filtered off through a layer of Al O (5 cm). The organic layer was dried over Na SO and evaporated. The residue was
2
3
2
4
analyzed by capillary GC.
Reduction of (R)-4-Menthen-3-one (1) by NaBH . d) A suspension of NaBH (0.15 g, 3.8 mmol) in anhydrous
4
4
EtOH or THF (25 mL) was stirred, treated (ꢁ78, 0, or 25°C, Ar) with enone 1 (0.30 g, 2.0 mmol), stirred for 2 h, treated
dropwise at these same temperatures with H O (4 mL), stirred for 0.5 h, and passed through a Schott filter. The filtrate was
2
evaporated. The residue was diluted with t-BuOMe (50 mL), washed with saturated NaCl solution (2 ꢄ 5 mL), dried over
Na SO , and evaporated. The residue was analyzed by capillary GC.
2
4
20
24
(1R,5R)-5-Methyl-2-(1-methylethyl)cyclohex-2-en-1-ol (2a). [ꢅ] ꢁ31.5°(c 0.6, EtOH), [ꢅ] ꢁ32.0° (c 1.0, EtOH),
D
D
ꢁ1
R 0.55 (PE:t-BuOMe, 2:1). IR spectrum (KBr, , cm ): 1664 (C=C), 3048–3600 (OꢁH). PMR spectrum (300.13 MHz,
f
CDCl , ꢆ, ppm, J/Hz): 0.82 (3H, d, J = 7.0, 5-CH ), 1.15 [3H, d, J = 6.7, CH(CH ) ], 1.19 [3H, d, J = 6.7, CH(CH ) ], 1.52
3
3
3 2
3 2
2
3
3
(1H, ddd, J = 11.3, J = 8.4, J = 2.0, H -6), 1.62–1.70 (1H, m, H -6), 1.62–1.75 (1H, m, H -4), 1.98–2.06 (1H, m, H-5),
2.18–2.20 (1H, m, H -4), 2.95 [1H, d, J = 6.7, CH(CH ) ], 4.57 (1H, dd, J = 5.4, J = 5.3, H -1), 4.80 (1H, br.s, OH), 5.48
(1H, dd, J = 5.4, J = 4.7, H-3).
a
e
a
2
3
e
3 2
a
2
3
13
C NMR spectrum (75.47 MHz, CDCl , ꢆ, ppm): 20.77 (q, 5-CH ), 21.80 [q, CH(CH ) ], 22.58 [q, CH(CH ) ],
3
3
3 2
3 2
29.16 (d, C-5), 29.18 [d, CH(CH ) ], 34.25 (t, C-4), 42.25 (t, C-6), 67.53 (d, C-1), 120.26 (d, C-3), 145.89 (s, C-2).
3 2
Hydroboration-Oxidation of (R)-4-Menthen-3-one (1). A suspension of 1 (0.70 g, 4.6 mmol) and NaBH (0.63 g,
4
16.6 mmol) in anhydrous THF (40 mL) under Ar at 20°C was treated dropwise with a solution of BF ·Et O (0.8 mL) in
3
2
anhydrous THF (15 mL), stirred for 3.5 h at 20°C, treated dropwise with H O (1.5 mL), stirred for 10 min, treated sequentially
2
with NaOH solution (1.6 mL, 3 N) and H O (1.6 mL, 30%), stirred for 16 h, diluted with t-BuOMe (70 mL), washed with
2
2
saturated NaCl solution (2 ꢄ 5 mL), dried over Na SO , and evaporated to afford a mixture (3:2) of diastereomeric diols 3a
2
4
and 3b (0.73 g, 93%) that were separated by column chromatography (SiO , PEꢇPE:EtOAc (5:1)ꢇEtOAc).
2
Hydroboration-Oxidation of (1R,3R)-menthen-3-ol (2a). A suspension of 2a (0.70 g, 4.5 mmol) and NaBH
4
(0.62 g, 17.5 mmol) in anhydrous THF (40 mL) under Ar at 20°C was treated dropwise with a solution of BF ·Et O (0.8 mL)
3
2
in anhydrous THF (15 mL), stirred for 3.5 h at 20°C, treated dropwise with H O (1.5 mL), stirred for 10 min, treated with
2
NaOH solution (1.6 mL, 3 N) and H O (1.6 mL, 30%), stirred for 16 h, diluted with t-BuOMe (70 mL), washed with saturated
2
2
NaCl solution (2 ꢄ 5 mL), dried over Na SO , and evaporated to afford a mixture (3:2) of diastereomeric diols 3a and 3b
2
4
(0.63 g, 80%) that were separated by column chromatography (SiO , PEꢇPE:EtOAc (5:1)ꢇEtOAc).
2
(1R,3S)-5-Methyl-2-(1-methylethyl)cyclohexane-1,3-diol (3a). R 0.35 (PE:EtOAc, 2:1). PMR spectrum
f
(300.13 MHz, CDCl , ꢆ, ppm, J/Hz): 1.09 [6H, d, J = 7.2, CH(CH ) ], 1.13 (3H, d, J = 6.9, 5-CH ), 1.25–1.60 (4H, m, 2H-4,
3
3 2
3
2
3
2H-6), 1.80–1.95 (2H, br.s, 2OH), 1.91 (1H, dd, J = 3.4, J = 10.6, H -2), 1.93–2.02 (1H, m, H -5), 2.23–2.38 [1H, m,
CH(CH ) ], 3.41 (2H, dt, J = 10.6, J = 4.2, H -3, H -1).
a
a
2
3
3 2
13
a
a
C NMR spectrum (75.47 MHz, CDCl , ꢆ, ppm): 21.62 [q, 2 ꢄ (CH )-i-Pr], 25.31 (q, 5-CH ), 26.00 (d, C-5), 27.17
3
3
3
[d, CH(CH ) ], 44.36 (d, C-4, C-6), 56.67 (d, C-2), 69.88 (d, C-1, C-3).
3 2
20
(1R,3R)-5-Methyl-2-(1-methylethyl)cyclohexane-1,3-diol (3b). [ꢅ] ꢁ1.2° (c 1.6, CH Cl ), R 0.25 (PE:EtOAc,
D
2
2
f
2:1). PMR spectrum (300.13 MHz, CDCl , ꢆ, ppm, J/Hz): 0.94 (3H, d, J = 6.9, 5-CH ), 0.96 [3H, d, J = 6.5, CH(CH ) ], 1.02
3
3
3 2
[3H, d, J = 6.5, CH(CH ) ], 1.22–1.37 (1H, m, H -6), 1.37–1.52 (1H, m, H -4), 1.60–1.72 (1H, m, H -2), 1.69 (1H, dt,
3 2
a
a
a
2
3
J = 12.9, J = 4.9, H -4), 1.80–1.95 (2H, br.s, 2OH), 1.85–1.95 (1H, m, H -6), 1.90–2.00 (1H, m, H -5), 2.05–2.16 [1H, m,
e
e
a
2
3
2
3
CH(CH ) ], 4.12 (1H, dt, J = 4.9, J = 3.1, H -1), 4.25 (1H, dt, J = 9.9, J = 4.1, H -3).
3 2
13
e
a
C NMR spectrum (75.47 MHz, CDCl , ꢆ, ppm): 20.20 [q, 2ꢄ(CH )-i-Pr], 21.91 (q, 5-CH ), 25.01 [d, CH(CH ) ],
3
3
3
3 2
25.31 (d, C-5), 37.62 (t, C-6), 38.70 (t, C-4), 51.70 (d, C-2), 68.68 (d, C-3), 69.63 (d, C-1).
REFERENCES
1.
2.
3.
4.
J. Katsuhara, H. Yamasaki, and N. Yamamoto, Bull. Chem. Soc. Jpn., 43, 1584 (1970).
W. Chen and J. Xiao, Tetrahedron Lett., 42, 2897 (2001).
B. M. Mikhailov and Yu. N. Bubnov, Organoboron Compounds in Organic Synthesis [in Russian], Nauka, Moscow, 1977.
H. C. Brown and P. V. Ramachandran, Reduction in Organic Synthesis: Sixty Years of Hydride Reductions, ACS
Symposium Series, 1996.
5.
O. N. Chupakhin, G. V. Zyryanov, V. L. Rusinov, V. P. Krasnov, G. L. Levit, M. A. Korolyova, and M. I. Kodess,
Tetrahedron Lett., 42, 2393 (2001).
6.
Y. Senda and S. Imaizumi, Tetrahedron, 31, 2905 (1975).
980