Facile assembly of indeno[1,2-c]chromenes via a palladium-catalyzed reaction of 2-alkynylhalobenzene

Article abstract of DOI:10.1039/c2ob26369f

2-Alkynylhalobenzene reacts with 2-alkynylphenol in the presence of a palladium catalyst, leading to indeno[1,2-c]chromenes in good to excellent yields. Furthermore, the scaffold of indeno[1,2-c]chromene could be constructed via a palladium-catalyzed reac

Full text of DOI:10.1039/c2ob26369f

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PAPER
Facile assembly of indeno[1,2-c]chromenes via a palladium-catalyzed reaction
of 2-alkynylhalobenzene†
Xiaolin Pan,a Hongming Nie,b Yong Luo,a Yueqiu Gao*b and Jie Wu*a,c
Received 16th July 2012, Accepted 21st August 2012
DOI: 10.1039/c2ob26369f
2-Alkynylhalobenzene reacts with 2-alkynylphenol in the presence of a palladium catalyst, leading to
indeno[1,2-c]chromenes in good to excellent yields. Furthermore, the scaffold of indeno[1,2-c]chromene
could be constructed via a palladium-catalyzed reaction of 2-alkynylbromobenzene with water, in which
four bonds are formed with high efficiency.
1. Introduction
It is well recognized that heterocyclic compounds with a core of
natural products have attracted considerable attention for the
study of chemical genetics.1 Efficient and novel approaches have
appeared for the construction of heterocyclic compounds using
the strategy of diversity-oriented synthesis. As a part of our con-
tinuing efforts for accessing natural product-like compounds,2
we are interested in the development of methods of tandem reac-
tions3 for the facile assembly of such small molecules. Gnetuhainin
Fig. 1 Structures of Gnetuhainin S.
S from Gnetum macrostachyum lianas, displays antioxidant
activity as a radical scavenging against DPPH (Fig. 1).4 The lack
of efficient ways to access this [6-5-6-6] tetracyclic skeleton5
narrows their broader and further applications in medicinal
chemistry. Therefore, it is highly desirable to develop efficient
synthetic protocols for the construction of the [6-5-6-6] tetra-
cyclic core, among which, the tandem reaction is highlighted to
us due to its well-known advantages.6,7
Recently, we reported a highly selective pathway for the prep-
aration of 5H-cyclopenta[c]quinolines starting from 2-alkynyl-
halobenzene with an amine in the presence of a palladium
catalyst (Scheme 1, eqn (1)).8 The preliminary biological evalu-
ation discovered that several hits showed anti-HBV activity. To
look for more active compounds, we need to generate a small
library of 5H-cyclopenta[c]quinolines with related compounds.
The mechanism study of the synthetic route revealed that the
reaction proceeded through a double insertion of triple bonds9
Scheme 1 The proposed synthetic route for the formation of indeno-
[1,2-c]chromene 3.
aDepartment of Chemistry, Fudan University, 220 Handan Road,
Shanghai 200433, China. E-mail: jie_wu@fudan.edu.cn;
Fax: +86 21 6564 1740; Tel: +86 21 6510 2412
bDepartment of Hepatology Disease, Shanghai Shuguang Hospital,
Shanghai University of T.C.M., Shanghai 201203, China.
E-mail: gaoyueqiu@hotmail.com
and 2-alkynylaniline was identified as the intermediate.
Encouraged by the results, we envisioned that 2-alkynylphenol
could be employed in the reaction of 2-alkynylhalobenzene as
well due to the structural similarity of 2-alkynylphenol with
2-alkynylaniline (Scheme 1, eqn (2)). The indeno[1,2-c]chromene
3 with [6-5-6-6] tetracyclic skeleton would be generated if the
cState Key Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032,
China
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2ob26369f
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reaction proceeded as expected. Additionally, we anticipated that
these compounds could be formed in the meantime from
the reaction of 2-alkynylhalobenzene with water (Scheme 1,
eqn (3)). We reasoned that 2-alkynylphenol would be produced
during the reaction process,10 which would then undergo the
subsequent transformation to afford indeno[1,2-c]chromene 3.
2-Alkynylphenols could be easily converted to benzo[b]furans
in the presence of a palladium catalyst.11 Usually, R-PdIIX
would activate the triple bond of 2-alkynylphenol, which would
promote the subsequent nucleophilic addition of the phenolic
oxide to the triple bond. Additionally, the direct coupling of aryl
halide with 2-alkynylphenol12 seems inevitable. Although theo-
retically the above two possible competitive pathways would
hamper the efficiency of the proposed synthetic route
(Scheme 1), we believed that the hypothesis would be feasible
due to the highly selective process of double insertion of triple
bonds. Therefore, we started to explore the possibility of this
transformation and a part of this work has been communicated.9c
Fig. 2 Phosphine ligands.
(PCy3) (Table 1, entry 8). Other bases were then screened and
the reaction worked efficiently when sodium methanolate
(NaOCH3) was utilized as the base (95% yield, Table 1, entry
14). Reactions in various solvents were explored as well and
1,4-dioxane was demonstrated as the best (96% yield, Table 1,
entry 16). Yet a lower temperature did not provide a satisfactory
result (data not shown in Table 1).
2. Results and discussion
For the model reaction, 1-bromo-2-(phenylethynyl)benzene 1a
and 2-(2-phenylethynyl)phenol 2a were adopted, and the pre-
liminary screening for the reaction was performed in the pres-
ence of Pd(OAc)2 (5 mol%) at 105 °C (Table 1). Different
ligands were examined first (Fig. 2), but with only a trace
amount of product, including L1–L4, tBu3P and BINAP
(Table 1, entries 1–6). The reaction became complex when
DPPF was employed as a replacement for the above ligands
(Table 1, entry 7). To our delight, the desired product 3a was
furnished in 59% yield in the presence of tricyclohexyphosphine
The protocol generality was then investigated under the opti-
mized conditions, as highlighted in Table 1 (entry 16). A range
of desired indeno[1,2-c]chromenes was obtained in good to
excellent yields through the palladium-catalyzed tandem
reactions of 2-alkynylbromobenzenes with 2-alkynylphenols
(Scheme 2). The starting materials with substituents, whether on
the aromatic ring of the substrates or attached on the triple bond,
reacted well to afford the desired products. Additionally, under the
standard conditions the reaction of 1-chloro-2-(2-phenylethynyl)-
benzene with 2-(2-phenylethynyl)phenol 2a was examined,
which gave rise to the corresponding product 3a in 78% yield.
This result indicated that the substrate scope of this transform-
ation could be expanded to 2-alkynylchlorobenzenes.
Table 1 Initial studies of the palladium-catalyzed reaction of 1-bromo-
2-(phenylethynyl)benzene 1a with 2-(2-phenylethynyl)phenol 2a
As mentioned above, 2-alkynylphenols could be obtained
from the reaction of 2-alkynylbromobenzenes with water.10
Therefore, it would provide a concise route to indeno[1,2-c]chro-
menes from 2-alkynylbromobenzenes if 2-alkynylphenols could
be formed in situ. Since both processes would be fulfilled in the
presence of a palladium catalyst, we envisioned that the direct
formation of indeno[1,2-c]chromenes via a palladium-catalyzed
reaction of 2-alkynylbromobenzene with water would be
possible under suitable conditions. If the conversion proceeded
as expected, four bonds would be formed in a tandem procedure.
Considering the high efficiency and the easy availability of start-
ing materials, we started to explore the possibility of this
transformation.
The initial studies were performed for the reaction of
1-bromo-2-((4-methoxyphenyl)ethynyl)benzene with water by
using 5 mol% of Pd(OAc)2, 10 mol% phosphine ligand and
5.0 equiv. of water in the presence of a suitable base (Table 2).
Initially, only a trace amount of product was detected when the
reaction occurred in 1,4-dioxane at 105 °C in the presence of
X-Phos and potassium carbonate (Table 2, entry 1). No reaction
took place when t-BuOK was employed as the base (Table 2,
entry 2). The reaction failed as well when NaOMe was used as a
replacement (Table 2, entry 3). Interestingly, the desired product
3t was obtained when the base was changed to t-BuONa
Entry
Ligand
Base
Solvent
Yielda (%)
1
2
3
4
5
6
7
8
L1
L2
L3
L4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
NaOtBu
K2CO3
KOtBu
LiOtBu
KOH
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
1,4-Dioxane
DMF
Trace
Trace
Trace
Trace
Trace
Trace
Complex
59
87
79
67
81
55
95
72
96
Trace
nr
tBu3P·HBF4
BINAP
DPPF
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
9
10
11
12
13
14
15
16
17
18
NaOCH3
Cs2CO3
NaOCH3
NaOCH3
NaOCH3
DMSO
a Isolated yield based on 1-bromo-2-(phenylethynyl)benzene 1a.
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Table 2 The initial studies for the palladium-catalyzed reaction of
2-alkynylbromobenzenes with watera
Entry Ligand
Base
Solvent
Temp (°C) Yieldb (%)
1
2
3
4
5
6
X-Phos K2CO3
X-Phos t-BuOK
X-Phos NaOMe
X-Phos t-BuONa 1,4-Dioxane 105
X-Phos t-BuONa 1,4-Dioxane 75
X-Phos t-BuONa 1,4-Dioxane 90
1,4-Dioxane 105
1,4-Dioxane 105
1,4-Dioxane 105
Trace
nr
Trace
32
26
70
7
8
9
X-Phos KOH
X-Phos K2CO3
X-Phos K3PO4
1,4-Dioxane 90
1,4-Dioxane 90
1,4-Dioxane 90
1,4-Dioxane 90
1,4-Dioxane 90
1,4-Dioxane 90
1,4-Dioxane 90
1,4-Dioxane 90
1,4-Dioxane 90
95
71
80
36
50
24
nr
25
10
11
12
13
14
15
16
17
L5
L6
L7
L8
DPPE
PCy3
KOH
KOH
KOH
KOH
KOH
KOH
30
61
Trace
X-Phos KOH
X-Phos KOH
Toluene
DMF
90
90
a Reaction conditions: 2-alkynylbromobenzene 1a (0.4 mmol), water
(2.5 equiv.), palladium catalyst (5 mol%), ligand (10 mol%),
base (2.0 equiv.), solvent (2.0 mL). b Isolated yield based on
2-alkynylbromobenzene 1a.
Scheme 2 The synthesis of indeno[1,2-c]chromenes via a palladium-
catalyzed reaction of 2-alkynylbromobenzene with 2-alkynylphenol.
(32% yield, Table 2, entry 4). A slightly lower yield was afforded
when the reaction was performed at 75 °C (Table 2, entry 5).
To our delight, a good result was obtained when the reaction
occurred at 90 °C (Table 2, entry 6). The yield could not be
improved when the amount of water was reduced or increased.
Further exploration revealed that KOH was the best choice for
this transformation (Table 2, entry 7). Other phosphine ligands
were then screened. However, no better results were observed
(Table 2, entries 10–15). No reaction occurred without the
addition of a phosphine ligand in a control experiment (data not
shown in Table 2). Other palladium sources were investigated in
the meantime, which furnished the inferior yields. No improve-
ment was found when the reaction was performed in other
solvents (Table 2, entries 16 and 17). Reducing the catalytic
amount of palladium acetate to 2.5 mol% resulted in a lower
yield.
The reaction scope was then examined under the optimized
conditions (5 mol% of Pd(OAc)2, 10 mol% of X-Phos,
2.0 equiv. of KOH, 1,4-dioxane, 90 °C). The results are summar-
ized in Scheme 3. For the R2 group attached on the triple bond
of 2-alkynylbromobenzene 1, it seems that alkyl groups, as well
as electron-donating aryl groups, are all tolerated under the con-
ditions. For instance, the n-butyl or cyclopropyl-substituted
indeno[1,2-c]chromenes 3v/3w were afforded in 58% and 68%
yields, respectively. However, when a p-chlorophenyl group was
Scheme 3 The synthesis of indeno[1,2-c]chromenes via a palladium-
catalyzed reaction of 2-alkynylbromobenzenes 1 with water.
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C, which would undergo a C–O coupling to give the desired
indeno[1,2-c]chromene 3.
In conclusion, we have described a facile assembly of indeno-
[1,2-c]chromenes via a palladium-catalyzed tandem reaction of
2-alkynylbromobenzenes with 2-alkynylphenol. The reaction
works efficiently with excellent selectivity. Additionally, the
scaffold of indeno[1,2-c]chromene could be constructed via a
palladium-catalyzed reaction of 2-alkynylbromobenzene with
water, in which four bonds are formed with high efficiency. The
related library construction is currently ongoing.
Scheme 4 The synthesis of indeno[1,2-c]chromenes via a palladium-
catalyzed reaction of 2-alkynylbromobenzenes 1 with water.
Experimental section
General experimental procedure for palladium-catalyzed
reaction of 2-alkynylbromobenzenes 1 with 2-alkynylphenols 2
2-Alkynylbromobenzene (0.20 mmol) was added to a mixture
of Pd(OAc)2 (5 mol%), tricyclohexylphosphine (10 mol%),
t-BuONa (0.8 mmol) and 2-alkynylphenol (0.24 mmol) in
1,4-dioxane (2.0 mL). The mixture was heated to reflux. After
completion of the reaction, as indicated by TLC, the reaction
was cooled and the solvent was diluted by EtOAc (10 mL),
washed with saturated brine (2 × 10 mL) and dried by anhydrous
Na2SO4. Evaporation of the solvent followed by purification on
silica gel provided the indeno[1,2-c]chromenes 3.
General experimental procedure for palladium-catalyzed
reaction of 2-alkynylbromobenzenes 1 with water
2-Alkynylbromobenzene (0.40 mmol) was added to a mixture of
Pd(OAc)2 (5 mol%,), X-Phos (10 mol%) and KOH (0.8 mmol)
in 1,4-dioxane (2.0 mL with 5 equiv. water). The mixture was
heated to reflux. After completion of the reaction, as indicated
by TLC, the reaction was cooled and the solvent was diluted by
EtOAc (10 mL), washed with saturated brine (2 × 10 mL) and
dried by anhydrous Na2SO4. Evaporation of the solvent followed
by purification on silica gel provided the indeno[1,2-c]chro-
menes 3.
Scheme 5 A possible mechanism for the palladium-catalyzed reaction
of 2-alkynylbromobenzenes 1 with water.
attached on the triple bond, only a trace amount of product 3y
was detected. Further investigation revealed that the substituents
on the aromatic ring of 2-alkynylbromobenzene 1 were also
crucial for the successful transformation. Methyl-substituted
2-alkynylbromobenzene worked well in the reaction. The reac-
tion failed when chloro-substituted 2-alkynylbromobenzene was
employed under the standard conditions. Therefore, to expand
the utility of this conversion, we re-explored the conditions for
the reactions of electron-deficient 2-alkynylbromobenzenes.
1-(2-(2-Bromophenyl)ethynyl)-4-chlorobenzene was selected
for reaction development (Scheme 4). The parameters of the
palladium catalyst, ligand, base, solvent and temperature were
re-screened. We finally identified that the reaction proceeded
smoothly when phosphine L5 was utilized as the ligand in the
presence of t-BuONa, leading to the desired product 3y in 56%
yield. The reaction of 2-alkynylbromobenzene with an acetyl
group was studied in the meantime, which gave rise to the
expected product 3z in 25% yield.
1
6,11-Diphenylindeno[1,2-c]chromene (3a). Red solid, H NMR
(400 MHz, CDCl3) δ 7.90–7.87 (m, 2H), 7.69 (dd, J = 8.0,
1.2 Hz, 1H), 7.62–7.44 (m, 10H), 7.38–7.29 (m, 3H), 7.11–7.04
(m, 2H). 13C NMR (100 MHz, CDCl3) δ 152.6, 150.1, 144.4,
136.6, 133.8, 130.5, 130.0, 129.7, 129.5, 128.9, 128.8, 127.7,
127.4, 126.7, 126.5, 124.9, 124.3, 123.8, 122.8, 121.5, 120.1,
119.3, 117.7, 117.3. HRMS (ESI) calculated for C28H18O
[M + H]+ 371.1436, found 371.1424.
6-Phenyl-11-(p-tolyl)indeno[1,2-c]chromene (3b). Red solid,
1H NMR (400 MHz, CDCl3) δ 7.89–7.87 (m, 2H), 7.75–7.73
(m, 1H), 7.63–7.60 (m, 3H), 7.50–7.43 (m, 4H), 7.39–7.35
(m, 3H), 7.33–7.29 (m, 2H), 7.10–7.05 (m, 2H), 2.49 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 152.4, 150.1, 144.5, 137.1,
133.9, 133.5, 130.5, 129.8, 129.6, 129.5, 128.8, 127.6, 126.65,
126.60, 124.9, 124.2, 123.6, 122.7, 121.4, 120.2, 119.4, 117.6,
117.3, 21.5. HRMS (ESI) calculated for C29H20O [M + H]+
385.1592, found 385.1599.
A possible mechanism was proposed, which is presented in
Scheme 5. We reasoned that an oxidative addition of Pd(0) to
2-alkynylbromobenzenes 1 would take place to afford Pd(II) A.
Then, hydroxylation would occur in the presence of water to
produce 2-alkynylphenol 2, which would enter into the reaction
with Pd(II) A to generate intermediate B. Intramolecular coordi-
nation and insertion of a triple bond would afford intermediate
11-(4-Methoxyphenyl)-6-phenylindeno[1,2-c]chromene (3c). Red
1
solid, H NMR (400 MHz, CDCl3) δ 7.90–7.88 (m, 2H), 7.73
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(dd, J = 8.0, 1.2 Hz, 1H), 7.64–7.62 (m, 3H), 7.52–7.49 (m,
3H), 7.46–7.44 (m, 1H), 7.39–7.31 (m, 3H), 7.12–7.07 (m, 4H),
3.95 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 158.9, 134.2,
131.1, 130.5, 129.5, 128.7, 127.6, 126.7, 124.8, 124.2, 122.7,
121.4, 119.3, 117.7, 114.3, 55.3. HRMS (ESI) calculated for
C29H20O2 [M + H]+ requires 401.1542, found 401.1530.
7.60–7.52 (m, 5H), 7.47–7.44 (m, 2H), 7.41–7.37 (m, 3H),
7.34–7.29 (m, 2H), 7.11–7.07 (m, 2H), 2.50 (s, 3H), 2.18 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 153.0, 148.3, 144.2, 140.7,
136.7, 133.6, 131.0, 130.0, 129.8, 129.4, 128.73, 128.67, 127.4,
126.4, 125.9, 124.8, 124.0, 122.5, 121.4, 119.7, 119.2, 117.4,
116.9, 21.6, 21.2. HRMS (ESI) calculated for C30H22O
[M + H]+ 399.1749, found 399.1760.
11-(4-Chlorophenyl)-6-phenylindeno[1,2-c]chromene (3d). Red
1
solid, H NMR (400 MHz, CDCl3) δ 7.88–7.86 (m, 2H), 7.66
6-(4-Methoxyphenyl)-11-phenylindeno[1,2-c]chromene (3j). Red
1
(dd, J = 8.4, 1.2 Hz, 1H), 7.62–7.60 (m, 3H), 7.54–7.49 (m,
5H), 7.46–7.44 (m, 1H), 7.35–7.32 (m, 3H), 7.11–7.08 (m, 2H).
13C NMR (100 MHz, CDCl3) δ 152.9, 150.1, 143.9, 135.1,
133.7, 133.2, 131.4, 130.6, 129.7, 129.5, 129.2, 128.8, 127.9,
126.8, 125.0, 124.7, 124.4, 124.1, 122.9, 121.5, 119.8, 119.0,
117.8, 117.2. HRMS (ESI) calculated for C28H17ClO [M + H]+
405.1046, found 405.1045.
solid, H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.4 Hz, 2H),
7.68 (d, J = 8.0 Hz, 1H), 7.63–7.53 (m, 5H), 7.48–7.42 (m, 2H),
7.38–7.28 (m, 3H), 7.13–7.10 (m, 3H), 7.07–7.03 (m, 1H), 3.92
(s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.3, 152.7, 150.1,
144.2, 136.7, 131.1, 130.0, 129.9, 128.9, 127.6, 127.4, 126.5,
126.0, 124.8, 124.1, 123.9, 122.6, 121.4, 120.1, 119.3, 117.6,
116.8, 114.1, 113.5, 55.4. HRMS (ESI) calculated for C29H20O2
[M + H]+ 401.1542, found 401.1525.
6-Butyl-11-phenylindeno[1,2-c]chromene (3e). Yellow solid,
1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 7.6 Hz, 1H), 7.64 (d,
J = 8.0 Hz, 1H), 7.55–7.51 (m, 4H), 7.47–7.27 (m, 6H),
7.05–7.00 (m, 1H), 3.23 (t, J = 7.6 Hz, 2H), 1.99–1.91 (m, 2H),
1.61–1.55 (m, 2H), 1.02 (t, J = 7.6 Hz, 3H). 13C NMR
(100 MHz, CDCl3) δ 157.2, 149.9, 144.1, 136.8, 130.1, 129.8,
128.8, 127.4, 127.3, 125.9, 125.2, 124.9, 124.1, 123.4, 122.9,
121.5, 120.2, 119.5, 117.4, 116.2, 32.4, 29.6, 22.7, 13.9. HRMS
(ESI) calculated for C26H22O [M + H]+ 351.1749, found
351.1746.
6-(4-Methoxyphenyl)-11-(p-tolyl)indeno[1,2-c]chromene (3k).
Red solid, H NMR (400 MHz, CDCl3) δ 7.83–7.81 (m, 2H),
1
7.73 (dd, J = 8.0, 1.2 Hz, 1H), 7.60 (d, J = 7.6 Hz, 1H),
7.47–7.45 (m, 2H), 7.43–7.26 (m, 6H), 7.11–7.03 (m, 4H), 3.90
(s, 3H), 2.48 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.2,
152.6, 150.1, 144.3, 136.9, 133.6, 131.1, 129.8, 129.6, 127.5,
126.5, 126.2, 126.1, 124.8, 124.1, 123.8, 122.6, 121.4, 120.2,
119.3, 117.6, 116.9, 114.1, 55.4, 21.4. HRMS (ESI) calculated
for C30H22O2 [M + H]+ 415.1698, found 415.1694.
6-Butyl-11-(p-tolyl)indeno[1,2-c]chromene (3f). Yellow solid,
1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.2 Hz, 1H), 7.69
(dd, J = 8.0, 0.9 Hz, 1H), 7.44–7.32 (m, 8H), 7.29–7.25 (m,
1H), 7.04–7.01 (m, 1H), 3.21 (t, J = 7.6 Hz, 2H), 2.47 (s, 3H),
1.97–1.90 (m, 2H), 1.59–1.53 (m, 2H), 1.01 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ 157.0, 149.9, 144.2, 136.8,
133.7, 129.9, 129.8, 129.5, 127.3, 125.9, 125.2, 124.9, 124.0,
123.2, 122.8, 121.5, 120.3, 119.6, 117.4, 116.3, 32.3, 29.6, 22.7,
21.4, 14.0. HRMS (ESI) calculated for C27H24O [M + H]+
365.1905, found 365.1890.
11-(4-Chlorophenyl)-6-(4-methoxyphenyl)-2-methylindeno-
[1,2-c]chromene (3l). Red solid, H NMR (400 MHz, CDCl3) δ
1
7.83 (d, J = 8.4 Hz, 2H), 7.61–7.59 (m, 1H), 7.53 (m, 4H), 7.47
(s, 1H), 7.37–7.32 (m, 3H), 7.16–7.10 (m, 4H), 3.95 (s, 3H),
2.24 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.3, 153.1,
148.3, 143.8, 135.3, 133.8, 133.1, 131.5, 131.1, 129.8, 128.9,
126.5, 126.0, 124.5, 124.4, 124.2, 122.7, 121.4, 119.5, 118.9,
117.5, 116.6, 114.1, 55.5, 21.3. HRMS (ESI) calculated for
C30H21ClO2 [M + H]+ 449.1308, found 449.1326.
6-(4-Chlorophenyl)-11-phenylindeno[1,2-c]chromene (3m). Red
1
11-Phenyl-6-(p-tolyl)indeno[1,2-c]chromene (3g). Red solid,
1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.68
(dd, J = 8.0, 1.2 Hz, 1H), 7.60–7.53 (m, 5H), 7.48–7.40 (m,
4H), 7.37–7.28 (m, 3H), 7.11–7.03 (m, 2H), 2.51 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 152.9, 150.1, 144.3, 140.8,
136.7, 130.9, 130.0, 129.8, 129.45, 129.43, 128.9, 127.6, 127.4,
126.6, 126.3, 124.8, 124.2, 123.8, 122.7, 121.5, 120.1, 119.3,
117.7, 117.0, 21.7. HRMS (ESI) calculated for C29H20O
[M + H]+ 385.1592, found 385.1579.
solid, H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.4 Hz, 2H),
7.67 (dd, J = 8.0, 1.2 Hz, 1H), 7.60–7.56 (m, 6H), 7.52–7.42
(m, 3H), 7.37–7.30 (m, 3H), 7.14–7.05 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ 151.2, 150.0, 144.5, 136.7, 136.5, 132.2,
130.9, 129.9, 129.5, 129.1, 128.9, 127.8, 127.5, 126.92, 126.86,
124.9, 124.4, 123.7, 122.9, 121.3, 119.9, 119.5, 117.6. HRMS
(ESI) calculated for C28H17ClO [M + H]+ 405.1046, found
405.1024.
6-(4-Chlorophenyl)-11-(p-tolyl)indeno[1,2-c]chromene (3n). Red
1
11-(4-Chlorophenyl)-6-(p-tolyl)indeno[1,2-c]chromene (3h). Red
solid, H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.4 Hz, 2H),
1
solid, H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.0 Hz, 2H),
7.72 (dd, J = 8.0, 1.2 Hz, 1H), 7.60–7.58 (m, 2H), 7.51–7.41
(m, 4H), 7.37–7.29 (m, 5H), 7.13–7.06 (m, 2H), 2.50 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 151, 150.0, 144.6, 137.2, 136.6,
134.2, 133.3, 132.2, 131.0, 129.7, 129.6, 129.1, 128.8, 127.7,
126.9, 124.9, 124.3, 123.5, 122.9, 121.3, 120.1, 119.5, 117.6,
21.5. HRMS (ESI) calculated for C29H19ClO [M + H]+
419.1203, found 419.1191.
7.66 (dd, J = 8.0, 1.2 Hz, 1H), 7.58–7.56 (m, 1H), 7.56–7.52
(m, 4H), 7.47–7.41 (m, 3H), 7.36–7.32 (m, 3H), 7.12–7.10 (m,
2H), 2.52 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 153.2, 150.2,
143.9, 140.9, 135.2, 134.2, 133.2, 131.5, 130.8, 129.8, 129.5,
129.4, 129.2, 127.9, 126.6, 124.7, 124.3, 122.8, 121.6, 119.8,
119.0, 117.8, 117.0, 21.7. HRMS (ESI) calculated for
C29H19ClO [M + H]+ 419.1203, found 419.1178.
6-(4-Chlorophenyl)-2-methyl-11-phenylindeno[1,2-c]chromene
(3o). Red solid, 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J =
8.0 Hz, 2H), 7.60–7.56 (m, 6H), 7.51–7.45 (m, 3H), 7.39–7.32
2-Methyl-11-phenyl-6-(p-tolyl)indeno[1,2-c]chromene (3i). Red
1
solid, H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.0 Hz, 2H),
8248 | Org. Biomol. Chem., 2012, 10, 8244–8250
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(m, 3H), 7.14–7.09 (m, 2H), 2.19 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 151.2, 148.2, 144.4, 136.5, 133.9, 132.3, 130.9, 129.9,
129.54, 129.51, 129.1, 128.8, 127.5, 126.8, 126.5, 124.8, 123.8,
122.8, 121.3, 119.6, 119.4, 117.3, 21.2. HRMS (ESI) calculated
for C29H19ClO [M + H]+ 419.1203, found 419.1178.
126.4, 124.9, 124.1, 123.7, 122.7, 121.5, 120.3, 119.3, 117.6,
117.1, 21.6, 21.5. HRMS (ESI) calculated for C30H23O:
399.1749 (M + H+), found 399.1758.
6,11-Dibutylindeno[1,2-c]chromene (3v). 1H NMR (400 MHz,
CDCl3) δ 8.11 (s, 1H), 7.90 (d, J = 7.4 Hz, 1H), 7.64 (d, J = 8.0
Hz, 1H), 7.44–7.41 (m, 2H), 7.34–7.32 (m, 3H), 3.17–3.11 (m,
4H), 1.91–1.88 (m, 2H), 1.74–1.73 (m, 2H), 1.57–1.53 (m, 4H),
1.25 (m, 4H), 1.00 (t, J = 7.1 Hz, 6H). 13C NMR (100 MHz,
CDCl3) δ 155.5, 149.9, 144.0, 130.1, 126.8, 125.7, 125.0, 124.3,
122.6, 122.2, 121.5, 121.2, 118.4, 117.5, 116.2, 32.1, 31.3, 29.6,
26.1, 23.2, 22.7, 14.2, 13.9. HRMS (ESI) calculated for
C24H27O: 331.2062 (M + H+), found 331.2066.
6,11-Bis(4-chlorophenyl)-2-methylindeno[1,2-c]chromene (3p).
1
Red solid, H NMR (400 MHz, CDCl3) δ 7.83–7.81 (m, 2H),
7.61–7.59 (m, 2H), 7.55–7.46 (m, 6H), 7.36–7.33 (m, 3H),
7.18–7.10 (m, 2H), 2.24 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ 151.5, 148.2, 144.1, 136.6, 135.0, 134.1, 133.3, 132.2, 131.4,
130.9, 129.4, 129.13, 129.09, 129.07, 126.9, 124.9, 124.6,
124.1, 122.9, 121.4, 119.4, 119.1, 117.5, 21.3. HRMS (ESI) cal-
culated for C29H18Cl2O [M + H]+ 453.0813, found 453.0780.
6,11-Dicyclopropylindeno[1,2-c]chromene (3w). 1H NMR
(400 MHz, CDCl3) δ 8.67–8.66 (m, 1H), 8.07 (d, J = 7.3 Hz,
1H), 7.93 (d, J = 7.3 Hz, 1H), 7.45–7.42 (m, 1H), 7.33–7.29 (m,
4H), 2.76–2.75 (m, 1H), 2.08–2.07 (m, 1H), 1.39–1.28 (m, 2H),
1.24–1.18 (m, 4H), 0.75–0.74 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ 154.9, 149.5, 144.3, 130.2, 126.9, 126.7, 125.4, 125.2,
124.2, 123.9, 122.4, 121.5, 120.9, 119.9, 116.8, 116.2, 12.8, 8.2,
7.7. HRMS (ESI) calculated for C22H19O: 299.1436 (M + H+),
found 299.1440.
2-Chloro-6-(4-chlorophenyl)-11-phenylindeno[1,2-c]chromene
1
(3q). Red solid, H NMR (400 MHz, CDCl3) δ 7.83 (m, 2H),
7.62–7.51 (m, 9H), 7.38–7.36 (3H), 7.28–7.27 (m, 1H),
7.17–7.13 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 148.4,
136.8, 135.6, 134.3, 131.9, 130.9, 129.7, 129.5, 129.2, 129.1,
127.9, 127.7, 127.1, 124.2, 123.4, 121.4, 121.3, 119.8, 118.9.
HRMS (ESI) calculated for C28H16Cl2O [M + H]+ 439.0656,
found 439.0635.
2,8-Dimethyl-6,11-diphenylindeno[1,2-c]chromene (3x). 1H NMR
(400 MHz, CDCl3) δ 7.66 (d, J = 7.8 Hz, 3H), 7.52–7.50 (m,
4H), 7.46–7.44 (m, 3H), 7.02 (m, 2H), 6.89 (d, J = 7.3 Hz, 2H),
6.69 (d, J = 7.3 Hz, 2H), 2.19 (s, 3H), 2.16 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 147.0, 142.4, 140.5, 137.3, 135.5, 134.1,
130.0, 130.3, 129.6, 129.1, 128.6, 128.5, 128.0, 127.9, 127.4,
127.3, 127.0, 122.8, 122.1, 119.0, 117.4, 110.5, 21.4. HRMS
(ESI) calculated for C30H23O: 399.1749 (M + H+), found
399.1764.
8-Methyl-6,11-diphenylindeno[1,2-c]chromene (3r). Red solid,
1H NMR (400 MHz, CDCl3) δ 7.89–7.87 (m, 2H), 7.67–7.53
(m, 8H), 7.47–7.41 (m, 2H), 7.31–7.21 (m, 3H), 7.16–7.14 (m,
1H), 7.06–7.02 (m, 1H), 2.30 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 152.3, 150.0, 142.1, 136.8, 133.9, 132.4, 130.5, 130.1,
129.9, 129.6, 128.8, 128.7, 127.8, 127.5, 127.4, 126.5, 124.7,
124.2, 123.0, 121.9, 120.2, 119.1, 117.6, 117.3, 21.8. HRMS
(ESI) calculated for C29H20O [M + H]+ 385.1592, found
385.1590.
6,11-Bis(4-chlorophenyl)indeno[1,2-c]chromene (3y). 1H NMR
(400 MHz, CDCl3) δ 7.84 (d, J = 6.9 Hz, 2H), 7.64–7.60 (m,
3H), 7.55–7.50 (m, 6H), 7.35–7.33 (m, 3H), 7.13–7.10 (m, 2H).
13C NMR (100 MHz, CDCl3) δ 136.8, 135.0, 133.3, 132.1,
131.4, 131.0, 129.2, 128.0, 127.0, 125.4, 124.8, 124.5, 123.1,
121.4, 119.8, 119.2, 117.8. HRMS (ESI) calculated for
C28H17Cl2O: 439.0656 (M + H+), found 439.0648.
8-Chloro-6,11-diphenylindeno[1,2-c]chromene (3s). Red solid,
1H NMR (400 MHz, CDCl3) δ 7.89–7.87 (m, 2H), 7.67–7.66
(m, 4H), 7.59–7.56 (m, 4H), 7.51–7.45 (m, 3H), 7.36–7.32 (m,
1H), 7.30–7.25 (m, 2H), 7.10–7.07 (m, 1H). 13C NMR
(100 MHz, CDCl3) δ 153.7, 150.1, 142.6, 136.2, 134.3, 133.3,
130.9, 129.9, 129.4, 128.98, 128.95, 128.5, 127.9, 127.6, 126.7,
125.8, 124.8, 124.5, 124.2, 121.4, 120.1, 119.9, 117.7, 116.5.
HRMS (ESI) calculated for C28H17ClO [M + H]+ 405.1046,
found 405.1033.
1,1′-(Indeno[1,2-c]chromene-6,11-diylbis(4,1-phenylene))-
diethanone (3z). 1H NMR (400 MHz, CDCl3) δ 8.21–8.15 (m,
4H), 8.02–8.00 (m, 2H), 7.71–7.69 (m, 3H), 7.51–7.49 (m, 2H),
7.35 (m, 3H), 7.12 (m, 2H), 2.74 (s, 3H), 2.72 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 197.9, 197.4, 151.5, 150.0, 143.9,
141.9, 138.5, 137.9, 136.2, 130.3, 129.9, 129.4, 129.0, 128.7,
128.2, 127.2, 125.7, 124.8, 124.6, 124.3, 123.3, 121.5, 119.6,
119.2, 117.8, 26.8, 26.7. HRMS (ESI) calculated for
C32H23O3: 455.1647 (M + H+), found 455.1662.
6,11-Bis(4-methoxyphenyl)indeno[1,2-c]chromene (3t). 1H NMR
(400 MHz, CDCl3) δ 7.83 (d, J = 7.8 Hz, 2H), 7.73–7.71 (m,
1H), 7.61–7.59 (m, 1H), 7.49 (d, J = 8.2 Hz, 2H), 7.44–7.42
(m, 1H), 7.38–7.36 (m, 1H), 7.29 (d, J = 6.9 Hz, 2H), 7.12–7.05
(m, 6H), 3.93 (s, 3H), 3.92 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 161.3, 158.9, 152.5, 150.2, 144.5, 131.1, 129.9, 128.8,
127.5, 126.5, 126.1, 125.9, 124.8, 124.1, 123.8, 122.6, 121.4,
120.3, 119.3, 117.6, 114.3, 114.1, 113.8, 55.4, 55.3. HRMS
(ESI) calculated for C30H23O: 431.1647 (M + H+), found
431.1640.
Acknowledgements
Financial support from the National Natural Science Foundation
of China (Nos. 21032007, 21172038) is gratefully acknowledged.
6,11-Di-p-tolylindeno[1,2-c]chromene (3u). 1H NMR (400 MHz,
CDCl3) δ 7.78–7.72 (m, 3H), 7.56 (d, J = 7.8 Hz, 1H),
7.48–7.45 (m, 2H), 7.42–7.39 (m, 2H), 7.36–7.35 (m, 3H),
7.33–7.30 (m, 3H), 7.09–7.06 (m, 2H), 2.51 (s, 3H), 2.49 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 152.8, 150.2, 144.4, 140.7,
137.0, 133.6, 131.0, 129.8, 129.6, 129.4, 128.4, 127.6, 126.5,
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8250 | Org. Biomol. Chem., 2012, 10, 8244–8250
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