Lewis acid promoted reactions of 1,1-diarylallenes and ketone derivatives: Synthesis of indenes by an addition/cyclization reaction

Article abstract of DOI:10.1055/s-0031-1290776

The Lewis acid promoted reaction of 1,1-diarylallenes with ketone derivatives was examined. The tin(IV) chloride promoted reaction of diarylallenes with vinyl ketones gave indene derivatives through a conjugate addition/cyclization reaction. The reaction of diphenylallene with diethyl oxomalonate in the presence of one equivalent of tin(IV) chloride at -40°C gave diethyl hydroxy(3-phenyl-1H-inden-2-yl)malonate as the major product through a carbonyl addition/cyclization reaction, whereas the same reactants in the presence of 0.2 equivalents of tin(IV) chloride at 80 °C gave diethyl (3-phenyl-1H-inden-2-yl)malonate. Diethyl hydroxy(3-phenyl-1H-inden-2-yl) malonate was also converted into the latter product on heating at 80 °C in the presence of 0.2 equivalents of tin(IV) chloride. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0031-1290776

SPECIAL TOPIC
▌2155
special topic
Lewis Acid Promoted Reactions of 1,1-Diarylallenes and Ketone Derivatives:
Synthesis of Indenes by an Addition/Cyclization Reaction
Lewis Acid Promoted Reactions of 1,1-Diarylallenes and Ketones
Shoko Yamazaki,*a Yugo Fukushima,a,b Tetsuma Ukai,a Kohei Tatsumi,a Akiya Ogawab
a
Department of Chemistry, Nara University of Education, Takabatake-cho, Nara 630-8528, Japan
b
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Gakuen-cho 1-1, Nakaku, Sakai, Osaka
599-8531, Japan
Fax +81(742)279289; E-Mail: yamazaks@nara-edu.ac.jp
Received: 19.12.2011; Accepted: 01.03.2012
mechanistic interest.6,7 We examined the Lewis acid pro-
Abstract: The Lewis acid promoted reaction of 1,1-diarylallenes
moted reactions of 1,1-diarylallenes with ketone deriva-
with ketone derivatives was examined. The tin(IV) chloride pro-
tives, such as vinyl ketones 4 (for 1,4-addition) and
diethyl oxomalonate (6) (for 1,2-addition). For compari-
moted reaction of diarylallenes with vinyl ketones gave indene de-
rivatives through a conjugate addition/cyclization reaction. The
reaction of diphenylallene with diethyl oxomalonate in the presence son, we also examined the Lewis acid catalyzed reactions
of one equivalent of tin(IV) chloride at –40 °C gave diethyl hy-
droxy(3-phenyl-1H-inden-2-yl)malonate as the major product
through a carbonyl addition/cyclization reaction, whereas the same
of diethyl oxomalonate (6) with 1,1-dialkylallenes.
As previously described,5 the tin(IV) chloride promoted
reaction of 1,1-diphenylallene (1a) with diethyl benzyli-
denemalonate as a Michael acceptor failed to proceed
through a conjugate addition/cyclization. Highly reactive
electrophiles may be required. We therefore examined the
reactions of simple reactive vinyl ketones. Because
tin(IV) chloride has been shown to be an effective catalyst
for indene formation through the reaction of ethylene-
1,1,2-tricarboxylates 2 with arylallenes,5 we first exam-
ined the tin(IV) chloride promoted reaction. The reaction
of 1,1-diarylallenes 1a–b with vinyl ketones 4 in the pres-
ence of tin(IV) chloride in dichloromethane or chloroform
at room temperature gave the corresponding indene deriv-
atives 5 (Scheme 2). Both reactants 1 and 4 are unstable in
the presence of the Lewis acid. Optimum yields of indenes
5 were obtained under the reaction conditions shown in
Table 1.8 For example, the reaction of allene 1a in the
presence of two equivalents of vinyl ketone 4a and one
equivalent of tin(IV) chloride in chloroform for five min-
utes gave the indene derivative 5a in 54% yield (Table 1,
entry 1). The reaction of allene 1a with ketone 4a in the
presence of zinc(II) iodide or aluminum(III) chloride re-
sulted in decomposition of the substrates and did not give
the indene product. Tin(IV) chloride may have suitable
Lewis acidity for this indene formation, as in the case of
ethylene-1,1,2-tricarboxylates.5
reactants in the presence of 0.2 equivalents of tin(IV) chloride at 80
°C gave diethyl (3-phenyl-1H-inden-2-yl)malonate. Diethyl hy-
droxy(3-phenyl-1H-inden-2-yl)malonate was also converted into
the latter product on heating at 80 °C in the presence of 0.2 equiva-
lents of tin(IV) chloride.
Key words: allenes, Lewis acids, ketones, cyclizations, Michael
additions, addition reactions
Because of their structural feature comprising two adja-
cent carbon–carbon double bonds, allene derivatives play
an important role in organic synthesis1 and the transition-
metal-catalyzed reactions of allenes to give a variety of
products have been studied extensively.2 Although Lewis
acids are important catalysts in organic synthesis,3 few ex-
amples of Lewis acid promoted reactions of allenes have
been reported.4 We recently showed that the reaction of
arylallenes 1 with ethylene-1,1,2-tricarboxylate triesters 2
in the presence of tin(IV) chloride gives the corresponding
indene derivatives 3 efficiently through a conjugate addi-
tion/cyclization reaction (Scheme 1).5 In this reaction, the
phenylallene moiety reacts with tin(IV) chloride coordi-
nated ethylene-1,1,2-tricarboxylates 2 to form a phenyl al-
lylic cation intermediate that undergoes cyclization.
The examination of other electrophiles that can be activat-
ed by Lewis acids to form indenes is of synthetic and
CO2Et
EtO2C
RO2C
CO2Et
EtO2C
Lewis acid
+
r.t. or 80 °C
17–19 h
RO2C
Z
Z
Z
1
2
Z = H, Cl, Me
Z
3
Scheme 1
SYNTHESIS 2012, 44, 2155–2161
Advanced online publication: 03.04.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0031-1290776; Art ID: SS-2011-C1160-ST
© Georg Thieme Verlag Stuttgart · New York

2156
S. Yamazaki et al.
SPECIAL TOPIC
O
R
O
SnCl4
(1 equiv)
+
R
r.t.
CH2Cl2 or
CHCl3
Z
Z
Z
4a: R = Me
4b: R = Et
1a: Z = H
1b: Z = Cl
Z
5a–d
(1 equiv)
(2 equiv)
Scheme 2
cyclohex-2-en-1-one, gave complex mixtures or unreact-
ed starting materials.
Table 1 Reactions of 1,1-Diarylallenes 1a–b with Vinyl Ketones
4a–b
Next, we examined the 1,2-addition reactions of activated
carbonyl compounds with diarylallenes. The reaction of
1,1-diphenylallene (1a) and diethyl oxomalonate (6) in
the presence of one equivalent of tin(IV) chloride in di-
chloromethane at –40 °C gave the hydroxy(indenyl)malo-
nate 7a in 56% yield (Scheme 3). The reaction of 1,1-
bis(4-chlorophenyl)allene (1b) and oxomalonate 6 at var-
ious temperatures gave complex mixtures, possibly in-
cluding indene derivatives. The products could not be
isolated or purified.
Entrya
Allene Ketone Solvent
Time
Product Yield
(%)c
5 minb
5 minb
1
2
3
4
1a
1a
1b
1b
4a
4b
4a
4b
CHCl3
CHCl3
CH2Cl2
CHCl3
5a
5b
54
58
58
50
overnight 5c
5d
1 hb
a Reactions were carried out with 1 (1.0 mmol), 4 (2.0 mmol), and
SnCl4 (1.0 mmol) in the appropriate solvent (4–8 mL).
When the reaction of 1a with 6 was carried out in the pres-
ence of 0.2 equivalents of tin(IV) chloride at 80 °C in 1,2-
dichloroethane, the indenylmalonate 8a was obtained as
the major product in 66% yield (Scheme 4). At room tem-
perature, this reaction gave a complex mixture of products
including hydroxy(indenyl)malonate 7a and indenylmal-
onate 8a. Zinc(II) iodide was also an effective catalyst for
indene formation.
b To monitor the progress of the reaction, parallel experiments were
carried out in an NMR tube (0.1-mmol scale).
c Isolated yield.
Under similar conditions, other α,β-conjugated carbonyl
compounds, such as trimethyl phosphonoacrylate, di-
methyl (dicyanomethylene)malonate,9 methyl acrylate, or
CO2Et
HO
SnCl4 or
EtO2C
CO2Et
EtO2C
ZnI2
+
Z
O
Z
Z
1a: Z = H
1c: Z = Me
6
Z
7a: Z = H, SnCl4 (1 equiv)
–40 °C, CH2Cl2, 56%
7b: Z = Me, ZnI2 (0.2 equiv)
r.t., CH2Cl2, 32%
Scheme 3
CO2Et
SnCl4 or
EtO2C
ZnI2
CO2Et
EtO2C
+
Z
O
Z
Z
Z
1a: Z = H
1c: Z = Me
8a: Z = H, SnCl4 (0.2 equiv)
80 °C, ClCH2CH2Cl, 66%
8a: Z = H, ZnI2 (0.2 equiv)
80 °C, ClCH2CH2Cl, 43%
8b: Z = Me, SnCl4 (1 equiv)
r.t., CH2Cl2, 36%
6
8b: Z = Me, SnCl4 (0.2 equiv)
80 °C, ClCH2CH2Cl, 36%
Scheme 4
Synthesis 2012, 44, 2155–2161
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Lewis Acid Promoted Reactions of 1,1-Diarylallenes and Ketones
2157
The reaction of 1,1-di(4-tolyl)allene (1c) and oxomalo-
nate 6 in the presence of 1.0 or 0.2 equivalents of tin(IV)
chloride at room temperature gave indenylmalonate 8b as
the major product (Scheme 4). The reaction of allene 1c
and oxomalonate 6 in the presence of 0.2 equivalents of
zinc(II) iodide at room temperature gave hydroxy(inde-
nyl)malonate 7b as the major product in 32% yield
(Scheme 3).
Cl4Sn
O
Cl4Sn
ΔE‡ = +12.03
kcal/mol
TSV1
O
3
2
1a
β
addition
Ph
1
Ph
V1
V2
ΔE = 0 kcal/mol
ΔE = –2.32 kcal/mol
Cl3
Sn
SnCl3
O
On heating at 80 °C in the presence of tin(IV) chloride, 7a
was transformed into 8a in 52% yield (Scheme 5). The
mechanism for the reduction of 7a to 8a is unclear. It
might involve a Lewis acid catalyzed process, possibly re-
lated to reported results for disproportionation of allylic
alcohols,10 although 8a was the only isolated and identi-
fied product. The stable enolate of the malonate generated
in situ may also facilitate the reaction.
ΔE‡ = +9.61
kcal/mol
Cl
ΔE‡ = –3.85
kcal/mol
Cl
O
H
H
TSV3
TSV2
H+-abstraction
ring closure
Ph
Ph
V3
V4
ΔE = –5.11 kcal/mol
ΔE = –14.29 kcal/mol
Cl3
Sn
ΔE‡ = –11.76
kcal/mol
TSV4
Cl4Sn
CO2Et
CO2Et
O
Cl
O
HO
HCl
H
EtO2C
EtO2C
transfer
SnCl4
protonation
80 °C
ClCH2CH2Cl
52%
Ph
Ph
V6
V5
ΔE = –12.82 kcal/mol
7a
8a
ΔE = –44.84 kcal/mol
Scheme 5
Scheme 6 Proposed mechanism and B3LYP/LANL2DZ calculated
energies for the reaction of 1,1-diphenylallene (1a) with but-3-en-2-
one (4a) in the presence of tin(IV) chloride (see Scheme 2); ΔE = sum
of electronic and zero-point energies (kcal/mol)
The reaction of 1a with other carbonyl compounds such as
ethyl glyoxylate, benzaldehyde, acetyl chloride, or acetic
anhydride under similar conditions gave complex mix-
tures or unreacted starting materials.
O
SnCl4
The mechanism for indene formation from a vinyl ketone
(Scheme 2) may be similar to the reaction with ethylene-
1,1,2-tricarboxylates (Scheme 1).5 To clarify the mecha-
nisms for indene formation, we carried out density func-
tional theory calculations for the addition–cyclization
reactions of the model compounds trimethyl ethylene-
1,1,2-tricarboxylate (2m) (Scheme S1 in the Supporting
Information), but-3-en-2-one (4a) (Scheme 6), and di-
methyl oxomalonate (6m) (Scheme 7). The structure of
each intermediate and transition state (TS) was optimized
by B3LYP/LANL2DZ calculations (see Supporting Infor-
mation).
Cl4Sn
MeO2C
3
O
ΔE‡ = +1.37
kcal/mol
OMe
O
O
1a
MeO
6m
2
MeO2C
TSK1
Ph
1
addition
Ph
K2
K1
ΔE = 0 kcal/mol
ΔE = –15.70 kcal/mol
O
SnCl3
Cl
O
SnCl3
Cl
ΔE‡ = –19.83
kcal/mol
MeO
ΔE‡ = –4.15
MeO
O
O
kcal/mol
MeO2C
Ph
H
MeO2C
H
TSK3
TSK2
Ph
H+-abstraction
ring closure
Initially, tin(IV) chloride might coordinate to the carbonyl
group of but-3-en-2-one (4a) (Scheme 6). The reaction
starts from the reactant complex V1. Transition state
TSV1, formed by conjugate addition of the allene at the
C2 position to the tin(IV) chloride coordinated 4a, leads
to intermediate V2. The cyclization transition state TSV2,
formed from intermediate V2 then leads to the indene
skeleton V3. The proton abstraction transition state TSV3
leads to intermediate V4, and subsequent transfer of hy-
drogen chloride gives intermediate V5. Protonation
through TSV4 gives the product complex V6.
K4
ΔE = –41.69 kcal/mol
K3
ΔE = –18.80 kcal/mol
O
SnCl3
O
SnCl4
H
ΔE‡ = –32.36
kcal/mol
MeO
MeO2C
MeO
MeO2C
O
Cl
O
H
HCl
transfer
TSK4
protonation
Ph
Ph
K6
ΔE = –55.75 kcal/mol
K5
ΔE = –44.30 kcal/mol
Scheme 7 Proposed mechanism and B3LYP/LANL2DZ calculated
energies for the reaction of 1,1-diphenylallene (1a) with dimethyl
oxomalonate (6m) in the presence of tin(IV) chloride (for Scheme 3)
The proposed mechanism for indene formation with an
oxomalonate is shown in Scheme 7. The reactant complex
K1 consists of allene 1a and tin(IV) chloride coordinated
to oxomalonate 6m through the ketone group and one es-
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2155–2161

2158
S. Yamazaki et al.
SPECIAL TOPIC
ter group.11 The coordination increases the electrophilici-
ty of the ketone carbonyl carbon of oxomalonate 6m.
Carbonyl addition at the C2 position of allene 1a from the
tin(IV) chloride coordinated 6m gives a phenyl allylic cat-
ion intermediate K2 via TSK1. Cyclization (TSK2) gives
the indene skeleton K3. Proton abstraction (TSK3) then
gives intermediate K3 and subsequent transfer of hydro-
gen chloride gives the intermediate K5. Protonation
(TSK4) leads to the product complex K6.
The cyclization of the phenyl allylic cation intermediates
may be considered as a 4π-electrocyclization.10b,12 Vibra-
tional analysis of the transition states for the cyclization
steps (TSV2 and TSK2) and for TST2 (for the cyclization
step in Scheme 1; Scheme S1) shows that a conrotatory
motion, consistent with 4π-electrocyclization, occurs
(Figure 1 and Figure S1 in the Supporting Information).
For all three reactions, the addition step is rate determin-
ing; the activation energy (TSK1, ΔE‡ = +1.37 kcal/mol)
for the addition step of oxomalonate 6m is the smallest
among these. The activation energy of the subsequent cy-
clization step (TSK2, ΔE‡ = –4.15 kcal/mol) is slightly
higher than that for ethylene-1,1,2-tricarboxylate 2m
(TST2, ΔE‡ = –6.63 kcal/mol). Side reactions4a may re-
sult in lower yields of the products 7.
For comparison, we also examined the Lewis acid-cata-
lyzed reactions of diethyl oxomalonate (6) with 1,1-dial-
kylallenes. The reaction of 1,1-dimethylallene (9) with
oxomalonate 6 in the presence of one equivalent of tin(IV)
chloride at room temperature gave the hydroxy γ-lactone
10 in 56% yield (Scheme 8). In the presence of titani-
um(IV) chloride, this reaction gave a small amount of 10,
which could not be isolated, along with a complex mix-
ture. Aluminum(III) chloride did not give 10, and a com-
plex mixture was obtained. Reduction of the hydroxy
group in product 10 was not observed.
EtO2C
CO2Et
SnCl4
EtO2C
HO
r.t.
CH2Cl2
+
Figure 1 B3LYP/LANL2DZ-optimized structures of TSV2 and
TSK2 and their reaction-coordinate vectors corresponding to the sole
imaginary frequency
O
O
O
56%
9
6
10
Scheme 8
The formation of the γ-lactone 10 from 6 and 9 may pro-
ceed through the allylic cationic intermediate A (Scheme
9). Similar hydroxy γ-lactone products have been reported
for the Lewis acid-catalyzed reactions of 6 with
phenylallene4a or with monoaryl-substituted methylene-
cyclopropanes.13
O
OEt
Cl4Sn
Et
CO2Et
EtO2C
+
O
SnCl4
O
O
6
9
O
A
In summary, Lewis Acid-catalyzed reactions of 1,1-diaryl-
allenes with ketone derivatives were examined. The
tin(IV) chloride-promoted reaction of diarylallenes with
vinyl ketones 4 gave indene derivatives 5 through a con-
jugate addition/cyclization reaction. The cyclization may
be considered as a 4π-electrocyclization. The reaction of
1,1-diphenylallene (1a) with diethyl oxomalonate (6) in
the presence of one equivalent of tin(IV) chloride at –40
O
OEt
EtO2C
HO
Cl4Sn
Et
H2O
O
– SnCl4
– EtOH
O
O
O
O
10
B
Scheme 9
Synthesis 2012, 44, 2155–2161
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Lewis Acid Promoted Reactions of 1,1-Diarylallenes and Ketones
2159
tween δ = 2.61–2.65 (CH2CO) and δ = 143.08 [indene C(2)]; and
between δ = 3.44 [indene C(1)H2] and δ = 143.08 [indene C(2)],
139.73 [indene C(3)].
MS (EI): m/z (%) =276 (79) [M+], 204 (100).
°C gave hydroxy(indenyl)malonate 7a as the major prod-
uct through a carbonyl addition/cyclization reaction. The
reaction of 1a with 6 in the presence of tin(IV) chloride at
80 °C gave indenylmalonate 8a. Lewis acid-catalyzed re-
actions of diethyl oxomalonate (6) and 1,1-dimethylallene HRMS (EI): m/z [M+] calcd for C20H20O: 276.1514; found:
276.1512.
gave the γ-lactone 10. Further investigation of the scope
of the cyclization reactions is under way.
4-[6-Chloro-3-(4-chlorophenyl)-1H-inden-2-yl]butan-2-one
(5c)
Pale-yellow oil; yield: 193 mg (58%); Rf = 0.6 (CH2Cl2).
Melting points are uncorrected. IR spectra were recorded in the FT-
1
IR (neat): 2921, 1716, 1591, 1573, 1489, 1361, 1158, 1093, 1015
cm–1.
mode on a JASCO FT/IR-460 Plus spectrophotometer. H NMR
spectra were recorded at 400 MHz and 13C NMR spectra were re-
1
1H NMR (400 MHz, CDCl3): δ = 2.11 (s, 3 H), 2.62–2.66 (m, 2 H),
2.73–2.77 (m, 2 H), 3.41 (s, 2 H), 7.02 (d, J = 8.1 Hz, 1 H), 7.19 (dd,
J = 8.1, 1.9 Hz, 1 H), 7.27 (d-like, J = 8.5 Hz, 2 H), 7.39 (br d,
J = 1.5 Hz, 1 H), 7.43 (d-like, J = 8.5 Hz, 2 H). Selected NOEs were
observed between δ = 3.41 [indene C(1)H2] and δ = 2.62–2.66
(CH2CO), 2.73–2.77 (CH2CH2CO), 7.39 [indene C(7)H].
13C NMR (100.6 MHz, CDCl3): δ = 22.98 (t), 29.89 (q), 40.49 (t),
43.28 (t), 120.19 (d), 124.04 (d), 126.59 (d), 129.01 (d), 130.36 (d),
130.57 (s), 133.18 (s), 133.44 (s), 138.11 (s), 143.82 (s), 143.82 (s),
144.32 (s), 207.41 (s). Selected HMBC correlations were observed
between δ = 2.73–2.77 (CH2CH2CO) and δ = 143.82 [indene C(2)],
138.11 [indene C(3)], 40.49 [indene C(1)H2]; between δ = 2.62–
2.66 (CH2CO) and δ = 143.82 [indene C(2)], and between δ = 3.41
[indene C(1)H2] and δ = 143.82 [indene C(2)], 133.18 [indene
C(3)].
corded at 100.6 MHz on a Varian INOVA-400 spectrometer. H
chemical shifts are reported in ppm relative to Me4Si and 13C chem-
ical shifts are reported in ppm relative to CDCl3 (77.1 ppm). 13C
multiplicities were determined by DEPT and HSQC experiments.
Mass spectra were recorded by EI or FAB techniques on a JEOL
JMS-700 mass spectrometer. All reactions were carried out under
N2.
Allenes 1a–c were prepared according to the literature.5,14
4-(3-Phenyl-1H-inden-2-yl)butan-2-one (5a): Typical Proce-
dure
SnCl4 (261 mg, 120 μL, 1 mmol) was added to a soln of vinyl ketone
4a (140 mg, 162 μL, 2 mmol) and allene 1a (192 mg, 1 mmol) in
CHCl3 (4 mL), and the mixture was stirred at r.t. for 5 min. The re-
action was quenched by successive addition of H2O (4 mL) and sat.
aq. NaHCO3 (40 mL). The mixture was extracted with CH2Cl2 (3 ×
60 mL) and the organic phase was dried (Na2SO4) and concentrated
in vacuo. The residue was purified by column chromatography (sil-
ica gel, CH2Cl2) to give a pale-yellow oil; yield: 142 mg (54%);
Rf = 0.7 (CH2Cl2).
MS (EI): m/z (%) = 332 (40) [M+], 331 (13) [M+], 330 (64) [M+],
274 (41), 272 (58), 237 (89), 86 (83), 84 (100).
HRMS (EI): m/z [M+] calcd for C19H16Cl2O: 330.0578, 331.0612,
332.0549; found: 330.0577, 331.0605, 332.0563.
IR (neat): 2924, 1713, 1659, 1447, 1270, 910, 733 cm–1.
1-[6-Chloro-3-(4-chlorophenyl)-1H-inden-2-yl]pentan-3-one
(5d)
Colorless crystals; yield: 174 mg (50%); mp 69–71 °C (EtOAc–
hexane); Rf = 0.6 (CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 2.10 (s, 3 H), 2.65 (t-like, J = 7.6
Hz, 2 H), 2.80 (t-like, J = 7.6 Hz, 2 H), 3.45 (s, 2 H), 7.15–7.25 (m,
3 H), 7.35–7.38 (m, 3 H), 7.44–7.48 (m, 3 H). Selected NOEs were
observed between δ = 3.45 [indene C(1)H2] and δ = 2.65 (CH2CO),
2.80 (CH2CH2CO).
13C NMR (100.6 MHz, CDCl3): δ = 23.15 (t), 29.88 (q), 40.67 (t),
43.71 (t), 119.72 (d), 123.59 (d), 124.43 (d), 126.37 (d), 127.36 (d),
128.64 (d), 129.12 (d), 135.23 (s), 139.83 (s), 142.30 (s), 142.83 (s),
146.20 (s), 207.93 (s). Selected HMBC correlations were observed
between δ = 2.80 (CH2CH2CO) and δ = 142.83 [indene C(2)],
139.83 [indene C(3)], 40.67 [indene C(1)H2]; between δ = 2.65
(CH2CO) and δ = 142.83 [indene C(2)]; and between δ = 3.45 [in-
dene C(1)H2] and δ = 142.83 [indene C(2)], 139.83 [indene C(3)].
IR (KBr): 2971, 2937, 2903, 2878, 1710, 1491, 1458, 1376, 1094,
1015, 819 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.04 (t, J = 7.3 Hz, 3 H), 2.39 (q,
J = 7.3 Hz, 2 H), 2.62 (t-like, J = 7.3 Hz, 2 H), 2.76 (t-like, J = 7.3
Hz, 2 H), 3.42 (s, 2 H), 7.02 (d, J = 8.1 Hz, 1 H), 7.20 (dd, J = 8.1,
2.0 Hz, 1 H), 7.28 (d-like, J = 8.5 Hz, 2 H), 7.40 (br d, J = 1.3 Hz,
1 H), 7.44 (d-like, J = 8.5 Hz, 2 H). Selected NOEs were observed
between δ = 3.42 [indene C(1)H2] and δ = 2.62 (CH2CO), 2.76
(CH2CH2CO), 7.40 [indene C(7)H].
13C NMR (100.6 MHz, CDCl3): δ = 7.86 (q), 23.08 (t), 35.97 (t),
40.56 (t), 41.98 (t), 120.21 (d), 124.07 (d), 126.62 (d), 129.03 (d),
130.39 (d), 130.59 (s), 133.25 (s), 133.45 (s), 138.08 (s), 143.85 (s),
144.06 (s), 144.38 (s), 210.17 (s). Selected HMBC correlations
were observed between δ = 2.76 (CH2CH2CO) and δ = 138.08 [in-
dene C(3)], 40.56 [indene C(1)H2]; and between δ = 3.42 [indene
C(1)H2] and δ = 133.18 [indene C(3)].
MS (EI): m/z (%) =262 (44) [M+], 204 (100).
HRMS (EI): m/z [M+] calcd for C19H18O: 262.1358; found:
262.1358.
Compounds 5b–d were similarly prepared.
1-(3-Phenyl-1H-inden-2-yl)pentan-3-one (5b)
Pale-yellow oil; yield: 161 mg (58%); Rf = 0.7 (CH2Cl2).
IR (neat): 2975, 2936, 1713, 1659, 1460, 1446, 1270, 1112 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.03 (t, J = 7.3 Hz, 3 H), 2.39 (q,
J = 7.3 Hz, 2 H), 2.61–2.65 (m, 2 H), 2.79–2.83 (m, 2 H), 3.44 (s, 2
H), 7.15–7.25 (m, 3 H), 7.34–7.38 (m, 3 H), 7.43–7.48 (m, 3 H). Se-
lected NOEs were observed between δ = 3.44 [indene C(1)H2] and
δ = 2.61–2.65 (CH2CO), 2.79–2.83 (CH2CH2CO).
MS (FAB): m/z = 346, 345 [M + 1]+.
HRMS (FAB): m/z [M + Na]+ calcd for C20H18Cl2NaO: 367.0632;
found: 367.0631.
Anal. Calcd for C20H18Cl2O: C, 69.57; H, 5.25. Found: C, 69.29; H,
5.11.
Diethyl Hydroxy(3-phenyl-1H-inden-2-yl)malonate (7a)
13C NMR (100.6 MHz, CDCl3): δ = 7.86 (q), 23.21 (t), 35.91 (t),
40.71 (t), 42.37 (t), 119.70 (d), 123.59 (d), 124.40 (d), 126.36 (d),
127.34 (d), 128.63 (d), 129.12 (d), 135.26 (s), 139.73 (s), 142.33 (s),
143.08 (s), 146.23 (s), 210.60 (s). Selected HMBC correlations
were observed between δ = 2.79–2.83 (CH2CH2CO) and δ = 143.08
[indene C(2)], 139.73 [indene C(3)], 40.71 [indene C(1)H2]; be-
SnCl4 (261 mg, 120 μL, 1 mmol) was added to a soln of diethyl
oxomalonate (6) (174 mg, 152 μL, 1 mmol) and allene 1a (192 mg,
1 mmol) in CH2Cl2 (2 mL) at –40 °C and the mixture was stirred at
–40 °C overnight. The reaction was quenched successively with
H2O (4 mL) and sat. aq NaHCO3 (40 mL). The mixture was extract-
ed with CH2Cl2 (3 × 60 mL) and the organic phase was dried
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2155–2161

2160
S. Yamazaki et al.
SPECIAL TOPIC
(Na2SO4) and concentrated in vacuo. The residue was purified by
column chromatography (silica gel, hexane–Et2O) to give a pale-
yellow oil; yield: 205 mg (56%); Rf = 0.3 (hexane–Et2O, 2:1).
1H NMR (400 MHz, CDCl3): δ = 1.27 (t, J = 7.1 Hz, 6 H), 3.80 (s,
2 H), 4.15–4.27 (m, 4 H), 4.76 (s, 1 H), 7.22–7.27 (m, 3 H), 7.39–
7.43 (m, 3 H), 7.47–7.52 (m, 3 H). Selected NOEs were observed
between δ = 3.80 [indene C(1)H2] and δ = 4.76 [CH(CO2Et)2], 7.47–
7.52 [indene C(7)H].
IR (neat): 3475, 2981, 1738, 1462, 1444, 1392, 1368, 1264, 1206,
1159, 1094, 1037 cm–1.
13C NMR (100.6 MHz, CDCl3): δ = 14.14 (q), 39.20 (t), 52.31 (d),
61.84 (t), 120.65 (d), 123.85 (d), 125.47 (d), 126.31 (d), 127.99 (d),
128.80 (d), 129.23 (d), 134.03 (s), 134.09 (s), 143.35 (s), 144.53 (s),
144.94 (s), 168.16 (s). Selected HMBC correlations were observed
between δ = 3.80 [indene C(1)H2] and δ = 52.31 [CH(CO2Et)2],
123.85 [indene C(7)]; and between δ = 4.76 [CH(CO2Et)2] and δ =
39.20 [indene C(1)H2].
1H NMR (400 MHz, CDCl3): δ = 1.19 (t, J = 7.1 Hz, 6 H), 3.71 (s,
2 H), 3.88 (dq, J = 10.8, 7.1 Hz, 2 H), 4.04 (dq, J = 10.8, 7.1 Hz, 2
H), 4.14 (br s, 1 H), 7.06–7.08 (m, 1 H), 7.22–7.26 (m, 2 H), 7.33–
7.45 (m, 5 H), 7.47–7.49 (m, 1 H). Selected NOEs were observed
between δ = 3.71 [indene C(1)H2] and δ = 7.47–7.49 [indene
C(7)H].
13C NMR (100.6 MHz, CDCl3): δ = 13.91 (q), 39.67 (t), 62.86 (t),
78.92 (s), 121.07 (d), 123.60 (d), 125.81 (d), 126.48 (d), 127.83 (d),
128.13 (d), 129.44 (d), 134.56 (s), 137.02 (s), 142.12 (s), 143.70 (s),
146.19 (s), 169.77 (s). Selected HMBC correlations were observed
between δ = 3.71 [indene C(1)H2] and δ = 78.92 [C(CO2Et)2OH],
123.60 [indene C(7)].
MS (EI): m/z = 350 [M+].
HRMS (EI): m/z [M+] calcd for C22H22O4: 350.1518; found:
350.1518.
Diethyl [6-Methyl-3-(4-tolyl)-1H-inden-2-yl]malonate (8b)
SnCl4 (130 mg, 60 μL, 0.5 mmol) was added to a soln of diethyl
oxomalonate (6) (87 mg, 76 μL, 0.5 mmol) and allene 1c (110 mg,
0.5 mmol) in CH2Cl2 (2 mL), and the mixture was stirred at r.t. over-
night. The reaction was quenched by successive addition of H2O (2
mL) and sat. aq NaHCO3 (20 mL). The mixture was extracted with
CH2Cl2 (3 × 30 mL) and the organic phase was dried (Na2SO4) and
concentrated in vacuo. The residue was purified by column chroma-
tography (silica gel, hexane–Et2O) to give a pale-yellow oil; yield:
69 mg (36%); Rf = 0.5 (hexane–Et2O, 2:1).
MS (EI): m/z (%) =366 (5) [M+], 348 (100).
HRMS (EI): m/z [M+] calcd for C22H22O5: 366.1467; found:
366.1461.
Diethyl Hydroxy[6-methyl-3-(4-methylphenyl)-1H-inden-2-
yl]malonate (7b)
ZnI2 (32 mg, 0.1 mmol) was added to a soln of diethyl oxomalonate
(6) (87 mg, 76 μL, 0.5 mmol) and allene 1c (110 mg, 0.5 mmol) in
CH2Cl2 (2 mL), and the mixture was stirred at r.t. overnight. The re-
action was quenched by successive addition of H2O (2 mL) and sat.
aq NaHCO3 (20 mL). The mixture was extracted with CH2Cl2 (3 ×
30 mL) and the organic phase was dried (Na2SO4) and concentrated
in vacuo. The residue was purified by column chromatography (sil-
ica gel, hexane–Et2O) to give a pale-yellow oil: yield: 63 mg (32%);
Rf = 0.2 (hexane–Et2O, 2:1).
IR (KBr): 2981, 1729, 1307, 1225, 1159, 1030 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.26 (t, J = 7.1 Hz, 6 H), 2.40 (s,
3 H), 2.42 (s, 3 H), 3.74 (s, 2 H), 4.14–4.26 (m, 4 H), 4.75 (s, 1 H),
7.10 (br d, J = 7.8 Hz, 1 H), 7.13 (d, J = 7.8 Hz, 1 H), 7.29 (br s, 4
H), 7.32 (br s, 1 H). Selected NOEs were observed between δ = 3.74
[indene C(1)H2] and δ = 7.10 [indene C(7)H].
IR (neat): 3478, 2981, 2923, 1788, 1742, 1509, 1445, 1368, 1268,
1173, 1096, 1037 cm–1.
13C NMR (100.6 MHz, CDCl3): δ = 14.14 (q), 21.41 (q), 21.53 (q),
38.89 (t), 52.31 (d), 61.75 (t), 120.32 (d), 124.73 (d), 126.96 (d),
129.07 (d), 129.47 (d), 131.20 (s), 132.68 (s), 135.22 (s), 137.62 (s),
142.48 (s), 143.65 (s), 144.27 (s), 168.30 (s). Selected HMBC cor-
relations were observed between δ = 3.74 [indene C(1)H2] and δ =
124.73 [indene C(7)]; and between δ = 4.75 [CH(CO2Et)2] and δ =
38.89 [indene C(1)H2].
1H NMR (400 MHz, CDCl3): δ = 1.18 (t, J = 7.1 Hz, 6 H), 2.38 (s,
3 H), 2.39 (s, 3 H), 3.65 (s, 2 H), 3.88 (dq, J = 10.6, 7.1 Hz, 2 H),
4.04 (dq, J = 10.6, 7.1 Hz, 2 H), 4.13 (br s, 1 H), 6.97 (d, J = 7.7 Hz,
1 H), 7.05 (br d, J = 7.7 Hz, 1 H), 7.22 (d, J = 7.9 Hz, 2 H), 7.28 (d,
J = 7.9 Hz, 2 H), 7.29 (br s, 1 H). Selected NOEs were observed be-
tween δ = 3.65 [indene C(1)H2] and δ = 7.29 [indene C(7)H].
MS (EI): m/z (%) =378 (84) [M+], 305 (55), 259 (31), 231 (100).
13C NMR (100.6 MHz, CDCl3): δ = 13.89 (q), 21.37 (q), 21.53 (q),
39.36 (t), 62.79 (t), 78.95 (s), 120.73 (d), 124.44 (d), 127.15 (d),
128.75 (d), 129.25 (d), 131.64 (s), 135.58 (s), 135.69 (s), 137.36 (s),
142.38 (s), 143.57 (s), 143.71 (s), 169.89 (s). Selected HMBC cor-
relations were observed between δ = 3.65 [indene C(1)H2] and δ =
78.95 [C(CO2Et)2OH], 124.44 [indene C(7)].
MS (EI): m/z (%) =394 (9.4) [M+], 376 (65), 321 (90), 303 (47), 247
(100).
HRMS (EI): m/z [M+] calcd for C24H26O5: 394.1780; found:
394.1779.
HRMS (EI): m/z [M+] calcd for C24H26O4: 378.1831; found:
378.1833.
Ethyl 3-Hydroxy-5,5-dimethyl-4-methylene-2-oxotetrahydro-
furan-3-carboxylate (10)
SnCl4 (130 mg, 60 μL, 0.5 mmol) was added to a soln of diethyl
oxomalonate (6) (87 mg, 76 μL, 0.5 mmol) and allene 9 (34 mg, 50
μL, 0.5 mmol) in CH2Cl2 (2 mL), and the mixture was stirred at r.t.
overnight. The reaction was quenched by successive addition of
H2O (2 mL) and sat. aq NaHCO3 (20 mL). The mixture was extract-
ed with CH2Cl2 (3 × 30 mL) and the organic phase was dried
(Na2SO4) and concentrated in vacuo. The residue was purified by
column chromatography (silica gel, hexane–Et2O) to give a color-
less oil; yield: 61 mg (56%); Rf = 0.6 (hexane–Et2O, 1:1).
Diethyl (3-Phenyl-1H-inden-2-yl)malonate (8a); Typical Proce-
dure
SnCl4 (5.2 mg, 2.4 μL, 0.02 mmol) was added to a soln of diethyl
oxomalonate (6) (17.4 mg, 0.1 mmol) and allene 1a (19.2 mg, 0.1
mmol) in ClCH2CH2Cl (0.4 mL), and the mixture was heated at 80
°C overnight. The reaction mixture was cooled to r.t. and quenched
by addition of sat. aq NaHCO3 (5 mL). The mixture was extracted
with CH2Cl2 (3 × 10 mL) and the organic phase was dried (Na2SO4)
and concentrated in vacuo. The residue was purified by column
chromatography (silica gel, hexane–Et2O) to give a pale-yellow oil;
yield: 23.1 mg (66%); Rf = 0.6 (hexane–Et2O, 2:1).
IR (neat): 3449, 2985, 1781, 1747, 1370, 1291, 1231, 1180, 1114,
1031 cm–1.
1H NMR (400 MHz, CDCl3: δ = 1.30 (t, J = 7.1 Hz, 3 H), 1.61 (s, 3
H), 1.66 (s, 3 H), 4.26–4.38 (m, 3 H), 5.36 (d, J = 1.5 Hz, 1 H), 5.43
(d, J = 1.5 Hz, 1 H). Selected NOEs were observed between δ =
5.36 (=CHH) and δ = 1.61, 1.66 [C(CH3)2].
13C NMR (100.6 MHz, CDCl3): δ = 13.85 (q), 28.17 (q), 29.69 (q),
63.91 (t), 76.71 (s), 86.80 (s), 112.35 (t), 150.98 (s), 169.19 (s),
171.29 (s). Selected HMBC correlations were observed between δ =
5.36, 5.43 (=CH2) and δ = 150.98 (C=CH2), 86.80 [C(CH3)2], 76.71
IR (neat): 2980, 2929, 1732, 1461, 1444, 1367, 1304, 1148, 1031
cm–1.
Synthesis 2012, 44, 2155–2161
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Lewis Acid Promoted Reactions of 1,1-Diarylallenes and Ketones
2161
[C(CO2Et)OH]; and between δ = 1.61, 1.66 [C(CH3)2] and δ =
150.98 (C=CH2).
MS (EI): m/z = 214 [M+].
HRMS (EI): m/z [M+] calcd for C10H14O5: 214.0841; found:
214.0841.
(6) For details of some bioactive compounds containing indene
moieties, see: (a) Ahn, J. H.; Shin, M. S.; Jung, S. H.; Kim,
J. A.; Kim, H. M.; Kim, S. H.; Kang, S. K.; Kim, K. R.;
Rhee, S. D.; Park, S. D.; Lee, J. M.; Lee, J. H.; Cheon, H. G.;
Kim, S. S. Bioorg. Med. Chem. Lett. 2007, 17, 5239. (b) Di
Stefano, A.; Sozio, P.; Cacciatore, I.; Cocco, A.; Giorgioni,
G.; Costa, B.; Montali, M.; Lucacchini, A.; Martini, C.;
Spoto, G.; Di Pietrantonio, F.; Di Matteo, E.; Pinnen, F.
J. Med. Chem. 2005, 48, 2646. (c) Guillon, J.; Dallemagne,
P.; Léger, J.-M.; Sopkova, J.; Bovy, P. R.; Jarry, C.; Rault,
S. Bioorg. Med. Chem. 2002, 10, 1043. (d) Kolanos, R.;
Siripurapu, U.; Pullagurla, M.; Riaz, M.; Setola, V.; Roth, B.
L.; Dukat, M.; Glennon, R. A. Bioorg. Med. Chem. Lett.
2005, 15, 1987. (e) Watanabe, N.; Nakagava, H.; Ikeno, A.;
Minato, H.; Kohayakawa, C.; Tsuji, J. Bioorg. Med. Chem.
Lett. 2003, 13, 4317.
Acknowledgment
This work was supported by the Ministry of Education, Culture,
Sports, Science, and Technology of the Japanese Government. We
thank Nara Institute of Science and Technology (NAIST) and Pro-
fessor K. Kakiuchi (NAIST) for recording the mass spectra.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.onmorinIfatgnonmSorti
i
npfurotIangSiuptor
(7) For some recent examples of indene-formation reactions,
see: (a) Xi, Z.; Guo, R.; Mito, S.; Yan, H.; Kanno, K.;
Nakajima, K.; Takahashi, T. J. Org. Chem. 2003, 68, 1252.
(b) Liu, C.-R.; Yang, F.; Jin, Y.-Z.; Ma, X.-T.; Cheng, D.-J.;
Li, N.; Tian, S.-K. Org. Lett. 2010, 12, 3832. (c) Kurouchi,
H.; Sugimoto, H.; Otani, Y.; Ohwada, T. J. Am. Chem. Soc.
2010, 132, 807. (d) Ignatenko, V. A.; Deligonul, N.;
Viswanathan, R. Org. Lett. 2010, 12, 3594.
(8) When a catalytic amount (0.2 equiv) of SnCl4 was used in the
reaction of 1a and 4a on a 0.1-mmol scale (CH2Cl2, 3–20 h),
the yields of the indene product 5a were comparable to that
shown in Table 1 (entry 1); however, the reactions between
1a and 4b and between 1b and 4a were less efficient under
these catalytic conditions.
(9) Hall, H. K. Jr., ; Sentman, R. C. J. Org. Chem. 1982, 47,
4572.
(10) (a) Wang, J.; Huang, W.; Zhang, Z.; Xiang, X.; Liu, R.;
Zhou, X. J. Org. Chem. 2009, 74, 3299. (b) Smith, C. D.;
Rosocha, G.; Mui, L.; Batey, R. A. J. Org. Chem. 2010, 75,
4716.
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2155–2161