TBHP/TBAI-promoted oxidative cyclization of o -acylphenols for the construction of 2-aryloxybenzofuran-3(2 H)-ones

Article abstract of DOI:10.1055/s-0033-1340672

An efficient metal-free approach to 2-aryloxybenzofuranonefuran-3(2H)-ones has been developed. Using tert-butyl hydroperoxide as oxidant and tetrabutylammonium iodide as catalyst, 2-acylphenols reacted with phenols to provide 2-aminobenzofuran-3(2H)-one d

Full text of DOI:10.1055/s-0033-1340672

LETTER
▌843
letter
TBHP/TBAI-Promoted Oxidative Cyclization of o-Acylphenols for the
Construction of 2-Aryloxybenzofuran-3(2H)-ones
2-Aryloxybenzofuran-3(2H)-ones
Hui Yu,* Fengling Zhang, Weihua Huang
Department of Chemistry, Tongji University, 1239 Siping Road, Shanghai 200092, P. R. of China
Fax +86(21)65981097; E-mail: yuhui@tongji.edu.cn
Received: 26.11.2013; Accepted after revision: 05.01.2014
system. Herein, to extend the application of this protocol,
we wish to report a TBHP/TBAI-promoted oxidative cy-
clization of o-acylphenols for the construction of 2-aryl-
oxybenzofuranonefuran-3(2H)-ones.
Abstract: An efficient metal-free approach to 2-aryloxybenzofura-
nonefuran-3(2H)-ones has been developed. Using tert-butyl hydro-
peroxide as oxidant and tetrabutylammonium iodide as catalyst,
2-acylphenols reacted with phenols to provide 2-aminobenzofuran-
3(2H)-one derivatives in moderate to good yields.
Initially, the reaction of 2-acetylphenol (1a) with 2.0
equivalents 4-nitrophenol (2a) was examined in MeCN
with TBAI (30 mol%) as the catalyst, and aqueous TBHP
(3.0 equiv) as the oxidant at room temperature. After 24
Key words: tert-butyl hydroperoxide, TBHP, tetrabutylammonium
iodide, TBAI, benzofuran-3(2H)-one, 2-acylphenol, oxidative cy-
clization
Table 1 Optimization of the Reaction Conditionsa
Benzofuran-3(2H)-ones (coumarones) play an important
role in medicinal and pharmaceutical chemistry due to
their broad pharmacological activities including in vitro
antibacterial, anticancer, antifeedant, and antiparasitic ac-
tivities.1 They are also important intermediates for the
synthesis of other bioactive compounds such as heliquino-
mycin analogues,2a a BKCa channel opener,2b and a 5-
HT1A receptor.2c Several traditional synthetic routes to the
construction of benzofuran-3(2H)-one framework have
been exploited, but most of these methods suffered from
multisteps or harsh conditions.3 Thus, development of
convenient methods for the preparation of benzofuran-
3(2H)-ones is still desirable. Oxidative cyclization of o-
acylphenols was found to be a simple pathway for the syn-
thesis of benzofuran-3(2H)-one derivatives.4 However,
excess PhI(OAc)2 was used as oxidant for such a transfor-
mation and two equivalents of PhI were generated as a
main byproduct, which caused this method less atom eco-
nomical. Therefore, to find an alternative oxidant system
for this oxidative cyclization process is quite necessary. In
recent years, due to its high efficiency and environmental
friendly properties, the tert-butyl hydroperoxide and tetra-
butylammonium iodide (TBHP/TBAI) system has
emerged as an attractive metal-free catalytic system and
has been used successfully for the formation of carbon–
carbon and carbon–heteroatom bonds.5 In most cases,
these reactions were carried out under mild conditions and
only small molecules such as H2O and t-BuOH were re-
leased as the main byproducts. With this novel method,
varied synthetically or pharmaceutically useful com-
pounds have been prepared in good yields. For example,
Wan and his coworkers reported an efficient synthesis of
imides,5a α-acyloxy ethers,5e allylic esters,5f N-nitros-
amines,5i and α-amino acid esters5j using the TBHP/TBAI
NO2
NO2
O
O
catalyst, oxidant
MeCN, r.t., 16 h
O
+
O
OH
O
NO2
OH
1a
2a
3a
Entry
Catalyst
Oxidant
Solvent
Yield
(%)
(30 mol%)
(4.0 equiv)
1
2
TBAI
NH4I
KI
aq TBHP
aq TBHP
aq TBHP
aq TBHP
aq TBHP
aq TBHP
aq TBHP
aq TBHP
aq TBHP
H2O2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
EtOAc
toluene
H2O
75 (59)b
55
3
65
4
NIS
27
5
I2
38
6
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
–
58c, 66d
64
7
8
36
9
30
10
11
12
13
14
MeCN
MeCN
MeCN
MeCN
MeCN
28
DTBPe
21
CHPf
10
–
<10
<10
aq TBHP
a The reactions were performed in a Schlenk tube with 1a (0.5 mmol),
2a (1.25 mmol), catalyst (30 mol%), and oxidant (4.0 equiv) in sol-
vent (2 mL) for 16 h.
b The reaction temperature was 40 °C
c Conditions: 15 mol% TBAI were used.
d Conditions: 50 mol% TBAI were used.
e DTBP = di-tert-butyl peroxide.
SYNLETT 2014, 25, 0843–0846
Advanced online publication: 10.02.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1340672; Art ID: ST-2013-W1091-L
© Georg Thieme Verlag Stuttgart · New York
f CHP = cumene hydroperoxide.

844
H. Yu et al.
LETTER
hours, a product identified as 2,2-bis(4-nitrophenoxy)- With the optimized reaction conditions established, the
benzofuran-3(2H)-one (3a) was isolated in 55% yield. substrate scope was examined, and the results are summa-
The yield of 3a could be improved to 75% when the rized in Table 2.8 Generally, electron-defect phenols, in-
amount of 2a and TBHP was increased to 2.5 equivalents cluding multisubstituted phenols, underwent smooth
and 4.0 equivalents, respectively. When the reaction was reaction with 2-acetylphenol (1a) to provide the corre-
carried out at higher temperature (40 °C), only 59% yield sponding products in good yields (Table 2, entries 1–7).
of the product was obtained (Table 1, entry 1). Changing Remarkable steric effect was observed in this reaction.
the iodine source to NH4I or KI under the same conditions When 2-ClC6H4OH was used instead of 4-ClC6H4OH to
gave moderate yield of 3a (Table 1, entries 2 and 3). In react with 1a, no corresponding product could be isolated
7
contrast, use of NIS6 or I2 in the reaction decreased the (Table 2, entry 3). Phenol and electron-rich phenols were
yields of 3a dramatically (Table 1, entries 4 and 5). So not suitable substrates to the reaction because of their in-
TBAI was selected as the catalyst, and different amounts stability under oxidative conditions (Table 2, entry 8).
were examined but the yield of 3a decreased (Table 1, en- Different 2-acetylphenols with electron-donating or elec-
try 6). Changing the solvent to EtOAc, toluene, or water tron-withdrawing groups on the benzene ring reacted with
resulted in the formation of 3a in lower yield (Table 1, en- 4-nitrophenol (2a) to give the corresponding benzofuran-
tries 7–9). Other commercial oxidants such as H2O2, DT- 3(2H)-ones in moderate to good yields (Table 2, entries 9–
BP, and CHP were also tested and only 10–24% yields of 14). Heterocyclic substrate such as 1-acetyl-2-hy-
3a were obtained (Table 1, entries 10–12). In the absence droxynaphthalene reacted with 4-nitrophenol (2a) to form
of TBAI or TBHP, no separable amount of product was the corresponding product in 60% yield (Table 2,
obtained (Table 1, entries 13 and 14).
entry15). Finally, EtOH and AcOH were also used to react
with 1a under the optimized conditions, and no significant
products could be found.
Table 2 One-Pot Synthesis of 2-Aryloxybenzofuran-3(2H)-ones
O
O
TBAI (30 mol%)
aq TBHP (4.0 equiv)
OAr
OAr
R1
R1
HOAr
+
MeCN, r.t., 16 h
O
OH
1
2
3a–o
Entry
Substrate 1
Substrate 2
Product 3
Yield (%)a
1
2
3
1a
1a
1a
4-O2NC6H4OH
3a
75
65
4-FC6H4OH
3b
4-ClC6H4OH/2-ClC6H4OH
3c/3c′
59
0
4
5
6
7
8
1a
1a
1a
1a
1a
4-NCC6H4OH
3d
61
50
68
60
4-F3CC6H4OH
3e
3,4-Cl2C6H4OH
3f
3-Me-4-O2NC6H4OH
PhOH/4-MeC6H4OH
3g
3h/3h′
0
0
O
9
4-O2NC6H4OH
4-O2NC6H4OH
3i
3j
62
60
OH
1b
O
EtO
10
OH
1c
Synlett 2014, 25, 843–846
© Georg Thieme Verlag Stuttgart · New York

LETTER
2-Aryloxybenzofuran-3(2H)-ones
845
Table 2 One-Pot Synthesis of 2-Aryloxybenzofuran-3(2H)-ones (continued)
O
O
TBAI (30 mol%)
aq TBHP (4.0 equiv)
OAr
OAr
R1
R1
HOAr
+
MeCN, r.t., 16 h
O
OH
1
2
3a–o
Entry
Substrate 1
Substrate 2
Product 3
Yield (%)a
O
F
11
12
13
14
4-O2NC6H4OH
3k
69
77
70
69
OH
1d
O
4-O2NC6H4OH
4-O2NC6H4OH
4-O2NC6H4OH
3l
F
OH
O
1e
Br
3m
3n
OH
1f
O
I
OH
O
1g
1h
15
4-O2NC6H4OH
3o
60
OH
a Isolated yield.
Subsequently, reactivity of 2-propionylphenol (1i) with 4- low (Scheme 2). The reaction of 2-acetylanisole (5) with
nitrophenol (2a) under the optimized conditions was also 2.0 equivalents 4-nitrophenol (2a) was examined under
examined, and 2-methyl-2-(4-nitrophenoxy)benzofuran- the optimized reaction conditions and no reaction oc-
3(2H)-one (4a) was obtained as the major product in ex- curred (Scheme 2, eq. 1), which indicated that intermolec-
cellent yield up to 90%. When 2-butyrylphenol (1j) was ular C–O bond formation might not be the first step of the
employed to the reaction, the corresponding product 4b reaction procedure, and the reaction perhaps started from
was obtained in 72% yield (Scheme 1).
an intramolecular cyclization reaction. Then benzofuran-
3-(2H)-one (6) was used to react with 2a under the same
O
O
TBAI (30 mol%)
aq TBHP (4.0 equiv)
X
R
+
X
R
O
HOAr
TBAI (30 mol%)
aq TBHP (4.0 equiv)
OAr
MeCN, r.t., 16 h
O
OH
Me
OMe
+
2a
2a
(1)
(2)
no reaction
1
2a
4 Ar = 4-O2NC6H4
MeCN, r.t., 16 h
1i X = H, R = Me
1j X = F, R = Et
4a X = H, R = Me, 90%
4b X = F, R = Et, 72%
5
O
TBAI (30 mol%)
aq TBHP (4.0 equiv)
Scheme 1 Reaction of 2-propionylphenol (1i) and 2-butyrylphenol
(1j) with 4-nitrophenol (2a)
+
3a
MeCN, r.t., 16 h
62%
O
6
To gain insights into the reaction mechanism, control ex-
periments were carried, out and the results are listed be-
Scheme 2 Control experiments
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 843–846

846
H. Yu et al.
LETTER
O
O
O
O
TBHP
TBAI
R
R
I
R
R
ArOH
cyclization
OAr
OAr
2 C–O bond
formations
O
OH
O
OH
1
7
8
3
Scheme 3 Proposed pathway
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conditions, 3a could be isolated in 62% yield (Scheme 2,
eq. 2).
These results suggested that benzofuran-3-(2H)-one (8)
might be the crucial intermediate of the reaction, which
was generated from 1 via sequence iodonation–cycliza-
tion reaction. Then 8 was converted into the final product
3 through two iodonation–C–O bond formation processes
(Scheme 3). More details of the mechanism still need fur-
ther investigation.
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In summary, we have developed a one-pot method for the
synthesis of 2-aryloxybenzofuran-3(2H)-ones from o-ac-
ylphenols and phenols under TBHP/TBAI-catalyzed con-
ditions. The procedure was easy to handle and various 2-
aryloxybenzofuran-3(2H)-ones have been synthesized by
such a strategy. Investigation for the details of the reaction
mechanism is still in progress in our lab.
Acknowledgment
Financial support from Tongji University (20123231) is gratefully
acknowledged.
(6) (a) Lamani, M.; Prabhu, K. R. Chem. Eur. J. 2012, 18,
14638. (b) Yan, Y.; Zhang, Y.; Zha, Z.; Wang, Z. Org. Lett.
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Supporting Information for this article is available online at
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(8) Typical Experimental Procedure for the Synthesis of
2,2-Bis(4-nitrophenoxy)benzofuran-3(2H)-one (3a)
In a 15 mL reaction tube a mixture of 2-acetylphenol (1a, 68
mg, 0.5 mmol), 4-nitrophenol (2a, 174 mg, 1.25 mmol), t-
BuOOH (70% in H2O, 2 mmol), TBAI (55 mg, 0.15 mol) in
MeCN (2.0 mL) was stirred at r.t. under air for 16 h, until
complete consumption of starting material as monitored by
TLC. After the reaction was finished, the mixture was
quenched with sat. Na2S2O3 solution, then extracted with
EtOAc, dried over anhydrous Na2SO4, and evaporated in
vacuum. The residue was purified by flash column
chromatography on silica gel (PE–EtOAc, 8:1) to give the
product 3a.
http://www.thieme-connect.com/ejournals/toc/synlett. Included are
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synthesis and characterization data and copies of the H and 13C
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References and Notes
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