Pd/C-catalyzed cyclization/isomerization: A new route to 2-aroyl-3-vinyl benzo[b]furans via carbon-carbon bond formation

Article abstract of DOI:10.1016/j.catcom.2009.10.028

{A figure is presented}A variety of 2-aroyl(acyl, or carboxyl)-3-vinyl benzo[b]furans have been prepared via C-C bond formation in good to excellent yields by Pd/C-catalyzed cyclization/isomerization of propargylic compounds. The reaction proceeded with easily accessible starting materials and inexpensive catalyst under mild conditions. Furthermore, a number of benzo[b]furan derivatives including an allene functional group have been prepared too.

Full text of DOI:10.1016/j.catcom.2009.10.028

Catalysis Communications 11 (2010) 346–350
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Pd/C-catalyzed cyclization/isomerization: A new route to 2-aroyl-3-vinyl
benzo[b]furans via carbon–carbon bond formation
Jie Hu a, Xiang-Chuan Wang a, Li-Na Guo a, Yuan-Yuan Hu a, Xue-Yuan Liu a, Yong-Min Liang a,b,
*
a State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
b State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 August 2009
Received in revised form 25 October 2009
Accepted 27 October 2009
Available online 30 October 2009
O
O
O
O
Pd (0), K2CO3
Solvent, 60 oC
Ph
Ph
OCO2Et
Keywords:
Pd/C
3a
1a
Benzo[b]furan
Allene
Cyclization
C–C bond formation
A variety of 2-aroyl(acyl, or carboxyl)-3-vinyl benzo[b]furans have been prepared via C–C bond formation
in good to excellent yields by Pd/C-catalyzed cyclization/isomerization of propargylic compounds. The
reaction proceeded with easily accessible starting materials and inexpensive catalyst under mild condi-
tions. Furthermore, a number of benzo[b]furan derivatives including an allene functional group have been
prepared too.
Ó 2009 Elsevier B.V. All rights reserved.
1. Introduction
vantages: (1) require harsh conditions and (2) cost the catalytic
system. In this paper, we describe our efforts toward the synthesis
Benzo[b]furan, are widely presented in many naturally occur-
ring and biologically active compounds, which display various
pharmacological activities [1–6]. Consequently, great efforts have
been devoted to the development of general methods for the
assembly of substituted benzo[b]furans on the basis of C–O
cyclization [7–22]. However, there have been few reports on ben-
zo[b]furans syntheses from alkynylbenzene derivations via
carbon–carbon bond (C–C) cyclization [23–26]. In particular there
have been only a few limited studies on the synthesis of 3-vinyl
benzo[b]furan [27]. The terminal olefins not only can further be
converted to methyl ketones with Pd(II) catalysts, which was
usually referred to as the Wacker reaction [28,29]; but also can
of such 2-aroyl(acyl, or carboxyl)-3-vinyl benzo[b]furans by a
phosphine-free Pd/C catalysis system in good to excellent yields
(Scheme 1).
Recently, we described a convenient approach to the synthesis
of 2,3-dihydro-benzo[b]furan derivatives via Pd-catalyzed carbo-
annulation of propargylic carbonates with nucleophiles [32], as
well as the synthesis of indene derivatives including an allene
functional group via a palladium catalyzed transformation [33].
So we envisaged that 1a might enable the formation of benzo[b]-
furan derivatives 2a including an allene functional group via a pal-
ladium catalyzed transformation (Scheme 2).
directly be converted into the corresponding
by potassium permanganate oxidation [30]. And the synthesis of
-hydroxy carbonyl compounds is a topic of interest because of
a-hydroxy ketones
2. Results and discussion
a
their use in organic synthesis and their widespread occurrence in
numerous important natural products [31]. Besides, many
methods for selectively constructing benzo[b]furans through the
transition metal-catalyzed transformations exhibits some disad-
Treatment of propargylic carbonate 1a with 5 mol% of Pd(PPh3)4
and 2.0 equiv. of K2CO3 in DMF at 60 °C for 1 h affords the single
product 3-vinyl-benzo[b]furan 3a with 86% yield. This result indi-
cated that the isomerization product 3a was more stable than 2a
which can be explained by the higher delocalization of the double
bonds after formation of the aromatic ring and encouraged us to
further investigate this reaction. Various solvents and catalysts
have been tested on substrate 1a. For solvents, as shown in Table
* Corresponding author. Address: State Key Laboratory of Applied Organic
Chemistry, Lanzhou University, Lanzhou 730000, PR China. Tel.: +86 931
8912593; fax: +86 931 8912582.
E-mail address: liangym@lzu.edu.cn (Y.-M. Liang).
1566-7367/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2009.10.028

J. Hu et al. / Catalysis Communications 11 (2010) 346–350
347
Table 1
O
Optimization of the Pd-catalyzed cyclization of propargylic carbonate 1a.a
O
O
R
O
Pd/C
R
O
O
O
O
Pd (0), K2CO3
Solvent, 60 oC
Ph
Ph
OCO2Et
OCO2Et
3a
1a
Scheme 1.
Entry
Catalyst
Pd mol (%)
Solvent
Time (h)
Yield (%)b
O
1
2
3
4
5
6
7
8
9
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd2(dba)3ꢀCHCl3
Pd2(dba)3
Pd/C
Pd/C
Pd/C
Pd/C
None
5
5
5
5
5
5
5
2
DMF
CH3CN
DMSO
THF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
1
1
1
8
1
1
1
1
3
8
10
86
70
O
74
Ph
n.r.c
79
56
O
86d
86d
60d
n.r.c,d,e
n.r.c,d
2a
O
Ph
0.5
2
10
11
a
Reactions were carried out on a 0.2 mmol scale in 2.0 mL of solvent at 60 °C for
the specified period of time with 1.0 equiv. of 1a, 2.0 equiv. of K2CO3, and [Pd].
OCO2Et
b
1a
Isolated yields.
n.r. = No reaction.
The reactions were run under air.
c
O
d
O
e
The reaction was run without K2CO3.
Ph
7). Finally, the amount of Pd/C was examined (entries 8 and 9).
We found that 10% of Pd/C (0.02 equiv.) also afforded product in
an excellent yield. It should be pointed out that no reaction occurs
without the base or Pd catalyst (entries 10 and 11). Thus, the opti-
mal procedure described in entry 8 has been employed to study the
scope of this reaction.
Under the optimized reaction conditions above, the scope of
this methodology was investigated, and the results are summa-
rized in Table 2. Initially we focused our attention on the reaction
of primary propargylic carbonate. First, when R3 = aryl, the influ-
ence of the substituents R1 and R2 on the aromatic moiety was
3a
Scheme 2.
1, DMF was found to be the best, while THF gave no reaction at all
(entries 1–4). The catalytic activity of palladium catalysts was also
examined. Pd2(dba)3ꢀCHCl3 gave a little lower yield and Pd2(dba)3
was less effective (Table 1, entries 5 and 6). To our delight, using
Pd/C as catalyst in the absence of phosphine ligand, the yield was
comparable to the corresponding reaction using Pd(PPh3)4 (entry
Table 2
Synthesis of 3-vinyl benzo[b]furans.a
R2
O
R2
R3
O
O
R3
2 mol % Pd/C, K2CO3
DMF, 60 oC
R1
R1
O
OCO2R4
3
1
Entry
R1
R2
R3
R4
Et
CH3
Et
CH3
CH3
Et
CH3
Et
Et
Et
Et
Et
1
Time (h)
3
Yieldc
1
2
3
4
5
6
7
8
9
10
11
12
13
H
H
H
CH3
H
H
H
H
H
H
H
H
CH3
H
Ph
Ph
Ph
Ph
Ph
1a
1b
1c
1d
1e
1f
1g
1h
1i
1
1
1
1
2
1
1
6
8
3
3
3
3
3a
3b
3c
3d
3e
3f
3g
3h
3i
86
89
95
90
90
96
93
76
CH3
CH3
Cl
t-Bu
H
p-BrC6H4
2,4-Dimethylphenyl
Cl
H
CH3
CH3
OEt
OEt
OEt
OEt
t-Bu
H
CH3
CH3
Cl
70
1j
1k
1l
3j
3k
3l
82b
95b
89b
80b
Et
1m
3m
a
b
c
Reactions were carried out on a 0.2 mmol scale in 2.0 mL of DMF at 60 °C using l.0 equiv. of 1, 2.0 equiv. of base, and 0.02 equiv. of Pd/C.
Using Cs2CO3 instead of K2CO3 as base.
Isolated yields.

348
J. Hu et al. / Catalysis Communications 11 (2010) 346–350
studied (Table 2, entries 1–7). To our delight, no matter the substi-
tuent is an electron-withdrawing group or an electron-donating
group in the para positions, the corresponding substituted ben-
zo[b]furans 3 were obtained in excellent yields (entries 2, 4 and
5). And also we got desired product in a very good yield using
disubstituted groups (entry 3). When 1f and 1g were employed
in the reaction, the desired products were isolated in 96% and
93% yields, respectively (entries 6 and 7). Furthermore, with sub-
stitution of phenyl by methyl or ethoxyl at the carbonyl position,
the reaction continued to proceed smoothly to the corresponding
cyclization/isomerization products in good to excellent yields (Ta-
ble 2, entries 8–13). To the best of our knowledge, there is no re-
port about the synthesis of 2-aroyl(acyl, or carboxyl)-3-vinyl
benzo[b]furans and these derivatives probably have antimicrobial
activity [34].
the synthesis of allenyl benzo[b]furan derivatives. So we prepared
6a and as we expected, the desired 3-allenyl benzo[b]furan deriv-
atives 7a was obtained in a good yield in the presence of Pd2(dba)3,
NaOAc in DMSO at 60 °C. We then examined the scope of the reac-
tion with the optimal condition (Table 4, entries 1–5).
From Table 4, we can see that primary propargylic 6a and 6b
gave the good yields while the secondary carbonates afforded the
mixture products. Tertiary acetate 6e can also give the desired
product in 62% with a longer time.
3. Reaction mechanism
A plausible mechanism is proposed in Scheme 3. It consists of
the following key steps: (a) palladium(0) attack at propargylic car-
bonate through SN20 substitution to form an allenylpalladium com-
plex [35] and (b) regioselective intarmolecular nucleophilic attack
of the carbanion forms the allenyl product 2a. When the R = H, the
vinyl product 3a was obtained after isomerization; when the
R = CH3, the product was 7a.
For secondary propargylic carbonate 4a, a good yield was given
in the Pd/C catalysts system, but a mixture product (E/Z = 50:50)
was obtained (Table 3, entry 1). For tertiary propargylic esters 4b
and 4c, the desired products were also afforded in the presence
of Pd2(dba)3 in moderate yields, while Pd/C showed poor results
(entries 2 and 3).
In light of the product 3a from the substrate 1a, we believe that
4. Conclusion
introducing a substituent in the a-position of carbonyl compounds
can inhibit the isomerization and allenyl benzo[b]furan derivatives
In conclusion, we have developed an efficient and versatile
can also be obtained. As far as we know, there is no report about
route to 2-aroyl-3-vinyl benzo[b]furans and 2-aroyl-3-allenyl ben-
Table 3
Synthesis of 3-vinyl benzo[b]furans.a
O
R3
O
O
R3
R2
Pd(0), K2CO3
DMF, 60 oC
R4
R4
O
R1
R1
R2
OR
4
5
Entry
R1
R2
R3
R4
R
4
5
Yield (%)
1
2
3
H
CH3
p-CH3C6H5
Ph
Ph
OEt
Cl
Cl
H
CO2Et
CO2Et
Ac
4a
4b
4c
5a
5b
5c
80b
60c
64d
CH3
R1–R2 = (CH2)4
a
b
c
Reactions were carried out on a 0.2 mmol scale in 2.0 mL of DMF at 60 °C using l.0 equiv. of 4, 2.0 equiv. of base, and 0.02 equiv. of [Pd]; all reactions were run for 2–3 h.
The product was isolated as a 50:50 E/Z mixture.
Using Pd2(dba)3 (5 mol%) as catalyst.
d
Using Cs2CO3 and Pd2(dba)3 (5 mol%) instead of K2CO3 and Pd/C.
Table 4
Synthesis of 2-aroyl-3-allenyl benzo[b]furans derivatives.a
O
O
O
O
Pd2(dba)3, NaOAc
DMSO, 60 oC
Ph
R1
R4
Ph
R4
R2
R1
OR3
R2
7
6
Entry
R1
R2
R3
R4
6
Time (h)
7
Yield (%)c
1
2
3
4
5
H
H
H
H
H
H
Ph
CO2Et
CO2Et
CO2Et
CO2Et
Ac
H
CH3
H
H
H
6a
6b
6c
6d
6e
1.5
1.5
4
4
6
7a
7b
7c
7d
7e
84
80
75b
74b
62
m-OCH3C6H5
CH3
CH3
a
b
c
Reactions were carried out on a 0.2 mmol scale in 2.0 mL of DMSO at 60 °C for the specified period of time with 1.0 equiv. of 6, 2.0 equiv. of NaOAc, and 5 mol% Pd2(dba)3.
The products were isolated as a 50:50 mixture.
Isolated yields.

J. Hu et al. / Catalysis Communications 11 (2010) 346–350
349
5.2. General procedure for the preparation of 2-aroyl-3-allenyl
benzo[b]furan derivatives 7
O
O
Ph
R
To a solution of propargylic compound 6 (0.20 mmol) in DMSO
(2.0 mL) was added anhydrous NaOAc (32.8 mg, 0.40 mmol). The
mixture was stirred for 1 min and Pd2(dba)3 (9.2 mg, 0.01 mmol,
5 mol%) was added. The resulting mixture was then heated under
an argon atmosphere at 60 °C. The work–up procedure was the
same as that described for 3-vinyl benzo[b]furan derivatives.
7a: Yellow oil: 1H NMR (300 MHz, CDCl3) d 7.75–7.72 (d,
J = 8.1 Hz, 2H), 7.41–7.38 (t, 1H), 7.28–7.13 (m, 4H), 6.95–6.90 (t,
1H), 6.80–6.77 (d, J = 8.4 Hz, 1H), 5.39–5.26 (q, 2H), 1.19 (s, 3H);
13C NMR (75 MHz, CDCl3) d 200.8, 197.5, 158.0, 134.3, 132.5,
129.8, 128.9, 128.0, 123.0, 122.5, 121.9, 110.6, 108.1, 92.1, 84.4,
24.9; IR (neat, cmꢁ1) 1688, 1460, 1084, 750, 690; Anal. Calcd for
C18H14O2: C, 82.42; H, 5.38. Found: C, 82.30; H, 5.50.
CO2
HOEt
O
OCO2Et
1a
Pdo
O
R
Ph
Pd
O
O
Acknowledgment
O
R
O
Ph
We thank the NSF
(NSF-20621091, NSF-20672049) and
Ph
0710RJZA019 for financial support.
3a
O
O
2a
Appendix A. Supplementary data
Ph
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.catcom.2009.10.028.
7a
Scheme 3.
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Cs2CO3 instead of K2CO3.
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8.06–8.03 (q, 2H), 7.99–7.96 (d, J = 6.9 Hz, 1H), 7.61–7.22 (m,
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