Model studies toward the synthesis of natural indans utilizing a thallium(III)-mediated ring-contraction reaction

Article abstract of DOI:10.1055/s-2003-39172

6-Methoxy-1-tetralone was transformed in six steps into an indan derivative related to the sesquiterpenes mutisianthol and jungianol. Key steps involve a thallium(III)-promoted ring-contraction (to assemble the indan unit) and a Wittig olefination (to attach the side chain).

Full text of DOI:10.1055/s-2003-39172

PAPER
1031
Model Studies Toward the Synthesis of Natural Indans Utilizing a
Thallium(III)-Mediated Ring-Contraction Reaction
Studies
T
oward th
e
e
S
ynthesis
l
of
N
at
e
ural Indansna M. C. Ferraz,* Andrea M. Aguilar, Luiz F. Silva Jr.
Instituto de Química, Universidade de São Paulo, CP 26077, CEP 05513-970, São Paulo SP, Brazil
E-mail: hmferraz@iq.usp.br
Received 10 December 2002; revised 25 March 2003
The starting material for this study was the commercially
available 6-methoxy-1-tetralone (3), which was trans-
formed into the corresponding 1,2-dihydronaphthalene 4
by reduction followed by dehydration. The next step was
the thallium(III)-promoted oxidative rearrangement of 4,
which gave the desired ring-contracted product 5 in excel-
lent yield (Scheme 2).
Abstract: 6-Methoxy-1-tetralone was transformed in six steps into
an indan derivative related to the sesquiterpenes mutisianthol and
jungianol. Key steps involve a thallium(III)-promoted ring-contrac-
tion (to assemble the indan unit) and a Wittig olefination (to attach
the side chain).
Key words: indan, jungianol, mutisianthol, ring contraction, thalli-
um trinitrate
MeO
O
OMe
The synthesis of sesquiterpenes possessing a fused bicy-
clic system has been an important theme in organic chem-
istry for decades.1 Synthetic targets include the indan ring
system, which is present in phenolic sesquiterpenes such
as mutisianthol2–4 and jungianol4,5 (Figure 1).
a, b
c
92%
90%*
MeO
MeO
MeO
5
3
4
* based on
recovered sm
Scheme 2 Reagents and Conditions: a) NaBH4, MeOH, r.t.; b) p-
TsOH, benzene, reflux; c) TTN, trimethyl orthoformate (TMOF),
0 °C
OH
During the oxidation of 4, the formation of non-rear-
ranged products, such as dimethoxylated diols did not oc-
cur, in contrast to the results observed with other
methoxy-substituted 1,2-dihydronaphthalenes previously
investigated (6 and 7, Figure 2).6 This different behavior
can be attributed to the position of the methoxy group in
the aromatic ring of 4, which is prone to donate electrons
to the migrating carbon, facilitating the rearrangement.
The same effect is not possible for olefins 6 and 7.
HO
Jungianol
Mutisianthol
Figure 1 Structures of sesquiterpenes mutisianthol and jungianol
Recently, we found that the ring contraction of 1-methyl-
1,2-dihydronaphthalene (1), promoted by thallium trini-
trate (TTN), led to the indan 2, as outlined in Scheme 1.6
Such an indan shows the same relative configuration of
mutisianthol and jungianol, as well as a protected alde-
hyde group, which could be used to introduce the olefin
moiety present in the side chain. Thus, we consider the
possibility of applying this ring contraction to the total
syntheses of mutisianthol and of jungianol. A model study
for these syntheses, namely the construction of the indan
15, closely related to the target molecules, is presented
here.
MeO
6
7
OMe
Figure 2 Structures of 6-methoxy-1,2-dihydronaphthalene (6) and
8-methoxy-1,2-dihydronaphthalene (7)
Similar to the olefin 4, the 1,2-dihydronaphthalene 8,
when treated with TTN, afforded the indan derivative 9,
as the only product (Scheme 3).
MeO
OMe
TTN
MeOH
87%
Therefore, these results show that the presence of an elec-
tron-donating group at the p-position of the migrating car-
1
2
Scheme 1
MeO
OMe
TTN
TMOF
MeO
MeO
77%
Synthesis 2003, No. 7, Print: 20 05 2003.
Art Id.1437-210X,E;2003,0,07,1031,1034,ftx,en;M05302SS.pdf.
8
9
© Georg Thieme Verlag Stuttgart · New York
Scheme 3

1032
H. M. C. Ferraz et al.
PAPER
Li
bon 4a plays an important role in the ring contraction of
1,2-dihydronaphthalenes. A plausible mechanism for
such a rearrangement is exemplified for the olefin 4 in
Scheme 4.7
HO
SePh
SePh
42%
10
MeO
SOCl2
NEt3
CH2Cl2
11
X
X
73%
X
X
Tl
TlX3
-X-
MeOH
-H+
Tl
4
OMe
Ph3PCH(CH3)2Br
(X=ONO2)
OMe
n-BuLi, THF
10
OMe
OMe
57%
MeO
X
12
OMe
Tl
-X-, -TlX
MeO
4a
X
Scheme 6
MeO
MeO
MeO
MeOH
-H+
OMe
mide 14 as the main product, together with minor amounts
of 13. Eventually, we succeeded in deprotecting 12 under
basic conditions. Thus, treatment of 12 with sodium
ethanethiolate gave the required indan derivative 15 in an
acceptable yield (Scheme 7).
5
Scheme 4
The next step in the synthetic sequence toward the target
molecule 15 is the deprotection of the acetal group in 5,
which was done by treatment with trifluoroacetic acid af-
fording the aldehyde 10 in 98% yield (Scheme 5). This re-
action was also performed utilizing AcOH, however, a
slightly lower yield (94%) was observed.
Br
i) 2 eq. BBr3, CH2Cl2
ii) H2O
12
71%
HO
13
Br
i) 0.5 eq. BBr3, CH2Cl2
ii) H2O
MeO
OMe
CHO
TFA, CHCl3
12
H2O
MeO
98%
MeO
(72%) + 13 (15%)
14
MeO
5
10
Scheme 5
i) EtSH, DMF, NaH
ii) NH4Cl
12
With the desired aldehyde 10 in hand, our attention turned
toward the introduction of the olefin moiety, which
proved to be the most difficult step in the synthetic se-
quence. Our first choice for the transformation of the al-
dehyde 10 into the olefin 12 was a Wittig reaction, which
indeed gave the best result. However, good yields for this
reaction were obtained only after significant experimenta-
tion of the reaction conditions, and during this time other
approaches, such as Peterson olefination8 and elimination
of -hydroxyselenides,9,10 were also tested. Scheme 6
summarizes the two best conditions to prepare indan 12
from aldehyde 10.
63%
HO
15
Scheme 7
In summary, an efficient six-step sequence was developed
to transform a commercially available tetralone into an in-
dan possessing structural features of the natural sesquiter-
penes mutisianthol and jungianol. The application of the
present sequence, in conjunction with our previous studies
for the construction of trans-1,3-disubstituted indans (see
Scheme 1), should lead to an efficient approach to the
mentioned target molecules.
The last step to obtain the indan 15 was the cleavage of the
methyl ether of 12 to the phenolic hydroxyl group. One of
the most used reagents to achieve such a transformation is
the Lewis acid, boron tribromide.11 The desired deprotec-
tion did take place utilizing 2 equivalents of BBr3 in
CH2Cl2. However, addition of HBr to the double bond was
also observed, and the bromide 13 was the only isolated
product.
Information concerning general experimental methods was recently
published.7a Warning! Thallium salts are toxic and must be handled
with care.
7-Methoxy-1,2-dihydronaphthalene (4)
To a stirred solution of the commercially available 6-methoxy-1-te-
tralone (0.503 g, 2.86 mmol) in anhyd EtOH (7 mL), was added
NaBH4 (54.7 mg, 1.45 mmol) in portions at r.t. The mixture was
heated at the reflux temperature for 15 min. After cooling, the reac-
tion was quenched with H2O (7 mL) and the solvent was removed
under reduced pressure. The remaining solution was extracted with
BBr3 has already been used in the deprotection of phenol-
ic ethers bearing an alkenyl moieties.12,13 Even by de-
creasing the amount of BBr3, addition to the double bond
continued to be the predominant pathway giving the bro-
Synthesis 2003, No. 7, 1031–1034 ISSN 1234-567-89 © Thieme Stuttgart · New York

PAPER
Studies Toward the Synthesis of Natural Indans
1033
benzene (2 × 11 mL) and dried (Na2SO4). After filtration, a few
crystals of p-TsOH were added to the filtrate and the mixture was
heated for 3 h using a Dean–Stark apparatus. The organic phase was
washed with 5% aq NaHCO3 (2 ×), brine, and dried (Na2SO4). The
solvent was removed under reduced pressure and the yellow oil ob-
tained was chromatographed on silica gel (80–230 mesh, 20%
EtOAc in hexanes) to afford 414 (0.320 g, 71%) as a colorless oil,
and 6-methoxy-1-tetralone (0.106 g, 21%).
8
IR (film): 1609, 1460, 707 cm–1.
1H NMR (300 MHz, CDCl3): = 2.18 (s, 3 H), 2.23–2.31 (m, 2 H),
2.66–2.71 (m, 2 H), 3.80 (s, 3 H), 5.97 (dt, 1 H, J = 9.6, 4.4 Hz),
6.41 (dt, 1 H, J = 9.6, 1.8 Hz), 6.53 (s, 1 H), 6.86 (s, 1 H).
13C NMR (75 MHz, CDCl3): = 15.9, 23.6, 26.6, 55.5, 108.3, 124.8,
127.1, 127.8, 128.0, 129.9, 132.6, 156.3.
MS: m/z (%) = 174 (M+, 100).
1-Dimethoxymethyl-5-methoxyindan (5); Typical Procedure
To a stirred solution of 4 (2.26 g, 14.1 mmol) in TMOF (70 mL),
was added TTN (6.90 g, 15.5 mmol) at 0 °C, which promptly dis-
solved. The mixture was stirred for 1 min at r.t. leading to an abun-
dant precipitation. The resulting suspension was filtered through a
silica gel pad (70–230 mesh, ca. 10 cm) using CH2Cl2 as eluent. The
filtrate was washed with H2O (2 ×), brine, and dried (MgSO4). The
solution was concentrated under reduced pressure to give a yellow
oil which was purified by flash chromatography [silica gel 200–400
mesh, eluent: hexanes (80%), CH2Cl2 (10%) and EtOAc (10%)] to
afford 5 (2.87 g, 92%) as a colorless oil.
Anal. Calcd for C12H14O: C, 82.72, H, 8.10. Found: C, 82.51, H,
7.91.
1-Dimethoxymethyl-6-methoxy-5-methylindan (9)
The reaction was performed following the procedure above de-
scribed for 5, but using 8 (0.0510 g, 0.293 mmol), TMOF (1.5 mL),
TTN·3H2O (0.143 g, 0.322 mmol) with a reaction time of 1 min.
The crude product was purified by flash chromatography [silica gel
200–400 mesh, eluent: hexanes (80%), CH2Cl2 (10%) and EtOAc
(10%)] to give the indan 9 (0.0533 g, 77%) as a colorless oil.
IR (film): 1121, 2830 cm–1.
IR (film): 1254, 2831 cm–1.
1H NMR (300 MHz, CDCl3): = 1.90–2.02 (m, 1 H), 2.14–2.26 (m,
1 H), 2.18 (s, 3 H), 2.70–2.90 (m, 2 H), 3.38 (s, 3 H), 3.41–3.44 (m,
1 H), 3.44 (s, 3 H), 3.82 (s, 3 H), 4.30 (d, J = 7.7 Hz, 1 H), 6.95 (s,
1 H), 6.97 (s, 1 H).
13C NMR (75 MHz, CDCl3): = 16.3, 27.9, 30.6, 47.6, 52.6, 54.3,
55.5, 107.4, 107.6, 125.3, 126.1, 136.1, 141.2, 156.6.
1H NMR (300 MHz, CDCl3): = 1.93–2.00 (m, 1 H), 2.17–2.24 (m,
1 H), 2.78–2.84 (m, 1 H), 2.88–2.94 (m, 1 H), 3.36 (s, 3 H), 3.37–
3.40 (m, 1 H), 3.42 (s, 3 H), 3.77 (s, 3 H), 4.27 (d, J = 4.5 Hz, 1 H),
6.71 (dd, J = 5.0, 1.5 Hz, 1 H), 6.75 (d, J = 1.5 Hz, 1 H), 7.30 (d,
J = 5.0 Hz, 1 H).
13C NMR (75 MHz, CDCl3): = 27.8, 31.6, 46.6, 52.9, 54.1, 55.3,
107.5, 109.7, 112.1, 126.0, 134.9, 146.3, 159.2.
MS: m/z (%) = 236 (M+, 8), 75 (100).
MS: m/z (%) = 222 (M+, 3), 75 (100).
Anal. Calcd for C14H20O3: C, 71.16, H, 8.53. Found: C, 71.22, H,
8.55.
Anal. Calcd for C13H18O3: C, 70.24; H, 8.16. Found: C, 70.11; H,
7.85.
5-Methoxyindan-1-carbaldehyde (10)
To a stirred solution of the acetal 5 (0.390 g, 1.76 mmol) in CHCl3
(5 mL), was added an aq 50% solution of trifluoroacetic acid (2.5
mL) at 0 °C. The mixture was stirred for 20 min at 0 °C and for 2.5
h at r.t. A sat. aq solution of NaHCO3 was added dropwise at 0 °C
until pH 7 and the mixture was extracted with CHCl3 (3 × 20 mL).
The combined organic phases were washed with aq sat. solution of
NaHCO3, H2O, and brine and dried (Na2SO4). The solution was
concentrated under reduced pressure to give 10 (0.303 g, 98%) as a
yellow oil.
6-Methoxy-7-methyl-1,2-dihydronaphthalene (8)
To a stirred solution of 7-methoxy-6-methyl-3,4-dihydro-2H-naph-
thalen-1-one15 (0.176 g, 0.927 mmol) in anhyd EtOH (2 mL) under
N2, was added NaBH4 (0.0442 g, 1.17 mmol) in portions at 0 °C.
The mixture was stirred for 26 h at r.t. and then the reaction was
quenched with H2O (3 mL) at 0 °C. Aq 10% HCl was added until
pH 5. The organic phase was extracted with Et2O (3 × 20 mL), and
the combined organic layers were washed with sat. aq solution of
NaHCO3 (2 ×), brine and dried (MgSO4). The crude product ob-
tained by removal of the solvent under reduced pressure was puri-
fied by flash chromatography [silica gel 200–400 mesh, eluent:
hexanes (80%) and EtOAc (20%)] to afford 7-methoxy-6-methyl-
1,2,3,4-tetrahydronaphthalen-1-ol (0.142 g, 80%) as a white solid;
mp 66.8–67.6 °C.
IR (film): 1720 cm–1.
1H NMR (300 MHz, CDCl3): = 2.26–2.49 (m, 2 H), 2.89–3.07 (m,
2 H), 3.79 (s, 3 H,), 3.86 (ddd, J = 8.5, 5.8 , 3.0 Hz, 1 H), 6.77 (dd,
J = 8.3, 2.5 Hz, 1 H), 6.83–6.84 (m, 1 H), 7.17 (d, J = 8.3 Hz, 1 H),
9.62 (d, J = 3.0 Hz, 1 H).
13C NMR (75 MHz, CDCl3): = 25.9, 32.0, 55.4, 57.1, 110.6, 112.7,
125.5, 130.4, 146.5, 160.1, 200.7.
MS: m/z (%) = 176 (M+, 7), 147 (100).
7-Methoxy-6-methyl-1,2,3,4-tetrahydronaphthalen-1-ol
1H NMR (300 MHz, CDCl3): = 1.68–2.01 (m, 5 H,), 2.17 (s, 3 H),
2.55–2.75 (m, 2 H), 3.80 (s, 3 H), 4.70 (t, J = 4.9 Hz, 1 H), 6.85 (s,
1 H), 6.88 (s, 1 H).
13C NMR (75 MHz, CDCl3): = 15.8, 19.1, 28.3, 32.6, 55.4, 68.4,
109.6, 126.3, 128.5, 131.0, 137.0, 156.2.
HRMS: m/z Calcd for C11H12O2: 176.0837. Found: 176.0816.
5-Methoxy-1-(2-methylpropenyl)indan (12)
Method A (via Wittig Reaction): To a stirred solution of
Ph3CHMe2Br16 (0.139 g, 0.362 mmol) in anhyd THF (2 mL) under
N2, was added dropwise BuLi (2.09 M in hexanes, 0.17 mL, 0.36
mmol) at 10 °C. The resulting red solution was stirred for 20 min at
10 °C. Then, a solution of the aldehyde 10 (0.0633 g, 0.360 mmol)
in anhyd THF (2 mL) was added dropwise and the mixture was
stirred for 30 min at 10 °C. The reaction was quenched with H2O (3
mL) and extracted with Et2O (3 × 20 mL). The combined organic
phases were washed with brine and dried (MgSO4). The solution
was concentrated under reduced pressure to give a yellow solid.
This was purified by flash chromatography [silica gel 200–400
mesh, eluent: hexanes (80%), CH2Cl2 (10%) and EtOAc (10%)] to
To a stirred solution of 7-methoxy-6-methyl-1,2,3,4-tetrahy-
dronaphthalen-1-ol (0.117 g, 0.610 mmol) in benzene (3 mL) were
added a few crystals of p-TsOH. The mixture was stirred at r.t. for
4 h and then diluted with hexanes. The mixture was washed with an
5% aq solution of NaHCO3 (2 ×), brine and dried (MgSO4). Re-
moval of the solvent under reduced pressure gave a colorless crude
product which was purified by flash chromatography [silica gel
200–400 mesh, eluent: hexanes (95%) and EtOAc (5%)] to give 8
(0.0784 g, 74%) as a white solid; mp 49.6–50.4 °C.
Synthesis 2003, No. 7, 1031–1034 ISSN 1234-567-89 © Thieme Stuttgart · New York

1034
H. M. C. Ferraz et al.
PAPER
afford the starting material 10 (0.0048 g, 8%), and the product 12
(0.0411 g, 57%) as a colorless oil.
IR (film): 1606, 805 cm–1.
1H NMR (300 MHz, CDCl3): = 1.64–1.75 (m, 1 H), 1.76 (s, 3 H),
1.77 (s, 3 H), 2.26–2.36 (m, 1 H), 2.76–2.93 (m, 2 H), 3.78 (s, 3 H),
3.85–3.94 (m, 1 H), 5.12–5.17 (m, 1 H), 6.70 (dd, J = 8.2, 2.5 Hz, 1
H), 6.77–6.78 (m, 1 H), 6.95–6.98 (m, 1 H).
13C NMR (75 MHz, CDCl3): = 18.2, 25.8, 32.0, 34.4, 43.5, 55.5,
109.9, 112.0, 124.5, 128.5, 132.0, 139.4, 145.4, 158.8.
and the resulting black oil was purified by flash chromatography
(30% EtOAc in hexanes) to give the impure starting material (0.026
g), and 15 (0.0270 g, 63%) as a yellow solid; mp 61.5–62.3 °C.
IR (film): 3786, 1222, 1671, 815 cm–1.
1H NMR (300 MHz, CDCl3): = 1.63–1.73 (m, 1 H), 1.76 (s, 3 H),
1.77 (s, 3 H), 2.25–2.35 (m, 1 H), 2.74–2.91 (m, 2 H), 3.87 (q,
J = 8.7 Hz, 1 H), 4.56 (br, 1 H), 5.11–5,15 (m, 1 H), 6.61 (dd,
J = 8.0, 2.4 Hz, 1 H), 6.69 (m, 1 H), 6.90 (d, J = 8.0 Hz, 1 H).
13C NMR (75 MHz, CDCl3): = 18.1, 25.8, 31.8, 34.3, 43.4, 111.3,
113.1, 124.7, 128.4, 132.0, 139.4, 145.7, 154.4.
MS: m/z (%) = 202 (M+, 47), 187 (100).
MS: m/z (%) = 188 (M+, 37), 173 (100).
HRMS: m/z Calcd for C14H18O: 202.1358. Found: 202.1370.
HRMS: m/z Calcd for C13H16O: 188.1201. Found: 188.1243.
Method B (via Selenide Addition Followed by SOCl2): To a stirred
solution of 2,2-bis(phenylseleno)propane17 (0.211 g, 0.595 mmol)
in anhyd THF (1.0 mL) under N2, was added dropwise BuLi (2.35
M in hexanes, 0.25 mL, 0.59 mmol) at –72 °C. The mixture was
stirred for 7 min and a solution of the aldehyde 10 (0.105 g, 0.594
mmol) in anhyd THF (1.5 mL) was added. The mixture was stirred
for 30 min at –72 °C. The reaction was quenched with an aq sat. so-
lution NH4Cl (3 mL) and allowed to warm to r.t. The aqueous phase
was extracted with Et2O (3 × 20 mL), washed with brine, and dried
(MgSO4). The solution was concentrated under reduced pressure to
give a yellow oil, which was purified by flash chromatography (sil-
ica gel 200–400 Mesh, 20% EtOAc in hexanes) to afford 11 (0.0930
g, 42%) as a pale yellow oil.
Acknowledgments
We are grateful for the continuous financial support provided by
FAPESP, CNPq and CAPES. The authors wish to thank the Institu-
to de Química of UNICAMP for the HRMS analysis.
References
(1) For examples, see: (a) Corey, E. J.; Cheng, X.-M. The Logic
of Chemical Synthesis; Wiley: New York, 1989. (b) Fraga,
B. M. Nat. Prod. Rep. 2001, 18, 650.
(2) Bohlmann, F.; Zdero, C.; Le Van, N. Phytochemistry 1979,
18, 99.
(3) Ho, T.-L.; Lee, K.-Y.; Chen, C.-K. J. Org. Chem. 1997, 62,
3365.
(4) The relative configuration of mutisianthol and of jungianol
was assigned by Bohlmann and co-workers2,5 as cis.
However, synthetic studies of Ho and his group3 have shown
that the correct configuration for mutisianthol is trans.
Moreover, the same group proposed that jungianol might
also have a trans relationship.
(5) Bohlmann, F.; Zdero, C. Phytochemistry 1977, 16, 239.
(6) Ferraz, H. M. C.; Silva, L. F. Jr.; Vieira, T. O. Tetrahedron
2001, 57, 1709.
11
IR (film): 1112, 3492 cm–1.
1H NMR (300 MHz, CDCl3): = 1.48 (s, 3 H), 1.49 (s, 3 H), 1.99–
2.10 (m, 1 H), 2.30 (br, 1 H), 2.25–2.38 (m, 1 H), 2.76–2.87 (m, 1
H), 2.91–3.00 (m, 1 H), 3.44–3.49 (m, 1 H), 3.76 (s, 3 H), 3.97 (d,
J = 1.4 Hz, 1 H), 6.69–6.76 (m, 2 H), 6.89–6.91 (m, 1 H), 7.30–7.44
(m, 3 H), 7.65–7.69 (m, 2 H).
13C NMR (75 MHz, CDCl3): = 25.2, 25.9, 27.4, 32.5, 45.0, 54.6,
55.4, 77.5, 109.9, 112.6, 123.4, 127.2, 128.9, 128.9, 137.4, 138.3,
145.9, 159.1.
MS: m/z (%) = 376 (M+, 0.5), 147 (100).
(7) For additional aspects of the mechanism of thallium(III)-
mediated ring contraction of 1,2-dihydronaphthalenes, see:
(a) Ferraz, H. M. C.; Silva, L. F. Jr. Tetrahedron 2001, 57,
9939. (b) Ferraz, H. M. C.; Silva, L. F. Jr. Synthesis 2002,
1033. (c) Silva, L. F. Jr. Tetrahedron 2002, 58, 9137.
(8) Cohen, T.; Sherbine, J. P.; Matz, J. R.; Hutchins, R. R.;
McHenry, B. M.; Willey, P. R. J. Am. Chem. Soc. 1984, 106,
3245.
(9) Rémion, J.; Krief, A. Tetrahedron Lett. 1976, 3743.
(10) Krief, A.; Dumart, W.; Clarembeau, M.; Bernard, G.;
Badaoui, E. Tetrahedron 1989, 45, 2005.
(11) McOmie, J. F. W.; Watts, M. L.; West, D. E. Tetrahedron
1968, 24, 2289.
(12) Kopcho, J. J.; Schaeffer, J. C. J. Org. Chem. 1986, 51, 1620.
(13) Inoue, M.; Carson, M. W.; Frontier, A. J.; Danishefsky, S. J.
J. Am. Chem. Soc. 2001, 123, 2289.
(14) Radcliffe, M. M.; Weber, W. P. J. Org. Chem. 1977, 42, 297.
(15) Zubaidha, P. K.; Chavan, S. P.; Racherle, U. S.; Ayyangar,
N. R. Tetrahedron 1991, 47, 5759.
(16) Fagerlund, U. H. M.; Idler, D. R. J. Am. Chem. Soc. 1957,
79, 6473.
(17) Clarembeau, M.; Cravador, A.; Dumont, W.; Hevesi, L.;
Krief, A.; Luchetti, J.; Van Ende, D. Tetrahedron 1985, 41,
4783.
Anal. Calcd for C20H24O2Se: C, 64.00; H, 6.44. Found: C, 64.17; H,
6.40.
To a stirred solution of the hydroxyselenide 11 (0.0894 g, 0.238
mmol) in anhyd CH2Cl2 (2 mL) under N2, was added Et3N (0.23
mL, 0.17 g, 1.7 mmol) at 20 °C. To this mixture was added a solu-
tion of SOCl2 (0.03 mL, 0.06 g, 0.5 mmol) in CH2Cl2 (1 mL) and
the mixture was stirred for 1 h at 20 °C. The reaction was quenched
with aq sat. NaHCO3 until pH 7. The solution was concentrated un-
der reduced pressure and the resulting residue was diluted with
Et2O. The organic phase was washed with an aq sat. solution of
NaHCO3, brine and dried (MgSO4). The solution was concentrated
under reduced pressure to give a yellow oil which was purified by
flash chromatography (silica gel 200–400 mesh, hexanes) to afford
12 (0.0353 g, 73%) as a colorless oil.
1-(2-Methylpropenyl)indan-5-ol (15)
To a stirred mixture of EtSH (0.40 mL, 5.4 mmol) and anhyd DMF
(3 mL) under N2 at 0 °C, was added NaH (0.204 g, 5.10 mmol, 60%
in mineral oil). The mixture was stirred for 30 min at r.t. and was
then added to a stirred solution of 12 (0.0461 g, 0.228 mmol) in
DMF (1 mL). The resulting mixture was stirred for 3 h at 140 °C
whereupon it became black in color. The mixture was cooled to r.t.
and an aq sat. solution of NH4Cl (4 mL) was added. EtOAc was add-
ed and the organic phase was washed with H2O and brine, and dried
(MgSO4). The solution was concentrated under reduced pressure
Synthesis 2003, No. 7, 1031–1034 ISSN 1234-567-89 © Thieme Stuttgart · New York