Synthesis of indeno[1,2-c ]furans via a pd-catalyzed bicyclization of 2-alkynyliodobenzene and propargylic alcohol

Article abstract of DOI:10.1021/jo302223y

A general and efficient synthesis of indeno[1,2]furans via a Pd-catalyzed bicyclization reaction between 2-alkynyliodobenzenes and propargylic alcohols is described. The procedure furnishes indeno[1,2]furans with moderate to excellent yields (51%-78%) and a broad substrate scope. The cascade process combines the formation of one C-O bond and two C-C bonds in a single step.

Full text of DOI:10.1021/jo302223y

Note
pubs.acs.org/joc
Synthesis of Indeno[1,2‑c]furans via a Pd-Catalyzed Bicyclization of
2‑Alkynyliodobenzene and Propargylic Alcohol
Jisong Jin, Yan Luo, Chao Zhou, Xiaopeng Chen, Qiaodong Wen, Ping Lu,* and Yanguang Wang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
S
* Supporting Information
ABSTRACT: A general and efficient synthesis of indeno[1,2]furans
via a Pd-catalyzed bicyclization reaction between 2-alkynyliodoben-
zenes and propargylic alcohols is described. The procedure furnishes
indeno[1,2]furans with moderate to excellent yields (51%−78%) and
a broad substrate scope. The cascade process combines the formation
of one C−O bond and two C−C bonds in a single step.
used heterocyclic compounds are important substructures
in many natural products and drugs.1−3 Among these fused
Scheme 1. Formation of 2 from 1
F
heterocycles, O-containing heterocycles act in an important and
indispensable role, such as the tricyclic indenofurans, which are
key substructures of (−)-galiellalactone,4 GR-24,5 leucoscept-
roid A,6,7 and ramelteon8 as well. Due to their biological
importance, a growing number of methods have been
developed to prepare various indenofurans. Among these,
there is only one publication related to the construction of the
indeno[1,2-c]furan skeleton which started from o-lithiated
aryloxiranes and α,β-unsaturated malonates via Micheal
addition and a sequential ring opening of oxirane.9
Recently, synthesis of fused heterocyclic compounds through
Pd-catalyzed bicyclization from alkyne has attracted significant
attention.10−15 These reactions construct fused-heterocycles in
cascade approach with high atom efficiency and fit the basic
requirements of green chemistry.16−20 For instance, our group
developed a cascade construction of 8H-acenaphtho[1,2-
c]pyrroles from 1,8-diarenynyl naphthalenes and primary
amines through an aminopalladation and a sequential
carbopalladation over two triple bonds.21 Wu and co-workers
revealed that fused heterocycles containing an indene skeleton
could be synthesized via a palladium-catalyzed bicyclization of
amine, phenol, or amide across two triple bonds.22−27
Nevertheless, to our knowledge, the preparation of indenofur-
ans via this cascade process was never reported. Herein, we
would like to report a palladium-catalyzed bicyclization
between 2-alkynyliodobenzene and propargylic alcohol, which
furnished the skeleton of indeno[1,2-c]furan in a single step.
Our initial effort focused on the palladium-catalyzed reaction
between 4-(2-iodophenyl)-2-methyl-3-butyn-2-ol (1) and ani-
line to construct an indole or quinoline skeleton under a
nitrogen atmosphere in DMF at 100 °C for 12 h (Scheme 1).
To our surprise, we obtained 2 in a 40% yield along with a 50%
recovery of 1. Aniline did not participate in the reaction. The
structure of 2 was confirmed by single crystal analysis (Figure
S1). Compound 2 included a tricyclic indeno[1,2-c]furan
substructure, resulting from a self-condensation of two
molecules of 1 accompanied by an elimination of HI. Prompted
by this result and the biological importance of indeno[1,2-
c]furans, we tested the cross-condensation reaction between 3a
and 4a under the same reaction conditions. In this manner,
product 5a was obtained in 38% yield.
Then we focused our attention toward optimizing the
reaction conditions, and the results are listed in Table 1.
Pd(OAc)2 presented the highest efficiency in comparison with
PdCl2, Pd(PPh3)4, and PdCl2(PPh3)2 (Table1, entries 1−4).
When PdCl2(PPh3)2 was used, only a trace amount of 5a was
detected by TLC, which indicated that this could be a
phosphine ligand free reaction. K2CO3 was found to be the best
base additive (Table 1, entries 5−8). No desired product was
detected when strong bases, such as DBU and KOH, were used
which indicated that addition of a suitable base additive was
critical to approach a practical reaction. The optimal solvent
was determined to be DMF (Table 1, entries 9−14). Both
lowering the reaction temperature to 90 °C and raising the
reaction temperature to 130 °C would decrease the yield of 5a
(Table 1, entries 15 and 16). It was noticeable that this reaction
could be conducted under air or by using 4 Å MS instead of
anhydrous MgSO4, but with slightly lower yields (Table 1,
entries 17 and 18). The suitable reaction time was found to be
12 h. Shortening the reaction time would decrease the yield
(entry 19), while extending the reaction time was not
necessary.
Received: October 10, 2012
Published: November 30, 2012
© 2012 American Chemical Society
11368
dx.doi.org/10.1021/jo302223y | J. Org. Chem. 2012, 77, 11368−11371

The Journal of Organic Chemistry
Note
Table 1. Screening of Reaction Conditions for the
Formation of 5a
Table 2. Pd-Catalyzed Reaction of 2-Alkynyliodobenzenes 3
with Propargylic Alcohols 4
a
a
temp
yield
b
b
entry
[Pd]
base
solvent
(°C)
(%)
entry
3 (R1/X)
3a (H/I)
4 (R2/R3/R4)
4a (Ph/Me/Me)
5/yield (%)
1
Pd(OAc)2
PdCl2(PPh3)2
Pd(PPh3)4
PdCl2
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Bu4N+OH−
DBU
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMAc
DMSO
Et3N
110
110
110
110
110
110
110
110
110
110
reflux
reflux
reflux
110
90
75
1
5a/75
5b/72
5c/60
5d/65
5e /51
5f/61
5g/67
5h/53
2
trace
36
2
3a
4b (p-MeC6H4/Me/Me)
3
3
3a
4c (p-MeOC6H4/Me/Me)
4
72
4
3a
4d (p-PhC6H4/Me/Me)
5
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
45
5
3a
4e (p-MeCOC6H4/Me/Me)
6
15
6
3a
4f (p-NO2C6H4/Me/Me)
7
0
7
3a
4g (3-thiophenyl/Me/Me)
8
KOH
0
8
3a
4h (3-thiophenyl/-(CH2)5-)
c
9
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
35
9
3a
4i (o-MeOC6H4/Me/Me)
−
−
−
−
c
10
11
12
13
14
15
16
29
10
11
12
13
14
15
16
17
18
19
20
3a
4j (m-MeC6H4/Me/Me)
c
trace
trace
trace
31
3a
4k (1-naphthalenyl/Me/Me)
c
CH3CN
CCl4
3a
4l (Ph/Ph/Me)
3b (Me/I)
3c (OMe/I)
3d (n-Bu/I)
3e (F/I)
3f (COMe/I)
3g (H/Br)
3h (OMe/Br)
3i (F/Br)
4a
4a
4a
4a
4a
4a
4a
4a
5i/56
5j/62
5k/55
5l /78
5m/66
5a/61
5j/57
5l /53
toluene
DMF
DMF
DMF
DMF
DMF
56
130
110
110
110
52
c
17
63
d
18
e
56
19
58
a
Reaction conditions: Reaction was conducted under N2 with 3a (0.5
mmol), 4a (0.75 mmol), Pd catalyst (5 mol %, 0.025 mmol), base (1
a
Reaction conditions: 3 (0.5 mmol), 4 (0.75 mmol), Pd(OAc)2 (5
mol %), K2CO3 (1 mmol), MgSO4 (2 mmol), and DMF (2 mL) were
mixed and reacted at 110 °C for 12 h under nitrogen. Isolated yield.
mmol), and anhydrous MgSO4 (2 mmol) in solvent (2 mL) for 12 h
b
c
d
b
unless specially indicated. Isolated yield. Under air. Using 4 Å MS
e
c
instead of anhydrous MgSO4. 8 h.
Recovery of propargylic alcohol.
With optimized reaction conditions in hand, the substrate
scope of this palladium-catalyzed tandem reaction was then
investigated (Table 2). With respect to propargylic alcohols 4,
the yields were not apparently affected by either electron-
donating or -withdrawing groups on the R2 moiety. The desired
products 4a−4f were isolated in moderate yields ranging from
51% to 75% (Table 2, entries 1−6). Single crystal analysis of 5d
further supported the products containing an indeno[1,2-
c]furan substructure. 4g and 4h, both with the thiophene,
afforded the corresponding 5g and 5h in moderate yields,
indicating that the thiophene ring tolerated this palladium-
catalyzed bicyclization (Table 2, entries 7 and 8). However, the
o-MeOC6H4 substituted 4i did not react although 3a was
completely consumed as indicated by TLC (Table 2, entry 9).
A similar result was observed for 4j−4l (Table 2, entries 10−
12). The possible reason might be the steric hindrance. We also
tested the substituent effect of R1 in 3 on this transformation. If
the substituent was an electron-donating group, such as methyl,
methoxy, and n-butyl, the yields decreased to 56%, 62%, and
55%, respectively (Table 2, entries 13−15). A slightly increased
yield was obtained when the substituent group was fluorine
(Table 2, entry 16). However, when we changed the C6H4R1
group of 3 into alkyl, such as 1-(hept-1-yn-1-yl)-2-iodobenzene,
no corresponding product was isolated with the recovery of two
starting materials. By altering 1-iodo-2-(phenylethynyl)benzene
(3a) to 1-bromo-2-(phenylethynyl)benzene (3g), we isolated
5a in a relatively lower yield (61%, Table 2, entry 18). Similarly,
1-bromo-2-(phenylethynyl)benzenes 3h (Table 2, entry 19)
and 3i (Table 2, entry 20) also gave lower yields of 5j (57%)
and 5l (53%) because of the relative reactivity of C−X bonds
for the oxidative addition of palladium. With further alternation
of bromo in 3g to chloro, the desired product 5a was not
detected with the recovery of two starting materials.
The plausible mechanism for this transformation is proposed
in Scheme 2. First, oxidative addition of palladium into the C−
X bond of 3 generates intermediate A. A cooperates with
propargylic alcohol 4 to form complex B, which then undergoes
Scheme 2. Proposed Mechanism for the Formation of 5
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The Journal of Organic Chemistry
Note
120.2, 86.7, 27.2. HRMS (EI) Calcd. for [C25H20O] ([M]+): 336.1514,
found: 336.1510.
a syn-carbopalladation to form complex C. Subsequently, a syn-
carbopalladation occurs, resulting in the formation of D, in
which palladium coordinated with the hydroxyl group. Finally,
assisted by a proper base, a reductive elimination affords
indeno[1,2-c]furan 5. During this cascade progress, one C−O
bond and two C−C bonds were formed in a single step.
Compared with classic C−C and C−O bond formation, this
strategy seems to be more effective and convenient as starting
materials, 2-alkynyliodobenzene and propargylic alcohols, were
easily prepared.28
1,1-Dimethyl-3-phenyl-8-(p-tolyl)-1H-indeno[1,2-c]furan
(5b). Rf = 0.3 (petroleum ether/DCM = 10:1). Yellow solid (126 mg,
1
72%), mp 145−146 °C. H NMR (400 MHz, CDCl3) δ 8.14 (d, J =
7.1 Hz, 2H), 8.03 (d, J = 7.4 Hz, 1H), 7.63−7.55 (m, 3H), 7.47 (d, J =
7.8 Hz, 3H), 7.28 (m, 5H), 2.48 (s, 3H), 1.74 (s, 6H). 13C NMR (100
MHz, CDCl3) δ 159.0, 152.5, 147.4, 136.6, 132.3, 131.1, 130.8, 129.2,
129.1, 128.8, 128.4, 127.6, 125.7, 124.4, 123.2, 121.3, 120.8, 120.2,
86.6, 27.2, 21.4. HRMS (EI) Calcd. for [C26H22O] ([M]+): 350.1671,
found: 350.1674.
8-(4-Methoxyphenyl)-1,1-dimethyl-3-phenyl-1H-indeno[1,2-
c]furan (5c). Rf = 0.3 (petroleum ether/DCM = 8:1). Yellow solid
(110 mg, 60%), mp 141−142 °C. 1H NMR (400 MHz, CDCl3) δ 8.11
(d, J = 7.6 Hz, 2H), 8.01 (d, J = 7.4 Hz, 1H), 7.64−7.52 (m, 3H), 7.48
(d, J = 8.4 Hz, 2H), 7.44 (d, J = 7.6 Hz, 1H), 7.26 (tt, J = 14.8, 7.3 Hz,
2H), 7.04 (d, J = 8.3 Hz, 2H), 3.91 (s, 3H), 1.71 (s, 6H). 13C NMR
(100 MHz, CDCl3) δ 158.8, 158.6, 152.2, 147.4, 131.0, 130.7, 130.2,
128.7, 128.3, 127.6, 125.6, 123.9, 123.1, 121.2, 120.6, 120.0, 113.8,
86.5, 55.3, 27.1. HRMS (EI) Calcd. for [C26H22O2] ([M]+): 366.1620,
found: 366.1620.
In conclusion, we demonstrated a palladium-catalyzed
bicyclization between 2-alkynylhalobenzene and propargylic
alcohols, furnishing indeno[1,2-c]furans with moderate to
excellent yields. A plausible mechanism for this cascade process
is proposed, which involves the formation of one C−O bond
and two C−C bonds in a single step. Regarding the biological
importance of indenofurans, our palladium-catalyzed bicycliza-
tion would find applications in pharmaceutical chemistry.
8-([1,1′-Biphenyl]-4-yl)-1,1-dimethyl-3-phenyl-1H-indeno-
[1,2-c]furan (5d). Rf = 0.2 (petroleum ether/DCM = 10:1). Yellow
solid (134 mg, 65%), mp 155−156 °C. 1H NMR (400 MHz, CDCl3) δ
8.16 (d, J = 7.6 Hz, 2H), 8.06 (d, J = 7.5 Hz, 1H), 7.75 (t, J = 6.1 Hz,
4H), 7.69−7.50 (m, 8H), 7.42 (t, J = 7.3 Hz, 1H), 7.37−7.25 (m, 2H),
1.78 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 159.4, 152.9, 147.0,
140.8, 139.5, 134.3, 130.9, 130.9, 129.5, 128.8, 128.8, 128.4, 127.6,
127.3, 127.1, 127.0, 125.7, 123.9, 123.2, 121.3, 120.8, 120.2, 86.7, 27.1.
HRMS (EI) Calcd. for [C31H24O] ([M]+): 412.1827, found: 412.1828.
1-(4-(1,1-Dimethyl-3-phenyl-1H-indeno[1,2-c]furan-8-yl)-
phenyl)ethanone (5e). Rf = 0.2 (petroleum ether/DCM = 6:1).
EXPERIMENTAL SECTION
■
1
General Methods. H NMR spectra were recorded at 400 or 500
MHz using TMS as an internal standard and 13C NMR spectra at 100,
or 125 MHz using CDCl3. High resolution mass spectra (HRMS)
were performed on an electron ionization time-of-flight (EI-TOF)
mass spectrometer. Melting points were measured with a micro
melting point apparatus.
The 2-alkynyliodobenzenes 3 and propargylic alcohols 4 were
prepared by the Sonogashira reaction according to the published
methods.29 Other materials were purchased from common commercial
sources and used without additional purification.
Procedure for Synthesis of Compound 2. A 10 mL round-
bottom flask was charged with 4-(2-iodophenyl)-2-methyl-3-butyn-2-
ol (1) (0.5 mmol), Pd(OAc)2 (0.025 mmol) and dry DMF (2 mL).
The reaction mixture was stirred at 100 °C (oil bath) under N2 for 12
h. After cooling to room temperature, the resultant mixture was added
to 30 mL of water, extracted with DCM (3 × 5 mL), and dried over
Na2SO4. The dichloromethane was evaporated under reduced pressure
and the residue was purified by flash column chromatography on a
silica gel to give the product 2.
General Procedures for the Reaction of 2-Alkynyliodoben-
zene 3 with Propargylic Alcohol 4. A 10 mL round-bottom flask
was charged with 2-alkynyliodobenzene 3 (0.5 mmol), propargylic
alcohol 4 (0.75 mmol), K2CO3 (1 mmol), MgSO4 (2 mmol),
Pd(OAc)2 (0.025 mmol) and dry DMF (2 mL). The reaction mixture
was stirred at 110 °C (oil bath) under N2 for 12 h. After cooling to
room temperature, the resultant mixture was added to 30 mL of water,
extracted with DCM (3 × 5 mL), and dried over Na2SO4. The
dichloromethane was evaporated under reduced pressure and the
residue was purified by flash column chromatography on a silica gel to
give the products.
2-(8-(2-Iodophenyl)-1,1-dimethyl-1H-indeno[1,2-c]furan-3-
yl)propan-2-ol (2). Rf = 0.2 (petroleum ether/DCM = 6:1). Yellow
solid (89 mg, 40%), mp 169−171 °C. 1H NMR (400 MHz, CDCl3) δ
8.05 (d, J = 7.7 Hz, 1H), 8.00 (d, J = 7.9 Hz, 1H), 7.43 (t, J = 7.4 Hz,
1H), 7.33 (d, J = 7.5 Hz, 1H), 7.20 (dd, J = 12.8, 6.3 Hz, 2H), 7.10 (t,
J = 7.6 Hz, 1H), 6.97 (d, J = 7.0 Hz, 1H), 2.46 (s, 1H), 1.71 (s, 6H),
1.56 (s, 3H), 1.50 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 169.1,
152.3, 146.5, 140.7, 138.9, 131.3, 129.0, 127.7, 127.0, 126.4, 125.2,
123.7, 122.9, 120.1, 118.3, 101.3, 86.7, 71.4, 28.7, 26.8, 25.3. HRMS
(EI) Calcd. for [C22H21IO2] ([M]+): 444.0586, found: 444.0589.
1,1-Dimethyl-3,8-diphenyl-1H-indeno[1,2-c]furan (5a). Rf =
0.3 (petroleum ether/DCM = 10:1). Yellow solid (126 mg, 75%), mp
143−145 °C. 1H NMR (400 MHz, CDCl3) δ 8.15−8.07 (m, 2H), 8.00
(d, J = 7.2 Hz, 1H), 7.62−7.51 (m, 5H), 7.52−7.42 (m, 3H), 7.41−
7.35 (m, 1H), 7.32−7.20 (m, 2H), 1.70 (d, J = 6.0 Hz, 6H). 13C NMR
(100 MHz, CDCl3) δ 159.3, 152.8, 147.2, 135.3, 131.0, 130.9, 129.2,
128.8, 128.45, 128.4, 127.6, 126.9, 125.8, 124.4, 123.2, 121.3, 120.7,
1
Yellow solid (96 mg, 51%), mp 183−184 °C. H NMR (400 MHz,
CDCl3) δ 8.16−8.07 (m, 4H), 8.03 (d, J = 7.4 Hz, 1H), 7.67 (d, J = 8.0
Hz, 2H), 7.60 (q, J = 6.4 Hz, 3H), 7.48 (d, J = 7.4 Hz, 1H), 7.35−7.23
(m, 2H), 2.70 (s, 3H), 1.73 (s, 6H). 13C NMR (100 MHz, CDCl3) δ
197.8, 160.3, 154.0, 146.3, 140.6, 135.4, 131.1, 130.6, 129.1, 128.8,
128.6, 128.4, 127.5, 125.8, 123.4, 123.1, 121.3, 120.8, 119.9, 86.8, 27.0,
26.7. HRMS (EI) Calcd. for [C27H22O2] ([M]+): 378.1620, found:
378.1624.
1,1-Dimethyl-8-(4-nitrophenyl)-3-phenyl-1H-indeno[1,2-
c]furan (5f). Rf = 0.3 (petroleum ether/DCM = 6:1). Yellow solid
(116 mg, 61%), mp 178−181 °C. 1H NMR (400 MHz, CDCl3) δ 8.33
(d, J = 8.3 Hz, 2H), 8.13−8.07 (m, 2H), 8.02 (d, J = 7.4 Hz, 1H), 7.70
(d, J = 8.3 Hz, 2H), 7.59 (d, J = 6.5 Hz, 3H), 7.44 (d, J = 7.5 Hz, 1H),
7.35−7.24 (m, 2H), 1.72 (s, 6H). 13C NMR (100 MHz, CDCl3) δ
161.2, 155.1, 146.4, 145.7, 142.7, 131.4, 130.4, 129.5, 128.9, 128.5,
127.4, 125.9, 123.9, 123.7, 121.9, 121.4, 120.9, 119.7, 86.9, 27.1.
HRMS (EI) Calcd. for [C25H19NO3] ([M]+): 381.1365, found:
381.1368.
1,1-Dimethyl-3-phenyl-8-(thiophen-3-yl)-1H-indeno[1,2-
c]furan (5g). Rf = 0.2 (petroleum ether/DCM = 8:1). Yellow solid
(115 mg, 67%), mp 173−175 °C. 1H NMR (400 MHz, CDCl3) δ 8.12
(d, J = 6.6 Hz, 2H), 8.02 (d, J = 7.5 Hz, 1H), 7.65−7.52 (m, 4H), 7.47
(s, 1H), 7.41 (s, 1H), 7.34 (dd, J = 16.9, 6.1 Hz, 2H), 7.29−7.22 (m,
1H), 1.76 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 159.2, 152.7,
147.0, 135.3, 130.8, 128.8, 128.6, 128.5, 128.3, 127.5, 125.7, 125.4,
123.2, 122.0, 121.2, 120.5, 120.2, 118.8, 86.6, 26.7. HRMS (EI) Calcd.
for [C23H18OS] ([M]+): 342.1078, found: 342.1077.
3′-Phenyl-8′-(thiophen-3-yl)spiro[cyclohexane-1,1′-indeno-
[1,2-c]furan] (5h). Rf = 0.2 (petroleum ether/DCM = 8:1). Yellow
solid (101 mg, 53%), mp 199−201 °C. 1H NMR (400 MHz, CDCl3) δ
8.14 (d, J = 6.8 Hz, 2H), 8.01 (d, J = 7.5 Hz, 1H), 7.58 (dq, J = 10.2,
7.1 Hz, 3H), 7.52−7.44 (m, 2H), 7.39 (d, J = 1.8 Hz, 1H), 7.34
−7.22(m, 3H), 2.01−1.74 (m, 9H), 1.35 (m, 1H).13C NMR (100
MHz, CDCl3) δ 159.4, 153.2, 147.4, 135.5, 131.3, 130.8, 129.1, 128.8,
128.5, 127.5, 125.7, 125.3, 123.1, 122.4, 121.4, 120.9, 120.2, 118.7,
88.2, 35.7, 25.0, 22.9. HRMS (EI) Calcd. for [C26H22OS] ([M]+):
382.1391, found: 382.1393.
1,1-Dimethyl-8-phenyl-3-(p-tolyl)-1H-indeno[1,2-c]furan
(5i). Rf = 0.3 (petroleum ether/DCM = 10:1). Yellow solid (98 mg,
11370
dx.doi.org/10.1021/jo302223y | J. Org. Chem. 2012, 77, 11368−11371

The Journal of Organic Chemistry
Note
1
56%), mp 142−143 °C. H NMR (400 MHz, CDCl3) δ 8.05 (d, J =
REFERENCES
■
7.7 Hz, 3H), 7.59 (d, J = 7.9 Hz, 2H), 7.51 (dd, J = 12.8, 5.6 Hz, 3H),
7.42 (t, J = 8.5 Hz, 3H),7.34−7.25(m,, 2H), 2.52 (s, 3H), 1.75 (s, 6H).
13C NMR (100 MHz, CDCl3) δ 159.7, 152.9, 147.1, 141.4, 135.5,
129.5, 129.3, 128.5, 128.4, 128.2, 127.6, 126.8, 125.5, 123.9, 123.1,
121.3, 120.2, 120.1, 86.6, 27.2, 21.8. HRMS (EI) Calcd. for [C26H22O]
([M]+): 350.1671, found: 350.1668.
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Chen, T.-W.; Lin, C.-H.; Chang, Y.-L.; Chang, Y.-Y.; Lo, Y.-K.; Tseng,
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Chen, C.-T. J. Med. Chem. 2003, 46, 1706.
3-(4-Methoxyphenyl)-1,1-dimethyl-8-phenyl-1H-indeno[1,2-
c]furan (5j). Rf = 0.2 (petroleum ether/DCM = 8:1). Yellow solid
(113 mg, 62%), mp 146−147 °C. 1H NMR (400 MHz, CDCl3) δ 8.10
(d, J = 8.3 Hz, 2H), 8.02 (d, J = 7.4 Hz, 1H), 7.56 (d, J = 7.9 Hz, 2H),
7.49 (t, J = 7.6 Hz, 3H), 7.38 (t, J = 7.2 Hz, 1H), 7.33−7.20 (m, 2H),
7.11 (d, J = 8.4 Hz, 2H), 3.93 (s, 3H), 1.71 (s, 6H). 13C NMR (100
MHz, CDCl3) δ 161.7, 159.6, 152.9, 146.8, 135.5, 130.2, 129.2, 128.4,
127.4, 126.7, 125.3, 123.4, 122.9, 121.1, 120.0, 119.3, 114.2, 86.5, 55.5,
27.2. HRMS (EI) Calcd. for [C26H22O2] ([M]+): 366.1620, found:
366.1619.
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Chen, M. S.; Shi, Q.; Lee, K.-H. J. Med. Chem. 2004, 47, 5140.
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K.; Miyamoto, M.; Ohkawa, S. J. Med. Chem. 2002, 45, 4222.
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1947.
3-(4-Butylphenyl)-1,1-dimethyl-8-phenyl-1H-indeno[1,2-
c]furan (5k). Rf = 0.2 (petroleum ether/DCM = 10:1). Yellow solid
1
(108 mg, 55%), mp 113−115 °C. H NMR (400 MHz, CDCl3) δ
8.10−8.01 (m, 3H), 7.57 (d, J = 4.7 Hz, 2H), 7.54−7.45 (m, 3H), 7.42
(d, J = 6.3 Hz, 3H),7.31−7.25(m, 2H), 2.76 (t, J = 6.7 Hz, 2H), 1.72
(d, J = 2.9 Hz, 8H), 1.45 (dd, J = 12.8, 6.8 Hz, 2H), 1.08−0.96 (m,
3H). 13C NMR (100 MHz, CDCl3) δ 159.8, 152.9, 147.1, 146.4, 135.5,
129.3, 128.9, 128.4, 128.4, 128.4, 127.6, 126.8, 125.5, 123.9, 123.1
121.3, 120.2, 120.1, 86.6, 35.9, 33.5, 27.2, 22.4, 14.0. HRMS (EI)
Calcd. for [C29H28O] ([M]+): 392.2140, found: 392.2141.
3-(4-Fluorophenyl)-1,1-dimethyl-8-phenyl-1H-indeno[1,2-
c]furan (5l). Rf = 0.3 (petroleum ether/DCM = 8:1). Yellow solid
(138 mg, 78%), mp 143−144 °C. 1H NMR (400 MHz, CDCl3) δ 8.12
(dd, J = 8.5, 5.5 Hz, 2H), 7.96 (d, J = 7.4 Hz, 1H), 7.55 (d, J = 7.1 Hz,
2H), 7.53−7.43 (m, 3H), 7.40 (t, J = 7.2 Hz, 1H), 7.34−7.21 (m,4H),
1.71 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 165.2 (1JC−F = 200 Hz),
158.1, 152.7, 147.3, 135.2, 130.6 (3JC−F = 7 Hz), 129.2, 128.5, 127.5,
127.3 (4JC−F = 3 Hz), 127.0, 125.8, 124.5, 123.3, 121.1, 120.5, 120.3,
116.2 (2JC−F = 21 Hz), 86.8, 27.2. HRMS (EI) Calcd. for [C25H19OF]
([M]+): 354.1420, found: 354.1418.
́
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1-(4-(1,1-Dimethyl-8-phenyl-1H-indeno[1,2-c]furan-3-yl)-
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phenyl)ethanone (5m). Rf = 0.2 (petroleum ether/DCM = 6:1).
1
Yellow solid (124 mg, 66%), mp 180−181 °C. H NMR (400 MHz,
CDCl3) δ 8.23−8.12 (m, 4H), 7.98 (d, J = 7.5 Hz, 1H), 7.57−7.46 (m,
4H), 7.41 (dd, J = 16.8, 7.5 Hz, 2H), 7.33−7.24(m, 2H), 2.71 (s, 3H),
1.71 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 197.4, 157.3, 152.5,
147.6, 138.2, 135.2, 135.0 129.1, 128.7, 128.5, 128.5, 127.4, 127.2,
126.3, 125.7, 123.6, 122.5, 121.5, 120.4, 86.8, 27.1, 26.8. HRMS (EI)
Calcd. for [C27H22O2] ([M]+): 378.1620, found: 378.1618.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of NMR spectra (1H and 13C) for 3a-3i, 4a-4l, 5a-5m
and crystallographic information (CIF files) for compounds 2
and 5d. This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: pinglu@zju.edu.cn; orgwyg@zju.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors gratefully acknowledge the financial support of the
National Natural Science Foundation of China (Nos. 21272203
and 21032005).
11371
dx.doi.org/10.1021/jo302223y | J. Org. Chem. 2012, 77, 11368−11371