Y. X. Jia et al. / Tetrahedron 58 (2002) 1697±1708
1705
in 150 mL of CH2Cl2 was added in one portion a solution of
21/22 in 40 mL of CH2Cl2 at room temperature. After the
resulting dark red black mixture was allowed to stir for 4.0 h
at room temperature, the mixture was diluted with diethyl
ether, ®ltered through Al2O3. The ®ltrate was evaporated in
vacuo and the residue was puri®ed by column chromato-
graphy to give 22 (5.0 g, 42% overall yield in four steps) as
a colorless oil. 1H NMR (400 MHz, CDCl3) d: 3.34 (s, 1H),
2.16±1.22 (m, 7H), 1.18 (s, 2£3H), 0.82 (d, 3H, J6.6 Hz):
13C NMR (100 MHz, CDCl3) d: 69.9, 64.8, 56.3, 33.7, 30.0,
25.3, 25.2, 24.5, 24.2, 21.3; EI-MS m/z (%): 155 (M1215,
4), 112 (13), 97 (34), 70 (100), 59 (43), 55 (35), 43 (86);
HRMS: m/z calcd for C9H15O2 (M12CH3) 155.1068; found
155.1055.
with ether and washed with saturated NaHCO3 and brine,
dried over Na2SO4 and evaporated in vacuo. The residue
was puri®ed by column chromatography to give 26 (two
diastereoisomers) (650 mg, 40% overall yield in three
1
steps) as a colorless oil. H NMR (400 MHz, CDCl3) d:
4.83 (d, 1H, J3.3 Hz), 4.60 (dd, 1H, J11.8, 2.5 Hz),
4.35 (dd, 1H, J2.1, 9.6 Hz), 4.22 (dd, 1H, J2.5,
11.9 Hz), 3.47 (s, 3H), 3.34 (s, 3H), 1.91±1.06 (m, 10H),
1.40 (s, 3H), 1.39 (s, 3H), 1.38 (s, 6H), 0.95 (d, 3H,
J6.5 Hz), 0.87 (d, 3H, J6.6 Hz); 13C NMR (100 MHz,
CDCl3) d: 211.9, 210.8, 103.7, 99.2, 79.4, 77.4 (2C), 72.5,
56.5, 55.3, 39.0, 37.7, 36.3, 35.7, 28.8, 26.4, 26.3, 26.2,
26.1, 24.0, 21.9, 21.6; EI-MS m/z (%): 185 (M1231, 3),
129 (18), 85 (100), 43 (49); ESI-HRMS: m/z calcd for
C11H20O4Na (M1Na): 239.1259; found 239.1253.
3.1.22. (1R,4S)-4-p-Menthen-3,8-diol (24). A mixture of
epoxide 22 (2 g, 11.8 mmol), aluminium isopropoxide
(4.0 g, 23.5 mmol) and 2-propanol (30 mL) was re¯uxed
with stirring under Ar for 8 h, then the solvent was removed
and the obtained gel residue was partitioned with ether and a
10% NaOH solution. The aqueous layer was extracted with
ether. The combined organic layer was washed with water
and brine, dried over Na2SO4 and puri®ed by column chro-
matography to afford a mixture of 23/24, which was directly
3.1.24.
2-[(2S,5S,6R)-4,5,6-Trihydroxy-2,6-dimethyl-
heptyl]-1,3-dithiane (28). To a cooled (2788C), stirred
solution of 26 (400 mg, 1.85 mmol) in 8 mL MeOH was
added NaBH4 (70 mg, 1.85 mmol). The mixture was stirred
for 1h, then the solvent was removed. The obtained residue
was diluted with EtOAc and 10 mL 5% HCl solution. The
aqueous layer was extracted with EtOAc and the combined
organic layer was washed with saturated NaHCO3 and brine,
dried over Na2SO4 and evaporated in vacuo. The residue
was puri®ed by column chromatography to give 27
(320 mg, 80%) as a mixture of four diastereoisomers,
which was directly used in the next step.
1
used in the next step. Compound 24: H NMR (400 MHz,
CDCl3) d: 5.73 (dd, 1H, J5.4, 2.4 Hz), 4.45 (d, 1H,
J1.3 Hz), 2.19±1.45 (m, 5H), 1.38 (s, 3H), 1.32 (s, 3H),
0.93 (d, 3H, J6.4 Hz); 13C NMR (100 MHz, CDCl3) d:
142.9, 124.3, 73.7, 64.4, 39.6, 34.1, 30.1, 29.7, 22.6, 21.5;
EI-MS m/z (%): 152 (M1215, 7), 137 (22), 109 (14), 95
(18), 43 (100); HRMS: m/z calcd for C10H18O (M12H2O)
152.1197; found 152.1177. Compound 23: 1H NMR
(400 MHz, CDCl3) d: 3.79 (q, 1H, J6.4 Hz), 3.66 (s,
1H), 0.96±1.83 (m, 7H), 1.08 (d, 3H, J6.4 Hz), 0.85 (d,
3H, J6.4 Hz), 0.37 (s, 3H); 13C NMR (100 MHz, CDCl3)
d: 76.7, 75.7, 39.4, 38.9, 29.6, 25.8, 23.8, 22.2, 19.6, 17.3;
GS-MS m/z (%): 154 (M1218, 2), 139 (7), 110 (77), 95
(100), 81 (33); HRMS: m/z calcd for C10H15O
(M12H2O2CH3) 139.1119; found 139.1105.
A mixture of 27 (800 mg, 3.67 mmol), 1,3-propanedithiol
(4 mL, 40.0 mmol) and BF3´Et2O (1.0 mL) in dry CH2Cl2
(10 mL) was stirred for 1.5 h at 08C. The mixture was
diluted with EtOAc and saturated NaHCO3. The aqueous
layer was extracted with EtOAc (3£20 mL), dried over
Na2SO4 and evaporated in vacuo. The residue was puri®ed
1
by column chromatography to give 28 (830 mg, 77%). H
NMR (400 MHz, CDCl3) d: 4.12 (t, 1H, J7.6 Hz), 4.06
(dd, 1H, J4.1, 9.2 Hz), 3.07 (brs, 1H), 2.93±2.78 (m, 4H),
2.13±1.12 (m, 7H), 1.29 (s, 3H), 1.28 (s, 3H), 0.97 (d, 3H,
J6.5 Hz); 13C NMR (100 MHz, CDCl3) d: 77.2, 74.2,
68.8, 45.3, 42.8, 41.2, 30.5, 30.3, 27.2, 26.3, 26.2, 26.0,
19.6; EI-MS m/z (%): 294 (M1, 20), 276 (5), 258 (3), 159
(54), 119 (100), 84 (59), 59 (46); ESI-HRMS: m/z calcd for
C13H26O3S2Na (M1Na): 317.1221; found 317.1210.
3.1.23. (4S,6S)-2-Methyloxy-4-methyl-6(20-hydroxy-20-
methylpropionyl)-tetrahydropyran (26). Through a cold
(2788C) solution of compound 23/24 (1.9 g) in 50 mL
CH2Cl2 ozone was bubbled. When the reaction was
complete (TLC) the reaction mixture was treated with
2 mL Me2S and stirred overnight and evaporated in vacuo.
The residue was puri®ed by column chromatography to
give 23/25 as a mixture of two isomers, which was
directly used in the next step. Compound 25 (two dia-
3.1.25. 2-[(2S,5S,6R)-4,5-Isopropylidenedioxy-6-hydroxy-
2,6-dimethylheptyl]-1,3-dithiane (29). To a solution of
28 (830 mg, 2.83 mmol) in 6 mL dry acetone was added a
catalytic amount of PTS and the mixture was stirred at room
temperature for 12 h. The reaction mixture was diluted with
ether (80 mL) and washed with saturated NaHCO3 (20 mL)
and brine (20 mL), dried over anhydrous Na2SO4 and
evaporated in vacuo. The residue was puri®ed by column
chromatography to afford 29 (890 mg, 95% yield). 1H NMR
(400 MHz, CDCl3) d: 4.15±4.03 (m, 2H), 3.50 (d, 1H,
J7.8 Hz), 2.92±2.78 (m, 4H), 2.14±1.10 (m, 7H), 1.39
(s, 3H), 1.38 (s, 3H), 1.25 (s, 3H), 1.19 (s, 3H), 0.99 (d,
3H, J6.5 Hz); 13C NMR (100 MHz, CDCl3) d: 108.4,
87.3, 74.6, 69.9, 45.3, 43.3, 42.7, 30.5, 30.3, 27.8, 27.6,
27.5, 27.1, 26.0, 24.7, 18.9; EI-MS m/z (%): 334 (M1, 4),
319 (6), 217 (23), 159 (37), 119 (91), 59 (100); FAB-
HRMS: m/z calcd for C16H31O3S2 (M1H:) 335.1715;
found 335.1695.
1
stereoisomers). H NMR (400 MHz, CDCl3) d: 5.43 (d,
1H, J3.0 Hz), 4.88 (dd, 1H, J11.8, 2.4 Hz), 4.78 (dd,
1H, J9.6, 2.0 Hz), 4.34 (dd, 1H, J11.8, 2.4 Hz), 2.14±
1.14 (m, 10H), 1.39 (s, 3H), 1.37 (s, 3H), 1.36 (s, 3H), 1.32
(s, 3H), 0.97 (d, 3H, J6.3 Hz); 0.93 (d, 3H, J6.3 Hz); 13C
NMR (100 MHz, CDCl3) d: 212.2, 210.8, 96.4, 92.0, 78.4,
77.6, 77.6, 71.8, 40.5, 37.9, 35.7, 35.2, 28.8, 26.7, 26.7,
26.2, 26.2, 23.2, 21.8, 21.4; EI-MS m/z (%): 169
(M12Me2H2O, 1), 98 (46) 83 (31), 71 (59), 59 (100), 43
(54).
To a solution of the above product in 25 mL acetone was
added 2 mL DMP and catalytic amount of PTS. The mixture
was stirred overnight at room temperature and then diluted