Ferna´ndez de la Pradilla et al.
were separated. The aqueous layer was extracted twice with
EtOAc (10 mL/mmol) and the combined organic extracts were
washed twice with a saturated solution of NaCl (20 mL/mmol),
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure to give a crude product, which was purified
by column chromatography on silica gel. Following this
procedure the corresponding hydroxy dienes 17 and 21 were
obtained along with small amounts (9-20%) of dimeric byprod-
ucts 19 and 22 whose structure was tentatively assigned as
the SN2′ addition products derived from vinyl epoxides 15 or
16 and hydroxy dienes 17 or 21. These products were obtained
as single isomers at C-8 although their stereochemistry was
not determined. P r oced u r e B: After complete oxirane forma-
tion (procedure A), the reaction mixture was diluted with
anhydrous THF (6.25 mL/mmol of chlorohydrin) and 2.0 equiv
of KO-t-Bu in THF (10 mL/mmol of chlorohydrin) was added
to give a ca. 0.033 M solution of oxirane in THF but with
similar concentration of base as in procedure A. The products
were isolated as described above. These experiments were
designed to study the effect of oxirane concentration on the
diene-dimer ratio. P r oced u r e C: Following procedure A, from
a solution of the chlorohydrin in THF (10-20 mL/mmol of
chlorohydrin), and with addition of a freshly prepared 0.5 M
solution of KO-t-Bu in THF. With this procedure we tried to
minimize experimental errors upon addition of suspensions
of base, particularly for small-scale experiments.
IR (film) 3391, 2929, 2858, 1595, 1492, 1435, 1378, 1303, 1207,
1177, 1119, 1082, 1038, 1014, 921, 808 cm-1; MS (ES) 333 [M
+ 1]+, 315 [(M - 18) + 1]+(100%). Anal. Calcd for C20H28O2S:
C, 72.24; H, 8.49; S, 9.64. Found: C, 72.02; H, 8.63; S, 9.83.
1
Data for 20g: Rf 0.32 (50% EtOAc-hexanes); H NMR (300
MHz) δ 0.91 (t, 3 H, J ) 7.1 Hz), 1.20-1.90 (m, 12 H), 1.95
(m, 2 H), 2.38 (s, 3 H), 3.30 (br s, 1 H), 4.97 (m, 1 H), 5.76
(ddd, 1 H, J ) 7.3, 3.7, 1.5 Hz), 6.03 (d, 1 H, J ) 7.3 Hz), 7.25
(d, 2 H, J ) 8.1 Hz), 7.50 (d, 2 H, J ) 8.3 Hz); 13C NMR (75
MHz) δ 14.0, 21.4, 22.5, 22.6, 25.4, 27.7, 29.2, 29.7, 37.0, 66.1,
124.7, 125.9 (2 C), 129.6 (2 C), 130.3, 131.8, 139.6, 141.4, 146.9;
IR (film) 3390, 2929, 2858, 1595, 1492, 1447, 1378, 1270, 1081,
1036, 807 cm-1; MS (ES) 665 [2M + 1], 355 [M + Na]+, 333
[M + 1]+ (100%).
Gen er a l P r oced u r e for Oxid a tion of Su lfoxid es w ith
MMP P . To a cold (0 °C) solution of sulfoxide in MeOH (10
mL/mmol) was added 1.5-3.0 equiv of magnesium monoper-
oxyphthalate hexahydrate (MMPP). The mixture was stirred
from 0 °C to room temperature, monitored by TLC until
completion and then quenched with a saturated solution of
NaHCO3 (4 mL/mmol). After removal of MeOH under reduced
pressure, the mixture was diluted with EtOAc (5 mL/mmol),
the layers were separated, and the aqueous phase was
extracted with EtOAc (3 times, 4 mL/mmol). The combined
organic layers were washed with a saturated solution of NaCl
(1 mL/mmol), dried over MgSO4, filtered, and concentrated
under reduced pressure to give a crude product that was
purified by gradient column chromatography with EtOAc-
hexanes mixtures.
Syn th esis of (+)-(3S,SS)-(1Z)-1-Cycloh exen yl-1-(p-tolyl-
su lfin yl)h ep t-1-en -3-ol (17g). From chlorohydrin 3g (37 mg,
0.1 mmol, 1.0 equiv) in 2 mL of THF with two successive
additions of KO-t-Bu (0.2 mL, 0.1 mmol, 1.0 equiv, and 0.1
mL, 0.05 mmol, 0.5 equiv after 1 h) according to the general
procedure C (1 h + 15 min) was obtained diene 17g. Purifica-
tion by chromatography (10-30% EtOAc-hexanes) afforded
Syn th esis of (+)-(5S)-(6Z,8E)-7-(p-Tolylsu lfon yl)dodeca-
6,8-d ien -5-ol (32a ). From sulfinyl diene 17a (26 mg, 0.080
mmol, 1.0 equiv) in MeOH (1.5 mL) and MMPP (130 mg, 0.220
mmol, 2.7 equiv), according to the general procedure (9 h), after
chromatography (5-10% EtOAc-hexane), was obtained sul-
fonyl diene 32a (26 mg, 0.077 mmol, 96%) as a colorless oil.
25 mg (0.075 mmol, 75%) of 17g as a colorless oil. Data for
1
17g: Rf 0.26 (30% EtOAc-hexanes); [R]20 +49.1 (c 1.00); H
D
Data for 32a : Rf 0.19 (20% EtOAc-hexanes); [R]20 +26.0 (c
NMR (300 MHz) δ 0.82 (t, 3 H, J ) 7.0 Hz), 1.16-1.30 (m, 4
H), 1.42-1.64 (m, 6 H), 1.91 (m, 2 H), 2.04 (m, 2 H), 2.37 (s, 3
H), 4.87 (dt, 1 H, J ) 8.3, 6.7 Hz), 5.97 (d, 1 H, J ) 8.3 Hz),
5.98 (m, 1 H), 7.23 (d, 2 H, J ) 8.2 Hz), 7.49 (d, 2 H, J ) 8.3
Hz); 13C NMR (50 MHz) δ 13.9, 21.3, 21.5, 22.4, 22.5, 25.6,
27.4, 28.3, 37.0, 66.3, 124.7 (2 C), 129.6 (2 C), 130.6, 132.5,
138.3, 140.2, 140.6, 148.4; IR (film) 3379, 3034, 2929, 2858,
1595, 1493, 1447, 1435, 1378, 1304, 1269, 1207, 1179, 1136,
1081, 1027, 1012, 921, 888, 842, 810 cm-1; MS (ES) 333 [M +
1]+, 315 [(M - 18) + 1]+(100%). Anal. Calcd for C20H28O2S: C,
72.24; H, 8.49; S, 9.64. Found: C, 72.53; H, 8.62; S, 9.50.
Syn th esis of (+)-(3R,SS)-(1E)-1-Cycloh exen yl-1-(p-tolyl-
su lfin yl)h ep t-1-en -3-ol (21g) a n d (3R,SS)-(1Z)-1-Cyclo-
h exen yl-1-(p-tolylsu lfin yl)h ep t-1-en -3-ol, (20g). From chlo-
rohydrin 4g (31 mg, 0.08 mmol, 1.0 equiv) in 2 mL of THF
with three successive additions of KO-t-Bu (0.16 mL, 0.08
mmol, 1.0 equiv, and 0.08 mL, 0.04 mmol, 0.5 equiv after 1
and 3 h) according to the general procedure C (1 h + 3 h +1
h) was obtained a 92:8 mixture of 21g and 20g. Purification
by chromatography (10-30% EtOAc-hexanes) afforded 2 mg
(0.005 mmol, 6%) of 20g and 20 mg (0.060 mmol, 71%) of 21g
both as a colorless oils. Data for 21g: Rf 0.26 (50% EtOAc-
D
1
0.15); H NMR (200 MHz) δ 0.81 (t, 3 H, J ) 7.3 Hz), 0.84 (t,
3 H, J ) 6.9 Hz), 1.23-1.65 (m, 8 H), 2.01 (qd, 2 H, J ) 6.7,
1.1 Hz), 2.40 (s, 3 H), 2.50 (br s, 1 H), 5.11 (m, 1 H), 5.85 (dt,
1 H, J ) 15.3, 6.6 Hz), 6.08 (dd, 1 H, J ) 15.5, 0.6 Hz), 6.11
(d, 1 H, J ) 8.6 Hz), 7.29 (d, 2 H, J ) 8.5 Hz), 7.71 (d, 2 H, J
) 8.3 Hz); 13C NMR (50 MHz) δ 13.5, 13.9, 21.5, 21.9, 22.5,
27.3, 34.8, 36.6, 66.7, 123.9, 127.5 (2 C), 129.7 (2 C), 137.7 (2
C), 141.2, 142.1, 144.4; IR (film) 3460, 2960, 2930, 2880, 1460,
1320, 1300, 1150, 1080, 1030, 960, 810, 680 cm-1; MS (EI) 336
[M]+, 319, 279, 181, 157, 139 (100%), 109, 97, 95, 91, 85, 67,
57. Anal. Calcd for C19H28O3S: C, 67.82; H, 8.39; S, 9.53.
Found: C, 68.04; H, 8.17; S, 9.77.
Ack n ow led gm en t. This research was supported by
DGICYT (BQU2001-0582 and BQU2003-02921) and
CAM (08.5/0028/2003 2). We thank J ANSSEN-CILAG
for generous additional support. We thank CAM and
MEC for doctoral fellowships to C.M. and M.T. We are
grateful to Professor S. Valverde for encouragement and
support.
hexanes); [R]20 +186.1 (c 1.13); 1H NMR (300 MHz) δ 0.87 (t,
D
3 H, J ) 7.0 Hz), 1.22-1.56 (m, 8 H), 1.64 (m, 2 H), 1.76 (m,
1 H), 1.80 (m, 1 H), 1.98 (m, 2 H), 2.36 (s, 3 H), 4.32 (ap q, 1
H, J ) 7.2 Hz), 5.40 (m, 1 H), 6.24 (d, 1 H, J ) 8.8 Hz), 7.21
(d, 2 H, J ) 8.1 Hz), 7.42 (d, 2 H, J ) 8.1 Hz); 13C NMR (50
MHz) δ 14.0, 21.4 (2 C), 22.4, 22.6, 25.3, 27.4, 29.9, 37.0, 68.9,
125.6 (2 C), 129.3, 129.4 (2 C), 131.8, 132.1, 139.9, 141.6, 149.1;
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O035750G
1986 J . Org. Chem., Vol. 69, No. 6, 2004