5820
H. M. C. Ferraz et al. / Tetrahedron 59 (2003) 5817–5821
3.1.2. 1-Dimethoxymethyl-5-methoxy-3,6-dimethyl-
indan (4). To a stirred solution of 5 (0.546 g, 2.90 mmol)
in TMOF (15 mL), was added TTN·3H O (1.42 g,
2
J¼1.3 Hz, 3H), 1.78 (d, J¼1.3 Hz, 3H), 1.87–2.02 (m, 2H),
2.18 (s, 3H), 3.18–3.29 (m, 1H), 3.81 (s, 3H), 3.95–4.03
1
3
(m, 1H), 5.10–5.14 (m, 1H), 6.67 (s, 1H), 6.83 (s, 1H);
NMR (75 MHz, CDCl ) d 16.3, 18.1, 21.0, 25.8, 38.5, 41.6,
C
3
.20 mmol) at 08C, which promptly dissolved. The mixture
3
was stirred for 1 min at 08C and an abundant precipitation
was observed. The resulting suspension was filtered through
a silica gel pad (200–400 mesh, ca. 10 cm), using CH Cl as
42.5, 55.6, 105.6, 124.9, 126.2, 128.8, 131.1, 138.0, 147.2,
157.1; MS m/z (%): 230 (M , 40), 215 (100); HRMS calc.
þ
for C H O: 230.1671. Found 230.1667.
2
2
16 22
eluent. The filtrate was washed with H O (twice), with
2
brine, and dried over anhydrous MgSO . The solvent was
4
concentrated under reduced pressure giving a yellow oil.
The residue was purified by flash chromatography (silica gel
200–400 mesh, eluent: hexanes (80%), CH Cl (10%) and
2 2
EtOAc (10%)) immediately after concentration of the
3.1.5. (6)-Mutisianthol (3). Under nitrogen, NaH (0.328 g,
8.20 mmol, 60% in mineral oil) was washed with anhydrous
hexanes (twice). After a few minutes under nitrogen,
anhydrous DMF (5 mL) was added. To this mixture was
slowly added a solution of EtSH (0.40 mL, 5.5 mmol) in
anhydrous DMF (0.4 mL) at 08C and the resulting yellow-
gray solution was stirred for 20 min at room temperature. A
solution of 14 (0.0419 g, 0.182 mmol) in DMF (1 mL) was
then added dropwise and the resulting mixture was stirred
for 5 h at 1408C, becoming slightly brown. The mixture was
cooled to the room temperature and a saturated solution of
solvent, affording 4 (0.660 g, 2.64 mmol, 91%) as a
1 1
2
colorless oil: IR (film): 2953, 2830, 1465 cm ; H NMR
300 MHz, CDCl ) d 1.23 (d, J¼6.9 Hz, 3H), 1.76 (ddd,
(
3
J¼13.0, 8.5, 6.7 Hz, 1H), 2.19 (s, 3H), 2.22–2.31 (m, 2H),
3
.18–3.27 (m, 1H), 3.35 (s, 3H), 3.40 (s, 3H), 3.35–3.40
(
m, 1H), 3.81 (s, 3H), 4.23 (d, J¼7.3 Hz, 1H), 6.65 (s, 1H),
1
3
7
3
1
.12 (s, 1H); C NMR (75 MHz, CDCl ) d 16.4, 20.9, 36.8,
3
NH Cl (5 mL) was added. The mixture was extracted with
4
Et O (3 times) and the organic phase was washed with
2
water, with brine, and dried over anhydrous MgSO . The
4
8.1, 45.6, 53.1, 54.5, 55.4, 105.1, 107.5, 124.6, 127.6,
þ
33.6, 148.2, 157.5; MS m/z (%): 250 (M , 9), 75 (100).
Anal. calcd for C H O : C, 71.97; H, 8.86. Found C,
7
solvent was removed under reduced pressure and the
resulting brown oil was purified by flash chromatography
1
5 22 3
1.85; H, 8.60.
.1.3. 3,6-Dimethyl-5-methoxy-indan-1-carbaldehyde
(30% AcOEt in hexanes) giving starting material (0.0078 g,
3
0.034 mmol, 19%) and 14 (0.0285 g, 0.132 mmol, 72%) as a
white solid: mp: 82.1–83.08C; IR (film): 3371, 1619, 1259,
(
0
13a). To a stirred solution of the acetal 4 (0.0558 g,
.223 mmol) in glacial acetic acid (0.7 mL), was added H O
813 cm2
1
;
1
H NMR (500 MHz, CDCl ) d 1.20 (d,
3
2
(
2 drops). The mixture was heated at a controlled range of
temperature (75–808C) for 40 min. The resulting solution
J¼7.0 Hz, 3H), 1.74 (d, J¼1.3 Hz, 3H), 1.77 (d,
J¼1.3 Hz, 3H), 1.88–1.97 (m, 2H), 2.21 (s, 3H), 3.14–
3.25 (m, 1H), 3.95–3.99 (m, 1H), 5.10–5.13 (m, 1H), 6.61
was diluted with Et O and a saturated solution of NaHCO
2
was added dropwise until pH 7. The organic phase was
washed with saturated aqueous solution of NaHCO (twice),
3
1
3
(s, 1H), 6.81 (s, 1H); C NMR (75 MHz, CDCl ) d 15.8,
3
18.1, 20.9, 25.8, 38.1, 41.5, 42.4, 110.1, 121.6, 126.3, 128.6,
þ
3
with brine and dried over MgSO . The solvent was removed
4
131.2, 138.7, 147.9, 152.8; MS m/z (%): 216 (M , 42), 187
(100).
under reduced pressure, giving 13a (0.0391 g, 0.192 mmol,
1
6%) as a yellow oil: IR (film): 1721 cm2 ; H NMR
1
8
(
300 MHz, CDCl ) d 1.29 (d, J¼7.3 Hz, 3H), 1.86 (ddd,
3
J¼13.2, 8.5, 7.3 Hz, 1H), 2.20 (s, 3H), 2.66 (ddd, J¼13.2,
Acknowledgements
7
3
1
5
.8, 3.8 Hz, 1H), 3.25–3.34 (m, 1H), 3.80–3.86 (m, 1H),
.83 (s, 3H), 6.71 (s, 1H), 7.04 (s, 1H), 9.58 (d, J¼2.9 Hz,
We are grateful for the financial support provided by
FAPESP, CNPq and CAPES. We also wish to thank the IQ-
UNICAMP for the HRMS analysis.
1
3
H); C NMR (75 MHz, CDCl ) d 16.3, 20.8, 35.1, 38.7,
3
5.5, 56.2, 105.8, 125.6, 126.8, 129.0, 148.3, 158.3, 200.6;
þ
MS m/z (%): 204 (M , 11), 175 (100); HRMS calc. for
C H O 204.1150. Found 204.1149.
1
3 16 2
3
indan (14). To a stirred solution of Ph CH(CH ) Br
.1.4. 3,6-Dimethyl-5-methoxy-1-(2-methyl-propenyl)-
2
References
2
3
3 2
(
0.151 g, 0.392 mmol) in anhydrous THF (3 mL) under
nitrogen, was added dropwise n-BuLi (2.09 M in hexanes,
.18 mL, 0.38 mmol) at 108C. The resulting red solution
1. For a recent leading reference, see: Kraus, G. A.; Choudhury,
P. K. J. Org. Chem. 2002, 67, 5857.
0
2. For examples of new indans recently isolated, see: Palermo,
J. A.; Brasco, M. F.; Spagnuolo, C.; Seldes, A. M. J. Org.
Chem. 2000, 65, 4482.
was stirred for 20 min at 108C. Then, a solution of the
aldehyde 13a (0.0786 g, 0.385 mmol) in anhydrous THF
(
3
2 mL) was added dropwise. The mixture was stirred for
0 min at 108C. The reaction was quenched with H O
3 mL) and extracted with Et O (three times). The organic
2
3. For a recent total synthesis of fredericamycin, see: Kita, Y.;
Higuchi, K.; Yoshida, Y.; Iio, K.; Kitagaki, S.; Ueda, K.; Akai,
S.; Fujioka, H. J. Am. Chem. Soc. 2001, 123, 3214.
4. For a recent total synthesis of ribasine, see: Ollero, L.;
Castedo, L.; Dom ´ı nguez, D. Tetrahedron 1999, 55, 4445.
5. Bohlmann, F.; Zdero, C.; Le Van, N. Phytochemistry 1979, 18,
99.
2
(
phase was washed with brine and dried over anhydrous
MgSO . The solvent was removed under reduced pressure,
4
giving a yellow solid. This solid was purified by flash
chromatography (silica gel 200–400 mesh, eluent: hexanes
(
starting material (0.0081 g) and 14 (0.0562 g, 0.244 mmol,
80%), CH Cl (10%) and EtOAc (10%)) affording impure
6. Ho, T.-L.; Lee, K.-Y.; Chen, C.-K. J. Org. Chem. 1997, 62,
3365.
2
2
2
1 1
6
3%) as a colorless oil: IR (film): 1614, 844 cm ; H NMR
7. For reviews concerning thallium(III) chemistry, see: (a)
Ferraz, H. M. C.; Silva, L. F., Jr.; Vieira, T. de O. Synthesis
(
300 MHz, CDCl ) d 1.23 (d, J¼7.0 Hz, 3H), 1.74 (d,
3