Asymmetric Synthesis of Sesaminone
J . Org. Chem., Vol. 62, No. 21, 1997 7417
1
9.2 mmol, 86%): [R]21 ) -99 (c 0.73, CHCl3); H NMR (300
TBDP S-P r otected Sesa m in on e 12 a n d r-Tetr a lon e 13.
To a solution of silyl enol ethers 11a ,b (193 mg, 255 µmol) in
CH2Cl2 (2 mL) at -78 °C was added TiCl4 (85 µL, 760 µmol).
After being stirred for 2.5 h, the reaction was quenched by
the addition of MeOH (2 mL), followed by saturated aqueous
NaHCO3 (2 mL) at -78 °C and was then stirred until the
mixture reached room temperature. The solution was then
diluted with Et2O (60 mL) and washed with H2O. The
combined aqueous layers were washed with Et2O. The com-
bined organic extracts were dried over MgSO4, filtered, and
concentrated under reduced pressure to give an oil that was
purified by SiO2 flash chromatography (40:1 hexane-EtOAc)
to give two compounds, protected sesaminone 12 (98 mg, 161
µmol, 63%) and R-tetralone 13 (8.5 mg, 14 µmol, 6%). Pro-
D
MHz, CDCl3) δ 9.69 (m, 1H), 7.61-7.29 (m, 10H), 6.72 (s, 1H),
6.66 (s, 2H), 4.58 (d, J ) 8.3 Hz, 1H), 4.42 (ABq, J ) 6.6 Hz,
2H), 3.51 (dd, J ) 10.2, 4.2 Hz, 1H), 3.40 (dd, J ) 10.2, 5.6
Hz, 1H), 3.30 (s, 3H), 2.71 (ddd, J ) 16.7, 6.6, 2.6 Hz, 1H),
2.59 (ddd, J ) 16.7, 6.2, 1.7 Hz, 1H), 2.53-2.41 (m, 1H), 1.04
(s, 9H); 13C NMR (75 MHz, CDCl3) δ 201.9, 147.9, 147.2, 135.5,
133.4, 133.1, 133.0, 129.7, 127.6, 121.3, 107.9, 107.2, 101.0,
93.8, 77.4, 63.1, 55.9, 43.6, 43.3, 26.8, 19.8; IR (neat) 2824,
2724, 1724 cm-1
.
Secon d a r y Alcoh ol 16. To a solution of 4-bromo-1,2-
(methylenedioxy)benzene (1.0 mL, 8.5 mmol) in freshly dis-
tilled THF (85 mL) at -78 °C was added tert-butyllithium (1.7
M in pentane, 10 mL, 17 mmol) dropwise over a 2 min period
and the resulting mixture was allowed to stir for 20 min. A
solution of aldehyde 15 (4.4 g, 8.4 mmol) in THF (85 mL) was
added via cannula over 30 min. After being stirred for 1 h at
-78 °C, the reaction mixture was allowed to stir at room
temperature for 2.5 h, and was then quenched by the addition
of saturated aqueous NH4Cl (30 mL). After removing the bulk
of the THF under reduced pressure, the resulting slurry was
extracted with CH2Cl2. The combined organic extracts were
dried over MgSO4, filtered, and concentrated under reduced
pressure. The resulting oil was purified by SiO2 flash chro-
matography (10:1 hexane-EtOAc) to give secondary alcohol
16 (4.6 g, 7.2 mmol, 85%) as an inseparable mixture (∼1:1) of
two diastereomers: 1H NMR (300 MHz, CDCl3) δ 7.66-7.30
(m, 10H), 6.78-6.55 (m, 4H), 5.96-5.91 (m, 4H) 4.65-4.48 (m,
4H), 3.56-3.10 (m, 6H), 2.14-1.92 (m, 2H), 1.90-1.78 (m, 1H),
1.10-0.98 (m, 9H); 13C NMR (75 MHz, CDCl3) δ 147.7, 147.6,
147.5, 147.1, 146.9, 146.4, 139.4, 138.7, 135.6, 135.6, 134.1,
133.8, 133.2, 133.1, 129.7, 129.6, 127.6, 127.6, 121.3, 120.9,
119.2, 107.8, 107.8, 107.3, 107.2, 106.3, 106.3, 100.8, 94.2, 93.9,
78.5, 78.1, 72.9, 72.6, 64.9, 64.4, 56.0, 45.0, 44.9, 38.5, 37.3,
tected sesaminone 12: [R]24 ) +17 (c 0.16, CHCl3); 1H NMR
D
(300 MHz, CDCl3) δ 7.63-7.26 (m, 12H), 6.84-6.82 (m, 2H),
6.69 (d, J ) 8.1 Hz, 1H), 6.63 (dd, J ) 8.1, 1.5 Hz, 1H), 6.07
(m, 2H), 5.93 (s, 2H), 4.77 (d, J ) 8.8 Hz, 1H), 4.25-4.18 (m,
3H), 3.77 (dd, J ) 10.7, 3.9 Hz, 1H), 3.68 (dd, J ) 10.7, 3.9
Hz, 1H), 2.80-2.70 (m, 1H), 1.07 (s, 9H); 13C NMR (75 MHz,
CDCl3) δ 197.1, 152.0, 148.4, 147.8, 147.2, 135.7, 135.5, 134.6,
133.1, 133.0, 131.6, 129.9, 129.8, 127.8, 127.7, 124.8, 120.3,
108.3, 107.9, 107.9, 107.2, 101.9, 100.9, 100.9, 83.3, 71.0, 61.3,
52.9, 48.9, 26.8, 19.3; IR (neat) 1674, 1604 cm-1. R-Tetralone
1
13: [R]21 ) +23 (c 0.26, CHCl3); H NMR (300 MHz, CDCl3)
D
δ 7.59-7.25 (m, 11H), 6.72 (d, J ) 7.8 Hz, 1H), 6.58 (dd, J )
7.8, 1.6 Hz, 1H), 6.50 (d, J ) 1.6 Hz, 1H), 6.31 (s, 1H), 5.98-
5.90 (m, 4H), 4.22 (d, J ) 8.8 Hz, 1H), 3.52 (dd, J ) 10.3, 4.4
Hz, 1H), 3.46 (dd, J ) 10.3, 6.1 Hz, 1H), 2.80-2.71 (m, 2H),
2.44-2.31 (m, 1H), 1.04 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
196.4, 152.3, 148.0, 147.0, 146.5, 143.1, 136.3, 135.5, 133.2,
133.0, 129.7, 129.6, 127.7, 127.6, 127.4, 122.7, 109.3, 108.9,
108.2, 105.6, 101.7, 101.0, 64.6, 46.9, 44.9, 40.3, 26.9, 19.3; IR
(neat) 1673, 1617 cm-1
.
26.9, 19.2; IR (neat) 3433, 1609, 1111, 1038 cm-1
.
(-)-Sesa m in on e ((-)-1). 48% aqueous HF (1.2 mL) was
added dropwise to a stirred solution of protected sesaminone
12 (49.0 mg, 80.0 µmol) and pyridine (1.1 mL) in CH3CN (9
mL) at 0 °C. The mixture was allowed to warm to ambient
temperature overnight and stirred for a total of 24 h. The
mixture was quenched with saturated aqueous NaHCO3 (12
mL). After gas evolution ceased, the mixture was extracted
with CH2Cl2. The combined organic layers were dried over
Na2SO4, filtered, and concentrated under reduced pressure to
give an oil which was purified by SiO2 flash chromatography
(15:1 to 2:1 petroleum ether-EtOAc) to give (-)-sesaminone
Keton e 10. MnO2 (25 g, 288 mmol) was added to a solution
of secondary alcohol 16 (4.6 g, 7.2 mmol) in CH2Cl2 (90 mL) at
room temperature and the resulting slurry was stirred for 19
h. The mixture was then filtered through a plug of Celite
using CH2Cl2 as eluant. The filtrate was concentrated under
reduced pressure to give an oil that was purified by SiO2 flash
chromatography (5:1 hexane-EtOAc) to give ketone 10 (4.2
g, 6.5 mmol, 90%): [R]25D ) -74 (c 0.61, CHCl3); 1H NMR (300
MHz, CDCl3) δ 7.57-7.20 (m, 12H), 6.80 (d, J ) 1.5 Hz, 1H),
6.79 (d, J ) 8.0 Hz, 1H), 6.73 (dd, J ) 8.0, 1.5 Hz, 1H), 6.68
(d, J ) 8.0 Hz, 1H), 6.02 (m, 2H), 5.93 (m, 2H), 4.78 (d, J )
7.8 Hz, 1H), 4.48 (ABq, J ) 6.6 Hz, 2H), 3.62 (dd, J ) 10.3,
4.6 Hz, 1H), 3.44 (dd, J ) 10.3, 4.2 Hz, 1H), 3.31 (s, 3H), 3.22
(dd, J ) 17.0, 4.6 Hz, 1H), 3.13 (dd, J ) 17.0, 8.1 Hz, 1H),
2.68-2.56 (m, 1H), 1.04 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
197.4, 151.3, 148.0, 147.8, 147.0, 135.5, 134.1, 133.3, 132.2,
129.5, 127.5, 124.1, 121.4, 108.0, 107.8, 107.7, 107.5, 101.7,
100.9, 94.3, 77.5, 63.0, 55.9, 44.0, 35.9, 26.9, 19.2; IR (neat)
(-)-1 (25.1 mg, 67 µmol, 84%): mp 133-134 °C; [R]21 ) -25
D
(c 0.11, MeOH) [lit.2 [R]25D ) -25.0 (c 0.140, MeOH)]; 1H NMR
(300 MHz, CDCl3) δ 7.58 (dd, J ) 8.1, 1.7 Hz, 1H), 7.47 (d, J
) 1.7 Hz, 1H), 6.97 (d, J ) 1.6 Hz, 1H), 6.88 (d, J ) 8.1 Hz,
1H), 6.85 (dd, J ) 8.0, 1.6 Hz, 1H), 6.77 (d, J ) 8.0 Hz, 1H),
6.06 (s, 2H), 5.95 (s, 2H), 4.67 (d, J ) 9.0 Hz, 1H), 4.28 (m,
1H), 4.14 (m, 1H), 4.11 (m, 1H), 3.77 (dd, J ) 10.8, 4.5 Hz,
1H), 3.66 (dd, J ) 10.8, 5.6 Hz, 1H), 2.80-2.91 (m, 1H), 1.75
(br s, 1H); 13C NMR (75 MHz, CDCl3) δ 197.3, 152.1, 148.3,
147.9, 147.4, 134.4, 131.3, 124.9, 120.3, 108.2, 108.0, 108.0,
107.0, 102.0, 101.0, 83.6, 70.8, 61.1, 52.3, 49.8; IR (KBr) 3452,
1677, 1605 cm-1
.
Silyl En ol Eth er s 11a ,b. To a solution of ketone 10 (557
mg, 868 µmol) and triethylamine (1.2 mL, 8.7 mmol) in CH2Cl2
(4.4 mL) was added tert-butyldimethylsilyl triflate (300 µL,
1.3 mmol) at room temperature. After being stirred for 2.5 h,
the reaction mixture was diluted with diethyl ether (50 mL)
and washed with 5% NaHCO3 and H2O. The organic extracts
were concentrated under reduced pressure to give an oil which
was purified by SiO2 flash chromatography (70:1 hexane-
EtOAc) to give silyl enol ethers 11a ,b (558 mg, 738 µmol, 85%)
1669, 1613 cm-1
.
Ack n ow led gm en t. We thank Brandeis University
and Procter & Gamble for their generous financial
support of this research. A.T.M. acknowledges partial
support from an NIH Training Grant to the Bioorganic
Chemistry Program at Brandeis University. B.M.F.
acknowledges both the NSF (CHE-9305789) and Po-
laroid Corporation for financing the purchase of an
X-ray diffractometer.
as a mixture of double bond isomers (7:1 by 1H NMR). 11a
(major enol ether isomer): [R]22 ) -106 (c 0.31, CHCl3); H
1
D
NMR (300 MHz, CDCl3) δ 7.68-7.58 (m, 5H), 7.41-7.26 (m,
6H), 6.86-6.55 (m, 5H), 5.94-5.91 (m 4H), 5.03 (d, J ) 10.1
Hz, 1H), 4.98 (d, J ) 4.6 Hz, 1H), 4.50 (ABq, J ) 6.6 Hz, 2H),
3.73 (dd, ) 9.7, 7.2 Hz, 1H), 3.52 (dd, J ) 9.7, 4.9 Hz, 1H),
3.26 (s, 3H), 3.23-2.96 (m, 1H), 1.07 (s, 9H), 0.86 (s, 9H), -0.25
(s, 3H), -0.30 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 151.2,
147.5, 147.1, 147.0, 146.7, 135.7, 135.6, 135.5, 134.5, 134.5,
129.5, 127.5, 127.5, 121.0, 120.7, 120.1, 107.8, 107.7, 107.6,
107.5, 100.9, 100.8, 94.5, 77.3, 64.2, 55.7, 46.1, 26.9, 25.8, 18.1;
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C NMR
spectra for all new compounds and an ORTEP-style drawing
for structure 1 (25 pages). This material is contained in many
libraries on microfiche, immediately follows this article in the
microfilm version of this journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
IR (neat) 1650, 1608 cm-1
.
J O971027C