acid to afford
Eupomatenoid 6 (26) in excellent yield. Thus, we succeeded
in the total synthesis of Eupomatenoid 6 in 52% overall
yield from 23 in five steps. Physical and spectral properties
of our prepared benzofuran 26 were identical with those of
natural Eupomatenoid 6 reported in the literature.[6] Our
Effective and Short Syntheses of Stemofuran A,
Eupomatenoid 6 and Coumestan
As mentioned above, our novel synthetic method for ben-
zofurans is an efficient and practical method because pro-
tection of the phenolic hydroxy groups is not required in the
synthesis of hydroxylated 2-arylbenzofurans. This finding
prompts us to explore a new efficient procedure for the syn-
thesis of biologically active natural benzofurans. Thus, we
started to synthesize natural and biologically active benzo-
furan products such as Stemofuran A (22)[5] Eupomatenoid
6 (26),[6] and Coumestan (29),[7] the latter of which does not
have a hydroxy group. Our short synthesis of these products
has been accomplished without protection of the phenolic
hydroxy groups (Scheme 3).
At first, we examined the synthesis of Stemofuran A (22),
recently isolated from Stemona collinsae.[5] The known syn-
thesis of Stemofuran A reported by Pasturel et al.[18] in-
volved many steps including the protection/deprotection of synthesis is superior to those reported by Bach’s and Ste-
the hydroxy group. O-Phenylhydroxylamine (5A), readily venson’s groups in both yield and number of steps.
Scheme 3. Short syntheses of Stemofuran A, Eupomatenoid 6, and Coumestan. Reaction conditions: a) 2 steps, 83%, ref.[8]; b) 3,5-
dihydroxyacetophenone, concd. aqueous HCl, EtOH, room temp., 3 h, 92%; c) TFAT, DMAP, CH2Cl2, room temp., 26 h, 95%; d) 2
steps, 62%, ref.[8]; e) 4-hydroxypropiophenone, concd. aqueous HCl, EtOH, room temp., 2 h, 92%; f) TFAT, DMAP, CH2Cl2, room
temp., 8.5 h, 95%; g) trans-propenylboronic acid, Pd(PPh3)4, CsF, DME, 100 °C, 7 h, 97%; h) 4-chromanone, concd. aqueous HCl, EtOH,
room temp., 2 h, 93%; i) TFAT, DMAP, CH2Cl2, room temp., 4 h, 78%; j) PCC, CH2Cl2, 40 °C, 4 h, 76 %.
1498
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Eur. J. Org. Chem. 2007, 1491–1509

Short Synthesis of Natural 2-Arylbenzofurans
FULL PAPER
The third target of our synthesis is Coumestan (29),[7]
which is a basic pharmacophore containing Coumestanes
such as Coumestrol[21] which shows estrogenic activity. Due
to its unique structure and biological activities, Coumestan
(29) had been synthesized by many organic chemists using
independent approaches.[22] Known synthetic methods in-
volved the preparation of the benzofuran part at the last
stage while we constructed the benzofuran part of Coumes-
tan as the first step. Condensation of a common O-phenyl-
hydroxylamine (5A) with 4-chromanone followed by se-
quential acylation and rearrangement of the resulting oxime
ether 27 furnished the desired tricyclic benzofuran 28 in
73% yield via two steps. Finally, introduction of the car-
bonyl group was achieved by treatment of tricyclic benzofu-
ran 28 with PCC to give Coumestan (29) in 76% yield. The
spectroscopic data of the product are identical with those
of Coumestan 29 reported in the literature.[7a] Thus, we suc-
ceeded in effective and short total synthesis of Stemofuran
A (22), Eupomatenoid 6 (26), and Coumestan (29) without
protection of the phenolic hydroxy groups in the former
two cases.
ture resulting in a light brown suspension. Reaction flask was open
to the atmosphere. After being stirred at the same temperature for
48 h, the reaction mixture became green as the reaction proceeded.
The reaction mixture was adsorbed to SiO2 (50 g) by removing the
solvent under reduced pressure in the presence of silica gel. Purifi-
cation of the residue by flash column chromatography (n-hexane/
AcOEt) afforded N-aryloxyphthalimides. Note: The use of not
freshly activated 4-Å molecular sieves gave poor yield.
N-Phenoxyphthalimide, N-(4-bromophenoxy)phthalimide, N-(4-
methylphenoxy)phthalimide, N-(3-methoxyphenoxy)phthalimide,
N-(3-methylphenoxy)phthalimide,
N-(2-methylphenoxy)phthal-
imide were prepared according to the literature procedure.[8]
N-(3-Bromophenoxy)phthalimide: Yield 42%; colorless crystals.
M.p. 138–139 °C (MeOH). 1H NMR (CDCl3, 300 MHz): δ = 7.96–
7.90 (m, 2 H), 7.86–7.80 (m, 2 H), 7.32 (br. t, J = 1.5 Hz, 1 H),
7.29 (br. dd, J = 8, 2 Hz, 1 H), 7.22 (t, J = 8 Hz, 1 H), 7.13 (br.
ddd, J = 8, 2, 1.5 Hz, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
162.7, 159.3, 135.0, 130.9, 128.7, 127.8, 124.1, 122.9, 117.8,
113.3 ppm. IR (CHCl ): ν = 1797 and 1745 cm–1 (CONCO).
˜
3
HRMS (EI, m/z) calcd. for C14H879BrNO3 (M+) 316.9688, found
316.9692. C14H8BrNO3: calcd. C 52.86, H 2.53, N 4.27; found C
53.02, H 2.40, N 4.27.
N-(3-Methylphenoxy)phthalimide: Yield 74%; colorless crystals.
M.p. 145.5–147 °C (MeOH). 1H NMR (CDCl3, 300 MHz): δ =
7.95–7.89 (m, 2 H), 7.84–7.78 (m, 2 H), 7.21 (br. t, J = 8 Hz, 1 H),
6.99–6.93 (m, 3 H), 2.34 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz):
δ = 163.0, 158.8, 140.1, 134.8, 129.4, 128.8, 125.4, 123.9, 114.9,
Conclusions
In conclusion, we have established a highly efficient and
general synthetic method for dihydrobenzofurans and ben-
zofurans by sequential acylation, rearrangement and cycli-
zation of oxime ethers under mild conditions. We found
that the [3,3]-sigmatropic rearrangement took place
smoothly during the course of trifluoroacetylation of
O-aryloxime ether at lower temperature to give the dihydro-
benzofuran or benzofuran as a result of concomitant cycli-
zation. Additionally the [3,3]-sigmatropic rearrangement
process promoted by the trifluoroacetyl group would repre-
sent a general strategy that may be of great use in the syn-
thesis of more complex heterocycles. Further studies includ-
ing the synthesis of biologically active compounds via our
methodology are now in progress in our laboratory.
111.3, 21.4 ppm. IR (CHCl ): ν = 1795 and 1741 cm–1 (CONCO).
˜
3
HRMS (EI, m/z) calcd. for C15H11NO3 (M+) 253.0738, found
253.0741. C15H11NO3: calcd. C 71.14, H 4.38, N 5.53; found C
71.19, H 4.15, N 5.49.
N-(2-Bromophenoxy)phthalimide: Yield 25%; colorless crystals.
M.p. 174.5–175.5 °C (MeOH). 1H NMR (CDCl3, 300 MHz): δ =
7.93–7.89 (m, 2 H), 7.86–7.81 (m, 2 H), 7.59 (br. d, J = 8 Hz, 1 H),
7.27–7.20 (m, 1 H), 7.04–6.98 (m, 2 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 162.5, 155.0, 135.0, 133.9, 128.7, 128.6, 125.4, 124.0,
113.6, 109.1 ppm. IR (CHCl ): ν = 1798 and 1744 cm–1 (CONCO).
˜
3
HRMS (EI, m/z) calcd. for C14H879BrNO3 (M+) 316.9688, found
316.9698. C14H8BrNO3: calcd. C 52.86, H 2.53, N 4.40; found C
53.05, H 2.79, N 4.40.
General Procedure for Preparation of O-Arylhydroxylamines 5: To
a solution of N-aryloxyphthalimide (7 mmol) in MeOH/CHCl3
(v/v, 1:9) (160 mL) was added hydrazine monohydrate (1.02 mL,
21 mmol) under nitrogen at room temperature, resulting in a color-
less solution. White precipitate appeared in a colorless solution as
the reaction proceeded. After being stirred at the same temperature
for 24 h, the reaction mixture was filtered and washed by CHCl3.
Then the filtrate was concentrated at reduced pressure. Purification
of the residue by flash column chromatography (n-hexane/AcOEt)
afforded O-arylhydroxylamines 5A–H.
Experimental Section
The melting points are uncorrected. 1H and 13C NMR spectra were
recorded at 200, 300, or 500 MHz and at 50, 75, 125 MHz, respec-
tively. IR spectra were recorded using FTIR apparatus. Mass spec-
tra were obtained by EI method. Flash column chromatography
(FCC) was performed using E. Merck Kieselgel 60 (230–400 mesh).
Medium-pressure column chromatography (MCC) was performed
using Lober Größe B (E. Merck 310–25, LiChroprep Si60). Prepar-
ative TLC separations were carried out on precoated silica gel
plates (E. Merck, 60F254). TFAA was obtained from Wako Pure
Chemical Industries (Wako). TFAT was obtained from Tokyo
Chemical industry (TCI).
O-(4-Bromophenyl)hydroxylamine (5B):[23] Yield 85%; colorless oil.
1H NMR (CDCl3, 300 MHz): δ = 7.36 (br. d, J = 8 Hz, 2 H), 7.03
(br. d, J = 8 Hz, 2 H), 5.86 (br. s, 2 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 160.4, 131.9, 115.0, 113.0 ppm. IR (CHCl ): ν =
˜
3
3334 cm–1 (NH2). HRMS (EI, m/z) calcd. for C6H679BrNO (M+)
General Procedure for Preparation of N-(Aryloxy)phthalimides: Ac-
cording to the literature procedure,[8] to a suspension of N-hydroxy-
phthalimide (1.63 g, 10 mmol) and CuCl (0.99 g, 10 mmol) in 1,2-
dichloroethane (50 mL) were added freshly activated 4-Å molecular
sieves (2.4 g) and arylboronic acid (20 mmol) at room temperature.
Then pyridine (0.83 mL, 11 mmol) was added to the reaction mix-
186.9632, found 186.9630.
O-(4-Methylphenyl)hydroxylamine (5C):[24] Yield 99%; colorless oil.
1H NMR (CDCl3, 300 MHz): δ = 7.04 (br. d, J = 8 Hz, 2 H), 6.99
(br. d, J = 8 Hz, 2 H), 5.65 (br. s, 2 H), 2.26 (s, 3 H) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 159.1, 130.1, 129.5, 112.9, 20.3 ppm.
Eur. J. Org. Chem. 2007, 1491–1509
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N. Takeda, O. Miyata, T. Naito
FULL PAPER
IR (CHCl ): ν = 3332 cm–1 (NH2). HRMS (EI, m/z) calcd. for 3 H), 1.14 (br. t, J = 7.5 Hz, 3 H) ppm. 13C NMR (CDCl3,
˜
3
C7H9NO (M+) 123.0684, found 123.0692.
50 MHz): δ = 166.7, 159.6, 129.1, 121.5, 114.5, 27.2, 22.0, 10.7,
10.5 ppm. IR (CHCl ): ν = 1638 cm–1 (C=N). HRMS (EI, m/z)
˜
3
O-(3-Bromophenyl)hydroxylamine (5D): Yield 73%; colorless oil.
1H NMR (CDCl3, 300 MHz): δ = 7.38 (t, J = 2 Hz, 1 H), 7.12 (t,
J = 8 Hz, 1 H), 7.06 (br. dt, J = 8, 2 Hz, 1 H), 7.02 (br. dt, J = 8,
2 Hz, 1 H), 5.82 (br. s, 2 H) ppm. 13C NMR (CDCl3, 75 MHz): δ
calcd. for C11H15NO (M+) 177.1153, found 177.1157.
2-Propanone O-Phenyloxime (7Ad):[3f] A colorless oil. 13C NMR
(CDCl3, 50 MHz): δ = 159.4, 158.3, 129.1, 121.6, 114.5, 21.7,
16.0 ppm.
= 162.0, 130.3, 124.1, 122.7, 116.5, 112.1 ppm. IR (CHCl ): ν =
˜
3
3333 cm–1 (NH2). HRMS (EI, m/z) calcd. for C6H679BrNO (M+)
General Procedure for Preparation of the Oxime Ethers 7Ae–7Au,
7Be–7He: To a solution of the O-arylhydroxylamine 5 (2 mmol) in
EtOH (4 mL) was added acetophenone or propiophenone
(2 mmol) and concd. aqueous HCl (0.10 mL) under nitrogen at
room temperature. After being stirred at the same temperature for
several hours, the reaction mixture was concentrated at reduced
pressure. Purification of the residue by medium-pressure column
chromatography (n-hexane/AcOEt) afforded the oxime ether 7Ae–
He as shown in Table 1.
186.9632, found 186.9648.
O-(3-Methylphenyl)hydroxylamine (5E):[24] Yield 91%; colorless oil.
1H NMR (CDCl3, 300 MHz): δ = 7.16 (t, J = 8 Hz, 1 H), 6.96 (br.
s, 1 H), 6.94 (br. d, J = 8 Hz, 1 H), 6.76 (br. d, J = 8 Hz, 1 H),
5.58 (br. s, 2 H), 2.33 (s, 3 H) ppm. 13C NMR (CDCl3, 75 MHz):
δ = 161.2, 139.1, 128.8, 121.7, 113.6, 110.0, 21.3 ppm. IR (CHCl3):
ν = 3331 cm–1 (NH2). HRMS (EI, m/z) calcd. for C7H9NO (M+)
˜
123.0684, found 123.0699.
O-(3-Methoxyphenyl)hydroxylamine (5F):[24] Yield 95%; colorless
oil. H NMR (CDCl3, 300 MHz): δ = 7.16 (t, J = 8 Hz, 1 H), 6.75
1
(E)-1-Phenylethanone O-Phenyloxime (7Ae):[25] A colorless oil. H
1
NMR (CDCl3, 300 MHz): δ = 7.79–7.75 (m, 2 H), 7.47–7.27 (m, 7
H), 7.03 (tt, J = 8, 1.5 Hz, 1 H), 2.45 (br. s, 3 H) ppm. 13C NMR
(CDCl3, 50 MHz): δ = 159.5, 157.6, 135.9, 129.6, 129.2, 128.4,
126.4, 122.1, 114.7, 13.2 ppm. HRMS (EI, m/z) calcd. for
C14H13NO (M+) 211.0996, found 211.0990.
(br. t, J = 2 Hz, 1 H), 6.71 (br. ddd, J = 8, 2, 1 Hz, 1 H), 6.50 (br.
ddd, J = 8, 2, 1 Hz, 1 H), 5.37 (br. s, 2 H), 3.79 (s, 3 H) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 162.5, 160.7, 129.7, 106.7, 105.5, 99.1,
55.2 ppm. IR (CHCl ): ν = 3332 cm–1 (NH2). HRMS (EI, m/z)
˜
3
calcd. for C7H9NO2 (M+) 139.0632, found 139.0647.
(E)-1-(4-Bromophenyl)ethanone O-Phenyloxime (7Af): A colorless
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.65 (br. d, J = 8.5 Hz, 2 H),
7.54 (br. d, J = 8.5 Hz, 2 H), 7.36–7.25 (m, 4 H), 7.04 (tt, J = 8,
1.5 Hz, 1 H), 2.42 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ =
159.4, 156.6, 134.8, 131.6, 129.3, 127.9, 124.0, 122.3, 114.7,
13.0 ppm. HRMS (EI, m/z) calcd. for C14H1279BrNO (M+)
289.0102, found 289.0099.
O-(2-Bromophenyl)hydroxylamine (5G):[24] Yield 97%; colorless oil.
1H NMR (CDCl3, 300 MHz): δ = 7.53 (br. dd, J = 8, 1.5 Hz, 1 H),
7.47 (br. dd, J = 8, 1.5 Hz, 1 H), 7.28 (br. td, J = 8, 1.5 Hz, 1 H),
6.84 (br. td, J = 8, 1.5 Hz, 1 H), 5.59 (br. s, 2 H) ppm. 13C NMR
(CDCl3, 50 MHz): δ = 157.3, 132.8, 128.4, 122.3, 114.0, 108.3 ppm.
IR (CHCl ): ν = 3333 cm–1 (NH2). HRMS (EI, m/z) calcd. for
˜
3
C6H679BrNO (M+) 186.9632, found 186.9660.
(E)-1-(4-Nitrophenyl)ethanone O-Phenyloxime (7Ag): Colorless
crystals. M.p. 78–79 °C (n-hexane/AcOEt). 1H NMR (CDCl3,
300 MHz): δ = 8.25 (br. d, J = 8.5 Hz, 2 H), 7.94 (br. d, J = 8.5 Hz,
2 H), 7.39–7.27 (m, 4 H), 7.08 (br. t, J = 8 Hz, 1 H), 2.48 (s, 3 H)
ppm. 13C NMR (CDCl3, 50 MHz): δ = 159.2, 155.7, 148.4, 141.9,
O-(2-Methylphenyl)hydroxylamine (5H):[24] Yield 78%; colorless
oil. H NMR (CDCl3, 300 MHz): δ = 7.35 (br. d, J = 8 Hz, 1 H),
1
7.14 (br. t, J = 8 Hz, 1 H), 7.05 (br. d, J = 8 Hz, 1 H), 6.82 (br. t,
J = 8 Hz, 1 H), 5.72 (br. s, 2 H), 2.16 (s, 3 H) ppm. 13C NMR
(CDCl3, 50 MHz): δ = 159.0, 130.3, 126.7, 123.8, 120.6, 111.3,
129.4, 127.2, 123.7, 122.8, 114.8, 13.2 ppm. IR (CHCl ): ν = 1523
˜
3
15.7 ppm. IR (CHCl ): ν = 3331 cm–1 (NH2). HRMS (EI, m/z)
and 1348 cm–1 (NO2). HRMS (EI, m/z) calcd. for C14H12N2O3
(M+) 256.0847, found 256.0850. C14H12N2O3: calcd. C 65.62, H
4.72, N 10.93; found C 65.64, H 4.88, N 10.89.
˜
3
calcd. for C7H9NO (M+) 123.0684, found 123.0685.
General Procedure for Preparation of Oxime Ethers 7Aa–Ad: To a
solution of O-phenylhydroxylamine 5A (2 mmol) in MeOH (4 mL)
was added the ketone (2.2 mmol) under nitrogen at room tempera-
ture. After being stirred at the same temperature for several hours,
the reaction mixture was concentrated at reduced pressure. Purifi-
cation of the residue by medium-pressure column chromatography
(n-hexane/AcOEt) afforded oxime ethers 7 as shown in Table 1.
(E)-1-(4-Hydroxyphenyl)ethanone O-Phenyloxime (7Ah): Colorless
crystals. M.p. 85–86 °C (n-hexane/AcOEt). 1H NMR (CDCl3,
300 MHz): δ = 7.69 (br. d, J = 8.5 Hz, 2 H), 7.35–7.25 (m, 4 H),
7.02 (tt, J = 8, 1.5 Hz, 1 H), 6.86 (br. d, J = 8.5 Hz, 2 H), 5.04 (br.
s, 1 H), 2.41 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 159.5,
157.9, 157.0, 129.2, 128.3, 128.1, 122.1, 115.4, 114.8, 13.3 ppm. IR
(CHCl ): ν = 3594 cm–1 (OH). HRMS (EI, m/z) calcd. for
Cyclopentanone O-Phenyloxime (7Aa): A colorless oil. 1H NMR
(CDCl3, 300 MHz): δ = 7.28 (br. t, J = 8 Hz, 2 H), 7.15 (br. d, J
= 8 Hz, 2 H), 6.97 (br. t, J = 8 Hz, 1 H), 2.65–2.60 (m, 2 H), 2.54–
2.49 (m, 2 H), 1.85–1.77 (m, 4 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 170.0, 159.6, 129.0, 121.5, 114.4, 31.0, 28.2, 25.0,
˜
3
C14H13NO2 (M+) 227.0946, found 227.0944. C14H13NO2: calcd. C
73.99, H 5.77, N 6.16; found C 73.97, H 5.85, N 6.13.
(E)-1-(4-Methoxyphenyl)ethanone O-Phenyloxime (7Ai): Colorless
crystals. M.p. 32–34 °C (n-hexane/AcOEt). 1H NMR (CDCl3,
300 MHz): δ = 7.73 (br. d, J = 8.5 Hz, 2 H), 7.35–7.24 (m, 4 H),
7.01 (tt, J = 8, 1.5 Hz, 1 H), 6.92 (br. d, J = 8.5 Hz, 2 H), 3.83 (s,
3 H), 2.41 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 160.9,
159.6, 157.2, 129.2, 128.4, 127.8, 121.9, 114.7, 113.8, 55.3,
13.1 ppm. HRMS (EI, m/z) calcd. for C15H15NO2 (M+) 241.1102,
found 241.1080. C15H15NO2: calcd. C 74.67, H 6.27, N 5.81; found
C 74.76, H 6.33, N 5.79.
24.5 ppm. IR (CHCl ): ν = 1659 cm–1 (C=N). HRMS (EI, m/z)
˜
3
calcd. for C11H13NO (M+) 175.0997, found 175.1000.
Cyclohexanone O-Phenyloxime (7Ab):[25] Colorless crystals. M.p.
45–46 °C (n-hexane) (ref.[25] 47° C). 13C NMR (CDCl3, 50 MHz): δ
= 163.6, 159.4, 129.1, 121.5, 114.4, 32.0, 26.9, 25.8, 25.7, 25.6 ppm.
HRMS (EI, m/z) calcd. for C12H15NO (M+) 189.1153, found
189.1167.
3-Pentanone O-Phenyloxime (7Ac): A colorless oil. 1H NMR
(E/Z)-1-Phenyl-1-propanone O-Phenyloxime (7Aj): The oxime
(CDCl3, 300 MHz): δ = 7.28 (br. t, J = 8 Hz, 2 H), 7.17 (br. d, J ethers (E)-7Aj and (Z)-7Aj were inseparable (E:Z = 10:1); colorless
= 8 Hz, 2 H), 6.96 (br. tt, J = 8, 1.5 Hz, 1 H), 2.48 (br. q, J =
7.5 Hz, 2 H), 2.34 (br. q, J = 7.5 Hz, 2 H), 1.17 (br. t, J = 7.5 Hz,
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.78–7.75 (m, 2 H), 7.45–
7.39 (m, 3 H), 7.36–7.27 (m, 4 H), 7.03 (br. tt, J = 8, 1.5 Hz, 1 H),
1500
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1491–1509

Short Synthesis of Natural 2-Arylbenzofurans
FULL PAPER
2.96 (q, J = 7.5 Hz, 20/11 H), 2.70 (q, J = 7.5 Hz, 2/11 H), 1.25 (t, (tt, J = 8, 1.5 Hz, 1 H), 6.89 (dm, J = 8 Hz, 1 H), 5.06 (br. s, 1 H),
J = 7.5 Hz, 30/11 H), 1.17 (t, J = 7.5 Hz, 3/11 H) ppm. 13C NMR 2.42 (s, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 159.3, 155.5,
(CDCl3, 50 MHz): δ = 162.7, 159.6, 129.6, 129.2, 128.5, 128.1, 137.2, 129.8, 129.3, 122.3, 119.1, 117.0, 114.9, 113.3, 13.4 ppm. IR
127.7, 122.0, 114.7, 20.7, 11.3 ppm. HRMS (EI, m/z) calcd. for
C15H15NO (M+) 225.1153, found 225.1165. The 13C NMR spectro-
scopic data of only (E)-7Aj was described.
(CHCl ): ν = 3595 cm–1 (OH). HRMS (EI, m/z) calcd. for
˜
3
C14H13NO2 (M+) 227.0946, found 227.0960.
(E)-1-(3-Methoxyphenyl)ethanone O-Phenyloxime (7Aq): A color-
1
(E/Z)-1-(4-Bromophenyl)-1-propanone O-Phenyloxime (7Ak): The
oxime ethers (E)-7Ak and (Z)-7Ak were inseparable (E:Z = 10:1);
colorless oil. 1H NMR (CDCl3, 300 MHz): δ = 7.64 (br. d, J =
8.5 Hz, 2 H), 7.54 (br. d, J = 8.5 Hz, 2 H), 7.33 (br. t, J = 8 Hz, 2
H), 7.27 (br. d, J = 8 Hz, 2 H), 7.04 (br. tt, J = 8, 1.5 Hz, 1 H),
2.92 (q, J = 7.5 Hz, 20/11 H), 2.67 (q, J = 7.5 Hz, 2/11 H), 1.23 (t,
J = 7.5 Hz, 30/11 H), 1.16 (t, J = 7.5 Hz, 3/11 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 161.7, 159.5, 133.8, 131.7, 129.3, 128.2,
124.0, 122.3, 114.8, 20.4, 11.3 ppm. HRMS (EI, m/z) calcd. for
C15H1479BrNO (M+) 303.0258, found 302.0262. The 13C NMR
spectroscopic data of only (E)-7Ak was described.
less oil. H NMR (CDCl3, 300 MHz): δ = 7.36–7.27 (m, 7 H), 7.03
(tt, J = 8, 1.5 Hz, 1 H), 6.98–6.94 (m, 1 H), 3.85 (s, 3 H), 2.44 (s,
3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 159.6, 159.5, 157.6,
137.3, 129.5, 129.2, 122.1, 119.0, 115.3, 114.8, 111.9, 55.3,
13.4 ppm. HRMS (EI, m/z) calcd. for C15H15NO2 (M+) 241.1102,
found 241.1098.
(E/Z)-1-(2-Bromophenyl)ethanone O-Phenyloxime (7Ar): The oxime
ethers (E)-7Ar and (Z)-7Ar were inseparable (E:Z = 4:1); colorless
1
oil. H NMR (CDCl3, 300 MHz): δ = 7.63 (br. d, J = 8 Hz, 1 H),
7.41–7.10 (m, 7 H), 7.03 (br. t, J = 8 Hz, 4/5 H), 6.98 (br. t, J =
8 Hz, 1/5 H), 2.44 (s, 12/5 H), 2.33 (s, 3/5 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 160.2, 159.2, 138.2, 133.1, 132.6, 130.31,
130.28, 129.8, 129.2, 129.1, 127.8, 127.4, 127.3, 122.3, 122.1, 121.6,
115.0, 114.8, 21.2, 17.3 ppm. HRMS (EI, m/z) calcd. for
C14H1279BrNO (M+) 289.0102, found 289.0112.
(E/Z)-1-(4-Hydroxyphenyl)-1-propanone O-Phenyloxime (7Al): The
oxime ethers (E)-7Al and (Z)-7Al were inseparable (E:Z = 10:1);
colorless oil. 1H NMR (CDCl3, 300 MHz): δ = 7.66 (br. d, J =
8.5 Hz, 2 H), 7.36–7.24 (m, 4 H), 7.02 (br. tt, J = 8, 1.5 Hz, 1 H),
6.84 (br. d, J = 8.5 Hz, 2 H), 5.36 (br. s, 1 H), 2.91 (q, J = 7.5 Hz,
20/11 H), 2.69 (q, J = 7.5 Hz, 2/11 H), 1.23 (t, J = 7.5 Hz, 30/11
H), 1.15 (t, J = 7.5 Hz, 3/11 H) ppm. 13C NMR (CDCl3, 75 MHz):
δ = 163.0, 159.6, 157.1, 129.2, 128.3, 127.2, 122.0, 115.5, 114.8,
(E/Z)-1-(2-Nitrophenyl)ethanone O-Phenyloxime (7As): The oxime
ethers (E)-7As and (Z)-7As were inseparable. Stereostructures of E
1
and Z isomers (4.5:1) have not been established; colorless oil. H
20.7, 11.4 ppm. IR (CHCl ): ν = 3590 cm–1 (OH). HRMS (EI, m/z)
NMR (CDCl3, 300 MHz): δ = 8.13 (br. d, J = 8 Hz, 2/11 H), 8.05
(br. d, J = 8 Hz, 9/11 H), 7.71 (br. t, J = 8 Hz, 2/11 H), 7.67 (br. t,
J = 8 Hz, 9/11 H), 7.60–7.52 (m, 20/11 H), 7.35–7.17 (m, 42/11 H),
˜
3
calcd. for C15H15NO2 (M+) 241.1102, found 241.1108. The 13C
NMR spectroscopic data of only (E)-7Al was described.
7.05–6.94 (m, 15/11 H), 2.43 (s, 6/11 H), 2.40 (s, 27/11 H) ppm. 13
C
(E/Z)-1-(4-Methoxyphenyl)-1-propanone O-Phenyloxime (7Am):
(E,Z)-7Am (E:Z = 10:1) as colorless crystals. M.p. 45–46 °C (Ac-
NMR (CDCl3, 75 MHz): δ = 159.0, 158.7, 157.6, 155.7, 147.8,
146.6, 133.7, 133.2, 132.2, 130.54, 130.46, 129.8, 129.5, 129.1,
129.0, 128.0, 124.5, 124.1, 122.4, 122.3, 114.7, 114.6, 21.0,
1
OEt); (E,Z)-7Am. H NMR (CDCl3, 300 MHz): δ = 7.72 (br. d, J
= 8.5 Hz, 2 H), 7.35–7.26 (m, 4 H), 7.01 (br. tt, J = 8, 1.5 Hz, 1
H), 6.93 (br. d, J = 8.5 Hz, 2 H), 3.83 (s, 3 H), 2.92 (q, J = 7.5 Hz,
20/11 H), 2.70 (q, J = 7.5 Hz, 2/11 H), 1.23 (t, J = 7.5 Hz, 30/11
H), 1.16 (t, J = 7.5 Hz, 3/11 H) ppm. HRMS (EI, m/z) calcd. for
C16H17NO2 (M+) 255.1259, found 255.1257.
16.6 ppm. IR (CHCl ): ν = 1531 and 1349 cm–1 (NO2). HRMS (EI,
˜
3
m/z) calcd. for C14H12N2O3 (M+) 256.0847, found 256.0857.
(E)-1-(2-Hydroxyphenyl)ethanone O-Phenyloxime (7At): A colorless
1
oil. H NMR (CDCl3, 300 MHz): δ = 11.10 (br. s, 1 H), 7.48 (dd,
(E)-7Am: 1H NMR (CDCl3, 300 MHz): δ = 7.72 (br. d, J = 8.5 Hz,
2 H), 7.36–7.26 (m, 4 H), 7.01 (br. tt, J = 8, 1.5 Hz, 1 H), 6.93 (br.
d, J = 8.5 Hz, 2 H), 3.83 (s, 3 H), 2.92 (q, J = 7.5 Hz, 2 H), 1.23
(t, J = 7.5 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 162.3,
160.8, 159.6, 129.2, 128.0, 127.2, 121.9, 114.7, 113.9, 55.2, 20.5,
11.4 ppm. C16H17NO2: calcd. C 75.27, H 6.71, N 5.49; found C
75.36, H 6.78, N 5.44.
J = 8, 1.5 Hz, 1 H), 7.38–7.28 (m, 3 H), 7.19 (br. d, J = 8 Hz, 2
H), 7.08 (br. t, J = 8 Hz, 1 H), 7.01 (br. dd, J = 8, 1.5 Hz, 1 H),
6.92 (br. t, J = 8 Hz, 1 H), 2.51 (s, 3 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 161.7, 158.6, 157.9, 131.6, 129.6, 128.1, 123.1, 119.3,
117.9, 117.6, 114.8, 12.4 ppm. IR (CHCl ): ν = 3456–2725 cm–1
˜
3
(OH). HRMS (EI, m/z) calcd. for C14H13NO2 (M+) 227.0946,
found 227.0960.
(E)-1-(3-Bromophenyl)ethanone O-Phenyloxime (7An): A colorless
oil. H NMR (CDCl3, 300 MHz): δ = 7.93 (t, J = 2 Hz, 1 H), 7.69
(E/Z)-1-(2-Methoxyphenyl)ethanone O-Phenyloxime (7Au): The ox-
ime ethers (E)-7Au and (Z)-7Au were inseparable (E:Z = 10:1); col-
orless oil. 1H NMR (CDCl3, 300 MHz): δ = 7.40 (br. td, J = 8,
1.5 Hz, 10/11 H), 7.35 (td, J = 8, 1.5 Hz, 11/11 H), 7.30–7.23 (m,
55/11 H), 7.19 (dd, J = 8, 1.5 Hz, 1/11 H), 7.10 (br. dd, J = 8,
1.5 Hz, 1/11 H), 7.02–6.92 (m, 21/11 H), 3.85 (s, 30/11 H), 3.79 (s,
3/11 H), 2.40 (s, 30/11 H), 2.30 (s, 3/11 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 160.0, 159.5, 157.5, 130.6, 129.7, 129.1, 126.3, 121.9,
120.5, 114.7, 111.0, 55.3, 16.6 ppm. HRMS (EI, m/z) calcd. for
C15H15NO2 (M+) 241.1102, found 241.1102. The 13C NMR spec-
troscopic data of only (E)-7Au was described.
1
(ddd, J = 8, 2, 1 Hz, 1 H), 7.54 (ddd, J = 8, 2, 1 Hz, 1 H), 7.37–
7.25 (m, 5 H), 7.05 (tt, J = 8, 1.5 Hz, 1 H), 2.42 (s, 3 H) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 159.8, 156.7, 138.3, 133.0, 130.4,
129.8, 129.7, 125.4, 123.1, 122.8, 115.2, 13.6 ppm. HRMS (EI, m/z)
calcd. for C14H1279BrNO (M+) 289.0102, found 289.0108.
(E)-1-(3-Nitrophenyl)ethanone O-Phenyloxime (7Ao): Colorless
crystals. M.p. 64–65 °C (n-hexane/AcOEt). 1H NMR (CDCl3,
300 MHz): δ = 8.59 (t, J = 2 Hz, 1 H), 8.25 (ddd, J = 8, 2, 1 Hz, 1
H), 7.58 (t, J = 8 Hz, 1 H), 7.35 (br. t, J = 8 Hz, 2 H), 7.29 (br. d,
J = 8 Hz, 2 H), 7.07 (br. tt, J = 8, 1.5 Hz, 1 H), 2.49 (s, 3 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 159.2, 155.5, 148.4, 137.6, 132.1,
(E)-1-Phenylethanone O-(4-Bromophenyl)oxime (7Be): Colorless
1
crystals. M.p. 93–94 °C (n-hexane). H NMR (CDCl3, 300 MHz):
129.5, 129.4, 124.2, 122.7, 121.3, 114.8, 13.2 ppm. IR (CHCl ): ν =
˜
3
δ = 7.78–7.75 (m, 2 H), 7.45–7.40 (m, 5 H), 7.18 (br. d, J = 8.5 Hz,
2 H), 2.45 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 158.7,
158.3, 135.7, 132.1, 130.0, 128.5, 126.5, 116.5, 114.3, 13.4 ppm.
HRMS (EI, m/z) calcd. for C14H1279BrNO (M+) 289.0102, found
289.0101. C14H12BrNO: calcd. C 57.95, H 4.17, N 4.83; found C
58.21, H 4.17, N 4.74.
1533 and 1353 cm–1 (NO2). HRMS (EI, m/z) calcd. for
C14H12N2O3 (M+) 256.0847, found 256.0845. C14H12N2O3: calcd.
C 65.62, H 4.72, N 10.93; found C 65.62, H 4.86, N 10.88.
(E)-1-(3-Hydroxyphenyl)ethanone O-Phenyloxime (7Ap): A color-
1
less oil. H NMR (CDCl3, 300 MHz): δ = 7.36–7.25 (m, 7 H), 7.03
Eur. J. Org. Chem. 2007, 1491–1509
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1501

N. Takeda, O. Miyata, T. Naito
FULL PAPER
(E)-1-Phenylethanone O-(4-Methylphenyl)oxime (7Ce): A colorless
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.79–7.73 (m, 2 H), 7.43–
7.38 (m, 3 H), 7.19–7.10 (m, 4 H), 2.43 (s, 3 H), 2.32 (s, 3 H) ppm.
3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 164.2, 160.2, 142.4,
135.0, 130.4, 128.7, 126.6, 125.7, 114.5, 13.7 ppm. IR (CHCl ): ν =
˜
3
1519 and 1343 cm–1 (NO2). HRMS (EI, m/z) calcd. for
13C NMR (CDCl3, 50 MHz): δ = 157.5, 157.3, 136.1, 131.4, 129.7, C14H12N2O3 (M+) 256.0847, found 256.0839.
129.6, 128.4, 126.4, 114.7, 20.6, 13,3 ppm. HRMS (EI, m/z) calcd.
(E)-1-Phenylethanone O-(2-Nitrophenyl)oxime (7Ke):[26] Yellow
for C15H15NO (M+) 225.1153, found 225.1163.
1
crystals. M.p. 32–33 °C (n-hexane/MeOH) (ref.[26] 151–152° C). H
(E)-1-Phenylethanone O-(3-Bromophenyl)oxime (7De): A colorless
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.78–7.75 (m, 2 H), 7.51 (br.
s, 1 H), 7.45–7.15 (m, 6 H), 2.44 (s, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 160.1, 158.5, 135.5, 130.3, 129.9, 128.5, 126.5, 125.0,
122.6, 117.9, 113.5, 13.4 ppm. HRMS (EI, m/z) calcd. for
C14H1279BrNO (M+) 289.0102, found 289.0107.
NMR (CDCl3, 300 MHz): δ = 7.97 (dd, J = 8, 1.5 Hz, 1 H), 7.86
(dd, J = 8, 1.5 Hz, 1 H), 7.79–7.74 (m, 2 H), 7.57 (br. td, J = 8,
1.5 Hz, 1 H), 7.47–7.40 (m, 3 H), 7.08 (br. td, J = 8, 1.5 Hz, 1 H),
2.54 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 161.0, 153.2,
137.3, 135.0, 134.6, 130.4, 128.6, 126.7, 125.5, 121.4, 117.1,
14.3 ppm. IR (CHCl ): ν = 1525 and 1349 cm–1 (NO2). HRMS (EI,
˜
3
m/z) calcd. for C14H12N2O3 (M+) 256.0847, found 256.0855.
(E)-1-Phenylethanone O-(3-Methylphenyl)oxime (7Ee): A colorless
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.79–7.75 (m, 2 H), 7.43–
7.39 (m, 3 H), 7.21 (t, J = 8 Hz, 1 H), 7.12 (br. s, 1 H), 7.09 (br. d,
J = 8 Hz, 1 H), 6.84 (br. d, J = 8 Hz, 1 H), 2.44 (s, 3 H), 2.36 (s,
3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 160.0, 157.6, 139.3,
136.0, 129.6, 129.0, 128.5, 126.5, 122.9, 115.4, 111.8, 21.5,
13.3 ppm. HRMS (EI, m/z) calcd. for C15H15NO (M+) 225.1153,
found 225.1160.
(E)-1-Phenylethanone O-(3-Nitrophenyl)oxime (7Je): To a mixture
of tBuOK (506.2 mg, 4.52 mmol) in dry DMF (4 mL) was added
acetophenone oxime (500 mg, 3.70 mmol) under nitrogen at 0 °C.
After being stirred at room temperature for 30 min, nitrofluoroben-
zene 8B (0.44 mL, 4.11 mmol) was added and the reaction mixture
was heated at 80 °C for 4 h. The reaction mixture was cooled to
room temperature, quenched with H2O and extracted with Et2O.
The organic phase was washed brine, dried with MgSO4, and con-
centrated at reduced pressure. Purification of the residue by me-
dium-pressure column chromatography (n-hexane/AcOEt) afforded
the oxime ether 7Je (913.1 mg, 87%) as a yellow oil.1H NMR
(CDCl3, 300 MHz): δ = 8.18 (t, J = 2 Hz, 1 H), 7.90 (ddd, J = 8,
2, 1 Hz, 1 H), 7.81–7.78 (m, 2 H), 7.59 (ddd, J = 8, 2, 1 Hz, 1 H),
7.51–7.43 (m, 4 H), 2.49 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz):
δ = 159.9, 159.4, 149.0, 135.1, 130.2, 129.7, 128.6, 126.6, 120.9,
(E)-1-Phenylethanone O-(3-Methoxyphenyl)oxime (7Fe): A colorless
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.81–7.75 (m, 2 H), 7.44–
7.39 (m, 3 H), 7.23 (br. t, J = 8 Hz, 1 H), 6.90 (br. s, 1 H), 6.88
(br. dm, J = 8 Hz, 1 H), 6.59 (br. dm, J = 8 Hz, 1 H), 3.82 (s, 3
H), 2.45 (s, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 160.7,
160.6, 157.7, 135.9, 129.7, 128.5, 126.5, 107.7, 107.1, 100.8, 55.3,
13.3 ppm. HRMS (EI, m/z) calcd. for C15H15NO2 (M+) 241.1102,
found 241.1102.
116.8, 109.9, 13.6 ppm. IR (CHCl ): ν = 1531 and 1354 cm–1
˜
3
(E)-1-Phenylethanone O-(2-Bromophenyl)oxime (7Ge): A colorless
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.79–7.76 (m, 2 H), 7.60 (dd,
J = 8, 1.5 Hz, 1 H), 7.54 (dd, J = 8, 1.5 Hz, 1 H), 7.45–7.40 (m, 3
H), 7.29 (br. td, J = 8, 1.5 Hz, 1 H), 6.90 (br. td, J = 8, 1.5 Hz, 1
H), 2.53 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 159.3,
155.3, 135.5, 132.9, 129.9, 128.5, 128.4, 126.6, 123.0, 115.9, 109.2,
13.8 ppm. HRMS (EI, m/z) calcd. for C14H1279BrNO (M+)
289.0102, found 289.0100.
(NO2). HRMS (EI, m/z) calcd. for C14H12N2O3 (M+) 256.0847,
found 256.0847.
(E)-1-Phenylethanone O-(3-Hydroxyphenyl)oxime (7Le): To a solu-
tion of the oxime ether 7Fe (216.2 mg, 0.90 mmol) in CH2Cl2
(6.8 mL) was added BBr3 (1.35 mL, 1.35 mmol) (1.0  in CH2Cl2
solution) under nitrogen at 0 °C. After being stirred at room tem-
perature for 2 h, the reaction mixture was quenched with H2O and
extracted with CHCl3. The organic phase was washed brine, dried
with MgSO4, and concentrated at reduced pressure. Purification of
the residue by medium-pressure column chromatography (n-hex-
ane/AcOEt) afforded the oxime ether 7Le (72.4 mg, 36%) as a col-
orless oil. 1H NMR (CDCl3, 300 MHz): δ = 7.78–7.74 (m, 2 H),
7.44–7.40 (m, 3 H), 7.17 (t, J = 8 Hz, 1 H), 6.87–6.82 (m, 2 H),
6.50 (ddd, J = 8, 2, 1 Hz, 1 H), 4.90 (br. s, 1 H), 2.44 (s, 3 H) ppm.
13C NMR (CDCl3, 50 MHz): δ = 160.8, 158.0, 156.5, 135.9, 130.0,
(E)-1-Phenylethanone O-(2-Methylphenyl)oxime (7He): A colorless
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.80–7.75 (m, 2 H), 7.50 (br.
d, J = 8 Hz, 1 H), 7.43–7.39 (m, 3 H), 7.19 (br. t, J = 8 Hz, 1 H),
7.15 (br. d, J = 8 Hz, 1 H), 6.94 (br. t, J = 8 Hz, 1 H), 2.47 (s, 3
H), 2.32 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 157.7,
157.5, 136.0, 130.5, 129.6, 128.4, 126.9, 126.4, 124.7, 121.8, 114.2,
16.0, 13,3 ppm. HRMS (EI, m/z) calcd. for C15H15NO (M+)
225.1153, found 225.1171.
129.8, 128.5, 126.5, 109.0, 107.2, 102.1, 13.4 ppm; ν = 3597 cm–1
˜
(OH). HRMS (EI, m/z) calcd. for C14H13NO2 (M+) 227.0946,
General Procedure for Preparation of the Oxime Ethers 7Ie, Ke: To
a mixture of NaH (164.5 mg, 4.11 mmol) (60% w/w dispersion in
mineral oil, washed with dry n-hexane) in dry THF (8.5 mL) was
added acetophenone oxime (500 mg, 3.70 mmol) in dry THF
(3.0 mL) under nitrogen at 0 °C. After being stirred at the same
temperature for 30 min, nitrofluorobenzene (8) (4.11 mmol) and
18-crown-6 (31.7 mg, 0.12 mmol) were added and the reaction mix-
ture was stirred at room temperature for 5 h. The reaction mixture
was quenched with H2O and extracted with CHCl3. The organic
phase was washed brine, dried with MgSO4, and concentrated at
reduced pressure. Purification of the residue by medium-pressure
column chromatography (n-hexane/AcOEt) afforded the oxime
ethers 7Ie,[26] 7Ke[26] as shown in Table 2.
found 227.0963.
2,2,2-Trifluoro-N-[2-(2-hydroxyphenyl)-1-cyclopenten-1-yl]acet-
amide (11Aa): (Table 3, Entry 1) To a solution of oxime ether 7Aa
(35.0 mg, 0.20 mmol) in CH2Cl2 (3 mL) were added Et3N
(0.042 mL, 0.30 mmol) and TFAA (0.028 mL, 0.20 mmol) under
nitrogen at 0 °C. After being stirred at the same temperature for
4 h, the reaction mixture was concentrated at reduced pressure. Pu-
rification of the residue by medium-pressure column chromatog-
raphy (n-hexane/AcOEt, 20:1) afforded the rearranged product
11Aa (4.5 mg, 8%) as a colorless oil and recovered 7Aa (30.5 mg,
87%). 1H NMR (CDCl3, 300 MHz): δ = 9.53 (br. s, 1 H), 7.26–
7.17 (m, 2 H), 7.01–6.91 (m, 2 H), 6.75 (br. s, 1 H), 3.11 (br. t, J =
7.5 Hz, 2 H), 2.76 (br. t, J = 7.5 Hz, 2 H), 2.06 (br. quint, J =
7.5 Hz, 2 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 154.4 (q,
COCF3), 150.6, 132.4, 129.02, 129.00, 124.3, 122.4, 121.5, 116.2,
(E)-1-Phenylethanone O-(4-Nitrophenyl)oxime (7Ie):[26] Yellow crys-
tals. M.p. 122–123 °C (MeOH) (ref.[26] 122–124° C). 1H NMR
(CDCl3, 300 MHz): δ = 8.25 (br. d, J = 8 Hz, 2 H), 7.80–7.76 (m,
2 H), 7.49–7.44 (m, 3 H), 7.43–7.37 (br. d, J = 8 Hz, 2 H), 2.50 (s,
115.9 (q, CF ), 35.0, 33.7, 22.0 ppm. IR (CHCl ): ν = 3240 (OH
˜
3
3
1502
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1491–1509

Short Synthesis of Natural 2-Arylbenzofurans
FULL PAPER
and NH), 1718 cm–1 (NCOCF3). HRMS (EI, m/z) calcd. for
10Aa (31.6 mg, 58 %) as colorless crystals and recovered 7Aa
(3.3 mg, 9%).
C13H12F3NO2 (M+) 271.0820, found 271.0816.
2,2,2-Trifluoro-N-(cis-1,2,3,8b-tetrahydro-3aH-cyclopenta[b]benzo-
furan-3a-yl)acetamide (10Aa): (Table 3, Entry 2) To a solution of
the oxime ether 7Aa (40 mg, 0.23 mmol) in CH2Cl2 (4 mL) was
added TFAA (0.033 mL, 0.23 mmol) under nitrogen at 0 °C. After
being stirred at the same temperature for 3 h, the reaction mixture
was concentrated at reduced pressure. Purification of the residue by
medium-pressure column chromatography (n-hexane/AcOEt, 7:1)
afforded 10Aa (61.2 mg, 99%) as colorless crystals. M.p. 78–80 °C
Reaction of 7Aa with TFAT-DMAP: (Table 3, Entry 14) To a solu-
tion of oxime ether 7Aa (35.0 mg, 0.20 mmol) in CH2Cl2 (3 mL)
were added DMAP (24.4 mg, 0.20 mmol) and TFAT (0.060 mL,
0.40 mmol) under nitrogen at 0 °C. After being stirred at the same
temperature for 0.5 h, the reaction mixture was diluted with H2O
and extracted with CHCl3. The organic phase was washed with
H2O, dried with MgSO4, and concentrated at reduced pressure. Pu-
rification of the residue by preparative TLC (n-hexane/AcOEt,
(n-hexane). 1H NMR (CDCl3, 500 MHz): δ = 7.16 (br. t, J = 8 Hz, 10:1) afforded 10Aa (48.0 mg, 89%) as colorless crystals.
1 H), 7.15 (br. d, J = 8 Hz, 1 H), 6.94 (br. t, J = 8 Hz, 1 H), 6.89
N-(1-Cyclopentyl)-2,2,2-trifluoro-N-(phenylmethoxy)acetamide (13):
(br. s, 1 H), 6.78 (br. d, J = 8 Hz, 1 H), 4.00 (br. d, J = 8.5 Hz, 1
(Table 4, Entry 1) To a solution of the oxime ether 12[11] (37.8 mg,
H), 2.41–2.24 (m, 3 H), 1.87–1.83 (m, 2 H), 1.63–1.58 (m, 1 H)
0.20 mmol), prepared by condensation of cyclopentanone with O-
ppm. 13C NMR (CDCl3, 125 MHz): δ = 158.3, 155.8 (q, COCF3),
benzylhydroxylamine, in CH2Cl2 (3 mL) was added TFAA
129.7, 128.5, 124.7, 121.8, 115.3 (q, CF3), 108.9, 105.7, 51.4, 38.7,
(0.028 mL, 0.20 mmol) under nitrogen at 0 °C. After being stirred
34.1, 24.1 ppm. IR (CHCl ): ν = 3423 (NH), 1726 cm–1 (NCOCF3).
˜
3
at the same temperature for 30 min, the reaction mixture was con-
centrated at reduced pressure. Purification of the residue by prepar-
ative TLC (n-hexane/AcOEt, 20:1) afforded 13 (46.3 mg, 81%) as
HRMS (EI, m/z) calcd. for C13H12F3NO2 (M+) 271.0820, found
271.0820. C13H12F3NO2: calcd. C 57.57, H 4.46, N 5.16; found C
57.43, H 4.32, N 5.11; NOE was observed between 8b-H (δ =
4.00 ppm) and NH (δ = 6.89 ppm) in NOESY spectroscopy.
1
a colorless oil. H NMR (CDCl3, 300 MHz): δ = 7.39 (br. s, 5 H),
5.88 (br. t, J = 2 Hz, 1 H), 4.92 (br. s, 2 H), 2.72 (br. s, 2 H), 2.52–
2.46 (m, 2 H), 2.01 (br. quint, J = 7 Hz, 2 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 154.4 (q, COCF3), 137.2, 133.1, 129.23,
129.18, 128.7, 121.0, 116.1 (q, CF3), 77.6, 31.8, 30.3, 22.0 ppm. IR
3a-Amino-1,2,3,8b-tetrahydro-3aH-cyclopenta[b]benzofuran (10d):
(Table 3, Entry 4) To a solution of the oxime ether 7Aa (40 mg,
0.23 mmol) in CH2Cl2 (4 mL) was added TFA (0.018 mL,
0.23 mmol) under nitrogen at room temperature. After being stirred
at the same temperature for 20 h, the reaction mixture was concen-
trated at reduced pressure. Purification of the residue by medium-
pressure column chromatography (n-hexane/AcOEt, 5:1) afforded
dihydrobenzofuran 10d (6.3 mg, 16 %) as a colorless solid. 1H
NMR (CDCl3, 300 MHz): δ = 7.51 (br. s, 2 H), 7.15 (br. t, J =
8 Hz, 1 H), 7.11 (br. d, J = 8 Hz, 1 H), 6.93 (br. t, J = 8 Hz, 1 H),
6.89 (br. d, J = 8 Hz, 1 H), 3.65 (br. t, J = 8.5 Hz, 1 H), 2.48–2.34
(m, 3 H), 2.27–2.19 (m, 2 H), 2.06–1.98 (m, 1 H) ppm. HRMS
(EI, m/z) calcd. for C11H13NO (M+) 175.0996, found 175.0995. The
stereostructures of 10d were not determined.
(CHCl ): ν = 1708 cm–1 (NCOCF3). HRMS (EI, m/z) calcd. for
˜
3
C14H14F3NO2 (M+) 285.0976, found 285.0973.
Reaction of 7Ab with TFAA: (Table 5, Entry 1) To a solution of the
oxime ether 7Ab (37.8 mg, 0.20 mmol) in CH2Cl2 (3 mL) was added
TFAA (0.028 mL, 0.20 mmol) under nitrogen at room temperature.
After being stirred at the same temperature for 23 h, the reaction
mixture was concentrated at reduced pressure. Purification of the
residue by medium-pressure column chromatography (n-hexane/
AcOEt, 10:1) afforded 10Ab (21.1 mg, 37%) as colorless crystals,
14Ab (6.6 mg, 19%) as a colorless oil, and 11Ab, 11ЈAb (combined
two isomers, 13.3 mg, 23%), respectively.
2,2,2-Trichloro-N-(cis-1,2,3,8b-tetrahydro-3aH-cyclopenta[b]benzo-
furan-3a-yl)acetamide (10b): (Table 3 Entry 5) To a solution of the
oxime ether 7Aa (40 mg, 0.23 mmol) in CH2Cl2 (4 mL) was added
TCAA (0.042 mL, 0.23 mmol) under nitrogen at room temperature.
After being heated at reflux for 3 h, the reaction mixture was con-
centrated at reduced pressure. Purification of the residue by me-
dium-pressure column chromatography (n-hexane/AcOEt, 5:1) af-
forded 10b (68.2 mg, 94%) as colorless crystals. M.p. 127–128 °C
2,2,2-Trifluoro-N-[cis-1,3,4,9b-tetrahydro-4a(2H)-dibenzofuranyl]-
acetamide (10Ab): M.p. 64–66 °C (n-hexane/AcOEt). 1H NMR
(CDCl3, 500 MHz): δ = 7.18 (br. t, J = 8 Hz, 1 H), 7.17 (br. d, J
= 8 Hz, 1 H), 6.96 (td, J = 8, 1 Hz, 1 H), 6.88 (dd, J = 8, 1 Hz, 1
H), 6.52 (br. s, 1 H), 3.76 (br. t, J = 8.5 Hz, 1 H), 2.43–2.36 (m, 1
H), 2.23 (dt, J = 14.5, 4 Hz, 1 H), 2.18–2.13 (m, 1 H), 1.75–1.71
(m, 1 H), 1.53–1.45 (m, 2 H), 1.38–1.25 (m, 2 H) ppm. 13C NMR
(CDCl3, 125 MHz): δ = 156.7, 156.3 (q, COCF3), 132.1, 128.4,
124.4, 122.2, 115.3 (q, CF3), 110.5, 98.0, 44.8, 30.4, 30.0, 20.4,
1
(n-hexane/AcOEt). H NMR (CDCl3, 500 MHz): δ = 7.26 (br. s, 1
H), 7.18–7.14 (m, 2 H), 6.94 (td, J = 8, 1 Hz, 1 H), 6.79 (br. d, J
= 8 Hz, 1 H), 4.03 (br. d, J = 8.5 Hz, 1 H), 2.40–2.26 (m, 3 H),
1.89–1.82 (m, 2 H), 1.65–1.55 (m, 1 H) ppm. 13C NMR (CDCl3,
125 MHz): δ = 160.3, 158.4, 129.9, 128.3, 124.6, 121.7, 108.8, 106.4,
20.1 ppm. IR (CHCl ): ν = 3417 (NH), 1726 cm–1 (NCOCF3).
˜
3
HRMS (EI, m/z) calcd. for C14H14F3NO2 (M+) 285.0976, found
285.0991. C14H14F3NO2: calcd. C 58.95, H 4.95, N 4.91; found C
58.65, H 4.97, N 4.92; NOE was observed between 8b-H (δ =
3.76 ppm) and NH (δ = 6.52 ppm) in NOESY spectroscopy.
51.2, 38.6, 34.2, 24.1 ppm. IR (CHCl ): ν = 3419 (NH), 1714 cm–1
˜
3
(NCOCF3). HRMS (EI, m/z) calcd. for C13H1235Cl3NO2 (M+)
318.9933, found 318.9941. C13H12Cl3NO2: calcd. C 48.70, H 3.77,
N 4.37; found C 48.72, H 3.80, N 4.36; NOE was observed between
8b-H (δ = 4.03 ppm) and NH (δ = 7.26 ppm) in NOESY spec-
troscopy.
1,2,3,4-Tetrahydrodibenzofuran (14Ab):[27] 1H NMR (CDCl3,
300 MHz): δ = 7.41–7.37 (m, 2 H), 7.19–7.17 (m, 2 H), 2.74 (m, 2
H), 2.62 (m, 2 H), 1.97–1.80 (m, 4 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 154.3, 154.0, 128.8, 122.9, 122.1, 118.3, 112.8, 110.7,
23.4, 22.9, 22.7, 20.4 ppm. HRMS (EI, m/z) calcd. for C12H12O
(M+) 172.0887, found 172.0901.
Reaction of 7Aa with TFAT: (Table 3, Entry 7) To a solution of the
oxime ether 7Aa (35.0 mg, 0.20 mmol) in CH2Cl2 (3 mL) was added
TFAT (0.030 mL, 0.20 mmol) under nitrogen at 0 °C. After being
stirred at the same temperature for 2 h, the reaction mixture was
neutralized with the saturated aqueous NaHCO3 and extracted
with CHCl3. The organic phase was washed with H2O, dried with
MgSO4, and concentrated under reduced pressure. Purification of
the residue by preparative TLC (n-hexane/AcOEt, 10:1) afforded
2,2,2-Trifluoro-N-[2-(2-hydroxyphenyl)-1-cyclohexen-1-yl]acetamide
(11Ab): A colorless oil (5.6 mg, 10 %). 1H NMR (CDCl3,
300 MHz): δ = 7.48 and 5.18 ppm(br. s, each 1 H), 7.22 (br. t, J =
8 Hz, 1 H), 7.06 (br. dd, J = 8, 1 Hz, 1 H), 6.96 (br. td, J = 8, 1 Hz,
1 H), 6.93 (br. dd, J = 8, 1 Hz, 1 H), 2.66 and 2.36 (m, each 2 H),
1.88–1.75 (m, 4 H). IR (CHCl ): ν = 3537 (OH), 3392 (NH),
˜
3
Eur. J. Org. Chem. 2007, 1491–1509
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1503

N. Takeda, O. Miyata, T. Naito
FULL PAPER
1718 cm–1 (NCOCF3). HRMS (EI, m/z) calcd. for C14H14F3NO2
155.83, 155.81, 155.80 (q, COCF3), 155.7 (q, COCF3), 131.7, 130.9,
128.6, 128.5, 124.6, 124.14, 122.1, 121.8, 115.5 (q, CF3), 115.3 (q,
CF3), 110.0, 109.7, 101.5, 101.3, 45.84, 45.80, 29.9, 24.7, 16.6, 15.0,
(M+) 285.0976, found 285.0981.
2,2,2-Trifluoro-N-[6-(2-hydroxyphenyl)-1-cyclohexen-1-yl]acetamide
(11ЈAb): A colorless oil (7.5 mg,13 %). 1H NMR (CDCl3,
200 MHz): δ = 7.26–7.11 (m, 2 H), 6.97 and 5.24 (br. s, each 1 H),
6.92 (br. t, J = 8 Hz, 1 H), 6.80 (br. dd, J = 8, 1 Hz, 1 H), 6.69 (br.
td, J = 4.5, 1.5 Hz, 1 H), 3.93–3.86 (m, 1 H), 2.33–2.25 (m, 2 H),
7.3, 7.2 ppm. IR (CHCl ): ν = 3418 (NH), 1729 cm–1 (NCOCF3).
˜
3
HRMS (EI, m/z) calcd. for C13H14F3NO2 (M+) 273.0975, found
273.0979.
2-Ethyl-3-methylbenzofuran (14Ac):[28] (Table 7, Entry 3) To a solu-
tion of the oxime ether 7Ac (36.8 mg, 0.21 mmol) in CH2Cl2 (3 mL)
were added DMAP (76.6 mg, 0.63 mmol) and TFAT (0.16 mL,
1.05 mmol) under nitrogen at 0 °C. After being stirred at the same
temperature for 2 h, the reaction mixture was diluted with H2O and
extracted with CHCl3. The organic phase was washed with H2O,
dried with MgSO4, and concentrated at reduced pressure. Purifica-
tion of the residue by medium-pressure column chromatography
(n-hexane/AcOEt, 10:1) afforded 14Ac (29.8 mg, 89%) as a color-
less oil. 1H NMR (CDCl3, 300 MHz): δ = 7.43–7.36 (m, 2 H), 7.22–
7.16 (m, 2 H), 2.75 (br. q, J = 7.5 Hz, 2 H), 2.16 (s, 3 H), 1.29 (t,
J = 7.5 Hz, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 155.5,
153.8, 130.5, 123.0, 121.9, 118.6, 110.5, 108.7, 19.7, 12.8, 7.8 ppm.
HRMS (EI, m/z) calcd. for C11H12O (M+) 160.0887, found
160.0881.
2.10–1.55 (m, 4 H). IR (CHCl ): ν = 3595 (OH), 3406 (NH),
˜
3
1718 cm–1 (NCOCF3). HRMS (EI, m/z) calcd. for C14H14F3NO2
(M+) 285.0976, found 285.0971.
Reaction of 7Ab with TFAA: (Table 5, Entry 3) To a solution of the
oxime ether 7Ab (37.8 mg, 0.20 mmol) in CH2Cl2 (3 mL) was added
TFAA (0.11 mL, 0.80 mmol) under nitrogen at 0 °C. After being
stirred at the same temperature for 23 h, the reaction mixture was
concentrated at reduced pressure. Purification of the residue by me-
dium-pressure column chromatography (n-hexane/AcOEt, 10:1) af-
forded 10Ab (53.3 mg, 94%) as colorless crystals.
Reaction of 7Ab with TFAT-DMAP: (Table 5, Entry 6) To a solu-
tion of the oxime ether 7Ab (37.8 mg, 0.20 mmol) in CH2Cl2 (3 mL)
were added DMAP (73.3 mg, 0.60 mmol) and TFAT (0.15 mL,
1.0 mmol) under nitrogen at room temperature. After being stirred
at the same temperature for 0.5 h, the reaction mixture was diluted
with H2O and extracted with CHCl3. The organic phase was
washed with H2O, dried with MgSO4, and concentrated at reduced
pressure. Purification of the residue by medium-pressure column
chromatography (n-hexane/AcOEt, 10:1) afforded 14Ab (31.6 mg,
92%) as a colorless oil.
N-(2,3-Dihydro-2-methyl-2-benzofuranyl)-2,2,2-trifluoroacetamide
(10Ad): (Table 7, Entry 4) To a solution of the oxime ether 7Ad
(210 mg, 1.41 mmol) in MeCN (15 mL) was added TFAA
(1.17 mL, 8.46 mmol) under nitrogen at room temperature. After
being heated at reflux for 4 h, the reaction mixture was concen-
trated at reduced pressure. Purification of the residue by medium-
pressure column chromatography (n-hexane/AcOEt, 10:1) afforded
10Ad (325.5 mg, 94 %) as a colorless solid. 1H NMR (CDCl3,
300 MHz): δ = 7.19 (br. d, J = 8 Hz, 1 H), 7.18 (br. t, J = 8 Hz, 1
H), 6.94 (br. t, J = 8 Hz, 1 H), 6.83 (br. d, J = 8 Hz, 1 H), 6.79
(br. s, 1 H), 3.69 and 3.30 (br. d, J = 16.5 Hz, each 1 H), 1.90 (s, 3
H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 157.2, 155.8 (q,
COCF3), 128.5, 125.3, 125.1, 121.9, 115.3 (q, CF3), 109.7, 96.2,
41.5, 25.7 ppm. IR (CHCl ): ν = 3421 (NH), 1728 cm–1 (NCOCF3).
cis-1,2,3,4,4a,9b-Hexahydrodibenzofuran (15):[12] To a solution of
the dihydrobenzofuran 10Ab (42.7 mg, 0.15 mmol) in TFA
(1.0 mL) was added NaBH3CN (94.2 mg, 1.50 mmol) under nitro-
gen at 0 °C. After being stirred at room temperature for 4 h, the
reaction mixture was neutralized with the saturated aqueous
NaHCO3 and extracted with CHCl3. The organic phase was
washed with H2O, dried with MgSO4, and concentrated under re-
duced pressure. Purification of the residue by preparative TLC (n-
hexane/AcOEt, 10:1) afforded 2,3-dihydrobenzofuran 15 (16.8 mg,
64%) as a colorless oil.
˜
3
HRMS (EI, m/z) calcd. for C11H10F3NO2 (M+) 245.0663, found
245.0654.
2-Methylbenzofuran (14Ad):[3f] (Table 7, Entry 6) To a solution of
the oxime ether 7Ad (31.1 mg, 0.21 mmol) in CH2Cl2 (3 mL) were
added DMAP (76.6 mg, 0.63 mmol) and TFAT (0.16 mL,
1.05 mmol) under nitrogen at room temperature. After being stirred
at the same temperature for 0.5 h, the reaction mixture was diluted
with H2O and extracted with CHCl3. The organic phase was
washed with H2O, dried with MgSO4, and concentrated at reduced
pressure. Purification of the residue by medium-pressure column
chromatography (n-hexane/AcOEt, 10:1) afforded 14Ad (18.0 mg,
65%) as a colorless oil. 13C NMR (CDCl3, 50 MHz): δ = 155.4,
154.7, 129.2, 123.0, 122.4, 120.0, 110.6, 102.6, 14.1 ppm. HRMS
(EI, m/z) calcd. for C9H8O (M+) 132.0575, found 132.0576.
Conversion of 10Ab to 14Ab: (Table 6, Entry 1) To a solution of the
dihydrobenzofuran 10Ab (30.9 mg, 0.11 mmol) in CH2Cl2 (1.8 mL)
was added TfOH (0.010 mL, 0.11 mmol) under nitrogen at room
temperature. After being stirred at the same temperature for 1 min,
the reaction mixture was neutralized with the saturated aqueous
NaHCO3 and extracted with CHCl3. The organic phase was
washed with H2O, dried with MgSO4, and concentrated under re-
duced pressure. Purification of the residue by preparative TLC (n-
hexane/AcOEt, 10:1) afforded benzofuran 14Ab (15.7 mg, 84%).
N-(2-Ethyl-2,3-dihydro-3-methyl-2-benzofuranyl)-2,2,2-trifluoro-
acetamide (10Ac): (Table 7, Entry 2) To a solution of the the oxime
ether 7Ac (36.8 mg, 0.21 mmol) in MeCN (3 mL) was added TFAA
(0.17 mL, 1.26 mmol) under nitrogen at room temperature. After
being heated at reflux for 5 h, the reaction mixture was concen-
trated at reduced pressure. Purification of the residue by medium-
pressure column chromatography (n-hexane/AcOEt, 10:1) afforded
an inseparable mixture of 10Ac (36.3 mg, 64%, cis:trans = 1:1) as
General Procedure for Synthesis of 2-Arylbenzofurans 14: To a solu-
tion of the oxime ether 7Ae–u and 7Be–Le (0.17 mmol) in CH2Cl2
(3 mL) were added DMAP (63.0 mg, 0.52 mmol) and TFAT
(0.13 mL, 0.86 mmol) under nitrogen at room temperature. After
being stirred at the same temperature for several hours, the reaction
mixture was diluted with H2O and extracted with CHCl3. The or-
ganic phase was washed with H2O, dried with MgSO4, and concen-
trated at reduced pressure. Purification of the residue by medium-
pressure column chromatography (n-hexane/AcOEt, 20:1–5:1) af-
forded benzofuran 14Ae–u and 14Be–Le in the yield shown in
Table 8 and Table 9.
1
colorless solid. H NMR (CDCl3, 300 MHz): δ = 7.20–7.13 (m, 4/
2 H), 6.97 and 6.95 (br. t, J = 8 Hz, each 1/2 H), 6.84 and 6.82 (br.
d, J = 8 Hz, each 1/2 H), 6.59 and 6.53 (br. s, each 1/2 H), 3.78
and 3.53 (br. q, J = 7.5 Hz, each 1/2 H), 2.53 and 2.43 (dq, J = 14,
7.5 Hz, each 1/2 H), 2.11 and 1.96 (dq, J = 14, 7.5 Hz, each 1/2
H), 1.33 and 1.30 (d, J = 7.5 Hz, each 3/2 H), 1.07 and 1.01 (t, J
= 7.5 Hz, each 3/2 H) ppm. 13C NMR (CDCl3, 125 MHz): δ =
2-Phenylbenzofuran (14Ae):[29] A colorless oil. M.p. 118–120 °C (n-
hexane) (ref.[29] 118–120° C). 13C NMR (CDCl3, 50 MHz): δ =
1504
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Eur. J. Org. Chem. 2007, 1491–1509

Short Synthesis of Natural 2-Arylbenzofurans
FULL PAPER
155.9, 154.9, 130.5, 129.2, 128.8, 128.5, 124.9, 124.3, 122.9, 120.9,
7.50 (dm, J = 8 Hz, 1 H), 7.48–7.44 (dm, J = 8 Hz, 1 H), 7.30 (td,
111.2, 101.3 ppm. HRMS (EI, m/z) calcd. for C14H10O (M+) J = 8, 1.5 Hz, 1 H), 7.24 (td, J = 8, 1.5 Hz, 1 H), 2.44 (s, 3 H)
194.0371, found 194.0719.
ppm. 13C NMR (CDCl3, 50 MHz): δ = 153.8, 150.0, 131.8, 131.0,
130.3, 128.0, 124.6, 122.5, 121.9, 119.4, 111.9, 111.0, 9.5 ppm.
HRMS (EI, m/z) calcd. for C15H1179BrO (M+) 285.9993, found
285.9998. C15H11BrO: calcd. C 62.74, H 3.86; found C 62.65, H
3.70.
2-(4-Bromophenyl)benzofuran (14Af):[29] Colorless crystals. M.p.
159–160 °C (n-hexane/AcOEt) (ref.[29] 159–161° C). 13C NMR
(CDCl3, 50 MHz): δ = 154.9, 154.8, 132.0, 129.4, 129.1, 126.4,
124.6, 123.1, 122.5, 121.0, 111.2, 101.8 ppm. HRMS (EI, m/z)
calcd. for C14H979BrO (M+) 271.9837, found 271.9828.
4-(3-Methyl-2-benzofuranyl)phenol (14Al):[33] Colorless crystals.
1
M.p. 85–87 °C (n-hexane/AcOEt). H NMR (CDCl3, 300 MHz): δ
2-(4-Nitrophenyl)benzofuran (14Ag):[30] Colorless crystals. M.p.
184.5–185 °C (MeOH/CHCl3) (ref.[30] 183.5–184.5 °C). 1H NMR
(CDCl3, 300 MHz): δ = 8.16 (br. d, J = 8.5 Hz, 2 H), 7.98 (br. d,
J = 8.5 Hz, 2 H), 7.65–7.62 (dm, J = 8 Hz, 1 H), 7.57–7.54 (dm, J
= 8 Hz, 1 H), 7.36 (td, J = 8, 1.5 Hz, 1 H), 7.27 (td, J = 8, 1.5 Hz,
1 H), 7.22 (d, J = 1 Hz, 1 H) ppm. 13C NMR (CDCl3, 50 MHz): δ
= 155.4, 153.2, 147.2, 136.3, 128.6, 125.2, 124.3, 123.5, 121.6, 111.5,
= 7.69 (br. d, J = 8.5 Hz, 2 H), 7.52–7.49 (dm, J = 8 Hz, 1 H),
7.47–7.44 (dm, J = 8 Hz, 1 H), 7.27 (td, J = 8, 1.5 Hz, 1 H), 7.23
(td, J = 8, 1.5 Hz, 1 H), 6.94 (br. d, J = 8.5 Hz, 2 H), 4.99 (br. s,
1 H), 2.43 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 155.3,
153.6, 150.7, 131.3, 128.4, 124.4, 123.9, 122.3, 119.0, 115.6, 110.8,
109.7, 9.4 ppm. IR (nujol): ν = 3294 cm–1 (OH). HRMS (EI, m/z)
˜
calcd. for C15H12O2 (M+) 224.0836, found 224.0841.
105.1 ppm. IR (CHCl ): ν = 1519 and 1346 cm–1 (NO2). HRMS
˜
3
2-(4-Methoxyphenyl)-3-methylbenzofuran (14Am):[19] Colorless
crystals. M.p. 87–88 °C (n-hexane) (ref.[19] 87 °C). 13C NMR
(CDCl3, 50 MHz): δ = 159.4, 153.6, 150.9, 131.3, 128.2, 124.2,
123.9, 122.3, 119.0, 114.1, 110.8, 109.7, 55.4, 9.4 ppm. HRMS (EI,
m/z) calcd. for C16H14O2 (M+) 238.0993, found 238.1000.
2-(3-Bromophenyl)benzofuran (14An):[34] Colorless crystals. M.p.
84–85 °C (n-hexane/AcOEt) (ref.[34] 85 °C). 13C NMR (CDCl3,
75 MHz): δ = 154.9, 154.2, 132.4, 131.3, 130.3, 128.9, 127.8, 124.8,
123.4, 123.1, 122.9, 121.1, 111.2, 102.4 ppm. HRMS (EI, m/z)
calcd. for C14H979BrO (M+) 271.9837, found 271.9837.
(EI, m/z) calcd. for C14H9NO3 (M+) 239.0582, found 239.0586.
4-(2-Benzofuranyl)phenol (14Ah):[31] Colorless crystals. M.p. 195–
196 °C (MeOH) (ref.[31] 195–197 °C). 1H NMR (CDCl3, 300 MHz):
δ = 7.76 (br. d, J = 8.5 Hz, 2 H), 7.57–7.54 (dm, J = 8 Hz, 1 H),
7.51–7.48 (dm, J = 8 Hz, 1 H), 7.25 (td, J = 8, 1.5 Hz, 1 H), 7.21
(td, J = 8, 1.5 Hz, 1 H), 6.91 (br. d, J = 8.5 Hz, 2 H), 6.88 (d, J =
1 Hz, 1 H), 4.92 (br. s, 1 H) ppm. 13C NMR (CDCl3, 50 MHz): δ
= 156.0, 154.7, 129.4, 126.7, 123.8, 123.7, 122.8, 120.6, 115.7, 111.0,
99.7 ppm. IR (CHCl ): ν = 3414 cm–1 (OH). HRMS (EI, m/z)
˜
3
calcd. for C14H10O2 (M+) 210.0681, found 210.0682.
2-(3-Nitrophenyl)benzofuran (14Ao):[35] Colorless crystals. M.p.
134–135 °C (MeOH/CHCl3) (ref.[35] 129–130 °C). 1H NMR
(CDCl3, 300 MHz): δ = 8.68 (t, J = 2 Hz, 1 H), 8.19–8.12 (m, 2
H), 7.62 (br. d, J = 8 Hz, 1 H), 7.61 (br. t, J = 8 Hz, 1 H), 7.55
(br. d, J = 8 Hz, 1 H), 7.35 (td, J = 8, 1.5 Hz, 1 H), 7.27 (td, J =
8, 1.5 Hz, 1 H), 7.17 (d, J = 1 Hz, 1 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 155.1, 153.1, 148.7, 132.1, 130.2, 129.8, 128.6, 125.3,
2-(4-Methoxyphenyl)benzofuran (14Ai):[29] Colorless crystals. M.p.
148–149 °C (n-hexane/AcOEt) (ref.[29] 146–147 °C). 13C NMR
(CDCl3, 50 MHz): δ = 160.0, 156.1, 154.7, 129.5, 126.4, 123.7,
123.4, 122.8, 120.6, 114.3, 111.0, 99.7, 55.4 ppm. HRMS (EI, m/z)
calcd. for C15H12O2 (M+) 224.0837, found 224.0856.
2,2,2-Trifluoro-1-[2-(4-methoxyphenyl)-3-benzofuranyl]ethanone
(14ЈAi): Yellow crystals. M.p. 73–75 °C (n-hexane). 1H NMR
(CDCl3, 300 MHz): δ = 7.94 (br. d, J = 8 Hz, 1 H), 7.86 (br. d, J
= 8.5 Hz, 2 H), 7.58 (br. d, J = 8 Hz, 1 H), 7.43–7.38 (m, 2 H),
7.03 (br. d, J = 8.5 Hz, 2 H), 3.90 (s, 3 H) ppm. 13C NMR
(CDCl3,125 MHz): δ = 177.7 (q, COCF3), 164.8, 162.1, 153.6,
131.4, 125.8, 125.3, 124.7, 121.4, 121.3, 116.2 (q, CF3), 113.9, 111.4,
123.4, 122.8, 121.4, 119.6, 111.4, 103.5 ppm. IR (CHCl ): ν = 1531
˜
3
and 1353 cm–1 (NO2). HRMS (EI, m/z) calcd. for C14H9NO3 (M+)
239.0582, found 239.0579.
3-(2-Benzofuranyl)phenol (14Ap):[36] Colorless crystals. M.p. 133–
134 °C (MeOH) (ref.[36] 131–133 °C). 1H NMR (CDCl3, 300 MHz):
δ = 7.58–7.55 (dm, J = 8 Hz, 1 H), 7.52–7.49 (dm, J = 8 Hz, 1 H),
7.44 (ddd, J = 8, 2, 1 Hz, 1 H), 7.35–7.19 (m, 4 H), 6.99 (d, J =
1 Hz, 1 H), 6.82 (ddd, J = 8, 2, 1 Hz, 1 H), 5.03 (br. s, 1 H) ppm.
13C NMR (CDCl3, 50 MHz): δ = 155.8, 155.4, 154.8, 132.0, 130.1,
129.1, 124.4, 123.0, 121.0, 117.6, 115.6, 111.7, 111.2, 101.7 ppm.
110.5, 55.4 ppm. IR (CHCl ): ν = 1698 cm–1 (CO). HRMS (EI,
˜
3
m/z) calcd. for C17H11F3O3 (M+) 320.0659, found 320.0666.
C17H11F3O3: calcd. C 63.75, H 3.46; found C 63.84, H 3.26.
4-(2-Benzofuranyl)phenyl Trifluoroacetate (14Av): The oxime ether
7Ah (80.3 mg, 0.35 mmol) was treated with DMAP (128.3 mg,
1.05 mmol) and TFAT (0.26 mL, 1.75 mmol). Workup and
recrystallization (n-hexane/AcOEt) afforded 14Av (99.9 mg, 92%)
as colorless crystals. M.p. 165–167 °C (n-hexane/AcOEt). 1H NMR
(CDCl3, 300 MHz): δ = 7.94 (br. d, J = 8.5 Hz, 2 H), 7.62–7.59
(dm, J = 8 Hz, 1 H), 7.54–7.52 (dm, J = 8 Hz, 1 H), 7.34–7.22 (m,
4 H), 7.05 (d, J = 1 Hz, 1 H) ppm. 13C NMR (CDCl3, 125 MHz):
δ = 155.8 (q, COCF3), 155.0, 154.3, 149.2, 129.8, 129.0, 126.3,
124.7, 123.2, 121.1, 121.0, 115.0 (q, CF3), 111.3, 102.2 ppm. IR
IR (nujol): ν = 3414 cm–1 (OH). HRMS (EI, m/z) calcd. for
˜
C14H10O2 (M+) 210.0681, found 210.0679.
2-(3-Methoxyphenyl)benzofuran (14Aq):[37] Colorless crystals. M.p.
48–49 °C (n-hexane/AcOEt) (ref.[37] 51 °C). 1H NMR (CDCl3,
300 MHz): δ = 7.59–7.56 (dm, J = 8 Hz, 1 H), 7.54–7.50 (dm, J =
8 Hz, 1 H), 7.45 (dm, J = 8 Hz, 1 H), 7.41 (t, J = 2 Hz, 1 H), 7.35
(t, J = 8 Hz, 1 H), 7.28 (td, J = 8, 1.5 Hz, 1 H), 7.22 (td, J = 8,
1.5 Hz, 1 H), 7.01 (d, J = 1 Hz, 1 H), 6.90 (ddd, J = 8, 2, 1 Hz, 1
H), 3.88 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 159.9,
155.7, 154.8, 131.8, 129.8, 129.2, 124.3, 122.9, 120.9, 117.5, 114.5,
111.2, 110.1, 101.6, 55.4 ppm. HRMS (EI, m/z) calcd. for C15H12O2
(M+) 224.0837, found 224.0841.
2-(2-Bromophenyl)benzofuran (14Ar):[38] Colorless crystals. M.p.
35–37 °C (n-hexane) (ref.[38] 36–37 °C). 1H NMR (CDCl3,
300 MHz): δ = 7.97 (dd, J = 8, 1.5 Hz, 1 H), 7.71 (dd, J = 8, 1.5 Hz,
1 H), 7.64 (br. d, J = 8 Hz, 1 H), 7.54 (br. s, 1 H), 7.53 (br. d, J =
8 Hz, 1 H), 7.42 (td, J = 8, 1.5 Hz, 1 H), 7.33 (td, J = 8, 1.5 Hz, 1
H), 7.25 (td, J = 8, 1.5 Hz, 1 H), 7.20 (td, J = 8, 1.5 Hz, 1 H) ppm.
(CHCl ): ν = 1799 cm–1 (OCOCF3). HRMS (EI, m/z) calcd. for
˜
3
C16H9F3O3 (M+) 306.0503, found 306.0512. C16H9F3O3·1/2H2O:
calcd. C 60.96, H 3.20; found C 60.96, H 3.09.
3-Methyl-2-phenylbenzofuran (14Aj):[32] A colorless oil. The spec-
troscopic data of 14Aj were identical with those previously re-
ported.[32]
2-(4-Bromophenyl)-3-methylbenzofuran (14Ak): Colorless crystals.
1
M.p. 80–81 °C (n-hexane/AcOEt). H NMR (CDCl3, 300 MHz): δ
= 7.66 (br. d, J = 8.5 Hz, 2 H), 7.58 (br. d, J = 8.5 Hz, 2 H), 7.54–
Eur. J. Org. Chem. 2007, 1491–1509
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1505

N. Takeda, O. Miyata, T. Naito
13C NMR (CDCl3, 50 MHz): δ = 154.3, 153.1, 134.3, 131.0, 129.8, rable (14De/14ЈDe = 1:1); colorless solid. 1H NMR (CDCl3,
FULL PAPER
129.4, 128.8, 127.5, 124.8, 123.0, 121.4, 120.7, 111.1, 107.0 ppm.
HRMS (EI, m/z) calcd. for C14H979BrO (M+) 271.9837, found
271.9835.
300 MHz): δ = 7.88 and 7.84 ppm (br. d, J = 8.5 Hz, each 2/2 H),
7.69 (br. s, 1/2 H), 7.49–7.34 (m, 10/2 H), 7.15 (br. t, J = 8 Hz, 1/
2 H), 7.06 and 6.98 (d, J = 1 Hz, each 1/2 H) ppm. 13C NMR
(CDCl3, 50 MHz): δ = 156.5, 156.4, 155.0, 154.4, 130.7, 129.9,
129.8, 129.2, 129.0, 128.8, 128.5, 128.2, 126.3, 125.9, 125.0, 124.9,
121.7, 117.3, 114.6, 113.8, 111.1, 110.2, 101.3, 101.0 ppm. HRMS
(EI, m/z) calcd. for C14H979BrO (M+) 271.9837, found 271.9862.
2,2,2-Trifluoro-N-[2-(2-hydroxyphenyl)-1-(2-nitrophenyl)-1-ethenyl]-
acetamide (19As): The rearranged products (E)-19As and (Z)-19As
were inseparable. Stereostructures of E and Z isomers (1:1) have
1
not been established; yellow oil. H NMR (CDCl3, 300 MHz): δ =
4-Nitro-2-phenylbenzofuran (14Je) and 6-Nitro-2-phenylbenzofuran
9.60 (br. s, 1/2 H), 8.04 (br. d, J = 8 Hz, 2/2 H), 7.98 (br. s, 1/2 H),
7,70–7.67 (m, 2/2 H), 7,52–7.49 (m, 2/2 H), 7,38–7.35 (m, 2/2 H),
7.25 (br. t, J = 8 Hz, 1/2 H), 7.24 (br. d, J = 8 Hz, 1/2 H), 7.20 (br.
s, 1/2 H), 7.03 (br. t, J = 8 Hz, 1/2 H), 7.01 (br. t, J = 8 Hz, 1/2
H), 6.92 (br. d, J = 8 Hz, 1/2 H), 6.70–6,61 (m, 3/2 H), 6.30 (br. s,
1/2 H) ppm. 13C NMR (CDCl3, 125 MHz): δ = 155.5 (q, COCF3),
154.6 (q, COCF3), 153.4, 151.6, 148.1, 147.6, 134.0, 133.6, 133.5,
132.6, 132.3, 131.3, 131.0, 130.4, 130.2, 130.0, 129.63, 129.58,
125.0, 124.6, 121.7, 121.2, 120.6, 120.5, 120.4, 116.8, 115.9, 115.6
(14ЈJe):[46] The benzofurans 14Je and 14ЈJe were inseparable (14Je/
1
14ЈJe = 2:1); yellow solid. H NMR (CDCl3, 300 MHz): δ = 8.40
(br. s, 1/3 H), 8.18 (br. d, J = 8 Hz, 1/3 H), 8.16 (br. dd, J = 8 Hz,
2/3 H), 7.93 (br. d, J = 8.5 Hz, 4/3 H), 7.89 (br. d, J = 8.5 Hz, 2/3
H), 7.81 (br. d, J = 8 Hz, 2/3 H), 7.74 (d, J = 1 Hz, 2/3 H), 7.63
(d, J = 8 Hz, 1/3 H), 7.52–7.41 (m, 9/3 H), 7.37 (t, J = 8 Hz, 2/3
H), 7.09 (d, J = 1 Hz, 1/3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ
= 161.3, 159.9, 155.9, 153.4, 144.7, 140.4, 135.2, 130.0, 129.1, 129.0,
125.6, 125.5, 125.3, 123.2, 120.5, 119.7, 118.9, 117.2, 107.6, 101.4,
(q, COCF ) ppm. IR (CHCl ): ν = 3589 (OH), 3406 (NH), 1730
˜
3
3
101.3 ppm. IR (CHCl ): ν = 1519 and 1337 cm–1 (NO2). HRMS
(NCOCF3), 1531 and 1353 cm–1 (NO2). HRMS (EI, m/z) calcd. for
˜
3
(EI, m/z) calcd. for C14H9NO3 (M+) 239.0582, found 239.0610.
C16H11F3N2O4 (M+) 352.0670, found 352.0682.
2-(2-Benzofuranyl)phenol (14At):[39] Colorless crystals. M.p. 94–
4-Methyl-2-phenylbenzofuran (14Ee) and 6-Methyl-2-phenylbenzo-
furan (14ЈEe):[47,48] The benzofurans 14Ee and 14ЈEe were insepa-
rable (14Ee/14ЈEe = 1:1.5); colorless solid. 1H NMR (CDCl3,
300 MHz): δ = 7.87 (br. d, J = 8.5 Hz, 4/5 H), 7.83 (br. d, J =
8.5 Hz, 6/5 H), 7.47–7.23 (m, 23/5 H), 7.18 (br. t, J = 8 Hz, 2/5 H),
7.06 (br. s, 3/5 H), 7.03 (d, J = 1 Hz, 2/5 H), 7.02 (br. d, J = 8 Hz,
2/5 H), 6.96 (d, J = 1 Hz, 3/5 H), 2.54 (s, 6/5 H), 2.48 (s, 9/5 H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 155.3, 154.7, 134.5, 130.8,
130.7, 130.6, 129.0, 128.7, 128.4, 128.2, 126.7, 124.8, 124.7, 124.3,
124.2, 123.2, 120.3, 111.4, 108.6, 101.1, 100.0, 21.7, 18.6 ppm.
HRMS (EI, m/z) calcd. for C15H12O (M+) 208.0888, found
208.0897.
1
95 °C (n-hexane) (ref.[39] 93–94 °C). H NMR (CDCl3, 300 MHz):
δ = 7.71 (dd, J = 8, 1.5 Hz, 1 H), 7.60 (br. d, J = 8 Hz, 1 H), 7.53
(br. d, J = 8 Hz, 1 H), 7.34–7.24 (m, 3 H), 7.14 (br. s, 1 H), 7.09
(d, J = 1 Hz, 1 H), 7.03–6.97 (m, 2 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 154.3, 154.0, 153.3, 130.3, 128.5, 127.2, 124.4, 123.4,
121.0, 120.8, 117.4, 116.1, 111.0, 103.3 ppm. IR (CHCl ): ν =
˜
3
3527 cm–1 (OH). HRMS (EI, m/z) calcd. for C14H10O2 (M+)
210.0681, found 210.0689.
2-(2-Methoxyphenyl)benzofuran (14Au):[40] Colorless crystals. M.p.
78–79 °C (n-hexane) (ref.[40] 78.5–80 °C). 1H NMR (CDCl3,
300 MHz): δ = 8.07 (br. dd, J = 8, 1.5 Hz, 1 H), 7.60–7.57 (dm, J
= 8 Hz, 1 H), 7.52–7.549 (dm, J = 8 Hz, 1 H), 7.35 (br. s, 1 H),
7.35–7.18 (m, 3 H), 7.08 (br. t, J = 8 Hz, 1 H), 7.00 (br. d, J =
8 Hz, 1 H), 4.00 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ =
155.9, 153.2, 151.5, 129.1, 128.6, 126.4, 123.4, 122.0, 120.4, 120.1,
118.7, 110.4, 110.4, 110.2, 105.7, 54.8 ppm. HRMS (EI, m/z) calcd.
for C15H12O2 (M+) 224.0837, found 224.0851.
5-Bromo-2-phenylbenzofuran (14Be):[41] Colorless crystals. M.p.
158–159 °C (MeOH) (ref.[41] 158–159 °C). 1H NMR (CDCl3,
300 MHz): δ = 7.85 (br. d, J = 8.5 Hz, 2 H), 7.71–7.70 (m, 1 H),
7.49–7.34 (m, 5 H), 6.96 (br. s, 1 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 157.3, 153.6, 131.2, 129.9, 129.0, 128.9, 127.1, 125.1,
123.5, 116.0, 112.6, 100.6 ppm. HRMS (EI, m/z) calcd. for
C14H979BrO (M+) 271.9837, found 271.9837.
2-Phenyl-4-benzofuranol (14Le) and 2-Phenyl-6-benzofuranol
(14ЈLe):[49] The benzofurans 14Le and 14ЈLe were inseparable
(14Le/14ЈLe = 1:1.5); colorless solid. 1H NMR (CDCl3, 300 MHz):
δ = 7.85 (br. d, J = 8.5 Hz, 4/5 H), 7.81 (br. d, J = 8.5 Hz, 6/5 H),
7.47–7.29 (m, 20/5 H), 7.14 (br. d, J = 8 Hz, 2/5 H), 7.10 (br. d, J
= 1 Hz, 2/5 H), 7.01 (br. d, J = 2 Hz, 3/5 H), 6.94 (br. d, J = 1 Hz,
3/5 H), 6.77 (br. dd, J = 8, 2 Hz, 3/5 H), 6.63 (br. dd, J = 8, 2 Hz,
2/5 H), 5.01 (br. s, 5/5 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
156.5, 155.8, 155.3, 154.9, 153.6, 149.1, 130.6, 130.4, 128.8, 128.7,
128.5, 128.1, 124.9, 124.8, 124.5, 122.9, 121.1, 118.5, 112.0, 108.0,
104.4, 101.1, 98.3, 98.0 ppm. IR (CHCl ): ν = 3597 cm–1 (OH).
˜
3
HRMS (EI, m/z) calcd. for C14H10O2 (M+) 210.0681, found
210.0681.
4-Methoxy-2-phenylbenzofuran (14Fe) and 6-Methoxy-2-phenylben-
zofuran (14ЈFe):[50,51] The benzofurans 14Fe and 14ЈFe were insepa-
rable (14Fe/14ЈFe = 1:4); colorless solid. 1H NMR (CDCl3,
300 MHz): δ = 7.84 (br. d, J = 8.5 Hz, 2/5 H), 7.80 (br. d, J =
8.5 Hz, 8/5 H), 7.45–7.39 (m, 14/5 H), 7.33 (br. t, J = 8.5 Hz, 1/5
H), 7.31 (br. t, J = 8.5 Hz, 4/5 H), 7.21 (t, J = 8 Hz, 1/5 H), 7.15
(br. d, J = 8 Hz, 1/5 H), 7.12 (d, J = 1 Hz, 1/5 H), 7.07 (br. d, J =
2 Hz, 4/5 H), 6.94 (d, J = 1 Hz, 4/5 H), 6.87 (br. dd, J = 8, 2 Hz,
4/5 H), 6.66 (br. d, J = 8 Hz, 1/5 H), 3.96 (s, 3/5 H), 3.87 (s, 12/5
H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 158.1, 156.1, 155.9,
155.1, 154.6, 153.4, 130.7, 130.5, 128.7, 128.2, 128.0, 124.9, 124.7,
124.4, 122.5, 121.0, 119.5, 111.9, 104.4, 103.3, 101.1, 98.8, 95.9,
55.7, 55.5 ppm. HRMS (EI, m/z) calcd. for C15H12O2 (M+)
224.0837, found 224.0852.
5-Nitro-2-phenylbenzofuran (14Ie):[42] Yellow crystals. M.p. 159–
161 °C (MeOH) (ref.[42] 158–161 °C). 1H NMR (CDCl3, 300 MHz):
δ = 8.48 (d, J = 2 Hz, 1 H), 8.20 (br. dd, J = 8, 2 Hz, 1 H), 7.86
(br. d, J = 8.5 Hz, 2 H), 7.57 (br. d, J = 8 Hz, 1 H), 7.51–7.39 (m,
3 H), 7.10 (d, J = 1 Hz, 1 H) ppm. 13C NMR (CDCl3, 50 MHz): δ
= 159.2, 157.6, 144.3, 129.7, 129.6, 129.1, 129.0, 125.2, 120.1, 117.2,
111.4, 101.6 ppm. IR (CHCl ): ν = 1525 and 1350 cm–1 (NO2).
˜
3
HRMS (EI, m/z) calcd. for C14H9NO3 (M+) 239.0582, found
239.0581.
5-Methyl-2-phenylbenzofuran (14Ce):[43] Colorless crystals.
M.p.128–130 °C (EtOH) (ref.[43] 125–126 °C). 13C NMR (CDCl3,
50 MHz): δ = 156.0, 153.3, 132.3, 130.6, 129.3, 128.7, 128.4, 125.5,
124.8, 120.7, 110.6, 101.1, 21.3 ppm. HRMS (EI, m/z) calcd. for
C15H12O (M+) 208.0888, found 208.0888.
7-Bromo-2-phenylbenzofuran (14Ge): A colorless oil. 1H NMR
(CDCl3, 300 MHz): δ = 7.89 (br. d, J = 8.5 Hz, 2 H), 7.52–7.35 (m,
5 H), 7.10 (br. t, J = 8 Hz, 1 H), 7.07 (s, 1 H) ppm. 13C NMR
4-Bromo-2-phenylbenzofuran (14De) and 6-Bromo-2-phenylbenzo-
furan (14ЈDe):[44,45] The benzofurans 14De and 14ЈDe were insepa-
1506
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1491–1509

Short Synthesis of Natural 2-Arylbenzofurans
FULL PAPER
(CDCl3, 50 MHz): δ = 156.7 152.0, 130.5, 129.8, 129.0, 128.8,
127.2, 125.2, 124.2, 120.0, 103.9, 101.8 ppm. HRMS (EI, m/z)
calcd. for C14H979BrO (M+) 271.9837, found 271.9843.
mophenyl)hydroxylamine (5B) (376.0 mg, 2 mmol) with 4-hydroxy-
propiophenone (300.0 mg, 2 mmol) and concd. aqueous HCl
(0.10 mL) in EtOH (4 mL) gave the oxime ether 24 (601.6 mg, 94%,
E:Z = 10:1) as a colorless oil. The oxime ethers (E)-24 and (Z)-24
7-Nitro-2-phenylbenzofuran (14Ke):[52] Yellow crystals. M.p. 118–
119 °C (n-hexane) (ref.[52] 119–120 °C). 1H NMR (CDCl3,
300 MHz): δ = 8.12 (br. dd, J = 8, 2 Hz, 1 H), 7.96 (br. d, J =
8 Hz, 2 H), 7.88 (dd, J = 8.5, 2 Hz, 1 H), 7.53–7.40 (m, 3 H), 7.35
(t, J = 8 Hz, 1 H), 7.13 (s, 1 H) ppm. 13C NMR (CDCl3, 75 MHz):
δ = 158.6, 146.8, 133.8, 133.2, 129.6, 128.9, 127.4, 125.4, 122.8,
1
were inseparable. H NMR (CDCl3, 300 MHz): δ = 7.65 (br. d, J
= 8.5 Hz, 2 H), 7.41 (br. d, J = 8.5 Hz, 2 H), 7.16 (br. d, J = 8.5 Hz,
2 H), 6.86 (br. d, J = 8.5 Hz, 2 H), 5.08 (br. s, 1 H), 2.90 (q, J =
7.5 Hz, 20/11 H), 2.68 (q, J = 7.5 Hz, 2/11 H), 1.22 (t, J = 7.5 Hz,
30/11 H), 1.15 (t, J = 7.5 Hz, 3/11 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 163.3, 158.6, 157.3, 132.0, 128.3, 126.9, 116.5, 115.5,
120.4, 100.8 ppm. IR (CHCl ): ν = 1529 and 1343 cm–1 (NO2).
˜
3
114.0, 20.7, 11.4 ppm. IR (CHCl ): ν = 3592 cm–1 (OH). HRMS
HRMS (EI, m/z) calcd. for C14H9NO3 (M+) 239.0582, found
˜
3
(EI, m/z) calcd. for C15H1479BrNO2 (M+) 319.0207, found
319.0210. The 13C NMR spectroscopic data of only (E)-24 was
described.
239.0584.
2,2,2-Trifluoro-N-[2-(2-hydroxy-3-nitrophenyl)-1-phenyl-1-ethenyl]-
acetamide (19Ke): The rearranged products (E)-19Ke and (Z)-19Ke
were inseparable. Stereostructures of E and Z isomers (2:1) have
4-(5-Bromo-3-methyl-2-benzofuranyl)phenol (25): According to the
procedure given for 14, reaction of the oxime ether 24 (37.4 mg,
0.12 mmol) with DMAP (42.8 mg, 0.35 mmol) and TFAT
(0.09 mL, 0.59 mmol) in CH2Cl2 (4 mL) gave the benzofuran 25
(32.7 mg, 92%) as colorless crystals. M.p. 157–159 °C (n-hexane/
1
not been established; yellow solid. H NMR (CDCl3, 300 MHz): δ
= 11.3 (br. s, 2/3 H), 10.9 (br. s, 1/3 H), 8.06 (br. d, J = 8 Hz, 2/3
H), 8.05 (br. s, 2/3 H), 7.85 (br. d, J = 8 Hz, 1/3 H), 7.58 (br. d, J
= 8 Hz, 2/3 H), 7.57 (br. s, 1/3 H), 7.46–7.19 (m, 16/3 H), 6.99 (br.
t, J = 8 Hz, 2/3 H), 6.93 (br. d, J = 8 Hz, 1/3 H), 6.73 (br. s, 2/3 H),
6.56 (br. t, J = 8 Hz, 1/3 H) ppm. 13C NMR (CDCl3, 125 MHz): δ
= 155.3 (q, COCF3), 154.8 (q, COCF3), 153.2, 151.9, 137.9, 137.2,
135.7, 134.7, 134.6, 134.5, 134.3, 133.8, 129.8, 129.6, 129.4, 128.94,
128.92, 126.6, 126.2, 125,0, 123.8, 120.1, 119.2, 117.4, 116.8, 115.7
1
Et2O). H NMR (CDCl3, 500 MHz): δ = 7.67 (br. d, J = 8.5 Hz, 2
H), 7.60 (dd, J = 2, 0.5 Hz, 1 H), 7.32 (d, J = 2 Hz, 1 H), 7.31 (d,
J = 0.5 Hz, 1 H), 6.94 (br. d, J = 8.5 Hz, 2 H), 5.12 (br. s, 1 H),
2.38 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 155.6, 152.3,
152.1, 133.3, 128.5, 126.6, 123.8, 121.8, 115.7, 115.4, 112.2, 109.3,
9.3 ppm. IR (CHCl ): ν = 3594 cm–1 (OH). HRMS (EI, m/z) calcd.
˜
(q, COCF ), 114.5 ppm. IR (CHCl ): ν = 3565 (OH), 3406 (NH),
3
˜
3
3
for C15H1179BrO2 (M+) 301.9941, found 301.9939. C15H11BrO2:
1739 (NCOCF3), 1540 and 1306 cm–1 (NO2). HRMS (EI, m/z)
calcd. for C16H11F3N2O4 (M+) 352.0670, found 352.0696.
calcd. C 59.43, H 3.66; found C 59.37, H 3.48.
7-Methyl-2-phenylbenzofuran (14He):[50] A colorless oil. 13C NMR
4-[3-Methyl-5-(1E)-1-propenyl-2-benzofuranyl]phenol (26) (Eupoma-
(CDCl3, 50 MHz): δ = 173.3, 155.5, 153.9, 130.7, 128.7, 128.4, tenoid 6): To a stirred mixture of the bromobenzofuran 25 (46.2 mg,
125.2, 124.9, 123.0, 121.4, 118.3, 101.6, 15.1 ppm. HRMS (EI, m/z)
0.15 mmol), powdered CsF (93.0 mg, 0.60 mmol), and trans-pro-
penylboronic acid (39 mg, 0.45 mmol) in DME (0.54 mL) was
added Pd(PPh3)4 (0.005 mg, 3 mol-%) at room temperature. The
reaction mixture was heated at reflux for 7 h under argon. The
reaction mixture was then cooled, diluted with AcOEt, and washed
with brine. The organic phase was dried with MgSO4 and concen-
trated at reduced pressure. Purification of the residue by medium-
pressure column chromatography (n-hexane/AcOEt, 5:1) afforded
Eupomatenoid 6 (26) (39.0 mg, 97%) as colorless crystals. M.p.
calcd. for C15H12O (M+) 208.0888, found 208.0894.
(E)-1-(3,5-Dihydroxyphenyl)ethanone O-Phenyloxime (21): Accord-
ing to the procedure given for 7, reaction of O-phenylhydroxyl-
amine 5A (218 mg, 2 mmol) with 3,5-dihydroxyacetophenone
(304.3 mg, 2 mmol) and concd. aqueous HCl (0.10 mL) in EtOH
(4 mL) gave the oxime ether 21 (447.1 mg, 92%) as colorless crys-
1
tals. M.p. 104–106 °C (CH2Cl2). H NMR (CD3OD, 300 MHz): δ
= 7.32 (br. t, J = 8 Hz, 2 H), 7.25 (br. d, J = 8 Hz, 2 H), 7.02 (br.
t, J = 8 Hz, 1 H), 6.77 (d, J = 2 Hz, 2 H), 6.41 (t, J = 2 Hz, 1 H),
3.89 (br. s, 2 H), 2.39 (s, 3 H) ppm. 13C NMR (CD3OD, 50 MHz):
δ = 161.1, 159.7, 159.5, 139.2, 130.4, 123.3, 115.9, 106.3, 105.3,
1
147.5–148 °C (benzene/petroleum ether) (ref.[20] 147.5–149 °C). H
NMR (CDCl3, 500 MHz): δ = 7.68 (br. d, J = 8.5 Hz, 2 H), 7.43
(br. d, J = 2 Hz, 1 H), 7.36 (br. d, J = 8.5 Hz, 1 H), 7.27 (br. dd,
J = 8.5, 2 Hz, 1 H), 6.93 (br. d, J = 8.5 Hz, 2 H), 6.52 (br. dd, J =
15.5, 2 Hz, 1 H), 6.33 (dq, J = 15.5, 6.5 Hz, 1 H), 4.90 (br. s, 1 H),
2.42 (s, 3 H), 1.91 (dd, J = 6.5, 2 Hz, 3 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 155.3, 152.9, 151.1, 132.6, 131.5, 131.3, 128.3, 124.4,
124.2, 122.2, 116.1, 115.6, 110.6, 109.8, 18.5, 9.4 ppm. IR (CHCl3):
13.8 ppm. IR (nujol): ν = 3242 cm–1 (OH). HRMS (EI, m/z) calcd.
˜
for C14H13NO3 (M+) 243.0894, found 243.0897. C14H13NO3·
1/30CH2Cl2: calcd. C 68.49, H 5.35, N 5.69; found C 68.61, H 5.48,
N 5.39.
5-(2-Benzofuranyl)-1,3-benzenediol (22) (Stemofuran A): According
to the procedure given for 14, reaction of the oxime ether 21
(32.7 mg, 0.13 mmol) with DMAP (127.0 mg, 1.04 mmol) and
TFAT (0.35 mL, 2.35 mmol) in CH2Cl2 (4 mL) gave Stemofuran A
(22) (28.7 mg, 95%) as colorless crystals. M.p. 182–183 °C (CHCl3).
1H NMR (CD3OD, 500 MHz): δ = 7.56 (br. dd, J = 8, 1.5 Hz, 1
H), 7.48 (br. dd, J = 8, 1.5 Hz, 1 H), 7.25 (td, J = 8, 1.5 Hz, 1 H),
7.20 (td, J = 8, 1.5 Hz, 1 H), 7.02 (br. d, J = 1 Hz, 1 H), 6.84 (d,
J = 2 Hz, 2 H), 6.30 (t, J = 2, Hz, 1 H) ppm. 13C NMR (CD3OD,
75 MHz): δ = 160.0, 157.4, 156.0, 133.4, 130.5, 125.3, 123.9, 121.9,
ν = 3596 cm–1 (OH). HRMS (EI, m/z) calcd. for C18H16O2 (M+)
˜
264.1149, found 264.1145. The spectroscopic data of 26 were iden-
tical with those previously reported.[6b,20]
2,3-Dihydro-4H-1-benzopyran-4-one O-Phenyloxime (27): Accord-
ing to the procedure given for 7, reaction of O-phenylhydroxyl-
amine (5A) (218 mg, 2 mmol) with 4-chromanone (296.3 mg,
2 mmol) and concd. aqueous HCl (0.10 mL) in EtOH (4 mL) gave
the oxime ether 27 (439.7 mg, 92%) as a colorless oil. 1H NMR
(CDCl3, 300 MHz): δ = 8.06 (dd, J = 8, 1.5 Hz, 1 H), 7.37–7.29
(m, 5 H), 7.09–6.91 (m, 3 H), 4.28 (t, J = 6 Hz, 2 H), 3.15 (t, J =
6 Hz, 2 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 159.4, 157.1,
151.5, 131.7, 129.3, 124.8, 122.3, 121.5, 117.8, 114.7, 64.9,
24.7 ppm. HRMS (EI, m/z) calcd. for C15H13NO2 (M+) 239.0946,
found 239.0942.
111.8, 104.4, 104.1, 102.2 ppm. IR (nujol): ν = 3294 cm–1 (OH).
˜
HRMS (EI, m/z) calcd. for C14H10O3 (M+) 226.0629, found
226.0645. C14H10O3: calcd. C 74.33, H 4.46; found C 74.31, H 4.33.
The spectroscopic data of 22 were identical with those previously
reported.[5]
(E/Z)-1-(4-Hydroxyphenyl)-1-propanone O-(4-Bromophenyl)oxime
6H-Benzofuro[3,2-c][1]benzopyran (28):[2i] According to the pro-
(24): According to the procedure given for 7, reaction of O-(4-bro- cedure given for 14, reaction of the oxime ether 27 (186.7 mg,
Eur. J. Org. Chem. 2007, 1491–1509
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1507

N. Takeda, O. Miyata, T. Naito
FULL PAPER
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0.78 mmol) with DMAP (285.0 mg, 2.34 mmol) and TFAT
(0.58 mL, 3.90 mmol) in CH2Cl2 (12 mL) gave the benzofuran 28
(135.0 mg, 78%) as colorless crystals. M.p. 76–78 °C (EtOH) (ref.[2i]
76.0–76.9 °C). HRMS (EI, m/z) calcd. for C15H10O2 (M+)
221.0681, found 221.0672.
6H-Benzofuro[3,2-c][1]benzopyran-6-one (29) (Coumestan): To the
solution of the benzofuran 28 (53.3 mg, 0.24 mmol) and silica gel
(53.0 mg) in CH2Cl2 (17 mL) was added 1 equiv. of PCC (53.0 mg,
0.24 mmol) and the mixture was heated at reflux. After a few hours,
two other portions of PCC (2 equiv.) were added to the mixture.
After 4 h, the cooled mixture was filtered through celite, then the
filtrate was concentrated at reduced pressure. Purification of the
residue by medium-pressure column chromatography (n-hexane/
AcOEt, 10:1) afforded Coumestan 29 (42.9 mg, 76%) as colorless
crystals. M.p. 186.5–187.5 °C (cyclohexane) (ref.[7a] 187–188 °C).
1H NMR (CDCl3, 500 MHz): δ = 8.16 (dd, J = 7.5, 1.5 Hz, 1 H),
8.05 (dd, J = 7.5, 1.5 Hz, 1 H), 7.68 (dd, J = 7.5, 1.5 Hz, 1 H), 7.62
(td, J = 7.5, 1.5 Hz, 1 H), 7.52 (dd, J = 7.5, 1.5 Hz, 1 H), 7.49 (td,
J = 7.5, 1.5 Hz, 1 H), 7.47 (td, J = 7.5, 1.5 Hz, 1 H), 7.43 (td, J =
7.5, 1.5 Hz, 1 H) ppm. 13C NMR (CDCl3, 125 MHz): δ = 132.0,
130.1, 127.6, 125.7, 98.8, 97.2, 96.7, 95.5, 93.90, 93.88, 89.5, 84.7,
[3]
83.8, 77.9 ppm. IR (CHCl ): ν = 1735 cm–1 (CO2). HRMS (EI, m/z)
˜
3
calcd. for C15H8O3 (M+) 236.0473, found 236.0466. The spectro-
scopic data of 29 were identical with those previously reported.[7a]
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We are grateful for Grant-in-Aid for Scientific Research on Priority
Areas from the Ministry of Education Culture, Sports, Science and
Technology (to T. N.) and for Scientific Research from the Japan
Society for the Promotion of Science (to O. M.). We also acknow-
ledge a research grant from the Science Research Promotion Fund
of the Japan Private School Promotion Foundation.
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Received: November 18, 2006
Published Online: January 25, 2007
Eur. J. Org. Chem. 2007, 1491–1509
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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