5
70
R. G. F. Giles, I. R. Green and S.-H. Li
+
(37Cl), 32%], 170 [M (35Cl), 41], 171 (91), 169 (100), 126 (18),
+
−1
[
9
M
199.0526). νmax (KBr disk)/cm 2924 (O–H), 1462 (C=C). δH 1.06
9 (28), 97 (19), 77 (26), 71 (32), 69 (34), 57 (55).
(3H, d, J 6.4, CH3), 1.98 (1H, d, J 5.3, 2-OH), 2.53 (1H, d, J 3.2, 1-
OH), 3.91 (3H, s, OCH3), 4.23 (1H, m, 2-H), 5.26 (1H, t, J 3.2, 1-H),
6.89 (1H, dd, J 1.9 & 7.8, 6 -H), 7.22 (1H, dd, J 1.9 & 7.8, 4 -H),
.26 (1H, t, J 7.8, 5 -H). δC 15.2 (CH3), 55.0 (OCH3), 68.0 (C-2),
2.5 (C-1), 109.7 (C-5 ) , 118.6 (C-6 ) , 124.7 (C-1 ), 126.0 (C-4 ) ,
ꢀ
ꢀ
ꢀ
ꢀ
(
Z)- and (E)-1-(2 -Chloro-3 -methoxyphenyl)prop-1-enes 9 and 10
ꢀ
7
7
1
Sodium hydride (60% dispersion in mineral oil, 1.658 g) was stirred
ꢀ
a
ꢀ a
ꢀ
ꢀ a
with dry dimethyl sulfoxide (4 mL) and dry tetrahydrofuran (16 mL) at
ꢀ
ꢀ
+
37
38.2 (C-2 ), 153.6 (C-3 ). m/z 201 [(M + 1-H2O)
( Cl), 33%], 199
◦
6
0 C for 2 h in an atmosphere of nitrogen. The mixture was cooled to
+
35
[
(M + 1-H2O)
( Cl), 100], 174 (12), 172 (39).
room temperature and ethyltriphenylphosphonium bromide (12.858 g,
4.72 mmol) in dry tetrahydrofuran (40 mL) was added to the mixture
and stirred at room temperature for 15 min. The aldehyde 8 (4.000 g,
3
ꢀ
ꢀ
rel-(2R,4S,5R)-4-(2 -Chloro-3 -methoxyphenyl)-2,5-dimethyl-1,3-
dioxolane 5
2
3.45 mmol) in dry tetrahydrofuran was added dropwise to the mixture
◦
and stirred for a further 1 h at 60 C. The cooled reaction mixture was
filtered and washed with dry tetrahydrofuran.The residue obtained upon
standard work-up was chromatographed (20% ethyl acetate–hexane)
to give a 3:1 mixture of (Z)- and (E)-olefins 9 and 10 (4.174 g, 97%)
as yellow oil. This mixture in dry methylene dichloride (140 mL) was
treated with bis(acetonitrile)dichloropalladium(ii) (205 mg), and boiled
for 7 days. The reaction mixture was filtered, then evaporated to afford
a residue that was chromatographed (20% ethyl acetate–hexane) to give
1,1-Dimethoxyethane (60 µL, 0.57 mmol) and (± )-10-camphorsulfonic
acid (6 mg, 0.03 mmol) were added to diol 13 in methylene dichlo-
ride (12 mL). The solution was boiled for 3 h and quenched with
saturated aqueous sodium hydrogencarbonate solution. The organic
layer was separated and the aqueous layer was extracted with more
methylene dichloride. The residue obtained upon standard work-up
was chromatographed (10% ethyl acetate–hexane) to afford the diox-
+
olane 5 (78 mg, 94%) as a colourless oil (Found C 58.95, H 6.3, M
242.0721. C12H15ClO3 requires C 59.4, H 6.25, M 242.0710). νmax
1
the (E)-olefin 10 (96% by H NMR) contaminated with the (Z)-olefin
9) (4% by H NMR) (Found: M 182.0503. C10H11ClO requires M
1
+
−1
(
1
(
1
(thin film)/cm 1585 & 1467 (C=C). δH 0.85 (3H, d, J 6.3, 5-CH3),
−
1
82.0498). νmax (thin film)/cm 1569 & 1468 (C=C). δH (for 10) 1.92
1.56 (3H, d, J 4.8, 2-CH3), 3.90 (3H, s, OCH3), 4.55 (1H, dq, J 6.3 &
7.2, 5-H), 5.19 (1H, q, J 4.8, 2-H), 5.48 (1H, d, J 7.2, 4-H), 6.88 (1H, dd,
3H, dd, J 1.7 & 6.6, CH3), 3.89 (3H, s, OCH3), 6.22 (1H, dq, J 6.6 &
ꢀ
ꢀ
ꢀ
5.7, 2-H), 6.79 (1H, dd, J 2.0 & 7.4, 6 -H), 6.82 (1H, dq, J 1.7 & 15.7,
-H), 7.11 (1H, dd, J 2.0 & 7.9, 4 -H), 7.15 (1H, dd, J 7.4 & 7.9, 5 -H). δC
for 10) 18.8 (CH3), 56.2 (OCH3), 109.9 (C-5 ) , 118.6 (C-6 ) , 126.8
C-2) , 127.4 (C-4 ) , 128.4 (C-1) , 129.1 (C-1 ), 137.5 (C-2 ), 155.2
C-3 ). m/z 184 [M
15), 115 (29), 103 (34), 97 (34), 91 (56), 86 (54), 85 (48), 83 (33), 81
46), 77 (33), 71 (45), 70 (32), 69 (44), 57 (100), 56 (31). Inspection of
the 3:1 mixture indicated the following data for the (Z)-olefin 9: δH 1.78
3H, dd, J 1.8 & 7.0, CH3), 3.90 (3H, s, OCH3), 5.90 (1H, dq, J 7.0 &
1.5, 2-H), 6.53 (3H, dq, J 1.8 & 11.5, 1-H), 6.93 (1H, dd, J 2.0 & 7.6,
J 1.5 & 7.9, 6 -H), 7.17 (1H, dd, J 1.5 & 7.9, 4 -H), 7.25 (1H, t, J 7.9,
ꢀ
ꢀ
ꢀ
1
5 -H). δC 16.4 (5-CH3), 19.7 (2-CH3), 56.2 (OCH3), 75.2 (C-5), 77.7
ꢀ
a
ꢀ a
ꢀ a
ꢀ a
ꢀ
(
(
(
(
(
(C-4), 100.5 (C-2), 110.9 (C-5 ) , 119.3 (C-6 ) , 120.1 (C-1 ), 127.1
b
ꢀ a
b
ꢀ
ꢀ
ꢀ a
ꢀ
ꢀ
+
37
+
(C-4 ) , 137.9 (C-2 ), 154.8 (C-3 ). m/z 244 [M
(
Cl), 5%], 242 [M
Cl), 14], 200 (34), 198 (100), 269 (35), 167 (35), 163 (31), 91 (40),
86 (33), 84 (48), 83 (33), 81 (26), 77 (15), 72 (34), 69 (37), 57 (33).
ꢀ
+
37
+
35
35
(
Cl), 24%], 182 [M
(
Cl), 74], 147 (68), 132
(
ꢀ
ꢀ
rel-(1R,2R)-1-(2 -Chloro-3 -methoxyphenyl)propane-1,2-diol 14
(
1
6
N-Methylmorpholine N-oxide (166 mg, 1.42 mmol) and osmium tetrox-
ide (5 mg) in tert-butyl alcohol (1 mL) were added to the 1:24 mixture
of olefins 9 and 10 (204 g, 1.12 mmol) in a 2:1 mixture of acetone–water
ꢀ
ꢀ
ꢀ
-H), 7.10 (1H, dd, J 2.0 & 8.0, 4 -H), 7.18 (1H, dd, J 7.6 & 8.0, 5 -H).
(
6 mL). The mixture was stirred in an atmosphere of nitrogen for 24 h.
ꢀ
ꢀ
cis- and trans-1-(2 -Chloro-3 -methoxyphenyl)-1,2-epoxypropanes
1 and 12
After this, acetone was removed under vacuum at room temperature.The
aqueous layer was added to dilute hydrochloric acid (2 M) and extracted
intoethylacetate.Theresidueobtaineduponstandardwork-upwaschro-
matographed (50% ethyl acetate–hexane) to give the diol 14 (207 mg,
86%) as white crystals, mp 109–110 C (Found C 55.8, H 6.15, M
216.0555. C10H13ClO3 requires C 55.45, H 6.05, M 216.0553). νmax
(KBr disk)/cm 3385 (O–H), 1584, 1524, & 1466 (C=C). δH 1.20 (3H,
d, J 6.4, CH3), 2.28 (1H, d, J 4.0, 2-OH), 2.72 (1H, d, J 5.3, 1-OH), 3.91
(3H, s, OCH3), 3.97 (1H, m, 2-H), 5.00 (1H, t, J 5.3, 1-H), 6.89 (1H,
dd, J 1.4 & 8.0, 6 -H), 7.12 (1H, dd, J 1.4 & 8.0, 4 -H), 7.27 (1H, t, J
8.0, 5 -H). δC 18.9 (CH3), 56.3 (OCH3), 71.3 (C-2), 74.5 (C-1), 111.2
(C-5 ) , 119.6 (C-6 ) , 121.0 (C-1 ), 127.4 (C-4 ) , 140.5 (C-2 ), 155.0
(C-3 ). m/z 218 [M
(100), 145 (13), 143 (41), 137 (35), 109 (21), 108 (32), 77 (21).
1
meta-Chloroperoxybenzoic acid (1.204 mg, 6.98 mmol) in chloroform
45 mL) at 0 C was added dropwise to the 1:24 mixture of olefins 9 and
0 (908 mg, 4.97 mmol) in chloroform (20 mL), and the solution was
stirred with anhydrous sodium hydrogencarbonate (219 mg) at room
temperature for 44 h. The reaction mixture was filtered and the filtrate
was poured into saturated aqueous sodium hydrogencarbonate solution.
The organic layer was separated and the aqueous layer was extracted
with cold chloroform. A 1:24 mixture of epoxides 11 and 12 (844 mg,
◦
(
◦
+
1
−
1
ꢀ
ꢀ
ꢀ
8
6%) was obtained upon standard work-up as an orange oil (Found:
+
ꢀ a
ꢀ a
ꢀ
ꢀ a
ꢀ
C 60.35, H 5.7, [FAB MS]: (M + 1) 199.0546. C10H11ClO2 requires
−
1
ꢀ
+ +
37
35
C 60.45, H 5.6, (M + 1) 199.0526). νmax (thin film)/cm 1576 & 1474
C=C). δH (for 12) 1.49 (3H, d, J 5.2, CH3), 2.88 (1H, dq, J 2.0 &
.2, 2-H), 3.90 (3H, s, OCH3), 3.93 (1H, d, J 2.0, 1-H), 6.86 (2H, dd,
( Cl), 3%], 216 [M ( Cl), 7], 174 (31), 172
(
5
ꢀ
ꢀ
ꢀ
ꢀ
J 1.5 & 8.0, 4 -H & 6 -H), 7.20 (1H, t, J 8.0, 5 -H). δC (for 12) 17.8
CH3), 56.2 (OCH3), 57.1 (C-2) , 58.4 (C-1) , 111.1 (C-5 ) , 117.5
C-6 ) , 121.3 (C-1 ), 127.4 (C-4 ) , 137.4 (C-2 ), 154.8 (C-3 ). m/z 201
rel-(2S,4R,5R)- and rel-(2R,4R,5R)-4-(2 -Chloro-
3 -methoxyphenyl)-2,5-dimethyl-1,3-dioxolanes 6 and 7
a
a
ꢀ b
ꢀ
(
(
[
ꢀ
b
ꢀ
ꢀ b
ꢀ
ꢀ
The diol 14 (2.000 g, 9.23 mmol) in dry methylene dichloride (200 mL)
was treated with 1,1-dimethoxyethane (1.0 mL, 9.43 mmol) and (± )-
+
37
+
35
(M + 1)
(
Cl), 19%], 200 (23), 199 [(M + 1)
( Cl), 54], 198 (54),
1
1
6
56 (14), 155 (41), 154 (100), 151 (10), 149 (40), 139 (35), 138 (53),
37 (99), 136 (85), 109 (13), 107 (36), 91 (34), 81 (33), 77 (25), 71 (25),
9 (54), 67 (31), 57 (77), 55 (64), 43 (65), 41 (73).
1
0-camphorsulfonic acid (151 mg, 0.65 mmol) and the solution was
boiled for 24 h in an atmosphere of nitrogen. The reaction mixture was
quenched with saturated aqueous sodium hydrogencarbonate solution.
The organic layer was separated and the aqueous layer was extracted into
more methylene dichloride. The residue obtained upon standard work-
up was chromatographed (10% ethyl acetate–hexane) to afford the 2:3
mixture of dioxolanes 6 and 7 (1.910 g, 85%) as pale yellow crystals.
The mixture was separated by preparative layer chromatography that
afforded the dioxolane 6, the minor product with the slightly higher RF,
ꢀ
ꢀ
rel-(1S,2R)-1-(2 -Chloro-3 -methoxyphenyl)propane-1,2-diol 13
The 1:24 mixture of epoxides 11 and 12 (360 mg, 1.81 mmol) in dry
dimethyl sulphoxide (15 mL) and aqueous potassium hydroxide solu-
tion (0.4 M, 6.1 mL) was stirred at 80 C.After 24 h, the reaction mixture
was cooled to room temperature and poured into water.The organic layer
was separated and the aqueous layer was extracted with ethyl acetate.
The residue obtained upon standard work-up was chromatographed
◦
+
as a yellow oil (Found C 59.4, H 6.3, [FAB MS]: (M − 1) 241.0647.
C12H15ClO3 requires C 59.4, H 6.25, (M − 1) 241.0631). νmax (thin
−
1
(
50% ethyl acetate–hexane) to give the diol 13 (107 mg, 27%) as white
film)/cm 1577 & 1472 (C=C). δH 1.43 (3H, d, J 6.3, 5-CH3), 1.53
(3H, d, J 4.8, 2-CH3), 3.91 (3H, s, OCH3), 4.03 (1H, dq, J 6.0 & 6.3,
5-H), 5.11 (1H, d, J 6.0, 4-H), 5.42 (1H, q, J 4.8, 2-H), 6.87 (1H, dd,
◦
crystals, mp 93–95 C (Found C 54.9, H 5.85, [FAB MS]: (M + 1-
+
H2O) 199.0533. C10H13ClO3 requires C 55.45, H 6.05, (M + 1-H2O)