requires 329.1423); dH (500 MHz, CD3OD) 1.98 (2H, m, H-6, H-
6¢), 2.28 (2H, m, H-6¢¢, H-6¢¢¢), 2.78 (2H, ddd, J5,6 2.5, J5,6¢¢ 6.4, J5,5¢¢
17.0, H-5, H-5¢), 3.12 (2H, ddd, J5¢¢,6 6.4, J5¢¢,6¢¢ 10.9, J5¢¢,5 17.0, H-5¢¢,
H-5¢¢¢), 4.42 (2H, m, H-7, H-7¢), 4.68 (2H, d, J8,7 3.0, H-8, H-8¢),
7.58 (2H, d, J4,3 8.0, H-4, H-4¢), 8.23 (2H, d, J3,4 8.0, H-3, H-3¢);
dC (125 MHz, CDCl3) 23.73, 25.66, 66.93, 71.02, 120.131, 131.81,
137.79, 153.29, 154.69; MS m/z (ES) 329 (M++H, 100%), M+
328 (12).
28.14, 69.87, 72.77, 73.78, 76.31, 108,37, 108.85, 125.27 (2C),
126.75, 134.87, 136.09, 137.16, 145.65, 145.70, 148.38, 153.24; MS
m/z (EI) 424 (M+, 45%), 408 (34).
(3aS,9bR,3a¢S,9b¢R)-2,2,7,2¢,2¢,7¢-Hexamethyl-
3a,4,5,9b,3a¢,4¢,5¢,9b¢-octahydro-[8,8¢]bi[[1,3]-
dioxolo[4,5h]quinolinyl]N-oxide 3IP
The oxidation of bipyridine 3F (0.3 g, 0.7 mmol) with MCPBA
yielded N-oxide 3I as a mixture of atropisomers 3IP : 3IM (3 : 1).
These were separated by multi-elution PLC (EtOAc) to afford
the major N-oxide (+)-3IP (0.09 g, 30%); mp 266–268 ◦C
(from EtOAc–MeOH); [a]D +104 (c 0.66, CHCl3); HRMS
(EI) (Found: M+, 452.2313. C26H32N2O5 requires 452.2311); dH
(300 MHz, CDCl3) 1.32 (3H, s, Me), 1.36 (3H, s, Me), 1.42 (3H, s,
Me), 1.46 (3H, s, Me), 1.82 (2H, m, H-4, H-4¢), 2.05 (3H, s, ArMe),
2.21 (5H, m, ArMe, H-4¢¢, H-4¢¢¢), 2.58 (2H, m, H-5, H-5¢), 3.00
(2H, m, H-5¢¢, H-5¢¢¢), 4.66 (2H, m, H-3a, H-3a¢), 5.19 (1H, d, J9¢b,3a
6.5, H-9b¢), 5.63 (1H, d, J9b,3a 6.9, H-9b), 6.98 (1H, s, H-6¢), 7.39
(1H, s, H-6); dC (125 MHz, CDCl3) 17.89, 19.06, 23.60, 24.02,
25.36, 25.47, 27.34, 27.40, 27.63, 28.07, 108.60, 109.13, 127.47,
133.53, 134.59, 135.31, 136.91, 138.51, 143.14, 147.06, 150.08,
152.40; MS m/z (EI) 452 (M+, 18%), 436 (100), 424 (13). Minor
atropisomer 3IM . dH (300 MHz, CDCl3) 1.25 (3H, s, Me), 1.29
(3H, s, Me), 1.33 (3H, s, Me), 1.38 (3H, s, Me), 1.75 (2H, m, H-4,
H-4¢), 1.82 (3H, s, ArMe), 1.95 (3H, m, ArMe), 2.05(2H, m, H-4¢¢,
H-4¢¢¢), 2.48 (2H, m, H-5, H-5¢), 2.91 (2H, m, H-5¢¢, H-5¢¢¢), 4.60
(2H, m, H-3a, H-3a¢), 5.07 (1H, d, J9¢b,3a 6.6, H-9b¢), 5.573 (1H, d,
J9b,3a 6.6, H-9b), 6.86 (1H, s, H-6¢), 7.30 (1H, s, H-6).
(7S,8R,7¢S,8¢R)-7,7¢-Di(1-(tert-butyl)-1,1-diphenylsilyloxy)-
5,6,7,8,5¢,6¢,7¢,8¢-octahydro[2,2¢]biquinolinyl-8,8¢-diol 9
To a stirred solution of tetrol 8 (0.3 g, 0.9 mmol) and imidazole
◦
(0.34 g, 5 mmol), in dry DMF (5 ml) maintained at 0 C under
nitrogen, was added, dropwise over 20 min, tert-butyldiphenylsilyl
chloride (0.3 ml, 1.09 mmol). The reaction mixture was stirred for
4 h at room temperature, diluted with dichloromethane (75 ml)
and the solution washed with water. The organic layer was
dried (Na2SO4), the solvent evaporated, and the crude product
purified by PLC (20% EtOAc in hexane). The disilyl derivative
9 was obtained as a white solid (0.33 g, 45%); mp 74 ◦C
(from EtOAc–hexane); [a]D -38 (c 0.72, CHCl3); HRMS (ES)
(Found: M++H, 807.3960. C50H57N2O4Si2 requires 807.4014); dH
(500 MHz, CDCl3, D2O exchange) 1.01 [18H, s, 2 ¥ C(Me)3], 1.75
(2H, m, H-6, H-6¢), 1.99 (2H, m, H-6¢¢, H-6¢¢¢), 2.68 (2H, ddd, J5,6
6.1, J5,6¢¢ 6.1, J5,5¢¢ 17.2, H-5, H-5¢), 3.02 (2H, ddd, J5¢¢,6 7.2, J5¢¢,6¢¢ 7.2,
J5¢¢,5 17.2, H-5¢¢, H-5¢¢¢), 4.40 (2H, m, H-7, H-7¢), 4.68 (2H, d, J8,7
3.0, H-8, H-8¢), 7.18-7.34 (12H, m, ArH), 7.46 (2H, d, J 8.0, ArH);
7.62 (4H, m, ArH), 7.71 (4H, m, ArH), 8.25 (2H, d, J 8.0, ArH); dC
(125 MHz, CDCl3) 19.41, 24.74, 26.20, 26.57, 26.98, 70.57, 72.13,
119.92, 127.45, 127.61, 127.76, 129.53, 129.60, 129.68, 131.52,
133.90, 134.31, 134.80, 135.93, 137.02, 153.19, 154.62; MS m/z
(ES) 807 (M++H, 30%), 806 (M+, 68%).
(3aS,9bR,3a¢S,9b¢R)-2,2,2¢,2¢-Tetraethyl-3a,4,5,9b,3a¢,4¢,5¢,9b¢-
octahydro-[8,8¢]bi[[1,3]-dioxolo[4,5h]quinolinyl] N-oxide 4I
Bipyridine 4F (1 g, 2.15 mmol) gave N-oxide 4I (0.74 g, 72%); mp
139 ◦C (from EtOAc–MeOH); [a]D +276 (c 1.08, CHCl3); (Found:
C, 69.8; H, 7.5; N, 5.7. C28H36N2O5 requires C, 70.0; H, 7.55; N,
5.8%); dH (500 MHz, CDCl3) 0.73 (6H, m, 2 ¥ CH2Me), 1.02 (6H,
m, 2 ¥ CH2Me) 1.62 (4H, m, 2 ¥ CH2Me), 1.58-1.83 (6H, m, 2 ¥
CH2Me, H-4, H-4¢), 2.34 (2H, m, H-4¢¢, H-4¢¢¢), 2.59 (2H, m, H-5,
H-5¢), 3.13 (2H, m, H-5¢¢, H-5¢¢¢), 4.73 (2H, m, H-3a, H-3a¢), 5.23
(1H, d, J9¢b,3a 6.8, H-9b¢), 5.75 (1H, d, J9b,3a 6.8, H-9b), 7.13 (1H,
d, J 8.2, ArH), 7.54 (1H, d, J 8.2, ArH), 8.19 (1H, d, J 8.2, ArH),
8.86 (1H, d, J 8.2, ArH); dC (125 MHz, CDCl3) 7.74, 7.94, 9.18,
23.45, 23.74, 27.15, 27.94, 29.25, 29.53, 29.91, 30.04, 50.90, 70.45,
72.94, 73.86, 76.61, 112.82, 113.01, 125.16, 125.81, 127.25, 134.86,
136.44, 137.49, 146.02, 146.54, 148.77, 154.15; MS m/z (EI) 480
(M+, 5%), 435 (20), 379 (24), 293 (35), 277 (100), 199 (25), 85 (53),
71 (62).
General procedure for the synthesis of N-oxides
m-Chloroperoxybenzoic acid (MCPBA, 50–55%, 1.1 equiv.) was
added, in small portions, to a stirred solution of bipyridine
(1 mmol) in dichloromethane (20 ml) at 0 ◦C, and the stirring
continued at 0 ◦C for a further 4 h. The reaction mixture was
washed, successively, with a saturated Na2SO3 solution, Na2CO3
solution and finally with water. The organic layers were dried
(Na2SO4), concentrated under reduced pressure, and the residue
purified by column chromatography (10% MeOH in CHCl3) to
give the corresponding N-oxide as a white crystalline solid. This
purification method was followed for all the N-oxides.
(3aS,9bR,3a¢S,9b¢R)-2,2,2¢,2¢-Tetramethyl-3a,4,5,9b,3a¢,4¢,5¢,9b¢-
octahydro-[8,8¢]bi[[1,3]-dioxolo[4,5h]quinolinyl] N-oxide 2I
(3aS,9bR,3a¢S,9b¢R)-8,8¢-bis{Spiro[[1,3]dioxolo[4,5h]quinoline-
2,1¢-cyclohexane]} N-oxide 5I
Bipyridine 2F (0.5 g, 1.22 mmol) gave N-oxide 2I (0.3 g,
60%); mp 201–202 ◦C (from CHCl3–MeOH); [a]D +215 (c 1.0,
CHCl3); HRMS (EI) (Found: M+, 424.2011. C24H28N2O5 requires
424.1998); dH (300 MHz, CDCl3) 1.37 (3H, s, Me), 1.39 (3H, s,
Me), 1.49 (3H, s, Me), 1.52 (3H, s, Me), 1.75 (2H, m, H-4, H-4¢),
2.23 (2H, m, H-4¢¢, H-4¢¢¢), 2.61 (2H, m, H-5, H-5¢), 3.04 (2H, m,
H-5¢¢, H-5¢¢¢), 4.74 (2H, m, H-3a, H-3a¢), 5.23 (1H, d, J9¢b,3a 7.0,
H-9b¢), 5.75 (1H, d, J9b,3a 7.0, H-9b), 7.10 (1H, d, J 8.1, Ar), 7.55
(1H, d, J 8.1, Ar), 8.21 (1H, d, J 8.4, Ar), 8.91 (1H, d, J 8.1, Ar); dC
(125 MHz, CDCl3) 23.42, 23.73, 24.73, 25.23, 26.81, 26.84, 27.14,
Bipyridine 5F (1 g, 2 mmol) yielded N-oxide 5I (0.67 g, 65%); mp
246 ◦C (from CHCl3–MeOH); [a]D +226 (c 1.09, CHCl3); (Found:
C, 71.1; H, 7.0; N, 5.5. C30H36N2O5 requires C, 71.4; H, 7.2; N,
5.6%); dH (300 MHz, CDCl3) 1.54-1.75 (22H, m, 2 ¥ (CH2)5, H-4,
H-4¢), 2.25 (2H, m, H-4¢¢, H-4¢¢), 2.59 (2H, m, H-5, H-5¢), 3.04
(2H, m, H-5¢¢, H-5¢¢¢), 4.73 (2H, m, H-3a, H-3a¢), 5.22 (1H, d,
J9¢b,3a 6.6, H-9b¢), 5.75 (1H, d, J9b,3a 6.6, H-9b), 7.16 (1H, d, J 8.4,
ArH), 7.54 (1H, d, J 7.8, ArH), 8.16 (1H, d, J 8.1, ArH), 8.85
1088 | Org. Biomol. Chem., 2010, 8, 1081–1090
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