1816
C.D. Mayer et al. / Tetrahedron 68 (2012) 1810e1818
(m, 1H, 2-H), 1.53 (m, 1H, 50-H), 1.45e0.97 (m, 11H, 1-H, 2-H, 3-H, 7-
H, 10-H, 20-H, 30-H, 40-H), 0.93 (d, J 6.6 Hz, 3H, 10-CH3), 0.87 (d, J
6.6 Hz, 3H, 50-CH3), 0.86 (d, J 6.6 Hz, 3H, 60-H), 0.68 (s, 3H, 7a-CH3);
dC (100 MHz, CDCl3) 134.0 (C-5), 121.8 (C-4), 118.1 (C-100), 83.3 (C-
400), 81.8 (C-500), 54.7 (C-1), 49.9 (C-3a), 41.8 (C-7a), 39.5 (C-40), 36.2
(C-10), 36.1 (C-20), 35.9 (C-7), 28.0 (C-50), 27.9 (C-3), 25.0 (C-6), 24.4
(C-2), 23.8 (C-30), 22.8, 22.5 (50-CH3 and C-60), 18.7 (10-CH3), 17.5 (C-
200),16.2 (C-300),11.0 (7a-CH3); (CI, CH5þ); m/z (%): 326 (100) [MþH]þ;
HRMS (EI, 70 eV) Mþ, found 325.2760. C23H35N requires 325.2769.
(liquid film) 2953, 1695, 1466, 1365, 1132, 946 cmꢀ1
; dH (400 MHz,
CDCl3) 5.90 (dd, J 6.5, 3.1 Hz, 1H, 5-H), 3.03 (t, J 7.0 Hz, 2H, 100-H),
2.57 (t, J 7.0 Hz, 2H, 200-H), 3.04 (s, 3H, 2000-H), 2.20e2.10 (m, 3H, 3a-
H, 6-H), 1.99e1.87 (m, 2H, 3-H, 7-H), 1.77 (m, 1H, 2-H), 1.51 (m, 1H,
50-H), 1.44e1.08 (m, 10H, 1-H, 2-H, 3-H, 7-H, 10-H, 20-H, 30-H, 40-H),
1.00 (m, 1H, 20-H), 0.93 (d, J 6.5 Hz, 3H, 10-CH3), 0.87 (d, J 6.6 Hz, 3H,
50-CH3), 0.86 (d, J 6.6 Hz, 3H, 60-H), 0.68 (s, 3H, 7a-CH3); dC
(100 MHz, CDCl3) 195.6 (C-1000), 133.0 (C-5), 122.2 (C-4), 85.8 (C-300),
81.9 (C-400), 54.8 (C-1), 50.1 (C-3a), 41.8 (C-7a), 39.5 (C-40), 36.2 (C-
10), 36.1 (C-20), 35.9 (C-7), 30.6 (C-2000), 28.7 (C-100), 28.0 (C-50), 27.9
(C-3), 25.0 (C-6), 24.1 (C-2), 23.8 (C-30), 22.8, 22.5 (50-CH3 and C-60),
20.4 (C-200), 18.7 (10-CH3), 11.0 (7a-CH3); (CI, CHþ5 ); m/z (%): 375
(100) [MþH]þ; HRMS (EI, 70 eV): Mþ, found 374.2653. C24H38OS
requires 374.2643.
4.1.6. (3R,3aR,5aS,6R,7R,9bR)-3-((R)-1,5-Dimethylhexyl)-3a-methyl-
2,3,3a,4,5,5a,6,7,8,9b-decahydro-1H-cyclopenta[a]naphthalene-6,7-
dicarbonitrile (12a) and (3R,3aR,5aS,6S,7S,9bR)-3-((R)-1,5-
dimethylhexyl)-3a-methyl-2,3,3a,4,5,5a,6,7,8,9b-decahydro-1H-cy-
clopenta[a]naphthalene-6,7-dicarbonitrile (12b). Diene 1123 (0.20 g,
0.73 mmol) and fumaronitrile (0.06 g, 0.73 mmol) were dissolved
in toluene (2.2 mL) and heated under reflux at 120 ꢁC for 12 h. The
reaction mixture was concentrated under reduced pressure. The
product was purified by silica column chromatography (hexane/
4.1.8. 4-[(1R,3aR,7aR)-1-((R)-1,5-Dimethylhexyl)-7a-methyl-
2,3,3a,6,7,7a-hexahydro-1H-inden-4-yl]-but-3-yne-1-thiol (14). A
solution of 13 (0.28 g, 0.75 mmol) in diethyl ether (4.6 mL) was
added slowly to a suspension of lithium aluminum hydride (0.11 g,
3.00 mmol) and diethyl ether (2.8 mL). The reaction mixture was
stirred 30 min at rt. The excess of lithium aluminum hydride was
destroyed carefully by addition of 1 M hydrogen chloride solution.
The mixture was extracted with diethyl ether (2ꢂ10 mL), the
combined organic layers were washed with water (2ꢂ20 mL). It
was dried over MgSO4 and concentrated under reduced pressure.
The raw product (0.23 g, 93%, colorless oil) was used directly for the
next reaction step without further purification.
ethyl acetate 4:1) to give 0.11 g (42%) 12a as white solid and 0.06 g
20
(23%) 12b as white solid. Compound 12a: mp 187e188 ꢁC; [
a]
D
þ121.8 (CHCl3); nmax (KBr) 2948, 2244, 1673, 1467, 1382, 1152, 1034,
846 cmꢀ1
dH (400 MHz, CDCl3) 5.29 (m, 1H, 9-H), 3.36 (dd, J 7.1,
;
3.3 Hz, 1H, 7-H), 3.13 (dd, J 4.2, 3.3 Hz, 1H, 6-H), 2.98 (m, 1H, 5a-H),
2.76 (m, 1H, 8-H), 2.53 (m, 1H, 8-H), 2.45 (m, 1H, 9b-H), 1.99e1.91
(m, 2H, 4-H, 2-H), 1.84e1.76 (m, 2H, 1-H, 5-H), 1.72 (m, 1H, 4-H),
1.59 (m, 1H, 5-H), 1.51 (m, 1H, 50-H), 1.40e1.26 (m, 6H, 1-H, 2-H, 3-
H, 10-H, 20-H, 30-H), 1.20e1.05 (m, 3H, 30-H, 2ꢂ40-H), 0.99 (m, 1H, 20-
H), 0.90 (d, J 5.7 Hz, 3H, 10-CH3), 0.87 (d, J 6.6 Hz, 3H, 50-CH3), 0.86
(d, J 6.6 Hz, 3H, 60-H), 0.76 (s, 3H, 3a-CH3); dC (100 MHz, CDCl3)
139.4 (C-9a), 119.7 (6-CN), 117.0 (7-CN), 115.1 (C-9), 57.4 (C-3), 49.1
(C-9b), 41.4 (C-3a), 39.4 (C-40), 36.6 (C-4), 35.9 (C-10), 35.8 (C-20),
32.8 (C-5a), 32.4 (C-6), 28.6 (C-2), 28.0 (C-50), 27.7 (C-7), 26.0 (C-8),
25.0 (C-5), 23.9 (C-30), 23.1 (C-1), 22.8, 22.6 (50-CH3 and C-60), 18.7
(3a-CH3), 18.4 (10-CH3); (CI, CHþ5 ); m/z (%): 353 (100) [MþH]þ;
HRMS (EI, 70 eV): Mþ, found 352.2921. C24H36N2 requires
4.1.9. General procedure for synthesis of unsymmetrical disulfides
(16aef). Over
a period of 30 min a solution of 14 (0.50,
1.50 mmol) and dichloromethane (3.75 mL) was added to a solu-
tion of the corresponding symmetrical disulfide (15aef;
1.50 mmol) and dichloromethane (22.5 mL). The reaction mixture
was stirred at rt for 12 h. The mixture was extracted with a 5%
sodium hydroxide solution (2ꢂ30 mL) and water (2ꢂ30 mL). The
organic layer was dried over MgSO4 and concentrated under re-
duced pressure.
352.2878. Compound 12b: mp 114e115 ꢁC; [
a
]
20 þ9.4 (CHCl3); nmax
D
(KBr) 2954, 2248, 1670, 1468, 1376, 1140, 1028, 851 cmꢀ1
;
dH
(400 MHz, CDCl3) 5.22 (m, 1H, 9-H), 3.11 (dt, J 11.0, 6.6 Hz, 1H, 7-H),
2.68 (m, 1H, 8-H), 2.59 (t, J 11.0 Hz, 1H, 6-H), 2.55 (m, 1H, 5a-H),
2.45 (m, 1H, 8-H), 2.35 (m, 1H, 9b-H), 2.01 (ddd, J 12.9, 8.2, 3.5 Hz,
1H, 5-H), 1.94 (m, 1H, 2-H), 1.90 (dd, J 14.2, 8.2 Hz, 1H, 4-H), 1.76 (m,
1H, 1-H), 1.69 (m, 1H, 4-H), 1.51 (m, 1H, 50-H), 1.45(m, 1H, 5-H),
1.40e1.21 (m, 6H, 1-H, 2-H, 3-H, 10-H, 20-H, 30-H), 1.20e1.04 (m, 3H,
30-H, 2ꢂ40-H), 0.98 (m, 1H, 20-H), 0.89 (d, J 6.0 Hz, 3H, 10-CH3), 0.86
(d, J 6.6 Hz, 3H, 50-CH3), 0.85 (d, J 6.6 Hz, 3H, 60-H), 0.71 (s, 3H, 7a-
CH3); dC (100 MHz, CDCl3) 140.3 (C-9a), 119.2 (6-CN), 118.8 (7-CN),
115.9 (C-9), 57.4 (C-3), 49.0 (C-9b), 41.4 (C-3a), 39.4 (C-40), 37.8 (C-
6), 36.6 (C-4), 36.0 (C-10), 35.7 (C-20), 35.4 (C-5a), 29.9 (C-7), 28.6
(C-2, C-8), 28.0 (C-50), 25.8 (C-5), 23.9 (C-30), 23.2 (C-1), 22.8, 22.5
(50-CH3 and C-60), 18.5 (3a-CH3), 18.3 (10-CH3); (CI, CHþ5 ); m/z (%):
353 (100) [MþH]þ; HRMS (EI, 70 eV): Mþ, found 352.2908.
C24H36N2 requires 352.2878.
4.1.9.1. 1-(4-[(1R,3aR,7aR)-1-((R)-1,5-Dimethylhexyl)-7a-methyl-
2,3,3a,6,7,7a-hexahydro-1H-inden-4-yl]-but-3-ynyl)-2-ethyldisulfane
(16a). Symmetrical disulfide: diethyl disulfide. The product was
purified by silica column chromatography (hexane/ethyl acetate
4:1) to give 0.07 g (15%) as pale yellow oil. [
a
]
20 þ13.9 (CHCl3); nmax
D
(liquid film) 2952, 1699, 1466, 1381, 1253, 1168, 1016 cmꢀ1
;
dH
(500 MHz, CDCl3) 5.90 (dd, J 6.8, 3.3 Hz,1H, 5-H), 2.81 (t, J 7.2 Hz, 2H,
100-H), 2.72 (t, J 7.3 Hz, 2H, 1000-H), 2.69 (t, J 7.2 Hz, 2H, 200-H),
2.20e2.10 (m, 3H, 3a-H, 6-H), 2.00e1.88 (m, 2H, 3-H, 7-H), 1.78 (m,
1H, 2-H),1.52 (m,1H, 50-H),1.45e1.08 (m,13H,1-H, 2-H, 3-H, 7-H,10-
H, 20-H, 30-H, 40-H, 2000-H), 0.99 (m, 1H, 20-H), 0.93 (d, J 6.6 Hz, 3H, 10-
CH3), 0.87 (d, J 6.6 Hz, 3H, 50-CH3), 0.86 (d, J 6.6 Hz, 3H, 60-H), 0.68 (s,
3H, 50-CH3); dC (125 MHz, CDCl3) 132.9 (C-5), 122.3 (C-4), 85.9 (C-
300), 81.7 (C-400), 54.7 (C-1), 50.1 (C-3a), 41.8 (C-7a), 39.5 (C-40), 38.0
(C-100), 36.2 (C-10), 36.1 (C-20), 35.9 (C-7), 32.9 (C-500), 28.0 (C-50), 27.9
(C-3), 25.0 (C-6), 24.1 (C-2), 23.9 (C-30), 22.8, 22.5 (50-CH3 and C-60),
20.1 (C-200), 18.7 (10-CH3), 14.4 (C-600), 11.0 (7a-CH3); (CI, CHþ5 ); m/z
(%): 393 (100) [MþH]þ; HRMS (EI, 70 eV): Mþ, found 392.2592.
C24H40S2 requires 392.2572.
4.1.7. Thioacetic acid S-{4-[(1R,3aR,7aR)-1-((R)-1,5-dimethylhexyl)-
7a-methyl-2,3,3a,6,7,7a-hexahydro-1H-inden-4-yl]-but-3-ynyl}ester
(13). Diisopropyl azodicarboxylate (1.01 mL, 5.00 mmol) was
added dropwise to a solution of triphenylphosphine (1.31 g,
5.00 mmol) and THF (11.5 mL). The reaction mixture was stirred for
30 min at 0 ꢁC. A solution of alcohol 8 (0.80 g, 2.53 mmol) and
thioacetic acid (0.36 mL, 5.00 mmol) in THF (2.67 mL) was added
slowly. The mixture was stirred for 1 h at 0 ꢁC and then it was
allowed to warm to rt over a period of 1 h. The reaction mixture was
concentrated under reduce pressure. The product was purified by
4.1.9.2. 1-(4-[(1R,3aR,7aR)-1-((R)-1,5-Dimethylhexyl)-7a-methyl-
2,3,3a,6,7,7a-hexahydro-1H-inden-4-yl]-but-3-ynyl)-2-isopropyl di-
sulfane (16b). Symmetrical disulfide: diisopropyl disulfide. The
product was purified by silica column chromatography (hexane/
ethyl acetate 4:1) to give 0.12 g (20%) as pale yellow oil. [
a
]
20 þ15.6
D
(CHCl3); nmax (liquid film) 2953, 1667, 1465, 1378, 1153, 1019 cmꢀ1
;
silica column chromatography (dichloromethane/hexane 1:1) to
dH (400 MHz, CDCl3) 5.90 (dd, J 6.8, 3.3 Hz, 1H, 5-H), 3.06e2.98 (m,
20
give 0.91 g (96%) 13 as pale yellow oil. [
a
]
þ10.61 (CHCl3); nmax
1H, 1000-H), 2.81 (t, J 7.1 Hz, 2H, 100-H), 2.68 (t, J 7.1 Hz, 2H, 200-H),
D