InCl3-catalyzed propargylation of indoles and phenols with propargylic acetates: Application to the syntheses of benzofurans and naphthofurans

Article abstract of DOI:10.1055/s-2007-983735

InCl₃-catalyzed propargylation of indoles and phenols was developed. A strategy combining propargylation with intramolecular cyclization was used to easily prepare 2-benzyl-3-arylbenzofurans and -naphthofurans, which are important pharmaceutica

Full text of DOI:10.1055/s-2007-983735

PAPER
1961
InCl3-Catalyzed Propargylation of Indoles and Phenols with Propargylic
Acetates: Application to the Syntheses of Benzofurans and Naphthofurans
I
nCl -Catalyze
d
h
Propargylat
e
ion of Indoles and
L
Phenols iu,a,b Li Liu,*a Zahid Shafiq,a,b Yan-Chao Wu,a,b Dong Wang,a Yong-Jun Chen*a
3
a
Beijing National Laboratory for Molecular Sciences (BNLMS), Laboratory for Chemical Biology, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100080, P. R. China
Fax +86(10)62554449; E-mail: lliu@mail.iccas.ac.cn; E-mail: yjchen@mail.iccas.ac.cn
Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100080, P. R. China
b
Received 16 March 2007; revised 25 April 2007
Benzofuran and naphthofuran derivatives are common
subunits because of their physiological properties12 and
potential applications as fluorescent dyes13 and probes.14
Moreover, 3-aryl-2-benzylbenzofurans and -naphtho-
furans have been found in wide pharmacological applica-
tions for drug discovery. For example, benzofuran A is a
potent inhibitor of PTPases15 with good oral antihypergly-
cemic activity, which can be utilized for the treatment of
Type II diabetes, and benzofuran B, is a promising antian-
drogenic agent,16 which was isolated from the stems of
Dalbergia cochinchinensis (Figure 1). Many methods
have been developed for the synthesis of benzofurans,
such as cyclodehydration of aryl ketones, palladium-me-
diated Heck reactions,17 and three-component Friedel–
Crafts reaction of arylglyoxal monohydrates, phenols, and
TsNH2, described by our group.18 Herein, we report InCl3-
catalyzed propargylation of indoles and phenols with pro-
pargylic acetates and their application to the synthesis of
benzofuran and naphthofuran derivatives.
Abstract: InCl3-catalyzed propargylation of indoles and phenols
was developed. A strategy combining propargylation with intramo-
lecular cyclization was used to easily prepare 2-benzyl-3-arylben-
zofurans and -naphthofurans, which are important pharmaceutical
intermediates.
Key words: Friedel–Crafts alkylation, propargylation, cyclization,
benzofuran, InCl3
Friedel–Crafts alkylation is one of the most versatile and
widely used C–C bond-forming reactions, which has at-
tracted great deal of attention in organic chemistry.1
Among them, the development of Friedel–Crafts
allylation2 and propargylation,3 is still a challenging task.
Although the uses of transition-metal complexes and
Lewis acid catalyzed allylation have been widely studied,
which provided novel protocols for the functionalization
of aromatic compounds, the propargylation of aromatic
compounds is relatively less investigated. The features
that alkynes can be readily transformed into many phar-
maceutically useful key motifs and fused ring systems
drove attention of chemists to develop practical and effi-
cient propargylation methods.
R1
R2
O
COOR3
Transition-metal complexes have been employed for pro-
pargylation of aromatic compounds,4 but have some
drawbacks, for example, requirement of a stoichiometric
amount of catalyst,5 limitation of the substrates,6 and high
cost.7 The propargylation of aromatic compounds with
propargylic alcohols can be also promoted by Lewis ac-
ids, such as Ti(O-iPr)4,8a TiCl4,8b,c CuCl,8d BF3·EtO2,8e,f
B(C6F5)3,8g and AuCl3.8h However, poor selectivity, nar-
row scope of the reaction, and handling with metal com-
plexes restricted their practical applications. Very
O
OMe
Aryl
A
OMe
HO
O
O
MeO
B
Ph
9
Figure 1
recently, it was reported that by using FeCl3 and
10
Bi(OTf)3 as catalysts, propargylic alcohols/acetates
could react with heteroatom nucleophiles under mild con-
ditions. To our knowledge there are only few examples of
the propargylation of heteroaromatic compounds, such as
indoles with propargylic acetate/alcohol had been report-
ed.11
Initially, the reactions of indole (1a) with 1,3-diphenyl-
propargyl acetate (2a) in the presence of various Lewis
acid catalysts (10 mol%) were carried out in MeCN at
room temperature, giving the propargylated product, 3-(3-
indolyl)-1,3-diphenylpropargylene (3a). It can be seen
from Table 1 that indium(III) chloride is the most efficient
Lewis acid catalyst for the reaction of indole with propar-
gylic acetate under mild conditions. This protocol
(Scheme 1) has a broad substrate scope for both electron-
rich and electron-poor indoles 1b–i. Good to excellent
SYNTHESIS 2007, No. 13, pp 1961–1969
x
x.
x
x
.
2
0
0
7
Advanced online publication: 18.06.2007
DOI: 10.1055/s-2007-983735; Art ID: F05507SS
© Georg Thieme Verlag Stuttgart · New York

1962
Z. Liu et al.
PAPER
Ar
OAc
Ar
InCl3 (10 mol%)
MeCN, r.t.
+
R2
R3
Ph
N
R1
R3
N
R1
R2
Ph
1a–i
2a–d
3a–j
Scheme 1
Table 1 Lewis Acid Catalyzed Propargylation of 1a with 2a
yields of propargylated products were obtained (Table 2),
except for N-substituted indoles 1c, 1g, which showed
low reactivity (entries 3,7). Various cross-substituted pro-
pargylic acetates 2b–d were prepared and used to examine
the regioselectivity of the InCl3-catalyzed propargylation
reaction. It is noteworthy that the propargylation only oc-
curred at the benzylic position, while no reaction took
place if the aryl group (Ar) of propargylic acetate was re-
placed by an alkyl group (Me). Furthermore, except for
2d, the propargylations of p-tolyl 2b and b-naphthyl 2c
acetates with indoles proceeded smoothly to give the pro-
pargylation products 3h–i in reasonable yields (Table 2,
entries 8,9).
Ph
LA
(10 mol%)
OAc
+
Ph
Ph
MeCN,
r.t.
N
N
H
Ph
H
1a
2a
3a
Entry
Catalyst
AgOTf
Sc(OTf)3
CuCl2
Yield of 3a (%)a
1
2
3
4
5
6
7
n.r.b
n.r.
8
In addition, InCl3 could also catalyze the propargylation
of less reactive aromatic C-nucleophiles such as phenols
4a–e with propargyl acetate 2a to afford mono- or bis-C-
propargylated products 5a–e instead of O-propargylated
isomers efficiently under mild reaction conditions in 54–
95% yields (Scheme 2, Table 3).
CuBr
n.r.
21
Cu(OTf)2
FeCl3
trace
68
InCl3
a Isolated yield.
b No reaction.
Table 2 InCl3-Catalyzed Propargylation of Indoles with Propargylic Acetatesa
Entry
Indole
Propargyl acetate
Time (h)
Product
Yield (%)b
68
Ph
Ph
Ph
OAc
1
1a
1b
2a
2a
3
3a
Ph
N
H
Ph
Ph
Ph
N
Ph
H
2
3
17
24
3b
3c
73
47
N
H
N
H
1c
2a
N
N
NO2
NO2
Ph
Ph
4
5
1d
1e
2a
2a
3
5
3d
3e
99
86
Ph
Ph
N
H
N
H
Br
Br
N
H
N
H
Synthesis 2007, No. 13, 1961–1969 © Thieme Stuttgart · New York

PAPER
InCl3-Catalyzed Propargylation of Indoles and Phenols
1963
Table 2 InCl3-Catalyzed Propargylation of Indoles with Propargylic Acetatesa (continued)
Entry
6
Indole
Propargyl acetate
Time (h)
18
Product
Yield (%)b
77
Ph
1f
2a
2a
3f
F
N
Ph
H
F
N
H
Ph
7
8
1g
16
17
3g
48
82
N
Ph
N
SO2Ph
SO2Ph
Me
OAc
1h
2b
3h
N
CO2Et
Ph
H
Me
Ph
N
H
CO2Et
OAc
Br
9
1i
2c
14
24
3i
3j
97
37
Br
N
Ph
H
Ph
N
H
OAc Br
Br
10
1a
2d
Ph
Ph
N
H
a 1/2 = 1:1. Reaction temperature: r.t., catalyst loading = 10 mol%.
b Isolated yield.
OH
OH Ph
transfer. The reaction sequence is presented in the pro-
posed mechanism shown in Scheme 3. Benzofurans can
be prepared under basic conditions through two synthetic
pathways (Scheme 4). Pathway I starts from propargylat-
ed products. With the optimized conditions in hand, sub-
strate scope of the reaction was studied. Several
propargylated phenols 5a–c afforded benzofurans and
naphthofurans 8a–c in good to excellent yields (Table 4).
One-pot protocol was also developed to directly synthe-
size benzofurans from phenols and propargylic acetate
without purification of the propargylation product
(Scheme 4, pathway II).
OAc
Ph
InCl3 (10 mol%)
MeCN, r.t.
+
Ph
R
R
Ph
4a–e
2a
5a–e
Scheme 2
As reported by Uemura,19 the reaction of 2-naphthol (4a)
with propagylic alcohols under the catalysis of ruthenium
complex gave propargylation/cyclization product, naph-
thopyran 7 (Scheme 3, equation 1). However, in contrast
to Uemura’s result, our investigation indicated that under
basic conditions (t-BuOK/THF), the propargylation/cy-
clization product was naphthofuran 8a in 74% yield
(Scheme 3, equation 2). The opposite result was attributed
to the use of base, which could trap the proton of propar-
gylated phenols 5, and facilitate exo-attack of the generat-
ed oxo-anion (i) to triple bond rather than endo-attack,
thus affording fused five-member ring system (ii).20 Final-
ly, the benzofuran product 8 was obtained by hydrogen
In order to pursue application of the developed protocol in
the synthesis of pharmaceutically useful intermediates,
2,4-dimethylphenol (4c) was employed to prepare [3-(4¢-
hydroxybiphenyl-4-yl)benzofuran-2-yl]phenylmethane
(9), a precursor and an analogue of benzofuran A, a potent
drug for the treatment of type II diabetes (Scheme 5).
After one-pot propargylation/cyclization, the desired
product 8e was obtained in good yield (72%). The follow-
ing Suzuki coupling reaction provided 9 in excellent yield
Synthesis 2007, No. 13, 1961–1969 © Thieme Stuttgart · New York

1964
Z. Liu et al.
PAPER
Ph
Ph
Ru complex
DCE, 60 °C
eq. 1
O
OH
OAc
Ph
+
7
Ph
Ph
Ph
InCl3
eq. 2
O
MeCN, r.t.
8a
Proposed mechanism
Ph
Ph
OH
O–
OAc
OH
InCl3
base
+
Ar
Ar
Ar
R
R
Ph
R
2
4
5
i
5-exo-dig
Ph
Ar
Ph
Ar
O
O
hydrogen transfer
R
R
8
ii
Scheme 3
Ph
OH
pathway I
t
Ph
R
Ph
Ph
O
5
R
OAc
Ph
8a–e
OH
+
pathway II
R
t
Ph
4
2
Scheme 4
(92%). In contrast to multi-step synthetic transforma- In conclusion, a mild, efficient and regioselective propar-
tions,15 the one-pot strategy provided a mild and efficient gylation of indoles and phenols catalyzed by InCl3 has
protocol to synthesize compound 9 and therefore ana- been developed, which combined with selective cycliza-
logues of A, following a sequence of the known transfor- tion provides 2-benzyl-3-arylbenzofurans and -naphtho-
mations (Scheme 5).
furans. Studies on detailed reaction mechanism and
Synthesis 2007, No. 13, 1961–1969 © Thieme Stuttgart · New York

PAPER
InCl3-Catalyzed Propargylation of Indoles and Phenols
1965
Table 3 InCl3-Catalyzed Propargylation of Phenols with 2aa
Entry
Phenol
Time (h)
Product
Yield (%)b
Ph
Ph
OH
1
4a
10
5a
95
OH
OH
OH Ph
2
3
4b
4c
8
4
5b
5c
54
82
Ph
MeO
OMe
MeO
OMe
OMe
OMe
OH Ph
OH
Ph
OH
OH Ph
4
4d
4e
5
6
5d
5e
61c
86
Ph
Ph
Ph
OH
5d
Ph
Ph
HO
HO
OH
a 4/2a = 1: 1, reaction temperature: r.t., catalyst loading: 10 mol%.
b Isolated yield.
c With disubstituted product 6 (11%).
d 4e/2a = 1:2.
Ph
OH
O
OAc
Me
Me
1) InCl3 (10mol%), MeCN, r.t., 14 h
2) t-BuOK, THF, r.t., overnight
+
Ph
Br
Br
Me
Me
2e
Ph
A
4c
8e, 72%
B(OH)2
OMe
Pd(PPh3)4/Na2CO3,
toluene,
reflux, 18 h
Ph
O
O
Me
Me
O
COOR1
Me
OMe
Me
R2
9, 92%
Scheme 5
Synthesis 2007, No. 13, 1961–1969 © Thieme Stuttgart · New York

1966
Z. Liu et al.
PAPER
Table 4 Syntheses of Benzofuran and Naphthofuran
Entry
1
Substrate
Time (h)
Pathway
Ib
Product
Yield (%)a
Ph
Ph
Ph
Ph
5a
5b
5c
5
8a
8b
8c
91
61
43
O
OH
Ph
Ph
OH Ph
O
2
3
8
5
I
I
Ph
MeO
OMe
MeO
OMe
OMe
OMe
OH Ph
Ph
Ph
O
Ph
OH
4
5
4a
4f
15
14
IIc
II
8a
8d
74
OH
Ph
Ph
O
46d
OH
Ph
O
6
4c
24
IIe
8e
72
Br
a Isolated yield.
b Pathway I: THF/t-BuOK, r.t.
c Pathway II: with 2a catalyzed by InCl3, then under THF/t-BuOK, r.t.
d With 38% propargylated 1-naphthol.
e Pathway II: with 2e.
idue was purified by flash chromatography on silica gel (eluent:
EtOAc–petroleum ether, 1:20) to give the desired product 5a9a in
95% yield.
asymmetric propargylation reactions are underway in our
laboratory.
1H NMR spectra were recorded on Bruker 300 (300 MHz) spec-
trometer. Chemical shifts are reported in ppm with TMS as an inter-
nal standard. EI and HRMS spectra were recorded on GCT-MS
Micromass UK. IR analyses were performed with a Bruker FT-IR
spectrophotometer. Melting points were measured with a Beijing-
Taike X- 4 apparatus and are uncorrected. Petroleum ether used re-
fers to the fraction boiling in the range 30–60 °C.
3-(1,3-Diphenylprop-2-ynyl)-1H-indole (3a)
Brown liquid.
IR (film): 3419, 3057, 2924, 1598, 1490, 1455, 744, 694 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.42 (s, 1 H) 6.96–7.59 (m, 15 H),
7.70 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 35.6, 83.5, 90.7, 111.4, 116.9,
119.7, 122.3, 122.8, 123.8, 126.2, 127.0, 128.0, 128.1, 128.4, 128.6,
131.8, 137.0, 141.4.
Propargylation of Indoles and Phenols; 1-(1,3-Diphenylprop-2-
ynyl)-2-naphthol (5a); Typical Procedure
HRMS (EI): m/z calcd for C23H17N: 307.1361; found: 307.1359.
To a solution of 2-naphthol (4a; 144 mg, 1.0 mmol) and propargylic
acetate (2a; 250 mg, 1.0 mmol) in MeCN (10 mL), was added InCl3
(22 mg, 0.1 mmol), followed by stirring at r.t. for 10 h. TLC showed
that the starting materials were consumed completely. Then H2O
(10 mL) was added to quench the reaction. The aqueous layer was
extracted with Et2O (3 × 20 mL) and the organic layers were com-
bined and dried (Na2SO4). The solvent was evaporated and the res-
3-(1,3-Diphenylprop-2-ynyl)-2-methyl-1H-indole (3b)
Green liquid.
IR (film): 3407, 3057, 2923, 1597, 1489, 1458, 753, 694 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.40 (s, 3 H), 5.51 (s, 1 H), 7.06–
7.668 (m, 14 H), 7.70 (s, 1 H).
Synthesis 2007, No. 13, 1961–1969 © Thieme Stuttgart · New York

PAPER
InCl3-Catalyzed Propargylation of Indoles and Phenols
1967
13C NMR (75 MHz, CDCl3): d = 12.2, 33.8, 83.6, 90.2, 110.3,
111.4, 119.0, 119.5, 121.2, 123.8, 126.5, 127.4, 127.5, 127.8, 128.2,
128.4, 131.6, 131.7, 135.2, 141.4.
Ethyl 3-[1-(4-Methylphenyl)-3-phenylprop-2-ynyl]-1H-indole-
2-carboxylate (3h)
Yellow oil.
HRMS (EI): m/z calcd for C24H19N: 321.1517; found: 321.1515.
IR (film): 3334, 3054, 2923, 1689, 1242, 743, 690 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.40 (t, J = 7.1 Hz, 3H ), 2.27 (s,
3-(1,3-Diphenylprop-2-ynyl)-1-methyl-1H-indole (3c)
Brown oil.
IR (film): 3056, 3027, 2927, 1597, 1489, 1369, 755, 739, 695 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.73 (s, 3 H), 5.45 (s, 1 H), 6.96–
7.63 (m, 15 H).
13C NMR (75 MHz, CDCl3): d = 32.7, 35.4, 83.2, 90.7, 109.3,
115.4, 119.1, 119.7, 131.8, 123.8, 126.5, 126.7, 127.3, 127.8, 127.9,
128.2, 128.5, 131.7, 137.5, 141.5.
3 H), 4.46 (m, 2 H), 6.52 (s, 1 H), 7.05–8.02 (m, 13 H), 8.95 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.5, 21.1, 33.4, 61.3, 84.0, 90.2,
112.0, 120.4, 122.67, 122.9, 123.0, 123.8, 125.7, 126.5, 127.4,
127.9, 128.3, 129.1, 131.7, 136.2, 136.3, 138.0, 162.3.
HRMS (EI): m/z calcd for C27H23NO2: 393.1729; found: 393.1726.
3-[1-(2-Naphthyl)-3-phenylprop-2-ynyl]-5-bromo-1H-indole
(3i)
Black liquid.
HRMS (EI): m/z calcd for C24H19N: 321.1517; found: 321.1520.
IR (film): 3430, 3056, 2923, 1599, 1451, 736, 689 cm–1.
3-(1,3-Diphenylprop-2-ynyl)-4-nitro-1H-indole (3d)
Red solid; mp 165–167 °C.
1H NMR (300 MHz, CDCl3): d = 5.52 (s, 1 H), 7.03–7.94 (m, 17 H).
13C NMR (75 MHz, CDCl3): d = 35.5, 84.0, 90.0, 112.8, 113.0,
116.5, 122.2, 123.5, 124.0, 125.2, 125.9, 126.2, 126.3, 127.7, 127.9,
128.0, 128.1, 128.3, 128.5, 131.8, 132.6, 133.5, 135.4, 138.3.
IR (KBr): 3358, 3020, 2921, 1562, 1321, 1286, 1225, 752, 730
cm–1.
1H NMR (300 MHz, CDCl3): d = 5.87 (s, 1 H), 7.19–7.78 (m, 14 H),
8.48 (s, 1 H).
HRMS (EI): m/z calcd for C27H18BrN: 435.0623; found: 435.0618.
13C NMR (75 MHz, CDCl3): d = 36.2, 83.8, 90.7, 117.1, 117.4,
117.8, 117.9, 121.1, 123.5, 127.0, 127.8, 127.9, 128.1, 128.3, 128.6,
131.7, 139.2, 141.0, 143.6.
3-[1-(2-Bromophenyl)-3-phenylprop-2-ynyl]-1H-indole (3j)
Brown liquid.
IR (film): 3419, 3057, 2925, 1489, 1457, 741, 691 cm–1.
HRMS (EI): m/z calcd for C23H16N2O2: 352.1212; found: 352.1209.
1H NMR (300 MHz, CDCl3): d = 5.90 (s, 1 H), 7.05–7.65 (m, 14 H),
7.99 (s, 1 H).
3-(1,3-Diphenylprop-2-ynyl)-4-bromo-1H-indole (3e)
Brown liquid.
IR (film): 3424, 3060, 2923, 1599, 1488, 909, 759, 692 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.25 (s, 1 H), 6.95–7.50 (m, 14 H),
8.01 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 35.4, 83.2, 89.7, 111.3, 115.7,
119.7, 119.7, 122.3, 123.1, 123.5, 123.9, 126.0, 127.9, 128.0, 128.2,
128.6, 130.2, 131.8, 132.9, 136.7, 140.5.
HRMS (EI): m/z calcd for C23H16BrN: 385.0466; found: 385.0464.
13C NMR (75 MHz, CDCl3): d = 34.5, 83.4, 91.6, 110.7, 114.0,
117.8, 123.1, 123.8, 124.4, 124.6, 125.4, 126.7, 127.8, 128.1, 128.2,
128.4, 131.7, 137.7, 142.3.
2-(1,3-Diphenylprop-2-ynyl)-3,4,5-trimethoxyphenol (5b)
Colorless liquid.
IR (film): 3466, 2925, 1602, 1462, 1200, 1081, 757, 696 cm–1.
HRMS (EI): m/z calcd for C23H16BrN: 385.0466; found: 385.0471.
1H NMR (300 MHz, CDCl3): d = 3.80 (s, 3 H), 3.83 (s, 3 H), 3.88
(s, 3 H), 5.83 (s, 1 H), 6.14 (s, 1 H), 6.30 (s, 1 H), 7.23–7.49 (m, 10
H).
13C NMR (75 MHz, CDCl3): d = 32.3, 55.8, 61.0, 61.4, 85.5, 88.4,
97.5, 112.2, 122.5, 127.1, 127.1, 128.4, 128.5, 128.7, 131.8, 136.1,
139.9, 151.1, 153.4.
3-(1,3-Diphenylprop-2-ynyl)-6-fluoro-1H-indole (3f)
Red liquid.
IR (film): 3427, 3063, 2925, 1617, 1494, 1137, 908, 836, 702, 604
cm–1.
1H NMR (300 MHz, CDCl3): d = 5.42 (s, 1 H), 6.83 (t, J = 8.9 Hz,
1 H), 7.04 (d, J = 7.4 Hz, 1 H), 7.11 (s, 1 H), 7.25–7.53 (m, 11 H),
7.99 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 35.5, 83.5, 90.2, 97.3, 97.7, 108.3,
108.6, 117.2, 120.4, 120.5, 122.7, 122.8, 122.8, 123.6, 127.0, 127.9,
127.9, 128.2, 128.5, 131.7, 136.63, 136.79, 141.0, 158.5, 161.6.
HRMS (EI): m/z calcd for C24H22O4: 374.1518; found: 374.1514.
2,4-Dimethyl-6-(1,3-diphenylpropyn-2-yl)phenol (5c)
Orange liquid.
IR (film): 3463, 2923, 1645, 1601, 1488, 757, 697 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.18 (s, 3 H), 2.23 (s, 3 H), 5.24
(s, 1 H), 5.38 (s, 1 H), 6.86 (s, 1 H), 6.99 (s, 1 H), 7.19–7.48 (m, 10
H).
13C NMR (75 MHz, CDCl3): d = 15.9, 20.6, 39.1, 85.6, 89.1, 123.1,
124.9, 126.6, 127.1, 127.7, 127.8, 128.3, 128.7, 129.7, 130.8, 131.8,
140.3, 149.6.
HRMS (EI): m/z calcd for C23H16FN: 325.1267; found: 325.1269.
3-(1,3-Diphenylprop-2-ynyl)-1-benzenesulfonylindole (3g)
Red liquid.
IR (film): 3062, 2923, 1597, 1490, 1372, 1178, 749, 687, 585 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.32 (s, 1 H), 7.12–7.98 (m, 20 H).
13C NMR (75 MHz, CDCl3): d = 35.4, 84.3, 88.7, 113.8, 120.4,
123.2, 123.3, 123.6, 124.3, 124.9, 126.8, 127.4, 127.9, 128.2, 128.3,
128.7, 129.3, 129.4, 131.7, 133.8, 135.8, 138.2, 139.5.
4-Methyl-2-(1,3-diphenylprop-2-ynyl)phenol (5d)
Colorless liquid.
IR (film): 3536, 3058, 2923, 1599, 1497, 1266, 812, 756, 695 cm–1.
HRMS (EI): m/z calcd for C29H21NO2S: 447.1293; found:
447.1289.
1H NMR (300 MHz, CDCl3): d = 2.26 (s, 3 H), 5.26 (s, 1 H), 5.43
(s, 1 H), 6.68–7.48 (m, 13 H).
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1968
Z. Liu et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 20.7, 38.5, 85.3, 89.2, 116.6,
123.1, 127.1, 127.2, 127.8, 128.3, 128.4, 128.7, 129.1, 130.1, 130.4,
131.8, 140.4, 151.1.
2-Benzyl-3-phenylnaphtho[1,2-b]furan (8d)
Pale yellow solid; mp 95–97 °C.
IR (KBr): 3058, 3029, 2923, 1494, 1392, 1005, 804, 736, 700 cm–1.
HRMS (EI): m/z calcd for C22H18O: 298.1358; found: 298.1361.
1H NMR (300 MHz, CDCl3): d = 4.07 (s, 2 H), 7.02–7.29 (m, 6 H),
7.37 (t, J = 7.0 Hz, 1 H), 7.48–7.53 (m, 5 H), 7.60–7.74 (m, 3 H),
7.90 (d, J = 8.3 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 32.7, 112.3, 120.0, 122.2, 123.2,
124.1, 125.0, 125.8, 126.5, 127.8, 128.1, 128.5, 128.7, 128.8, 130.6,
130.8, 133.9, 138.2, 151.7, 152.7.
2,4-Bis(1,3-diphenylprop-2-ynyl)resorcinol (5e)
Red liquid.
IR (film): 3533, 2946, 1602, 1491, 1278, 1195, 836, 757, 693 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.34 (d, J = 4.8 Hz, 2 H), 5.49 (s,
2 H), 6.31 (d, J = 3.1 Hz, 1 H), 7.22–7.46 (m, 21 H).
13C NMR (75 MHz, CDCl3): d = 38.2, 38.3, 85.5, 85.6, 89.0, 89.1,
105.2, 105.3, 120.0, 122.9, 127.1, 127.6, 127.7, 128.3, 128.7, 130.5,
131.8, 140.4, 140.5, 153.6, 153.7.
HRMS (EI): m/z calcd for C25H18O: 334.1358, found: 334.1361.
2-Benzyl-5,7-dimethyl-3-(4-bromophenyl)benzofuran (8e)
Yellow liquid.
HRMS (EI): m/z calcd for C36H26O2: 490.1933; found: 490.1937.
IR (film): 3029, 2923, 1605, 1492, 1284, 1201, 983, 848, 729 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.38 (s, 3 H), 2.46 (s, 3 H), 4.15
3-Aryl-2-benzylbenzofurans and 3-Aryl-2-benzylnaphtho-
furans; 2-Benzyl-1-phenylnaphtho[2,1-b]furan (8a);
Typical One-Pot Procedure
(s, 2 H), 6.90–7.57 (m, 11 H).
13C NMR (75 MHz, CDCl3): d = 15.0, 21.3, 33.0, 116.7, 117.3,
120.9, 121.2, 126.5, 126.6, 127.9, 128.4, 128.6, 130.7, 131.9, 132.0,
132.5, 138.0, 151.8, 152.6.
To a solution of 2,4-dimethylphenol (4c; 183 mg, 1.5 mmol) and 1-
phenyl-3-(4¢-bromophenyl)propargyl-3-ol acetate (2e; 493 mg, 1.5
mmol) in MeCN (10 mL), was added InCl3 (33 mg, 0.15 mmol), fol-
lowed by stirring at r.t. for 14 h. Then the solvent was evaporated
and the residue was dissolved in THF (15 mL). t-BuOK (179 mg,
1.0 equiv) was added and the resulting mixture was stirred over-
night at r.t. Then H2O (15 mL) was added to quench the reaction and
the aqueous media was extracted with Et2O (2 × 25 mL). The organ-
ic layers were combined, and dried (Na2SO4). The crude product
was purified by flash chromatography on silica gel (EtOAc–petro-
leum ether, 1:25) to give the product 8e in 72% overall yield.
HRMS (EI): m/z calcd for C23H19BrO: 390.0619; found: 390.0622.
2-Benzyl-5,7-dimethyl-3-(4-methoxybiphenyl)benzofuran (9)
White solid; mp 128–130 °C.
IR (KBr): 3030, 2923, 1606, 1498, 1249, 983, 823, 735 cm–1.
1H NMR (300 MHz,CDCl3): d = 2.39 (s, 3 H), 2.47 (s, 3 H), 3.84 (s,
3 H), 4.23 (s, 2 H), 6.91–7.65 (m, 15 H).
13C NMR (75 MHz, CDCl3): d = 15.0, 21.3, 33.0, 55.4, 114.3,
117.1, 118.0, 120.8, 126.3, 126.5, 127.0, 128.1, 128.3, 128.5, 128.6,
129.4, 131.3, 132.3, 133.4, 138.3, 139.6, 151.8, 152.4, 159.3.
Colorless liquid.
IR (film): 3058, 3029, 2924, 1606, 1392, 1277, 1232, 1005, 804,
738, 701 cm–1.
HRMS (EI): m/z calcd for C30H26O2: 418.1933; found: 418.1936.
1H NMR (300 MHz, CDCl3): d = 4.06 (s, 2 H), 7.18–7.89 (m, 16 H).
13C NMR (75 MHz, CDCl3): d = 32.7, 112.3, 120.0, 122.2, 123.2, Acknowledgment
124.1, 125.0, 125.8, 126.5, 127.9, 128.1, 128.6, 128.8, 128.9, 130.6,
130.8, 133.9, 138.2, 151.7, 152.8.
We thank the National Natural Science Foundation of China and
Chinese Academy of Sciences for financial support.
HRMS (EI): m/z calcd for C25H18O: 334.1358; found: 334.1361.
2-Benzyl-4,5,6-trimethoxy-3-phenylbenzofuran (8b)
Orange liquid.
References
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IR (film): 3060, 3028, 2933, 1615, 1468, 1238, 1000, 810, 765, 702
cm–1.
1H NMR (300 MHz, CDCl3): d = 3.50 (s, 3 H), 3.85 (s, 3 H), 3.88
(s, 3 H), 4.05 (s, 2 H), 6.82 (s, 1 H), 7.20–7.51 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 32.6, 56.3, 61.3, 61.4, 91.5, 115.0,
117.9, 126.5, 127.1, 127.9, 128.5, 128.5, 130.1, 132.8, 138.2, 138.8,
146.7, 151.1, 151.5, 151.8.
HRMS (EI): m/z calcd for C24H22O4: 374.1518; found: 374.1520.
2-Benzyl-5,7-dimethyl-3-phenylbenzofuran (8c)
Yellow liquid.
IR (film): 3028, 2922, 1605, 1201, 982, 848, 732, 702 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.38 (s, 3 H), 2.46 (s, 3 H), 4.20
(s, 2 H), 6.90–7.48 (m, 12 H).
13C NMR (75 MHz, CDCl3): d = 14.9, 21.3, 32.9, 117.0, 118.3,
120.8, 126.2, 126.4, 127.1, 128.3, 128.5, 128.6, 128.7, 129.1, 132.2,
133.0, 138.2, 151.8, 152.3.
HRMS (EI): m/z calcd for C23H20O: 312.1514; found: 312.1516.
Synthesis 2007, No. 13, 1961–1969 © Thieme Stuttgart · New York

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Synthesis 2007, No. 13, 1961–1969 © Thieme Stuttgart · New York