R. S. Diez et al. / Tetrahedron 58 (2002) 8341–8344
8343
mixture was vigorously stirred at 238C for 2 h before the
corresponding alkyne (1 equiv.) was added. After 15 min of
stirring the aldehyde (1.1 equiv.) was added in one portion
by syringe. The reaction was stirred and heated at 608C
99% ee and 84% de as determined by HPLC analysis
i
(Chiracel OD, hexane/ PrOH (99:1), 254 nm), t 19.9
r
2
6
(major), 22.1 (minor); colourless oil. [a] ¼26.98 (c¼0.3,
D
1
CHCl ). H NMR (300 MHz, CDCl ) d 8.1–8.0 (m, 2H),
3
3
for 5 h. The mixture was quenched with NH Cl(aq) and
4
7.6–7.4 (m, 3H), 5.5 (dd, J¼5.6 and 1.6 Hz, 1H), 4.2 (dd,
extracted with Et O or AcOEt (3£20 mL). The combined
J¼5.6 and 1.6 Hz, 1H), 2.2 (s broad, 1H, OH), 2.0–1.6 (m,
2
1
3
organic layers were dried over anhydrous MgSO and
4
13H), 1.3–1.1 (m, 10H), 1.0–0.95 (m, 6H). C NMR
(75.5 MHz, CDCl ) d 165.7, 133.1, 130.1, 129.8, 128.4,
concentrated in vacuo. The residue was purified by
column chromatography on silica gel using pentane/Et O
3
86.2, 81.9, 68.9, 67.8, 42.0, 34.4, 28.6, 28.3, 26.3, 25.8,
25.7, 18.2, 17.5. FTIR (thin film) 3468, 2930, 2855, 1723,
2
(
5:1 to 3:1).
1
602, 1584, 1451, 1378, 1345, 1316, 1266, 1177, 1155,
1
2
1
.2.1. (1R,4R)-Benzoic acid 4-hydroxy-1-isopropyl-5-
methyl-2-hexynyl ester (11). Isolated in 76% yield and
9% ee and 86% de as determined by HPLC analysis
1109, 1069, 1026, 972 cm . Anal. Calcd for C H O : C,
20 26 3
76.40%; H, 8.33%; found: C, 76.57%; H, 8.43%. MS (EI,
þ
9
70 eV): m/z (%): 314 (M , 1), 149 (19), 122 (22), 105 (100),
77 (24).
i
(
(
0
2
4
1
Chiracel OD, hexane/ PrOH (99:1), 254 nm), t 17.6
r
2
6
major), 22.6 (minor); colourless oil. [a] ¼þ14.88 (c¼
D
1
.56, CHCl ). H NMR (300 MHz, CDCl ) d 8.1–8.0 (m,
3
1.2.5. (1S,4S)-Benzoic acid 1-cyclohexyl-4-hydroxy-4-
phenyl-2-butynyl ester (14). Isolated in 41% yield and
3
H), 7.6–7.4 (m, 3H), 5.5 (dd, J¼5.6 and 1.6 Hz, 1H),
.25–4.2 (m, 1H), 2.2 (d, J¼5.3 Hz, 1H), 2.2–2.1 (m, 1H),
.95–1.8 (m, 1H), 1.1 (dd, J¼8.1 and 6.8 Hz, 6H), 1.0 (dd,
1
9
99% ee and 80% de as determined by F NMR of the
1
corresponding Mosher ester; colourless oil. H NMR
(300 MHz, CDCl ) d 8.1–8.0 (m, 2H), 7.6–7.25 (m, 8H),
1
3
J¼6.6 and 5.9 Hz, 6H). C NMR (75.5 MHz, CDCl ) d
3
3
1
3
3
1
1
7
7
7
65.6, 133.1, 130.0, 129.7, 128.4, 86.1, 81.7, 69.6, 67.8,
4.4, 32.6, 18.3, 18.2, 17.7, 17.4. FTIR (thin film) 3463,
064, 2965, 2931, 2874, 1723, 1602, 1584, 1469, 1452,
388, 1369, 1337, 1315, 1266, 1177, 1157, 1111, 1098,
5.6–5.5 (m, 2H), 2.6–2.5 (m, 1H), 2.0–1.6 (m, 7H), 1.4–
3
1
1.1 (m, 5H). C NMR (75.5 MHz, CDCl ) d 165.7, 140.3,
3
133.2, 130.0, 129.8, 128.6, 128.4, 128.35, 126.7, 85.9, 83.3,
68.9, 64.6, 42.0, 28.6, 28.4, 26.2, 25.8, 25.7. FTIR (thin
film) 3437, 3064, 3033, 2930, 2855, 1722, 1602, 1584,
1493, 1451, 1377, 1343, 1316, 1264, 1177, 1108, 1069,
2
1
070, 1026, 977 cm . Anal. Calcd for C H O : C,
1
7 22 3
4.42%; H, 8.08%; found: C, 74.59%; H, 7.97%. MS (EI,
þ
21
0 eV): m/z (%): 274 (M , 1), 122 (24), 109 (27), 105 (100),
7 (29).
1026, 971 cm . Anal. Calcd for C H O : C, 79.28%; H,
2
3 24 3
6.94%; found: C, 79.01%; H, 6.96%. MS (EI, 70 eV): m/z
(%): 346 (M 22, 1), 128 (22), 122 (42), 106 (24), 105
þ
(100), 77 (37).
1
.2.2. (1R,4S)-Benzoic acid 4-hydroxy-1-isopropyl-5-
methyl-2-hexynyl ester (12). Isolated in 73% yield and
9% ee and 84% de as determined by HPLC analysis
9
1.2.6. (1S,4S)-Benzoic acid 4-tert-butyl-1-cyclohexyl-4-
hydroxy-2-butynyl ester (15). Isolated in 77% yield and
99% ee and 90% de as determined by HPLC analysis
i
(
(
0
2
4
1
Chiracel OD, hexane/ PrOH (99:1), 254 nm), t 17.9
r
2
6
minor), 22.4 (major); colourless oil. [a] ¼þ26.78 (c¼
D
1
i
.99, CHCl ). H NMR (300 MHz, CDCl ) d 8.1–8.0 (m,
3
(Chiracel OD, hexane/ PrOH (99:1), 254 nm), tr 15.7
2
3
5
H), 7.6–7.4 (m, 3H), 5.5 (dd, J¼5.6 and 1.6 Hz, 1H),
.25–4.2 (m, 1H), 2.2 (d, J¼5.3 Hz, 1H), 2.2–2.1 (m, 1H),
.95–1.8 (m, 1H), 1.1 (dd, J¼9.0 and 6.8 Hz, 6H), 1.0 (dd,
(major), 17.0 (minor), 18.3 (minor); colourless oil. [a] ¼
D
1
221.08 (c¼0.86, CHCl ). H NMR (300 MHz, CDCl ) d
3
3
8.1–8.0 (m, 2H), 7.6–7.4 (m, 3H), 5.5 (dd, J¼5.9 and
1
3
J¼6.5 and 6.2 Hz, 6H). C NMR (75.5 MHz, CDCl ) d
1.5 Hz, 1H), 4.05–4.0 (m, 1H), 2.6–2.5 (m, 1H), 2.1–1.6
(m, 7H), 1.4–1.1 (m, 5H), 1.0 (s, 9H). C NMR (75.5 MHz,
CDCl ) d 165.6, 133.1, 130.1, 129.8, 128.4, 86.2, 82.0, 71.2,
3
1
3
1
3
65.6, 133.1, 130.0, 129.7, 128.4, 86.0, 81.6, 69.6, 67.8,
4.4, 32.6, 18.3, 18.1, 17.8, 17.4.
3
69.0, 42.0, 35.9, 28.7, 28.3, 26.3, 25.8, 25.7, 25.4. FTIR
1
2
9
.2.3. (1R,4R)-Benzoic acid 4-hydroxy-1,4-dicyclohexyl-
-butynyl ester (7). Isolated in 75% yield and 99% ee and
0% de as determined by HPLC analysis (Chiracel OD,
(thin film) 3481, 3064, 2931, 2856, 1722, 1602, 1585, 1479,
1452, 1364, 1316, 1267, 1177, 1109, 1069, 1026, 1009,
972 cm2 . Anal. Calcd for C H O : C, 76.79%; H, 8.59%;
1
2
1 28 3
i
hexane/ PrOH (99:1), 254 nm), t 22.9 (major), 28.9
r
found: C, 76.85%; H, 8.58%. MS (EI, 70 eV): m/z (%): 328
(M , 1), 188 (13), 150 (38), 149 (27), 122 (34), 105 (100),
2
7
þ
77 (30).
(
0
2
minor), 30.4 (minor); colourless oil. [a] ¼þ16.68 (c¼
D
1
.92, CHCl ). H NMR (300 MHz, CDCl ) d 8.1–8.0 (m,
3
3
H), 7.6–7.4 (m, 3H), 5.5 (dd, J¼5.9 and 1.5 Hz, 1H), 4.2
(
(
dd, J¼5.9 and 1.5 Hz, 1H), 2.0–1.5 (m, 13H), 1.4–1.05
1.3. Preparation of 8
1
3
m, 10H). C NMR (75.5 MHz, CDCl ) d 165.7, 133.1,
3
1
2
30.1, 129.8, 128.4, 86.5, 82.0, 68.9, 67.1, 44.0, 42.0, 28.7,
8.6, 28.3, 28.0, 26.4, 26.3, 25.9, 25.85, 25.8, 25.7. FTIR
To a solution of the corresponding benzoate 7 (1 equiv.) in
Et O was added finely powdered KOH (1.5 equiv.) and the
2
(
1
thin film) 3470, 3064, 2927, 2853, 1723, 1602, 1585, 1451,
376, 1344, 1316, 1265, 1178, 1108, 1069, 1026, 972 cm21
Anal. Calcd for C H O : C, 77.93%; H, 8.53%; found: C,
7.68%; H, 8.56%. MS (EI, 70 eV): m/z (%): 354 (M , 1),
14 (13), 150 (12), 149 (16), 122 (54), 105 (100), 91 (22), 83
28), 81 (21), 79 (19), 77 (47), 55 (31).
mixture was stirred at room temperature until consumption
of the starting material (usually overnight). The mixture was
quenched with NH Cl(aq) and extracted with Et O or
.
2
3
30
3
4
2
þ
7
2
(
AcOEt (3£20 mL). The combined organic layers were dried
over anhydrous MgSO and concentrated in vacuo. The
4
residue was purfied by column chromatography on silica gel
using pentane/Et O (3:1 to 1:1).
2
1.2.4. (1S,4S)-Benzoic acid 1-cyclohexyl-4-hydroxy-4-
isopropyl-2-butynyl ester (13). Isolated in 72% yield and
1.3.1. (R,R)-1,4-Dicyclohexyl-2-butyn-1,4-diol (8). Isolated