The synthesis of 1,2-diarylindenes via DDQ-mediated dehydrogenative intramolecular cyclization

Article abstract of DOI:10.1016/j.tet.2014.05.088

A direct DDQ-mediated dehydrogenative intramolecular cyclization of (Z)-1,2,3-triaryl substituted propylenes promoted by Cu(OAc)₂ was developed, providing 1,2-diarylindene derivatives in moderate to good yields (up to 92%) under mild conditions

Full text of DOI:10.1016/j.tet.2014.05.088

Accepted Manuscript
The synthesis of 1, 2-diarylindenes via DDQ-mediated dehydrogenative
intramolecular cyclization
Yi Li , Li Cao , Xiaoyan Luo , Wei-Ping Deng
PII:
S0040-4020(14)00794-7
10.1016/j.tet.2014.05.088
TET 25637
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 2 April 2014
Revised Date: 15 May 2014
Accepted Date: 22 May 2014
Please cite this article as: Li Y, Cao L, Luo X, Deng W-P, The synthesis of 1, 2-diarylindenes via
DDQ-mediated dehydrogenative intramolecular cyclization, Tetrahedron (2014), doi: 10.1016/
j.tet.2014.05.088.
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The synthesis of 1,2-diarylindenes via DDQ-
mediated dehydrogenative intramolecular
cyclization
Yi Li, Li Cao, Xiaoyan Luo,* Wei-Ping Deng*
Leave this area blank for abstract info.
Shanghai Key Laboratory of FunctionalMaterials Chemistry & School of Pharmacy,, East China University of
Science and Technology, 130 Meilong Road, Shanghai 200237, China

1
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Tetrahedron
journal homepage: www.elsevier.com
The synthesis of 1, 2-diarylindenes via DDQ-mediated dehydrogenative
intramolecular cyclization
Yi Li, Li Cao, Xiaoyan Luo, Wei-Ping Deng
Shanghai Key Laboratory of FunctionalMaterials Chemistry & School of Pharmacy, East China University of Science and Technology, 130 Meilong Road,
Shanghai 200237, China;
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A direct DDQ-mediated dehydrogenative intramolecular cyclization of (Z)-1,2,3-triaryl
substituted propylenes promoted by Cu(OAc)2 was developed, providing 1,2-diarylindene
derivatives in moderate to good yields (up to 92%) under mild conditions. This protocol
provides a straightforward access to 1,2-diarylindenes via DDQ-mediated benzylic/ allylic sp3
C-H bond activation.
Available online
2014 Elsevier Ltd. All rights reserved
.
Keywords:
Cyclization
Diarylindene
C-H activation
DDQ
1. Introduction
Indene derivatives are important cyclic compounds that serve
as building blocks for biologically active compounds,1 valuable
ligands for indenyl metal complexes,2 as well as functional
materials.3 Thus, a great number of approaches for constructing
indene have been well developed. For example, intramolecular
cyclization of phenyl-substituted allylic alcohols, via an in-situ
formed allylic cation key intermediate, can generate indenes in
good to excellent yields in the presence of strong acid or boron
trifluoride etherate.4 In additionꢀtransition metals were also
widely used for the intermolecular5 or intramolecular6 cyclization
to form indene derivatives. Moreover, transition metals-catalyzed
carbocyclization via C-H activation7 represents a straightforward
and powerful method. However, most of the carbocyclization
reactions for indene formation were rhodium-catalyzed
intermolecular reaction of alkynes with different arene substrates.
To the best of our knowledge, direct intramolecular cyclization
for the synthesis of indene via catalyzed C-H activation has been
rarely reported.7c
Scheme 1. Intermolecular cyclization of (E)-1 via oxidative activation of
terminal allylic C-H bond.
We proposed that the initially formed allylic radical 1-B is
active enough for coupling to another equivalent of (E)-1,
followed by forming the cyclopentene, instead of generating the
allylic cation 1-A via further oxidation. Therefore, we further
envisaged that introduction of a proper substituent on the
terminal methyl group of (E)-1 could inhibit the intermolecular
coupling of allylic radical 1-B. Thus, this relative stable radical
of 1-B analog could then be subjected to a further SET process to
form an allyic cation species, which may facilitate the direct
intramolecular dehydrogenative cyclization. In this paper, we
would like to demonstrate an efficient approach to 1,2-
diarylindene derivatives via DDQ-mediated dehydrogenative
intramolecular cyclization of (Z)-1,2,3-triaryl substituted
propylenes promoted by Cu(OAc)2 .
Recently, we were dedicated to testing the feasibility of direct
intramolecular dehydrogenative cyclization by employing 1,2-
diarylpropylene substrate (E)-1 as model substrate to construct
indene compound via DDQ-mediated oxidative activation of
terminal allylic C–H bond. Interestingly, an unexpected product
1,2,3,4-tetraphenyl cyclopentene was obtained instead of
desired
———
indene compound (Scheme 1).8
e-mail: xyluo@ecust.edu.cn (X. Luo)
e-mail: weiping_deng@ecust.edu.cn (W.-P. Deng)

2
Tetrahedron
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2. Results and discussion
Temp.
(°C)
Yield
(%)b
Entry
Additive
Solvent
Initially, a series of substituted propenes 2-6 were prepared to
test the feasibility of direct cyclization to construct indene ring as
shown in scheme 2. Unfortunately, (E)- and (Z)-2, as well as (E)-
and (Z)-5 all failed to give desired indene products, while (Z)-2
and (E)-5 were found to afford ketone products presumably via
the nucleophilic attack to in-situ formed cations by water instead
of the cyclization. Phenoxy and bromide substituted compounds
(E)-3 and (E)-4 were found not proper for the intramolecular
oxidative cyclization. It should be pointed out that Batey and his
coworkers4c recently reported a synthesis of highly substituted
indenes by treating 1,3-diaryl substituted allylic alcohols with
Lewis acids. They found that 2-unsubstituted (E)-1,3-
diphenylprop-2-en-1-ol was not suitable for the indene formation
as well. To our delight, the cyclization of (Z)-1,2,3-triphenyl
propylene 6 was successful to provide 1,2-diphenyl indene 7 in
44% yield (Table 1, entry 1), although (E)-isomer 6 failed to
afford the desired product 7 presumably due to the steric
hindrance from three adjacent phenyl groups in the step of
DDQ-mediated cation formation.
1
2
/
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
Toluene
THF
80
80
60
r.t.
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
44
68
PdCl2
PdCl2
PdCl2
3
70
4
46
5
44
Pd(OAc)2
FeCl2
6
24
7
20
FeCl3
8
42
CuBr
9
69
CuCl2
10
11
12
13
14
15
16
17
18c
19d
Cu(OAc)2•H2O
92
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
trace
trace
N.R.
N.R.
43
DMSO
1,4-Dioxane
DCM
DCE
70
CH3CN
CH3NO2
CH3NO2
80
85
85
a Unless otherwise noted, the reaction was performed under N2 atmosphere,
with 6a (0.2 mmol) and DDQ (1.4 equiv.), in the presence of 10 mol% of
catalyst in 2 mL of solvent. b Isolated yields. c 5 mol% of catalyst was used. d
DDQ (1.2 equiv.) was used.
With optimized reaction conditions in hand, a series of 1, 2, 3-
triaryl propylene derivatives 6b-i were then investigated.
Substrates with different substituted at para position of ring B
were explored since substituent at C-2 of propylene was
necessary as mentioned before. It was found that substrates with
strong electron-withdrawing groups such as CN and CF3 afforded
slightly higher yields than 4-Cl substituted compound (Scheme 3,
7b-7d). Interestingly, the transformation of substrates with strong
electron-donating substituent such as methoxy group was also
successful (Scheme 3, 7e), unlike the cases of naphthalenes8a and
cyclopentenes8b synthesis, in which the substrates with methoxy
group on aryl ring failed to afford the desired products. It was
also found that bulky 2-naphthyl indene 7f can be obtained, albeit
in lower yield (Scheme 3, 23%). The reaction of substrate 6g
with 4-Cl substituent on both ring A and C underwent also
smoothly, affording the corresponding product in 70% yield
(Scheme 3, 7g). However, only moderate yields were obtained
when substrates containing substituent on all three aryl rings.
(Scheme 3, 7h-7i).
Scheme 2. Substrates investigation for intramolecular dehydrogenative
cyclization
.
Encouraged by this result, we then turned to optimize the
reaction condition as shown in table 1. Initially, palladium salts
which are commonly used in the sp3 C-H bond activation9 were
tested as promoter. To our delight, the yield of 7a was improved
to 70% from 44% by using 10 mol% of PdCl2 at 60 °C (Table 1,
entries 1-3). However, Pd(OAc)2 was found not effective (Table
1, entry 5). Further screening of a series of Fe and Cu salts turned
out that 7a can be obtained in 92% of yield in the presence of
Cu(OAc)2•H2O (Table 1, entries 6-10). Other solvents were
tested and nitromethane was found most suitable (Table 1, entries
11-17). Moreover, decreasing the amount of DDQ or
Cu(OAc)2•H2O slightly decreased the yield (Table 1, entries 18-
19).
Table 1. Optimization of reaction conditions for the formation
of compound 7aa
Further investigation of mono-substituted substrates suggested
a substituent effect on regioselectivity of cyclization. It should be
noticed that cyclization of 6j-6s generated the inseparable
mixture of regioisomers in moderate overall yields. For ortho-
and para-substituted substrates with electron-withdrawing groups,
cyclization occurred preferentially at the non-substituted ring
(Table 2, entries 1-5), while reaction of 6o with a p-F group
afforded an exclusive regioisomer product 7o (Table 2, entry 6).
In contrast, p-methyl-substituted substrate 6p showed the
opposite selectivity because of the rich electron density of
electron-donating group substituted ring (Table 2, entry 7). For
the substrates with meta-substituent, 6q and 6r, three isomers
were found with poor regioselectivity, and the structure

3
yields. A mixture of regioisomers which cannot be separated was isolated
together following silica gel column chromatographic purification.
assignment for 8 over 8’ was not determined (Table 2, entries 8-
9). Similarly, transformation of di-fluoro substituted 6s gave two
iosmers with poor selectivity of regioisomer of 7s and 8s (Table
2, entry 10).
ACCEPTED MANUSCRIPT
Scheme 4. Proposed reaction mechanism
.
On the basis of these observations, a tentative mechanism was
proposed in scheme 4. Initially, substrate 6a underwent hydrogen
abstraction through a copper-promoted single electron transfer
process by DDQ to form the radical specie 6a-A.10 The radical
species 6a-A was then further oxidized to generate “M”
conformation of allylic cation 6a-B which cannot directly
undergo cyclization.4c Isomerization of 6a-B through bond
rotation gave “S” conformation of intermediate 6a-C and 6a-D,
followed by Friedel–Crafts cyclization,5e and subsequent proton
elimination afforded the final indene product 7a. In the case that
ring A is different from ring C, cyclization of intermediate 6a-C
and 6a-D would generate regioisomers as mentioned before, and
the regioselectivity is mainly depended on the electronical effect
of the substituent. For example, substrate 6o with strong electron-
withdrawing group underwent Friedel–Crafts cyclization to
afford 7o with an exclusive regioselectivity.
Scheme 3. Indene formation from (Z)- triaryl substituted propylenes 6
.
To further understand this intramolecular dehydrogenative
cyclization reaction, excess amount of TEMPO was added to the
reaction of 6a and the yield of product 7a decreased significantly
to 29% under the optimal reaction condition. Moreover, the
reaction was fully suppressed by TEMPO without the additive,
which implies that a radical process was involved in the initial
oxidative step.
3. Conclusion
In conclusion, an efficient copper-promoted dehydrogenative
intramolecular cyclization was developed for the synthesis of
1,2-diarylindenes in moderate to excellent yields from (Z)-1,2,3-
Table 2. Regioselectivity study of the cyclization of various
substituted 6 a
triaryl substituted propylenes. This protocol provides
a
straightforward approach to 1,2-diarylindenes via DDQ-mediated
benzylic/ allylic sp3 C-H bond activation. Further studies on the
scope, mechanism and applications of this transformation are in
progress in our laboratory.
Isolated indene
7/ 8/ 8’
Yieldc
(%)
Entry
R1
Ratiob
4. Experimental section
1
2
3
4
5
6
7
2-F (6j)
2-Br (6k)
4-Cl (6l)
4-Br (6m)
4-CF3 (6n)
4-F(6o)
7j (2’-F)/ 8j (4-F)
7k (2’-Br)/ 8k (4-Br)
7l (4’-Cl)/ 8l (6-Cl)
7m (4’-Br)/ 8m (6-Br)
7n (4’-CF3)/ 8n (6-CF3)
7o (4’-F)
5:1
2.8:1
2.2:1
1.7:1
5:1
68
62
40
45
49
53
30
4-1 General methods
Melting points were obtained in open capillary tubes using a
micro melting point apparatus SGW X-4, which were
uncalibrated. Mass spectra were recorded by the HP5989A
service; HRMS (EI) spectra were obtained on a Finigann
MAT8401 instrument. 1H nuclear magnetic resonance (NMR)
spectra were recorded using an internal deuterium lock for the
residual protons in CDCl3 (δH = 7.26) at ambient temperatures on
the following instruments: Bruker AVANCE DPX-400 (400
MHz). Data are presented as follows: Chemical shift (in ppm on
the scale relative to δTMS = 0), integration, multiplicity (s = singlet,
d = doublet, t = triplet, q = quartet and m = multiplet), coupling
constant (J/ Hz) and interpretation. 13C NMR spectra were
recorded by broadband spin decoupling using an internal
deuterium lock for CDCl3 (δ = 77.2) at ambient temperatures on
the following instruments: Bruker AVANCE DPX-400 (100
MHz). Chemical shift values are reported in ppm on the scale
100:0
1:2
4-Me (6p)
7p (4’-Me)/ 8p (6-Me)
7q (3’-F)/ 8q (5-F)/
8’q (7-F)
7.4:9.1:
1
8
3-F (6q)
60
7r (3’-Br)/ 8r (5-Br)/
8’r (7-Br)
10:3.5:
1
9
3-Br (6r)
3,5-F (6s)
57
66
10
7s (3’,5’-F)/ 8s (5,7-F)
1.6:1
a
Unless otherwise noted, the reaction was performed under N2 atmosphere,
with 6 (0.2 mmol) and DDQ (1.4 equiv.), in the presence of 10 mol% of
Cu(OAc)2•H2O in 2 mL of CH3NO2.b Crude ratio was calculated from 1H
c
NMR analysis, according to the empirical regularity of ref. 4c. Overall

4
Tetrahedron
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(δTMS = 0). All reagents and solvents were used as purchased if
not otherwise stated.
saturated K2CO3, extracted by DCM. The organic layers washed
by saturated brine, dried over anhydrous sodium sulfate. Remove
the solvent to obtain crude 1,2-dibromo-1,2-diphenylethane.12
4-2 Typical procedure for synthesis of substrates 6a-6i
To a 40 mL solutiom of THF/ MeOH (1: 1) was added 1, 2-
dibromo-1, 2-diphenylethane (6 mmol), and K2CO3 (12 mmol) in
one portion. The resulting solution was heated to reflux for 1
hour. After completion, the reaction mixture was quenched with
saturated ammonium chloride, extracted by ethyl acetate. The
organic layers were washed by saturated brine, dried over
anhydrous sodium sulfate. Remove the solvent to obtain (E)-(1-
bromoethene-1, 2-diyl) dibenzene.
Into a 2-necked 100 mL round-bottomed flask equipped with a
magnetic stirring bar, condenser, and addition funnel was added
hydrazine hydrate (160 mmol).
A
solution of 1,3-
diphenylpropan-2-one (20 mmol) in absolute ethanol (25 mL)
was added very slowly to the hydrazine hydrate with vigorous
stirring. After the addition was complete, the contents of the flask
were heated to reflux for 1 h and then cooled to room
temperature, after which most of the ethanol was removed under
aspirator pressure. The reaction mixture was then extracted with
chloroform (2 × 25 mL). The combined chloroform layers were
washed successively with saturated brine (2 × 10 mL) and dried
over anhydrous sodium sulfate. Filtered, and concentrated in
vacuo without further purification.11
Substituted benzyl halide (4.5 mmol) in THF (20 mL) was
added dropwise to the suspension of Zn dust (6.75 mmol) in 50
mL of dry THF under N2. The reaction mixture was heated to
reflux for half an hour. The reaction mixture was then transferred
to another Schlenk tube containing (E)-(1-bromoethene-1,2-diyl)
dibenzene (3.0 mmol) and PdCl2(PPh3)2 (0.03 mmol) and
refluxed until the complete consumption of the starting material,
quenched with saturated ammonium chloride, extracted by ethyl
acetate. The organic layers were washed by saturated brine, dried
over anhydrous sodium sulfate. After the mixture was filtered
and evaporated, the residue was purified by flash column
chromatography, recrystallized by EtOH to provide desired
substrate 6j-6s.13
A solution of above hydrazone (20 mmol) in dry triethylamine
(30 mL) was placed into a 100 mL round-bottomed flask
equipped with an addition funnel, magnetic stirring bar, and
calcium sulfate drying tube. The flask was cooled to 0 °C in an
ice bath and a saturated solution of iodine in THF, which had
been distilled with LiAlH4, was added rapidly via the addition
funnel to the hydrazone solution with vigorous stirring until the
evolution of nitrogen ceased. The reaction mixture was stirred at
room temperature for 1 h and then poured into 100 mL ice
solution of sodium thiosulfate. The aqueous layer was extracted
with PE (3 × 25 mL) and the combined organic layers were
washed with cold 1 N hydrochloric acid (3 × 25 mL). The
organic layer was then washed with one 25 mL portion each of
saturated NaHCO3, saturated brine, dried over anhydrous sodium
sulfate, and filtered. Removal of the solvent and purification by
flash chromatography on silica gel with petroleum ether as a
dilute afforded pure (Z)-(2-iodoprop-1-ene-1,3-diyl) dibenzene as
colorless oil.11
4-4 Typical procedure for synthesis of indene 7/ 8/ 8’
To a flame-dried 10 mL Schlenk tube under N2 was added 6
(0.20 mmol), Cu(OAc)2•H2O (0.02 mmol), followed by CH3NO2
(2 mL). DDQ (1.4 equiv.) was added after the starting material
was dissolved. The reaction mixture was then heated at 60 ºC.
After completion determined by TLC, the solvent was removed
by rotary evaporator and the reaction residue was purified by
column chromatography to afford the desired product 7/ 8/ 8’.
4-4-1. 1,2-diphenyl-1H-indene 7a14
White solid (92%). Mp: 186 – 187 ºC; H NMR (400 MHz,
1
CDCl3): δ 7.52 – 7.48 (m, 2H), 7.41 (d, J = 7.5 Hz, 1H), 7.36 (s,
1H), 7.28 – 7.07 (m, 11H), 4.97 (s, 1H). 13C NMR (100 MHz,
CDCl3): δ 150.1, 149.4, 143.4, 140.2, 135.2, 129.1, 128.7, 128.2,
128.1, 127.5, 127.2, 126.9, 126.8, 125.7, 124.0, 121.3, 56.4.
To a 25 mL Schlenk tube was added (Z)-2-iodoprop-1-enes
(1.0 mmol), arylboronic acid (2.0 mmol), palladium chloride (0.1
mmol), 1,1'-bis(diphenylphosphino)ferrocene (0.1 mmol) and
potassium carbonate (5.5 mmol) under N2, followed by DMF (8
mL). The mixture was then heated to 80 °C for 24 hours until
TLC analysis showed complete conversion of starting material.
After cooled to room temperature, the reaction solution was
filtered with EA through a short flash chromatography on silica
gel to remove the undesired salts. The solvent was washed by 50
mL of water, exacted by ethyl acetate (3 × 20 mL) and washed
with saturated brine, dried over anhydrous sodium sulfate, and
filtered. Removal of the solvent and purification by flash
chromatography on silica gel with petroleum ether as a dilute
afforded pure (Z)-1,2,3-triphenyl substituted propylene 6a- 6i.
4-4-2. 2-(4-chlorophenyl)-1-phenyl-1H-indene 7b
1
White solid (63%). Mp: 186 – 187 ºC; H NMR (400 MHz,
CDCl3): δ 7.44 – 7.38 (m, 3H), 7.34 (s, 1H), 7.28 – 7.08 (m,
10H), 4.92 (s, 1H). 13C NMR (100 MHz, CDCl3): δ 149.3, 148.8,
143.2, 139.8, 133.7, 133.2, 129.2, 128.9, 128.7, 128.0, 127.3,
127.1, 125.9, 124.1, 121.4, 56.4. HRMS (EI): calcd for C21H15Cl
([M]+): 302.0862, found 302.0859.
4-4-3. 4-(1-phenyl-1H-inden-2-yl)benzonitrile 7c
1
Pale yellow solid (65%). Mp: 152 – 153 ºC; H NMR (400
MHz, CDCl3): δ 7.59 – 7.44 (m, 6H), 7.32 – 7.08 (m, 8H), 4.95
(s, 1H). 13C NMR (100 MHz, CDCl3): δ 149.3, 147.7, 142.3,
139.3, 138.9, 132.2, 131.4, 129.1, 127.6, 127.3, 127.1, 126.8,
126.5, 123.9, 121.8, 119.0, 110.2, 56.1. HRMS (EI): calcd for
C22H15N ([M]+): 293.1204, found 293.1205.
4-3 Typical procedure for synthesis of substrates 6j-6s
To a 100 mL round-bottomed flask was added (E)-1,2-
diphenylethene (30 mmol), DCM (60 mL). Bromine (30 mmol)
was added dropwise under ice bath and stirred for another 4
hours. After completion, the reaction mixture was quenched with
4-4-4. 1-phenyl-2-(4-(trifluoromethyl)phenyl)-1H-indene 7d
1
White solid (77%). Mp: 141 – 142 ºC; H NMR (400 MHz,
CDCl3): δ 7.58 (d, J = 8.2 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 7.45

5
(d, J = 8.5 Hz, 2H), 7.30 – 7.10 (m, 8H), 4.97 (s, 1H). 13C NMR
113.8, 113.6, 56.8, 48.1. HRMS (EI): calcd for C21H15F ([M]+):
286.1158, found 286.1158.
ACCEPTED MANUSCRIPT
(100 MHz, CDCl3): δ 149.5, 148.5, 142.8, 139.5, 138.6, 130.5,
129.2, 128.9, 128.0, 127.4, 127.2, 126.8, 126.4, 125.7, 125.6 (q, J
= 3.8 Hz), 124.2, 121.8, 56.4. HRMS (EI): calcd for C22H15F3
([M]+): 336.1126, found 336.1127.
4-4-11. Indene 7k and 8k
Yellow oil (62%), 7k/ 8k = 2.8:1; 1H NMR (400 MHz, CDCl3):
δ 7.65 (d, J = 7.9 Hz, 1H) (7k), 7.50 (d, J = 7.6 Hz, 0.78H) (8k),
7.47-7.41 (m, 3H), 7.40 – 7.36 (t, J = 5.4 Hz, 2H) (7k), 7.34 (d, J
= 7.0 Hz, 1H) (7k), 7.28 – 7.06 (m, 7.6H), 7.01 – 6.90 (m, 2.6H),
6.60 (dd, J = 7.6, 1.6 Hz, 1H) (7k), 5.68 (s, 1H) (7k), 5.03 (s,
0.36H) (8k). 13C NMR (100 MHz, CDCl3): δ 151.0, 150.6, 150.0,
148.6, 143.6, 143.4, 139.8, 139.3, 134.7, 134.6, 133.1, 130.3,
129.2, 128.8, 128.7, 128.5(50), 128.5(47), 128.3, 128.2,
128.0(00), 128.0(96), 127.7, 127.4, 127.3, 127.2, 127.1, 127.0,
126.7, 125.7, 125.2, 123.9, 122.9, 121.5, 115.2, 57.4, 54.7.
HRMS (EI): calcd for C21H15Br ([M]+): 346.0357, found
346.0355.
4-4-5. 2-(4-methoxyphenyl)-1-phenyl-1H-indene 7e
1
Pale yellow solid (56%). Mp: 184 – 185 ºC; H NMR (400
MHz, CDCl3): δ 7.43 (d, J = 8.9 Hz, 2H), 7.37 (d, J = 7.5 Hz,
1H), 7.24 – 7.19 (m, 4H), 7.18 – 7.12 (m, 4H), 7.07 (t, J = 7.4
Hz, 1H), 6.78 (d, J = 8.9 Hz, 2H), 4.92 (s, 1H), 3.75 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 159.1, 149.7, 149.1, 143.7, 140.5,
129.0, 128.0(4), 128.0(1), 127.1, 126.8, 126.3, 125.2, 123.9,
120.9, 114.1, 56.6, 55.4. HRMS (EI): calcd for C22H18O ([M]+):
298.1358, found 298.1354.
4-4-6. 1-(1-phenyl-1H-inden-2-yl)naphthalene 7f
1
Orange oil (23%). H NMR (400 MHz, CDCl3): δ 8.32 (d, J =
4-4-12. Indene 7l and 8l
8.7 Hz, 1H), 7.82 (d, J = 6.8 Hz, 1H), 7.69 (d, J = 8.1 Hz, 1H),
7.53 – 7.41 (m, 3H), 7.38 – 7.31 (m, 2H), 7.30 – 7.24 (m, 2H),
7.19 (t, J = 7.4 Hz, 1H), 7.14 (s, 1H), 7.11 – 7.00 (m, 5H), 5.19
(s, 1H). 13C NMR (100 MHz, CDCl3): δ 150.2, 148.7, 144.2,
139.2, 134.5, 134.1, 132.2, 128.7, 128.6, 128.3, 127.7, 127.3,
126.8(84), 126.8(78), 126.2, 125.9, 125.8, 125.7, 125.3, 124.3,
121.3, 59.5. HRMS (EI): calcd for C25H18 ([M]+): 318.1409,
found 318.1400.
Yellow solid (40%), 7l/ 8l = 2.2:1; 1H NMR (400 MHz,
CDCl3): δ 7.48 – 7.44 (m, 2.9H), 7.40 (d, J = 7.5 Hz, 1H) (7l),
7.33 (s, 1H) (7l), 7.31 – 7.26 (m, 2.3H), 7.24 – 7.08 (m, 11H),
7.06 (d, J = 8.4 Hz, 2H) (7l), 4.94 (s, 0.45H) (8l), 4.93 (s, 1H)
(7l). 13C NMR (100 MHz, CDCl3): δ 150.8, 150.4, 149.7, 148.8,
143.3, 141.8, 139.2, 138.7, 137.6, 134.8, 134.7, 132.5, 131.4,
129.3, 129.2(18), 129.2(16), 128.7, 128.6, 128.4, 127.9, 127.7,
127.4, 127.3, 127.2, 127.1, 126.8, 126.7, 125.7, 124.5 123.9,
122.0, 121.4, 56.3, 55.6. HRMS (EI): calcd for C21H15Cl ([M]+):
302.0862, found 302.0863.
4-4-7. 6-chloro-1-(4-chlorophenyl)-2-phenyl-1H-indene 7g
1
Yellow solid (70%). Mp: 171 – 172 ºC; H NMR (400 MHz,
CDCl3): δ 7.44 (d, J = 7.3 Hz, 2H), 7.33 – 7.17 (m, 8H), 7.11 (s,
1H), 7.05 (d, J = 8.4 Hz, 2H), 4.92 (s, 1H). 13C NMR (100 MHz,
CDCl3): δ 150.4, 150.2, 141.9, 137.9, 134.5, 132.9, 131.6, 129.4,
129.3, 128.8, 128.0, 127.7, 127.5, 126.8, 124.5, 122.2, 55.6.
HRMS (EI): calcd for C21H14Cl2 ([M]+): 336.0473, found
336.0468.
4-4-13. Indene 7m and 8m
Yellow solid (45%), 7m/ 8m = 1.7:1; H NMR (400 MHz,
1
CDCl3): δ 7.50 – 7.44 (m, 3.3H), 7.41 (d, J = 7.5 Hz, 1H) (7m),
7.37 (d, J = 8.2 Hz, 0.6H) (8m), 7.35 – 7.31 (m, 3.2H), 7.30 –
7.16 (m, 9H), 7.15 – 7.09 (m, 3.2H), 7.02 (d, J = 8.2 Hz, 2H)
(7m), 4.95 (s, 0.6H) (8m), 4.93 (s, 1H) (7m). 13C NMR (100
MHz, CDCl3): δ 151.1, 150.5, 149.6, 148.7, 143.3, 142.3, 139.3,
139.1, 134.8, 134.7, 132.1, 130.2, 129.7, 129.2, 128.6(8),
128.6(6), 128.4, 127.89, 127.8, 127.7, 127.4, 127.3, 127.2,
127.2(15), 126.8, 126.7, 125.7, 123.9, 122.4, 121.4, 120.6, 119.4,
56.4, 55.6. HRMS (EI): calcd for C21H15Br ([M]+): 346.0357,
found 346.0354.
4-4-8. 6-chloro-1,2-bis(4-chlorophenyl)-1H-indene 7h
1
White solid (48%). Mp: 170 – 171 ºC; H NMR (400 MHz,
CDCl3): δ 7.35 (d, J = 8.6 Hz, 2H), 7.31 (d, J = 8.0 Hz, 1H), 7.26
(d, J = 8.1 Hz, 1H), 7.25 – 7.19 (m, 5H), 7.11 (s, 1H), 7.03 (d, J =
8.4 Hz, 2H), 4.88 (s, 1H). 13C NMR (100 MHz, CDCl3): δ 150.2,
148.9, 141.5, 137.4, 133.7, 133.1, 132.9, 131.8, 129.5, 129.2,
129.0, 127.9(91), 127.9(88), 127.7, 124.4, 122.3, 55.5. HRMS
(EI): calcd for C21H13Cl3 ([M]+): 370.0083, found 370.0085.
4-4-14. Indene 7n and 8n
Yellow solid (49%), 7n/ 8n = 5:1; 1H NMR (400 MHz, CDCl3):
δ 7.52 – 7.44 (m, 5H), 7.43 (d, J = 7.5 Hz, 1H) (7n), 7.40 – 7.35
(m, 1.5H), 7.30 – 7.23 (m, 5H), 7.21 – 7.15 (m, 2H), 7.14 – 7.10
(m, 2H), 5.02 (s, 1H) (7n), 5.01 (s, 0.2H) (8n). 13C NMR (100
MHz, CDCl3): δ 153.0, 149.5, 149.3, 148.4, 144.5, 143.4, 143.0,
138.8, 134.7, 134.4, 130.0, 129.4, 129.3, 129.2, 129.0, 128.8,
127.7(72), 127.7(67), 128.5(52), 128.5(48), 128.4, 128.3, 128.2,
128.0, 127.8, 127.5, 127.3, 127.0, 126.7, 126.0 (q, J = 3.8 Hz),
125.8, 125.6, 123.9, 123.8, 122.9, 121.5, 121.1, 56.4, 55.9.
HRMS (EI): calcd for C22H15F3 ([M]+): 336.1126, found
336.1128.
4-4-9. 6-chloro-1-(4-chlorophenyl)-2-(4-methoxyphenyl)-1H-
indene 7i
1
Orange solid (55%). Mp: 112 – 113 ºC; H NMR (400 MHz,
CDCl3): δ 7.36 (d, J = 8.1 Hz, 2H), 7.28 – 7.17 (m, 4H), 7.14 (s,
1H), 7.08 (s, 1H), 7.04 (d, J = 7.8 Hz, 2H), 6.79 (d, J = 8.1 Hz,
2H), 4.85 (s, 1H), 3.75 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
159.4, 150.1, 149.8, 142.2, 138.2, 132.8, 131.0, 129.4, 129.3,
128.0, 127.5, 127.2, 125.5, 124.3, 121.7, 114.2, 55.6, 55.4.
HRMS (EI): calcd for C22H16OCl2 ([M]+): 366.0578, found
366.0580.
4-4-15. Indene 7o
Yellow solid (53%). Mp: 128 – 129 ºC; H NMR (400 MHz,
4-4-10. Indene 7j and 8j
1
Yellow solid (68%), 7j/ 8j = 5:1; 1H NMR (400 MHz, CDCl3):
δ 7.49 (d, J = 7.5 Hz, 2H), 7.41 (d, J = 7.5 Hz, 1H), 7.36 (s, 1H),
7.29 – 7.08 (m, 8H), 6.86 – 6.78 (m, 1H), 6.69 (t, J = 7.2 Hz,
1H), 5.43 (s, 1H) (7j); 7.49 (d, J = 7.5 Hz, 2H), 7.45 (s, 1H), 7.31
(d, J = 4.3 Hz, 1H), 7.29 – 7.08 (m, 7H), 7.07 – 7.02 (m, 1H),
6.99 – 6.89 (m, 2H), 5.01 (s, 1H) (8j). 13C NMR (100 MHz,
CDCl3): δ 162.6, 160.1, 149.5, 148.5, 143.6, 139.5, 134.8, 134.7,
129.1, 128.71, 128.7 (65), 128.5, 128.4, 128.3, 127.9, 127.8,
127.6, 127.3, 127.1 (d, J = 1.8 Hz), 127.0, 126.9 (94), 126.9 (87),
126.6, 125.7, 124.7 (d, J = 3.5 Hz), 123.9, 123.9 (d, J = 1.2 Hz),
122.4 (d, J = 1.7 Hz), 121.3, 119.9 (d, J = 3.3 Hz), 115.9, 115.7,
CDCl3): δ 7.49-7.44 (m, 2H), 7.41 (d, J = 7.4 Hz, 1H), 7.35 –
7.06 (m, 9H), 6.97 – 6.86 (m, 2H), 4.95 (s, 1H). 13C NMR (100
MHz, CDCl3): δ 162.7, 160.3, 142.3, 139.2, 137.8, 135.4, 130.6,
129.9, 129.8, 128.7, 128.6, 127.6, 127.3, 126.7, 115.6, 115.4,
35.5. HRMS (EI): calcd for C21H15F ([M]+): 286.1158, found
286.1154.
4-4-16. Indene 7p and 8p
Yellow solid (30%), 7p/ 8p = 1:2; 1H NMR (400 MHz, CDCl3):
δ 7.52 – 7.45 (m, 3H) (8p), 7.39 (d, J = 7.5 Hz, 1H) (8p), 7.34 –
7.31 (m, 1.5H) (7p), 7.25 – 7.12 (m, 8H), 7.10 (d, J = 7.3 Hz,
1H) (8p), 7.06 (d, J = 4.5 Hz, 0.5H) (7p), 7.05 – 6.99 (m, 5H),

6
Tetrahedron
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Piazza, G. A.; Paranka, N. S. Pamukcu, R.; Ahnen, D. J. Cancer
Res. 1997, 57, 6. (e) Maguire, A. R.; Papot, S.; Ford, A.; Touhey,
S.; O’Connor, R.; Clynes, M. Synlett 2001, 41. (f) Clegg, N. J.;
Paruthiyil, S.; Leitman, D. C.; Scanlan, T. S. J. Med. Chem. 2005,
48, 5989. (g) Majetich, G.; Shimkus, J. M. J. Nat. Prod. 2010, 73,
284. (h) Tseng, C.-H.; Tzeng, C.-C.; Yang, C.-L.; Lu, P.-J.; Chen,
H.-L.; Li, H.-Y.; Chuang, Y.-C.; Yang, C.-N.; Chen, Y.-L. J. Med.
Chem. 2010, 53, 6164.
4.94 (s, 1H) (8p), 4.92 (s, 0.5H) (7p), 2.29 (s, 1.5H) (7p), 2.25 (s,
3H) (8p). 13C NMR (100 MHz, CDCl3): δ 150.1, 149.6, 149.5,
149.0, 143.3, 140.7, 140.4, 137.0, 136.3, 135.4, 135.3, 135.2,
129.7, 129.0, 128.6, 128.5, 128.1, 128.0, 127.9, 127.8, 127.4,
127.2, 127.0, 126.8, 126.7, 126.6, 125.6, 124.8, 123.9, 121.2,
120.9, 56.2, 56.0, 21.7, 21.2. HRMS (EI): calcd for C22H18 ([M]+):
282.1409, found 282.1411.
2. (a) Alt, H. G.; Koppl, A. Chem. Rev. 2000, 100, 1205. (b) Wang,
B. Coord. Chem. Rev. 2006, 250, 242.
3. (a) Barbera, P. G.; Rakitin, O. A.; Ros, M. B.; Torroba, T. Angew.
Chem., Int. Ed. 1998, 37, 296. (b) Yang, J.; Lakshmikantham, M.
V.; Cava, M. P. J. Org. Chem. 2000, 65, 6739.
4-4-17. Indene 7q, 8q and 8’ q
Yellow solid (60%), 7q/ 8q (5-F)/ 8’q (7-F) = 7.4:9.1: 1; H
1
NMR (400 MHz, CDCl3): δ 7.40 (d, J = 7.4 Hz, 4H) (8q), 7.33
(d, J = 7.5 Hz, 1H) (8q), 7.22 – 6.98 (m, 18H), 6.90 (d, J = 7.6
Hz, 1H) (8q), 6.79 – 6.67 (m, 3H), 5.08 (s, 0.11H) (8’q), 4.88 (s,
1H) (8q), 4.85 (s, 0.81H) (7q). 13C NMR (100 MHz, CDCl3): δ
164.4, 163.9, 162.0, 161.5, 152.2, 149.5, 148.6, 145.1(14),
145.1(05), 144.6(d, J = 2.5 Hz), 143.3, 142.8, 142.7, 139.8, 134.8,
134.7, 130.5, 130.4, 129.1, 128.8, 128.7, 128.6(64), 128.6(60),
128.6(58), 128.4, 128.2, 127.9, 127.8, 127.6, 127.4, 127.3(d, J =
3.3 Hz), 127.0, 126.9, 126.8, 126.7, 125.7, 124.8, 124.7, 123.9,
123.8(d, J = 2.8 Hz), 121.4, 114.8, 114.5, 114.0, 113.8, 112.2,
120.0, 108.3, 108.1, 55.9, 55.8, 55.7. HRMS (EI): calcd for
C21H15F ([M]+): 286.1158, found 286.1154
4. For selective examples, see: (a) Miller, W. G.; Pittman, C. U., Jr. J.
Org. Chem. 1974, 39, 1955. (b) Olah, G. A.; Asensio, G.; Mayer,
H. J. Org. Chem. 1978, 43, 1518. (c) Zhou, X.; Zhang, H.; Xie, X.;
Li, Y. J. Org. Chem. 2008, 73, 3958. (c) Smith, C. D.; Rosocha,
G.; Mui, L.; Batey, R. A. J. Org. Chem. 2010, 75, 4716. (d)
Panteleev, J.; Huang, R. Y.; Lui, H. E. K.; Lautens, M. Org. Lett.
2011, 13, 5314.
5. For transition metal catalyzed intermolecular cyclization examples,
see: (a) Singer, R. A.; McKinley, J. D.; Barbe, G.; Farlow, R. A.
Org. Lett. 2004, 6, 2357. (b) Deng, R.; Sun, L.; Li, Z. Org. Lett.
2007, 9, 5207. (c) Ye, S.; Yang, X.; Wu, J. Chem. Commun. 2010,
46, 2950. (d) Ye, S.; Wu, J. Org. Lett. 2011, 13, 5980. (e) Liu, C.-
R.; Wang, T.-T.; Qi, Q.-B.; Tian, S.-K. Chem. Commun. 2012, 48,
10913. (f) Yamazaki, S.; Fukushima, Y.; Ukai, T.; Tatsumi, K.;
Ogawa, A. Synthesis 2012, 44, 2155.
6. For transition metal catalyzed intramolecular cyclization examples,
see: (a) Rahman, S. M. A.; Sonoda, M.; Itahashi, K.; Tobe, Y. Org.
Lett. 2003, 5, 3411. (b) Rahman, S. M. A.; Sonoda, M.; Ono, M.;
Miki, K.; Tobe, Y. Org. Lett. 2006, 8, 1197. (c) Ye, S.; Gao, K.;
Zhou, H.; Yang, X.; Wu, J. Chem. Commun. 2009, 45, 5406. (d)
Zhou, F.; Han, X.; Lu, X. J. Org. Chem. 2011, 76, 1491. (e) Sato,
T.; Onuma, T.; Nakamura, I.; Terada, M. Org. Lett. 2011, 13,
4992. (f) Usanov, D. L.; Yamamoto, H. Org. Lett. 2012, 14, 414.
(g) Zhao, J.; Clark, D. A. Org. Lett. 2012, 14, 1668. (h) Ma, Z.-X.;
He, S.; Song, W.; Hsung, R. P. Org. Lett. 2012, 14, 5736. (i)
Dethe, D. H.; Murhade, G. Org. Lett. 2013, 15, 429.
7. For transition metal catalyzed carbocyclization via C-H activation
examples, see: (a) Kuninobu, Y.; Kawata, A.; Takai, K. J. Am.
Chem. Soc. 2005, 127, 13498. (b) Kuninobu, Y.; Tokunaga, Y.;
Kawata, A.; Takai, K. J. Am. Chem. Soc. 2006, 128, 202. (c)
Furuta, T.; Asakawa, T.; Iinuma, M.; Fujii, S.; Tanaka, K.; Kan, T.
Chem. Commun. 2006, 34, 3648. (d) Nishikata, T.; Kiyomura, S.;
Yamama, P. Chem.-Eur. J. 2010, 16, 2619. (e) Tran, D. N.;
Cramer, N. Angew. Chem., Int. Ed. 2011, 50, 11098. (f) Patureau,
F. W.; Besset, T.; Kuhl, N.; Glorius, F. J. Am. Chem. Soc. 2011,
133, 2154. (g) Chinnagolla, R. K.; Jeganmohan, M. Eur. J. Org.
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1476.
4-4-18. Indene 7r, 8r and 8’r
Yellow oil (57%), 7r/ 8r (5-Br)/ 8’r (7-Br) = 10:3.5:1; H
1
NMR (400 MHz, CDCl3): δ 7.51 (d, J = 8.8 Hz, 0.7H) (8r), 7.46
(d, J = 8.2 Hz, 2H) (7r), 7.39 (t, J = 10.3 Hz, 1H) (7r), 7.34 (s,
1H) (7r), 7.31 – 7.04 (m, 15.2H), 7.01 (d, J = 7.8 Hz, 0.36H)
(8r), 5.26 (s, 0.1H) (8’r), 5.03 (s, 0.35H) (8r), 4.90 (s, 1H) (7r).
13C NMR (100 MHz, CDCl3): δ 152.5, 151.7, 149.4, 148.5, 148.0,
147.9, 146.3, 145.4, 143.3, 142.6, 139.3, 136.9, 134.7, 134.6(58),
134.6(57), 130.9, 130.6, 130.1, 129.4, 129.2(22), 129.2(18),
129.1, 128.7, 128.6(65), 128.6(58), 128.5, 128.4, 128.2,
127.9(91), 127.9(89), 127.9(86), 127.7, 127.4, 127.1, 126.9(93),
126.9(90), 126.9(88), 126.8, 126.7(71), 126.7(66), 126.6, 125.8,
125.3, 124.2, 123.9, 122.9, 121.4, 121.1, 120.2, 119.7, 57.9, 56.0,
55.7. HRMS (EI): calcd for C21H15Br ([M]+): 346.0357, found
346.0359.
4-4-19. Indene 7s, and 8s
Yellow solid (66%), 7s/ 8s = 1.6:1; 1H NMR (400 MHz,
CDCl3): δ 7.42 – 7.36 (m, 5.4H), 7.33 (d, J = 7.5 Hz, 1.6H) (7s),
7.23 – 7.16 (m, 6.8H), 7.16 – 7.04 (m, 13.2H), 6.84 (d, J = 8.1
Hz, 1H) (8s), 6.60 (d, J = 6.5 Hz, 3.2H) (7s), 6.51 (t, J = 8.9 Hz,
1.6H) (7s), 6.43 (t, J = 9.4 Hz, 1H) (8s), 5.05 (s, 1H) (8s), 4.84 (s,
1.6H) (7s). 13C NMR (100 MHz, CDCl3): δ 164.5, 162.1, 153.4,
149.1, 147.9, 144.3, 143.3, 137.7, 134.6, 134.1, 128.9, 128.8,
138.7, 128.3, 128.1, 127.9, 127.7, 127.0, 126.7, 125.9, 123.9,
121.6, 110.9 (d, J = 6.7 Hz), 110.7 (d, J = 6.8 Hz), 104.8 (d, J =
3.6 Hz), 104.6 (d, J = 3.6 Hz), 102.8, 102.6, 102.3, 101.2, 100.9,
100.7, 55.7, 53.7. HRMS (EI): calcd for C21H14F2 ([M]+):
304.1064, found 304.1066.
8.
(a) Liu, H.; Cao, L.; Sun, J.; Fossey, J. S.; Deng, W.-P. Chem.
Commun. 2012, 48, 2674. (b) Li, Y.; Cao, L.; Luo, X.; Deng, W.-P.
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9. For selective examples, see: (a) Lin, S.; Song, C.-X.; Cai, G.-X.;
Wang, W.-H.; Shi, Z.-J. J. Am. Chem. Soc. 2008, 130, 12901. (b)
Lie´gault, B.; Fagnou, K. Organometallics 2008, 27, 4841. (c) Mo,
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Kündig, E. P. Angew. Chem. Int. Ed. 2009, 48, 1636. (e) Perry, A.;
Taylor, R. J. K. Chem. Commun. 2009, 3249. (f) Meng, L.; Wu, K.;
Liu, C.; Lei, A. Chem. Commun. 2013, 49, 5853.
Acknowledgments
10. Wang, T.; Zhou, W.; Yin, H.; Ma, J.-A.; Jiao, N. Angew. Chem.
Int. Ed. 2012, 51, 10823.
11. Kroop, P. J.; McNeely, S. A.; Davis, R. D. J. Am. Chem. Soc.
1983, 105, 6907.
12. Nunes, C. M.; Limberger, J.; Poersch, S.; Seferin, M.; Monteiro, A.
L. Synthesis 2009, 16, 2761
This work was supported by the Fundamental Research Funds
for the Central Universities, and the Natural Science Foundation
of China (No. 21172068).
13. Krasovskiy, A.; Lipshutz, B. H. Org. Lett. 2011, 13, 3822.
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References and notes
Supplementary Material
1. (a) Palm, J.; Boegesoe, K. P.; Liljefors, T. J. Med. Chem. 1993,
36, 2878. (b) Rao, C. V.; Rivenson, A.; Simi, B; Zang, E.; Kelloff,
G.; Steele, V.; Reddy, B. S. Cancer Res. 1995, 55, 1464. (c)
Hagishita, S.; Yamada, M.; Shirahase, K.; Okada, T.; Murakami,
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39, 3636. (d) Thompson, H. J.; Jiang, C.; Lu, J.; Menta, R. G.;
1
The H NMR and 13C NMR copies of all compounds were
attached as supplementary material.

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Supporting Information
DDQ-mediated dehydrogenative intramolecular cyclization for the synthesis of 1,2-diarylindenes
Yi Li, Li Cao, Xiaoyan Luo, * Wei-Ping Deng *
Shanghai Key Laboratory of Functional Materials Chemistry & School of Pharmacy, East China University of Science and
Technology, 130 Meilong Road, Shanghai 200237, China
weiping_deng@ecust.edu.cn
1H NMR and 13C NMR spectra for compounds 7 and 8

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