Direct syntheses of benzofuran-2(3H)-ones and benzofuran-3(2H)-ones from 1-(2-hydroxyphenyl)alkan-1-ones by CuBr2 or CuCl2

Article abstract of DOI:10.1246/cl.2007.332

New syntheses of benzofuran-2(3H)-ones and benzofuran-3(2H)-ones from 1-(2-hydroxyphenyl)alkan-1-ones via oxidative cyclization by CuBr₂ or CuCl₂ are described. A new synthesis of 1H-isochromene-1,4(3H)- diones via similar procedures is also described. Copyright

Full text of DOI:10.1246/cl.2007.332

332
Chemistry Letters Vol.36, No.2 (2007)
Direct Syntheses of Benzofuran-2(3H)-ones and Benzofuran-3(2H)-ones
from 1-(2-Hydroxyphenyl)alkan-1-ones by CuBr2 or CuCl2
Hideyoshi Miyake,ꢀ1 Akinori Nishimura,2 Misato Yago,2 and Mitsuru Sasaki2
1Faculty of Agriculture, Kobe University, Rokkodai, Nada-ku, Kobe 657-8501
2Graduate School of Science and Technology, Kobe University, Rokkodai, Nada-ku, Kobe 657-8501
(Received November 28, 2006; CL-061403; E-mail: miyakeh@kobe-u.ac.jp)
New syntheses of benzofuran-2(3H)-ones and benzofuran-
Table 1. Oxidative reactions of aromatic ꢀ-haloketones
3(2H)-ones from 1-(2-hydroxyphenyl)alkan-1-ones via oxida-
tive cyclization by CuBr2 or CuCl2 are described. A new synthe-
sis of 1H-isochromene-1,4(3H)-diones via similar procedures is
also described.
CuX2 (equiv.)
Products
Solvent
Substrate (1)
Isolated yield/%
Conditions
OH
O
O
CuBr2 (2)
EG
150 °C, 10 min.
O
Me
Me
Me
2a 56%
1a
1a
1b
O
OH
O
CuCl2 (3)
EG
150 °C, 60 min.
Oxidative reactions using CuBr2 are useful in organic syn-
thesis.1 The reaction with aromatic ketone in CHCl3–AcOEt is
an especially useful method for chemoselective ꢀ-bromination.2
In this paper, we report new types of reactions of aromatic
ketones with CuBr2 or CuCl2.
When 1-(2-hydroxyphenyl)alkan-1-ones (1) were treated
with CuBr2 or CuCl2 in ethylene glycol (EG) or di(ethylenegly-
col) dimethyl ether (2-methoxyethyl ether: MEE) at 150 ꢁC,
oxidative cyclization occurred to give benzofuran-2(3H)-ones
(2), benzofuran-3(2H)-ones (3), and ꢀ-methyleneketone (4)3
(Scheme 1). The ratio of 2, 3, and 4 depends on the structure
of 1 and the reaction conditions. Results are summarized in
Table 1.
When both R1 and R2 are alkyl groups, 2 was obtained as a
major product, and in most cases a small amount of 3 was also
obtained. The reaction, which produced 2, proceeded with a
migration of the aryl group (1,2-aryl shift). On the other hand,
when the R2 is phenyl group, 1,2-aryl shift did not occur to yield
3 and a small amount of 4. Similar examples of the 1,2-aryl shift
of acetophenone derivatives have already been reported. For
example, ZnBr2,4 Ag2CO3,5a and AgBF45b promote the 1,2-aryl
shift of aromatic ꢀ-bromoketones. Thallium(III) nitrate6 and
lead(IV) acetate7 promote the oxidative 1,2-aryl shift of aceto-
phenone. Because of the similarity to our results, the photoalco-
holysis of aromatic ꢀ-haloketones by Tomioka et al.8 is quite in-
teresting. When aromatic ꢀ-haloketones were irradiated with
300-W high-pressure Hg lamp, three different types of reactions
occured: (1) 1,2-aryl shift, (2) cyclization without 1,2-aryl shift,
and (3) elimination to give ꢀ-methyleneketone;8 all also occur-
red in our experiments. This suggests that the photoalcoholysis
of aromatic ꢀ-haloketones and our CuX2-mediated reaction
O
Me
Me
O
O
3a 3%
3b 6%
2a 80%
OH
O
O
CuCl2 (3)
EG
150 °C, 60 min.
O
O
O
2b 75%
O
OH
O
O
CuCl2 (3)
EG
O
Et
Et
i-Pr
Cl
Et
2c 72%
150 °C, 60 min.
O
1c
3c 6%
OH
O
CuCl2 (3)
EG
150 °C, 60 min.
O
i-Pr
1d
1e
O
OH
2d 59%
O
O
O
O
CuCl2 (3)
EG
150 °C, 60 min.
O
O
O
Cl
Br
Cl
2e 35%
O
O
3e 9%
3f 11%
OH
O
CuCl2 (3)
EG
180 °C, 30 min.
Br
Br
O
1f
O
2f 63%
2g 59%
OH
O
CuCl2 (3)
EG
150 °C, 60 min.
Et
Et
Et
O
1g
O
3g 9%
OH
OH
O
O
CuBr2 (2)
MEE
150 °C, 10 min.
Ph
Ph
Ph
Ph
1h
1i
O
O
3h 42%
3i 54%
4h 18%
4i 30%
OH
OH
O
CuBr2 (2)
MEE
150 °C, 10 min.
Ph
Ph
Me
Et
Me
Me
Et
Ph
Ph
O
O
O
OH
OH
O
CuBr2 (2)
MEE
150 °C, 10 min.
Et
Ph
O
O
O
3j 50%
1j
4j 10%
OH
R1
proceed in somehow similar mechanisms. Tomioka suggested
that an intermediate of the photoalcoholysis was a keto cation,
which is generated via an electron transfer between keto radical
ꢂ
and Br . The mechanism of CuX2-mediated reaction can also be
explained in this context. The tentative mechanism is as follows
(Scheme 2).
CuBr2 or CuCl2
R
R2
150 °C
O
1
OH
O
O
O
R1
R2
O
+
+
R
R
R2
R
R2 R1
O
ꢂ
Initially, halogen radical X generated from CuX2 (or X2
4
2
3
( R1 = Me )
R1= alkyl
R2= alkyl or aryl
generated from CuX2) abstract the a-hydrogen of 1 to give radi-
cal 8. Single electron transfer from 8 to CuX2 gives keto cation
9, CuX, and Xꢃ. An oxidation of enol 10 is also plausible route to
Scheme 1.
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.2 (2007)
333
O
OH
O
X
OH
O
O
O
OH
O
H
R2
O
•
CuCl2 (3 equiv.)
O
R2
+
R2
O
EG, 150 °C, 60 min.
2
1
8
12
13 20%
14 14%
electron transfer
OH
O
CuX2
O
O
CuBr2 (4 equiv.)
OH
OH
OH
OH
Ph
oxidation
R2
R1 = alkyl
Me
Me
Ph
EG, 150 °C,10 min
+
O
R2
15
16 63%
HO
+
R2
O
+ CuX
+ X-
9
1'
10
O
Scheme 4.
R
2 = phenyl
O
O
OH
O
O
COOH
R2
CuCl2
O
O
R2
R2
R1
R2
R1
HO
OH
O
4
3
150 °C, 1 h
17a R1 =R2 = Me
17b R1 = Me, R2 = Et 18b 71%
O
18a 70%
Scheme 2.
17c R1, R2 = -(CH2)5-
18c 48%
OH
O
O
CuBr2
Scheme 5.
EG,150 °C, 10 min.
Ph
Ph
O
4h
35%
11
poured into water (20 mL), and extracted with ethyl acetate.
After usual work-up, it was purified by column chromatography
on silica gel to give 2a (0.28 g, 1.6 mmol) in 80% yield and 3a
(0.010 g, 0.056 mmol) in 3% yield.
Scheme 3.
9. When both R1 and R2 are alkyl groups, the keto cation 9 is not
stable and isomerise to the more stable acyl cation 10 presuma-
bly through an arenium ion intermediate. The following intramo-
lecular nucleophilic attack of hydroxy group gives 2. When R2 is
phenyl group, the cation 9 is stabilized by the phenyl group, and
the 1,2-aryl shift lose a driving force, and the following reactions
proceed without migration of the aryl group. The intramolecular
nucleophilic attack of an oxygen atom of the hydroxy group pro-
duces 3, and E1-type elimination produces 4.
Note that the ꢀ-methylene ketone 4 is not an intermediate in
this reaction. When 4h was treated with CuBr2, isoflavone (11)
was obtained as a main product, but not 3h (Scheme 3).
Naphthalene derivative 12 also reacted with CuCl2 under
similar conditions to give 13 and 14 (Scheme 4). However,
probably due to the difficulty of the migration of the naphthyl
group, the yield of lactone 13 is lower than the examples of
acetophenone derivatives 1a–1g. When R0 is a hydrogen, the re-
action with 2 equiv. of CuBr2 usually gave a mixture of uniden-
tified products, probably because of further oxidative reactions.
However, benzylketone 15 was gave acetal 16 in 63% yield by
the reaction with 4 equiv. of CuBr2 in EG (Scheme 4).
Similarly, 2-carboxy acetophenones 17 reacted with CuCl2
under similar conditions to yield 1H-isochromene-1,4(3H)-
diones 18 (Scheme 5). In these cases, 1,2-aryl shift was not ob-
served. The cationic migration of the aryl group was suppressed,
probably reflecting the electron-withdrawing effect of the
carboxy group.
References and Notes
1
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4
5
In conclusion, oxidative cyclization of 1-(2-hydroxy-
phenyl)alkan-1-ones with CuBr2 or CuCl2 is useful for the
synthesis of benzofuran-2(3H)-ones and benzofuran-3(2H)-
ones. Generally speaking, CuCl2 is less reactive than CuBr2
for the reactions described above. And CuCl2 usually gave better
results.
As typical procedures, the synthesis of 2a and 3a by the re-
action of 1a with CuCl2 is described as follows. An ethylenegly-
col (5 mL) solution of 1a (0.36 g, 2.0 mmol) and CuCl2 (0.80 g,
6.0 mmol) was stirred at 150 ꢁC for 60 min. The mixture was
6
7
8
B. Myrboh, H. Ila, H. Junjappa, Synthesis 1981, 126.
Y. Izawa, Y. Watoh, H. Tomioka, Chem. Lett. 1984, 33.
Published on the web (Advance View) January 27, 2007; doi:10.1246/cl.2007.332