Scope of the formal [3+2] cycloaddition for the synthesis of five-membered ring of functionalized indanes

Article abstract of DOI:10.1016/j.tet.2011.10.089

We report our research about the synthesis of functionalized indanes in the pentagonal ring by a formal [3+2] cycloaddition using benzhydrols and styrene derivatives with electron-withdrawing groups joined to C-β, such as carboxyl, carboxymethyl, carbonyl

Full text of DOI:10.1016/j.tet.2011.10.089

Tetrahedron 68 (2012) 913e921
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Scope of the formal [3þ2] cycloaddition for the synthesis of five-membered ring
of functionalized indanes
a
,
b
b
a
a
a
~
ꢀ
Beatriz Lantano , Jose Manuel Aguirre , Esteban Ariel Ugliarolo , Rosario Torviso , Nicolas Pomilio ,
Graciela Yolanda Moltrasio a
Departamento de Química Organica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
,
*
a
ꢀ
b
ꢀ
ꢀ
ꢀ
Departamento de Ciencias Basicas, Universidad Nacional de Lujan, Lujan, Argentina
a r t i c l e i n f o
a b s t r a c t
Article history:
We report our research about the synthesis of functionalized indanes in the pentagonal ring by a formal
Received 20 September 2011
Received in revised form 21 October 2011
Accepted 25 October 2011
[3þ2] cycloaddition using benzhydrols and styrene derivatives with electron-withdrawing groups joined
to C-b, such as carboxyl, carboxymethyl, carbonyl of ketones, and nitro groups. We also report the
configurational assignment of the indanic structures synthesized using several experiments of NMR.
Ó 2011 Published by Elsevier Ltd.
Available online 22 November 2011
Keywords:
Indanes
Formal [3þ2] cycloaddition
Stereochemistry
1. Introduction
groups at C-1 and C-3, such as compounds SB-209670 and SB-
217242 (III),3 are potent antagonists of endothelin receptors.
The dihydroindene ring system is a structural subunit found
in a large number of naturally occurring compounds with anti-
tumor activity, such as ‘secaloside’ A (I).1 In addition, several
synthetic compounds with this skeleton, show a broad range of
biological activities, such as the hydroxylated derivative of 3-
Endothelin ET-1 and closely related compounds, such as the
isopeptides ET-2 and ET-3, cause a profound vasoconstriction and
mitogenic activity in the cardiovascular system4,5 and play an
important role in the pathogenesis of cardiovascular diseases
(Fig. 1).
Fig. 1. Natural and synthetic products with dihydroindene ring system.
(3,4-dichlorophenyl)-1-N-methylindanamine (II), which has high
affinity for the serotonin transporter, dopamine, and norepi-
nephrine.2 Furthermore, indan-2-carboxylic acid with aryl
A variety of synthetic strategies to obtain this type of systems
have been developed. These range from the dimerization of pro-
penylbenzenes in acid medium6 to multi-step synthesis of poly-
cyclic indane structures,7 among other syntheses.8 The synthesis of
functionalized indane structures in the pentagonal ring is complex,
requires several steps, and generally results in low total yield.
* Corresponding author. E-mail address: gmoltra@ffyb.uba.ar (G.Y. Moltrasio).
0040-4020/$ e see front matter Ó 2011 Published by Elsevier Ltd.
doi:10.1016/j.tet.2011.10.089

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B. Lantano et al. / Tetrahedron 68 (2012) 913e921
914
Therefore, the discovery of new synthetic strategies has become an
interesting challenge. A reaction that has been very successful in
the synthesis of highly substituted indanes9 and indanic structures
in three and tetracyclic systems10 has been the formal [3þ2] cy-
cloaddition (FCA [3þ2]) from benzyl alcohols and benzhydrols with
styrenes, stilbenes, and cycloalkenes. This reaction offers the pos-
sibility to form three stereogenic centers in one step, exhibiting
excellent regiochemistry (Scheme 1).9,10
The reaction between benzhydrol 2 and methyl cinnamate (11)
afforded indane 12 with transetrans configuration as a single
product, whereas with the substituted esters 13 and 14, mixtures of
diastereomers transetrans (16 and 18) and 1,2-cis-2,3-trans (15 and
17) were obtained (entry 4e6).
A single stereoisomer (transetrans configuration) was obtained
from chalcone 19 and benzydrols 1 and 2 (entry 7,8), while three
indane diastereoisomers were obtained from chalcones 22 and 23.
The main product in both cases presented the transetrans config-
uration (24 and 27), while the minority products presented the 1,2-
cis-2,3-trans (25 and 28) and 1,2-trans-2,3-cis (26 and 29) config-
urations (entry 9,10).
This reaction was also performed using other acid catalysts
(Table 2). We tested this catalyst with benzhydrol 2 and cinnamic
acid 5, which turned out to be one of the most reactive in pre-
vious reactions. Chloroform was used as a solvent at reflux tem-
perature for 24 h with substoichiometric amounts of catalyst.
The products obtained in all the cases were the same as those
obtained using SnCl4 as catalyst and in the same rate (Table 2
entry 2).
Scheme 1. Formal [3þ2] cycloaddition.
In this paper, we report our research and results that led to the
synthesis of functionalized indanes in the pentagonal ring, using
benzhydrols and styrene derivatives with electron-withdrawing
2.2. Reaction of benzhydrols 1, 2, and 3 with nitrostyrenes
Table 3 shows the results obtained by the reaction between
benzhydrols and nitrostyrenes 30 and 31. Nitrostyrene 30 did not
react with any of the benzhydrols used. However, nitrostyrene 31
reacted with benzhydrols 1 and 2, giving two stereoisomers,
transetrans (32 and 33) and 1,2-cis-2,3-trans (34 and 35), in iden-
tical proportion (entry 3,4). When the reaction was carried out at rt,
a third minor isomer, 1,2-trans-2,3-cis diastereomer (36 and 37)
(entry 5,6), was obtained. The reaction between 3 and 31 afforded
indanes 38 and 39 (2:1 ratio) (entry 7).
groups joined to C-
of ketones, and nitro groups. We also report the configurational
assignment of the indanic structures synthesized using 1H and 13
b, such as carboxyl, carboxymethyl, carbonyl
C
NMR analysis and a set of two-dimensional experiments (NOESY,
ROESY, HMQC, and HSQC).
2. Results and discussion
The benzhydrols (1e3) and substituted styrenes used were
synthesized according to techniques previously described.11 The
catalyst used for the cycloaddition reaction was SnCl4,9,12 and
methylene chloride as solvent (Scheme 2). The temperature and
reaction time are indicated in each case. Other acid catalysts, which
had shown good results in obtaining indanic structures
[H3PMo12O40 (MPA), MPA supported on C (MPA/C), H3PW12O40
(TPA), TPA supported on SiO2 (TPA/S)],13 as well as other catalysts,
such as AIPMo12O40 (MPAl) and HClO4 supported on SiO2 (HClO4/S)
were also tested in this work.
2.3. Structural and configurational assignment of the indanes
obtained
The regiochemistry of reaction FCA [3þ2] and the stereochem-
ical assignment of all compounds were carried out taking into
consideration the data NMR spectra (chemical shifts, coupling
constants, and a set of two-dimensional experiments: NOESY,
ROESY, HMQC, HSQC). Table 4 summarizes the chemical shift data
of protons, carbons, and coupling constants of the compounds
obtained from benzhydrols and cinnamic acids, methyl esters, and
ketones.
Compounds 8, 10, 12, 16, 18, 20, 21, 24, and 27, showed very
similar values of dH for the hydrogen atoms H-1 and H-3
(Ddꢀ0.05 ppm). Identical situation was observed for the chemical
shifts of the carbon atoms C-1 and C-3 (Ddꢀ0.07 ppm). These data
indicate that the regioisomers formed are those with phenyl and/or
aryl residues linked to C-1 and C-3. Another evidence that supports
the 1,3 diaryl substitution is that the values of dC published by
Appelbe et al.14 for transetrans methyl 3-(4-methoxyphenyl)-2-
phenylindan-1-carboxylate, are markedly different in the chem-
ical shifts from those that appear in Table 4 for the esters 12, 15e18.
Scheme 2. Synthesis of functionalized indanes in the pentagonal ring.
2.1. Reaction of benzhydrols with styryl carboxylic acids,
esters, and ketones
Table 1 shows the results obtained from benzhydrols 1, 2 and
carbonyl derivatives of styrenes.
Alcohol 2 did not react with cinnamic acid (4) (entry 1); instead,
substituted cinnamic acids 5 and 6 showed a very good perfor-
mance. In these cases, a mixture of diastereoisomers were ob-
tained: 1,2-cis-2,3-trans (7 and 9) and transetrans (8 and 10), in
a proportion 2:1, respectively (entry 2, 3).
Moreover, this regiochemistry is consistent with the study of
nucleophilicity of double bond carbons of chalcones 19 and 23,
conducted with the program Spartan 2.0.1.15 The molecules were
optimized using the density functional method (DFT), using the

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B. Lantano et al. / Tetrahedron 68 (2012) 913e921
915
Table 1
FCA [3þ2] of benzhydrols with styryl carboxylic acids, esters, and ketones
Entry
Alcohol
Alkene
Product
Yield %
1
2
d
2
2
86a
3
4
5
2
2
2
88b
61c
44d
6
2
74e
7
8
1
2
31a
30a
9
2
2
40f
10
52f
Ar1¼4-methoxyphenyl; Ar2¼3,4-methylenedioxyphenyl; Ar3¼3,5-dimethoxyphenyl.
gRatio was determined by 1H NMR.
a
120 min.
30 min.
60 min.
10 min.
15 min.
5 min.
b
c
d
e
f

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916
Table 2
which are not useful for the configurational assignment of these
diastereomers. On the other hand, taking into account the chemical
shifts of hydrogen and carbon atoms of these compounds, they can
be joined into two groups: (a) compounds in which the values of dH
of H-1 and H-3 and dC of C-1 and C-3 are similar (8, 10, 12, 16, 18, 20,
21, 24, 27), which might present cisecis or transetrans stereo-
chemistry; and (b) compounds with different values (7, 9, 15, 17, 25,
26, 28, 29), which would be in agreement with a 1,2-trans-2,3-cis or
FCA [3þ2] of benzhydrol 2 and cinnamic acid 5 with different catalysts
Catalysts
Yield (%)
MPA
TPA
MPAl
MPA/C2
TPA/S
HClO4/S
31.2
32.0
No reaction
No reaction
No reaction
46.4
Table 3
FCA [3þ2] between benzhydrols and nitrostyrenes
Entry
Alcohol
Alkene
Product
Yield %
1
2
1
2
d
d
30
3
4
5
1
2
1
50a
30a
56b
31
31
6
7
2
3
31
31
44b
52b
Ar¼3,4-dimethoxyphenyl.
cRatio was determined by 1H NMR.
a
0
ꢁC, 120 min.
b
rt, 60 min.
base B3LyP/6-311þ6**, and it was found that the most nucleophilic
1,2-cis-2,3-trans configuration. In particular, compound 27 (group
a) was assigned the transetrans configuration taking into account
that the signal d 4.24 ppm (H-2) showed NOE with Hortho (7.23 ppm)
carbon in both chalcones is the carbon
(Fig. 2).
a at the carbonyl group
The substitution in the pentagonal ring of the synthesized
indanes allows four possible diastereomers: transetrans, cisecis,
transecis, and cisetrans. In previous works, configurational as-
signment of 1,2,3-triphenyl indanes was based on the coupling
constants of the hydrogen atoms of the pentagonal ring16 and
carbon chemical shifts (dC).17 However, the compounds included in
Table 4 present very similar values of J1,2 and J2,3 (9.1e9.9 Hz),
of the phenyl group, which is bound at C-1 and the Hortho (6.69 and
6.75 ppm) of the aryl attached to C-3, indicating that H-1 and H-3
are in trans arrangement with H-2 (Fig. 3). By comparison, com-
pounds 20, 21, and 24 were assigned identical configuration.
In the case of the diastereomers 28 and 29 (group b), data of
HSQC (Table 5) and ROESY (Fig. 4) were used to differentiate be-
tween the 1,2-cis-2,3-trans and 1,2-trans-2,3-cis isomers.

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Table 4
Chemical shifts of hydrogen, carbon, and coupling constants of indanes substituted
Compound H-1 H-2 H-3 J1,2 J2,3 C-1 C-2 C-3
transetrans 4.51 3.44 4.51 10.2 10.2 58.4 67.6 58.4
Triphenyl
indanes cisecis
cisetrans
4.88 4.05 4.88
4.74 4.04 4.76
7.2
7.2 56.2 62.8 56.2
8.2 10.1 54.1 62.1 56.1
Acids
7b
4.76 3.65 4.83
4.58 3.19 4.61
4.74 3.64 4.83
4.65 3.00 4.68
9.2
9.2
9.8
9.9
9.8 52.8 63.4 51.1
9.8 54.4 65.3 54.7
9.8 52.7 63.2 51.6
9.9 53.9 65.0 54.3
8a
9b
10a
Esters
12a
15b
16a
17b
18a
4.66 3.27 4.66
4.78 3.64 4.90
4.58 3.24 4.61
4.78 3.64 4.90
4.56 3.19 4.61
9.6
9.2
9.6
9.3
9.5
9.6 54.8 65.7 54.8
9.2 53.4 61.1 51.2
9.6 54.5 64.9 54.6
9.5 53.2 61.4 51.2
9.8 54.3 65.5 54.2
Fig. 4. NOEs data of compounds 28 and 29.
to
d
4.90 ppm. Thus, the H-1/H-3 atoms present
a
trans-
a cis-
configuration, whereas the H-2/H-3 atoms present
configuration (1,2-trans-2,3-cis). Using a similar study, in com-
pound 28 the signal at 4.94 ppm was assigned to H-1 and the
signal at 5.31 ppm was assigned to H-3. Therefore, the configu-
Ketones
20a
21a
24a
25b
26b
27a
28b
29a
4.73 4.27 4.76
4.80 4.27 4.80
4.80 4.26 4.77
4.94 4.62 5.31
5.36 4.63 4.93
4.76 4.24 4.76
4.94 4.61 5.31
5.35 4.61 4.90
9.2
9.2
9.2
9.2
9.2
9.2
9.0
9.0
9.4 54.9 68.0 55.1
9.2 55.1 68.2 55.1
9.1 54.5 68.4 55.1
9.2 54.7 64.4 50.8
9.2 50.5 64.3 54.1
9.2 54.9 68.3 55.2
9.5 54.7 64.3 50.4
9.8 50.5 64.2 54.5
d
d
ration of diastereomer 28 is 1,2-cis-2,3-trans. For compounds 25
and 26, the configuration was assigned by comparison.
The configuration of acids 7 and 8 was assigned by HMQC (Table
6) and NOESY data (Fig. 5).
In compound 7, H-2 (3.65 ppm) showed NOE with the signal at
4.76 ppm and the Hortho (7.19 ppm) of the aryl group attached to C-
a
transetrans or cisecis configuration.
1,2-cis-2,3-trans or 1,2-trans-2,3-cis configuration.
d
b
3. The signal at 4.83 ppm showed NOE with Hortho (6.98 ppm) of
d
Fig. 2. Results of the study of nucleophilicity of compounds 19 and 23.
Table 6
Correlation CeH for compounds 7 and 8 (HMQC)
Compound 7
Compound 8
C- (ppm)
H- (ppm)
C- (ppm)
H- (ppm)
52.8
63.4
51.1
4.76 (d)
3.65 (t)
4.83 (d)
54.4
65.3
54.7
4.58 (d)
3.19 (t)
4.61 (d)
Fig. 3. NOEs data of compound 27.
Table 5
Correlation CeH for compounds 28 and 29 (HSQC)
Compound 28
Compound 29
C- (ppm)
H- (ppm)
C- (ppm)
H- (ppm)
54.7
64.3
50.4
4.94 (d)
4.61 (t)
5.31 (d)
50.5
64.2
54.5
5.35 (d)
4.61 (t)
4.90 (d)
The signal at
d 4.90 ppm (doublet) of compound 29 presented
Fig. 5. NOEs data of compounds 7 and 8.
NOE with H-2 and the Hortho of the aryl group attached to C-3. The
signal at 5.35 ppm (doublet) showed NOE with Hortho of the
phenyl group attached to C-1 and also with the Hortho of the aryl
attached to C-3 (6.09, 6.17 ppm). These correlations indicate that
d
the phenyl group attached to C-1 and with the Hortho (7.19 ppm) of
the aryl group attached to C-3, indicating that H-1 and H-3 are in
trans-configuration to each other. Based on these data, the con-
figuration of 7 is 1,2-cis-2,3-trans. Therefore, the configuration of 8
the H-1 signal corresponds to d 5.35 ppm and that H-3 corresponds

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918
is transetrans, and it was assigned because of the great similarity
between the chemical shift values of C-1 and C-3 and the correla-
tions observed in the NOESY (Fig. 5). Considering the NMR data of
compounds 7 and 8 it was possible to establish the configuration
transetrans of compounds 10, 12, 16, 18 and the configuration 1,2-
cis-2,3-trans of diastereomers 9, 15, and 17.
The configuration of compounds 32e39 could not be assigned
based on the coupling constants J1,2 and J2,3 because the values were
very similar (8.3e8.8 Hz). In order to identify unambiguously the H-
1 and H-3 atoms of the three diastereomeric nitroindanes, we per-
formed the FCA [3þ2] using alcohol 2 deuterated in the bibenzylic
carbon (2d). The reaction between 3,4-dimethoxybromobenzene
with n-butyllithium and subsequent treatment with deuterated
benzaldehyde (C6H5CDO) gave rise to the deuterated alcohol 2d. The
reaction of FCA [3þ2] between 2d and 31 at rt afforded a mixture of
the three products 33d, 35d, and 37d (Scheme 3).
Fig. 7. NOEs data of compounds 33d and 35d.
In compound 35d, the H-2 (
d
5.43 ppm) correlated with the
Hortho
(d
6.72 and 6.77 ppm) of the aryl group attached at C-3.
Therefore, in this compound, H-2 and H-3 have a trans spatial re-
lationship. Moreover, the H-3 ( 5.17 ppm) showed NOE with Hortho
7.00 ppm) of the phenyl group bound at C-1. This correlation
d
(d
indicates that H-3 and the phenyl group are in cis arrangement and
that 35d has the 1,2-cis-2,3-trans configuration (Fig. 7).
Finally, by comparison, we were able to assign the configuration
transetrans to indanes 32, 33, and 38; the configuration 1,2-cis-2,3-
trans to 34, 35, and 39; and the configuration 1,2-trans-2,3-cis to
compounds 36 and 37.
3. Conclusion
FCA [3þ2] of benzhydrols and styrene derivatives with
electron withdrawing bound at C-
b allowed obtaining inda-
nes functionalized at C-2, with different yields. Several kinds of
acids were used to catalyze this reaction. SnCl4 resulted to be
the most efficient catalyst of all the catalysts tested.
We observed that the reactivity of benzhydrols against this type
of styrenes and the stereoselectivity of the reaction depend of the
substitution on the aromatic ring and on the electron-withdrawing
group present in the styrenes. The best yields (80%) and the highest
stereoselectivity (1,2-cis-2,3-trans vs transetrans (2:1)) were ob-
tained from cinnamic acids 5 and 6 (entry 2,3). Chalcones 22 and 23
and 3,4-dimethoxynitrostyrene 31 (Table 1 entry 9,10 and Table 3
entry 6) afforded a third diastereomer (1,2-trans-2,3-cis), which
was not previously obtained using this type of reaction.
FCA [3þ2] allowed the synthesis of endothelin analogs (trans-
etrans-1,3-diaryl-2-indane carboxylic acid) in a single step in
contrast to other syntheses used. These products can be also ob-
tained by hydrolysis of esters 12 and 15e18.
Scheme 3. Synthesis of deuterated nitroindanes.
The chemical shifts of the bibenzylic hydrogens of 33d, 35d, and
37d allowed an unambiguous assignment of H-1 and H-3 (Table 7).
The configuration of the nitroindanes was assigned by NOESY ex-
periments performed on the main stereoisomers (33d and 35d).
Table 7
1H NMR selected chemical shifts
d (ppm) and J (Hz) of nitroindanes
Compound
H-1
H-2
H-3
J1,2
J2,3
33
35
37
33d
35d
37d
4.93 (d)
4.99 (d)
5.19 (d)
d
4.99 (dd)
5.43 (t)
5.41 (dd)
5.02 (d)
5.43 (d)
5.41 (d)
4.91 (d)
5.17 (d)
4.97 (d)
4.92 (d)
5.17(d)
4.97 (d)
8.8
8.7
8.6
d
8.3
8.5
8.5
8.4
8.4
8.4
4. Experimental
4.1. General
d
d
d
d
1H and 13C NMR spectra were recorded (CDCl3) on a Bruker AC
300 spectrometer at 300 and 75 MHz. The bidimensional experi-
ments (NOESY, ROESY, HMQC, and HSQC) were recorded (CDCl3) on
an Avance 500 spectrometer. Shifts reported are relative to internal
standard Si(Me)4 and coupling constants are reported in hertz. Ab-
breviations used are as follows: 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 performed on
Merck aluminum sheets Silica Gel 60 GF254. Commercial compounds
were purchased from Aldrich Chemical Co. THF and CH2Cl2 were
distilled from sodium/benzophenone and CaH2, respectively. Melt-
ingpoints areuncorrected and weredetermined in aThomasHoover
apparatus. In cases were synthetic intermediates or products were
isolated by ‘aqueous workup (aqueous solution, organic solvent)’,
the procedure was to quench the reaction mixture with the
The diastereomer 33d presented the lowest chemical shift for
the H-2 (5.02 ppm) (Fig. 6). This is indicative of a cis relationship
with the phenyl group attached to C-1 and the aryl group bound to
C-3, due to the shielding effect exerted by them. Furthermore, the
H-2 presented NOE with the Hortho (d 6.73 and 6.82 ppm) of the aryl
attached at C-3. This correlation confirms that the H-2 and the aryl
group bound at C-3 are in a cis arrangement and that the H-3 and
H-2 are in a trans relationship (Fig. 7).
Fig. 6. Chemical shift of the deuterated nitroindanes.

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919
indicated aqueous solution, dilute with the indicated organic sol-
vent, separate the organic layer, extract the aqueous layer several
times with the organic solvent, dry the combined organic extracts
over Na2SO4 and remove the solvent under reduced pressure (water
s, OCH3), 4.58 (1H, d, J¼9.2 Hz, CHPh), 4.61 (1H, d, J¼9.8 Hz, CHAr),
6.43 (1H, s, Ar), 6.44 (1H, s, Ar), 6.89 (2H, d, J¼8.0 Hz, Ar), 7.10 (3H,
m, Ar), 7.22 (2H, m, Ar), 7.29 (2H, d, J¼8.0 Hz, Ar). dC (ppm): 54.4,
54.7, 55.0, 55.9, 65.3, 107.4, 107.6, 113.3, 126.2, 126.5, 128.5, 129.5,
136.0, 137.4, 137.8, 144.3, 148.7, 148.9, 152.2, 181.2. Anal. Calcd for
C25H24O5: C, 74.24; H, 5.98. Found: C, 74.26; H, 6.0.
€
aspirator) with a Buchi Rotavapor. Benzhydrolic alcohols 1 and 2
were prepared from corresponding aldehydes and phenyl-
magnesium bromide.10 Alcohol 3 was obtained by reduction of
3,30,4,40-tetramethoxybenzophenone with NaBH4 in methanol. dH
(ppm): 2.25 (1H, bs, OH); 3.87 (6H, s, OCH3); 3.89 (6H, s, OCH3); 5.77
(1H, s, CHOH); 6.84 (2H, d, J¼8.4 Hz, Ar); 6.90 (2H, dd, J¼1.5, 8.4 Hz,
Ar); 6.94 (2H, d, J¼1.5 Hz, Ar). dC (ppm): 55.8, 55.9, 79.9, 110.8,110.9,
119.6, 134.9, 148.3, 148.9. The chalcones 19, 22, and 2318 were syn-
thesized from acetophenone and the corresponding arylaldehyde.11
Nitrostyrene 30 and 3.4-dimethoxynitrostyrene 31 were synthe-
sized following standard methodology.11
4.2.2. r-1-Phenyl-c-2-carboxy-t-3-(3,4-methylenedioxyphenyl)-5,6-
dimethoxyindane (9) and r-1-phenyl-t-2-carboxy-c-3-(3,4-
methylenedioxyphenyl)-5,6-dimethoxyindane (10). General pro-
cedure was carried out with alcohol 2 (0.14 g, 0.58 mmol), 3,4-
methylenedioxycinnamic acid 6 (0.11 g, 0.58 mmol), and SnCl4
(0.19 g, 0.75 mmol) during 30 min at rt p-TLC (1:1, hexane/ethyl
acetate) afforded 0.106 g (88.2%) of 9 and 10 as a 2:1 mixture (solid).
Compound 9 dH (ppm): 3.64 (1H, t, J¼9.8 Hz, CHCOOH), 3.68 (3H, s,
OCH3), 3.69 (3H, s, OCH3), 4.74 (1H, d, J¼9.8 Hz, CHPh), 4.83 (1H,d,
J¼9.8 Hz, CHAr), 5.86 (1H, s, OCH2O), 5.89 (1H, s, OCH2O), 6.50 (1H,
s, Ar), 6.64 (1H, s, Ar), 6.65e6.82 (2H, m, Ar), 6.9e7.3 (6H, m, Ar). dC
(ppm): 51.6, 52.7, 55.9, 63.2, 100.7, 107.4, 107.6, 108.0, 109.0, 121.9,
126.8, 127.8, 128.4, 136.6, 137.4, 137.8, 146.0, 147.5, 148.7, 148.8,
148.9, 178.4. Compound 10 dH (ppm): 3.00 (1H, t, J¼9.9 Hz,
CHCOOH), 3.62 (3H, s, OCH3), 3.65 (3H, s, OCH3), 4.65 (1H, d,
J¼9.9 Hz, CHPh), 4.68 (1H, d, J¼9.9 Hz, CHAr), 5.83 (1H, s, OCH2O),
5.84 (1H, s, OCH2O), 6.40 (1H, s, Ar), 6.47 (1H, s, Ar), 6.65e6.82 (2H,
m, Ar), 6.9e7.3 (6H, m, Ar). dC (ppm): 53.9, 54.3, 55.9, 65.0, 100.7,
107.4, 107.6, 108.8, 109.1,121.6, 126.5, 128.4, 128.7, 136.8, 138.8, 142.1,
144.1, 147.5, 148.7, 148.8, 148.9, 180.6. Anal. Calcd for C25H22O6: C,
71.76; H, 5.30. Found: C, 71.78; H, 5.32.
4.1.1. (3,4-Dimethoxyphenyl)phenylmethanol (2d). To a solution of
3,4-dimethoxybromobenzene (1.0 g, 4.6 mmol) in dry THF (10 mL)
was added at ꢂ78 ꢁC, a solution of BuLi 1.1 M (5.06 mL) and stirred for
1 h. Then a solution of deuterated benzaldehyde (C6H5CDO) in THF
(0.47 mL, 4.6 mmol) was added slowly and stirred by 1 h. The mix-
ture at room temperature (rt) was quenched with saturated solution
of aqueous ammonium chloride. The aqueous layer was extracted
with CH2Cl2. Organic layer washed with water, dried with anhydrous
Na2SO4, and concentrated to give 0.92 g (82%) of alcohol 2d.
4.1.2. Methyl 3,5-dimethoxycinnamate (13). A solution of 3,5-
dimethoxybenzaldehyde (1.0 g, 6.02 mmol) in dry THF (10 mL) at
0
ꢁC was added to methyl (triphenylphosphoranylidene)acetate
(2.58 g, 7.22 mmol), and stirred for 24 h at rt. The solvent was re-
moved,theresiduewasextractedwithboilinghexane(15mLꢃ3)and
then the solvent was evaporated. Recrystallization (ethanol/water)
afforded 1.05 g (78.3%) of 13 as a solid, mp: 70e71 ꢁC dH (ppm): 3.80
(9H, s, OCH3), 6.40 (1H, d, J¼16.0 Hz, CH]), 6.49 (1H, t, J¼2.2 Hz, Ar),
6.66 (2H,d, J¼2.2 Hz, Ar), 7.60 (1H, d, J¼16.0 Hz, CH]).19
4.2.3. r-1,c-3-Diphenyl-t-2-methoxycarbonyl-5,6-dimethoxyindane
(12). General procedure was carried out with alcohol 2 (0.10 g,
0.39 mmol), methyl cinnamate 11 (0.075 g, 0.46 mmol), and SnCl4
(0.13 g, 0.51 mmol) during 1 h at rt p-TLC (Cl2CH2) afforded 0.087 g
(60.4%) of 12 (pale yellow solid), mp: 160e161 ꢁC dH (ppm): 3.27
(1H, t, J¼9.6 Hz, CHCOOCH3), 3.61 (3H, s, COOCH3), 3.76 (6H, s,
OCH3), 4.66 (2H, d, J¼9.6 Hz, CHPh), 6.45 (2H, s, Ar), 7.30 (5H, m, Ar),
7.38 (5H, m, Ar). dC (ppm): 52.1, 54.8, 56.5, 65.7, 107.9, 127.5, 128.9,
129.1, 136.7, 143.5. 149.5, 174.6. Anal. Calcd for C25H24O4: C, 77.30; H,
6.23. Found: C, 77.32; H, 6.25.
4.1.3. Methyl (3,4-methylenedioxy)cinnamate (14). The same pro-
cedure described for the preparation of 13 was carried out with
3,4-methylenedioxybenzaldehyde (0.5 g, 3.6 mmol) and methyl
(triphenylphosphoranylidene)acetate (1.30 g, 3.6 mmol). Re-
crystallization (ethanol/water) afforded 0.48 g (70.6%) of 14, mp:
125e126 ꢁC dH (ppm): 3.78 (3H, s, OCH3), 6.00 (2H, s, OCH2O), 6.25
(1H, d, J¼15.9 Hz, CH]), 6.81 (1H, d, J¼8.0 Hz, Ar), 6.99 (1H, dd,
J¼1.5, 8.0 Hz, Ar), 7.02 (1H, d, J¼1.5 Hz), 7.60 (1H, d, J¼15.9 Hz, CH]).
4.2.4. r-1-Phenyl-c-2-methoxycarbonyl-t-3-(3,5-dimethoxyphenyl)-
5,6-dimethoxyindane (15) and r-1-phenyl-t-2-methoxycarbonyl-c-3-
(3,5-dimethoxyphenyl)-5,6-dimethoxyindane (16). General pro-
cedure was carried out with alcohol 2 (0.10 g, 0.40 mmol), methyl
3,5-dimethoxycinnamate 13 (0.09 g, 0.41 mmol), and SnCl4 (0.09 g,
0.34 mmol) during 10 min at rt. p-TLC (CHCl2) afforded 0.08 g
(43.7%) of 15 and 16 as a 1:2.3 (white solid). Compound 15 dH
(ppm): 3.28 (3H, s, COOCH3), 3.64 (4H, overlap with OCH3,
CHCOOCH3), 3.70 (3H, s, OCH3), 3.73 (3H, s, OCH3), 3.83 (3H, s,
OCH3), 4.78 (1H, d, J¼9.2 Hz, CHPh), 4.90 (1H, d, J¼9.2 Hz, CHAr),
6.36 (1H, t, J¼2.2 Hz, Ar), 6.39 (2H, d, J¼2.2 Hz, Ar), 6.54 (1H, s, Ar),
6.62 (1H, s, Ar), 7.10e7.30 (5H, m, Ar). dC (ppm): 51.2, 51.5, 53.8, 55.4,
55.7, 55.9, 56.0, 61.1, 99.0, 106.6, 107.4, 111.8, 125.0, 127.1, 128.5,
129.4, 136.0, 145.5, 145.9, 148.8, 149.2, 160.8, 171.9. Compound 16 dH
(ppm): 3.24 (1H, t, J¼9.2 Hz, CHCOOCH3), 3.51 (3H, s, OCH3), 3.61
(3H, s, COOCH3), 3.63 (3H, s, OCH3), 3.70 (3H, s, OCH3), 3.79 (3H, s,
OCH3), 4.58 (1H, d, J¼9.6 Hz, CHPh), 4.61 (1H, d, J¼9.6 Hz, CHAr),
6.08 (1H, s, Ar), 6.39 (1H, t, J¼2.1 Hz, Ar), 6.48 (1H, s, Ar), 6.66 (2H, d,
J¼2.1 Hz, Ar), 7.10e7.30 (5H, m, Ar). dC (ppm): 54.5, 54.6, 55.5, 55.8,
56.0, 56.1, 56.2, 64.9, 98.9, 106.5, 107.4, 107.5, 127.6, 128.4, 131.0,
136.5, 136.7, 143.6, 144.3, 147.3, 147.5, 160.9, 174.3. Anal. Calcd for
C27H28O6: C, 72.30; H, 6.29. Found: C, 72.32; H, 6.31.
4.2. General procedure for the formal [3D2] cycloaddition of
a benzhydrol and a substituted styrene in the presence of
SnCl4
4.2.1. r-1-Phenyl-c-2-carboxy-t-3-(4-methoxyphenyl)-5,6-
dimethoxyindane (7) and r-1-phenyl-t-2-carboxy-c-3-(4-
methoxyphenyl)-5,6-dimethoxyindane
(8). 4-Methoxycinnamic
acid 5 (0.10 g, 0.58 mmol) and SnCl4 (0.19 g, 0.75 mmol) were se-
quentially added to a solution of alcohol 2 (0.14 g, 0.58 mmol), in
CH2Cl2 (10 mL), at rt. The resulting solution was stirred for 2 h at rt
and then poured into a rapidly stirred solution of NaHCO3 5%.
Aqueous workup (NaHCO3, CH2Cl2) followed by p-TLC (1:1, hexane/
ethyl acetate) afforded 0.20 g (85.6%) of 7 and 8 as a 2:1 (solid).
Compound 7 dH (ppm): 3.65 (1H, t, J¼9.5 Hz, CHCOOH), 3.79 (3H, s,
OCH3), 3.81 (3H, s, OCH3), 3.82 (3H, s, OCH3), 4.76 (1H, d, J¼9.2 Hz,
CHPh), 4.83 (1H, d, J¼9.8 Hz, CHAr), 6.49 (1H, s, Ar), 6.65 (1H, s, Ar),
6.87 (2H, d, J¼8.0 Hz, Ar), 6.98 (2H, d, J¼8.0 Hz, Ar), 7.19 (2H, d,
J¼8.0 Hz, Ar), 7.30e7.40 (3H, m, Ar). dC (ppm): 51.1, 52.8, 55.0, 55.9,
63.4, 107.4, 107.6, 113.8, 127.8, 128.4, 128.7, 129.7, 136.1, 136.8, 137.9,
142.4, 148.7, 148.9, 158.2, 178.8. Compound 8 dH (ppm): 3.19 (1H, t,
J¼9.5 Hz, CHCOOH), 3.75 (3H, s, OCH3), 3.76 (3H, s, OCH3), 3.82 (3H,
4.2.5. r-1-Phenyl-c-2-methoxycarbonyl-t-3-(3,4-methylenenedioxy-
phenyl)-5,6-dimethoxyindane (17) and r-1-phenyl-t-2-methoxy-
carbonyl-c-3-(3,4-methylenedioxyphenyl)-5,6-dimethoxyindane

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B. Lantano et al. / Tetrahedron 68 (2012) 913e921
920
(18). General procedure was carried out with alcohol 2 (0.10 g,
0.40 mmol), methyl 3,4-methylenedioxyphenylcinnamate 14
(0.085 g, 0.41 mmol), and SnCl4 (0.09 g, 0.34 mmol) during 15 min
at rt. p-TLC (CHCl2) afforded 0.13 g (73.4%) of 17 and 18 as a 1.3:1
(white solid). Compound 17 dH (ppm): 3.29 (3H, s, COOCH3), 3.64
(1H, t, J¼9.5 Hz, CHCOOCH3), 3.77 (3H, s, OCH3), 3.79 (3H, s, OCH3),
4.78 (1H, d, J¼9.3 Hz, CHPh), 4.90 (1H, d, J¼9.5 Hz, CHAr), 5.90 (1H,
d, J¼1.5 Hz, OCH2O), 5.91 (1H, d, J¼1.5 Hz, OCH2O), 6.51 (1H, s, Ar),
6.62 (1H, s, Ar), 6.77 (3H, m, Ar), 7.16e7.36 (5H, m, Ar). dC (ppm):
51.2, 53.2, 55.9, 56.0, 56.1, 61.4,100.9,107.4,107.5,107.6,108.3,122.0,
128.4,128.5,128.7,135.8,137.0,137.2,141.0,143.0,149.5,149.1,149.2,
171.9. Compound 18 dH (ppm): 3.19 (1H, t, J¼9.6 Hz, CHCOOCH3),
3.59 (3H, s, COOCH3), 3.72 (3H, s, OCH3), 3.76 (3H, s, OCH3), 4.56
(1H, d, J¼9.5 Hz, CHPh), 4.61 (1H, d, J¼9.8 Hz, CHAr), 5.94 (1H, d,
J¼1.5 Hz, OCH2O), 5.96 (1H, d, J¼1.5 Hz, OCH2O), 6.41 (1H, s, Ar),
6.45 (1H, s, Ar), 6.71 (1H, d, J¼1.2 Hz, Ar), 6.96 (2H, m, Ar), 7.16e7.36
(5H, m, Ar). dC (ppm): 51.2, 54.2, 54.3, 55.9, 56.0, 65.5, 101.0, 108.4,
108.5, 108.7, 108.8, 121.8, 127.0, 128.2, 128.3, 136.2, 136.3, 136.9,
143.0, 146.7, 147.9, 148.0, 149.3, 174.2. Anal. Calcd for C26H24O6: C,
72.21; H, 5.59. Found: C, 72.23; H, 5.61.
55.3, 56.1, 64.4, 107.8, 113.3, 114.0, 126.8, 128.0, 128.2, 128.4, 128.6,
128.8, 132.6, 132.7, 136.0, 136.8, 137.0, 137.6, 140.6, 149.1, 158.4,
198.2. Compound 26 dH (ppm): 3.70 (3H, s, OCH3), 3.80 (3H, s,
OCH3), 3.81 (3H, s, OCH3), 4.63 (1H, t, J¼9.2 Hz, CHCOPh), 4.93 (1H,
d, J¼9.2 Hz, CHAr), 5.36 (1H, d, J¼9.2 Hz, CHPh), 6.54 (1H, s, Ar), 6.55
(1H, s, Ar), 6.60 (5H, m, Ar), 7.28 (2H, m, Ar), 7.35 (4H, m, Ar), 7.50
(1H, m, Ar), 7.74 (2H, d, J¼8.6 Hz, Ar). dC (ppm): 50.5, 54.1, 56.0, 56.1,
64.3, 107.2, 107.3, 113.6, 126.7, 128.0, 128.2, 128.5, 128.6, 129.1, 129.5,
132.3, 136.3, 136.8, 137.6, 137.8, 144.4, 149.2, 158.3, 198.1. Anal. Calcd
for C31H28O4: C, 80.15; H, 6.08. Found: C, 80.17; H, 6.10.
4.2.9. r-1-Phenyl-t-2-benzoyl-c-3-(3,4-methylenedioxyphenyl)-5,6-
dimethoxyindane (27), r-1-phenyl-c-2-benzoyl-t-3-(3,4-methylene-
dioxyphenyl)-5,6-dimethoxyindane (28) and r-1-phenyl-t-2-
benzoyl-t-3-(3,4-methylenedioxyphenyl)-5,6-dimethoxyindane
(29). General procedure was carried out with alcohol 2 (0.19 g,
0.79 mmol), chalcone 23 (0.2 g, 0.79 mmol), and SnCl4 (0.09 g,
0.34 mmol) during 5 min at rt. p-TLC (70: 30, hexane/ethyl ace-
tate) afforded 0.19 g (51.5%) of 27, 28 and 29 as a 1.9:1.67:1 (27/28/
29) mixture. p-TLC (80: 20, hexane/ethyl acetate) allowed the
separation of 27 (white crystalline solid), mp: 75e76 ꢁC. Com-
pound 27 dH (ppm): 3.78 (3H, s, OCH3), 3.81 (3H, s, OCH3), 4.24
(1H, t, J¼9.2 Hz, CHCOPh), 4.76 (2H, d, J¼9.2 Hz, CHAr, CHPh), 5.95
(2H, s, OCH2O), 6.47 (1H, s, Ar), 6.50 (1H, s, Ar), 6.69 (2H, s, Ar),
6.75 (1H, s, Ar), 7.17 (2H, t, J¼8.2 Hz, Ar), 7.23 (3H, m, Ar), 7.29 (2H,
m, Ar), 7.39 (1H, m, Ar), 7.41 (2H, d, J¼8.5 Hz, Ar). dC (ppm): 54.9,
55.2, 56.1, 68.3, 101.0, 107.5, 107.6, 108.4, 122.0, 127.0, 128.1, 128.5,
128.6, 128.7, 132.9, 137.4, 146.5, 147.9, 148.8, 149.2, 151.6, 206.4.
Compound 28 dH: 3.79 (3H, s, OCH3), 3.84 (3H, s, OCH3), 4.61 (1H,
t, J¼9.3 Hz, CHCOPh), 4.94 (1H, d, J¼9.0 Hz, CHPh), 5.31 (1H, d,
J¼9.5 Hz, CHAr), 5.90 (2H, s, OCH2O), 6.61 (1H, s, Ar), 6.63 (1H, s,
Ar), 6.76 (1H, d, J¼7.8 Hz, H-60), 6.82 (1H, d, J¼1.5 Hz, H-20), 6.89
(1H, dd, J¼1.5, 7.8 Hz, H-50), 7.05 (3H, m. Ar), 7.39 (3H, m, Ar), 7.51
(2H, m, Ar), 7.74 (2H, d, J¼7.3 Hz, Ar). dC (ppm): 50.4, 54.7, 56.1,
64.3, 100.9, 107.3, 107.8, 108.3, 108.9, 122.1, 126.8, 128.2, 128.4,
128.5, 132.8, 136.3, 137.1, 137.6, 137.8, 140.5, 144.0, 147.8, 149.2,
149.3, 198.1. Compound 29 dH (ppm): 3.81 (3H, s, OCH3), 3.82 (3H,
s, OCH3), 4.61 (1H, t, J¼9.3 Hz, CHCOPh), 4.90 (1H, d, J¼9.0 Hz,
CHAr), 5.35 (1H, d, J¼9.8 Hz, CHPh), 5.82 (1H, d, J¼1.2 Hz, OCH2O),
5.84 (1H, d, J¼1.2 Hz, OCH2O), 6.09 (1H, dd, J¼1.5, 7.1 Hz, H-60),
6.13 (1H, d, J¼1.5 Hz, H-20), 6.45 (1H, d, J¼7.8 Hz, H-50), 6.59 (1H, s,
Ar), 6.62 (1H, s, Ar), 7.05 (3H, m. Ar), 7.39 (3H, m, Ar), 7.51 (2H, m,
Ar), 7.77 (2H, d, J¼7.3 Hz, Ar). dC (ppm): 50.5, 54.5, 56.0, 64.2,
100.8, 107.2, 107.5, 107.9, 108.8, 121.7, 126.7, 128.0, 128.6, 128.8,
132.8, 134.4, 136.5, 137.0, 140.6, 146.3, 146.4, 147.4, 149.2, 149.3,
198.0. Anal. Calcd for C31H26O5: C, 77.81; H, 5.48. Found: C, 77.82;
H, 5.50.
4.2.6. r-1,c-3-Diphenyl-t-2-benzoyl-5-hydroxy-6-methoxyindane
(20). General procedure was carried out with alcohol 1 (0.10 g,
0.46 mmol), chalcone 19 (0.15 g, 0.74 mmol), and SnCl4 (0.15 g,
0.60 mmol) during 2 h at rt. p-TLC (CHCl3) afforded 0.06 g (31%) of
20 (yellow solid), mp: 150e152 ꢁC dH (ppm): 3.77 (3H, s, OCH3);
4.27 (1H, dd, J¼9.2, 9.4 Hz, CHCOPh), 4.73 (1H, d, J¼9.2 Hz, CHPh),
4.76 (1H, d, J¼9.4 Hz, CHPh), 5.57 (1H, s, OH), 6.43 (1H, s, Ar), 6.51
(1H, s, Ar), 7.07 (2H, m, Ar), 7.24 (11H, m, Ar), 7.33 (2H, d, J¼8.6 Hz,
Ar). dC (ppm): 54.9, 55.1, 56.1, 68.0, 106.9, 110.5, 126.9, 128.0, 128.4,
128.5, 128.6, 128.7, 132.8, 135.9, 137.2, 137.5, 143.2, 143.6, 145.5,
146.6, 201.3. Anal. Calcd for C29H24O3: C, 82.83; H, 5.75. Found: C,
82.85; H, 5.77.
4.2.7. r-1,c-3-Diphenyl-t-2-benzoyl-5,6-dimethoxyindane
(21). General procedure was carried out with alcohol 2 (0.11 g,
0.46 mmol), chalcone 19 (0.15 g, 0.74 mmol), and SnCl4 (0.15 g,
0.60 mmol) during 2 h at rt. p-TLC (CHCl3) afforded 0.06 g (30%) of
21 (white solid), mp: 153e154 ꢁC dH (ppm): 3.76 (6H, s, OCH3), 4.27
(1H, t, J¼9.2 Hz, CHCOPh), 4.80 (2H, d, J¼9.2 Hz, CHPh), 6.46 (2H, s,
Ar), 7.10 (2H, m, Ar), 7.23 (11H, m, Ar), 7.33 (2H, d, J¼8.1 Hz, Ar). dC
(ppm): 55.1, 56.1, 68.2, 107.4, 126.9, 128.0, 128.5, 128.7, 132.8, 136.4,
137.2, 143.5, 149.1, 201.3. Anal. Calcd for C30H26O3: C, 82.92; H, 6.03.
Found: C, 82.94; H, 6.05.
4.2.8. r-1-Phenyl-t-2-benzoyl-c-3-(4-methoxyphenyl)-5,6-dimetho-
xyindane (24), r-1-phenyl-c-2-benzoyl-t-3-(4-methoxyphenyl)-5,6-
dimethoxyindane (25) and r-1-phenyl-t-2-benzoyl-t-3-(4-
methoxyphenyl)-5,6-dimethoxyindane (26). General procedure was
carried out with alcohol 2 (0.2 g, 0.82 mmol), chalcone 21 (0.19 g,
0.82 mmol), and SnCl4 (0.09 g, 0.34 mmol) during 5 min at rt p-TLC
(70: 30, hexane/ethyl acetate) afforded 0.15 g (39.5%) of 24, 25 and
26 as a 1.6:1:1 (24/25/26) mixture. p-TLC (80: 20, hexane/ethyl
acetate) allowed the separation of 24 (clear oil). Compound 24 dH
(ppm): 3.78 (3H, s, OCH3), 3.79 (3H, s, OCH3), 3.80 (3H, s, OCH3),
4.26 (1H, t, J¼9.2 Hz, CHCOPh), 4.77 (1H, d, J¼9.1 Hz, CHAr), 4.80
(1H, d, J¼9.2 Hz, CHPh), 6.49 (2H, s, Ar), 6.82 (2H, d, J¼8.5 Hz, Ar),
7.14 (2H, m, Ar), 7.17 (2H, m, Ar), 7.24 (3H, m, Ar), 7.28 (2H, m, Ar),
7.34 (1H, m, Ar), 7.39 (2H, d, J¼8.2 Hz, Ar). dC (ppm): 54.5, 55.1, 55.2,
56.1, 68.4, 107.5, 107.6, 114.0, 126.9, 128.5, 128.6, 128.7, 129.5, 132.8,
135.5, 136.3, 136.8, 137.4, 143.6, 149.2, 158.6, 161.6, 163.0, 201.5.
Compound 25 dH: 3.79 (3H, s, OCH3), 3.80 (3H, s, OCH3), 3.82 (3H, s,
OCH3), 4.62 (1H, t, J¼9.2 Hz, CHCOPh), 4.94 (1H, d, J¼9.2 Hz, CHPh),
5.31 (1H, d, J¼9.2 Hz, CHAr), 6.50 (1H, s, Ar), 6.60 (1H, s, Ar), 6.87
(2H, d, J¼8.8 Hz, Ar), 7.06 (3H, m, Ar), 7.28 (2H, m, Ar), 7.35 (4H, m,
Ar), 7.50 (1H, m, Ar), 7.74 (2H, d, J¼8.6 Hz, Ar). dC (ppm): 50.8, 54.7,
4.2.10. r-1-Phenyl-t-2-nitro-c-3-(3,4-dimethoxyphenyl)-5-hydroxy-
6-methoxyindane (32), r-1-phenyl-c-2-nitro-t-3-(3,4-dimethoxy-
phenyl)-5-hydroxy-6-methoxyindane (34) and r-1-phenyl-t-2-nitro-
t-3-(3,4-dimethoxyphenyl)-5-hydroxy-6-methoxyindane
(36). General procedure was carried out with alcohol 1 (0.13 g,
0.58 mmol), 3,4-dimethoxynitrostyrene 31 (0.19 g, 0.93 mmol), and
SnCl4 (0.19 g, 0.75 mmol) during 2 h at 0 ꢁC. p-TLC (CHCl3) afforded
0.11 g (50%) of 32 and 34 as 1:1. p-TLC (70:30, hexane/ethyl acetate)
allowed the separation of 32 (pale yellow solid), mp: 118e120 ꢁC
and 34 (pale yellow solid), mp: 179e181 ꢁC.
General procedure was carried out with alcohol 1 (0.13 g,
0.58 mmol), 3,4-dimethoxynitrostyrene 31 (0.19 g, 0.93 mmol), and
SnCl4 (0.19 g, 0.75 mmol) during 1 h at rt. p-TLC (CHCl3) afforded
0.13 g (56%) of 32, 34, and 36 as a 1:1:0.08 (32:34:36) mixture.
Compound 32 dH (ppm): 3.79 (3H, s, OCH3), 3.84 (3H, s, OCH3), 3.89
(3H, s, OCH3), 4.90 (1H, d, J¼8.4 Hz, CHPh), 4.97 (1H, d, J¼8.2 Hz,
CHAr), 5.04 (1H, t, J¼8.4 Hz, CHNO2), 5.67 (1H, s, OH), 6.44 (1H, s,
Ar), 6.58 (1H, s, Ar), 6.73 (1H, d, J¼1.8 Hz, Ar), 6.83 (2H, m, Ar), 7.27

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B. Lantano et al. / Tetrahedron 68 (2012) 913e921
921
(3H, m, Ar), 7.36 (2H, m, Ar). dC (ppm): 55.3, 55.5, 55.9, 56.0, 56.1,
102.0, 106.9, 110.6, 111.1, 111.4, 120.5, 128.0, 128.3, 129.1, 132.1, 132.2,
133.8, 140.1, 146.3, 147.2, 148.7, 149.3. Compound 34 dH (ppm): 3.81
(3H, s, OCH3), 3.82 (3H, s, OCH3), 3.83 (3H, s, OCH3), 4.98 (1H, d,
J¼8.7 Hz, CHPh), 5.13 (1H, d, J¼9.0 Hz, CHAr), 5.44 (1H, t, J¼8.7 Hz,
CHNO2), 5.7 (1H, s, OH), 6.62 (1H, s, Ar), 6.64 (1H, s, Ar), 6.71e6.83
(2H, m, Ar), 7.0 (1H, m, Ar), 7.20e7.33 (5H, m, Ar). dC (ppm): 52.0,
53.8, 55.9, 56.0, 56.1, 97.5, 107.6, 111.4, 111.5, 120.8, 128.2, 128.6,
128.7, 132.3, 132.4, 133.9, 137.0, 148.7, 149.3, 149.9, 150.0. Compound
36 dH (ppm): 3.82 (3H, s, OCH3), 3.86 (3H, s, OCH3), 3.87 (3H, s,
OCH3), 4.95 (1H, d, J¼8.7 Hz, CHPh), 5.16 (1H, d, J¼9.0 Hz, CHNO2),
5.29 (1H, s, OH), 5.40 (1H, dd, J¼7.7, 8.5 Hz, CHAr), 6.51 (1H, s, Ar),
6.54 (1H, s, Ar), 6.71e6.83 (2H, m, Ar), 7.0 (1H, m, Ar), 7.20e7.33
(5H, m, Ar). dC (ppm): 52.5, 53.7, 55.8, 56.1, 97.6, 107.6, 111.0, 111.8,
112.0, 121.0, 127.8, 128.5, 129.0, 132.7, 133.9, 140.2, 145.3, 148.9,
149.0, 149.8, 150.0. Anal. Calcd for C24H23NO6: C, 68.40; H, 5.50; N
3.32. Found: C 68.42, H 5.52, N 3.34.
4.2.12. r-1-c-3-Bis-(3,4-dimethoxyphenyl)-t-2-nitro-5,6-
dimethoxyindane (38) and r-1-t-3-bis-(3,4-dimethoxyphenyl)-c-2-
nitro-5,6-dimethoxyindane (39). General procedure was carried
out with alcohol 3 (0.42 g, 1.37 mmol), 3,4-dimethoxynitrostyrene
31 (0.24 g, 1.37 mmol), and SnCl4 (0.20 g, 0.78 mmol) during 1 h at
rt. p-TLC (Cl2CH2) afforded 0.35 g (51.5%) of 38 and 39 as a 2:1
(38:39) mixture. p-TLC (70:30, hexane/ethyl acetate) allowed the
separation of 38 (cream white solid), mp: 155e156 ꢁC and 39 (white
solid), mp: 95e96 ꢁC. Compound 38 dH (ppm): 3.80 (6H, s, OCH3),
3.85 (6H, s, OCH3), 3.90 (6H, s, OCH3), 4.92 (2H, d, J¼8.1 Hz, CHAr),
5.00 (1H, t, J¼8.1 Hz, CHNO2), 6.51 (2H, s, Ar), 6.74 (2H, d, J¼1.5 Hz,
Ar), 6.83 (2H, dd, J¼1.4, 8.1 Hz, Ar), 6.88 (2H, d, J¼8.4 Hz, Ar). dC
(ppm): 55.8, 56.3, 56.4, 56.5, 102.8, 107.8, 111.6, 112.0, 121.0, 132.9,
133.2, 149.2, 149.8, 150.2. Compound 39 dH (ppm): 3.79 (3H,s,
OCH3), 3.81 (3H, s, OCH3), 3.82 (3H, s, OCH3), 3.83 (3H, s, OCH3),
3.84 (3H, s, OCH3), 3.88 (3H, s, OCH3), 4.95 (1H, d, J¼8.5 Hz, CHAr),
5.13 (1H, d, J¼7.9 Hz, CHAr); 5.39 (1H, t, J¼8.1 Hz, CHNO2), 6.50 (3H,
m, Ar), 6.70e6.85 (5H, m, Ar). dC (ppm): 52.0, 52.8, 53.6, 55.7, 55.8,
55.9, 56.0, 56.2, 97.6, 107.6, 110.9, 111.3, 111.5, 111.8, 112.0, 120.8,
121.0, 129.2, 132.6, 133.2, 133.8, 148.6, 148.7, 148.8, 149.6, 149.7,
149.8. Anal. Calcd for C27H29NO8: C, 65.44, H 5.90; N, 2.83. Found: C,
65.47; H, 5.93; N, 2.86.
4.2.11. r-1-Phenyl-t-2-nitro-c-3-(3,4-dimethoxyphenyl)-5,6-dimeth-
oxyindane (33), r-1-phenyl-c-2-nitro-t-3-(3,4-dimethoxyphenyl)-
5,6-dimethoxyindane (35) and r-1-phenyl-t-2-nitro-t-3-(3,4-dimeth-
oxyphenyl)-5,6-dimethoxyindane (37). General procedure was car-
ried out with alcohol
2
(0.14 g, 0.58 mmol), 3,4-
dimethoxynitrostyrene 31 (0.19 g, 0.93 mmol), and SnCl4 (0.19 g,
0.75 mmol) during 2 h at 0 ꢁC. p-TLC (CHCl3) afforded 0.07 g (30%)
of 33 and 35 as a 1:1 mixture. p-TLC (70:30, hexane/ethyl acetate)
allowed the separation of 33 (yellow solid), mp: 285e287 ꢁC and 35
(yellow solid), mp: 170e172 ꢁC.
Acknowledgements
This work was supported by grants from the Consejo Nacional
de Investigaciones Científicas y Tecnicas (CONICET) and Uni-
versidad de Buenos Aires.
ꢀ
General procedure was carried out with alcohol 2 (0.14 g,
0.58 mmol), 3,4-dimethoxynitrostyrene 31 (0.19 g, 0.93 mmol), and
SnCl4 (0.19 g, 0.75 mmol) during 1 h at rt. p-TLC (CHCl3) afforded
0.10 g (44%) of 33, 35, and 37 as a 1:1:0.08 (33:35:37) mixture.
Compound 33 dH (ppm): 3.76 (3H, s, OCH3), 3.77 (3H, s, OCH3), 3.82
(3H, s, OCH3), 3.87 (3H, s, OCH3), 4.91 (1H, d, J¼7.9 Hz, CHAr), 4.93
(1H, d, J¼8.8 Hz, CHPh), 4.99 (1H, dd, J¼7.9, 8.5 Hz, CHNO2), 6.45
(1H, s, Ar), 6.48 (1H, s, Ar), 6.71 (1H, d, J¼1.7 Hz, Ar), 6.85 (2H, m,
Ar), 7.25 (2H, m, Ar), 7.36 (3H, m, Ar). dC (ppm): 55.5, 55.9, 56.1,
102.2, 107.3, 107.4, 111.0, 111.4, 120.6, 128.0, 128.2, 129.1, 132.4, 132.7,
132.9, 140.0, 148.8, 149.3, 149.8, 149.8. Compound 35 dH (ppm): 3.80
(3H, s, OCH3), 3.81 (3H, s, OCH3), 3.82 (3H, s, OCH3), 3.88 (3H, s,
OCH3), 4.99 (1H, d, J¼8.7 Hz, CHPh), 5.17 (1H, d, J¼8.5 Hz, CHAr),
5.43 (1H, t, J¼8.7 Hz, CHNO2), 6.54 (1H, s, Ar), 6.66 (1H, s, Ar), 6.71
(1H, d, J¼2.0 Hz, Ar), 6.77 (1H, dd, J¼2.0, 8.3, Hz, Ar), 6.84 (1H, d,
J¼8.3 Hz, Ar), 7.0 (2H, m, Ar), 7.25e7.33 (3H, m, Ar). dC (ppm): 51.9,
53.6, 53.7, 55.9, 56.0, 56.1, 97.4, 107.5, 110.9, 111.3, 111.4, 120.8, 128.1,
128.4, 128.6, 132.3, 132.4, 133.9, 136.9, 148.6, 149.2, 149.8, 149.9.
Compound 37 dH (ppm): 3.79 (3H, s, OCH3), 3.80 (3H, s, OCH3), 3.82
(3H, s, OCH3), 3.85 (3H, s, OCH3), 4.97 (1H, d, J¼8.5 Hz, CHPh), 5.19
(1H, d, J¼7.4 Hz, CHAr), 5.41 (1H, dd, J¼7.4, 8.5 Hz, CHNO2), 6.53
(1H, s, Ar), 6.66 (1H, s, Ar), 6.71 (1H, d, J¼2.0 Hz, Ar), 6.77 (1H, dd,
J¼2.0, 8.3 Hz, Ar), 6.84 (1H, d, J¼8.3 Hz, Ar), 7.00 (2H, m, Ar),
7.23e7.33 (3H, m, Ar). dC (ppm): 52.4, 53.6, 55.7, 55.9, 56.0, 56.1,
97.5, 107.5, 110.9, 111.3, 111.9, 120.9, 127.8, 129.0, 129.1, 132.3, 132.4,
132.6, 140.1, 148.6, 148.8, 149.8, 149.9. Anal. Calcd for C25H25NO6: C,
68.95; H, 5.79; N, 3.22. Found: C, 68.98; H, 5.8; N, 3.24. Compound
33d dH (ppm): 3.76 (3H, s, OCH3), 3.78 (3H, s, OCH3), 3.83 (3H, s,
OCH3), 3.88 (3H, s, OCH3), 4.92 (1H, d, J¼8.4 Hz, CHAr), 5.02 (1H, d,
J¼8.4 Hz, CHNO2), 6.46 (1H, s, Ar), 6.49 (1H, s, Ar), 6.73 (1H, d,
J¼1.8 Hz, Ar), 6.82 (1H, dd, J¼1.8, 8.4 Hz, Ar), 6.87 (1H, d, J¼8.4 Hz,
Ar), 7.28 (2H, m, Ar), 7.35 (3H, m, Ar). Compound 35d dH (ppm): 3.80
(3H, s, OCH3), 3.81 (3H, s, OCH3), 3.82 (3H, s, OCH3), 3.87 (3H, s,
OCH3), 5.17 (1H, d, J¼8.4 Hz, CHAr), 5.43 (1H, d, J¼8.4 Hz, CHNO2),
6.55 (1H, s, Ar), 6.65 (1H, s, Ar), 6.72 (1H, d, J¼1.7 Hz, Ar), 6.77 (1H,
dd, J¼1.7, 8.3, Hz, Ar), 6.84 (1H, d, J¼8.3 Hz, Ar), 7.0 (2H, m, Ar),
7.25e7.33 (3H, m, Ar).
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