(
1R,2R,3S,5R)-5-(tert-Butyldimethylsiloxy)-2,3-epoxycyclo-
acetate, and the extract was dried (Na SO ) and concentrated to
leave a residue, which was purified by column chromatography
on silica gel with hexane–EtOAc (1 : 1, v/v) as eluent to give
2
4
hexanol 5 and (1S,2R,3S,5R)-5-(tert-butyldimethylsiloxy)-2,3-
epoxycyclohexanol 6
ketal 10 (15 mg, 48%) as a colorless oil, [α] ϩ20.8 (c 0.4,
D
To a stirred solution of ketone 4 (100 mg, 0.42 mmol) in MeOH
Ϫ1
1
CHCl ); IR 3400 cm ; H NMR δ 1.72 (1H, dd, J = 7.9 and
3
(
3 mL) was added portionwise NaBH (19 mg, 0.50 mmol) at
4
1
2
3.3 Hz), 1.85–1.95 (2H, m), 2.31 (1H, dd, J = 4.9 and 15.0 Hz),
.64 (1H, br d, J = 5.9 Hz), 3.24 (1H, d, J = 4.9 Hz), 3.35–3.38
0
ЊC, and the resulting mixture was stirred for a further 10 min
at the same temperature. After treatment with brine, the
mixture was extracted with ethyl acetate, and the extract was
dried (Na SO ), and concentrated to leave a residue, which was
13
(
1H, m), 3.35 (3H, s), 3.38 (3H, s), 3.90 (1H, br s); C NMR
δ 33.4, 36.7, 48.4, 49.0, 53.1, 53.5, 63.7, 98.8. The ketal 10 was
used in the next step without further purification.
2
4
purified by column chromatography on silica gel with hexane–
EtOAc (5 : 1, v/v) as eluent to afford alcohol 5 (26 mg, 25%) as a
Ϫ1
1
(2S,3S,5S)-2,3-Epoxy-5-hydroxycyclohexanone 11
colorless oil, [α] ϩ41.3 (c 0.5, CHCl ); IR 3460 cm ; H NMR
D
3
δ 0.04 (6H, s), 0.68 (9H, s), 1.48 (1H, ddd, J = 1.5, 10.6, and 12.1
A solution of ketal 10 (82 mg, 0.47 mmol) in 1% hydrochloric
acid (10 mL) and MeOH (2 mL) was stirred at room tem-
perature for 3 h. After treatment with saturated aq. NaHCO3,
the mixture was extracted with ethyl acetate. The extract was
dried (Na SO ) and concentrated to leave a residue, which was
Hz), 1.74–1.85 (2H, m), 2.00 (2H, dd, J = 5.8 and 10.6 Hz), 3.37
13
(
2H, m), 3.98 (1H, m), 4.32 (1H, br t, J = 5.8 Hz); C NMR
δ Ϫ5.1, Ϫ5.0, 17.9, 25.6, 32.6, 36.2, 54.0, 55.3, 65.0, 65.3;
HRMS (EI) [Calc. for C H O Si: (M Ϫ Bu) 187.0790. Found:
8
15
3
2
4
m/z, 187.0787]. Further elution with the same solvent system
gave a diastereoisomeric alcohol 6 (43.0 mg, 43%) as a colorless
purified by column chromatography on silica gel with hexane–
EtOAc (1 : 1, v/v) as eluent to give ketone 11 (43 mg, 71%) as a
Ϫ1
1
Ϫ1 1
oil, [α]D Ϫ17.3 (c 0.4, CHCl ); IR 3500 cm ; H NMR δ 0.10
colorless oil, [α] Ϫ31.3 (c 0.3, CHCl ); IR 3420, 1718 cm ; H
3
D
3
(
6H, s), 0.91 (9H, s), 1.68 (2H, ddd, J = 1.8, 4.0, and 14.5 Hz),
NMR δ 1.90 (1H, br s), 2.02–2.13 (1H, m), 2.24 (1H, dd, J = 6.2
and 15.2 Hz), 2.51 (1H, dd, J = 3.4 and 15.2 Hz), 2.92 (1H, d,
J = 3.4 and 15.2 Hz), 3.30 (1H, d, J = 3.4 Hz), 3.60 (1H, br s),
1
3
.76–1.87 (1H, m), 2.03–2.09 (1H, m), 3.18–3.24 (1H, m), 3.29–
.34 (1H, m), 4.00–4.06 (1H, m), 4.15–4.24 (1H, m); C NMR
13
13
δ Ϫ5.2, Ϫ5.0, 17.8, 25.7, 32.0, 32.9, 49.6, 54.4, 65.2, 65.3;
HRMS (EI) [Calc. for C H O Si: (M Ϫ Bu) 187.0790. Found:
4.36 (1H, br s); C NMR δ 31.8, 35.5, 54.8, 55.7, 66.8, 205.3;
ϩ
8
15
3
HRMS (EI) (Calc. for C H O : M, 128.0473. Found: M ,
6
8
3
m/z, 187.0778].
128.0491).
(
1R,3R,4R,5S)-4,5-Epoxycyclohexane-1,3-diol 7
To a stirred solution of silyl ether 5 (44 mg, 0.18 mmol) in THF
1 mL) was added TBAF (0.54 mL, 0.54 mmol) at ambient
temperature and the resulting mixture was stirred for a further
h at the same temperature. The mixture was treated with
saturated aq. NH Cl and extracted with ethyl acetate. The
(
4
1R,3R,4R,5S)-4,5-Epoxycyclohexane-1,3-diol 7 and (1R,3S,-
R,5S)-4,5-epoxycyclohexane-1,3-diol 12
(
To a stirred solution of ketone 11 (14.8 mg, 0.116 mmol)
in MeOH (1 mL) was added portionwise NaBH (5.2 mg,
0
a further 10 min at the same temperature. After addition of
acetone (1 mL), the mixture was concentrated, and extracted
with ethyl acetate. The extract was dried (Na SO ) and concen-
trated to leave a residue, which was purified by column chroma-
tography on silica gel with hexane–EtOAc (1 : 3, v/v) as eluent
to give diol 12 (2.7 mg, 18%) as the first eluant as a colorless oil,
4
1
.139 mmol) at 0 ЊC, and the resulting mixture was stirred for
4
extract was dried (Na SO ) and concentrated to leave a residue,
which was purified by column chromatography on silica gel
with hexane–EtOAc (1 : 3, v/v) as eluent to give diol 7 (23 mg,
2
4
2
4
Ϫ1
9
8%) as a colorless oil, [α] ϩ20.8 (c 0.4, CHCl ); IR 3345 cm ;
D
3
1
H NMR δ 1.52–1.88 (4H, m), 2.04 (1H, d, J = 2.8 Hz), 2.19
Ϫ1
1
(
(
6
1H, dd, J = 4.8 and 15.8 Hz), 3.41 (2H, br s), 4.07 (1H, m), 4.36
IR 3345 cm ; H NMR δ 1.70–1.92 (2H, m), 2.02–2.23 (2H,
13
13
1H, br t, J = 6.3 Hz); C NMR δ 32.1, 36.3, 54.2, 55.0, 64.5,
m), 2.54 (1H, br s), 4.04 (1H, br s), 4.25 (1H, br s); C NMR
δ 32.0, 33.0, 49.9, 54.4, 64.0, 65.3; HRMS (EI) [Calc. for
C H O : (M ϩ 1) 131.0708. Found: m/z, 131.0685]. Further
4.7; HRMS (EI) [Calc. for C H O : (M ϩ 1) 131.0708. Found:
6 11 3
m/z, 131.0685].
6
11
3
elution with the same solvent system gave 7 (8.1 mg, 54%),
which was identical with the sample obtained above.
(
1R,2R,3S,5R)-1,5-Dibenzyloxy-2,3-epoxycyclohexane 8
To a stirred suspension of diol 7 (4.5 mg, 0.035 mmol), sodium
hydride (60% in mineral oil; 2.9 mg, 0.073 mmol), and
tetrabutylammonium iodide (TBAI) (2.6 mg, 6.9 µmol) in THF
Acknowledgements
(
0.5 mL) was added benzyl bromide (12.3 µL, 0.10 mmol) at
ЊC, and the resulting mixture was stirred for a further 24 h at
Support was provided by a Grant-in-Aid from the Ministry of
Education, Culture, Sports, Science and Technology of Japan.
0
room temperature. The mixture was treated with saturated aq.
NH Cl and extracted with ethyl acetate. The extract was dried
4
References
(
Na SO ) and concentrated to leave a residue, which was puri-
2 4
fied by column chromatography on silica gel with hexane–
EtOAc (10 : 1, v/v) as eluent to give di(benzyl ether) 8 (7.4 mg,
1 (a) E. Winterfeldt, Chem. Rev., 1993, 93, 827; (b) C. Borm,
D. Meibom and E. Winterfeldt, Chem. Commun., 1996, 887;
13b
9%) as a colorless oil, [α]D 1ϩ65.6 (c 0.2, MeOH) {lit.,
(
c) A. J. K. Klunder, J. Zhu and B. Zwanenburg, Chem. Rev., 1999,
99, 1163; (d ) K. Ogasawara, J. Synth. Org. Chem. Jpn., 1999, 57,
57.
R. J. Ferrier and S. Middleton, Chem. Rev., 1993, 93, 2779.
C. Chapuis, R. Brauchli and W. Thommen, Helv. Chim. Acta, 1993,
76, 535 and references therein.
6
[α]D ϩ72.6 (c 0.208, MeOH)}; H NMR δ 1.60–1.71 (1H, m),
9
2
3
.04–2.18 (3H, m), 3.26–3.32 (1H, m), 3.40–3.44 (1H, m),
.68–3.75 (1H, m), 4.13–4.20 (1H, m), 4.41 (2H, s), 4.67 (1H, d,
2
3
J = 12.4 Hz), 4.72 (1H, d, J = 12.4 Hz), 7.22–7.53 (10H, m);
ϩ
HRMS (EI) (Calc. for C H O : M, 310.1569. Found: M ,
4 M. T. Barros, C. D. Maycock and M. R. Ventura, J. Org. Chem.,
997, 62, 3984 and references therein.
20
22
3
1
3
10.1561). These spectroscopic data were identical with those
13b
5 D. H. R. Barton, S. Bath, D. C. Billington, S. D. Gero, B. Quiclet-
Site and M. Samadi, J. Chem. Soc., Perkin Trans. 1, 1995, 1551
and references therein.
reported.
(
1S,3S,4S)-4,5-Epoxy-3,3-dimethoxycyclohexanol 10
6
(a) M. Polla and T. Frejd, Tetrahedron, 1991, 47, 5883; (b) H.
Miyaoka, S. Sagawa, T. Inoue, H. Nagaoka and Y. Yamada, Chem.
Pharm. Bull., 1994, 42, 405; (c) A. N. E. Weissfloch and R. J.
Kazlauskas, J. Org. Chem., 1995, 60, 6959.
A solution of ketone 4 (43.2 mg, 0.18 mmol) in 1 wt % I2–
MeOH was stirred at room temperature for 24 h. The mixture
was treated with 5% aq. Na S O , and then concentrated
2
2
3
7 (a) E. Wada, H. Yasuoka and S. Kanemasa, Chem. Lett., 1994,
1637; (b) S. A. Kozumin and V. H. Rawal, J. Am. Chem. Soc., 1997,
in vacuo. The residual aqueous layer was extracted with ethyl
2
918 J. Chem. Soc., Perkin Trans. 1, 2001, 2915–2919