Scope of the formal [3+2] cycloaddition for the synthesis of substituted 3-arylindanes and related compounds

Article abstract of DOI:10.1016/j.tet.2008.02.034

We report the single step synthesis of several 3-arylindanes and related compounds via a formal [3+2] cycloaddition. A study of the influence of the aromatic ring substitution pattern on the reaction was carried out.

Full text of DOI:10.1016/j.tet.2008.02.034

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 4090e4102
www.elsevier.com/locate/tet
Scope of the formal [3þ2] cycloaddition for the synthesis of
substituted 3-arylindanes and related compounds
a
Beatriz Lantano , Jose Manuel Aguirre , Esteban Ariel Ugliarolo ,
b
a
´
Marıa Laura Benegas , Graciela Yolanda Moltrasio
~
a
a,
*
´
a Departamento de Qu´ımica Orga´nica, Facultad de Farmacia y Bioqu´ımica, Universidad de Buenos Aires, Buenos Aires, Argentina
b Departamento de Ciencias Ba´sicas, Universidad Nacional de Luja´n, Luja´n, Argentina
Received 26 December 2007; received in revised form 8 February 2008; accepted 11 February 2008
Available online 15 February 2008
Abstract
We report the single step synthesis of several 3-arylindanes and related compounds via a formal [3þ2] cycloaddition. A study of the influence
of the aromatic ring substitution pattern on the reaction was carried out.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Indanes; Formal [3þ2] cycloaddition; Stereochemistry
1. Introduction
treatment of propenylbenzenes with acidic reagents to obtain
dimeric products, but was in 1940 the indane structure was
proposed for those dimers.8 In 1969 MacMillan et al.9 as-
signed the correct stereochemical structure for the dimers de-
rived from (E)-isosafrole and diisohomogenol. Some years
later, Marcuzzi et al.10 reported that the reaction of phenyl-
substituted alkenes and alkynes with diphenylmethyl cations
led to good yields of indanes and indenes. The lack of stereo-
selectivity of these procedures led Angle and Arnaiz11 to de-
velop a cycloaddition-type method for the preparation of
highly substituted indanes in a single step via the reaction of
an activated p-quinone methide or a benzylic cation with an
electron-rich alkene. These reactions are catalyzed by a Lewis
acid such as ZnCl2 or a stronger one as SnCl4. Primary and
secondary benzylic alcohols led to good yields of cycloadducts
as long as there was a phenol para to the benzylic alcohol and
at least one meta alkoxy or alkyl group.
There are numerous natural and synthetic products that pos-
sess a indane ring system showing significant biological activ-
ity, including simple natural compounds such as the asarone
dimer a component of the essential oil of Acarus calamus1 or
complex compounds, such as pallidol a resveratrol dimer
from Cissus pallida.2 In addition, there are many synthetic
compounds possessing the indane skeleton that show significant
biological activity, for example, indinavirÒ and indacrinoneÒ.
OCH3
HO
H
OH
HO
H3CO
OCH3
H
OCH3
H3CO
OH
HO
OH
OCH3
In previous papers we reported the synthesis of several in-
danes via the reaction of dibenzylic cations, generated from
benzhydrols, with several nucleophilic alkenes, such as sty-
renes, and with other relatively electron-poor alkenes, such
as stilbenes and diphenylacetylene.10 Using this methodology
we obtained the natural dimer of asarone11 and finally, we
studied the formal [3þ2] cycloaddition reaction using
Asarone dimer
Pallidol
As a consequence, a large number of methods were devel-
oped for their synthesis.3e7 The first synthetic strategy was the
* Corresponding author.
E-mail address: gmoltra@ffyb.uba.ar (G.Y. Moltrasio).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.02.034

B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
4091
R3
R3
R3
R3
R2
R2
SnCl4
R2
R2
Ph
+
+
R1
OH
R1
R1
R1
Ph
I
II
Ph
Scheme 1. Proposed mechanism for the formal [3þ2] cycloaddition.
silica-supported Keggin heteropolyacids with similar results to
those obtained with SnCl4.14
The proposed mechanism for the formal [3þ2] cycloaddi-
tions (Scheme 1) is similar to the dimerization of isosafrole
and other styrenes, in acid medium.11
It is clear that intermediary I carbocation formation is im-
proved by electron releasing substituents in C-4 and the cycla-
tion step due to the presence of substituents in C-3.
The aim of this work is to study the scope of this cycload-
dition. We hereby report the results from the formal [3þ2]
cycloaddition reaction using different starting materials:
in any case. We had previously reported that 1-(3,4-dimethoxy-
phenyl)propan-1-ol (4) reacts with 11, under identical condi-
tions those used in this work, producing the corresponding
indane with a 55% yield.13 Otherwise, Angle and Arnaiz11
had reported that monosubstituted benzylic alcohols with elec-
tron releasing groups in C-3 or C-4 did not react with (E)-b-
methylstyrene. Our results (Table 1) indicate that the electron
richness of the alkenes used (11 and 12) compensates the
lack of one of the electron releasing substituents in the aryl
group of the starting benzylic alcohol.
2.2. Reaction of benzylic alcohols substituted with electron
releasing groups and cyclic alkenes
ꢀ Benzylic alcohols, with a single electron releasing substit-
uent in C-3 or C-4 of the benzenic ring and (E)-b-methyl-
styrene with electron releasing groups.
The reaction between benzylic alcohols with diverse substi-
tution type and grade (1e6) and alkenes such as indene (13),
4-phenyl-2,3-dihydronaphthalene (14), dihydronaphthalene
(15), was also explored and the results are shown in Table 2.
Alcohols 1 and 2 did not react with 13 (Table 2, entries 5
and 6), however, this alkene reacts with alcohols 3 and 4 lead-
ing to formation of tetracyclic systems (24, 25, and 26) (Table
2, entries 7 and 8). Disubstituted alcohols, with electron re-
leasing groups in C-3 and C-4 (4 and 5) react with 14 to
give, with poor yield (30 and 40%), one single stereoisomer
27 and 28, respectively (Table 2, entries 9 and 10). Alcohol
6, trisubstituted in C-3, C-4, and C-5 with electron releasing
groups, showed higher reactivity and lower stereoselectivity
when reacting with alkene 14, and a mixture of two diastereo-
mers 29 and 30 in a 2:1 rate was obtained (Table 2, entry 11).
A similar behavior to alcohols 4e6, with alkene 14 is ob-
served for benzhydrols 7 and 8. The compound 8 reacts with
alkene 14 to obtain the cycloadduct 33, while 7 reacts with al-
kenes 13, 14, and 15 to obtain, in all cases, a mixture of dia-
stereomers 34,35, 36,37 and 38,39, respectively, at similar
rates (Table 3).
ꢀ Benzylic alcohols substituted with electron releasing
groups and cyclic alkenes.
ꢀ Benzylic and benzhydrolic alcohols and (E)-asarone.
ꢀ Benzylic alcohol substituted with methoxyl groups in C-2,
C-4, and C-5 and different alkenes.
ꢀ Finally we also studied the stereocontrol in formal [3þ2]
cycloaddition reactions.
2. Results and discussion
Benzylic and benzhydrolic alcohols were prepared from
corresponding aldehydes and ethylmagnesium bromide13,15,16
and phenylmagnesium bromide,12 respectively. SnCl4 was
chosen as catalyst for this study. Experimental conditions
were mild (0e25 ꢁC, time: 5e60 min) and methylene chloride
was the solvent.
2.1. Reaction of benzylic alcohols with an electron releasing
substituent in C-3 or C-4 of the benzenic ring and (E)-b-
methylstyrenes with electron releasing groups
The products of the reaction of benzylic alcohols with a sub-
stituent in C-4, 1-(4-methoxyphenyl)propan-1-ol (1) and in
C-3, 1-(3-hydroxyphenyl)propan-1-ol (2) and styrenes 11 and
12, in the presence of SnCl4 are shown in Table 1. The reaction
between alcohol 1 with 11 and 12 gave a low yield (about 20%)
and the adduct obtained, in each case, corresponded to one
single diastereomer (18 and 19, respectively) (Table 1, entries
1 and 2). On the other side, alcoho1 2 presented lower reactivity
and diastereoselectivity than alcohol 1 with the same alkenes
(Table 1, entries 3 and 4) producing 20,21 and 22,23 cyclic di-
mers as a diastereomeric mixture. The yield did not exceed 15%
2.3. Reaction of substituted benzylic alcohols and
benzhydrols with asarone (16)
The results of the formal [3þ2] cycloaddition between sty-
rene 16 and alcohols 1e4, 6, 8, and 9 are presented in Table 4.
Compound 16 presents the typical behavior of an electron-rich
styrene (Table 4 entries 17, 19e23). However, compound 41,
the result of the cyclodimerization of 16, was isolated as a sole
reaction product between 2 and 16 (Table 4, entry 18). Cyclo-
dimerization products, under these reaction conditions, have
not been previously observed. To assess the competition

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B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
Table 1
Formal [3þ2] cycloaddition of benzylic alcohols and styrenes
Entry
Alcohol
Alkene
Product
Yield %
OH
H3CO
1
19
H3CO
H3CO
11
OCH3
1
15
18
H3CO
O
O
2
1
20
O
O
12
19
HO
HO
OH
HO
3
11
7
OCH3
OCH3
2
20
21
2:1
HO
HO
4
2
12
15
O
O
O
O
22
23
1,3:1
reaction between cyclodimerization and formal [3þ2] cyclo-
addition, alcohol 5 and styrene 12 were selected. Alkene 12
was treated under same conditions as in cycloaddition
(SnCl4, methylene chloride, 0 ꢁC) and the cyclodimer forma-
tion could only be observed after 1 h of reaction while the cy-
cloaddition between styrene 12 and alcohol 5 led to the
cycloadduct within 5 min of reaction with a 51% yield.
and 52 (70%) is observed. It is clear that the presence of a me-
thoxyl group in C-4 of 10 promotes the formation of cationic
intermediaries (Scheme 1), but the presence of methoxyl group
in C-2 and the lack of an electron releasing group in C-3 do not
promote the formation of the tetracyclic system.
2.5. Stereocontrol in formal [3þ2] cycloaddition reactions
2.4. Reaction of benzylic alcohol substituted with methoxyl
groups in C-2, C-4, and C-5 (10) and different alkenes
Stereocontrol in reactions with adequately substituted benz-
ylic alcohols and (E)- and (Z)-b-methylstyrenes was studied in
the reaction of alcohols 4 and 5 with geometric isomers 16 and
17 (Scheme 2, Table 6). In this case, indane structures with
three stereogenic centers are formed thus, four different race-
mic diastereomers might be obtained named a, b, g, and
d (Fig. 1).
Likewise, the relation of diastereoisomeric products from
benzhydrol alcohols 8 and 9 with styrenes 16 and 17 were
analyzed.
The results of the reaction of alcohol 10 and alkenes 11, 13e
16 are collected in Table 5. As we have previously reported in
a synthesis and stereochemistry study on benzylindane natural
dimer of asarone,13 alcohol 10 reacts with alkenes 11 and 16 ac-
cording to the expected regiochemistry and stereochemistry
(Table 5, entry 24). Nevertheless, this alcohol does not react
with 13 and the reaction course with 14 and 15 (Table 5, entries
27 and 28) does not lead to expected cycloadducts. In these re-
actions, the formation of the non-indane compounds 51 (73%)
In all cases studied, a mixture of the two diastereomers III
and IV was obtained. In the reaction between (E)-styrene 16

B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
4093
Table 2
Formal [3þ2] cycloaddition of benzylic alcohols and cyclic alkenes
Entry
Alcohol
Alkene
Product
Yield %
No rxn
5
1
d
13
6
7
2
13
d
No rxn
36
H3CO
H3CO
OH
H3CO
H3CO
13
3
24
H3CO
H3CO
H3CO
H3CO
OH
H3CO
8
13
26
H3CO
25
26
4
1,5:1
H
H3CO
H3CO
Ph
Ph
9
4
30
14
27
H
O
O
OH
O
O
Ph
10
14
40
5
28
H
H
H3CO
H3CO
H3CO
H3CO
OH
H3CO
H3CO
Ph
Ph
OCH3
OCH3
11
14
65
OCH3
29
30
2:1
6
H3CO
H3CO
H3CO
H3CO
H
H
H
H
12
4
42
15
31
32
1:1.2
and the alcohols 4, 5, 8, 9 the cisetrans diastereomer (IV,
r-1,t-2,t-3) was mainly obtained. However, (Z)-styrene 17
mainly rendered the transetrans diastereomer (III, r-1,t-
2,c-3) only with benzylic alcohols 4 and 5. Benzhydrols 8
and 9 led to the formation of the two indane stereoisomers
at equivalent rates.
2.6. Structural and stereochemical assignment
Stereochemical assignment of 3-arylindane-like com-
pounds was conducted taking into consideration 1H NMR
spectra, chemical shifts, coupling constants, and double irradi-
ation techniques. MacMillan et al.9 had already reported

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B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
Table 3
Formal [3þ2] cycloaddition of benzhydrolic alcohols and cyclic alkenes
Entry
Alcohol
Alkene
Product
Yield %
H3CO
H3CO
H3CO
OCH3
H
OCH3
H
H3CO
OH
Ph
H3CO
H3CO
H
13
13
26
H
Ph
34
Ph
35
OCH3
1:1.2
Ph
7
Ph
H
H3CO
OH
Ph
H3CO
H3CO
H3CO
14
15
16
14
14
15
5112
8
33
Ph
Ph
H3CO
H3CO
H3CO
H
H
H3CO
CH3O
Ph
Ph
CH3O
7
52
36
37
1:1,3
Ph
Ph
H3CO
H3CO
H3CO
H
H
H3CO
CH3O
H
H
7
20
CH3O
38
39
1:1
J values for the a, b, and g configuration for three of the iso-
homogenol cyclodimers.
and besides there are four signals corresponding to one hydro-
gen (d 2.55, 2.83, 2.98, and 3.05 ppm).
As it can be noticed, there is a marked consistency between
J values (Hz) obtained by MacMillan et al.9 and those found
by us, thus, it would be valid to assign the a-configuration
to the 3-arylindanes 20 and 22 and the g-configuration to
the 3-arylindanes 18, 19, 21, 23, and 40.
Besides, chemical shifts published for the nonaromatic hy-
drogens of g-diisohomogenol are similar to those found for
compounds 18, 19, 21, 23, 40 (Table 7) and identical situation
is observed for indanes 20 and 22 respecting a-diisohomoge-
nol. Configuration of cyclodimers 41, 42e45, and 50 was as-
signed by us in a previous work.13 Coupling constants for the
1,3-diaryl-2-methylindanes 46e49 (Table 8) have similar
values to those published by Marcuzzi and Melloni18 for the
1,3-diphenyl-2-methylindanes V and VI (Fig. 2). Based on
this concordance we have assigned the cisetrans (r-1,c-2,t-3)
configuration to the compounds 47 and 49, and the transetrans
(r-1,t-2,c-3) configuration to 46 and 48.
Irradiation of the triplet at d 0.97 ppm corresponding to the
methyl group, simplified the signal at d 1.72 ppm to a doublet.
When irradiated, this signal (d 1.72 ppm) produces the ex-
pected simplification of the signal at d 0.97 ppm to a singlet
and the signal at d 3.05 ppm (multiplet) to a doublet. These re-
sults allow the assignment of the chemical shifts of the ali-
phatic protons of benzylic alcohol-derived portion of the
cycloadduct. The signal at d 2.55 ppm was assigned to the
bridgehead hydrogen as its irradiation reduces signal multi-
plicity at d 3.05 ppm and also that of the signal at
d 1.88 ppm. This allows assigning this last 1.88 ppm value
to the non-benzylic methylene group, from the hexagonal
ring. Remaining signals, d 2.83 and 2.98 ppm, correspond to
benzylic hydrogens from the hexagonal ring. This fact was
confirmed as the signal at d 1.88 ppm is unique to be affected
by irradiation of the signals at d 2.83 and 2.98 ppm. Relative
configuration of stereocenters from the structure of 28, trans
between hydrogens (d 2.55 and 3.05 ppm) and cis between
phenyl group and bridgehead hydrogen, was established taking
Structure assignment for compounds 27e30 was performed
taking into consideration the results from the double irradia-
1
1
tion experiments in H NMR. Chemical shifts in H NMR
spectrum for compound 28 (Fig. 3) present two multiplets at
d 1.72 and 1.88 ppm, both integrating for two hydrogens,
into consideration the value of JH
8.8 Hz from sig-
benzylic=Hbridgehead
nal at d 2.55 ppm, and the results already published for similar
structures.12 The J value 8.8 Hz for bridgehead hydrogen (d

B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
4095
Table 4
Formal [3þ2] cycloaddition of benzylic alcohols and asarone
Entry
Alcohol
H3CO
HO
Alkene
Product
Yield %
OCH3
OH
H3CO
OCH3
17
23
21
30
H3CO
H3CO
OCH3
OCH3
1
16
40
OCH3
OH
H3CO
OCH3
OCH3
H3CO
18
16
OCH3
2
13
41
H3CO
H3CO
OH
OCH3
H3CO
H3CO
19
16
H3CO
OCH3
3
42
H3CO
H3CO
H3CO
H3CO
OCH3
OCH3
OH
H3CO
H3CO
20
16
8413
H3CO
H3CO
44
OCH3
OCH3
4
43
7:1
H3CO
H3CO
OH
OCH3
H3CO
H3CO
OCH3
21
16
9813
H3CO
OCH3
OCH3
6
45
Ph
Ph
H3CO
H3CO
H3CO
H3CO
OCH3
OCH3
Ph
OH
H3CO
H3CO
22
16
55
H3CO
H3CO
OCH3
OCH3
8
46
47
1:2.9
Ph
Ph
H3CO
HO
H3CO
Ph
OH
HO
OCH3
OCH3
H3CO
HO
23
16
40
H3CO
H3CO
9
OCH3
OCH3
48
49
1:2.2

4096
B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
Table 5
Formal [3þ2] cycloaddition of benzylic alcohol and alkenes
Entry Alcohol
Alkene
Product
Yield %
OCH3
OCH
3OH
H3CO
OCH3
24
4113
H3CO
H3CO
OCH3
11
OCH3
10
50
OCH3
OCH3
H3CO
OCH3
OCH3
OCH3
25
26
27
10
10
10
6113
No rxn
73
H3CO
OCH3
H3CO
16
41
d
13
OCH3
Ph
H3CO
Ph
OCH3
14
51
OCH3
28
10
70
H3CO
15
OCH3
52
2.55 ppm) was obtained by irradiation of the signal at
d 1.88 ppm. Structures for compounds 27, 29 and 30 were
assigned by comparison with that for compound 28.
Compounds 36 and 37 (Fig. 4) present a cis fusion between
the five- and six-membered rings and are epimers in the diben-
zylic carbon. The J value 11.8 Hz in 36 and 7.2 Hz in 37 for the
hydrogens bound to these carbons indicate that they present
a trans and cis array, respectively, with the bridgehead
hydrogen.
The structures of 38 and 39 (Fig. 5) were assigned by
comparison with compounds previously published by us.12
The cycloadduct 38 presents cis fusion of the rings (Ja,b
7.7 Hz) and trans configuration by dibenzylic protons Hc
and Hb (Jb,c11.3 Hz). Compound 39 possesses identical fu-
sion rings (Ja,b 7.7 Hz) and cis relationship for Hc and Hb
(Jb,c 7.2 Hz).
1
Data from H and 13C NMR for 51 and 52 (Fig. 6) show
that they are dihydronaphthalene-derived structures. Both
16
OCH3
R3
R3
R1
R2
R1
R2
H3CO
OH
OCH3
R1
R2
+
R3
H3CO
H3CO
OCH3
OCH3
OCH3
OCH3
OCH3
H3CO
III
IV
OCH3
17
Scheme 2.

B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
4097
Table 6
Alcohol
0.97
2.55
1.72
3.05
H
Alkene
Ratio III (t-t):IV (c-t)
1 (43):7.1 (44)
H
O
O
H
1.88
2.83
H
4 R1¼R2¼OCH3;
R3¼CH3CH2
16
H
H
Ph
2.98
4 R1¼R2¼OCH3;
R3¼CH3CH2
17
16
17
1.5 (43):1 (44)
1 (53):4.5 (54)
4.35 (53):1 (54)
28
5 R1¼R2¼OeCH2eO;
R3¼CH3CH2
Figure 3.
5 R1¼R2¼OeCH2eO;
R3¼CH3CH2
Ph
Ph
H
H
H3CO
H3CO
H3CO
8 R1¼R2¼OCH3; R3¼Ph
8 R1¼R2¼OCH3; R3¼Ph
9 R1¼OCH3; R2¼OH;
R3¼Ph
16
17
16
1 (46):3 (47)
1 (46):1 (47)
1 (48):3 (49)
H
H
H3CO
Ph
Ph
CH3O
CH3O
9 R1¼OCH3; R2¼OH;
R3¼Ph
17
1 (48):1 (49)
36
37
Figure 4.
1
2
R
R
R
Ph
Ph
R
Hc
Hc
3
Ar
H3CO
H3CO
H3CO
Hb
Hb
Ar
Ar
Ar
H3CO
CH3O
Ha
Ha
: cis-trans (r-1,c-2 t-3),
: cis-cis (r-1,c-2,c-3),
: trans-trans (r-1,t-2,c-3)
: trans-cis (r-1,t-2,t-3)
CH3O
38
39
Figure 5.
Figure 1.
Table 7
Coupling constant and 1H NMR chemical shift data of 3-arylindanes
Cycloadducts
J1,2
7.25
J2,3
9.5
Configuration
H-1
H-2
H-3
CH3
CH3CH2
CH3CH2
a: cisetransa
cisetrans
cisecis
2.90
2.95
2.69
2.95
2.92
2.67
2.67
2.75
2.69
2.67
2.40
2.77
2.00
2.49
2.44
2.02
2.02
2.01
2.02
2.06
3.77
4.27
3.65
3.78
3.76
3.65
3.62
3.63
3.62
4.22
1.04
0.47
1.15
1.04
1.03
1.15
1.14
1.16
1.12
1.14
1.65
1.61
0.96
1.07
0.97
1.01
0.97
0.97
0.98
0.99
0.97
1.00
b: cisecisa
7.0
9.0
7.1
7.3
9.9
9.8
9.1
9.3
10.0
7.0
9.0
9.6
9.5
9.8
9.6
10.1
9.8
9.5
g: transetransa
transetrans
cisetrans
cisetrans
1.70
1.83
20
22
18
19
21
23
40
1.40/1.68
1.83
1.85
transetrans
transetrans
transetrans
transetrans
transetrans
1.43/1.75
1.84
1.82
a
See Ref. 9.
Table 8
Coupling constants of aliphatic hydrogen atoms in 1,3-diarylindanes
OCH3
OCH3
Cycloadducts
J1,2 (Hz)
J2,3 (Hz)
Configuration
H3CO
H3CO
Ph
OCH3
VIa
46
48
Va
47
49
10.5
9.9
9.9
8.5
8.3
7.9
10.5
9.9
9.9
9.7
9.1
8.8
transetrans
transetrans
transetrans
cisetrans
cisetrans
cisetrans
OCH3
51
52
Figure 6.
present two singlet signals at d 6.78, 6.42 for 51 and d 6.74,
6.54 for 52 corresponding to H-3 and H-6 from the trime-
thoxy-substituted aryl group (C-2, C-4 and C-5) from the ben-
zylic substrate (alcohol 10). Besides, compound 52 presents
a signal at d 6.38 ppm, characteristic for a vinylic hydrogen.
13C NMR spectra from 51 and 52 show signals at d 97.6,
111.2 and at d 97.9 and 111.8, respectively, which correspond
to carbons sp2, C-3 and C-6, from the aryl group trisubstituted.
All these data confirm the proposed structures for compounds
51 and 52.
a
See Ref. 18.
Ph
Ph
CH3
CH3
Ph
V
Ph
VI
Figure 2.

4098
B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
3. Conclusions
d, J¼8.6 Hz, H-7, H-20). dC 10.9, 17.3, 24.7, 50.9, 51.1,
55.2, 55.4, 58.3, 109.9, 112.6, 113.8, 123.6, 129.7, 136.2,
138.8, 148.3, 158.2, 158.8. Anal. Calcd for C20H24O2: C, 81.0;
H, 8.2. Found: C, 81.1; H, 8.3.
The reaction of benzylic cations with diverse alkenes al-
lows to obtain complex indane structures. Yields are highly
variable and dependent on the electronic effects of the substit-
uents on both the benzylic alcohols and the alkenes. Regio-
chemistry is controlled and the stereocontrol is excellent at
two of the three stereogenic centers formed. We have also
found that the formal [3þ2] cycloaddition reaction between
benzylic alcohols and cyclic alkenes regioselectively afforded
6,6a,7,11b-tetrahydro-5H-benzo[c]fluorene derivatives in mild
conditions. Finally, with a simple one-step process, using read-
ily available starting compounds, several complex structures
have been synthetized that makes this cycloaddition reaction
an attractive option.
4.2.2. r-1-Ethyl-t-2-methyl-c-3-(3,4-methylenedioxyphenyl)-
5-methoxyindane (19)
General procedure was carried out with alcohol 1 (0.11 g,
0.69 mmol), styrene 12 (0.11 g, 0.69 mmol), and SnCl4
(0.23 g, 0.90 mmol). p-TLC (95:5, hexane/isopropanol) af-
forded 0.04 g (20%) of 19 (pale yellow solid), mp: 99e
100 ꢁC. dH 0.98 (3H, t, J¼7.5 Hz, CH2CH3), 1.14 (3H, d,
J¼6.6 Hz, CH3), 1.85 (2H, m, CH2), 2.02 (1H, m, J¼6.6,
9.6, 9.8 Hz, CHCH3), 2.67 (1H, m, J¼5.3, 9.8 Hz, ArCHCH2),
3.62 (1H, d, J¼9.6 Hz, ArCHAr), 3.70 (3H, s, OCH3), 5.93
(2H, d, J¼1.8 Hz, OCH2O), 6.39 (1H, s, H-4), 6.63 (1H, d,
J¼1.5 Hz, H-20), 6.68 (1H, dd, J¼1.5, 8.1 Hz, H-60), 6.75
(1H, dd, J¼2.0, 7.6 Hz, H-6), 6.80 (1H, d, J¼7.8 Hz, H-7),
7.10 (1H, d, J¼8.1 Hz, H-50). dC 10.8, 17.3, 24.6, 29.7, 51.0,
55.4, 58.7, 100.9, 108.0, 108.8, 109.9, 112.6, 122.1, 123.7,
138.1, 138.8, 142.6, 146.2, 148.0, 158.8. Anal. Calcd for
C20H22O3: C, 77.4; H, 7.1. Found: C, 77.5; H, 7.2.
4. Experimental
4.1. General
NMR spectra were recorded (CDCl3) on a Bruker AC 300
or Avance 500 spectrometers. Shifts reported are relative to in-
ternal standard Si(Me)4 and coupling constants are reported in
hertz (s: singlet, br s: broad singlet, d: doublet, t: triplet, q:
quartet, dd: double doublet, dt: double triplet, m: multiplet).
Microanalyses were performed by Elemental Analyser Carlo
Erba. Preparative thin layer chromatography (p-TLC) was
done on Merck Silica Gel 60 GF254 and analytical TLC was
4.2.3. r-1-Ethyl-c-2-methyl-t-3-(4-methoxyphenyl)-6-hydroxy-
indane (20) and r-1-ethyl-t-2-methyl-c-3-(4-methoxyphenyl)-
6-hydroxyindane (21)
General procedure was carried out with alcohol 2 (0.10 g,
0.65 mmol), styrene 11 (0.10 g, 0.66 mmol), and SnCl4
(0.23 g, 0.90 mmol). p-TLC (CH2Cl2) afforded 0.01 g (7%)
of 20 and 21 as a 2:1 (20/21) inseparable mixture (clear oil).
Major diastereomer 20: dH 1.01 (3H, t, J¼7.4 Hz, CH2CH3),
1.04 (3H, d, J¼7.7 Hz, CH3), 1.83 (2H, m, CH2), 2.49 (1H,
m, J¼7.1, 7.7, 9.6 Hz, CHCH3), 2.95 (1H, m, J¼6.0, 7.1 Hz,
ArCHCH2), 3.78 (1H, d, J¼9.6 Hz, ArCHAr), 3.83 (3H, s,
OCH3), 5.31 (1H, s, OH), 6.59 (1H, d, J¼2.9 Hz, H-7), 6.74
(2H, m, H-4, H-5), 6.89 (2H, d, J¼9.4 Hz, H-20), 7.12 (2H,
d, J¼9.4 Hz, H-30). dC 11.9, 13.4, 21.6, 48.3, 49.0, 55.3, 54.9,
111.6, 113.1, 113.4, 125.3, 129.1, 136.0, 138.9, 149.7, 153.6,
154.0. Minor diastereomer 21: dH 0.99 (3H, t, J¼7.4 Hz,
CH2CH3), 1.16 (3H, d, J¼6.5 Hz, CH3), 1.43 (1H, m, CH2),
1.75 (1H, m, CH2), 2.01 (1H, m, J¼6.5, 9.1, 10.1 Hz,
CHCH3), 2.75 (1H, m, ArCHCH2), 3.63 (1H, d, J¼10.1 Hz,
ArCHAr), 3.82 (3H, s, OCH3), 5.18 (1H, s, OH), 6.62 (1H,
dd, J¼2.9, 9.1 Hz, H-5), 6.70 (1H, d, J¼8.4 Hz, H-4), 6.77
(1H, d, J¼2.6 Hz, H-7), 6.86 (2H, d, J¼9.8 Hz, H-30), 7.08
(1H, d, J¼9.8 Hz, H-20). dC 10.5, 16.9, 23.8, 50.7, 51.3, 54.9,
57.1, 109.8, 113.0, 113.5, 125.0, 129.3, 137.1, 138.8, 148.3,
157.4, 158.2. Anal. Calcd for C19H22O2: C, 80.8; H, 7.8. Found:
C, 80.9; H, 7.9.
performed on Merck aluminum sheets Silica Gel 60 GF254
.
Commercial compounds were purchased from Aldrich Chemi-
cal Co. THF and CH2Cl2 were distilled from sodium/
benzophenone and CaH2, respectively. Melting points are un-
corrected and were determined in a Thomas Hoover apparatus.
The products were isolated by quenching the reaction mixture
with a solution of NaCO3H 5%, separate the organic layer, ex-
tract the aqueous layer several times with the organic solvent,
dry the combined organic extracts over Na2SO4 and remove
the solvent under reduced pressure.
4.2. General procedure for the formal [3þ2] cycloaddition of
an alcohol and an alkene in the presence of SnCl4
4.2.1. r-1-Ethyl-t-2-methyl-c-3-(4-methoxyphenyl)-5-
methoxyindane (18)
Styrene 11 (0.10 g, 0.67 mmol) and SnCl4 (0.23 g,
0.90 mmol) were sequentially added to a solution of alcohol
1 (0.11 g, 0.69 mmol) in CH2Cl2 (10 mL) at 0 ꢁC. The result-
ing solution was stirred for 30 min at 0 ꢁC and then poured
into a rapidly stirred solution of NaCO3H 5%. Aqueous
workup (NaCO3H, CH2Cl2) followed by p-TLC (95:5, hex-
ane/isopropanol) afforded 0.04 g (19%) of 18 (solid), mp:
134e135 ꢁC.17 dH 0.97 (3H, t, J¼7.4 Hz, CH2CH3), 1.15
(3H, d, J¼6.6 Hz, CH3), 1.83 (2H, m, CH2), 2.02 (1H, m, J¼
6.6, 9.8, 9.9 Hz, CHCH3), 2.67 (1H, m, J¼5.3, 9.9 Hz,
ArCHCH2), 3.65 (1H, d, J¼9.8 Hz, ArCHAr), 3.68 (3H, s,
OCH3), 3.81 (3H, s, OCH3), 6.38 (1H, s, H-4), 6.75 (1H, dd,
J¼2.3, 8.1 Hz, H-6), 6.86 (2H, d, J¼8.6 Hz, H-30), 7.11 (3H,
4.2.4. r-1-Ethyl-c-2-methyl-t-3-(3,4-methylenedioxyphenyl)-
6-hydroxyindane (22) and r-1-ethyl-t-2-methyl-c-3-(3,4-
methylenedioxyphenyl)-6-hydroxyindane (23)
General procedure was carried out with alcohol 2 (0.10 g,
0.66 mmol), styrene 12 (0.10 g, 0.66 mmol), and SnCl4
(0.23 g, 0.90 mmol). p-TLC (CH2Cl2) afforded 0.03 g (15%)
of 22 and 23 as a 1.3:1 (22/23) inseparable mixture (clear

B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
4099
oil). Major diastereomer 22: dH 0.97 (3H, t, J¼7.2 Hz,
CH2CH3), 1.03 (3H, d, J¼6.9 Hz, CH3), 1.4 (1H, m, CH2),
1.68 (1H, m, CH2), 2.44 (1H, m, J¼6.9, 7.2, 9.5 Hz,
CHCH3), 2.92 (1H, m, ArCHCH2), 3.76 (1H, d, J¼9.5 Hz,
ArCHAr), 4.66 (1H, br s, OH), 5.93 (2H, s, OCH2O), 6.59e
6.71 (6H, m, Ar). dC 12.1, 13.6, 21.9, 48.5, 49.2, 56.1, 100.7,
107.8, 108.4, 111.8, 113.3, 121.7, 125.6, 129.0, 137.2, 144.0,
145.5, 148.2, 154.8. Minor diastereomer 23: dH 0.97 (3H, t,
J¼7.2 Hz, CH2CH3), 1.12 (3H, d, J¼6.4 Hz, CH3), 1.84 (2H,
m, CH2), 2.02 (1H, m, J¼6.4, 9.3, 9.8 Hz, CHCH3), 2.69
(1H, m, ArCHCH2), 3.62 (1H, d, J¼9.8 Hz, ArCHAr), 4.66
(1H, br s, OH), 5.92 (2H, s, OCH2O), 6.59e6.71 (6H, m,
Ar). dC 10.7, 17.1, 24.1, 50.9, 51.5, 57.9, 100.7, 107.9, 108.6,
110.0, 113.4, 121.8, 125.2, 128.6, 137.5, 143.1, 145.8, 149.3,
156.7. Anal. Calcd for C19H20O3: C, 77.0; H, 6.8. Found: C,
77.1; H, 6.9.
55.9, 56.0, 106.8, 107.6, 123.6, 124.6, 126.4, 126.6, 134.4,
137.6, 142.9, 145.3, 148.4, 148.5. Anal. Calcd for C20H22O2:
C, 81.6; H, 7.5. Found: C, 81.7; H, 7.7.
4.2.7. (4bS/R,9R/S,9aS/R)-9-Ethyl-6,7-dimethoxy-4b-phenyl-
10,11,4b,9a-tetrahydrobenzo[c]fluorene (27)
General procedure was carried out with alcohol 4 (0.04 g,
0.23 mmol), 4-phenyl-1,2-dihydronaphthalene 14 (0.05 g,
0.25 mmol), and SnCl4 (0.08 g, 0.30 mmol). p-TLC
(CH2Cl2) afforded 0.03 g (30%) of 27 (white solid), mp:
250e251 ꢁC. dH 0.99 (3H, t, J¼7.2 Hz, CH2CH3), 1.74 (2H,
m, CH2CH3), 1.86 (2H, m, CHCH2CH2), 2.51 (1H, m,
CHCHCH2), 2.84 (1H, m, CH2CH2Ar), 2.96 (1H, m,
CH2CH2Ar), 3.03 (1H, m, ArCHCH2CH3), 3.81 (3H, s,
OCH3), 3.87 (3H, s, OCH3), 6.72 (1H, s, Ar), 6.82 (1H, s,
Ar), 7.00e7.31 (9H, m, Ar). dC 11.5, 21.1, 26.7, 30.1, 45.1,
54.6, 55.6, 55.7, 58.5, 111.0, 111.6, 125.0, 125.4, 125.6,
126.8, 126.9, 128.9, 131.6, 135.2, 137.8, 138.0, 139.8,
145.3, 146.0, 147.5. Anal. Calcd for C27H28O2: C, 84.3; H,
7.3. Found: C, 84.5; H, 7.5.
4.2.5. 2,3-Dimethoxyindano[1,2-a]indane (24)
General procedure was carried out with alcohol 3 (0.09 g,
0.58 mmol), indene 13 (0.07 g, 0.62 mmol), and SnCl4 (0.19 g,
0.75 mmol). p-TLC (80:20, hexane/ethyl acetate) afforded
0.06 g (36%) of 24 (clear oil). dH 2.88 (1H, dd, J¼4.2, 15.6 Hz,
CH2CHCH2), 2.93 (1H, dd, J¼5.1, 15.4 Hz, CH2CHCH2), 3.38
(2H, m, J¼8.5, 8.6, 15.4, 15.6 Hz, CH2CHCH2), 3.60 (1H, m,
J¼4.2, 5.1, 7.5, 8.5, 8.6 Hz, CH2CHCH2), 3.97 (3H, s, OCH3),
4.03 (3H, s, OCH3), 4.74 (1H, d, J¼7.5 Hz, ArCHAr), 6.86
(1H, s, Ar), 7.05 (1H, s, Ar), 7.31 (3H, m, Ar), 7.54 (1H, d,
J¼7.2 Hz, Ar). dC 38.9, 39.1, 43.5, 55.9, 56.1, 56.6, 107.3,
107.9, 123.9, 124.8, 126.6, 126.7, 134.4, 136.0, 143.0, 144.7,
148.3, 148.4. Anal. Calcd for C18H18O2: C, 81.3; H, 6.9. Found:
C, 81.2; H, 6.8.
4.2.8. (4bS/R,9R/S,9aS/R)-9-Ethyl-6,7-methylendioxy-4b-
phenyl-10,11,4b,9a-tetrahydrobenzo[c]fluorene (28)
General procedure was carried out with alcohol 5 (0.08 g,
0.46 mmol), 4-phenyl-1,2-dihydronaphthalene 14 (0.10 g,
0.48 mmol), and SnCl4 (0.15 g, 0.60 mmol). p-TLC (80:20,
hexane/ethyl acetate) afforded 0.07 g (40%) of 28 (clear oil).
dH 0.97 (3H, t, J¼7.4 Hz, CH2CH3), 1.72 (2H, m, CH2CH3),
1.88 (2H, m, CH2CH2CH3), 2.55 (1H, m, CHCHCH2), 2.83
(1H, m, CH2CH2Ar), 2.98 (1H, m, CH2CH2Ar), 3.05 (1H,
m, ArCHCH2CH3), 5.88 (1H, d, J¼1.4 Hz, OCH2O), 5.97
(1H, d, J¼1.4 Hz, OCH2O), 6.68 (1H, s, Ar), 6.78 (1H, s,
Ar), 6.98 (1H, m, Ar), 7.0e7.26 (8H, m, Ar). dC 11.0, 21.6,
26.4, 29.7, 45.8, 55.7, 58.4, 100.9, 104.2, 106.8, 125.8, 126.0,
127.7, 128.7, 128.8, 128.9, 135.3, 136.5, 140.0, 142.3, 143.5,
144.3, 148.5, 150.3. Anal. Calcd for C26H24O2: C, 84.7; H,
6.6. Found: C, 84.6; H, 6.7.
4.2.6. (5aR/S,5R/S,10bS/R)-5-Ethyl-2,3-dimethoxyindano-
[1,2-a]indane (25) and (5S/R,5aR/S,10bS/R)-5-ethyl-
2,3-dimethoxyindano[1,2-a]indane (26)
General procedure was carried out with alcohol 4 (0.10 g,
0.51 mmol), indene 13 (0.06 g, 0.52 mmol), and SnCl4
(0.19 g, 0.75 mmol). p-TLC (80:20, hexane/ethyl acetate) af-
forded 0.09 g (60%) of 25 and 26 as a 1.5:1 (25/26) insepara-
ble mixture (clear oil). Major diastereomer 25: dH 1.06 (3H, t,
J¼7.3 Hz, CH3), 1.59 (1H, m, CH2CH3), 1.85 (1H, m, J¼4.6,
7.3, 14.9 Hz, CH2CH3), 2.84 (1H, dd, J¼4.6, 16.2 Hz, CH2Ar),
2.86 (1H, m, CHCH2), 3.10 (1H, m, J¼4.6, 8.9, 12.0 Hz,
CH2CHCH), 3.29 (1H, dd, J¼8.7, 16.2 Hz, CH2Ar), 3.84
(3H, s, OCH3), 3.90 (3H, s, OCH3), 4.62 (1H, d, J¼7.8 Hz,
ArCHAr), 6.68 (1H, s, Ar), 6.91 (1H, s, Ar), 7.13e7.24 (3H,
m, Ar), 7.39 (1H, d, J¼8.3 Hz, Ar). dC 11.7, 28.8, 36.8, 49.8,
52.6, 55.4, 56.0, 56.0, 107.2, 107.5, 124.0, 124.8, 126.5,
126.6, 135.9, 138.2, 143.6, 144.7, 148.4, 148.5. Minor diaste-
reomer 26: dH 1.18 (3H, t, J¼7.3 Hz, CH3), 1.59 (1H, m,
CH2CH3), 2.08 (1H, m, CH2CH3), 2.75 (1H, dd, J¼9.4,
16.0 Hz, CH2Ar), 2.92 (1H, dd, J¼8.7, 16.0 Hz, CH2Ar), 3.25
(1H, m, J¼5.5, 5.7, 11.2 Hz, CH2CHCH), 3.50 (1H, m,
J¼5.7, 7.1, 8.7, 9.4 Hz, CHCHCH2), 3.81 (3H, s, OCH3),
3.86 (3H, s, OCH3), 4.45 (1H, d, J¼7.1 Hz, ArCHAr), 6.71
(1H, s, Ar), 6.72 (1H, s, Ar), 7.13e7.24 (3H, m, Ar), 7.50
(1H, d, J¼7.8 Hz, Ar). dC 12.9, 23.3, 31.9, 47.5, 48.3, 54.9,
4.2.9. (4bS/R,9R/S,9aS/R)-9-Ethyl-5,6,7-trimethoxy-4b-
phenyl-10,11,4b,9a-tetrahydrobenzo[c]fluorene (29) and
(4bS/R,9S/R,9aS/R)-9-ethyl-5,6,7-trimethoxy-4b-phenyl-
10,11,4b,9a-tetrahydrobenzo[c]fluorene (30)
General procedure was carried out with alcohol 6 (0.10 g,
0.46 mmol), 4-phenyl-1,2-dihydronaphthalene 14 (0.10 g,
0.48 mmol), and SnCl4 (0.15 g, 0.60 mmol). p-TLC
(CH2Cl2) afforded 0.12 g (65%) of 29 and 30 as a 2:1 (29/
30) mixture and the same chromatographic system allowed
the separation of 29 (white solid), mp: 131e133 ꢁC, and 30
(white solid), mp: 132e134 ꢁC. Major diastereomer 29: dH
0.95 (3H, t, J¼7.4 Hz, CH3), 1.58 (2H, m, CH2CH3), 1.81
(2H, m, CH2CH2Ar), 2.74 (2H, m), 2.88 (2H, m), 3.01 (3H,
s, OCH3), 3.85 (3H, s, OCH3), 3.88 (3H, s, OCH3), 6.58 (1H,
s, Ar), 7.01e7.34 (9H, m, Ar). dC 12.0, 20.9, 21.0, 29.3, 46.2,
53.1, 56.0, 59.6, 60.7, 60.8, 102.8, 124.5, 125.6, 125.7, 128.4,
130.6, 131.5, 133.3, 133.9, 138.0, 141.2, 141.4, 142.6, 148.5,
152.2, 153.1. Minor diastereomer 30: dH 1.02 (3H, t,
J¼7.4 Hz, CH3), 1.83 (4H, m, CH2CH3, CH2CH2Ar), 2.59

4100
B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
(1H, dt, J¼3.8, 3.8, 10.5 Hz, CHCHCH2), 2.74 (1H, m,
ArCHCH), 2.93 (2H, m, CH2CH2Ar), 3.39 (3H, s, OCH3),
3.78 (3H, s, OCH3), 3.84 (3H, s, OCH3), 6.50 (1H, s, Ar),
7.11e7.21 (8H, m, Ar), 7.74 (1H, m, Ar). dC 10.9, 20.4, 23.8,
26.0, 45.3, 56.1, 56.5, 58.8, 59.7, 60.5, 102.2, 125.3, 126.0,
126.3, 127.3, 128.0, 128.5, 131.7, 134.4, 136.9, 140.1, 141.2,
142.2, 150.0, 150.5, 155.4. Anal. Calcd for C28H30O3: C,
81.1; H, 7.3. Found: C, 81.3; H, 7.4.
4.2.12. (4bS/R,9S/R,9aS/R)-5,6,7-Trimethoxy-9,4b-diphenyl-
10,11,4b,9a-tetrahydrobenzo[c]fluorene (36) and (4bS/R,
9R/S,9aS/R)-5,6,7-trimethoxy-9,4b-diphenyl-10,11,4b,9a-
tetrahydrobenzo[c]fluorene (37)
General procedure was carried out with alcohol 7 (0.12 g,
0.46 mmol), 4-phenyl-1,2-dihydronaphthalene 14 (0.10 g,
0.50 mmol), and SnCl4 (0.15 g, 0.30 mmol). p-TLC (CHCl3)
afforded 0.11 g (52%) of 36 and 37 as a 1:1.3 (36/37) mixture
and the same chromatographic system allowed the separation
of 36 (white solid), mp: 193e195 ꢁC, and 37 (white solid),
mp: 210e212 ꢁC. Major diastereomer 37: dH 1.5 (1H, m,
CH2), 1.6 (1H, m, CH2), 2.38 (1H, m, CHCHCH2), 2.61 (1H,
m, CHCH2Ar), 3.07 (1H, m, CHCH2Ar), 3.10 (3H, s, OCH3),
3.77 (3H, s, OCH3), 3.88 (3H, s, OCH3), 4.36 (1H, d,
J¼7.2 Hz, ArCHAr), 6.50 (1H, d, J¼0.8 Hz, Ar), 6.94 (2H,
m, Ar), 7.02e7.19 (4H, m, Ar), 7.20e7.29 (8H, m, Ar). dC
23.1, 28.6, 53.3, 56.0, 56.1, 56.5, 59.8, 60.8, 104.4, 124.9,
125.0, 125.9, 126.8, 127.4, 127.8, 128.0, 128.1, 129.9, 132.8,
133.0, 135.0, 136.8, 138.7, 140.7, 141.0, 149.0, 151.9, 153.4.
Minor diastereomer 36: dH 1.68 (2H, m, CH2), 2.81 (2H, m,
CH2CH2Ar), 3.10 (1H, m, CHCHCH2), 3.49 (3H, s, OCH3),
3.67 (3H, s, OCH3), 3.80 (3H, s, OCH3), 4.13 (1H, d,
J¼11.8 Hz, ArCHAr), 6.17 (1H, d, J¼0.8 Hz, Ar), 7.14e7.40
(13H, m, Ar), 7.86 (1H, m, Ar). dC 25.7, 28.5, 51.9, 56.1,
58.3, 59.8, 60.5, 62.2, 103.7, 125.5, 126.3, 126.6, 126.7,
127.5, 128.5, 128.6, 128.8, 128.9, 131.7, 132.4, 133.3, 137.9,
140.8, 143.0, 143.1, 149.4, 152.5, 153.9. Anal. Calcd for
C32H30O3: C, 83.1; H, 6.5. Found: C, 83.2; H, 6.6.
4.2.10. (4bR/S,9R/S,9aS/R)-9-Ethyl-6,7-dimethoxy-10,11,
4b,9a-tetrahydrobenzo[c]fluorene (31) and (4bR/S,9S/R,
9aS/R)-9-ethyl-6,7-dimethoxy-10,11,4b,9a-
tetrahydrobenzo[c]fluorene (32)
General procedure was carried out with alcohol 4 (0.17 g,
0.86 mmol), 1,2-dihydronaphthalene 15 (0.11 g, 0.85 mmol),
and SnCl4 (0.31 g, 1.20 mmol). p-TLC (80:20, hexane/ethyl
acetate) afforded 0.11 g (42%) of 31 and 32 as a 1:1.2 (31/
32) inseparable mixture (clear oil). Mixture diastereomer 31
and 32: dH 0.95 (3H, t, J¼7.4 Hz, CH3), 1.06 (3H, t,
J¼7.1 Hz, CH3), 1.65 (7H, m), 1.81 (1H, m), 2.55 (1H, m),
2.67 (2H, m), 2.75 (3H, m), 3.80 (3H, s, OCH3), 3.86 (6H,
s, OCH3), 3.88 (4H, overlaps with OCH3), 4.39 (1H, d,
J¼6.9 Hz, ArCHAr), 6.76 (6H, m, Ar), 7.15 (2H, m, Ar),
7.27 (3H, m, Ar), 7.41 (d, J¼7.7 Hz, Ar). dC 12.4, 13.8,
18.8, 20.6, 24.7, 27.4, 27.5, 28.6, 37.6, 42.6, 44.2, 46.2, 48.4,
52.7, 55.7, 55.8, 55.9, 56.0, 107.1, 107.8, 107.9, 108.3, 111.1,
111.7, 120.1, 125.6, 125.7, 125.8, 126.0, 135.3, 136.6, 136.7,
136.8, 137.2, 137.5, 137.7, 137.8, 138.0, 147.0, 147.6, 148.0,
148.7. Anal. Calcd for C21H24O2: C, 81.8; H, 7.8. Found: C,
81.9; H, 7.7.
4.2.13. (4bR/S,9S/R,9aS/R)-5,6,7-Trimethoxy-9-phenyl-
10,11,4b,9a-tetrahydrobenzo[c]fluorene (38) and (4bR/
S,9R/S,9aS/R)-5,6,7-trimethoxy-9-phenyl-10,11,4b,9a-
4.2.11. (5aR/S,5S/R,10bS/R,)-1,2,3-Trimethoxy-5-phenyl-
indano[1,2-a]indane (34) and (5R/S,5aR/S,10bS/R,)-
1,2,3-trimethoxy-5-phenylindano[1,2-a]indane (35)
tetrahydrobenzo[c]fluorene (39)
General procedure was carried out with alcohol 7 (0.11 g,
0.42 mmol), 1,2-dihydronaphthalene 15 (0.08 g, 0.67 mmol),
and SnCl4 (0.14 g, 0.54 mmol). p-TLC (CHCl3) afforded
0.03 g (20%) of 38 and 39 as a 1:1 (38/39) mixture (white
solid). p-TLC (70:30, hexane/ethyl acetate) allowed the sepa-
ration of 38 (white solid), mp: 79e80 ꢁC, and 39 (white solid),
mp: 58e60 ꢁC. Diastereomer 38: dH 1.72 (1H, m, J¼4.9, 5.1,
10.0, 15.3 Hz, CHCH2), 1.96 (1H, m, J¼5.1, 5.4, 10.0,
15.3 Hz, CH2), 2.73 (1H, m, J¼5.1, 5.4, 16.1 Hz, CHCH2Ar),
2.88 (1H, m, J¼5.1, 7.7, 10.2, 11.3 Hz, CHPhCHCH2), 2.95
(1H, m, J¼4.9, 10.0, 16.1 Hz, CHCH2Ar), 3.66 (3H, s,
OCH3), 3.90 (3H, s, OCH3), 4.02 (3H, s, OCH3), 4.04 (1H,
d, J¼11.3 Hz, ArCHPh), 4.50 (1H, d, J¼7.7 Hz, ArCHAr),
6.15 (1H, s, Ar), 7.14 (3H, m, Ar), 7.23 (3H, m, Ar), 7.33
(2H, m, Ar), 7.63 (1H, d, J¼7.2 Hz, Ar). dC 23.8, 27.1, 44.4,
50.5, 54.3, 56.3, 60.7, 61.0, 104.3, 125.8, 126.3, 128.2, 128.5,
128.7, 129.5, 129.8, 130.7, 137.3, 138.2, 140.7, 142.6, 143.2,
150.1, 153.3. Diastereomer 39: dH 1.28 (1H, m, CHCH2),
1.45 (1H, m, CHCH2), 2.51 (2H, m, CHCH2Ar, CHCH2Ar),
3.01 (1H, m, CHCH2Ar), 3.43 (3H, s, OCH3), 3.74 (3H, s,
OCH3), 3.87 (3H, s, OCH3), 4.45 (1H, d, J¼7.2 Hz, ArCHPh),
4.51 (1H, d, J¼7.7 Hz, ArCHAr), 6.48 (1H, s, Ar), 7.04e7.16
(4H, m, Ar), 7.19e7.26 (4H, m, Ar), 7.53 (1H, d, J¼7.4 Hz,
Ar). dC 22.9, 29.0, 45.3, 47.1, 55.4, 56.2, 60.5, 61.0, 104.6,
General procedure was carried out with alcohol 7 (0.13 g,
0.46 mmol), indene 13 (0.08 g, 0.74 mmol), and SnCl4
(0.15 g, 0.60 mmol). p-TLC (CHCl3) afforded 0.02 g (26%)
of 34 and 35 as a 1:1.2 (34/35) inseparable mixture (yellow
solid). Major diastereomer 35: dH 2.59 (2H, d, J¼7.5 Hz,
CHCH2Ar), 3.64 (1H, m, J¼7.5, 7.9, 8.8 Hz, CHPhCHCH2),
3.67 (3H, s, OCH3), 3.91 (4H, overlaps with OCH3, ArCHPh),
3.74 (3H, s, OCH3), 3.89 (3H, s, OCH3), 3.94 (3H, s, OCH3),
4.62 (1H, d, J¼8.8 Hz, ArCHAr), 6.42 (1H, s, Ar), 7.04 (3H,
m, Ar), 7.17e7.39 (5H, m, Ar), 7.67 (1H, d, J¼7.5 Hz, Ar). Mi-
nor diastereomer 34: dH 3.00 (1H, dd, J¼1.8, 16.2 Hz, CH2),
3.15 (1H, dd, J¼7.2, 16.2 Hz, CH2), 3.31 (1H, m, J¼1.8, 7.2,
7.5, 7.7 Hz, CHPhCHCH2), 3.66 (3H, s, OCH3), 3.90 (3H, s,
OCH3), 4.12 (3H, s, OCH3), 4.85 (1H, d, J¼7.7 Hz, ArCHPh),
4.92 (1H, d, J¼7.7 Hz, ArCHAr), 6.10 (1H, s, Ar), 6.88 (1H, d,
J¼7.5 Hz, Ar), 7.17e7.39 (7H, m, Ar), 7.58 (1H, m, Ar). Mix-
ture diastereomer 34 and 35: dC 34.1, 36.5, 49.2, 53.1, 54.0,
54.2, 55.3, 56.1, 58.1, 60.5, 60.7, 60.8, 60.9, 103.7, 104.4,
124.0, 125.0, 125.9, 126.0, 126.1, 126.3, 126.5, 126.6,
126.8, 126.9, 127.9, 128.6, 129.3, 141.8, 142.1, 143.4, 144.4.
Anal. Calcd for C25H24O3: C, 80.6; H, 6.5. Found: C, 80.7;
H, 6.6.

B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
4101
125.2, 125.8, 126.4, 127.3, 128.1, 129.9, 130.6, 137.4, 138.8,
140.9, 141.2, 141.3, 143.5, 153.1. Anal. Calcd for C26H26O3:
C, 80.8; H, 6.8. Found: C, 80.9; H, 6.9.
6.47 (1H, s, Ar), 6.58 (1H, s, Ar), 7.21e7.36 (5H, m, Ar). dC
15.9, 54.3, 55.8, 55.9, 56.0, 56.6, 56.7, 56.8, 58.3, 97.8,
107.2, 107.5, 112.7, 123.3, 123.8, 126.4, 138.1, 138.7, 143.3,
143.8, 147.9, 148.1, 148.3, 152.3, 152.4. Anal. Calcd for
C27H30O5: C, 74.6; H, 6.9. Found: C, 74.7; H, 7.0.
4.2.14. r-1-Ethyl-t-2-methyl-c-3-(2,4,5-trimethoxyphenyl)-5-
methoxyindane (40)
General procedure was carried out with alcohol 1 (0.11 g,
0.69 mmol), styrene 16 (0.14 g, 0.69 mmol), and SnCl4
(0.23 g, 0.90 mmol). p-TLC (95:5, hexane/isopropanol) af-
forded 0.09 g (23%) of 40 (clear oil). Compound 40: dH
1.00 (3H, t, J¼7.4 Hz, CH2CH3), 1.14 (3H, d, J¼6.7 Hz,
CH3), 1.82 (2H, m, CH2CH3), 2.06 (1H, m, J¼6.7, 9.5,
10.0 Hz, CHCH3), 2.67 (1H, m, J¼4.6, 5.4, 10.0 Hz,
ArCHCH2), 3.69 (3H, s, OCH3), 3.71 (3H, s, OCH3), 3.80
(3H, s, OCH3), 3.91 (3H, s, OCH3), 4.22 (1H, d, J¼9.5 Hz,
ArCHAr), 6.38 (1H, d, J¼2.5 Hz, H-4), 6.54 (1H, s, Ar),
6.59 (1H, s, Ar), 6.73 (1H, dd, J¼2.5, 8.2 Hz, H-6), 7.12
(1H, d, J¼8.2 Hz, H-7). dC 11.1, 17.8, 25.0, 50.1, 50.6, 51.3,
55.4, 56.1, 56.7, 57.0, 98.1, 109.6, 112.3, 113.2, 123.6,
124.2, 139.1, 143.4, 148.0, 148.3, 152.5, 158.8. Anal. Calcd
for C22H28O4: C, 74.1; H, 7.9. Found: C, 74.2; H, 8.0.
4.2.17. r-1-(2,4,5-Trimethoxyphenyl)-t-2-methyl-c-3-phenyl-
5-methoxy-6-hydroxyindane (48) and r-1-(2,4,5-trimethoxy-
phenyl)-t-2-methyl-t-3-phenyl-5-methoxy-6-hydroxy-
indane (49)
General procedure was carried out with alcohol 9 (0.12 g,
0.53 mmol), styrene 16 (0.14 g, 0.69 mmol), and SnCl4
(0.18 g, 0.69 mmol). p-TLC (CHCl3) afforded 0.12 g (55%)
of 48 and 49 as a 1:2.2 (48/49) mixture(solid). P-TLC (80:
20 hexane/ethyl acetate) allowed the separation of 48 (yellow
solid), mp: 155e157 ꢁC, and 49 (yellow solid), mp: 168e
170 ꢁC. Major diastereomer 49: dH 0.68 (3H, d, J¼7.0 Hz,
CH3), 2.72 (1H, m, CHCH3), 3.72 (3H, s, OCH3), 3.77 (3H,
s, OCH3), 3.81 (3H, s, OCH3), 3.90 (3H, s, OCH3), 4.38
(1H, d, J¼8.1 Hz, ArCH), 4.41 (1H, d, J¼9.2 Hz, ArCH),
5.54 (1H, s, OH), 6.54 (1H, s, Ar), 6.55 (1H, s, Ar), 6.56
(1H, s, Ar), 6.67 (1H, s, Ar), 6.99 (2H, m, Ar), 7.00e7.31
(3H, m, Ar). dC 15.6, 48.6, 49.4, 54.2, 55.9, 56.0, 56.6, 56.7,
97.7, 107.3, 110.4, 112.4, 123.6, 126.0, 127.9, 129.0, 137.6,
139.8, 142.2, 143.2, 144.9, 145.8, 147.9, 152.4. Minor diaste-
reomer 48: dH 1.05 (3H, d, J¼6.6 Hz, CH3), 2.40 (1H, m,
J¼6.6, 9.9, 9.9 Hz, CHCH3), 3.74 (4H, overlaps with OCH3,
CHAr), 3.75 (3H, s, OCH3), 3.81 (3H, s, OCH3), 3.90 (3H,
s, OCH3), 4.31 (1H, d, J¼9.9 Hz, ArCH), 5.49 (1H, s, OH),
6.40 (1H, s, Ar), 6.46 (1H, s, Ar), 6.47 (1H, s, Ar), 6.58
(1H, s, Ar), 7.25e7.39 (5H, m, Ar). dC 15.9, 56.1, 56.2,
56.7, 57.0, 58.4, 98.0, 107.0, 110.1, 112.7, 123.1, 126.4,
128.4, 128.8, 137.5, 139.7, 143.4, 143.9, 144.8, 145.6,
148.0, 152.5. Anal. Calcd for C26H28O5: C, 74.2; H, 6.7.
Found: C, 74.3; H, 6.8.
4.2.15. r-1-(2,4,5-Trimethoxyphenyl)-t-2-methylindane (42)
General procedure was carried out with alcohol 3 (0.08 g,
0.46 mmol), styrene 16 (0.11 g, 0.56 mmol), and SnCl4
(0.15 g, 0.60 mmol). p-TLC (70:30, hexane/ethyl acetate) af-
forded 0.05 g (30%) of 42 (clear oil). Compound 42: dH
1.15 (3H, d, J¼6.7 Hz, CH3), 2.35 (1H, m, CHCH3), 2.55
(1H, dd, J¼8.7, 14.9 Hz, CH2), 3.04 (1H, dd, J¼7.5, 14.9 Hz,
CH2), 3.68 (3H, s, OCH3), 3.72 (3H, s, OCH3), 3.83 (3H, s,
OCH3), 3.88 (3H, s, OCH3), 3.91 (3H, s, OCH3), 4.28 (1H, d,
J¼8.5 Hz, ArCH), 6.41 (1H, s, Ar), 6.49 (1H, s, Ar), 6.59
(1H, s, Ar), 6.79 (1H, s, Ar). dC 17.9, 39.6, 42.8, 52.5, 55.6,
55.7, 55.8, 56.7, 56.4, 96.4, 111.3, 113.1, 116.2, 123.8, 131.4,
132.2, 141.0, 147.2, 147.7, 148.1, 149.5. Anal. Calcd for
C21H26O5: C, 70.4; H, 7.3. Found: C, 70.5; H, 7.4.
4.2.18. 3-[1-(2,4,5-Trimethoxyphenyl)-propyl]-1,2-dihydro-
naphthalene (51)
4.2.16. r-1-(2,4,5-Trimethoxyphenyl)-t-2-methyl-c-3-phenyl-
5,6-dimethoxyindane (46) and r-1-(2,4,5-trimethoxyphenyl)-
t-2-methyl-t-3-phenyl-5,6-dimethoxyindane (47)
General procedure was carried out with alcohol 10 (0.10 g,
0.46 mmol), 4-phenyl-1,2-dihydronaphthalene 14 (0.10 g,
0.50 mmol), and SnCl4 (0.15 g, 0.30 mmol). p-TLC (80:20,
hexane/ethyl acetate) afforded 0.14 g (73%) of 51 (clear oil).
dH 0.83 (3H, t, J¼7.4 Hz, CH2CH3), 1.80 (2H, m, J¼6.5,
7.4 Hz, CH2CH3), 2.24 (1H, m, CH2CH2Ar), 2.36 (1H, m,
CH2CH2Ar), 2.75 (3H, m, CH2Ar, CHCH2), 3.59 (3H, s,
OCH3), 3.84 (3H, s, OCH3), 3.86 (3H, s, OCH3), 6.42 (1H,
s, Ar), 6.55 (1H, dd, J¼6.6, 7.7 Hz, Ar), 6.78 (1H, s, Ar),
6.96e7.11 (3H, m, Ar), 7.26 (2H, m, Ar), 7.29e7.44 (3H,
m). dC 12.6, 24.1, 25.6, 28.8, 43.0, 55.9, 56.1, 56.9, 97.6,
111.2, 122.9, 125.8, 126.0, 126.1, 126.4, 126.7, 127.8, 129.5,
134.8, 138.1, 138.2, 140.9, 141.8, 148.2, 148.6, 157.3. Anal.
Calcd for C28H30O3: C, 81.1; H, 7.3. Found: C, 81.2; H, 7.4.
General procedure was carried out with alcohol 8 (0.13 g,
0.53 mmol), styrene 16 (0.14 g, 0.69 mmol), and SnCl4
(0.18 g, 0.69 mmol). p-TLC (CHCl3) afforded 0.09 g (40%)
of 46 and 47 as a 1:2.9 (46/47) inseparable mixture (clear
oil). Major diastereomer 47: dH 0.68 (3H, d, J¼7.1 Hz,
CH3), 2.68 (1H, m, CHCH3), 3.70 (3H, s, OCH3), 3.78 (6H,
s, OCH3), 3.80 (3H, s, OCH3), 3.91 (3H, s, OCH3), 4.38
(1H, d, J¼8.3 Hz, ArCH), 4.43 (1H, d, J¼9.1 Hz, ArCH),
6.49 (1H, s, Ar), 6.52 (1H, s, Ar), 6.58 (1H, s, Ar), 6.70
(1H, s, Ar), 6.98 (2H, m, Ar), 7.21e7.36 (3H, m, Ar). dC
15.4, 48.9, 50.0, 54.3, 55.8, 55.9, 56.0, 56.5, 56.6, 97.6,
107.4, 107.8, 112.4, 126.1, 127.9, 128.7, 129.0, 138.3, 138.8,
142.1, 143.2, 147.8, 148.3, 148.4, 152.3. Minor diastereomer
46: dH 1.07 (3H, d, J¼6.7 Hz, CH3), 2.28 (1H, m, J¼6.7, 9.8,
9.9 Hz, CHCH3), 3.73 (3H, s, OCH3), 3.74 (3H, s, OCH3),
3.75 (3H, s, OCH3), 3.83 (3H, s, OCH3), 3.92 (5H, overlaps
with OCH3, CHAr, CHPh), 6.40 (1H, s, Ar), 6.46 (1H, s, Ar),
4.2.19. 4-Phenyl-3-[1-(2,4,5-trimethoxyphenyl)-propyl]-
1,2-dihydronaphthalene (52)
General procedure was carried out with alcohol 10 (0.10 g,
0.46 mmol), 1,2-dihydronaphthalene 15 (0.097 g, 0.74 mmol),

4102
B. Lanta~no et al. / Tetrahedron 64 (2008) 4090e4102
4. Misra, R.; Pandey, R. C.; Silverton, J. V. J. Am. Chem. Soc. 1982, 104,
4478e4479.
´
5. Adesanya, S. A.; Nia, R.; Martın, M.; Boukamcha, N.; Montagnac, A.;
Pais, M. J. Nat. Prod. 1999, 62, 1694e1695.
and SnCl4 (0.15 g, 0.60 mmol). p-TLC (70:30, hexane/ethyl
acetate) afforded 0.11 g (70%) of 52 (clear oil). dH 0.90
(3H, t, J¼7.4 Hz, CH2CH3), 1.71 (1H, m, CH2CH3), 1.96
(1H, m, CH2CH3), 2.12 (3H, m, CHCH2, CH2CH2Ar), 2.70
(2H, m, CH2CH2Ar), 3.80 (3H, s, OCH3), 3.82 (3H, s,
OCH3), 3.89 (3H, s, OCH3), 6.38 (1H, s, CH]), 6.54 (1H,
s, Ar), 6.74 (1H, s, Ar), 7.04e7.12 (4H, m, Ar). dC 12.3,
25.8, 26.8, 28.4, 44.9, 56.0, 56.7, 56.8, 97.9, 111.8, 121.7,
123.8, 125.6, 126.1, 126.3, 127.1, 134.7, 135.0, 143.2,
144.6, 147.7, 152.0. Anal. Calcd for C22H26O3: C, 78.1; H,
7.7. Found: C, 78.2; H, 7.8.
6. Sterling, J.; Herzig, Y.; Goren, T.; Finkelstein, N.; Lerner, D.; Goldenberg,
W.; Miskolezi, I.; Molnar, S.; Rantal, F.; Tamas, T.; Toth, G.; Zagyva, A.;
Zekany, A.; Lavian, G.; Gross, A.; Friedman, R.; Razin, M.; Huang, W.;
Krais, B.; Clorev, M.; Yoidim, M. B.; Weinstock, M. J. Med. Chem.
2002, 5260e5279.
7. Yu, H.; Kim, I. Y.; Folk, Y. E.; Tian, X.; Rothman, R. B.; Buamann, M. H.;
Dersch, C. M.; Flippen-Anderson, J. L.; Parrish, D.; Jacobson, A. E.; Rice,
K. C. J. Med. Chem. 2004, 47, 2624e2634.
8. Baker, W.; Enderby, J. J. Chem. Soc. 1940, 1094e1098.
9. MacMillan, J.; Martin, I. L.; Morris, D. J. Tetrahedron 1969, 25, 905e914.
10. Marcuzzi, F.; Melloni, G.; Modena, G. J. Org. Chem. 1979, 44, 3022e3028.
11. Angle, S.; Arnaiz, D. O. J. Org. Chem. 1992, 57, 937e947.
Acknowledgements
~
12. Lantano, B.; Aguirre, J. M.; Finkielsztien, L. M.; Alesso, E. N.; Brunet,
This work supported by grants from the Consejo Nacional
E.; Moltrasio, G. Synth. Commun. 2004, 34, 625e641.
~
13. Alesso, E.; Torviso, R.; Lantano, B.; Erlich, M.; Finkielsztein, L. M.;
Moltrasio, G.; Aguirre, J. M.; Brunet, E. ARKIVOC 2003, X, 283e297.
´
´
de Investigaciones Cientıficas y Tecnicas (CONICET) and
Universidad de Buenos Aires.
´
14. Pizzio, L. R.; Vazquez, P. G.; Caceres, C. V.; Blanco, M. N.; Alesso, E. N.;
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