682
Á. Cant´ın et al. / Tetrahedron: Asymmetry 12 (2001) 677–683
mmol) in dry CH2Cl2 (5 mL) was added dropwise.
After stirring the mixture for 6 h it was poured onto
10% aqueous NaHCO3 solution and extracted with
CH2Cl2. The combined organic extracts were dried over
Na2SO4 and concentrated in vacuo. Chromatography
of the residue on silica gel provided both isomeric
epoxyacetates.
The second eluting epoxide was obtained in 32% yield.
[h]2D0=−138 (c 1.81, CHCl3); HRMS (EI): m/z 212.1416
(C12H20O3 requires 212.1412); IR: wmax 2950, 2870,
1740, 1370, 1240 and 1100; 1H NMR: lH 5.1 (dd, J=10
and 2 Hz, 1H, H-3), 3.2 (d, J=2 Hz, 1H, H-2), 2.1 (s,
3H, CH3CO), 1.8–1.6 (m, 2H, H-6), 1.6–1.4 (m, 4H,
H-4+H-5+(CH3)2CH), 1.3 (s, 3H, CH3), 0.9 and 0.7
(d+d, J=7 Hz, 6H, (CH3)2CH); 13C NMR: lC 171.2
(CO), 72.6 (C3), 61.3 (C1), 61.1 (C2), 38.6 (C4), 28.1
(C6), 25.7 (CH3)2CH), 23.9 (CH3CO), 21.1 (C5), 20.8,
20.5 and 16.3 (3×CH3); MS: m/z 212 (M+, 9), 170 (8),
169 (9), 154 (100), 152 (54), 134 (14), 129 (13), 112 (32)
and 81 (4). After diastereoselective synthesis (see below)
this product was assigned to be (1S,2R,3R,4R)-1,2-
epoxy-1-methyl-4-(1-methylethyl)-cyclohex-3-yl acetate
9.
4.10. Epoxides from (3S,4R)-1-methyl-4-(1-methyl-
ethyl)-cyclohex-1-en-3-yl acetate 5
A mixture of two epoxides was obtained from (3S,4R)-
1-methyl-4-(1-methylethyl)-1-cyclohexen-3-yl
acetate;
the major compound (60% yield) had the following
spectral data: [h]2D0=−80 (c 1.16, CHCl3); HRMS (EI):
m/z 212.1410 (C12H20O3 requires 212.1412); IR: wmax
1
2960, 2930, 2870, 1740, 1370 and 1245; H NMR: lH
5.4 (br s, 1H, H-3), 3.0 (d, J=3 Hz, 1H, H-2), 2.1 (s,
3H, CH3CO), 2.0 (m, 1H, H-4), 1.8 (m, 2H, H-6),
1.5–1.3 (m, 3H, H-5+(CH3)2CH), 1.3 (s, 3H, CH3), 0.9
and 0.8 (d+d, J=7 Hz, 6H, (CH3)2CH); 13C NMR: lC
170.7 (CO), 69.7 (C3), 59.3 (C2), 58.3 (C1), 39.0 (C4),
28.1 (C6), 24.1 (CH3CO), 21.1 (CH3)2CH), 20.9, 20.4,
20.3 (3×CH3) and 19.6 (C5); MS: m/z 212 (M+, 9), 194
(4), 170 (12), 169 (8), 154 (100), 152 (85), 134 (23), 112
(40) and 109 (30). After diastereoselective synthesis (see
below) this product was assigned to be (1S,2R,3S,4R)-
1,2-epoxy-1-methyl-4-(1-methylethyl)-cyclohex-3-yl ace-
tate 7.
4.12. Selective synthesis of the epoxides by Sharpless
reaction
,
A mixture of activated 4 A molecular sieves and anhy-
drous CH2Cl2 (7 mL) was cooled to −10°C under N2.
Then
L
-(+)-diethyl tartrate or
D
-(−)-diethyl tartrate
(0.91 mmol) and titanium iso-propoxide (1.35 mmol)
were added; this was followed by slow addition of a
solution of dry tert-butyl hydroperoxide (7.6 mmol) in
anhydrous CH2Cl2. When the addition was finished (ca.
20 min) the mixture was cooled at −20°C and a new
solution of the corresponding allylic alcohol, 3 or 4 (4.5
mmol), in anhydrous CH2Cl2 (0.7 mL) was added drop-
wise. The mixture was stirred overnight at −20°C, and
then H2O was added (about 20 times the weight of
titanium iso-propoxide). After stirring at 0°C for 30
min and then allowing the mixture to warm to room
temperature and stirring for a further 15 min, aqueous
NaOH (30%) solution saturated in NaCl (1.0 mL) was
added. The mixture was vigorously stirred for 10 min
and then extracted with CH2Cl2. The combined organic
extracts were filtered through a Celite column and
concentrated in vacuo. Chromatography of the residue
on silica gel provided the corresponding epoxide.
The second eluted epoxide was obtained in 32% yield as
a yellow oil. This had identical spectral data to those
reported above for the natural product except for the
specific rotation, [h]2D0=−146 (c 1.15, CHCl3). As the
available amount was higher, repeated chromatography
allowed a more pure product to be obtained. In addi-
tion, more accurate specific rotation measurements
could be performed. Moreover, after diastereoselective
synthesis (see below) this epoxyacetate was assigned to
be (+)-(1R,2S,3S,4R)-1,2-epoxy-1-methyl-4-(1-methyl-
ethyl)-cyclohex-3-yl acetate 1.
4.11. Epoxides from (3R,4R)-1-methyl-4-(1-methyl-
Both enantiomeric tartrates provided (1R,2S,3S,4R)-
1,2-epoxy-1-methyl-4-(1-methylethyl)-cyclohexan-3-ol
10 when (3S,4R)-1-methyl-4-(1-methylethyl)-cyclo-
hexan-3-ol 3 was used as the starting alcohol. Yields
were about 52% although ca. 15% of starting material
was recovered. [h]2D0=−85 (c 2.93, CHCl3); HRMS (EI):
m/z 170.1316 (C10H18O2 requires 170.1306); IR: wmax
ethyl)-cyclohex-1-en-3-yl acetate 6
A mixture of two epoxides was obtained. The first
eluting product was isolated in a 60% yield; [h]2D0=+29
(c 1.00, CHCl3); HRMS (EI): m/z 213.1495 (M+H+,
C12H21O3 requires 213.1490); IR: wmax 2955, 2875, 1735,
1375, 1240 and 990; 1H NMR: lH 4.9 (d, J=10 Hz, 1H,
H-3), 2.8 (s, 1H, H-2), 2.1 (s, 3H, CH3CO), 2.1–1.9 (m,
2H, H-6), 1.6 (m, 4 H, H-4+H-5+(CH3)2CH), 1.3 (s,
3H, CH3), 0.8, 0.7 (d+d, J=7 Hz, 6H, (CH3)2CH); 13C
NMR: lC 170.4 (CO), 70.3 (C3), 61.7 (C2), 58.3 (C1),
43.8 (C4), 30.1 (C6), 27.6 (CH3)2CH), 22.3 (CH3CO),
21.1 (C5), 20.4, 16.8 and 16.1 (3×CH3); MS: m/z 213
[(M+1)+, 4], 212 (M+, 1), 169 (5), 154 (86), 152 (26), 137
(11), 127 (65), 112 (100), 109 (30), 84 (20), 81 (51), 71
(14) and 55 (16). After diastereoselective synthesis (see
below) this product was assigned to be (1R,2S,3R,4R)-
1,2-epoxy-1-methyl-4-(1-methylethyl)-cyclohex-3-yl acet-
ate 8.
1
3600–3200, 2957, 2926, 2868, 1384, 1073 and 842; H
NMR: lH 4.1 (m, 1H, H-3), 3.2 (d, J=8 Hz, 1H, H-2),
2.2–2.0 (m, 2H, H-4+OH), 1.6 (m, 2H, H-6), 1.3 (s, 3H,
CH3), 1.3–0.6 (m, 3H, H-5+(CH3)2CH), 1.0 and 0.9
(d+d, J=7 Hz, 6H, (CH3)2CH); 13C NMR: lC 64.5
(C3), 62.1 (C2), 61.0 (C1), 46.8 (C4), 31.0 (C6), 27.7
(CH3)2CH), 22.8 (C5), 20.8, 20.7 and 17.3 (3×CH3 MS:
m/z 170 (M+, 1), 137 (4), 127 (11), 123 (5), 112 (66), 109
(16), 99 (25), 97 (18), 86 (50), 84 (83), 81 (100), 72 (46),
71 (76), 57 (20) and 55 (35). Acetylation of this product
under the conditions described above provided (+)-
(1R,2S,3S,4R)-1,2-epoxy-1-methyl-4-(1-methylethyl)-
cyclohex-3-yl acetate, (+)-1, in 84% yield.