Helvetica Chimica Acta – Vol. 90 (2007)
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pressure to give an oily product (22.77 g). The crude product was separated by CC (silica gel, toluene):
(1R,3R)-3a (11.2 g, 40%) and (1S,3S)-2 (12.6 g, 53%).
Data of (1R,3R)-3a: Viscous oil. [a]2D4 ¼ þ28.58 (c ¼ 1.13, CHCl3). IR (neat): 2928, 2857, 1735, 1457,
1363, 1243. 1H-NMR (CDCl3): 0.92 (d, J ¼ 6.7, Me); 1.04 – 1.13 (m, 1 H); 1.24 – 1.60 (m, 26 H); 1.64 – 1.72
(m, 1 H); 2.02 (s, MeCO); 4.94 – 5.01 (m, HÀC(1)). 13C-NMR (CDCl3): 21.2 (Me); 21.4 (Me); 23.7
(CH2); 25.2 (CH2); 26.5 (CH2); 26.6 (3 CH2); 26.7 (CH2); 26.8(2 CH 2); 27.1 (CH2); 28.5 (CH); 31.8
(CH2); 34.4 (CH2); 41.2 (CH2); 72.5 (CH); 170.7 (CO). EI-MS: 282 (1, Mþ), 239 (4), 222 (89), 206 (15),
194 (4), 180 (11), 166 (7), 152 (7), 138 (11), 124 (19), 110 (41), 96 (74), 82 (74), 69 (37), 59 (67), 43
(100).
Data of (1S,3S)-2: trans/cis 92 :8by GC. Optical purity: 77% ee by GC (chiral column). M.p. 36 – 37 8.
[a]2D4 ¼ À55.76 (c ¼ 1.04, MeOH). IR (CHCl3): 3684, 3619, 3020, 2930, 2858, 2400, 1521, 1460. 1H-NMR
(CDCl3): 0.92 (d, J ¼ 6.7, Me); 0.99 – 1.08( m, 1 H); 1.25 – 1.52 (m, 27 H); 1.64 – 1.70 (m, 1 H); 3.74 – 3.79
(m, HÀC(1)). 13C-NMR (CDCl3): 21.4 (Me); 23.7 (CH2); 25.2 (CH2); 26.5 (CH2); 26.6 (2 CH2); 26.7
(CH2); 26.8(CH 2); 26.9 (CH2); 27.1 (CH2); 27.4 (CH2); 28.7 (CH); 34.4 (CH2); 34.7 (CH2); 45.4 (CH2);
69.2 (CH). EI-MS: 222 (30, [M À 18]þ), 196 (19), 180 (4), 166 (4), 152 (4), 138 (8), 124 (15), 110 (30), 96
(70), 82 (13), 71 (100), 57 (30), 43 (22).
(1R,3R)-3-Methylcyclopentadecanol ((1R,3R)-2) from (1R,3R)-3a. At r.t., (1R,3R)-3a (10 g,
35.5 mmol) was hydrolyzed by 10% KOH in MeOH for 17 h (100% conversion, by GC). The mixture
was concentrated, and 10% aq. AcOH soln. was added for neutralization. The product was extracted with
hexane and the extract washed with 5% NaHCO3 soln., dried (MgSO4), and concentrated: (1R,3R)-2
(7.84 g, 92%). Ratio trans/cis 98:2 by GC. Optical purity: 96% ee by GC (chiral column). M.p. 43 – 44 8.
[a]2D4 ¼ þ69.0 (c ¼ 1, MeOH). Anal. data: identical to those of (1S,3S)-2.
(1S,3R)-3-Methylcyclopentadecanol ((1S,3R)-2) from (1R,3R)-2 by the Mitsunobu Reaction. A 40%
diethyl diazenedicarboxylate soln. in toluene (38ml, 87.4 mmol) was added dropwise to the mixture of
(1R,3R)-2 (15.0 g, 62.4 mmol), benzoic acid (8.38 g, 68.6 mmol), and triphenylphosphine (19.64 g,
74.9 mmol) in THF (90 ml), under N2 at À 158 for 1.5 h. After 4 h at À 158, the insoluble solid was
filtered off, and the filtrate was concentrated to give crude benzoate (1S,3R)-4 (42.0 g) which was purified
by CC (silica gel, toluene): (1S,3R)-3-methylcyclopentadecyl benzoate (1S,3R)-4; 12.3 g, 57%). Viscous
1
oil. [a]2D4 ¼ þ0.2 (c ¼ 0.5, CHCl3)2). IR (neat): 2980, 2857, 1716, 1451, 1274. H-NMR (CDCl3): 0.95 (d,
J ¼ 6.7, Me); 1.33 – 1.49 (m, 25 H); 1.57 – 1.62 (m, 1 H); 1.69 – 1.80 (m, 3 H); 5.18– 5.23 ( m, 1 H); 7.26 –
7.45 (m, 2 H); 7.52 – 7.56 (m, 1 H); 8.04 – 8.05 (m, 2 H). 13C-NMR (CDCl3): 20.7 (Me); 22.9 (CH2);
24.1 (CH2); 26.5 (CH2); 26.6 (CH2); 26.7 (2 CH, CH2); 26.8(CH ); 27.1 (CH2); 27.4 (CH2); 28.7 (CH);
2
32.9 (CH2); 35.5 (CH2); 39.9 (CH2); 73.8(CH); 128.3 (2 CH); 129.5 (2 CH); 131.0 (C); 132.6 (CH); 166.2
(CO). EI-MS: 344 (1, Mþ), 316 (2), 222 (32), 120 (100), 105 (8), 77 (13), 55 (11), 43 (6).
The benzoate (1S,3R)-4 was hydrolyzed by 5% KOH in MeOH at 508 for 5 h. The mixture was
concentrated, and 10% aq. AcOH soln. was added for neutralization. The product was extracted with
hexane, the extract washed with 5% NaHCO3 soln., dried (MgSO4), and concentrated, and the residue
purified by CC (silica gel, AcOEt/hexane 1:3): (1S,3R)-2 (9.15 g, 61%). Ratio cis/trans 98:2 by GC.
Optical purity: 96% ee by GC (chiral column). M.p. 38– 38.5 8. [a]2D4 ¼ þ11.65 (c ¼ 1.0, MeOH). IR
(CHCl3): 3684, 3619, 3021, 2926, 2858, 2400, 1521, 1430. 1H-NMR (CDCl3): 0.92 (d, J ¼ 6.7, Me); 1.17 –
1.22 (m, 1 H); 1.23 – 1.43 (m, 23 H); 1.49 – 1.58( m, 3 H); 1.59 – 1.65 (m, 1 H); 3.73 – 3.79 (m, HÀC(1)).
13C-NMR (CDCl3): 21.2 (Me); 22.8(CH 2); 23.9 (CH2); 26.6 (2 CH2); 26.7 (2 CH2); 26.8(CH 2); 27.2
(CH2); 27.4 (CH2); 28.8 (CH); 35.5 (CH2); 36.3 (CH2); 43.7 (CH2); 69.8(CH). EI-MS: 222 (22, [ Mþ À
18]), 196 (19), 180 (4), 166 (8), 152 (4), 137 (4), 124 (11), 110 (26), 96 (59), 82 (89), 71 (100), 57 (41), 43
(22).
(1R,3S)-3-Methylcyclopentadecanol ((1R,3S)-2) from (1S,3S)-2 by Mitsunobu Reaction. As descri-
bed for (1S,3R)-2, from (1S,3S)-2: intermediate benzoate (1R,3S)-4 (63%) as a viscous oil with [a]D24
¼
þ0.37 (c ¼ 1.02, CHCl3)2) and anal. data identical to those of (1S,3R)-4. Subsequent hydrolysis gave
(1R,3S)-2 (67%). Ratio cis/trans 92 :8by GC. Optical purity: 77% ee by GC (chiral column). M.p. 43 –
448. [a]2D4 ¼ þ3.57 (c ¼ 1.0, MeOH)2). Anal. data: identical to those of (1S,3R)-2.
2
)
The presence of 8% of another isomer may account for the unexpected identical sense of rotation as
compared to the pure enantiomer.