Metal-free synthesis of indanes by iodine(iii)-mediated ring contraction of 1,2-dihydronaphthalenes

Article abstract of DOI:10.1590/S0103-50532011000900024

A metal-free protocol was developed to synthesize indanes by ring contraction of 1,2-dihydronaphthalenes promoted by PhI(OH)OTs (HTIB or Koser's reagent). This oxidative rearrangement can be performed in several solvents (MeOH, CH3CN, 2,2,2-trifluoroethanol (TFE), 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), and a 1:4 mixture of TFE:CH₂Cl₂) under mild conditions. The ring contraction diastereoselectively gives functionalized trans-1,3-disubstituted indanes, which are difficult to obtain in synthetic organic chemistry. ?2011 Sociedade Brasileira de Qui?mica.

Full text of DOI:10.1590/S0103-50532011000900024

J. Braz. Chem. Soc., Vol. 22, No. 9, 1795-1807, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
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Article
A
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated Ring Contraction of
1,2-Dihydronaphthalenes
Fernanda A. Siqueira,a,# Eloisa E. Ishikawa,a André Fogaça,a Andréa T. Faccio,a
Vânia M. T. Carneiro,a Rafael R. S. Soares,a,§ Aline Utaka,a Iris R. M. Tébéka,a
Marcin Bielawski,a,b Berit Olofssonb and Luiz F. Silva Jr.*,a,‡
aDepartamento de Química Fundamental, Instituto de Química, Universidade de São Paulo,
CP 26077, 05513-970 São Paulo-SP, Brazil
bDepartment of Organic Chemistry, Arrhenius Laboratory, Stockholm University,
SE-106 91 Stockholm, Sweden
Um protocolo livre de metais foi desenvolvido para sintetizar indanos através da contração
de anel de 1,2-di-hidronaftalenos promovida por PhI(OH)OTs (HTIB ou reagente de Koser). Este
rearranjo oxidativo pode ser realizado em diversos solventes (MeOH, CH3CN, 2,2,2-trifluoroetanol
(TFE), 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), e uma mistura 1:4 de TFE:CH2Cl2) em condições
brandas. A contração de anel fornece indanos trans-1,3-dissubstituídos diastereosseletivamente,
os quais são difíceis de obter em química orgânica sintética.
A metal-free protocol was developed to synthesize indanes by ring contraction of
1,2-dihydronaphthalenes promoted by PhI(OH)OTs (HTIB or Koser’s reagent). This oxidative
rearrangement can be performed in several solvents (MeOH, CH3CN, 2,2,2-trifluoroethanol
(TFE), 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), and a 1:4 mixture of TFE:CH2Cl2) under mild
conditions. The ring contraction diastereoselectively gives functionalized trans-1,3-disubstituted
indanes, which are difficult to obtain in synthetic organic chemistry.
Keywords: indanes, hypervalent iodine, ring contraction, 1,2-dihydronaphthalenes,
rearrangements
Introduction
In the last years, hypervalent iodine reagents have
become an essential tool in synthetic organic chemistry
due to the plethora of reactions that can be performed
with them in excellent yield and selectivities.5 Moreover,
hypervalent iodine compounds represent in many cases an
alternative to toxic heavy metals.5 Although the oxidative
rearrangement of alkenes mediated by iodine(III) has
been described in some papers,6 the ring contraction of
1,2-dihydronaphthalenes was reported for a few substrates
using only p-Me-C6H4-IF2,6 which led to fluorinated
indanes.
Herein, we describe an efficient metal-free protocol
for the synthesis of indanes under mild conditions. In a
preliminary communication, we report the ring contraction
of 1,2-dihydronaphthalenes (which are obtained from
1-tetralones) mediated by PhI(OH)OTs (HTIB or Koser’s
reagent) for a few substrates.7 In this article, the oxidation of
several additional substrates is presented, better defining the
reaction scope.Additionally, other reaction conditions were
The indane ring system is present in several
natural products and in non-natural compounds with
remarkable biological activity.1 Consequently, efforts
have continuously been made to develop new routes
to obtain molecules with this unit.2 A typical strategy
to synthesize a functionalized indane is by selecting
an appropriate indanone, which is then elaborated into
the target molecule.2,3 As tetralones are usually cheaper
than indanones, the preparation of indanes starting from
a tetralone (or a derivative) through a ring contraction
rearrangement could be advantageous.4
*e-mail: luizfsjr@iq.usp.br
Present addresses: #Universidade Federal de São Paulo, Campus Diadema,
Rua Artur Riedel, 275, 09972-270, Diadema-SP, Brazil
§Instituto Federal de Educação, Ciência e Tecnologia de São Paulo, Rua
Pedro Vicente, 625, 01109-010 São Paulo-SP, Brazil
‡Dedicated with deep respect to Prof. Miuako K. Kuya

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Metal-Free Synthesis of Indanes by Iodine(III)-Mediated Ring Contraction
J. Braz. Chem. Soc.
Table 1. Oxidation of 1,2-dihydronaphthalenes with HTIB in MeOH
discovered using fluoroalcohols as solvent, which highly
improved isolated yields. The best condition employed a
4:1 mixture of CH2Cl2-TFE that led to indanes in very good
yield and with high diastereoselectivity.
entry
1
Substrate
Product (yield)
MeO
OMe
OMe
OMe
Results and Discussion
1a
2a (36%)
3a (trans: 28%)
(cis: 14%)
Ring contractions in methanol
MeO
OMe
OMe
OMe
The required 1,2-dihydronaphthalenes are readily
available substrates that can be prepared from 1-tetralones
by reduction or Grignard reaction followed by dehydration7,8
(see Supplementary Information, SI, for details). This
work was initiated studying the oxidation of 1a with the
readily available iodine(III) reagents HTIB, PhI(OAc)2, and
PhI(OCOCF3)2 in methanol. Mixtures of several compounds
and/or starting material were obtained using PhI(OAc)2 or
PhI(OCOCF3)2. Albeit the addition product 3a was isolated
as the major component, the desired indane 2a was isolated
using HTIB (Table 1, entry 1). Thus, HTIB was selected for
further tests. When the reaction was performed at −10 ºC,
the overall isolated yield was lower (2a: 24%, trans-3a:
20%, cis-3a: 15%) than at room temperature. The use
of trimethylorthoformate (TMOF) as solvent, instead of
MeOH, also decreased the global yield (2a: 14%, trans-3a:
12%, cis-3a: 2%). These two trends are opposite to that
observed in analogous thallium(III) promoted oxidation of
1,2-dihydronaphthalenes.9 Although indane 2a was obtained
in only 36%, we decided to study the behavior of the methyl-
substituted 1,2-dihydronaphthalene 1b, hoping to obtain a
higher yield of the ring contraction product.9 Indeed, when
1b was treated with HTIB, the desired trans-indane 2b was
obtained in 55% yield, together with the addition products
3b (entry 2). The ring contraction of 1,2-dihydronaphthalene
1c was performed with 3.6 equiv. of HTIB, which delivered
indane 2c in 62% yield, as a single diastereomer, together
with the addition product 3c in 35% yield (entry 3). With a
lower amount of HTIB, the yield of 2c is smaller. A similar
pattern was also observed in Tl(III) reactions, where an
excess of the oxidant increased the yield of the indane.8 It
is important to note that the diastereoselective synthesis of
trans-1,3-disubstituted indanes is a difficult task in synthetic
organicchemistry.10 Compound2cisasyntheticintermediate
in the synthesis of ( )–indatraline, which displays several
interesting biological activities.7 The presence of donating
groups at the aromatic ring may facilitate the rearrangement
of 1,2-dihydronaphthalenes by increasing the migratory
aptitude of the migrating carbon.8 Indeed, the oxidation of
alkene 1d, that bears an amide group para to the migrating
carbon, with HTIB gave the desired acetal 2d in much higher
yield than the corresponding non-substituted substrate 1a
2
3
1b
2b
3b (12%)
(cis:trans = 3:4)
(55%)
MeO
OMe
OMe
OMe
Cl
2c
(62%)
Cl
1c
Cl
Cl
3c (35%)
Cl
(cis:trans =1:4)
Cl
MeO
OMe
OMe
OMe
4
5
6
AcHN
AcHN
1d
AcHN
2d (72%)
3d (trans: 10%)
(cis: 7%)
MeO
OMe
OMe
OMe
1e
2e (29%)
3e (trans: 27%)
(cis: 17%)
MeO
OMe
MeO
OMe
MeO
MeO
OMe
1f
2f (3%)
3f (trans: 26%)
(cis: 17%)
MeO
OMe
MeO
OMe
MeO
MeO
MeO
MeO
OMe
7
8
1g
MeO
2g (12%)
3g (trans: 8%)
OMe
OMe
3h (trans: 60%)
(cis: 31%)
1h
(entry 4). However, the treatment of alkene 1e with HTIB
gave indane 2e in comparable yield to that obtained for the
substrate 1a (cf. entries 1 and 5). When HTIB was added to
a methanol solution of substrates 1f-g, which bear a methoxy
group at the aromatic ring, the mixture immediately became
black, leading to indanes 2f-g in low yield (entries 6 and 7).
Low yields in iodine(III)-mediated oxidation of methoxy-
substituted substrates has also been observed by others.11,12
Considering our experience in the oxidations of alkenes
mediated by Tl(III),9 we expected that the trisubstituted
1,2-dihydronaphthalene 1h would have a different behavior

Vol. 22, No. 9, 2011
Siqueira et al.
1797
Table 2. Oxidation of 1,2-dihydronaphthalenes with HTIB in CH3CN
toward HTIB from that of the disubstituted alkene 1a.
Indeed, when 1h was treated with HTIB in MeOH only the
addition product 3h was isolated (entry 8). It is important to
note that the acetal moiety in indanes like 2a-g can be easily
transformed without epimerization into the corresponding
aldehyde.2
entry
1
Substrate
Product (yield)
O
H
1a
5aa
4a (30%)
O
Ring contractions in acetonitrile
2
3
4
The conditions used by Kirschning and co-workers6
in the oxidation of carbohydrates were also applied in the
oxidation of 1,2-dihydronaphthalenes. Naphthalene (4a)
was isolated in 30% yield when 1a was treated with HTIB
in CH3CN (Table 2, entry 1). NMR analysis of the crude
product indicates the presence of indane 5a as a minor
component, which decomposed during the purification
step.13 Similarly, 4a was obtained in 48% yield when the
reaction was performed in CH2Cl2, as solvent. However,
when 1h was treated with HTIB in CH3CN indane 5h was
isolated in 51% yield (entry 2), which should be compared to
exclusive formation of addition products in MeOH reactions
(Table 1, entry 8). Ring contractions of epoxides can also
be performed by treatment with Brønsted or Lewis acids.4
However, compound 5h can not be prepared in this manner,
as no ring contraction product was obtained from the epoxide
prepared from 1h.14-17 The oxidative rearrangement of other
4-alkyl-1,2-dihydronaphthalenes was also investigated. The
reaction of alkenes 1i and 1g, which bear a methoxy group in
the aromatic ring, with HTIB in CH3CN furnished indanes 5i
and 5g, respectively, in low yield (Table 2, entries 3 and 4),
similarly to the disubstituted alkenes (Table 1, entries 6-7).
Trisubstituted alkenes 1k-m were transformed into indanes
5k-m13 in good yield (entries 5-7). Thus, the ring contraction
is not precluded by the presence of bulky alkyl groups. The
behavior of alkene 1n is slightly different to that observed
for other substrates.The reaction of 1n with HTIB in CH3CN
led mainly to indane 5n and ketone 6n18 in 26 and 23%
yield, respectively. The tetralone 6n is formed by migration
of the phenyl group.6 The reaction of 1n with HTIB led to a
nearly 1:1 mixture of the rearrangement products 5n and 6n,
because the aromatic rings have similar migratory aptitude.
In theory, if the migratory aptitude of the aromatic rings was
different, the ratio of the rearrangement products could be
modified. Indeed, when 1o, which has two Cl atoms in one
of the rings, was treated with HTIB, trans-indane 5o was
isolated and the product of migration of the C6H3Cl2 group
was not formed, because of the low migratory aptitude
of C6H3Cl2. However, a small amount of the tetralone 7o,
which is formed by migration of hydride,13,16 was isolated
(entry 9). Finally, we investigated the ring contraction in
a seven-membered ring substrate. When alkene 1p was
1h
5h (51%)
O
MeO
MeO
MeO
1i
5i (12%)
4ib
O
MeO
MeO
MeO
1j
5j (20%)
4j (20%)
O
5
6
7
8
1k
5k (60%)
(trans:cis = 10:1)
O
n-Bu
n-Bu
n-Bu
1l
5l (49%)
4l (2%)
(trans:cis = 10:1)
O
i-Pr
i-Pr
i-Pr
1m
5m (48%)
(trans:cis = 5:1)
4m (13%)
O
Ph
Ph
O
Ph
Ph
5n (26%)
1n
6n (23%)
(cis:trans 6:1)
4n (4%)
O
C6H3-3,4-Cl2
C6H3-3,4-Cl2
O
C6H3-3,4-Cl2
9
5o (35%)
1o
7o (6%)
(trans:cis = 11:1)
O
10
5p (52%)
1p
aYield not determined; btogether with 1i, ca. 20%.
treated with HTIB in CH3CN, the substituted tetralin 5p was
obtained in good yield (entry 10). The ring contractions in
CH3CN were performed under inert atmosphere and in the
presence of molecular sieves. When these conditions were

1798
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated Ring Contraction
J. Braz. Chem. Soc.
Table 3. Reaction of 1,2-dihydronaphthalenes with HTIB in fluoroalcoholsa
not followed, lower yields were observed. The preparation
of indanes analogues to 5 from 1,2-dihydronaphthalenes
has been reported in a two-step protocol using NBS/water
followed by reaction with Et2Zn, which requires anhydrous
conditions.17
Entry
1
Substrate
Product (isolated yield)
F3CH2CO
OCH2CF3
1a
8a
(A: 73%)
(B: 67%)
Ring contractions in fluorinated solvents
F3CH2CO
OCH2CF3
After investigating the oxidation of 1,2-dihydro-
naphthalenes with HTIB in methanol and in acetonitrile, we
focused on the more polar solvents 2,2,2-trifluoroethanol
(TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP)
because we envisioned that the formation of by products
could be decreased performing the reaction in these high
polar low nucleophilic solvents. Since the first report by
Kita et al.,19 the fluoroalcohols TFE20 and HFIP21 have been
used as solvent in several reactions with hypervalent iodine
compounds. However, TFE and HFIP have never been used
in the oxidative rearrangement of alkenes.5,6
2
3
1b
8b
(A: 70%, trans:cis = 5:1)
F3CH2CO
OCH2CF3
1q
8q
F
F
(A: 65%, trans:cis = 10:1)
(B: 69%, trans:cis = 17:1)
For the alkene 1a, the yield of the desired product jumped
from 36% (cf. entry 1,Table 1) to more than the double (73%,
Table 3, entry 1). The reaction of 1b with HTIB in TFE led
to indane 8b in higher yield than in MeOH (55% vs. 70%),
although the diastereoselectivity is lower (entry 2 of Tables 1
and 3, respectively). The ring contraction of 1q inTFE led to
8q in 65% yield, as a 10:1 mixture of trans:cis diastereomers,
respectively. Considering our previous work on the synthesis
of 3-phenyl-1-indanamines,7 the indane 8q could be used as
anintermediateinthesynthesisof( )-irindalone.22Moreover,
this new method to obtain fluorinated acetals, which have
different applications,23 is more efficient than the previous
described.24-26 The oxidation of trisubstituted alkenes 1h and
1p with HTIB in TFE gave indanes 5h and 5p, respectively,
in higher yield than using acetonitrile (cf. Table 2,
entries 2 and 10 with entries 4 and 7 ofTable 3). On the other
hand, 1k led to 5k in lower yield and diastereoselectivity than
in acetonitrile (entry 5 of Tables 2 and 3).
O
4
5
5h
(A: 72%)
1h
O
5k
1k
(A: 53%, trans:cis = 2:1)
(B: 76%, trans:cis = 7:1)
O
i-Pr
i-Pr
6
7
1m
5m
(B: 62%, trans:cis = 9:1)
O
5p
(A: 62%)
1p
Although the HTIB-mediated oxidation of
1,2-dihydronaphthalenes in TFE led to the rearrangement
products in higher yields than in other solvents, the
diastereoselectivity is lower. Thus, several conditions were
tested trying to optimize the diastereoselectivity, without
decreasing the isolated yields. Eventually, this goal was
achieved by performing the reaction in a 4:1 mixture of
CH2Cl2:TFE as solvent. Although CH2Cl2 is the major
component of the mixture, TFE must have a crucial role
because the reaction of 1a with HTIB in pure CH2Cl2
gave naphthalene (cf. entry 1, Table 2). The indane 8a was
obtained from 1a in a yield comparable to the reaction
in only TFE (73% vs. 67% yield, entry 1, Table 3). The
alkene 1q gave the indane 8q in 69% yield, as a trans:cis
8
9
1a
5a (C: 58%)
OH
1a
9a
(D: 34%)
TsO
OH
OTs
10
11
1a
1a
9a
(E: 48%)
10a
(E: 17%)
9a (F: 74%)
aA: TFE; B: 4:1 mixture of CH2Cl2/TFE; C: HFIP; D: i) HFIP, ii) NaBH4;
E: i) CH2Cl2:HFIP (4:1), ii) NaBH4; F: i) 22 equiv. H2O, CH2Cl2:HFIP
(4:1), ii) NaBH4.

Vol. 22, No. 9, 2011
Siqueira et al.
1799
Me
Me
H
Me
Ph
OMe
H
HTIB
MeOH
H
MeOH
-H+
8a
H
1b
H
I
8a
δ+
OMe
H
δ+
Ph
I
Ph
12b
I
12a
Ha
OH
11
OH
OH
Me
H
Me
H
8a
H
H+
MeOH
-H+
OMe
trans-2b
OMe
-H2O
-IPh
Ph
I
H
Ha
OH2
14
H
13
Scheme 1. Mechanism for the ring contraction of 1b in MeOH.
ratio of 17:1, i.e., in better yield and selectivity than using
only TFE (entry 3, Table 3). The reaction in CH2Cl2/TFE
is also appropriate for trisubstituted alkenes. Ketones 5k
and 5m were obtained in higher yield than in acetonitrile
or in TFE. Furthermore, the diastereoselectivity is higher
than in TFE and comparable to the reaction in acetonitrile
(cf. entries 5 and 7 of Table 2 and entries 5 and 6 of Table 3).
In summary, treatment of 1,2-dihydronaphthalenes with
HTIB in TFE or in CH2Cl2/TFE gave the desired indanes
in higher yields than using MeOH or CH3CN for either
di- or trisubstituted double bonds.
Considering the very good results withTFE, the obvious
extension would be the study of the reaction in the even
more polar solvent HFIP. The oxidation of alkene 1a in
HFIP was very fast and led to indane 5a. The yield of the
ring contraction product was, however, lower than in TFE
(cf. entries 1 and 8, Table 3). In the presence of the bulky and
low nucleophilic solvent HFIP an aldehyde (5a) is isolated
instead of acetals, as in MeOH or in TFE (2a and 8a).
Aldehyde 5a is not very convenient for manipulation and
storage because it decomposes. We thus investigated if 5a
could be reducedin situ, giving a stable alcohol.The reaction
of 1a with HTIB in HFIP followed by addition of NaBH4
gave the desired alcohol 9a in only 34% yield (entry 9).
Changing the solvent to a mixture of CH2Cl2:HFIP (4:1),
the alcohol 9a was isolated in better yield, however together
with the gem ditosylate 10a6 in 17% yield (entry 10).
We envisioned that the addition of H2O could favor the
formation of 9a, avoiding the undesired product 10a.
Indeed, a smooth ring contraction/reduction was observed
when 1a was treated with HTIB in the presence of H2O
in CH2Cl2/HFIP (4:1) as solvent, followed by addition of
NaBH4, giving 9a in 74% isolated yield (entry 11).
explained by the mechanism detailed below. The
electrophilic anti-addition of HTIB to the double bond
would lead to 12a, through the cyclic organoiodine
intermediate 11. The approach of the electrophile occurs
opposite to the remote methyl group,27-29 explaining the
stereoselectivity of this ring contraction, as well as of the
other reactions discussed below. The adduct 12a would
equilibrate to its more stable conformational isomer
12b, on which the required anti-periplanarity for the
rearrangement is achieved. Migration of the aryl group
(carbon 8a) on 13 would displace PhI giving the oxonium
14, which would furnish the trans-indane 2b after addition
of MeOH (Scheme 1). The diastereoselective formation
of the trans products in ring contractions in TFE or in
CH2Cl2/TFE can be explained by similar mechanisms.
However, considering the anhydrous conditions of the
ring contraction in CH3CN, the mechanism is probably
different, as shown in Scheme 2 for 1n. The stereoselective
electrophilic addition of HTIB to the alkene 1n would give
the bis-benzylic carbocation 15. The hydroxyl group would
attack the C1 position of 15, giving the four-membered ring
intermediate 16,6 which would ring open to form 17. The
ring contraction would take place on its conformer (18)
giving trans-5n (path a, Scheme 2). The solvent may have
some influence in the stereoselectivity of the electrophilic
addition of the iodine(III), explaining the formation of
Ph
Me
H
Me
H
HTIB
CH3CN
1n
Ph
15
O
I
Ph
I
Ph
H
16
8a
H
O
Me
H
Me
H
Ph
a
5n
b
H
Ph
H
b
b
OH
b
I
I
17
Mechanism discussion
Ph
O
Ph
18
cis-6n
Scheme 2. Rearrangements of 1n in CH3CN.
The exclusive formation of trans-1,3-disubstituted
indanes in the ring contractions in methanol can be

1800
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated Ring Contraction
J. Braz. Chem. Soc.
cis-1,3-disubstituted indanes.Alternatively, the cis indanes
can be formed by epimerization of the ketone moiety of the
corresponding trans isomers. Starting from trisubstituted
double bonds, the ring contraction lead to ketones which
are always obtained as a free carbonyl. Aldehydes are
formed from disubstituted alkenes. In the presence of a
nucleophilic solvent, such as MeOH or TFE, acetals were
isolated. On the other hand, free aldehydes were obtained
in CH3CN or in HFIP.
The formation of the cis-2,4-disubstituted-1-tetralone
6n can be explained by the mechanism shown in path b of
Scheme 2. The Ph group would migrate on intermediate
17, with the exit of PhI, leading to cis-6n. trans-6n can
be formed either by isomerization of cis-isomer or the
addition of I(III) to 1n could take place by the other face. In
acetonitrile oxidations, small amounts of naphthalenes were
isolated in some reactions, which are formed by addition
followed by elimination.13
the rearrangements are disfavored with an additional methyl
group (12b and 13 with Me instead Ha in Scheme 1). In
anhydrous acetonitrile, there is no good nucleophile and
ring contraction of trisubstituted alkenes occurs through
the formation of a tertiary benzylic carbocation (like 15).
For disubstituted double bonds, the ring contraction would
occur through a less favored secondary benzylic carbocation
and, thus, the formation of naphthalenes predominates. In
TFE or in CH2Cl2/TFE, ring contraction was observed for
either di- or trisubstituted 1,2-dihydronaphthalenes. The
mechanism described for MeOH is the major pathway,
as acetals are isolated for disubstituted alkenes. Ring
contraction also takes place with trisubstituted substrates,
because a less nucleophilic species is present, making the
formation of addition products more difficult.
Conclusions
A plausible mechanism to explain the formation of
the products of addition of MeOH is shown in Scheme 3,
using substrate 1a as example.6,8 The methoxy group
of 19 would intramolecularly displace PhI, giving the
oxonium 20. Methanol would attack the C1 benzylic
position of 20, furnishing trans-3a (path a). Alternatively,
the intermolecular displacement of PhI by MeOH in
the intermediate 19 would lead to cis-3a (path b). The
preferential formation of the trans isomers (Table 1)
indicates that the intramolecular process is favored. The
formation of cis- and trans-isomers has also been observed
in the reaction of indene with iodosobenzene derivatives in
methanol.30 However, the oxidation of cyclohexenes with
iodine(III) led to rearrangement products,6 cis-isomers6,31-33
or trans-isomers,31,34 depending mainly on the reaction
conditions.
A one-step, fast, mild and metal-free protocol was
developed for the synthesis of indanes through ring
contraction of readily available 1,2-dihydronaphthalenes
mediated by HTIB. This oxidative rearrangement is
diastereoselective giving 1,3-trans-disubstituted indanes
preferentially or exclusively. The developed methodology
facilitates the access to this structural motif, which is
difficult to construct. Moreover, indanes bearing different
functional groups can be easily obtained by changing
the reaction conditions. In summary, the protocol herein
presented will be useful in synthetic organic chemistry
and in medicinal chemistry to access functionalized
indanes in an expeditious manner. The protocol represents
a green alternative to the analogous reaction using toxic
thallium(III) salts.8,9,13,35,36
Experimental
OH2
MeOH
δ+
a,b
Ph
General procedure
a,b
I
HTIB
MeOH
a
1a
O
Synthesis of 4-(4-fluorophenyl)-3,4-dihydronaphthalen-
1(2H)-one
δ+
Me
-H2O
-PhI
b
19
20
a
MeO
H
OMe
-H2O
-PhI, -H+
To a dry round bottom flask under nitrogen atmosphere,
AlCl3 (7.8 g, 59 mmol) was added followed by the addition
of fluorobenzene (10.8 mL, 11.1 g, 115 mmol). After
cooling the flask to 0 oC, 1-naftol (3.0 g, 20.8 mmol) was
added portion-wise under strong stirring (cake forms).
After the addition, the flask was charged with a condenser
and stirred at 75 oC for 1.5 h. The reaction was again cooled
to 0 oC and quenched by adding ice through the condenser
(strongly exothermic), until no gas evolution could be
observed. The reaction mixture was extracted with CH2Cl2
(3 × 25 mL), the organics washed with 1 mol L-1 NaOH
-H+
b
MeOH
cis-3a
trans-3a
Scheme 3. Mechanism for the formation of addition products 3a.
As described above, the solvent has a crucial role in
the oxidation of 1,2-dihydronaphthalenes with HTIB. In
methanol, ring contraction is favored toward the addition
of solvent for disubstituted double bonds. However, for
trisubstituted substrates, the nucleophilic attack of MeOH
is faster, probably because the required conformations for

Vol. 22, No. 9, 2011
Siqueira et al.
1801
(2 × 20 mL) and brine, dried with Na2SO4, filtered and
concentrated to give a thick brown oil (5.48 g). The crude
oil was purified by column chromatography (10% Et2O
in hexane), where the o-isomer elutes first followed by
the m- and p-isomers. As the m- and p-isomers have the
same Rf value, the mixed fractions were checked by GC to
collect fractions with pure p-product 4-(4-fluorophenyl)-
3,4-dihydronaphthalen-1(2H)-one37 (1.14 g, 4.75 mmol,
23%).
for 1 h. The reaction was extracted with EtOAc, washed
with H2O, with brine, and dried over anhydrous MgSO4.
The solvent was removed under reduced pressure. The
crude product was purified by column (0-25% EtOAc in
hexane), affording 2f9 (0.0137 g, 0.0616 mmol, 3%), as
colorless oil, trans-3f9 (0.117 g, 0.526 mmol, 26%) and
cis-3f (0.0779 g, 0.350 mmol, 17%), both as yellow oils.
cis-1,2,3,4-Tetrahydro-1,2,7-trimethoxynaphthalene (3f):
colorless oil; IR nmax/cm-1 (film) 1101, 1249, 1499, 2834,
1
2933; H NMR (500 MHz, CDCl3) d 1.91-1.94 (m, 1H),
Synthesis of 1-(4-fluorophenyl)-1,2-dihydronaphthalene
(1c)
2.16-2.23 (m, 1H), 2.67-2.74 (m, 1H), 2.92-2.96 (m, 1H),
3.47 (s, 3H), 3.50 (m, 3H,), 3.61-3.69 (m, 1H), 3.79 (s, 3H),
4.30 (d, 1H, J 3.1 Hz), 6.80 (dd, 1H, J 8.3, 2.6 Hz), 6.86 (d,
1H, J 2.6 Hz), 7.04 (d, 1H, J 8.3 Hz); 13C NMR (75 MHz,
CDCl3) d 22.7, 26.1, 55.3, 56.5, 57.4, 77.9, 78.2, 114.3,
114.4, 128.5, 129.7, 135.7, 157.5; LRMS (m/z, %) 222 (M+•,
17), 191 (7), 190 (52); 189 (9), 164 (100); HRMS (m/z)
calcd. for C13H18O3 [M + Na]+ 245.1148, found 245.1141.
4-(4-fluorophenyl)-3,4-dihydronaphthalen-1(2H)-one
(806 μL, 3.36 mmol) was added to a round bottom flask,
diluted with MeOH (25 mL) followed by cooling to 0 oC
and addition of NaBH4 (140 mg, 3.68 mmol). The reaction
was quenched with H2O after 1 h and adjusted to pH 5 with
10% HCl. After evaporation of the MeOH, the aqueous
phase was extracted with EtOAc (3 × 15 mL), followed
by the washing of the organics with brine, dried with
Na2SO4, filtered and concentrated to give a crude yellow
oil of 4-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-
1-ol (928 mg), which was used in the next step without
any further purification. The crude tetralol (928 mg) was
added to a dry round bottom flask, followed by dry toluene
(20 mL) and a few crystals of p-TsOH (cat.). The flask
was equipped with a dean-stark trap and refluxed until no
alcohol remained according toTLC (ca. 1.5 h). The reaction
was quenched with a saturated NaHCO3 solution and diluted
with EtOAc. The organic phase was washed with saturated
NaHCO3 (2 × 15 mL), brine (2 × 15 mL), dried with
Na2SO4, filtered and concentrated to give a crude brown
oil (761 mg). It was purified by column chromatography
(hexane) to afford 1c as colorless oil (728 mg, 3.25 mmol,
Reaction of 1,2-dihydro-6,7-dimethoxynaphthalene (1g)
with HTIB in MeOH
As 1f, but using 1g (0.0744 g, 0.391 mmol), HTIB
(0.153 g, 0.391 mmol), and MeOH (2.0 mL). The reaction
was stirred for 1 h at 0 ºC. The crude product was purified by
column (0-30% EtOAc in hexane), affording 2g8 (0.0116 g,
0.0460 mmol, 12%) and trans-3g (0.0080 g, 0.032 mmol,
8%), both as a colorless oil. trans-1,2,3,4-Tetrahydro-
1,2,6,7-tetramethoxynaphthalene (3g): colorless oil;
IR nmax/cm-1 (film) 1121, 1258, 1515, 2830, 2934; 1H NMR
(300 MHz, CDCl3) d 1.88-1.97 (m, 1H), 2.05-2.15 (m,
1H), 2.62-2.82 (m, 2H), 3.44 (s, 3H), 3.51 (s, 3H), 3.71
(ddd, 1H, J 7.2, 4.8, 2.7 Hz), 3.84 (s, 3H), 3.87 (3H, s),
4.21 (d, 1H, J 4.8 Hz), 6.58 (1H), 6.83 (s, 1H); 13C NMR
(75 MHz, CDCl3) d 23.4, 25.1, 55.9, 56.0, 56.7, 57.2, 77.2,
79.5, 111.1, 112.4, 126.5, 129.3, 147.5, 148.7; HRMS (m/z)
calcd. for C14H20O4 [M + Na]+ 275.1254, found 275.1252.
1
97% over 2 steps); H NMR (400 MHz, CDCl3) d 2.56
(dddd, 1H, J 13.8, 9.7, 4.2 and 2.0 Hz), 2.67 (dddd, 1H,
J 12.1, 7.4, 4.6 and 1.8 Hz), 4.12 (dd, 1H, J 9.3 and 7.7 Hz),
5.99 (dt, 1H, J 9.6 and 4.4 Hz), 6.55 (dt, 1H, J 9.6 and
1.5 Hz), 6.81 (d, 1H, J 7.7 Hz), 7.03-6.95 (m, 2H), 7.14-7.07
(m, 2H), 7.22-7.14 (m, 3H); 13C NMR (75 MHz, CDCl3)
d 32.2, 43.2, 115.3 (d, J 21 Hz), 126.4, 127.1, 127.1, 127.5,
127.9, 128.2, 129.9 (d, J 8 Hz), 134.2, 137.8, 140.3 (d,
J 3 Hz), 161.7 (d, J 245 Hz); HRMS (m/z) calcd. for C16H13F
247.0893 [M + Na]+, found 247.0901.
Synthesis of 1-(dimethoxymethyl)-5-acetamido-indane (2d)
To a stirred mixture of 1d (0.254 g, 1.36 mmol) and
MeOH (27 mL), was added HTIB (0.590 g, 1.50 mmol)
at once at 0 °C. After 35 min the reaction was quenched
with saturated solution of NaHCO3. The aqueous phase
was extracted with EtOAc (3 × 10 mL), washed with brine
(2 × 10 mL) and dried over anhydrous MgSO4. The solvent
was removed under reduced pressure. The crude product
was purified by column (hexane:EtOAc, 3:7) giving 2d
(72%, 0.244 g, 0.98 mmol) as a yellow solid, trans-3d
(10%, 0.035 g, 0.14 mmol) as a solid and cis-3d (7%,
0.025 g, 0.10 mmol) as a solid. 1-(Dimethoxymethyl)-
5-acetamido-indane (2d): mp 68.4-69.3 ºC; IR nmax/cm-1
(film) 828, 1058, 1124, 1372, 1426, 1492, 1546, 1602,
Reaction of 1,2-dihydro-6-methoxynaphthalene (1f) with
HTIB in MeOH
To a solution of 1f (0.328 g, 2.05 mmol) in MeOH
(8 mL) was added HTIB (0.941 g, 2.40 mmol) at 0 °C.
Immediately after addition of HTIB the reaction became
dark. The mixture was stirred at room temperature

1802
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated Ring Contraction
J. Braz. Chem. Soc.
1
1667; H NMR (200 MHz, CDCl3) d 1.85-2.28 (m, 3H),
2.13 (s, 3H), 2.70-2.90 (m, 2H), 3.37 (s, 3H), 3.41 (s, 3H),
4.27 (d, 1H, J 7.4 Hz), 7.16 (dd, 1H, J 1.4, 8.2 Hz), 7.32
(d, 1H, J 8.0 Hz), 7.46 (s, 1H), 7.84 (s, 1H); 13C NMR
(75 MHz, CDCl3) d 24.3, 27.5, 31.4, 47.0, 52.9, 54.2,
107.2, 116.4, 118.2, 125.6, 136.8, 138.7, 145.6, 168.6;
LRMS (m/z, %) 249 (M+•, 2.4%), 218 (6), 186 (3), 174 (4),
144 (6), 132 (13), 115 (5), 103 (3), 75 (100); HRMS (m/z)
calcd. for C14H19NO3 [M + H]+ 250.1438, found 250.1440.
N-(trans-5,6-dimethoxy-5,6,7,8-tetrahydronaphthalen-
2-yl)acetamide (trans-3d): mp 108.7-110.5 ºC; IR nmax/cm-1
(film) 830, 915, 1091, 1331, 1372, 1419, 1505, 1544, 1598,
1614, 1671, 2934, 3302, 3507; 1H NMR (200 MHz, CDCl3)
d 1.81-2.18 (m, 2H), 2.13 (s, 3H), 2.58-2.90 (m, 2H), 3.44 (s,
3H), 3.48 (s, 3H), 3.67-3.74 (m, 1H) 4.21 (d, 1H, J 4.8 Hz),
7.21-7.27 (m, 2H), 7.34 (s, 1H), 7.56 (s, 1H). 13C NMR
(75 MHz, CDCl3) d 23.3, 24.5, 25.5, 56.5, 57.3, 77.8, 79.2,
117.5, 119.4, 130.5, 130.6, 137.3, 137.9, 168.3; LRMS
(m/z, %) 249 (M+•, 23%), 217 (27), 191 (100); HRMS (m/z)
calcd. for C14H19NO3 [M + Na]+ 272.1257, found 272.1262.
N-(cis-5,6-dimethoxy-5,6,7,8-tetrahydronaphthalen-2-yl)
acetamide (cis-3d): IR nmax/cm-1 (film) 817, 882, 1081,
1106, 1372, 1419, 1505, 1544, 1602, 1614, 1671, 2933,
3311, 3509; 1H NMR (200 MHz, CDCl3) d 1.86-2.30 (m,
2H), 2.16 (s, 3H), 2.68-3.07 (m, 2H), 3.45 (s, 3H), 3.47 (s,
3H), 3.57-3.67 (m, 1H), 4.32 (d, 1H, J 2.8 Hz), 7.25-7.34
(m, 4H); 13C NMR (75 MHz, CDCl3) d 22.3, 24.6, 27.3,
56.4, 57.1, 77.5, 78.2, 117.1, 119.8, 130.5, 130.6, 137.6,
137.7, 168.3.; LRMS (m/z, %) 249 (M+•, 21%), 217 (28),
191 (100); HRMS (m/z) calcd. for C14H19NO3 [M + Na]+
272.1257, found 272.1260.
J 6.9 Hz), 1.81-1.85 (m, 2H), 3.21 (sext, 1H, J 7.2 Hz) (other
signals overlap with the trans form); 13C NMR (75 MHz,
CDCl3) d (trans isomer) 13.8, 20.2, 22.3, 25.8, 37.8, 38.5,
40.1, 57.0, 123.8, 124.7, 126.6, 127.6, 140.7, 149.3, 210.8,
(cis isomer) 13.9, 19.7, 22.4, 25.9, 38.3, 40.8, 123.5,
124.6, 127.4, 141.0, 148.8, 211.3 (other signals overlap
with the trans form); LRMS (m/z, %) 216 (M+•, 5), 131
(100); HRMS (m/z) calcd. for C15H20O [M + H]+ 217.1587,
found 217.1586.
Reaction of 4-isopropyl-1-methyl-1,2-dihydronaphthalene
(1m) with HTIB in CH3CN
The typical procedure for reactions in CH3CN was
followed, but using 5m (0.187 g, 1.00 mmol). The crude
product was purified by flash column chromatography
(gradient elution, 0-20% EtOAc in hexanes), affording
indane 5m (0.0981 g, 0.485 mmol, 48%)13 as a trans:cis
(5:1 by 1H NMR after purification) mixture, as yellow oil.
Naphthalene 4m (0.0244 g, 0.132 mmol, 13%)38 was also
isolated as colorless oil.
Reaction of 1,2-dihydro-7-methoxy-4-methylnaphthalene
(1i) with HTIB in CH3CN
To a solution of 1i (0.178 g, 1.02 mmol) and molecular
sieves (3 Å, 0.100 g) in CH3CN (10 mL) under N2 was
added HTIB (0.442 g, 1.13 mmol) at 0 °C. The ice bath
was removed. The mixture was stirred for 15 min at room
temperature. A saturated solution of NaHCO3 was added
until pH 7. The organic phase was washed with H2O, with
brine and dried over anhydous MgSO4. The solvent was
removed under reduced pressure. The crude product was
purified by column (0-40% EtOAc in hexane), affording
5i39 (0.0231 g, 0.121 mmol, 12%), as a yellow oil and a
mixture 1:1 of 4i40 and starting material (0.0361 g), as a
colorless oil.
Syntheses of cis and trans-1-(2,3)-dihydro-1-metyl-
1H-inden-3-yl)pentan-1-one (5l)
To a solution of 1l (0.129 g, 0.647 mmol) and molecular
sieves (3 Å,0.065 g) in anhydrous CH3CN (6.5 mL) under
N2 was added HTIB (0.489 g, 1.25 mmol) at 0 °C. The
reaction was stirred for 15 min at 0 °C.A saturated solution
of NaHCO3 was added until pH 7. The organic phase was
washed with H2O, with brine and dried over anhydrous
MgSO4. The solvent was removed under reduced pressure.
The crude product was purified by column (0-10% EtOAc
in hexane), affording 5l (0.0681 g, 0.315 mmol, 49%)
as a trans:cis (10:1) mixture. Naphthalene 4l9 (0.0031 g,
0.016 mmol, 2%) was also isolated as a colorless oil. cis
and trans-5l: yellow oil; IR nmax/cm-1 (film) 755, 1460, 1711,
Reactionof1,2-dihydro-6-methoxy-4,7-dimethynaphthalene
(1j) with HTIB in CH3CN
As for 1i, but using 1j (0.197 g, 1.05 mmol), molecular
sieves (3 Å, 0.100 g), HTIB (0.489 g, 1.25 mmol),
CH3CN (10 mL). The mixture was stirred for 30 min at
room temperature. The crude product was purified by
column (0-40% EtOAc in hexane) affording 5j8 (0.0420 g,
0.204 mmol, 20%) and impure 4j (0.0594 g). Impure 4j
was purified by column (10% EtOAc in hexane), affording
4j41 (0.0381 g, 0.205 mmol, 20%).
1
2870, 2931, 2959; H NMR (300 MHz, CDCl3) d (trans
isomer) 0.87 (t, 3H, J 7.3 Hz), 1.21-1.25 (m, 1H), 1.28 (d,
3H, J 6.9 Hz), 1.51-1.56 (m, 2H), 2.41-2.62 (m, 3H), 3.40
(sext, 1H, J 6.8 Hz), 4.08 (dd, 1H, J 8.7, 3.4 Hz), 7.14-7.28
(m, 4H), (cis isomer) 0.91 (t, 3H, J 7.5 Hz), 1.35 (d, 3H,
Reaction of 1,2-dihydro-1-methyl-4-phenylnaphthalene
(1n) with HTIB in CH3CN
As for 5l, but using 1n (0.165 g, 0.750 mmol), molecular
sieves (3 Å, 0.0750 g), HTIB (0.353 g, 0.901 mmol), and

Vol. 22, No. 9, 2011
Siqueira et al.
1803
CH3CN (7.5 mL). The mixture was stirred for 20 min
at room temperature. The product crude was purified
by column (0-10% EtOAc in hexane) affording 5n
(0.0452 g, 0.191 mmol, 26%),13 and 6n (0.0414 g,
0.175 mmol, 23%),18 as yellow oil and as a cis:trans mixture
(6:1). 4n (7.00 mg, 0.0321 mmol, 4%)42 was isolated, as
a colorless oil.
Synthesis of 1-[bis(trifluoromethoxy)methyl]-2,3-dihydro-
1H-indene (8a)
To a stirred mixture of 1a (0.102 g, 0.78 mmol) and
TFE (6 mL), was added HTIB (0.34 g, 0.86 mmol) at
once at 0 °C. After 30 min the reaction was quenched with
saturated solution of NaHCO3 until pH 7. The aqueous
phase was extracted with EtOAc (3 × 10 mL), washed with
brine (2 × 10 mL) and dried over anhydrous MgSO4. The
solvent was removed under reduced pressure. The crude
product was purified by column (hexane:EtOAc, 9:1)
giving 8a (73%, 0.19 g, 0.57 mmol) as a light yellow oil;
IR nmax/cm-1 (film) 2949, 2855, 1460, 1281, 1164, 1078;
1H NMR (300 MHz, CDCl3) d 1.96-2.08 (m, 1H), 2.18-2.30
(m, 1H), 2.82-3.03 (m, 2H), 3.47 (q, 1H, J 7.9 Hz), 3.86-
4.07 (m, 4H), 4.70 (d, 1H, J 7.9 Hz), 7.15-7.24 (m, 3H),
7.38-7.41 (m, 1H); 13C NMR (75 MHz, CDCl3) d 27.1,
31.2, 47.2, 61.9 (q, J 34.9 Hz), 63.4 (q, J 34.9 Hz), 105.4,
123.7 (q, J 276 Hz), 123.8 (q, J 276 Hz), 124.6, 125.5,
126.5, 127.6, 140.8, 144.6; LRMS (m/z, %) 328 (M+·,
1.3%), 211 (70), 129 (21), 117 (100); HRMS (m/z) calcd.
for C14H14F6O2 [M + Na]+ 351.0790, found 351.0801.
Reaction of 4-(3,4-dichlorophenyl)-1-methyl-1,2-dihydro-
naphthalene (1o) with HTIB in CH3CN
As for 1i, but using 1o (0.118 g, 0.408 mmol), molecular
sieves (3 Å, 0.0413 g), HTIB (0.194 g, 0.495 mmol), and
CH3CN (4.0 mL). The mixture was stirred for 20 min at
room temperature. The product was purified by column (0-
30% EtOAc in hexane) affording 5o (0.0430 g, 0.141 mmol,
35%) and 7o (0.0070 g, 0.023 mmol, 6%), both as a yellow
oil. trans-(3,4-Dichlorophenyl)-2,3-dihydro-1-methyl-
1H-inden-3-yl)methanone (5o): IR nmax/cm-1 (film) 755,
1030, 1206, 1687, 2867, 2925, 2958; 1H NMR (500 MHz,
CDCl3) d 1.34 (d, 3H, J 6.9 Hz), 2.0.2 (ddd, 1H, J 12.8,
7.6, 8.7 Hz), 2.68 (ddd, 1H, J 12.5, 7.8, 4.0 Hz), 3.49
(sext, 1H, J 7.2 Hz), 4.95 (dd, 1H, J 8.8, 3.9 Hz), 7.04
(d, 1H, J 7.5 Hz), 7.11-7.14 (m, 1H), 7.24-7.25 (m, 2H),
7.59 (d, 1H, J 8.4 Hz), 7.86 (dd, 1H, J 8.3, 2.0 Hz), 8.11
(d, 1H, J 2.0 Hz); 13C NMR (75 MHz, CDCl3) d 20.4,
38.4, 38.5, 51.3, 124.0, 124.0, 126.6, 127.9, 127.9, 130.8,
130.8, 133.5, 136.4, 137.7, 140.0, 149.4, 198.2; LRMS
(m/z, %) 305 (M+•, 1%), 131 (100); HRMS (m/z) calcd.
for C17H14Cl2O [M + H]+ 305.0494, found 305.0486.
1-(3,4-Dichlorophenyl)-3,4-dihydro-4-methylnaphthalen-
2(1H)-one (7o): IR nmax/cm-1 (film) 755, 1030, 1206, 1687,
2867, 2925, 2958; 760, 1031, 1175, 1380, 1467, 1722,
2928, 2963; 1H NMR (300 MHz, CDCl3) d 2.31 (dd, 1H,
J 16.8, 7.5 Hz), 2.98 (dd, 1H, J 16.8, 6.6 Hz), 3.12 (sext,
1H, J 6.9 Hz), 4.77 (s, 1H), 6.88 (dd, 1H, J 8.4, 2.4 Hz),
7.16 (d, 1H, J 2.1 Hz), 7.30-7.47 (m, 4H), 7.62-7.71 (m,
1H,); 13C NMR (75 MHz, CDCl3) d 20.1, 32.5, 41.8, 54.2,
125.5, 126.5, 127.5, 127.8, 128.9, 129.2, 130.6, 132.8,
133.9, 137.2, 140.2, 141.1, 208.8; HRMS (m/z) calcd. for
C17H14Cl2O [M + H]+ 305.0494, found 305.0486.
Synthesis of 1-[bis(trifluoromethoxy)methyl]-2,3-dihydro-
3-methyl-1H-indene (8b)
As for 1a, but using 1b (0.146 g, 1.01 mmol). HTIB
was added at once. The reaction was quenched after
7 min. Compound 8b was obtained as a yellow oil
(70%, 0.243 g, 0.710 mmol) as a 5:1 trans:cis mixture;
IR nmax/cm-1 (film) 2961, 2932, 2872, 1458, 1281, 1174,
1078, 758; 1H NMR (300 MHz, CDCl3) d (trans isomer)
1.27 (d, 3H, J 6.9 Hz), 1.81 (ddd, 1H, J 13.2, 8.5,
7.3 Hz), 2.32 (ddd, 1H, J 13.2, 7.8, 4.2 Hz), 3.22-3.34
(m, 1H), 3.43-3.50 (m, 1H), 3.82-4.06 (m, 4H), 4.64 (d,
1H, J 8.1 Hz), 7.18-7.36 (m, 4H), (cis isomer) 1.33 (d,
3H, J 6.9 Hz), 2.40-2.55 (m, 1H), 4.75 (d, 1H, J 8.4 Hz),
7.08-7.13 (m, 1H), 7.41-7.44 (m, 1H), 7.68-7.72 (m, 1H)
(other signals overlap with the trans form); 13C NMR
(75 MHz, CDCl3) d (trans isomer) 20.5, 35.9, 37.6, 46.0,
61.6 (q, J 34.7 Hz), 63.8 (q, J 34.7 Hz), 105.1, 123.5, 123.6
(q, J 276 Hz), 123.8 (q, J 276 Hz), 125.8, 126.6, 127.8,
140.3, 149.2, (cis isomer) 19.7, 36.9, 37.7, 45.6, 105.7,
123.3, 124.8, 126.7, 127.6, 130.2, 137.5 (other signals
overlap with the trans form); LRMS (m/z, %) (major
diastereomer) 242 (M+· - CF3CH2OH, 17%), 211 (69),
131 (100), (minor diastereomer) 342 (M+·, 3%), 242 (9),
211 (75), 131 (100); HRMS (m/z) calcd. for C15H16F6O2
[M + Na]+ 365.0947, found 365.0960.
Reaction of 9-methyl-6,7-dihydro-5H-benzo[7]annulene
(1p) with HTIB in CH3CN
The typical procedure for reactions in CH3CN was
followed, but using 1p (0.0416 g, 0.263 mmol), molecular
sieves (3 Å, 0.0179 g), HTIB (0.118 g, 0.301 mmol) in
anhydrous CH3CN (2.5 mL). The mixture was stirred
for 15 min at room temperature. The crude product was
purified by flash column chromatography (15% EtOAc in
hexanes) affording 5p43 (0.0241 g, 0.138 mmol, 52%), as
a colorless oil.
Synthesis of 1-(2,3-dihydro-1H-inden-3-yl)ethanone (5h)
As for 1a, but using 1h (0.158 g, 1.10 mmol). The
reaction was quenched after 30 min. The crude product was

1804
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated Ring Contraction
J. Braz. Chem. Soc.
purified by column (5-10% EtOAc in hexane) affording 5h7
(72%, 0.127 g, 0.791 mmol), as a light yellow oil.
Synthesis of 1-(2,3-dihydro-1-methyl-1H-inden-3-yl)-
2-methylpropan-1-one (5m)
As for 1q, but using 1m (0.108 g, 0.580 mmol).
HTIB (1.3 equiv.) was added at 0 ºC and the reaction
was quenched after 2 min at 0 ºC. The crude product was
purified by column (2-30% EtOAc in hexane) affording
5m13 (62%, 0.073 g, 0.359 mmol), as a light yellow oil.
Synthesis of 1-(1,2,3,4-tetrahydronaphthalene-4-yl)
ethanone (5p)
As for 1a, but using 1p (0.158 g, 1.00 mmol). The
reaction was quenched after 20 min. The crude product
was purified using column (hexane:EtOAc, 9:1) giving 5p13
(62%, 0.107 g, 0.62 mmol), as a light yellow oil.
Synthesis of 2,3-dihydro-1H-indene-1-carbaldehyde (5a)
To a stirred solution of 1a (0.122 g, 0.937 mmol) in
HFIP (4.0 mL) was added HTIB (0.404 g, 1.04 mmol) at
0 ºC.After 1 min the reaction was quenched with saturated
solution of Na2S2O3 (5.0 mL). The resulting mixture was
extracted with EtOAc (3 × 10 mL). The organic layer was
washed with brine and dried over anhydrous MgSO4. The
solvent was removed under reduce pressure and the crude
product was purified by column (5-10% EtOAc in hexane)
giving 5a13 (58%, 0.080 g, 0.55 mmol) as a light yellow oil.
Synthesis of 1-(bis(2,2,2-trifluoroethoxy)methyl)-
3-(4-fluorophenyl)-2,3-dihydro-1H-indene (8q)
A dry round bottom flask was charged with 1q
(240 mg, 1.07 mmol), CH2Cl2/TFE (4:1 v/v) followed
by HTIB (550 mg, 1.40 mmol) at room temperature. The
reaction color changed towards yellow within a minute.
After 10 min at room temperature, the reaction was
quenched with H2O, washed with H2O (2 × 20 mL), with
50% NaHCO3 solution (2 × 20 mL), with H2O (20 mL),
with brine (2 × 20 mL), dried over anhydrous Na2SO4, and
filtered. The solvent was removed under reduced pressure
to give a brownish oil. The crude product was purified by
column (0-25% EtOAc in hexane) giving 8q (312 mg,
0.739 mmol, 69%), as a trans:cis (17:1) mixture as colorless
oil; 1H NMR (300 MHz, CDCl3) d (trans isomer) 2.18 (ddd,
1H, 13.5, 8.5, 7.7 Hz), 2.60 (ddd, 1H, J 13,5, 8.2, 4.2 Hz),
3.58 (dt, 1H, J 8.2, 4.2 Hz), 4.11-3.80 (m, 4H), 4.43 (t,
1H, J 8.0 Hz), 4.74 (d, 1H, J 7.9 Hz), 7.03-6.93 (m, 3H),
7.10-7.03 (m, 2H), 7.29-7.20 (m, 2H), 7.47-7.39 (m, 1H);
13C NMR (125 MHz, CDCl3) d (trans isomer) 38.0, 46.5,
49.2, 62.0 (q, J 35 Hz), 64.1 (q, J 35 Hz), 105.3, 115.5 (d,
J 21 Hz), 123.8 (q, J 278 Hz), 123.9 (q, J 278 Hz), 125.4,
126.0, 127.4, 128.3, 129.5 (d, J 8 Hz), 140.8 (d, J 3 Hz),
141.2, 147.2, 161.8 (d, J 245 Hz); HRMS (m/z) calcd. for
C20H17F7O2 [M + Na]+ 445.1009, found 445.1017.
Reaction of 1,2-dihydronaphthalene (1a) with HTIB in
HFIP/CH2Cl2 followed by in situ reduction with NaBH4
To a stirred solution of 1a (0.050 g, 0.38 mmol) in
HFIP (0.8 mL) and CH2Cl2 (3.2 mL) was added at 0 °C
HTIB (0.19 g, 0.49 mmol). The mixture was stirred for
15 min. Then, NaBH4 (0.72 g, 1.9 mmol) was added
and the reaction was allowed to reach room temperature
while stirring for 20 min. Alcohol 9a was obtained as a
mixture with ditosilate 10a as a yellow oil after column
chromatography (AcOEt in hexanes, 1 to 30%). A second
column chromatography (20%AcOEt in hexanes) allowed
complete separation of the products giving 9a44 (48%,
0.027 g, 0.18 mmol) as a yellow oil and 10a (17%, 0.031 g,
0.066 mmol) as a white solid. (2,3-dihydro-1H-inden-
1-yl)methylene bis(4-methylbenzenesulfonate) (10a):
IR nmax/cm-1 (film) 1376, 1193, 1178, 750 cm-1; 1H RMN
(200 MHz, CDCl3) d 2.10-2.21 (m, 2H), 2.41 (s, 3H),
2.44 (s, 3H), 2.75-2.87 (m, 2H), 3.55-3.64 (m, 1H), 6.50
(d, J 3.8 Hz, 1,H), 6.99-7.20 (m, 6H), 7.28-7.32 (m, 2H),
7.44-7.50 (m, 2H), 7.71-7.77 (m, 2H); 13C RMN (75 MHz,
CDCl3) d 21.7, 21.7, 25.3, 31.3, 50.2, 100.6, 124.7, 125.2,
126.3, 127.8, 128.1, 129.6, 129.7, 133.2, 133.5; 138.5,
145.0, 145.1, 145.2; HRMS (m/z) calcd. for C24H24O6S2
[M + Na]+ 495.0907, found 495.0910.
Synthesis of 1-(bis(2,2,2-trifluoroethoxy)methyl)-
2,3-dihydro-1H-indene (8a)
As for 1q, but using 1a (0.130 g, 1.00 mmol). HTIB
(0.510 g, 1.30 mmol) was added at 0 ºC. The reaction was
stirred for 10 min at room temperature. The crude product
was purified by column (1-10% EtOAc in hexane) affording
8a (67%, 0.221 g, 0.673 mmol), as a yellow oil.
Synthesis of 1-(2,3-dihydro-1-methyl-1H-inden-3-yl)
ethanone (5k)
Synthesis of (2,3-dihydro-1H-inden-1-yl)methanol (9a)
To a stirred mixture of 1a (0.13 g, 1.0 mmol) and H2O
(0.40 mL, 22 mmol) was added CH2Cl2/HFIP (16 mL/4 mL)
at 0 ºC. HTIB (0.51 g, 1.3 mmol) was added dropwise.
The mixture was stirred for 5 min at the same temperature.
NaBH4 was added (0.19 g, 5.0 mmol) at room temperature.
The mixture was stirred for 70 min and H2O was added. The
As for 1q, but using 1k (0.158 g, 1.00 mmol). HTIB
(1.3 equiv.) was added at 0 ºC. The reaction was stirred for
10 min at room temperature. The crude product was purified
by column (1-20% EtOAc in hexane) affording 5k7 (76%,
0.132 g, 0.758 mmol), as a light yellow oil.

Vol. 22, No. 9, 2011
Siqueira et al.
1805
resulting mixture was extracted with EtOAc. The organic
layer was washed with brine and dried over anhydrous
MgSO4. The solvent was removed under reduce pressure
and the crude product was purified by column (0-20%
EtOAc in hexane) giving 9a44 (0.109 g, 0.736 mmol, 74%)
as a light yellow oil.
2. For some recent examples, see: Zhang, L.; Herndon, J. W.;
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Ferraz, H. M. C.; Aguilar, A. M.; Silva Jr., L. F.; Tetrahedron
2003, 59, 5817; for a review, see: Ferraz, H. M. C.; Aguilar, A.
M.; Silva Jr., L. F.; Craveiro, M. V.; Quim. Nova 2005, 28, 703.
3. For some recent examples, see: Clark, W. M.; Tickner-Eldridge,
A. M.; Huang, G. K.; Pridgen, L. N.; Olsen, M. A.; Mills, R. J.;
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Marien, M.; J. Med. Chem. 2010, 53, 6986; Baur, F.; Beattie, D.;
Beer, D.; Bentley, D.; Bradley, M.; Bruce, I.; Charlton, S. J.;
Cuenoud, B.;Ernst, R.;Fairhurst, R.A.;Faller, B.;Farr, D.;Keller,
T.; Fozard, J. R.; Fullerton, J.; Garman, S.; Hatto, J.; Hayden,
C.; He, H. D.; Howes, C.; Janus, D.; Jiang, Z. J.; Lewis, C.;
Loeuillet-Ritzler, F.; Moser, H.; Reilly, J.; Steward,A.; Sykes, D.;
Tedaldi, L.; Trifilieff, A.; Tweed, M.; Watson, S.; Wissler, E.;
Wyss, D.; J. Med. Chem. 2010, 53, 3675;Wood, J. L.; Pujanauski,
B. G.; Sarpong, R.; Org. Lett. 2009, 11, 3128; Dinges, J.;Albert,
D. H.; Arnold, L. D.; Ashworth, K. L.; Akritopoulou-Zanze, I.;
Bousquet, P. F.;Bouska, J. J.;Cunha, G.A.;Davidsen, S. K.;Diaz,
G. J.; Djuric, S.W.; Gasiecki,A. F.; Gintant, G.A.; Gracias,V. J.;
Harris,C.M.;Houseman,K.A.;Hutchins,C.W.;Johnson,E.F.;Li,
H.; Marcotte, P.A.; Martin, R. L.; Michaelides, M. R.; Nyein, M.;
Sowin, T. J.; Su, Z.; Tapang, P. H.; Xia, Z. R.; Zhang, H. Q.;
J. Med. Chem. 2007, 50, 2011.
Supplementary Information
Supplementary information concerning spectroscopic
data, experimental procedures and NMR copies are
available free of charge at http://jbcs.sbq.org.br as PDF file.
Acknowledgments
The authors wish to thank The Swedish Foundation
for International Cooperation in Research and Higher
Education (STINT), Fundação de Amparo à Pesquisa do
Estado de São Paulo (FAPESP), Conselho Nacional de
Desenvolvimento Científico e Tecnológico (CNPq) and
Coordenação de Aperfeiçoamento de Pessoal de Nível
Superior (CAPES) for financial support. We thank F.Y. M.
Vieira and E. C. Pedrozo for initial experiments.
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J. Braz. Chem. Soc., Vol. 22, No. 9, S1-S25, 2011.
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Supplementary Information
SI
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated Ring Contraction of
1,2-Dihydronaphthalenes
Fernanda A. Siqueira,a,# Eloisa E. Ishikawa,a André Fogaça,a Andréa T. Faccio,a
Vânia M. T. Carneiro,a Rafael R. S. Soares,a,§ Aline Utaka,a Iris R. M. Tébéka,a
Marcin Bielawski,a,b Berit Olofssonb and Luiz F. Silva Jr.*,a,§
aDepartamento de Química Fundamental, Instituto de Química, Universidade de São Paulo,
CP 26077, 05513-970 São Paulo-SP, Brazil
bDepartment of Organic Chemistry, Arrhenius Laboratory, Stockholm University,
SE-106 91 Stockholm, Sweden
Experimental
Ac2O (2.0 mL). The mixture was stirred for 1 h at room
temperature. The reaction was quenched with MeOH
(10 mL) and H2O (15 mL), extracted with EtOAc
(3 × 15 mL), washed with brine (2 × 10 mL) and dried over
anhydrous MgSO4. The solvent was removed under reduced
pressure and the resulting residue was purified by flash
chromatography (silica gel 200-400 mesh, 60% EtOAc in
hexanes) giving 6-acetamido-1-tetralone5 (92%, 1.16 g,
5.72 mmol) as a light-yellow solid; mp 124.5-126.7 ºC
(124.5-125 ºC)5; 1H NMR (200 MHz, CDCl3) d 2.02-2.17
(m, 2H), 2.22 (s, 3H), 2.62 (t, 2H, J 6.5 Hz), 2.92 (t, 2H,
J 6.0 Hz), 7.27 (dd, 1H, J 2.4 and 8.6 Hz), 7.72 (s, 1H),
7.96 (d, 1H, J 8.4 Hz), 8.31 (1H, s); 13C NMR (75 MHz,
CDCl3) d 23.2, 24.7, 29.9, 38.9, 117.5, 118.5, 128.4, 142.7,
146.3, 169.0, 197.7.
General information
HTIB was used as received. Methanol and acetonitrile
were distilled from magnesium turnings and CaH2,
respectively. These solvents were storaged in a bottle
containing 4 Å molecular sieves. THF and Et2O were
freshly distilled from sodium/benzophenone. Column
chromatography was performed using silica gel
200-400 mesh. TLC analyses were performed using silica
gel plates, using solutions of phosphomolybdic acid and
p-anisaldehyde for visualization. NMR spectra were
recorded using CDCl3 as solvent and TMS as internal
pattern. The substrates 1a, 1b, 1c, 1e, 1g, 1h, 1j and 1k
were prepared as previously described.1-3 See the previous
communication for experimental procedures of the HTIB
oxidations in MeOH with 1a, 1b, 1c, 1d and 1g, and in
MeCN with 1a, 1g and 4l.4
To a stirred solution of 6-acetamido-1-tetralone (1.12 g,
5.50 mmol) in anhydrous MeOH (70 mL) was added NaBH4
(0.25 g, 6.61 mmol) in portions at 0 ºC. The mixture was
stirred for 1 h at room temperature. The reaction was
quenched with H2O (20 mL) and a 10% aqueous solution
of HCl was added dropwise until pH ca. 7. The resulting
solution was extracted with EtOAc (3 × 15 mL), washed
with brine (20 mL) and dried over anhydrous MgSO4.
The solvent was removed under reduced pressure giving
6-acetamido-1-tetralol (78%, 0.882 mg, 4.30 mmol) as a
pale-yellow solid. The 1-tetralol (0.841 g, 4.10 mmol) was
used without purification in a dehydration reaction using
toluene (45 mL), a few crystals of p-TsOH and reaction time
of 3 h at 130 ºC, using a Dean-Stark apparatus. The resulting
residue was purified by flash chromatography (silica gel
200-400 mesh, 80% EtOAc in hexanes) affording 1d6 (95%,
0.728 g, 3.89 mmol) as a pale-yellow solid. Experimental
data has not been previously reported: mp: 89.3-90.6 ºC; IR
Preparation of 1,2-dihydronaphthalenes
7-Acetamido-1,2-dihydronaphthalene (1d)
AcHN
In a solution of 6-amino-1-tetralone (1.00 g, 6.21 mmol)
and DMAP (0.020 g) in Et3N (25 mL) was added
*e-mail: luizfsjr@iq.usp.br
Present addresses: #Universidade Federal de São Paulo, Campus Diadema,
RuaArtur Riedel no. 275, 09972-270, Diadema-SP, Brazil, and §Instituto
Federal de Educação, Ciência e Tecnologia de São Paulo, Rua Pedro
Vicente no. 625, São Paulo-SP, Brazil
n
max/cm-1 (film) 497, 566, 684, 834, 883, 1018, 1266, 1328,
1370, 1421, 1536, 1594, 1666, 2829, 2883, 2933, 3032,
§Dedicated with deep respect to Prof. Miuako K. Kuya

S2
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated
J. Braz. Chem. Soc.
3297; 1H NMR (200 MHz, CDCl3) d 2.14 (s, 3H), 2.20-2.31
(m, 2H), 2.72 (t, 2H, J 8.1 Hz), 5.90-5.99 (m, 1H), 6.40 (d,
1H, J 9.6 Hz), 6.92 (d, 1H, J 8.0 Hz), 7.23 (dd, 1H, J 2.2
and 8.0 Hz), 7.31 (s, 1H), 7.89 (s, 1H); 13C NMR (75 MHz,
CDCl3) d 22.9, 24.4, 27.6, 117.8, 119.4, 126.1, 127.0, 127.6,
130.4, 136.3, 136.5, 168.6; LRMS m/z (%) 187 (M+•, 72%),
146 (9), 145 (61), 144 (100), 130 (29), 115 (24), 91 (8),
77 (6), 51 (5), 43 (23); HRMS (m/z) calcd. for C12H13NO
[M + H]+ 188.1070, found 188.1067.
washed with brine and dried over anhydrous MgSO4. The
solvent was removed under reduced pressure. The crude
product was purified by flash column chromatography
(gradient elution, 0-30% of EtOAc in hexanes), affording
5j7 (1.08 g, 6.20 mmol, 62%), as a colorless oil.
4-n-Butyl-1,2-dihydro-1-methylnaphthalene (1l)
n-Bu
1,2-Dihydro-6-methoxynaphthalene (1f)
MeO
The reaction was performed as indicated for 1i. A
mixture of 4-methyl-1-tetralone (1.42 g, 8.86 mmol)
in Et2O (12.0 mL) was added to a solution of n-BuMgI
[prepared from 1-bromobutane (1,46 g, 10.6 mmol), Mg
(0.245 g, 10.1 mmol), I2 (some crystals) and anhydrous Et2O
(12.0 mL)]. The mixture was refluxed for 3 h. The crude
product was purified by flash column chromatography
(gradient elution, 0-5% of EtOAc in hexanes), affording
the olefin 1l2 (0.805 g, 4.02 mmol, 45%), as a colorless oil.
Starting material was recovered (0.214 g, 1.34 mmol, 15%).
NaBH4 (0.455 g, 12.0 mmol) was added dropwise to
a solution of 7-methoxy-1-tetralone (1.52 g, 8.63 mmol)
in MeOH (50 mL) at 0 ºC. The mixture was stirred at
room temperature. After 2 h, the reaction was quenched
with H2O and a 10% aqueous solution of HCl was added
dropwise until pH ca. 5. The MeOH was removed under
reduced pressure and the residue was extracted with EtOAc,
washed with brine, and dried over anhydrous MgSO4. The
solvent was removed under reduced pressure. The crude
corresponding 1-tetralol was dissolved in THF (10 mL)
and H3PO4 85% (4.5 mL) was added dropwise at room
temperature. The mixture was refluxed at 95 ºC for 2 h. The
crude product was transferred to an Erlenmeyer and diluted
with Et2O. A sat. solution of NaHCO3 was added until
ca. pH 7. The solution was extracted with Et2O, washed
with sat. solution of NaCl and dried over anhydrous MgSO4.
The residue was purified by flash column chromatography
(gradient elution, 0-30% EtOAc in hexanes), affording
1f2 (0.885 g, 5.52 mmol, 64%), as a colorless oil. Starting
material was also recovered (0.0089 g, 0.0555 mmol, 1%),
as a colorless oil.
1,2-Dihydro-4-isopropyl-1-methylnaphthalene (1m)
The reaction was performed as indicated for 1i. A
mixture of 4-methyl-1-tetralone (0.961 g, 6.00 mmol) in
Et2O (4.0 mL), i-PrMgI [prepared from 2-bromopropane
(1.93 g, 15.7 mmol), Mg (0.321 g, 13.2 mmol), I2 (some
crystals) in anhydrous Et2O (6.0 mL)] was stirred for
5.5 h. The crude product was purified by flash column
chromatography (gradient elution, 0-20% of EtOAc in
hexanes), affording 1m8 (0.387 g, 2.08 mmol, 35%) as a
colorless oil.
1,2-Dihydro-7-methoxy-4-methylnaphthalene (1i)
1,2-Dihydro-1-methyl-4-phenylnaphthalene (1n)
MeO
Ph
A solution of 6-methoxy-1-tetralone (1.76 g, 10.0 mmol)
in Et2O (7.0 mL) was added to a solution of MeMgI
[prepared from MeI (1.7 mL, 27.0 mmol), Mg (0.673 g,
27.7 mmol) and I2 (some crystals) in anhydrous Et2O
(7.0 mL)]. The mixture was refluxed for 4.5 h. After that,
a solution of HCl 6 mol L-1 (6 mL) was added dropwise
at 0 °C. The solution was stirred for 15 min at room
temperature. The organic layer was extracted with Et2O,
The reaction was performed as indicated for 1i. A
mixture of 4-methyl-1-tetralone (0.641 g, 4.00 mmol) in
Et2O (0.5 mL) and PhMgBr [prepared from bromobenzene

Vol. 22, No. 9, 2011
Siqueira et al.
S3
(0.792 g, 5.04 mmol), Mg (0.117 g, 4.81 mmol), I2 (some
crystals) in anhydrous Et2O (1.0 mL)] was refluxed for
1.5 h. The crude product was purified by flash column
chromatography (gradient elution, 10-15% of EtOAc
in hexanes), affording the 1,2-dihydronaphthalene 1n9
(0.682 g, 3.10 mmol, 78%), as a colorless oil.
(75 MHz, CDCl3) d 19.8, 31.4, 32.1, 125.3, 126.2, 126.2,
127.4, 127.7, 128.1, 130.2, 130.5, 131.0, 132.3, 133.4,
137.5, 140.9, 141.5; HRMS (m/z) calcd. for C14H20O4
[M + Na]+ 275.1254, found 275.1252.
6,7-Dihydro-9-methyl-5H-benzo[7]annulene (1p)
4-(3,4-Dichlorophenyl)1,2-dihydro-1-methylnaphthalene
(1o)
Cl
Cl
The reaction was performed as indicated for 1i. A
mixture of 1-benzosuberone (0.481 g, 3.00 mmol) in
anhydrous Et2O (2.0 mL), MeMgI [prepared from MeI
(0.5 mL, 8.10 mmol), Mg (0.202 g, 8.31 mmol) and I2
(some crystals) in anhydrous Et2O (2.0 mL)] was stirred
for 4 h under reflux. The crude product was purified by
flash column chromatography (gradient elution, 0-10% of
EtOAc in hexanes), affording 1p10 (0.403 g, 2.55 mmol,
85%), as a colorless oil.
The reaction was performed as indicated for 1i. A
mixture of 4-methyl-1-tetralone (0.645 g, 4.03 mmol) in
Et2O (0.5 mL) and 1,2-ClPhMgBr [prepared from 4-bromo-
1,2-dichlorobenzene (1.15 g, 5.09 mmol), Mg (0.117 g,
4.81 mmol), I2 (some crystals) in anhydrous Et2O (1.0 mL)]
was refluxed for 2 h. The crude product was purified by
flash column chromatography (gradient elution, 10-30% of
EtOAc in hexanes), affording the 1-(3,4-dichloropheny)-
1,2,3,4-tetrahydro-4-methylnaphthalen-1-ol (0.870 g,
2.83 mmol, 70%), as a colorless oil. The isolated alcohol
was dissolved in anhydrous toluene (3.5 mL). Some crystals
of p-toluenesulfonic acid were added to that solution. The
reaction was refluxed for 6 h. The reaction was extracted
with EtOAc. The organic phase was washed with H2O,
saturated solution of NaHCO3, saturated solution of NaCl
and dried over anhydrous MgSO4. The crude product
was purified by flash column chromatography (isocratic
elution with hexanes), furnishing the desired alkene 1o
(0.385 g, 1.33 mmol, 56%), as a colorless oil; IR nmax/cm-1
(film) 1121, 1258, 1515, 2830, 2934; 1H NMR (300 MHz,
CDCl3) d 1.30 (d, 1H, J 7,0 Hz), 2.22 (ddd, 1H, J 16.8,
7.7 and 5.0 Hz), 2.55 (ddd, 1H, J 16.8, 6.5 and 4.4 Hz),
2.98 (sext, 1H, J 7.0 Hz), 6.00 (t, 1H, J 4.7 Hz), 6.93-6.96
(m, 1H), 7.10-7.26 (m, 4H), 7.42-7.46 (m, 1H); 13C NMR
References
1. Ferraz, H. M. C.; Carneiro, V. M. T.; Silva Jr., L. F.; Synthesis
2009, 385 (see ref. 13 in the article).
2. Ferraz, H. M. C.; Silva Jr., L. F.; Vieira, T. O.; Tetrahedron
2001, 57, 1709 (see ref. 9 in the article).
3. Silva Jr., L. F.; Sousa, R. M. F.; Ferraz, H. M. C.;Aguilar,A. M.;
J. Braz. Chem. Soc. 2005, 16, 1160 (see ref. 8 in the article).
4. Silva Jr., L. F.; Siqueira, F. A.; Pedrozo, E. C.; Vieira, F. Y. M.;
Doriguetto, A. C.; Org. Lett. 2007, 9, 1433 (see ref. 7 in the
article).
5. Allinger, N. L.; Jones, E. S.; J. Org. Chem. 1962, 27 70.
6. Kato, K.; Terauchi, J.; Mori, M.; Suzuki, N.; Shimomura, Y.;
Takekawa, S.; Ishihara, Y.; PCT Int. Appl. WO 2001021577
2001, 363.
7. Radcliffe, M. M.; Weber, W. P.; J. Org. Chem. 1977, 42, 297.
8. Bhonsle, J. B.; Indian J. Chem. B 1995, 34B, 372.
9. Newman, M. S.; Anderson, H. V.; Takemura, K. H.; J. Am.
Chem. Soc. 1953, 75, 347.
10. Russel, M. G. N.; Baker, R.; Billington, D. C.; Knight, A. K.;
Middlemiss, D. N.; Noble,A. J.; J. Med. Chem. 1992, 35, 2025.

S4
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated
J. Braz. Chem. Soc.
Figure S1. 1H NMR spectrum of 2d (CDCl3, TMS, 200 MHz, d).
Figure S2. 13C NMR spectrum of 2d (CDCl3, TMS, 50 MHz, d).

Vol. 22, No. 9, 2011
Siqueira et al.
S5
Figure S3. 1H NMR spectrum of trans-3d (CDCl3, TMS, 200 MHz, d).
Figure S4. 1H NMR spectrum of cis-3d (CDCl3, TMS, 200 MHz, d).

S6
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated
J. Braz. Chem. Soc.
Figure S5. 13C NMR spectrum of cis-3d (CDCl3, TMS, 75 MHz, d).
Figure S6. 1H NMR spectrum of cis-3f (CDCl3, TMS, 500 MHz, d).

Vol. 22, No. 9, 2011
Siqueira et al.
S7
Figure S7. 13C NMR spectrum of cis-3f (CDCl3, TMS, 75 MHz, d).
Figure S8. 1H NMR spectrum of 2g (CDCl3, TMS, 300 MHz, d).

S8
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated
J. Braz. Chem. Soc.
Figure S9. 13C NMR spectrum of 2g (CDCl3, TMS, 75 MHz, d).
Figure S10. 1H NMR spectrum of trans-3g (CDCl3, TMS, 300 MHz, d).

Vol. 22, No. 9, 2011
Siqueira et al.
S9
Figure S11. 13C NMR spectrum of trans-3g (CDCl3, TMS, 75 MHz, d).
Figure S12. 1H NMR spectrum of 1o (CDCl3, TMS, 300 MHz, d).

S10
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated
J. Braz. Chem. Soc.
Figure S13. 1H NMR spectrum of 1o (CDCl3, TMS, 300 MHz, d) - expansion.
Figure S14. 13C NMR spectrum of 1o (CDCl3, TMS, 75 MHz, d).

Vol. 22, No. 9, 2011
Siqueira et al.
S11
Figure S15. 13C NMR spectrum of 1o (CDCl3, TMS, 75 MHz, d) - expansion.
Figure S16. DEPT 135 spectrum of 1o (CDCl3, TMS, 75 MHz, d).

S12
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated
J. Braz. Chem. Soc.
Figure S17. 1H NMR spectrum of 1q (CDCl3, TMS, 400 MHz, d).
Figure S18. 13C NMR spectrum of 1q (CDCl3, TMS, 75 MHz, d).

Vol. 22, No. 9, 2011
Siqueira et al.
S13
Figure S19. 1H NMR spectrum of 5l (CDCl3, TMS, 300 MHz, d).
Figure S20. 13C NMR spectrum of 5l (CDCl3, TMS, 75 MHz, d).

S14
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated
J. Braz. Chem. Soc.
Figure S21. 1H NMR spectrum of 5m (CDCl3, TMS, 300 MHz, d).
Figure S22. 13C NMR spectrum of 5m (CDCl3, TMS, 75 MHz, d).

Vol. 22, No. 9, 2011
Siqueira et al.
S15
Figure S23. 1H NMR spectrum of 5n (CDCl3, TMS, 500 MHz, d).
Figure S24. 13C NMR spectrum of 5n (CDCl3, TMS, 75 MHz, d).

S16
Metal-Free Synthesis of Indanes by Iodine(III)-Mediated
J. Braz. Chem. Soc.
Figure S25. DEPT 135 spectrum of 5n (CDCl3, TMS, 75 MHz, d).
Figure S26. 1H NMR spectrum of 6n (CDCl3, TMS, 300 MHz, d).

Vol. 22, No. 9, 2011
Siqueira et al.
S17
Figure S27. 13C NMR spectrum of 6n (CDCl3, TMS, 75 MHz, d).
Figure S28. 1H NMR spectrum of 5o (CDCl3, TMS, 500 MHz, d).