2566 J . Org. Chem., Vol. 65, No. 8, 2000
Lei and Atkinson
(2R,3R,4S)-3-Br om o-6-{[ter t-bu tyl(d im eth yl)silyl]oxy}-
2,5,7,8-tetr a m eth yl-2-[(4R,8R)-4,8,12-tr im eth yltr id ecyl]-
3,4-d ih yd r o-2H -ch r om en -4-ol (17a ) a n d (2R,3S,4R)-3-
b r om o-6-{[ter t-b u t yl(d im et h yl)silyl]oxy}-2,5,7,8-t et r a -
m eth yl-2-[(4R,8R)-4,8,12-tr im eth yltr id ecyl]-3,4-d ih yd r o-
2H-ch r om en -4-ol (17b). 16b (100 mg, 0.19 mmol) was
dissolved in a mixture of DME:H2O ) 6:2.4 at O°C in an ice
bath.57 Then the NBS solution (49.27 mg, 0.2768 mmol in 2
mL of DME) was added to the well-stirred mixture and kept
at 4 °C overnight, at which point no starting material 16b was
detected by TLC. Two spots were visible by TLC; Rf ) 0.74
and 0.54 (CH2Cl2:hexane ) 5:1). The DME was removed under
reduced pressure, and the residue was extracted with ether
and dried over Na2SO4. Purification by column chromatogra-
phy yielded two compounds. These two product’s 1H NMR, 13C,
and MS are nearly identical, but the TLC Rf values are
different. The total yield of both isomers 17a and 17b was 96%.
TLC for 17a Rf ) 0.47 (CH2Cl2:hexane ) 5:1) The yield was
63.0 mg (51.8%). 1H NMR δ 5.05 (t, 1H, J ) 6 Hz), 4.34 (d,
1H, J ) 6 Hz), 2.25 (s, 3H), 2.13 (s, 3H), 2.10 (s, 3H), 1.82 (m,
2H), 1.60 (m, 2H), 1.53 (s, 3H), 1.29-1.14 (br, 17H), 1.06 (s,
9H), 0.88 (m, 12H), 0.15 (d, 6H, J ) 10 Hz); 13C NMR 146.35,
144.82, 129.73, 125.65, 123.68, 119.48, 79.54, 71.71, 64.42,
39.77, 37.80, 37.71, 37.68, 37.37, 33.53, 33.19, 32.98, 28.38,
26.50, 25.20, 24.75, 24.68, 23.12, 23.03, 20.71, 20.14, 19.92,
14.94, 14.84, 12.49, -2.67; EI-MS m/z 640 (M+, 6.6), 638 (6.2),
558 (8.2), 540 (39.2), 397 (11.1), 317 (100).
bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino-man-
ganese(III) chloride (10 mg) and 4-(3-phenylpropyl)pyridine
N-oxide, (15 mg) were dissolved in dichloromethane (1.5 mL),
and the mixture was added to the hypochlorite solution. The
solution was stirred for 15 min at 0 °C, and then 16b (50 mg,
0.092 mmol) in 0.5 mL of CH2Cl2 and the remaining hypochlo-
rite solution (0.5 mL) were added over 30 min via syringe. The
reaction was completed in 2 h at 0 °C. The mixture was filtered
through a pad of Celite, washed once with brine, and dried
over Na2SO4. The solvent was removed under reduced pressure
to afford 42.1 mg (85%) of the epoxide 18a . The same yield
was obtained for 18b. All spectral data for the epoxides
obtained by this method were identical to those obtained by
cyclization of the bromohydrins 17a and 17b.
(2R,3R)-6-{[ter t-Bu t yl(d im et h yl)silyl]oxy}-2,5,7,8-t et -
r am eth yl-2-[(4R,8R)-4,8,12-tr im eth yltr idecyl]-3,4-dih ydr o-
2H-ch r om en -3-ol (19a ). Lithium aluminum hydride (0.3 mL
of a 1.0 M solution in THF) and aluminum chloride (15 mg)
were suspended in dry THF (2 mL), and the suspension was
stirred for 20 min under argon at 0 °C. A solution of 27.5 mg
of 18a in 1.0 mL of dry THF was then added dropwise at 0
°C. After 3 h, the reaction was quenched with water and
extracted with ether. The product was purified by column
chromatography (hexane:ethyl acetate, 10:1). The overall yield
from 17a to 19a was 25.2 mg (78%). TLC Rf ) 0.30 (hexane:
ethyl acetate ) 10:1); 1H NMR δ 3.86 (overlapped dd, X of ABX,
1H, J XA ) 5 Hz, J XB ) 5 Hz), 2.86 (dd, A of ABX, J AB ) 17 Hz,
J AX ) 5 Hz), 2.61 (dd, B of ABX, J BA ) 17 Hz, J BX ) 5 Hz),
2.12 (s, 6H, 2CH3), 2.07 (s, 3H, CH3), 1.68 (s, 1H, C-3OH), 1.55
(m, 2H, CH2), 1.50-1.10 (br, 17H), 1.21 (s, 3H), 1.07 (s, 9H),
0.90 (m, 12H), 0.14 (s, 6H); 13C NMR 145.32, 145.01, 126.85,
124.58, 123.44, 116.07, 77.00, 69.56, 39.78, 37.88, 37.70, 35.48,
33.21, 33.12, 30.72, 28.39, 26.50, 25.22, 24.89, 23.14, 23.04,
21.33, 21.06, 20.16, 20.05, 14.73, 13.86, 12.44, -2.88; EI-MS
m/z 560 (M+, 100), 317 (14.7), 279 (14.1), 221 (6.4), 149 (8.8).
HREIMS calcd for C35H64O3Si 560.4625, found 560.4644.
17b: TLC Rf ) 0.54 (CH2Cl2:hexane ) 5:1). The yield was
53.9 mg (44.3%). 1H NMR δ 5.05 (t, 1H, C-4 H, J ) 6 Hz), 4.34
(d, 1H, J ) 6 Hz), 2.25 (s, 3H), 2.13 (s, 3H), 2.10 (s, 3H), 1.82
(m, 2H), 1.60 (m, 2H), 1.53 (s, 3H), 1.29-1.14 (br, 17H), 1.06
(s, 9H), 0.88 (m, 12H), 0.15 (d, 6H, J ) 10 Hz); 13C NMR 146.35,
144.82, 129.73, 125.65, 123.68, 119.48, 79.54, 71.71, 64.42,
39.77, 37.80, 37.71, 37.68, 37.37, 33.53, 33.19, 32.98, 28.38,
26.50, 25.20, 24.75, 24.68, 23.12, 23.03, 20.71, 20.14, 19.92,
14.94, 14.84, 12.49, -2.67; EI-MS m/z 640 (M+, 6.7), 638 (4.8),
558 (8.4), 540 (39.0), 397 (11.2), 317 (100). HREIMS for C35H63
BrO3Si 638.3730 found 638.3773.
-
(2R,3S)-6-{[ter t-Bu t yl(d im et h yl)silyl]oxy}-2,5,7,8-t et -
r am eth yl-2-[(4R,8R)-4,8,12-tr im eth yltr idecyl]-3,4-dih ydr o-
2H-ch r om en -3-ol (19b). The synthesis of 19b was conducted
under identical conditions with the synthesis of 19a . The
overall yield from 19b to 17b was 24.1 mg (77%). TLC Rf )
0.30 (hexane:ethyl acetate ) 10:1); 1H NMR δ 3.85 (overlapped
dd, X of ABX, 1H, J XA ) 5 Hz, J XB ) 5 Hz), 2.80 (dd, A of ABX,
(1a R,2R,7bR)-2,4,5,7-Tetr a m eth yl-2-[(4R,8R)-4,8,12-tr i-
m eth yltr idecyl]-1a,7b-dih ydr o-2H-oxir en o[2,3-c]ch r om en -
6-yl ter t-Bu tyl(d im eth yl)silyl Eth er (18a ). To the suspen-
sion of sodium hydride (12 mg, 0.225 mmol) in dry THF (1
mL) was added 17a (36 mg, 0.056 mmol) in THF (0.5 mL) at
0 °C under argon. The resulting mixture was stirred at room
temperature for 6 h. Precipitated NaBr was filtered, and the
solvent removed under reduced pressure to yield the epoxide
18a which was reduced directly in the next step without
further purification. A small sample was retained for spectral
analysis. TLC Rf ) 0.60 (hexane:ethyl acetate ) 10:1). 1H NMR
δ 4.09 (d, 1H, J ) 6 Hz), 3.48 (d, 1H, J ) 4 Hz), 2.31 (s, 3H),
2.11 (s, 3H), 2.06 (s, 3H), 1.70 (m, 2H), 1.55 (m, 2H), 1.36-
1.09 (br, 17H), 1.10 (s, 3H), 1.06 (s, 9H), 0.88 (m, 12H), 0.14
(d, 6H, J ) 5 Hz); 13C NMR 145.76, 144.95, 129.74, 125.43,
124.87, 116.21, 77.00, 74.03, 62.42, 48.43, 39.91, 39.78, 37.92,
37.87, 37.70, 33.21, 33.15, 28.38, 26.49, 25.21, 24.93, 23.13,
23.04, 21.10, 20.44, 20.17, 20.10, 15.01, 13.09, 12.14, -2.90;
EI-MS m/z 558 (M+, 3.4), 280 (2.6), 245 (21.5), 203 (6.4), 151
(10.1), 137 (12.3), 125 (17.4), 97 (58.2).
1H, J AB ) 17 Hz, J AX ) 5 Hz), 2.68 (dd, B of ABX, 1H, J BA
)
17 Hz, J BX ) 5 Hz), 2.12 (s, 6H), 2.07 (s, 3H), 1.68 (s, 1H),
1.55 (m, 2H), 1.50-1.10 (br, 17H), 1.21 (s, 3H), 1.07 (s, 9H),
0.90 (m, 12H), 0.14 (s, 6H); 13C NMR 145.32, 145.01, 126.85,
124.58, 123.44, 116.07, 77.00, 69.56, 39.78, 37.88, 37.70, 35.48,
33.21, 33.12, 30.72, 28.39, 26.50, 25.22, 24.89, 23.14, 23.04,
21.33, 21.06, 20.16, 20.05, 14.73, 13.86, 12.44, -2.88; EI-MS
m/z 560 (M+, 100), 317 (14.5), 279 (13.9), 221(6.5), 149 (8.9).
Glyoxylic Acid Ch lor id e p-Tolu en esu lfon yl Hyd r a zon e
(20). A mixture of glyoxylic acid (2.5 g, 27.2 mmol) and
p-toluenesulfonyl hydrazide (5.11 g, 27.18 mmol) in 30 mL of
dry THF was stirred overnight at room temperature. The
solvent was removed under reduced pressure, and then the
residue was washed with cold water and air-dried for 2 days.
The crude, dry hydrazone was recrystallized from a carbon
tetrachloride-ethyl acetate mixture to give white crystals. The
yield was 5.3 g (81%). mp 151-153 °C (lit.61 149.5-152 °C)
1H NMR (DMSO-d6) δ 12.29 (s, 1H, COOH), 7.64 (d, 2H, J )
5 Hz), 7.53 (d, 2H, J ) 5 Hz), 7.18 (s,1H), 2.39 (s, 3H); 13C
NMR (DMSO-d6 ) 164.43, 144.90, 138.31, 136.55, 130.30,
127.96, 21.89; FAB-MS (NBA as matrix) m/z 727 (3M + 1, 2.1),
485 (2M + 1, 14.0), 243 (M + 1, 100), 225 (37.9), 139 (49.3), 91
(49.7).
Glyoxylic acid chloride p-toluenesulfonyl hydrazone 20 was
prepared as described below but was not isolated for analytical
characterization. A suspension of 81.0 mg (0.32 mmol) of
glyoxylic acid p-toluenesulfonyl hydrazone in a solution of 3
mL of dry benzene and 0.5 mL of thionyl chloride (2 M in CH2-
Cl2, 1.0 mmol ) was refluxed with stirring for 1.5 h under an
argon atmosphere. The solvent was removed under reduced
pressure, and then the residue was placed on a high vacuum
(1a S,2R,7bS)-2,4,5,7-Tetr a m eth yl-2-[(4R,8R)-4,8,12-tr i-
m eth yltr idecyl]-1a,7b-dih ydr o-2H-oxir en o[2,3-c]ch r om en -
6-yl ter t-Bu tyl(d im eth yl)silyl Eth er (18b). The synthesis
of 18b was conducted under identical conditions with the
synthesis of 18a . TLC Rf ) 0.60 (hexane;ethyl acetate ) 10:
1
1); H NMR δ 4.09 (d, 1H, J ) 6 Hz), 3.48 (d, 1H, J ) 4 Hz),
2.31 (s, 3H), 2.11 (s, 3H), 2.06 (s, 3H), 1.70 (m, 2H), 1.55 (m,
2H), 1.36-1.09 (br, 17H), 1.10 (s, 3H), 1.06 (s, 9H), 0.88 (m,
12H), 0.14 (d, 6H, J ) 5 Hz); 13C NMR 145.76, 144.95, 129.74,
125.43, 124.87, 116.21, 77.00, 74.03, 62.42, 48.43, 39.91, 39.78,
37.92, 37.87, 37.70, 33.21, 33.15, 28.38, 26.49, 25.21, 24.93,
23.13, 23.04, 21.10, 20.44, 20.17, 20.10, 15.01, 13.09, 12.14,
-2.90; EI-MS m/z 558 (M+, 3.2), 280 (2.5), 245 (21.7), 203 (6.6),
151 (9.9), 137 (12.1), 125 (17.7), 97 (58.4).
Syn th esis of 18a and 18b Usin g J a cobsen ’s Ca ta lysts.
A 12% solution of NaOCl (0.3 mL) was cooled in an ice bath to
0 °C. J acobsen’s catalyst either (R,R)-(-)- or (S,S)-(+)-N,N′-