7522
P. Crotti et al. / Tetrahedron 56 (2000) 7513–7524
FTIR spectrophotometer: the concentration of the solution
was 5×10Ϫ3 M, or lower. All reactions were followed by
TLC on Alugram SIL G/UV254 silica gel sheets (Mach-
ery–Nagel) with detection by UV. Silica gel 60 (Mach-
ery–Nagel 230–400 mesh) was used for flash
chromatography. THF was distilled from sodium/benzophe-
none ketyl under a nitrogen atmosphere immediately prior
to use. Epoxides 1–8, HEs 13–15, 17–20, 27–29 and 31–
341a,c–e and alcohol 434 were prepared as previously
described.
of HEs 30 and 15 which was subjected to preparative TLC
(an 8:2 hexane/AcOEt mixture was used as the eluant).
Extraction of the two most intense bands afforded pure
HE 15 (0.010 g) and t-3-benzyloxy-t-2-methoxy-r-1-cyclo-
hexanol (30), pure as a liquid (0.030 g) (Found: C, 70.91;
H, 8.30. C14H20O3 requires C, 71.16; H, 8.53%): IR (CCl4)
1
3597 cmϪ1(1,2 OH···O). H NMR d 7.24–7.40 (m, 5H),
4.66 (d, 1H, J12.2 Hz), 4.54 (d, 1H, J12.2 Hz), 3.90–
4.02 (m, 2H), 3.36 (s, 3H), 2.94 (dd, 1H, J9.3, 2.9 Hz),
1.98–2.06 (m, 2H). 13C NMR d 139.4, 128.9, 128.3, 128.1,
87.4, 72.4, 71.4, 69.7, 57.4, 32.2, 28.3, 18.9.
Acid hydrolysis (0.2N H2SO4–H2O/dioxane) of epoxides
2 and 6
The same procedure carried out on trans-1,2-cyclohexane-
diol afforded pure trans-2-benzyloxy-cyclohexanol (44),1c as
a liquid: 13C NMR d 129.2, 128.4, 128.3, 84.2, 74.5, 72.8,
29.9, 24.9, 24.6.
The following procedure is typical. Epoxide 6 (0.090 g,
0.44 mmol) was added to a 1:1 0.2N H2SO4/dioxane
(15 ml) and the reaction mixture was stirred at rt for
40 min. Dilution with saturated aqueous NaHCO3, extrac-
tion with ether and evaporation of the ether extracts afforded
c-3-benzyloxy-r-1,t-2-cyclohexanediol (35) (0.080 g), as a
liquid (Found: C, 70.42; H, 7.95. C13H18O3 requires C,
70.24; H, 8.16%): IR (CCl4) 3600 (1,2 OH···O) and
Dimethoxy derivatives 21–26
Typical procedure. Following the usual procedure, the treat-
ment of HE 27 (0.10 g, 0.42 mmol) in anhydrous THF
(12 ml) with MeI (0.05 ml) in the presence of 60% NaH
(0.050 g, 1.3 mmol) afforded a crude product mostly
consisting of DM 22 which was subjected to preparative
TLC (an 8:2 hexane/AcOEt mixture was used as the eluant).
Extraction of the most intense band afforded pure r-1-
benzyloxy-t-3,c-4-dimethoxycyclohexane (22), as a liquid
(0.080 g) (Found: C, 71.72; H, 8.59. C15H22O3 requires C,
1
3525 cmϪ1(1,3 OH···O). H NMR d 7.19–7.39 (m, 5H),
4.58 (d, 1H, J11.2 Hz), 4.42 (d, 1H, J11.2 Hz), 3.08–
3.43 (m, 4H), 3.26 (t, 1H, J8.8 Hz). 13C NMR d 139.7,
129.1, 128.9, 128.4, 81.5, 80.0, 73.5, 72.0, 32.1, 29.7, 20.6.
The same reaction carried out on epoxide 2 (0.10 g,
0.49 mmol) afforded pure t-3-benzyloxy-r-1,t-2-cyclo-
hexanediol (36), as a liquid (0.070 g) (Found: C, 69.98; H,
8.04. C13H18O3 requires C, 70.24; H, 8.16%): IR (CCl4)
1
71.97; H, 8.86%): H NMR d 7.22–7.37 (m, 5H), 4.55 (d,
1H, J11.9 Hz), 4.47 (d, 1H, J11.9 Hz), 3.63–3.75 (m,
1H), 3.41–3.54 (m, 1H), 3.40 (s, 3H), 3.38 (s, 3H), 3.14–
3.23 (m, 1H), 2.00–2.12 (m, 1H). 13C NMR d 139.7, 128.9,
128.0, 80.6, 79.5, 73.7, 70.6, 57.8, 57.3, 33.6, 32.7, 27.5,
24.3.
1
3593 and 3596 cmϪ1(1,2 OH···O). H NMR d 7.26–7.41
(m, 5H), 4.66 (d, 1H, J11.7 Hz), 4.40 (d, 1H,
J11.7 Hz), 3.86–3.89 (m, 1H), 3.67–3.81 (m, 1H), 3.32
(dd, 1H, J8.8, 3.4 Hz). 13C NMR d 138.9, 129.2, 128.5,
128.3, 78.2, 77.1, 72.2, 71.6, 32.0, 27.9, 19.0.
Application of the same procedure to HE 13 (0.070 g,
0.30 mmol) afforded pure r-1-benzyloxy-c-3,t-4-dimethoxy-
cyclohexane (21), as a liquid (0.070 g) (Found: C, 72.15; H,
Monomethylation of trans 1,2-cyclohexanediol and diols
35 and 36
1
8.54. C15H22O3 requires C, 71.97; H, 8.86%): H NMR d
7.23–7.35 (m, 5H), 4.55 (s, 2H), 3.44 (s, 6H), 3.30–3.44 (m,
1H), 3.02–3.16 (m, 2H), 2.42–2.53 (m, 1H), 2.05–2.17 (m,
2H). 13C NMR d 139.2, 129.0, 128.2, 83.4, 81.7, 75.7, 71.0,
58.1, 57.9, 36.4, 30.3, 26.6.
The following procedure is typical. A solution of diol 35
(0.080 g, 0.36 mmol) in anhydrous THF (2.0 ml) was added
at 40ЊC to a suspension of NaH (0.020 g of a 60% dispersion
in mineral oil, 0.50 mmol) in anhydrous THF (2 ml). After
4 h stirring at the same temperature, MeI (0.2 ml) was added
and the resulting reaction mixture was stirred at 50ЊC for
18 h. Dilution with ether and water, and evaporation of the
washed (water) organic solution afforded a crude liquid
product (0.080 g) consisting of a 7:3 mixture of HEs 16
and 29 which was subjected to preparative TLC (an 8:2
hexane/AcOEt mixture was used as the eluant). Extraction
of the two most intense bands afforded pure HE 29 (0.010 g)
and c-3-benzyloxy-t-2-methoxy-r-1-cyclohexanol (16), as a
liquid (0.010 g) (Found: C, 71.39; H, 8.25. C14H20O3
requires C, 71.16; H, 8.53%): IR (CCl4) 3588 (1,2
Application of the same procedure to HE 33 (0.10 g,
0.40 mmol) afforded pure r-1-benzyloxymethyl-t-2,c-3-
dimethoxycyclohexane (26), as a liquid (0.010 g) (Found:
C, 72.94; H, 8.95. C16H24O3 requires C, 72.69; H, 9.15%):
1H NMR d 7.26–7.35 (m, 5H), 4.51 (s, 2H), 3.55–3.59 (m,
2H), 3.50 (s, 3H), 3.44 (s, 3H), 2.92–3.15 (m, 2H), 2.03–
2.13 (m, 2H J19.0 Hz). 13C NMR d 139.5, 129.0, 128.2,
85.7, 84.8, 73.8, 71.9, 61.0, 58.0, 44.1, 30.9, 29.0, 23.6.
The same reaction carried out on HE 34 (0.10 g, 0.40 mmol)
afforded pure r-1-benzyloxymethyl-c-2,t-3-dimethoxycyclo-
hexane (25), as a liquid (0.010 g) (Found: C, 72.41; H, 8.90.
1
OH···O) and 3509 cmϪ1(1,3 OH···O). H NMR d 7.26–
1
7.35 (m, 5H), 4.67 (d, 1H, J11.2 Hz), 4.58 (d, 1H,
J11.2 Hz), 3.66 (s, 3H), 3.33–3.55 (m, 2H), 3.02 (t, 1H,
J8.8 Hz). 13C NMR d 129.3, 129.1, 128.4, 128.3, 88.9,
81.6, 72.9, 72.3, 67.6, 31.8, 30.4, 20.1.
C16H24O3 requires C, 72.69; H, 9.15%): H NMR d 7.25–
7.35 (m, 5H), 4.51 (s, 2H), 3.30–3.71 (m, 4H), 3.36 (s, 6H),
2.10–2.21 (m, 1H, W1/221.0 Hz). 13C NMR d 139.6,
129.0, 128.2, 128.0, 78.7, 78.3, 76.3, 73.6, 58.8, 57.1,
37.5, 25.7, 24.3, 19.9.
Application of the same procedure to diol 36 afforded a
crude liquid product (0.080 g) consisting of an 8:2 mixture
The same reaction carried out on diol 35 (0.090 g,