Reaction behavior of cumulene: Diels-Alder, Friedel-Crafts, and Pb-catalyzed domino reactions

Article abstract of DOI:10.3987/COM-09-S(S)96

Diels-Alder, Friedel-Crafts, and domino reactions mediated by Pd-catalyst of [3]cumulene 1 were investigated. Although the Diels-Alder reaction with cyclopentadiene occurred selectively on the C2, C3 double bond to give tetrasubstituted allenyl products, the Friedel-Crafts type addition of electron-rich heteroaromatics and subsequent protonation cleanly occurred on the C3, C4 double bond to afford tetrasubstituted conjugated dienes. In the Heck reaction with aryl iodide, the arylpalladium species was selectively inserted into the C3, C4 double bond and a subsequent C-H activation reaction with a neighboring phenyl group gave indene derivatives with a tetrasubstituted olefin moiety. Furthermore, Pd-catalyzed domino cyclization-allylation reaction of in situ generated [3]cumulene alkoxide afforded tetrasubstituted furan.

Full text of DOI:10.3987/COM-09-S(S)96

HETEROCYCLES, Vol. 80, No. 2, 2010
1125
HETEROCYCLES, Vol. 80, No. 2, 2010, pp. 1125 - 1147. © The Japan Institute of Heterocyclic Chemistry
Received, 31st July, 2009, Accepted, 4th September, 2009, Published online, 9th September, 2009
DOI: 10.3987/COM-09-S(S)96
REACTION BEHAVIOR OF CUMULENE: DIELS–ALDER,
FRIEDEL–CRAFTS, AND Pd-CATALYZED DOMINO REACTIONS‡
Tomohiro Asakawa, Mie Iinuma, Yuko Wakasugi, Mayumi Kuno,
Takumi Furuta,*,§ Satoshi Fujii, Kiyoshi Tanaka, and Toshiyuki Kan*
School of Pharmaceutical Sciences, University of Shizuoka and Global COE
program, 52-1 Yada, Shizuoka, 422-8526, Japan.
E-mail: furuta@fos.kuicr.kyoto-u.ac.jp, kant@u-shizuoka-ken.ac.jp
‡Dedicated to Professor Akira Suzuki on the occasion of his 80th birthday.
Abstract – Diels–Alder, Friedel–Crafts, and domino reactions mediated by
Pd-catalyst of [3]cumulene 1 were investigated. Although the Diels–Alder
reaction with cyclopentadiene occurred selectively on the C2, C3 double bond to
give tetrasubstituted allenyl products, the Friedel–Crafts type addition of
electron-rich heteroaromatics and subsequent protonation cleanly occurred on the
C3, C4 double bond to afford tetrasubstituted conjugated dienes. In the Heck
reaction with aryl iodide, the arylpalladium species was selectively inserted into
the C3, C4 double bond and a subsequent C–H activation reaction with a
neighboring phenyl group gave indene derivatives with a tetrasubstituted olefin
moiety. Furthermore, Pd-catalyzed domino cyclization–allylation reaction of in
situ generated [3]cumulene alkoxide afforded tetrasubstituted furan.
INTRODUCTION
Cumulene derivatives have attracted much attention due to their characteristic structures, which are
composed of linearly extended cumulated polyene systems, as well as their unique physiological
properties.1 Cumulenes are found as partial structures in natural products; one prominent example is the
neocarzinostatin chromophore where a biradical species generated by a Bergman type cycloaromatization
of the eneyne[3]cumulene plays a key role in its potent anti-tumor activity.2
Although the reactivity of allene,3 which is the structurally simplest cumulene related molecule, has been
thoroughly investigated, the reactivities of cumulene derivatives, such as [3]cumulenes, have not been

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HETEROCYCLES, Vol. 80, No. 2, 2010
well explored like as the case of allene. Thus, the reaction behavior of cumulenes toward reagents,
including nucleophiles, electrophiles, and enophiles, is not well understood, although the cumulene
ꢀ-system should possess remarkable reactivity. Furthermore, only few reports on the reactivity of
cumulenes have investigated unsymmetrically substituted derivatives.4 Therefore, further surveys on the
reaction behavior of unsymmetrically substituted cumulenes are needed.5
The tetrasubstituted alkene moiety, which could be readily derived from cumulated polyene, has
promising bioactivities.6 As shown in Figure 1, tamoxifen and raloxifene, which are representative
compounds, are promising anti-cancer drugs.7 Thus, the development of a stereoselective synthesis of
tetrasubstituted alkene derivatives from cumulated polyenes is also required in medicinal chemistry.6
NMe2
N
O
O
O
OH
Me
Tamoxifen
S
HO
Raloxifene
Figure 1. Bioactive compounds containing a tetrasubstituted olefin moiety
Although allenes have been utilized as valuable substrates to prepare tetrasubstituted alkene derivatives,6
similar cumulene derivatives may be superior due to the presence of additional and convertible double
bonds. For these reason, we have surveyed the reaction behavior of an unsymmetrically substituted
[3]cumulene derivative. Herein, we describe details of the Diels–Alder (DA), Friedel–Crafts, and Heck
reactions of 2-methyl-5,5’-diphenyl-penta-2,3,4-trienal (1),8 which yields allene 2, diene 3,9 and indene
4,10 respectively, and all include a tetrasubstituted allene or an alkene structure. Furthermore, we wish to
present a Pd(II)-catalyzed domino cyclization–allylation reaction to afford tetrasubstituted furan 5 (Figure
2).
Ph
OHC
I
Pd(0) cat.
Friedel–Crafts
type reaction
Diels–Alder
reaction
4
Lewis acid
2
3
Me
Ph
3
Ph
Heck–C–H
activation reaction
Diels–Alder reaction
CHO
Ph
Ph
Me
Ph
2
Me
4
5 4 3 2
4
1
Ph
Ph
H
O
O
H
4
Me
CHO
H
Lewis acid
Me
Me
1
3
3
1) MeMgBr
Ph
Ph
2) Pd(II) cat.
allyl bromide
cyclization–
Heck reaction
and
Pd(II)-catalyzed
cyclization
Friedel–Crafts
type reaction
O
O
3
5
allylation reaction
Figure 2. Reaction behavior of cumulene 1

HETEROCYCLES, Vol. 80, No. 2, 2010
1127
RESULTS AND DISCUSSION
Preparation of [3]cumulenes:ꢀ1 is a suitable [3]cumulene substrate due to its stability and three distinct
double bonds, which possess different electronic and steric properties due to the electron-withdrawing
nature of the formyl group and steric bulkiness of the diphenyl moiety. Cumulene 1 was prepared
according to the literature.8 Lithiation of 2-methyl-1-butene-3-yne (6) with n-BuLi and the subsequent
addition of benzophenone (7) afforded the alkynyl alcohol. Without further purification, oxidation of the
double bond with dimethyldioxirane gave 9 in a quantitative yield. Treatment of 9 with BF3·Et2O afforded
desired cumulene derivative 1 (Scheme 1). This procedure is applicable to the gram-scale synthesis of 1.
[3]Cumulene 11 was prepared from 4,4´-dimethylbenzophenone (8) in a similar manner as 1.
R
R
H
1) n-BuLi, Et2O;
BF3·Et2O, THF
Me
OH
O
O
CHO
Me
6
R
R
Me
7: R = H
8: R = Me
1: R = H (60%)
11: R = Me (58%)
R
R
9: R = H (quant.)
10: R = Me (74%)
2) DMDO, acetone
Scheme 1. Preparation of [3]cumulenes
Diels–Alder Reaction: We initially tested the DA reaction of 1 with cyclopentadiene as depicted in Table
1. The DA reaction while heating at 150 °C in toluene proceeded at the C2, C3 double bond of 1 to give
tetrasubstituted allenyl product 2 with exo selectively (entry 1).
Table 1. DA reaction with cyclopentadiene
NOE
H
Ph
Ph
H
Ph
Ph
(20 equiv.)
Me
1
OHC
H
H
Lewis acid
solvent
temp
CHO
Me
2-exo
2-endo
Yieldb)
(%)
Ratioc)
(exo : endo)
Entry
Temp
Lewis acid Solvent
(1.0 equiv.)
Time
(h)
1
2
3
4
5
6
7
6
48
15
15
20
24
23
43
63
–
2.0 : 1.0
1.0 : 1.0
–
-
150 °C
60 °C
toluene
Yb(OTf)3
CH2Cl2
SnCl4
-78 °C ꢀ rt
-78 °C ꢀ rt
-78 °C ꢀ rt
-78 °C ꢀ rt
-78 °C ꢀ rt
CH2Cl2
88
43
18
45
2.0 : 1.0
1.9 : 1.0
1.8 : 1.0
1.1 : 1.0
SnCl4
THF
AlCl3
THF
Me3Al
THF
TMSOTfa)
THF
a) TMSOTf (0.3 equiv.) was used. b) Combined yield of exo, endo isomers.
c) Determined by 1H NMR data.
This exo selectivity might originate from the unfavorable endo transition state due to the steric repulsion
between the methyl substituent of 1 and the methylene moiety of cyclopentadiene. A similar exo

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HETEROCYCLES, Vol. 80, No. 2, 2010
selectivity has been observed in the DA reaction with methacrolein.11
To increase both the reactivity and selectivity, Lewis acid catalysts were screened. An equivalent amount
of Yb(OTf)3 improved the yield of 2 in CH2Cl2 (entry 2). However, a unique solvent effect was observed
in SnCl4 catalyzed reactions; although SnCl4 in CH2Cl2 was ineffective (entry 3), the reaction in THF
gave the best yield (entry 4). Other Lewis acids, including AlCl3, Me3Al, and TMSOTf, also facilitated the
DA reaction, but in diminished yields (entries 5–7). Table 1 shows the structures of the endo- and
exo-isomers as determined by NOE experiments.
The reactivity of 1 was further investigated with Danishefsky’s diene.12 The DA reaction proceeded
smoothly on the C2, C3 double bond to afford unstable allenyl cycloadduct 12, but further treatment with
TBAF afforded trisubstituted benzene derivative 15as the major product. This unexpected aromatization
might occur via isomerization of allene 13 to diene 14 and successive deformylation of 14 by nucleophilic
attack of the hydroxide ion (Scheme 2). None of the DA reactions gave products on the C3, C4 or C4, C5
double bonds. Hence, cumulene 1 has a sufficient reactivity toward DA reactions, and is an excellent
dienophile with a reactive C2, C3 double bond due to the presence of the electron-withdrawing formyl
group.
OTMS
OMe
OHC
Me
OHC
Me
TBAF (2 eq)
THF, rt, 24 h
MeO
(10 eq)
1
Ph
OTMS
Ph
O
130 °C, 1 h
Ph
Ph
12
13
H2O
–OH
OH
Ph
H
Me
–O
Me
O
Me
OH
58% (2 steps)
O
O
Ph
Ph
15
Ph
Ph
Ph
14
Scheme 2. DA reaction with Danishefsky’s diene
Friedel–Crafts type reaction: These promising results inspired us to examine the reactivity of 1 with
electron-rich heteroaromatics. Although the reaction conditions were similar to the DA reactions, the
Friedel–Crafts reaction proceeded smoothly by treating 1 and furan with 50 mol% of Yb(OTf)3 to give
corresponding tetrasubstituted conjugated dienes 3 as an E/Z mixture in 93% yield (Scheme 3).13 Similar
observations for the different reactivities of dimethylallene-1,3-dicarboxylate in DA and Friedel-Crafts
reactions have been reported.14 Allene derivative 17, which could be generated by the protonation at C2 of
enolate 16 (path b), was not detected, clearly demonstrating that the conjugate addition of the aryl group
and subsequent protonation of enolate 16 selectively occur at C3 and C4, respectively (path a).

HETEROCYCLES, Vol. 80, No. 2, 2010
1129
E/Z mixture
1.0 : 2.0
93%
a
O
b
H+
3
LA
LA
O
O
H
Yb(OTf)3
(0.5 eq)
2
Me
4
Me
O
H
H
a
+
3
1
3
Me
O
CH2Cl2
0 °C
O
H
Ph
Ph
rt
b
O
Ph
Ph
H+
Ph
16
Ph
17
Scheme 3. Friedel–Crafts type reactions of 1 with furan
The Friedel–Crafts reaction with nitrogen containing heteroaromatics, including pyrrole and indoles, was
also investigated (Table 2). In all cases, the reactions proceeded smoothly to give corresponding dienes
1813 and 19–22 in excellent yields. Moreover, neither the DA product nor the corresponding allene
derivative was detected. With the indole derivatives, introducing methyl substituents at the 1 and 2
positions on the indole ring improved the Z-selectivity of the product (entries 4 and 5).
Table 2. Friedel–Crafts type reactions of 1 with nitrogen containing electron-rich aromatics
Ar-H
Ph
Ph
H
4
Yb(OTf)3 (0.5 equiv.)
Me
1
CH2Cl2
3
Ar
CHO
rt
0 °C
Ar-H (equiv.)
(20)
Ratiob)
(E : Z)
Time Product Yielda)
(h)
Entry
(%)
1.0 : 1.5
1.0 : 3.0
1.0 : 2.3
1.0 : 4.0
1.0 : 8.0
24
12
24
10
6
18
19
20
21
22
70
70
73
76
78
1
2
3
4
5
H
N
H
(2.0)
(2.0)
R
R
1 = R2 = H
1 = Me, R2 = H
H
R2
R1 = H, R2 = Me
N
(2.0)
(1.0)
R1
R
1 = R2 = Me
a) Combined yield of E, Z isomers. b) Determined by 1H NMR data.
X-Ray analysis established the structure of compound 22 (Figure 3). Because the chemical shift of the
Z-isomer aldehyde proton is at a higher-field than the corresponding E-isomer, the major isomers of
19–21 should be the Z-isomer due to anisotropic shielding of the neighboring indole ring.
Figure 3. ORTEP view of 22

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HETEROCYCLES, Vol. 80, No. 2, 2010
These Friedel–Crafts type conjugate addition–protonations are formal 3, 4-additions to form
tetrasubstituted conjugated dienes, which sharply contrasts the DA reaction because the DA reaction
occurred at the C2, C3 positions of 1 to give tetrasubstituted allene derivatives.
Domino Heck–CꢀH activation reaction: Next, we explored the Heck reaction of 1, and initially
expected a reactivity similar to the DA reaction would provide allene 24 via insertion of the arylpalladium
species into the carbonyl conjugated C2, C3 double bond15 (path a) and successive ꢁ-hydride elimination
of 23. However, the reaction afforded 2,3-diaryl indene derivative 26.16 This product can be explained by
a reaction that proceeds through a domino process, and includes selective insertion of an arylpalladium
species at the C3, C4 double bond (path b) and a subsequent CꢀH activation reaction17 with a neighboring
phenyl moiety to afford palladacycle 25 (Scheme 4).
Ph
Ar
Ph
Ar
a
H
H
Ar-Pd-I
Ph
Me
OHC PdI
23
Ph
a
b
OHC
24
Ph
Ph
Me
4
3
2
CHO
Ph
Ar
Ph
1
b
Ar
CHO
Pd
CHO
Me
Me
25
26
Scheme 4. Domino Heck–C–H activation reaction of 1
Next, the appropriate conditions for the Heck reaction with various aryl halides were surveyed (Table 3).
Upon treating 1 and phenyl iodide with 10 mol% Pd(OAc)2 and i-Pr2NEt, the reaction proceeded
smoothly to afford indene derivative 4 as an E/Z mixture in good yield (entry 1). Using 2.0 equivalents of
phenyl iodide improved the chemical yield (entry 2), but adding more phenyl iodide did not remarkably
improve the yield (entry 3). Moreover, functionalized phenyl iodides were applied to this reaction (entries
5–11). The reaction with p-methoxyphenyl iodide gave corresponding indene derivative 27 in 46% yield
(entry 5). In addition, aryl iodides with electron-withdrawing groups were compatible. Although
p-mesyloxyphenyl iodide gave a moderate result (entry 6), a nitro substituent increased the yield to 66%
(entry 7). Because phenyl bromide did not react (entry 4), the transformation with p-bromophenyl iodide
afforded 30 without bromo substituent loss (entry 8). Aryl iodides with both electron-releasing and
withdrawing groups at the meta-position also yielded the corresponding products in good yields (entries
9–11).
Because the aromatic region in the NMR spectra of products 4, 27–33 was highly overlapped, structural
confirmations and stereochemistry determinations of the tetrasubstituted double bond were problematic.
Therefore, the structures of the domino products were determined using the reaction with cumulene 11, an
appropriate substrate to produce simple NMR signals. The domino reaction of 11 with p-nitrophenyl

HETEROCYCLES, Vol. 80, No. 2, 2010
1131
iodide proceeded smoothly to give an E/Z mixture of 34, which has much simpler signals in the aromatic
region than 4 due to both the methyl and nitro substituents on the phenyl rings.
Table 3. Domino Heck–C–H activation reaction with various substrates
Ph
Ar-X
Ph
Me
4
3
Pd(OAc)2 (10 mol%)
Ar
CHO
i-Pr2NEt (3.0 equiv.)
MeCN, 80 °C
CHO
1
Me
Yielda
(%)
Ratiob
(E : Z)
Entry
Time
(h)
Equiv.
Product
Ar-X
1c
2
PhI
PhI
PhI
1.0
2.0
3.0
1.0
2
1
1
3
1
1
1
1
2
1
1
4
54
59
61
–
1.0 : 3.7
1.0 : 3.6
1.0 : 3.4
–
4
3
4
4
PhBr
–
I
5
R = OMe 2.0
27
28
29
30
31
32
33
46
39
66
55
47
62
47
1.0 : 3.6
1.0 : 3.1
1.0 : 4.3
1.0 : 2.7
1.0 : 2.3
1.0 : 2.3
1.0 : 2.5
6
R = OMs
R = NO2
R = Br
2.0
2.0
2.0
7
8
R
I
9
R = OMe 2.0
10
11
R = OMs
R = NO2
2.0
2.0
R
a) Combined yield of E, Z isomers. b) Determined by 1H NMR data.
c) The reaction mixture was heated to 100 °C.
Therefore, each signal could be assigned. The NOE correlations between the aromatic (Ha) and the
methyl protons, and the aromatic (Hb) and the formyl proton clearly indicated that the Z-isomer on the
tetrasubstituted olefin was the major product. On the other hand, the NOEs between (Hc) and formyl
proton, (Hd) and methyl protons were observed for the E-isomer (Scheme 5). Moreover, X-ray
crystallographic analysis of 34, which included the stereochemistry, was unambiguously determined as
shown in Figure 4. Because anisotropic shielding of the neighboring p-nitrophenyl moiety caused the
Z-isomer aldehyde proton of 34 to shift to a higher-field compared to the corresponding E-isomer, the
major isomer of 4, 27-33 should be the Z-isomer.
p-tol
NO2
NO2
Me
Me
Hb
CHO
I
Ha
Me
CH3
(Z)-34
Pd(OAc)2 (10 mol%)
+
CHO
p-tol
i-Pr2NEt (3.0 equiv.)
MeCN, 80 °C, 1 h
NO2
49%, E : Z = 1.0 : 2.4
Me
Me
Hd
11
Hc
OHC
Me
(E)-34
Scheme 5. NOE correlations of E- and Z-34

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HETEROCYCLES, Vol. 80, No. 2, 2010
Figure 4. ORTEP drawing of (Z)-34
Moreover, we investigated the Heck reaction with nitrogen and sulfur containing heteroaromatics, such as
indole and thiophene (Table 4). In addition to an excellent yield, N-non-protected 5-iodoindole improved
the Z-selectivity of the product (entry 1). Employing N-methyl and N-tosylindoles in this reaction gave 36
and 37, respectively (entries 2 and 3), but using N-Boc indole, the product decomposed (entry 4).
2-Iodothiophene was also applicable to the domino reaction to afford 38 in excellent yield (entry 5).
Table 4. Domino Heck–C–H activation reactions of 1 with iodoheteroaromatics
Ph
Ar-I (2.0 eq.)
Pd(OAc)2 (0.1 eq)
Ph
Me
4
3
Ar
CHO
i-Pr2NEt (3.0 eq)
MeCN, 80 °C
CHO
1
Me
Yielda
Ratiob
(E : Z)
Entry
Ar-I
Time Product
(h)
(%)
R = H
3
4
35
36
37
–
71
30
39
–
1.0 : 4.7
1.0 : 3.0
1.0 : 7.0
–
1
2
3
4
5
I
R = Me
R = Ts
N
R
21
18
1
R = Boc
38
80
1.0 : 5.9
S
I
a) Combined yield of E, Z-isomers. b) Determined by 1H NMR data.
Scheme 6 depicts a plausible mechanism for the domino Heck–CꢀH activation reaction. The first crucial
step of the Heck reaction is insertion of arylpalladium iodide into the C3, C4 double bond to give
intermediate 39.18 Because ꢁ-hydride elimination of 39 is not accessible, CꢀH activation of the
neighboring phenyl moiety proceeds smoothly to afford six-membered palladacycle 25, which is
successively cyclized to give indene derivative 26 via reductive elimination of the palladium intermediate.
The addition of arylpalladium iodide to 1 is regioselective so that palladium(II) and the aryl group are
positioned at C3 and C4, respectively, in 39. 16a,19
Multiple aryl modified tetrasubstituted alkenes have attracted attention as key structural elements for
bioactive compounds, including tamoxifen,7 which is a clinically used drug for breast cancer. The
Heck–C–H activation reaction of unsymmetrically substituted cumulenes described herein may be useful

HETEROCYCLES, Vol. 80, No. 2, 2010
1133
and valuable for constructing such bioactive tetrasubstituted alkenes with the appropriate functional
groups on both the aromatic and alkene moieties.
ArI
1
26
Pd(0)
reductive
elimination
Ph
Pd
Ar
Ar-Pd-I
Ph
Ph
Me
CHO
4
3
CHO
25
Me
C-H
activation
Insertion to
C3, 4
HI
double bond
Ph
Ar
4
PdI
3
Ar
Ph
Me
CHO
Me
Pd
I
Ph
CHO
H
39
Scheme 6. Plausible reaction pathway of Heck–C–H activation reaction
These bioactive tetrasubstituted alkenes may be key substituents for interactions with receptors as well as
pivotal in further chemical transformations. Moreover, products 4, 26–38 can be regarded as
conformationally locked analogs of tamoxifen where one of the aromatic rings is fixed as the partial
structure of the indene framework. Using these indene derivatives as bioprobes for tamoxifen related
nuclear receptors are also interesting.
Domino cyclization–allylation reaction: Furthermore, we investigated Pd-catalyzed domino cyclization
and allylation of 1 via nucleophilic addiditon of Grignard reagent (Table 5). After addition of MeMgBr to
1, Pd(OAc)2 (5 mol%) and allyl bromide were successively introduced to the reaction mixture to afford
tetrasubstituted furan 5 in 38% yield (entry 1). The use of 10 mol% of Pd(OAc)2 increased the yield of 5
up to 42% (entry 2). Although employment with PdCl2 was also effective, the yield was diminished (entry
3).
Table 5. Pd(II)-catalyzed domino cyclization reaction
1) MeMgBr (1.5 equiv)
Me
Ph
Me
toluene, –78 °C 0 °C
Ph
Ph
2) Pd cat.
allyl bromide (5 equiv)
rt
CHO
Me
O
5
1
Entry
Pd cat. (mol%)
Time (h)
Yield (%)a
Pd(OAc)2 (5)
Pd(OAc)2 (10)
PdCl2 (5)
48
24
24
48
38
42
23
–
1
2a
3
Pd(PPh)4 (10)
4
a) MeMgBr (1.1 equiv) was used.

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HETEROCYCLES, Vol. 80, No. 2, 2010
On the other hand, Pd(PPh3)4 was ineffective for the reaction (entry 4). Therefore, the cyclization reaction
would proceed with Pd(II) catalyst from the corresponding in situ generated cumulene alkoxide 40 by
MeMgBr addition.20 Intramolecular oxypalladation at the C3, C4 double bond of 40 would afford
cyclized intermediate 41, and successive allylation reaction and dehalopalladation to give 42, which could
readily aromatize to 5 (Scheme 7).21
1
MeMgBr
Me
aromatization
5
Ph
Ph
Me
4
3
Ph
Ph
Me
Pd(II)
O
Me
–O
42
40
Br
Pd(II)
Me
Me
Ph
Ph
Me
Pd(II)
4
3
Ph
Me
O
–O
Ph
Me
Pd(II)
Ph
Ph
Br
Me
O
41
Scheme 7. Possible reaction pathway of cyclization–allylation reaction
Highly substituted furans have attracted attention for their occurrence in a variety of bioactive natural
products and pharmaceuticals.22 The Grignard reagent addiditon–Pd(II)-catalyzed cyclization–allylation
sequence from 1 would be one of the most promissing and covenient way to access tetrasubstituted
furans.23
In conclusion, we have found characteristic Diels–Alder and Friedel–Crafts type conjugate addition
reactions of 1, which have concerted and stepwise reaction pathways. Furthermore, both reactions provide
novel and useful routes to highly substituted allene and diene derivatives. Moreover, we have found
unique Pd-catalyzed domino Heck–C–H activation reaction and cyclization–allylation reaction, which
provides indene derivatives with tetrasubstituted alkene moieties and tetrasubstituted furan, respectively.
Thus, a detailed mechanistic study and further chemical transformations of the reaction products to
bioactive tetrasubstituted olefins such as tamoxifen related molecules as well as tetrasubstituted furan
derivatives are currently under investigation.
EXPERIMENTAL
1H NMR spectra were obtained on JEOL ECA-500 at 500 MHz or JEOL EX-270 at 270 MHz with
13
chemical shifts reported as ppm from tetramethylsilane as an internal standard. C NMR spectra were
measured on JEOL ECA-500 at 125 MHz or JEOL EX-270 at 68 MHz. The mass spectra were measured

HETEROCYCLES, Vol. 80, No. 2, 2010
1135
on a JEOL MStation JMS-700 spectrometer. IR spectra were recorded on a JASCO WS/IR-8000. Unless
otherwise noted, all reactions were carried out under an argon atmosphere. Column chromatography was
performed using silica gel 60N spherical (63-210 mesh, KANTO CHEMICAL). Silica Gel 60 F254 plates
(Merck) were used for preparative TLC (prep. TLC).
3-(2-Methyloxiran-2-yl)-1,1-di-p-tolylprop-2-yn-1-ol (10).
n-BuLi (2.5 mL, 4.0 mmol) was added to a solution of 2-methyl-1-butene-3-yne (0.38 mL, 4.0 mmol) in
Et2O (2 mL) under an argon atmosphere at –50 °C, and the mixture was stirred for 30 min.
4,4’-Dimethylbenzophenone (8) (840 mg, 4.0 mmol) in THF (5 mL) was added, and the mixture was
stirred and warmed to room temperature for 24 h. Then the mixture was washed with satd. aq. NH4Cl and
brine, and extracted with Et2O. The organic layer was dried over anhydrous MgSO4, filtered, and
evaporated under reduced pressure. The residue was dissolved in a DMDO acetone solution, and stirred at
room temperature for 1 h. The reaction mixture was evaporated, and CH2Cl2 was added. The residue was
purified by column chromatography (n-hexane:AcOEt = 4:1) to afford 10 (866 mg, 74%, 2 steps) as a
colorless oil.
1
10: H NMR (270 MHz, CDCl3): ꢀ 1.59 (s, 3H), 2.31 (s, 6H), 2.77 (d, 1H, J = 5.9 Hz), 2.81 (s, 1H), 3.05
(d, 1H, J = 5.9 Hz), 7.11 (d, 4H, J = 8.4 Hz), 7.42 (d, 4H, J = 8.4 Hz); 13C NMR (68 MHz, CDCl3): ꢀ 21.0,
22.8, 47.3, 55.3, 73.9, 84.9, 86.0, 125.8, 128.9, 137.4, 141.8; IR (film) 1913, 2210, 3400 cm-1; FAB (m/z)
293 (M+H)+; HRMS (FAB) calcd for C20H21O2 293.1541 (M+H)+, found 293.1527.
2-Methyl-5,5-di-p-tolylpenta-2,3,4-trienal (11).
To a solution of 10 (245 mg, 0.84 mmol) in THF (7 mL), BF3•OEt2 (22 mL, 0.17 mmol) was added under
an argon atmosphere at –78 °C. The mixture was stirred and warmed to room temperature for 3 h. The
mixture was washed with brine, and extracted with Et2O. The organic layer was dried over anhydrous
MgSO4, filtered, and evaporated under reduced pressure. The residue was purified by column
chromatography (n-hexane:AcOEt = 9:1) to afford 11 (134 mg, 58%) as a yellow solid.
1
11: H NMR (500 MHz, CDCl3): ꢀ 2.08 (s, 3H), 2.42 (s, 6H), 7.24 (d, 4H, J = 8.6 Hz), 7.48 (dd, 2H J =
8.6 Hz), 7.50 (dd, 2H, J = 8.6 Hz), 9.62 (s, 1H); 13C NMR (125 MHz, CDCl3): ꢀ 14.3, 21.4, 115.5, 128.9,
129.35, 129.37, 129.6, 129.7, 130.2, 133.1, 134.8, 140.1, 140.2, 149.9, 169.9, 189.5; IR (film, cm-1) 1714,
1733, 2045 cm-1; FAB (m/z) 275 (M+H)+; HRMS (FAB) calcd for C20H19O 275.1436 (M+H)+, found
275.1460.
General Procedure for Diels–Alder Reaction of 1.
To a solution of 1 in a solvent, cyclopentadiene and a Lewis acid were added under an argon atmosphere,
and the mixture was stirred. The mixture was added satd. aq. NaHCO3, and extracted with Et2O. The
organic layer was washed with brine, dried over anhydrous MgSO4, filtered and evaporated under reduced
pressure to give a residue. The residue was purified by column chromatography (n-hexane:AcOEt = 20:1)

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HETEROCYCLES, Vol. 80, No. 2, 2010
to afford 2 as a mixture of two isomers. The mixture was further purified by column chromatography
(n-hexane:AcOEt = 30:1) to afford 2-exo and 2-endo isomers.
2-exo: 1H NMR (500 MHz, CDCl3): ꢀ 1.20 (s, 3H), 1.73 (d, 1H, J = 9.1 Hz, 1H), 1.90 (d, 1H, J = 9.1 Hz),
13
3.17 (s, 1H), 3.55 (s, 1H), 6.30–6.35 (m, 1H), 6.45–6.50 (m, 1H), 7.20–7.40 (m, 10H), 9.76 (s, 1H); C
NMR (125 MHz, CDCl3): ꢀ 20.5, 48.6, 48.8, 50.4, 60.5, 109.2, 114.1, 127.3, 127.4, 128.2, 128.4, 128.5,
128.6, 136.0, 137.1, 137.2, 137.7, 199.2, 202.8; IR (film) 1719, 3016 cm-1; FAB (m/z) 313 (M+H)+;
HRMS Calcd for C23H21O (M+H)+ 313.1592, found 313.1597.
1
2-endo: H NMR (500 MHz, CDCl3): ꢀ 1.45 (s, 3H) 1.75 (d, 1H, J = 10 Hz, 1H), 2.00 (d, 1H, J = 10 Hz),
13
2.91 (s, 1H), 3.61 (s, 1H), 6.25–6.32 (m, 1H), 6.35–6.40 (m, 1H), 7.20-7.40 (m, 10H), 9.28 (s, 1H); C
NMR (125 MHz, CDCl3): ꢀ 21.0, 48.6, 50.2, 51.3, 60.7, 108.7, 114.2, 127.3, 127.4, 128.35, 128.42,
128.44, 134.8, 136.3, 137.2, 199.3, 203.6; IR (film) 1657, 3017 cm-1; FAB (m/z) 313 (M+H)+; HRMS
Calcd C23H21O (M+H)+ 313.1592, found 313.1585.
3-(2,2-Diphenylvinyl)-4-methylphenol (15).
A solution of 1 (30 mg, 0.12 mmol) in trans-1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (0.23 mL,
1.2 mmol) was stirred at 130 °C for 1 h. Then the solution was evaporated. The residue was dissolved in
THF (0.5 mL) and added to TBAF in THF (1 M) (0.24 mL, 0.24 mmol). The mixture was stirred at room
temperature for 24 h, treated with satd. aq. NH4Cl, and extracted with Et2O. The organic layer was dried
over anhydrous MgSO4, filtered, and evaporated under reduced pressure to give a residue, which was
purified by column chromatography (n-hexane:Et2O = 2:1) to afford 9 (20 mg, 58%) as a dark yellow oil.
1
15: H NMR (270 MHz, CDCl3): ꢀ 2.24 (s, 3H), 6.28 (d, 1H, J = 2.7 Hz), 6.55 (dd, 1H, J= 2.7, 7.8 Hz),
13
6.91 (s, 1H), 6.99 (d, 1H, J = 7.8 Hz), 7.04-7.40 (m, 10H); C NMR (68 MHz, CDCl3): ꢀ 19.3, 113.9,
116.2, 126.8, 127.3, 127.6, 128.1, 128.2, 129.3, 130.6, 130.8, 137.9, 140.0, 143.4, 152.9; IR (film) 3362
cm-1; FAB (m/z) 287 (M+H)+; HRMS Calcd for C21H19O (M+H)+ 287.1436, found 287.1390.
3-(Furan-2-yl)-2-methyl-5,5-diphenylpenta-2,4-dienal (3).
To a solution of 1 (25 mg, 0.10 mmol) in CH2Cl2 (1 mL), Yb(OTf)3 (31 mg, 0.05 mmol) and furan (136
mg, 2.0 mmol) were added under an argon atmosphere at 0 °C. The mixture was stirred at room
temperature for 24 h, washed with H2O and brine, extracted with CH2Cl2, dried over anhydrous MgSO4,
and evaporated under reduced pressure. The residue was purified by column chromatography
(n-hexane:AcOEt = 6:1) to afford 3 (29 mg, 92%, major isomer : minor isomer = 2.0 : 1.0) as a mixture of
two isomers.
1
3 (E/Z mixture): H NMR (500 MHz, CDCl3): ꢀ 1.87 (minor isomer), 1.94 (major isomer) (s, 3H),
13
6.10–7.60 (m, 14H), 9.86 (minor isomer), 10.05 (major isomer) (s, 1H); C NMR (125 MHz, CDCl3): ꢀ
12.3, 13.2, 111.5, 112.1, 115.8, 116.1, 121.9, 125.1, 127.9, 127.9, 128.3, 128.4, 128.5, 128.6, 128.6, 128.7,
129.7, 129.7, 131.9, 135.5, 138.9, 139.4, 141.7, 141.9, 142.3, 142.6, 144.0, 144.7, 149.8, 150.3, 150.5,

HETEROCYCLES, Vol. 80, No. 2, 2010
1137
152.9, 193.2, 193.8; IR (film, cm-1) 1630, 1659, 1692 cm-1; FAB (m/z) 315 (M+H)+; HRMS (FAB) calcd
for C22H19O2 315.1385 (M+H)+, Found 315.1357.
2-Methyl-5,5-diphenyl-3-(1H-pyrrol-2-yl)penta-2,4-dienal (18).
To a solution of 1 (25 mg, 0.10 mmol) in CH2Cl2 (1 mL) were added Yb(OTf)3 (31 mg, 0.05 mmol) and
pyrrole (134 mg, 2.0 mmol) under an argon atmosphere at 0 °C, and the mixture was stirred at room
temperature for 24 h. The mixture was washed with H2O and brine, extracted with CH2Cl2, dried over
anhydrous MgSO4, and evaporated under reduced pressure. The residue was purified by the column
chromatography (n-hexane : AcOEt = 10 : 1) to afford 17 (22 mg, 70%, major isomer : minor isomer =
1.5 : 1.0) as a dark purple oil.
1
18 (E/Z mixture): H NMR (270 MHz, CDCl3): ꢀ 1.82 (minor isomer), 1.92 (major isomer) (s, 3H),
6.00–7.40 (m, 14H), 8.47 (minor isomer), 8.76 (major isomer) (br s, 1H), 9.75 (minor isomer), 9.99
(major isomer) (s, 1H); 13C NMR (68 MHz, CDCl3): ꢀ 12.7, 97.2, 110.0, 111.1, 115.4, 117.2, 120.8, 121.6,
122.5, 127.9, 128.0, 128.2, 128.2, 128.3, 128.3, 128.4, 128.5, 128.7, 129.4, 130.0, 132.4, 137.5, 138.6,
141.5, 155.4, 192.7; IR (film) 1630, 1645 cm-1; FAB (m/z) 314 (M+H)+; HRMS (FAB) calcd for
C22H20NO 314.1545 (M)+, found 314.1519.
3-(1H-Indol-3-yl)-2-methyl-5,5-diphenylpenta-2,4-dienal (19).
To a solution of 1 (17 mg, 0.07 mmol) in CH2Cl2 (0.7 mL) were added Yb(OTf)3 (22 mg, 0.035 mmol)
and indole (17 mg, 0.14 mmol) under an argon atmosphere at 0 °C, and the mixture was stirred at room
temperature for 12 h. The mixture was washed with H2O and brine, extracted with CH2Cl2, dried over
anhydrous MgSO4, and evaporated under reduced pressure. The residue was purified by the column
chromatography (n-hexane : AcOEt = 4 : 1) to afford 19 (18 mg, 70%, E : Z = 1.0 : 3.0) as a dark yellow
solid.
19 (E/Z mixture). 1H NMR (270 MHz, CDCl3) ꢀ 1.81 (E-isomer), 1.96 (Z-isomer) (s, 3H), 6.70–7.70 (m,
13
15H), 8.41 (Z-isomer), 8.76 (E-isomer) (br s, 1H), 9.64 (Z-isomer), 10.13 (E-isomer) (s, 1H); C NMR
(125 MHz, CDCl3) ꢀ 13.1, 14.1, 111.2, 113.3, 113.5, 115.9, 120.1, 120.5, 120.7, 122.5, 127.05, 127.11,
127.2, 127.3, 127.4, 127.5, 127.9, 128.2, 128.28, 128.33, 128.4, 128.9, 129.6, 130.0, 134.8, 135.9, 139.3,
142.5, 149.2, 149.3, 149.9, 193.0, 194.2; FAB (m/z) 363 (M+H)+; HRMS (FAB) calcd for C26H21NO
363.1623 (M)+, found 363.1626.
2-Methyl-3-(1-methyl-1H-indol-3-yl)-5,5-diphenylpenta-2,4-dienal (20).
To a solution of 1 (49 mg, 0.20 mmol) in CH2Cl2 (2 mL) were added Yb(OTf)3 (62 mg, 0.10 mmol) and
1-methylindole (52 mg, 0.40 mmol) under an argon atmosphere at 0 °C, the mixture was stirred at room
temperature for 24 h. The mixture was washed with H2O and brine, extracted with CH2Cl2, dried over
MgSO4, and evaporated under reduced pressure. The residue was purified by the column chromatography
(n-hexane : AcOEt = 7 : 1) to afford 20 (55 mg, 73%, E : Z = 1.0 : 2.3) as an orange yellow solid.

1138
HETEROCYCLES, Vol. 80, No. 2, 2010
1
20 (E/Z mixture). H NMR (270 MHz, CDCl3) ꢀ 1.82 (E-isomer), 1.96 (Z-isomer) (s, 3H), 3.54
13
(Z-isomer), 3.76 (E-isomer) (s, 3H), 6.60–7.80 (m, 16H), 9.67 (Z-isomer), 10.11 (E-isomer) (s, 1H); C
NMR (68 MHz, CDCl3) ꢀ 12.9, 14.1, 32.5, 33.0, 109.2, 109.6, 112.5, 120.2, 120.3, 121.3, 122.2, 126.77,
126.84, 127.2, 127.8, 127.9, 128.27, 128.34, 129.6, 130.0, 131.7, 133.5, 134.5, 136.9, 139.6, 142.5, 148.9,
149.7, 192.5, 194.1; IR (CHCl3) 1643 cm-1; FAB (m/z) 378 (M+H)+; HRMS (FAB) calcd for C27H24NO
378.1858 (M+H)+, found 378.1906.
2-Methyl-3-(2-methyl-1H-indol-3-yl)-5,5-diphenylpenta-2,4-dienal (21).
To a solution of 1 (49 mg, 0.20 mmol) in CH2Cl2 (2 mL) were added Yb(OTf)3 (62 mg, 0.10 mmol) and
2-methylindole (52 mg, 0.40 mmol) under an argon atmosphere at 0 °C, the mixture was stirred at room
temperature for 10 h. The mixture was washed with H2O and brine, extracted with CH2Cl2, dried over
MgSO4, and evaporated under reduced pressure. The residue was purified by the column chromatography
(n-hexane : AcOEt = 7 : 1) to afford 21 (57 mg, 76%, E : Z = 1.0 : 4.0) as a orange yellow solid.
1
21 (E/Z mixture). Mp198–200 °C; H NMR (270 MHz, CDCl3) ꢀ 1.71 (E-isomer), 2.03 (Z-isomer) (s,
3H), 2.04 (E-isomer), 2.09 (Z-isomer) (s, 3H), 6.50–7.80 (m, 16H), 9.45 (Z-isomer), 10.40 (E-isomer) (s,
1H); 13C NMR (68 MHz, CDCl3) ꢀ 12.5, 12.9, 23.7, 38.7, 109.9, 110.6, 119.6, 120.1, 121.6, 126.6, 126.9,
127.2, 128.2, 128.3, 128.4, 128.8, 129.2, 135.0, 135.5, 139.5, 142.6, 148.6, 150.0, 183.3, 194.2; IR
(CHCl3) 1643 cm-1; FAB (m/z) 378 (M+H)+; HRMS (FAB) calcd for C27H24NO 378.1858 (M+H)+, found
378.1864.
3-(1,2-Dimethyl-1H-indol-3-yl)-2-methyl-5,5-diphenylpenta-2,4-dienal (22).
To a solution of 1 (24 mg, 0.10 mmol) in CH2Cl2 (1 mL) were added Yb(OTf)3 (31 mg, 0.05 mmol) and
1,2-dimethylindole (14 mg, 0.10 mmol) under an argon atmosphere at 0 °C, the mixture was stirred at
room temperature for 6 h. The mixture was washed with H2O and brine, extracted with CH2Cl2, dried over
anhydrous MgSO4, and evaporated under reduced pressure. The residue was purified by the column
chromatography (n-hexane : AcOEt = 9 : 1 to 5 : 1) to afford 22 (30 mg, 78%, E : Z = 1.0 : 8.0) as an
orange yellow crystal.
1
22 (E/Z mixture). Mp 204–207 °C; H NMR (270 MHz, CDCl3) ꢀ 1.72 (E-isomer), 1.96 (Z-isomer) (s,
3H), 1.99 (E-isomer), 2.11 (Z-isomer) (s, 3H), 3.30 (Z-isomer), 3.40 (E-isomer) (s, 3H), 6.40–7.70 (m,
13
15H), 9.44 (Z-isomer), 10.42 (E-isomer) (s, 1H); C NMR (68 MHz, CDCl3) ꢀ 11.7, 12.3, 29.1, 108.3,
110.0, 119.5, 119.8, 121.1, 126.1, 126.3, 127.5, 128.1, 128.25, 128.30, 128.6, 135.2, 136.5, 137.5, 139.7,
142.6, 149.0, 149.8, 194.2; FAB (m/z) 392 (M+H)+; HRMS (FAB) calcd for C28H26NO 392.2014 (M+H)+,
found 392.2010; Crystallographic data: C28H25NO, M = 391.51, triclinic, P-1 (#2), T = 298 K, a =
9.9399(10) Å, b = 11.8748(8) Å, c = 9.7921(6) Å, a = 95.791(5)ꢀ, b = 92.372(7)ꢀ, g = 108.820(6)ꢀ, V
= 1085.07(15) Å3, Z = 2, Dc = 1.198 g/cm3, l (CuKa) = 1.54178 Å, R = 0.0456, wR2[F2] = 0.1798 for 865
unique reflections.

HETEROCYCLES, Vol. 80, No. 2, 2010
1139
Typical procedure for domino Heck–C–H activation reaction (Table 3, entries 1–3).
To a solution of 1 (100 mg, 0.41 mmol) in MeCN (4 mL), iodobenzene (91 mL, 0.81 mmol), Pd(OAc)2
(9.2 mg, 0.041 mmol) and i-Pr2NEt (0.21 mL, 1.2 mmol) under an argon atmosphere, and the mixture was
stirred at 80 °C for 1 h. The reaction mixture was evaporated, and CH2Cl2 was added. The mixture was
washed with satd. aq. NH4Cl and brine, and extracted with CH2Cl2. The organic layer was dried over
anhydrous MgSO4, filtered, and evaporated under reduced pressure to give a residue, which was purified
by column chromatography (n-hexane : AcOEt = 9 : 1) to afford 4 (78 mg, 59%, E : Z = 1.0 : 3.6) as a red
solid (Table 3, entry 2).
2-(2,3-Diphenyl-1H-inden-1-ylidene)propanal (4) (E/Z mixture). 1H NMR (270 MHz, CDCl3): ꢀ 1.65
13
(E-isomer), 2.50 (Z-isomer) (s, 3H), 7.00–7.90 (m, 14H), 9.52 (Z-isomer), 10.9 (E-isomer) (s, 1H); C
NMR (68 MHz, CDCl3): ꢀ 14.1, 14.2, 121.2, 121.4, 126.2, 126.4, 126.6, 126.8, 127.3, 127.5, 127.6, 127.8,
128.0, 128.1, 128.2, 128.3, 128.5, 128.6, 128.9, 129.1, 129.2, 129.5, 129.95, 129.99, 130.1, 132.3, 133.6,
136.7, 136.8, 137.4, 137.8, 143.6, 145.9, 152.0, 192.5, 193.0; IR (film) 1659 cm-1; FAB (m/z) 323
(M+H)+; HRMS (FAB) calcd for C24H19O 323.1436 (M+H)+, found 323.1450.
2-[2-(4-Methoxyphenyl)-3-phenyl-1H-inden-1-ylidene]propanal (27).
To a solution of 1 (50 mg, 0.20 mmol) in MeCN (2 mL) were added 4-iodoanisole (95 mg, 0.41 mmol),
Pd(OAc)2 (4.6 mg, 0.020 mmol) and i-Pr2NEt (0.11 mL, 0.63 mmol) under an argon atmosphere, and the
mixture was stirred at 80 °C for 1 h. The reaction mixture was evaporated, and added CH2Cl2. The
mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic layer was dried
over anhydrous MgSO4, filtered and evaporated under reduced pressure. The residue was purified by the
column chromatography (n-hexane : CHCl3 = 9 : 1) to afford 27 (33 mg, 46%, E : Z = 1.0 : 3.6) as a red
solid.
1
27 (E/Z mixture). H NMR (270 MHz, CDCl3): ꢀ 1.68 (E-isomer), 2.49 (Z-isomer) (s, 3H), 3.78
13
(Z-isomer), 3.80 (E-isomer) (s, 3H), 6.70–7.90 (m, 13H), 9.57 (Z-isomer), 10.88 (E-isomer) (s, 1H); C
NMR (68 MHz, CDCl3): ꢀ 14.15, 14.18, 55.1, 113.8, 114.1, 121.1, 121.3, 121.9, 126.0, 126.38, 126.41,
126.8, 127.6, 127.7, 127.8, 128.0, 128.07, 128.13, 128.4, 128.9, 129.1, 129.2, 129.4, 129.8, 131.05,
131.12, 133.8, 136.6, 136.7, 137.4, 143.7, 145.4, 152.2, 158.9, 192.8, 193.2; IR (film) 1028, 1234, 1242,
1654 cm-1; FAB (m/z) 353 (M+H)+; HRMS (FAB) calcd for C25H21O2 353.1542 (M+H)+, found 353.1558.
4-[1-(1-Oxopropan-2-ylidene)-3-phenyl-1H-inden-2-yl]phenylmethanesulfonate (28). To a solution of
1 (50 mg, 0.20 mmol) in MeCN (2 mL) were added 4-iodophenyl methanesulfonate (121 mg, 0.41 mmol),
Pd(OAc)2 (4.6 mg, 0.020 mmol) and i-Pr2NEt (0.11 mL, 0.63 mmol) under an argon atmosphere, and the
mixture was stirred at 80 °C for 1 h. The reaction mixture was evaporated, and added CH2Cl2. The
mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic layer was dried
over anhydrous MgSO4, filtered and evaporated under reduced pressure. The residue was purified by the

1140
HETEROCYCLES, Vol. 80, No. 2, 2010
column chromatography (n-hexane : AcOEt = 7 : 3) to afford 28 (32 mg, 39%, E : Z = 1.0 : 3.1) as a red
solid.
1
28 (E/Z mixture). H NMR (270 MHz, CDCl3): ꢀ 1.68 (E-isomer), 2.51 (Z-isomer) (s, 3H), 3.11
(Z-isomer), 3.17 (E-isomer) (s, 3H), 7.00–7.90 (m, 13H), 9.57 (s, 1H, Z-isomer), 10.88 (s, 1H, E-isomer);
13C NMR (68 MHz, CDCl3): ꢀ 8.9, 14.2, 37.3, 38.0, 121.5, 121.6, 121.8, 122.1, 122.4, 126.5, 127.0, 127.1,
128.0, 128.2, 128.3, 128.6, 128.96, 129.02, 129.6, 131.6, 131.8, 133.2, 135.0, 136.6, 137.2, 137.4, 139.8,
140.0, 143.2, 147.0, 148.5, 151.8, 191.9, 192.8; IR (film) 1150, 1174, 1356, 1651 cm-1; FAB (m/z) 417
(M+H)+; HRMS (FAB) calcd for C25H21O4S 417.1161 (M+H)+, found 417.1165.
2-[2-(4-Nitrophenyl)-3-phenyl-1H-inden-1-ylidene]propanal (29).
To a solution of 1 (50 mg, 0.20 mmol) in MeCN (2 mL) were added 1-iodo-4-nitrobenzene (101 mg, 0.41
mmol), Pd(OAc)2 (4.6 mg, 0.020 mmol) and i-Pr2NEt (0.11 mL, 0.63 mmol) under an argon atmosphere,
and the mixture was stirred at 80 °C for 1 h. The reaction mixture was evaporated, and added CH2Cl2. The
mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic layer was dried
over anhydrous MgSO4, filtered and evaporated under reduced pressure. The residue was purified by the
column chromatography (n-hexane : AcOEt = 9 : 1) to afford 29 (49 mg, 66%, E : Z = 1.0 : 4.3) as a red
solid.
29 (E/Z mixture). 1H NMR (270 MHz, CDCl3): ꢀ 1.67 (E-isomer), 2.52 (Z-isomer) (s, 3H), 7.00–8.50 (m,
13H), 9.52 (Z-isomer), 10.88 (E-isomer) (s, 1H); 13C NMR (68 MHz, CDCl3): ꢀ 14.2, 15.2, 121.8, 121.9,
123.5, 123.8, 129.3, 126.9, 127.4, 128.3, 128.38, 128.42, 128.5, 128.8, 128.9, 129.2, 129.8, 130.8, 131.1,
132.8, 134.2, 136.6, 137.5, 143.0, 144.9, 145.0, 146.8, 148.1, 151.5, 191.4, 192.4; IR (film) 1340, 1508,
1595, 1658 cm-1; FAB (m/z) 368 (M+H)+; HRMS (FAB) calcd for C24H18NO3 368.1287 (M+H)+, found
368.1302.
2-[2-(4-Bromophenyl)-3-phenyl-1H-inden-1-ylidene]propanal (30).
To a solution of 1 (50 mg, 0.20 mmol) in MeCN (2 mL) were added 1-bromo-4-iodobenzene (115 mg,
0.41 mmol), Pd(OAc)2 (4.6 mg, 0.020 mmol) and i-Pr2NEt (0.11 mL, 0.63 mmol) under an argon
atmosphere, and the mixture was stirred at 80 °C for 1 h. The reaction mixture was evaporated, and added
CH2Cl2. The mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic
layer was dried over anhydrous MgSO4, filtered and evaporated under reduced pressure. The residue was
purified by the column chromatography (n-hexane : AcOEt = 9 : 1) to afford 30 (44 mg, 55%, E : Z =
1.0 : 2.7) as a red solid.
30 (E/Z mixture). 1H NMR (270 MHz, CDCl3): ꢀ 1.68 (E-isomer), 2.50 (Z-isomer) (s, 3H), 7.00–7.90 (m,
13H), 9.58 (Z-isomer), 10.87 (E-isomer) (s, 1H); 13C NMR (68 MHz, CDCl3): ꢀ 14.2, 14.6, 121.4, 121.6,
121.8, 126.5, 126.9, 127.9, 128.25, 128.33, 129.0, 129.1, 129.6, 131.5, 131.8, 131.9, 133.3, 135.4, 136.67,
136.73, 137.4, 143.4, 151.8, 192.1, 192.9; IR (film) 771, 1660 cm-1; FAB (m/z) 400 (M)+; HRMS (FAB)

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1141
calcd for C24H17BrO 400.0463 (M)+, found 400.0444.
2-[2-(3-Methoxyphenyl)-3-phenyl-1H-inden-1-ylidene]propanal (31).
To a solution of 1 (50 mg, 0.20 mmol) in MeCN (2 mL) were added 3-iodoanisole (95 mg, 0.41 mmol),
Pd(OAc)2 (4.6 mg, 0.020 mmol) and i-Pr2NEt (0.11 mL, 0.63 mmol) under an argon atmosphere, and the
mixture was stirred at 80 °C for 2 h. The reaction mixture was evaporated, and added CH2Cl2. The
mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic layer was dried
over anhydrous MgSO4, filtered and evaporated under reduced pressure. The residue was purified by the
column chromatography (n-hexane : AcOEt = 9 : 1) to afford 31 (33mg, 47%, E : Z = 1.0 : 2.3) as a red
solid.
1
31 (E/Z mixture). H NMR (270 MHz, CDCl3): ꢀ 1.70 (E-isomer), 2.49 (Z-isomer) (s, 3H), 3.66
13
(Z-isomer), 3.71 (E-isomer) (s, 3H), 6.50–7.90 (m, 13H), 9.55 (Z-isomer), 10.88 (E-isomer) (s, 1H); C
NMR (68 MHz, CDCl3): ꢀ 14.1, 14.2, 55.1, 55.3, 113.0, 113.3, 113.7, 115.4, 115.6, 121.3, 121.5, 122.6,
123.0, 126.2, 126.4, 126.6, 126.8, 127.7, 127.8, 128.08, 128.14, 128.2, 128.9, 129.0, 129.1, 129.4, 129.5,
129.7, 129.8, 130.0, 130.7, 133.7, 136.6, 136.7, 137.4, 139.0, 139.4, 143.5, 151.9, 159.6, 192.7, 193.1; IR
(film) 1454, 1575, 1599, 1659 cm-1; FAB (m/z) 353 (M+H)+. HRMS (FAB) calcd for C25H21O2 353.1542
(M+H)+, found 353.1506.
Preparation of 3-iodophenyl methanesulfonate for Table 3 (entry 10).
To a solution of m-iodophenol (1.0 g, 4.5 mmol) in CH2Cl2 (25 mL) were added MsCl (0.70 mL, 9.0
mmol) and Et3N (1.9 mL, 14 mmol) under an argon atmosphere at 0 °C. The mixture was stirred at room
temperature for 30 min. The mixture was washed with brine. The organic layer was dried over anhydrous
MgSO4, filtered and evaporated under reduce pressure to give 3-iodophenyl methanesulfonate (1.3 g,
98%) as a white solid.
1
3-Iodophenyl methanesulfonate. H NMR (270 MHz, CDCl3): ꢀ 3.17 (s, 3H), 7.15 (t, 1H, J = 8.0 Hz,
13
1H), 7.29 (br d, 1H, J = 8.0 Hz), 7.60–7.73 (m, 2H); C NMR (68 MHz, CDCl3): ꢀ 37.6, 93.8, 121.5,
131.0, 131.2, 136.5, 149.1; IR (film) 1331, 1576, 3034 cm-1; FAB (m/z) 299 (M+H)+; HRMS (FAB) calcd
for C7H8O3IS 298.9239 (M+H)+, found 298.9239.
3-[1-(1-Oxopropan-2-ylidene)-3-phenyl-1H-inden-2-yl]phenylmethanesulfonate (32). To a solution
of 1 (50 mg, 0.20 mmol) in MeCN (2 mL) were added 3-iodophenyl methanesulfonate (121 mg, 0.41
mmol), Pd(OAc)2 (4.6 mg, 0.020 mmol) and i-Pr2NEt (0.11 mL, 0.63 mmol) under an argon atmosphere,
and the mixture was stirred at 80 °C for 1 h. The reaction mixture was evaporated, and added CH2Cl2. The
mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic layer was dried
over anhydrous MgSO4, filtered and evaporated under reduced pressure. The residue was purified by the
column chromatography (CHCl3) to afford 32 (52mg, 62%, E : Z = 1.0 : 2.3) as a red solid.
1
32 (E/Z mixture). H NMR (270 MHz, CDCl3): ꢀ 1.71 (E-isomer), 2.51 (Z-isomer) (s, 3H), 2.80

1142
HETEROCYCLES, Vol. 80, No. 2, 2010
13
(Z-isomer), 2.86 (E-isomer) (s, 3H), 7.00–8.00 (m, 13H), 9.60 (Z-isomer), 10.88 (E-isomer) (s, 1H); C
NMR (68 MHz, CDCl3): ꢀ 14.2, 14.7, 36.7, 36.9, 121.1, 121.2, 121.5, 121.6, 123.1, 123.6, 126.5, 126.6,
126.9, 127.1, 127.9, 128.1, 128.3, 128.4, 129.0, 129.1, 129.3, 129.7, 129.9, 130.3, 133.3, 134.8, 136.5,
137.5, 140.0, 143.1, 147.2, 148.5, 149.2, 149.5, 151.4, 192.0, 192.7; IR (film) 829, 1338, 1655 cm-1; FAB
(m/z) 417 (M+H)+; HRMS (FAB) calcd for C25H21O4S 417.1161 (M+H)+, found 417.1161.
2-[2-(3-Nitrophenyl)-3-phenyl-1H-inden-1-ylidene]propanal (33).
To a solution of 1 (50 mg, 0.20 mmol) in MeCN (2 mL) were added 1-iodo-3-nitrobenzene (101 mg, 0.41
mmol), Pd(OAc)2 (4.6 mg, 0.020 mmol) and i-Pr2NEt (0.11 mL, 0.63 mmol) under an argon atmosphere,
and the mixture was stirred at 80 °C for 1 h. The reaction mixture was evaporated, and added CH2Cl2. The
mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic layer was dried
over anhydrous MgSO4, filtered and evaporated under reduced pressure. The residue was purified by the
column chromatography (n-hexane : AcOEt = 9 : 1) to afford 33 (35mg, 47%, E : Z = 1.0 : 2.5) as a red
solid.
33 (E/Z mixture). 1H NMR (270 MHz, CDCl3): ꢀ 1.66 (E-isomer), 2.53 (Z-isomer) (s, 3H), 7.10–8.20 (m,
13H), 9.57 (Z-isomer), 10.89 (E-isomer) (s, 1H); 13C NMR (68 MHz, CDCl3): ꢀ 14.2, 15.0, 121.8, 121.9,
122.4, 124.7, 125.1, 126.6, 126.9, 127.0, 127.4, 128.2, 128.36, 128.43, 128.5, 128.9, 129.0, 129.2, 129.3,
129.6, 129.8, 132.7, 132.8, 133.9, 135.9, 136.3, 136.5, 137.5, 139.7, 143.0, 148.1, 148.3, 151.5, 191.4,
192.5; IR (film) 1232, 1346, 1528 1655 cm-1; FAB (m/z) 368 (M+H)+; HRMS (FAB) calcd for C24H18NO3
368.1287 (M+H)+, found 368.1301.
2-[6-Methyl-2-(4-nitrophenyl)-3-p-tolyl-1H-inden-1-ylidene]propanal (34).
To a solution of 10 (55 mg, 0.20 mmol) in MeCN (2 mL) were added 1-iodo-4-nitrobenzene (100 mg,
0.40 mmol), Pd(OAc)2 (4.5 mg, 0.020 mmol) and i-Pr2NEt (0.10 mL, 0.57 mmol) under an argon
atmosphere, and the mixture was stirred at 80 °C for 1 h. The reaction mixture was evaporated, and added
CH2Cl2. The mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic
layer was dried over anhydrous MgSO4, filtered and evaporated under reduced pressure. The residue was
purified by the column chromatography (n-hexane : AcOEt = 9 : 1) to afford 34 (39 mg, 49%, E : Z =
1.0 : 2.4) as a red crystal.
34 (E/Z mixture). Mp 202–204 °C; 1H NMR (500 MHz, CDCl3): ꢀ 1.65 (E-isomer), 2.50 (Z-isomer) (s,
3H), 2.32 (E-isomer), 2.33 (Z-isomer) (s, 3H), 2.42 (E-isomer), 2.47 (Z-isomer) (s, 3H), 6.98 (Z-isomer),
7.02 (E-isomer) (d, 2H, J = 7.9 Hz), 7.06–7.12 (E/Z isomer) (m, 2H), 7.13–7.19 (E/Z isomer) (m, 2H),
7.32 (Z-isomer, Hb), 7.35 (E-isomer, Hd) (d, 2H, J = 8.5 Hz), 7.43 (E-isomer, Hc), 7.72 (Z-isomer, Ha) (s,
1H), 8.11 (Z-isomer), 8.14 (E-isomer) (d, 2H, J = 8.5 Hz), 9.51 (Z-isomer), 10.86 (E-isomer) (s, 1H); 13C
NMR (68 MHz, CDCl3): ꢀ 14.2, 15.1, 21.3, 21.8, 21.9, 121.6, 121.8, 123.5, 123.8, 127.7, 128.2, 128.7,
128.9, 129.1, 129.2, 129.6, 129.8, 129.9, 130.2, 130.9, 131.2, 133.2, 135.0, 136.7, 136.9, 137.1, 137.4,

HETEROCYCLES, Vol. 80, No. 2, 2010
1143
138.2, 138.4, 138.5, 140.3, 140.6, 144.9, 145.5, 146.7, 148.2, 151.9, 191.5, 192.7; FAB (m/z) 396
(M+H)+; HRMS (FAB) calcd for C26H22NO3 396.1599 (M+H)+, found 396.1592; Crystallographic data:
C26H21NO3, M = 395.46, triclinic, P-1 (#2), T = 298 K, a = 10.7108(14) Å, b = 11.2338(13) Å, c =
10.2696(12) Å, ꢀ = 96.444(10)ꢀ, ꢁ = 110.963(9)ꢀ, ꢂ = 110.197(9)ꢀ, V = 1043.0(2) Å3, Z = 2, Dc =
1.259 g/cm3, ꢃ (CuKꢀ) = 1.54178 Å, R = 0.1183, wR2[F2] = 0.3072 for 833 unique reflections. CCDC
609878.
2-[2-(1H-Indol-5-yl)-3-phenyl-inden-1-ylidene]-propionaldehyde (35).
To a solution of 1 (200 mg, 0.81 mmol) in MeCN (8 mL) were added 5-iodoindole (394 mg, 1.62 mmol),
Pd(OAc)2 (18 mg, 0.080 mmol) and i-Pr2NEt (0.42 mL, 2.43 mmol) under an argon atmosphere, and the
mixture was stirred at 80 °C for 3 h. The reaction mixture was evaporated, and added CH2Cl2. The
mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic layer was dried
over anhydrous MgSO4, filtered and evaporated under reduce pressure. The residue was purified by the
column chromatography (n-hexane : AcOEt = 98 : 2 to 93 : 7) to afford 35 (209 mg, 71%, E : Z = 1.0 :
4.7) as a red solid.
35 (E/Z mixture). 1H NMR (500 MHz, CDCl3): ꢀ 1.59 (E-isomer), 2.50 (Z-isomer) (s, 3H), 6.30–8.30 (m,
15H), 9.38 (Z-isomer), 10.89 (E-isomer) (s, 1H); 13C NMR (68 MHz, CDCl3): ꢀ 14.0, 14.2, 102.8, 102.9,
111.0, 111.4, 121.0, 121.3, 122.15, 122.24, 124.2, 124.3, 124.5, 124.8, 125.9, 126.2, 126.4, 126.8, 127.4,
127.6, 127.9, 128.0, 128.1, 128.8, 129.0, 129.2, 129.3, 129.4, 135.1, 137.4, 144.0, 193.1, 193.5; IR (film)
765, 1647, 3356 cm-1; FAB (m/z) 362 (M+H)+; HRMS (FAB) calcd for C26H20NO 362.1545 (M+H)+,
found 362.1540.
2-[2-(1-Methyl-1H-indol-5-yl)-3-phenyl-inden-1-ylidene]-propionaldehyde (36).
To a solution of 1 (39 mg, 0.16 mmol) in MeCN (2 mL) were added 1-methyl-5-iodoindole (81 mg, 0.32
mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol) and i-Pr2NEt (0.08 mL, 0.47 mmol) under an argon atmosphere,
and the mixture was stirred at 80 °C for 4 h. The reaction mixture was evaporated, and added CH2Cl2. The
mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic layer was dried
over anhydrous MgSO4, filtered and evaporated under reduce pressure. The residue was purified by the
column chromatography (n-hexane : AcOEt = 98 : 2) to afford 36 (18 mg, 30%, E : Z = 1.0 : 3.0) as a red
solid.
1
36 (E/Z mixture). H NMR (500 MHz, CDCl3): ꢀ 1.58 (E-isomer), 2.50 (Z-isomer) (s, 3H), 3.77
13
(Z-isomer), 3.78 (E-isomer) (s, 3H), 6.30–8.00 (m, 14H), 9.34 (Z-isomer), 10.90 (E-isomer) (s, 1H); C
NMR (125 MHz, CDCl3): ꢀ 14.0, 14.2, 32.9, 101.1, 101.2, 109.2, 121.0, 121.3, 122.4, 123.7, 123.8, 126.2,
126.3, 126.8, 127.4, 127.5, 128.0, 128.1, 128.4, 128.6, 128.8, 129.15, 129.24, 129.3, 129.4, 134.2, 136.0,
136.9, 137.4, 138.3, 144.0, 144.8, 152.9, 193.0, 193.5; FAB (m/z) 375 (M)+; HRMS (FAB) calcd for
C24H19O 375.1623 (M)+, found 375.1609.

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HETEROCYCLES, Vol. 80, No. 2, 2010
2-[2-(1-Tosyl-1H-indol-5-yl)-3-phenyl-inden-1-ylidene]-propionaldehyde (37).
To a solution of 1 (25 mg, 0.10 mmol) in MeCN (1 mL) were added 1-tosyl-5-iodoindole (80 mg, 0.20
mmol), Pd(OAc)2 (2 mg, 0.01 mmol) and i-Pr2NEt (0.05 mL, 0.30 mmol) under an argon atmosphere, and
the mixture was stirred at 80 °C for 21 h. The reaction mixture was evaporated, and added CH2Cl2. The
mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic layer was dried
over anhydrous MgSO4, filtered and evaporated under reduced pressure. The residue was purified by the
column chromatography (n-hexane : AcOEt = 99 : 1 to 90 : 10) to afford 37 (20 mg, 39%, E : Z = 1.0 :
7.0) as an orange solid.
1
37 (E/Z mixture). H NMR (500 MHz, CDCl3): ꢀ 1.47 (E-isomer), 2.48 (Z-isomer) (s, 3H), 2.37
13
(E-isomer), 2.38 (Z-isomer) (s, 3H), 6.50–8.00 (m, 18H), 9.37 (Z-isomer), 10.87 (E-isomer) (s, 1H); C
NMR (125 MHz, CDCl3): ꢀ 14.1, 21.6, 109.1, 109.3, 113.8, 121.3, 122.7, 126.5, 126.6, 126.8, 127.1,
127.6, 128.1, 129.1, 129.5, 129.8, 130.0, 130.9, 132.9, 133.6, 134.1, 135.1, 137.3, 143.6, 145.1, 146.2,
152.4, 192.4; IR (film) 763, 1117, 1165, 1363, 1657 cm-1; FAB (m/z) 516 (M+H)+; HRMS (FAB) calcd
for C33H26NO3S 516.1633 (M+H)+, found 516.1642.
2-(3-Phenyl-2-thiophen-2-yl-inden-1-ylidene)-propionaldehyde (38).
To a solution of 1 (50 mg, 0.20 mmol) in MeCN (2 mL) were added 2-iodothiophene (0.04 mL, 0.40
mmol), Pd(OAc)2 (4.6 mg, 0.02 mmol) and i-Pr2NEt (0.11 mL, 0.60 mmol) under an argon atmosphere,
and the mixture was stirred at 80 °C for 1.3 h. The reaction mixture was evaporated, and added CH2Cl2.
The mixture was washed with satd. aq. NH4Cl and brine, extracted with CH2Cl2. The organic layer was
dried over anhydrous MgSO4, filtered and evaporated under reduced pressure. The residue was purified
by the column chromatography (n-hexane : AcOEt = 98 : 2 to 95 : 5) to afford 38 (53 mg, 80%, E : Z =
1.0 : 5.9) as a red solid.
38 (E/Z mixture). 1H NMR (270 MHz, CDCl3): ꢀ 1.81 (E-isomer), 2.51 (Z-isomer) (s, 3H), 6.70–8.00 (m,
12H), 9.59 (Z-isomer), 10.87 (E-isomer) (s, 1H); 13C NMR (125 MHz, CDCl3): ꢀ 13.3, 14.3, 121.7, 121.9,
126.4, 126.6, 126.7, 126.9, 127.0, 127.1, 127.3, 127.5, 128.06, 128.14, 128.2, 128.3, 128.5, 128.7, 128.8,
128.9, 128.95, 129.03, 129.1, 129.2, 129.5, 129.7, 130.0, 130.4, 132.4, 133.5, 136.8, 138.0, 138.4, 143.3,
147.8, 151.8, 192.4, 193.1; IR (film) 1659, 2916, 3067 cm-1; FAB (m/z) 329 (M+H)+; HRMS (FAB) calcd
for C22H17OS 329.1000 (M+H)+, found 329.1023.
Typical procedure for domino cyclization–allylation reaction (Table 3, entry 2).
1 (40 mg, 0.16 mmol) was dissolved in dry toluene (2 mL). MeMgBr (0.84 M THF solution) (0.21 mL,
1.1 eq) was added to the solution at –78 °C under an Ar atmosphere. After stirring at –78 °C for 1 h, the
mixture was warmed to rt. Then Pd(OAc)2 (3.6 mg, 0.1 eq) and allyl bromide (42 μL) were added to the
mixture and stirred for 14 h. the mixture was filtered and evaporated under reduced pressure. The residue
was purified by silica gel column chromatography (n-hexane/EtOAc = 20/1) to afford 5 (21 mg, 42%) as

HETEROCYCLES, Vol. 80, No. 2, 2010
1145
colorless clear oil.
1
3-Allyl-2-benzhydryl-4,5-dimethylfuran (5): H NMR (270 MHz, CDCl3) ꢀ 1.83 (s, 3H), 2.14 (s, 3H),
2.37 (d, J = 5.9 Hz, 1H), 4.92-4.97 (m, 2H), 5.38 (s, 1H), 5.75 (m, 1H), 7.12-7.27 (m, 10H); 13C NMR (68
MHz, CDCl3) ꢀ 8.4, 11.6, 28.1, 48.5, 114.8, 115.0, 118.8, 126.3, 128.2, 128.9, 136.5, 142.4, 146.0, 148.0;
IR (film) 743, 752, 910, 1031, 1116, 1597, 2920 cm-1; FAB (m/z) 302 (M)+, HRMS m/z calcd. for
C22H22O; 302.1671 (M)+, found: 302.1628.
ACKNOWLEDGEMENTS
This work was financially supported by the 21st Century COE Program.
REFERENCES AND NOTES
‡
This paper is also dedicated to the memory of the late professor Kiyoshi Tanaka, who passed away
on December 8, 2004.
§
Present address:Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
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