Notes
J . Org. Chem., Vol. 64, No. 7, 1999 2553
(CDCl3, 400 MHz): δ 7.26 (m, 5H), 3.95-3.90 (m, 4H),
3.66 (s, 3H), 3.45 (ABq, 2H, J ) 13.4, ∆δ ) 40.0), 2.35
(m, 5H), 1.83-1.9 (m, 8H). 13C NMR (CDCl3, 400 MHz):
δ 176.5, 138.7, 128.7, 128.0, 126.8, 108.6, 64.3, 64.0, 63.0,
62.5, 60.3, 51.7, 46.1, 35.5, 32.4, 31.3, 28.0. FT-IR (neat)
cm-1: 2979 (s), 2811 (s), 1735 (s), 1603 (w), 1449 (m).
HREIMS m+/z (%): C20H27NO4 (calcd) ) 345.1940, C20H27-
NO4 (found) ) 345.1943 (100.0).
yield, as a colorless oil, following the above procedure
from 20. 1H NMR (CDCl3, 400 MHz): δ 3.93 (m, 4H), 3.60
(d, 2H, J ) 2.4), 2.66 (d, 1H, J ) 8.4), 2.51 (m, 3H), 2.56
(s, 3H), 2.17 (t, 1H, J ) 11.6), 1.93 (m, 1H), 1.88 (t, 1H,
J ) 13.2), 1.55 (m, 2H), 1.42-1.26 (m, 4H). 13C NMR
(CDCl3, 400 MHz): δ 109.1, 64.3, 64.2, 57.9, 54.8, 50.2,
46.1, 37.0, 35.7, 34.8, 30.7, 30.4, 28.3. FT-IR (neat) cm-1
:
3429 (br), 2947-2884 (m), 1475 (m), 1446 (m), 1104 (s).
HREIMS m+/z (%): C13H23NO3 (calcd) ) 241.1678, C13H23-
NO3 (found) ) 241.1662 (100.0).
2-Ben zyl-6-oxo-8a -(h yd r oxym et h yl)-cis-oct a h y-
d r oisoqu in olin e 6-Eth ylen e Keta l (11). Obtained in
89% yield, as a colorless oil, following the above procedure
from 9 and purification by flash chromatography (hex-
anes/ethyl acetate ) 1/1). 1H NMR (CDCl3, 400 MHz): δ
7.37-7.24 (m, 5H), 3.95-3.90 (m, 4H), 3.57 (ABq, 2H, J
) 10.4, ∆δ ) 24.0), 3.46 (s, 2H), 2.68 (d, 1H, J ) 10.4),
2.52 (q, 2H, J ) 11.6), 2.51 (m, 1H), 2.17 (t, 1H, J ) 11.6),
1.97 (m, 1H), 1.90 (t, 1H, J ) 13.2), 1.55-1.51 (m, 2H),
1.40-1.21 (m, 4H). 13C NMR (CDCl3, 400 MHz): δ 137.4,
128.9, 128.4, 127.3, 109.1, 76.2, 64.2, 64.1, 63.3, 56.1,
2-Be n zyl-6-oxo-cis-oct a h yd r oisoq u in olin e -8a -
ca r ba ld eh yd e. Obtained from the following procedure:
0.42 g of 11 (1.41 mmol) was stirred with 3 equiv of
pTsOH in wet acetone (15 mL) for 15 h at room temper-
ature. After neutralization with NaHCO3 and extraction
with Et2O (3×), the crude product was then subjected to
Swern oxidation which provided 0.28 g of a clear oil in
75% yield after SiO2 chromatography (hexanes/ethyl
1
acetate ) 4:1). H NMR (CDCl3, 400 MHz): δ 9.56 (s,
48.2, 35.7, 35.5, 35.4, 30.6, 30.3, 28.4. FT-IR (neat) cm-1
:
1H), 7.30 (m, 5H), 3.54 (d, 1H, J ) 13.2), 3.47 (s, 1H, J
) 13.2), 2.73 (m, 1H), 2.59 (dd, 1H, J ) 0.8, 11.4), 2.51-
2.19 (m, 8H), 1.95 (m, 1H), 1.70 (m, 1H), 1.50 (m, 1H).
13C NMR (CDCl3, 400 MHz): δ 210.0, 204.4, 138.0, 128.6,
128.3, 128.2, 127.9, 127.2, 62.7, 55.3, 52.1, 49.6, 43.3,
37.7, 35.1, 27.8, 26.5. FT-IR (neat) cm-1: 2937 (m), 2711
(m), 1720 (s), 1603 (w), 1493 (m). HREIMS m+/z (%):
C16H21NO2 - H (calcd) ) 270.1521, C16H21NO2 - H
(found) ) 270.1527 (32.2).
3416 (br), 2841 (s), 1460 (m). HREIMS m+/z (%): C19H25
-
NO3 (calcd) ) 317.1992, C19H25NO3 (found) ) 317.1992
(12.2).
2-Ben zyl-6-h yd r oxy-tr a n s-octa h yd r oisoqu in olin e-
8a -ca r boxylic Acid Meth yl Ester . Obtained in 95%
yield, as a colorless oil, following the above procedure
from 7 with 10% CH2Cl2 in ethanol as solvent, and
purification by flash chromatography (hexanes/ethyl
1
acetate ) 2/1). H NMR (CDCl3, 400 MHz): δ 7.30-7.21
2-Ben zyl-6-oxo-tr a n s-oct a h yd r oisoq u in olin e-8a -
ca r ba ld eh yd e. Obtained by the following procedure:
0.52 g of the product obtained from hydrogenation of 7
(1.82 mmol) was reduced with 1.5 equiv of LiAlH4 in THF
at 0 °C for 30 min. Workup following the procedure given
for 9, followed by Swern oxidation, gave 0.32 g of a clear
oil in 71% overall yield after SiO2 chromatography
(hexanes/ethyl acetate ) 4:1). 1H NMR (CDCl3, 400
MHz): δ 9.62 (d, 1H, J ) 2.4), 7.34-7.26 (m, 5H), 3.61
(d, 1H, J ) 13.2), 3.41 (d, 1H, J ) 13.2), 3.10 (dd, 1H, J
) 2.0, 11.6), 3.03 (m, 1H), 2.96 (d, 1H, J ) 14.0), 2.33-
2.25 (m, 3H), 2.23 (dt, 1H, J ) 3.2, 12.4), 1.99-1.93 (m,
2H), 1.82 (d, 1H, J ) 11.2), 1.71 (m, 1H), 1.54-1.46 (m,
2H). 13C NMR (CDCl3, 400 MHz): δ 210.0, 204.7, 138.1,
128.7, 128.3, 127.2, 62.7, 61.1, 53.9, 48.8, 44.2, 42.1, 37.8,
29.4, 28.7. FT-IR (neat) cm-1: 2937 (m), 2811 (m), 1713
(s), 1603 (w), 1493 (m), 1449 (m). HREIMS m+/z (%):
C16H21NO2 + H (calcd) ) 272.1676, C16H21NO2 + H
(found) ) 272.1670 (38.4).
8a -F or m yl-6-oxo-tr a n s-octa h yd r oisoqu in olin e-2-
ca r boxylic Acid Meth yl Ester . To 5 mL of THF at -78
°C was condensed 5 mL of ammonia, followed by addition
of 0.30 g (13.0 mmol) of sodium. After stirring for 30 min,
hydroxy-enone 21 (0.21 mg, 0.88 mmol) in 1 mL of THF
was added. The reaction mixture was stirred at -78 °C
for 20 min and then quenched with saturated NH4Cl
until the blue color disappeared. The mixture was then
warmed to room temperature and extracted with ether
(3×). The combined organic phase was washed with
brine, dried over K2CO3, and concentrated under reduced
pressure. The crude was subjected to oxidation without
purification. To the stirred solution of oxalyl chloride
(0.22 g, 1.76 mmol) in 1.0 mL of THF at -78 °C was
added dimethyl sulfoxide (0.28 g, 3.52 mmol) in 1 mL of
THF. The solution was stirred at -78 °C for 30 min at
which time a solution of crude alcohol (about 0.88 mmol)
in 1 mL of THF was added. The resulting solution was
warmed to -40 °C and after 15 min was treated with
(m, 5H), 3.71 (q, 1H, J ) 7.0), 3.63 (s, 3H), 3.43 (ABq,
2H, J ) 13.5, ∆δ ) 100), 3.14 (d, 1H, J ) 10.8), 2.94 (d,
1H, J ) 10.8), 2.21 (dq, 1H, J ) 4.6, 12.6), 2.09-1.61 (m,
5H), 1.62 (d, 1H, J ) 5.5), 1.38 (dd, 1H, J ) 2.4, 13.0),
1.26-1.13 (m, 3H). 13C NMR (CDCl3, 400 MHz): δ 174.5,
138.7, 128.6, 127.9, 126.8, 70.8, 63.2, 62.6, 54.9, 51.1,
47.7, 42.0, 37.7, 32.4, 32.3, 28.8. FT-IR (neat) cm-1: 3398
(br), 2935-2805 (m), 1738 (s), 1596 (w), 1453 (m).
HREIMS m+/z (%): C18H25NO3 (calcd) ) 303.1829, C18H25-
NO3 (found) ) 303.1834 (100.0).
6-Oxo-8a -(h yd r oxym eth yl)-cis-octa h yd r oisoqu in -
olin e-2-ca r b oxylic Acid Met h yl E st er 6-E t h ylen e
Keta l. Obtained in 95% yield, as a colorless oil, following
the above procedure from 18 and purification by flash
1
chromatography (hexanes/ethyl acetate ) 1/2). H NMR
(CDCl3, 400 MHz): δ 4.00-3.10 (m, 4H), 3.82-3.69 (m,
7H), 3.13 (broad, 3H), 1.94-1.76 (m, 4H), 1.67-1.50 (m,
4H). 13C NMR (CDCl3, 400 MHz): δ 157.3, 108.8, 67.4,
64.3, 64.2, 53.0, 43.2, 40.2, 37.6, 35.3, 32.6, 30.3, 29.5,
26.7. FT-IR (neat) cm-1: 3460 (br), 2936 (m), 1698 (s),
1684 (s), 1478 (m), 1456 (m). HREIMS m+/z (%): C14H23
-
NO5 (calcd) ) 285.1576, C14H23NO5 (found) ) 285.1563
(100.0).
6-Oxo-cis-octa h yd r oisoqu in olin e-2,8a -d ica r boxy-
lic Acid Meth yl Ester 6-Eth ylen e Keta l. Obtained in
88% yield, as a colorless oil, following the above procedure
from 19 and purification by flash chromatography (hex-
anes/ethyl acetate ) 2/1). 1H NMR (CDCl3, 400 MHz): δ
3.97-3.88 (m, 4H), 3.71 (s, 3H), 3.69 (s, 3H), 3.61-3.52
(m, 3H), 3.40-3.14 (broad, 1H), 2.54 (m, 1H), 1.97-1.54
(m, 8H). 13C NMR (CDCl3, 400 MHz): δ 175.4, 156.0,
108.0, 64.3, 63.9, 52.5, 52.1, 47.3, 41.4, 35.7, 33.7, 31.2,
27.9, 27.0. FT-IR (neat) cm-1: 2937 (s), 1735 (s), 1698
(s). HREIMS m+/z (%): C15H23NO6 (calcd) ) 313.1525,
C15H23NO6 (found) ) 313.1502 (82.8).
2-Met h yl-6-oxo-8a -(h yd r oxym et h yl)-cis-oct a h y-
d r oisoqu in olin e 6-Eth ylen e Keta l. Obtained in 86%