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C. Fuganti et al. / Tetrahedron: Asymmetry 19 (2008) 2425–2437
1H), 4.10–4.27 (m, 2H); 13C NMR (100.6 MHz), d 14.2, 19.1, 22.3,
23.6, 24.6, 25.0, 30.3, 34.9, 38.0, 48.6, 52.0, 60.6, 74.0, 173.5; MS,
m/z (%) 242 (M+, C14H26O3, 1), 227 (2), 224 (1), 197 (2), 186 (5),
172 (4), 157 (100), 137 (13), 130 (29), 111 (26), 95 (11), 81 (9),
69 (28), 55 (13).
The same procedure described above was applied in the reduc-
tion of hydroxy esters (ꢀ)-17, (+)-16, (+)-17, (ꢀ)-21, (+)-21, 24, and
25 to give diols (ꢀ)-19 (92%), (+)-18 (91%), (+)-19 (89%), (ꢀ)-22
(94%), (+)-22 (92%), 26 (91%), and 27 (93%), respectively.
Data for (1R,3R,4S)-3-(20-hydroxyethyl)-p-menthan-3-ol (ꢀ)-18:
(1S,3S,4R)-3-Ethoxycarbonylmethyl-p-menthan-3-ol (+)-16 and
Colorless crystals; mp 80–82 °C; ½a D20
¼ ꢀ16 (c 2, CHCl3); IR (Nujol,
ꢃ
(1S,3R,4R)-3-ethoxycarbonylmethyl-p-menthan-3-ol
(+)-17
cmꢀ1), mmax 3378, 3295, 1074, 1030, 854; 1H NMR (250 MHz), d
0.77–0.98 (m, 2H), 0.90 (d, 3H, J = 6.5 Hz), 0.91 (d, 6H, J = 6.7 Hz),
1.03 (ddd, 1H, J = 12.9, 3.5, 2.0 Hz), 1.27–1.59 (m, 3H), 1.60–1.93
(m, 3H), 2.12–2.36 (m, 2H), 2.23 (br s, 2H), 3.70–3.83 (m, 1H),
3.99 (ddd, 1H, J = 14.5, 10.3, 4.1 Hz); 13C NMR (62.8 MHz), d 17.9,
20.3, 22.3, 23.6, 25.5, 27.7, 34.9, 40.8, 46.2, 50.0, 58.9, 75.2; MS,
m/z (%) 200 (M+, C12H24O2, 1), 185 (1), 155 (15), 137 (6), 115
(100), 97 (20), 81 (13), 69 (28), 55 (13).
showed ½a 2D0
ꢃ
¼ þ15:0 (c 1, CHCl3) and ½a D20
¼ þ17:3 (c 1, CHCl3),
ꢃ
respectively; IR, 1H NMR, 13C NMR, and MS data in accordance with
those of (ꢀ)-16 and (ꢀ)-17, respectively.
Data for (1S,3R,4S)-3-ethoxycarbonylmethyl-p-menthan-3-ol (ꢀ)
-21: Colorless oil; ½a D20
ꢃ
¼ ꢀ25:1 (c 2, CHCl3); IR (film, cmꢀ1), mmax
3515, 1714, 1458, 1371, 1323, 1219, 1187, 1030; 1H NMR
(400 MHz), d 0.92 (d, 3H, J = 6.8 Hz), 0.96 (d, 3H, J = 6.8 Hz), 1.02
(d, 3H, J = 6.8 Hz), 1.06–1.19 (m, 1H), 1.21–1.38 (m, 2H), 1.26 (t,
3H, J = 7.1 Hz), 1.39–1.56 (m, 3H), 1.57–1.70 (m, 1H), 1.71–1.81
(m, 1H), 2.01 (m, 1H), 2.45 (d, 1H, J = 15.3 Hz), 2.73 (d, 1H,
J = 15.3 Hz), 3.42 (s, 1H), 4.10–4.22 (m, 2H); 13C NMR
(100.6 MHz), d 14.2, 20.4, 21.7, 22.1, 25.1, 26.3, 28.7, 30.9, 43.2,
44.7, 48.5, 60.4, 74.4, 173.4; MS, m/z (%) 242 (M+, C14H26O3, 1),
227 (2), 224 (1), 197 (1), 186 (4), 172 (5), 157 (100), 139 (16),
130 (24), 111 (27), 95 (13), 81 (10), 69 (36), 55 (17).
Data for (1R,3S,4S)-3-(20-hydroxyethyl)-p-menthan-3-ol (ꢀ)-19:
Colorless crystals; mp 84–86 °C; ½a D20
¼ ꢀ33:4 (c 2, CHCl3); IR (Nu-
ꢃ
jol, cmꢀ1), max 3308, 1157, 1071, 865; 1H NMR (250 MHz), d 0.80–
m
1.06 (m, 2H), 0.85 (d, 3H, J = 6.7 Hz), 0.90 (d, 3H, J = 6.2 Hz), 0.98 (d,
3H, J = 6.7 Hz), 1.1 (m, 2H), 1.26–1.50 (m, 1H), 1.57–1.80 (m, 3H),
1.83–2.00 (m, 1H), 2.04–2.26 (m, 2H), 2.30 (s, 2H), 3.72–3.85 (m,
1H), 3.93 (ddd, 1H, J = 13.9, 10.8, 3.1 Hz); 13C NMR (62.8 MHz), d
19.4, 22.3, 24.0, 24.7, 24.8, 30.1, 32.4, 35.0, 46.9, 53.9, 59.1, 76.9;
MS, m/z (%) 200 (M+, C12H24O2, 1), 185 (1), 155 (6), 137 (4), 129
(2), 121 (2), 115 (100), 97 (19), 88 (6), 81 (11), 69 (26), 55 (12).
(1S,3S,4R)-3-(20-Hydroxyethyl)-p-menthan-3-ol (+)-18 and
(1S,3R,4R)-3-(20-hydroxyethyl)-p-menthan-3-ol (+)-19 showed
(1R,3S,4R)-3-Ethoxycarbonylmethyl-p-menthan-3-ol
(+)-21
showed ½a 2D0
ꢃ
¼ þ25:6 (c 2, CHCl3); IR, 1H NMR, 13C NMR, and MS
data in accordance with those of (ꢀ)-21.
Racemic isopulegone (40 g, 263 mmol) and ethyl bromoacetate
(65 g, 389 mmol) were condensed by a Reformatsky reaction
according to the procedure described for the preparation of (ꢀ)
-16 and (ꢀ)-17. Chromatography and purification afforded 24 (first
eluted diastereoisomer, 29.5 g, 47% yield) and 25 (last eluted dia-
stereoisomer, 10.2 g, 16% yield).
½
a 2D0
ꢃ
¼ þ15:8 (c 2, CHCl3) and ½a D20
¼ þ32:5 (c 2, CHCl3), respec-
ꢃ
tively; IR, 1H NMR, 13C NMR, and MS data in accordance with those
of (ꢀ)-18 and (ꢀ)-19, respectively.
Data for (1S,3R,4S)-3-(20-hydroxyethyl)-p-menthan-3-ol (ꢀ)-22:
Colorless crystals; mp 79–81 °C; ½a D20
¼ ꢀ28:6 (c 1, CHCl3); IR (Nu-
ꢃ
Data for (1RS,3RS,4SR)-3-ethoxycarbonylmethyl-p-menth-8(9)-
en-3-ol 24: Colorless oil; IR (film, cmꢀ1), mmax 3511, 1713, 1636,
1373, 1339, 1231, 1186, 1095, 1023, 892; 1H NMR (400 MHz), d
0.84–1.04 (m, 2H), 0.87 (d, 3H, J = 6.7 Hz), 1.27 (t, 3H, J = 7.1 Hz),
1.39–1.46 (m, 1H), 1.71–1.81 (m, 2H), 1.79 (s, 3H), 1.82–2.01 (m,
3H), 2.22 (d, 1H, J = 15.6 Hz), 2.65 (d, 1H, J = 15.6 Hz), 3.37 (br s,
1H), 4.15 (q, 2H, J = 7.1 Hz), 4.74 (br s, 1H), 4.81 (br s, 1H); 13C
NMR (100.6 MHz), d 14.1, 21.5, 22.2, 27.0, 27.4, 34.9, 44.7, 46.7,
53.9, 60.4, 72.0, 113.4, 147.4, 173.5; MS, m/z (%) 240 (M+,
C14H24O3, 2), 222 (100), 207 (16), 179 (89), 166 (31), 157 (59),
134 (43), 123 (24), 109 (59), 95 (64), 81 (24), 69 (70), 55 (23).
Data for (1RS,3SR,4SR)-3-ethoxycarbonylmethyl-p-menth-8(9)-
en-3-ol 25: Colorless oil; IR (film, cmꢀ1), mmax 3512, 1713, 1641,
1456, 1372, 1332, 1192, 1093, 1042, 891; 1H NMR (400 MHz), d
0.85–1.03 (m, 2H), 0.89 (d, 3H, J = 6.5 Hz), 1.27 (t, 3H, J = 7.1 Hz),
1.39–1.56 (m, 2H), 1.64 (ddd, 1H, J = 3.6, 3.8, 13.9 Hz), 1.72 (m,
1H), 1.76–1.90 (m, 1H), 1.89 (s, 3H), 2.12 (dd, 1H, J = 3.6,
13.2 Hz), 2.55 (s, 2H), 3.80 (br s, 1H), 4.16 (m, 2H), 4.66 (br s,
1H), 4.95 (br s, 1H); 13C NMR (100.6 MHz), d 14.1, 22.1, 25.8,
28.5, 30.0, 34.7, 37.6, 48.1, 53.0, 60.4, 73.5, 112.3, 147.4, 173.5;
MS, m/z (%) 240 (M+, C14H24O3, 2), 222 (99), 207 (17), 179 (100),
166 (33), 157 (67), 134 (50), 123 (29), 109 (69), 95 (73), 81 (30),
69 (81), 55 (28).
Hydroxy ester (ꢀ)-16 (15 g, 62 mmol) in dry THF (50 mL) was
added dropwise and under nitrogen to a stirred suspension of
LiAlH4 (3 g, 79 mmol) in dry THF (150 mL). The reaction mixture
was heated for 1 h at reflux then cooled to 0 °C, and quenched by
dropwise addition of ethyl acetate (50 mL) followed by addition
of 5% aqueous HCl (300 mL). The organic phase was separated,
and the aqueous layer was extracted with diethyl ether
(3 ꢂ 100 mL). The combined organic phases were washed with
brine (100 mL), dried over sodium sulfate, filtered, and concen-
trated under reduced pressure. The residue was purified by chro-
matography eluting with hexane/ethyl acetate (9:1 v/v) to afford
pure diol (ꢀ)-18 (11.2 g, 90% yield).
jol, cmꢀ1), max 3321, 3255, 1374, 1307, 1178, 1115, 1055, 1040; 1H
m
NMR (250 MHz), d 0.95 (d, 3H, J = 6.9 Hz), 0.96 (d, 3H, J = 6.6 Hz),
1.06 (d, 3H, J = 6.6 Hz), 1.03–1.14 (m, 1H), 1.29–1.50 (m, 4H),
1.53–1.67 (m, 2H), 1.68–1.83 (m, 2H), 1.90–2.06 (m, 2H), 2.18 (s,
1H), 2.71 (br t, 1H, J = 4.9 Hz), 3.86 (m, 2H); 13C NMR (62.8 MHz),
d 20.8, 22.1, 22.7, 25.4, 25.9, 29.0, 30.9, 41.0, 43.4, 48.2, 59.6,
77.1; MS, m/z (%) 200 (M+, C12H24O2, 1), 185 (2), 155 (15), 137
(8), 115 (100), 97 (23), 81 (17), 69 (31), 55 (15).
Data for (1R,3S,4R)-3-(20-hydroxyethyl)-p-menthan-3-ol (+)-22:
Colorless crystals; mp 80–82 °C; ½a D20
ꢃ
¼ þ28:2 (c 1, CHCl3); IR, 1H
NMR, 13C NMR, and MS data in accordance with those of (ꢀ)-22.
Data for (1RS,3RS,4SR)-3-(20-hydroxyethyl)-p-menth-8(9)-en-3-ol
26: Colorless crystals; mp 73–74 °C; IR (Nujol, cmꢀ1), mmax 3374,
1637, 1374, 1034, 948, 889, 856, 812; 1H NMR (400 MHz), d
0.85–1.00 (m, 2H), 0.91 (d, 3H, J = 6.5 Hz), 1.37–1.49 (m, 2H),
1.70–2.03 (m, 6H), 1.82 (s, 3H), 2.37 (s, 1H), 2.68 (m, 1H), 3.75
(m, 1H), 3.96 (m, 1H), 4.75 (s, 1H), 4.87 (br s, 1H); 13C NMR
(100.6 MHz), d 22.3, 23.5, 27.5, 27.5, 34.8, 41.9, 45.0, 53.9, 59.1,
73.8, 112.6, 148.0; MS, m/z (%) 198 (M+, C12H22O2, 2), 180 (4),
165 (5), 153 (12), 136 (16), 128 (12), 115 (52), 110 (34), 95 (63),
81 (26), 73 (58), 69 (100), 55 (52).
Data for (1RS,3SR,4SR)-3-(20-hydroxyethyl)-p-menth-8(9)-en-3-ol
27: Colorless crystals; mp 70–71 °C; IR (Nujol, cmꢀ1), mmax 3360,
1639, 1045, 972, 931, 889, 865; 1H NMR (400 MHz), d 0.92 (d,
3H, J = 6.5 Hz), 0.93–1.09 (m, 2H), 1.36–1.48 (m, 1H), 1.45–1.58
(m, 1H), 1.61–1.70 (m, 1H), 1.70–1.84 (m, 3H), 1.83 (s, 3H), 2.08
(dm, 2H, J = 12.9 Hz), 2.64 (s, 1H), 2.99 (m, 1H), 3.75 (m, 1H),
3.89 (m, 1H), 4.76 (s, 1H), 4.99 (br s, 1H); 13C NMR (100.6 MHz),
d 22.3, 23.6, 28.1, 29.9, 33.7, 34.7, 45.6, 55.5, 59.3, 75.3, 114.0,
146.1; MS, m/z (%) 198 (M+, C12H22O2, 2), 180 (3), 165 (6), 153
(13), 136 (14), 128 (12), 115 (50), 110 (32), 95 (65), 81 (26), 73
(59), 69 (100), 55 (58).
A sample of (ꢀ)-18 (2.5 g, 12.5 mmol) was dissolved in pyridine
(10 mL) and acetic anhydride (2 mL, 21 mmol). The solution was
set aside at rt overnight, and then the solvent was removed at re-