5224
M. Nikac et al. / Tetrahedron 63 (2007) 5220–5226
0
3.4 Hz, 1-H), 3.37 (1H, m, 15-H), 3.41 (1H, ddd, J
3
2
.96–4.28 (4H, m, 2ꢂOCH CHO), 9.68–9.74 (2H, m,
3 -Heq), 2.72–2.82 (12H, m, 6ꢂCH S), 3.09 (1H, t, J
2
2
1,19
ꢂHC]O); d (75 MHz; CDCl ) 17.9 (CH , C-10), 25.0
6.8,
J3A,4A 9.0 and J3A,4B 9.0 Hz, 3-H ), 3.55–3.68 (4H, m, 16-
C
3
2
A,B
(
CH , C-9), 26.5 (CH , C-4), 29.8 (CH , C-11), 61.2 (CH ,
2
2
2
2
A
0
C-8), 61.8 (CH , C-2), 74.5, 75.4 (CH , 2ꢂOCH CHO),
CH and 13-CH ), 3.72–3.82 (3H, m, 3-H and 6 -CH );
2
2
2
2
2
2
B
0
7
2
1
2.7 (CH, C-3), 76.8 (CH, C-5), 96.6 (quat, C-6), 201.1,
01.3 (quat, 2ꢂC]O); m/z (EI) 272 (M , 1%), 172 (10),
d (100 MHz; CDCl ) 18.0 (CH , C-4 ), 24.3 (CH , C-19),
C
3
2
2
+
0 0
25.2 (CH , C-5 ), 31.2 (CH , C-3 ), 31.4, 31.8, 32.3, 32.4,
2 2
0
01 (100), 69 (81), 43 (27).
33.2, 33.5 (CH , 6ꢂCH S), 60.9 (CH , C-6 ), 62.2 (CH ,
2
2
2
2
C-16), 70.1 (CH , C-13), 70.3 (CH , C-3), 72.0 (CH, C-
2 2
+
4
.1.4. [3R*,5S*,6S*]-1,7-Dioxaspiro[5.5]undecan-3,5-
15), 77.2 (CH, C-1), 96.6 (quat, C-18); m/z (EI) 394 (M ,
23%), 120 (54), 103 (57), 87 (100), 61 (76), 41 (46).
diyl bis(2-hydroxyethyl) ether 8. [3R*,5S*,6S*]-1,7-Di-
oxaspiro[5.5]undecan-3,5-diyl bisallyl ether 7 (75 mg,
0
.28 mmol) was dissolved in methanol (8 mL) and the solu-
4.1.6. [1S*,18R*,21S*]-Spiro[2,17,20-trioxa-5,8,11,14-
0
ꢁ
tion cooled to ꢀ78 C. Ozone was bubbled through the solu-
tion until a pale blue colour persisted (10–15 min). Excess
ozone was removed by passing oxygen through the solution.
The reaction was taken out of the cooling bath and sodium
borohydride (42 mg, 1.12 mmol) was added. The reaction
was allowed to warm to room temperature and left to stir
for 16 h. The solution was diluted with brine (5 mL) and
the methanol removed. The aqueous solution was extracted
with dichloromethane (5ꢂ15 mL). The combined extracts
were dried over sodium sulfate and the dichloromethane re-
moved under reduced pressure. The pale yellow oil was pu-
tetrathiabicyclo[16.3.1]-docosane-21,2 -tetrahydro-
pyran] 10b. The title compound 10b was prepared from the
spiroacetal ditosylate 5 (140 mg, 0.24 mmol), 3,6-dithia-
octane-1,8-dithiol 9b (50 mg, 0.24 mmol) and caesium carbon-
ate (230 mg, 0.72 mmol) using a similar procedure to that
described above for crown ether 10a. The crude product
was purified by flash chromatography using hexane–ethyl
acetate (4:1) as eluent to afford the title compound 10b
+
(75 mg, 68%) as a colourless oil; found (EI): M ,
454.13397. C H O S requires M, 454.13400; dH
1
9 34 4 4
(400 MHz; CDCl ) 1.32 (1H, ddd, J
0
0
13.6, J
0 0
3
3 ax,3 eq
3 ax,4 ax
0 0
4.4 Hz, 3 -Hax), 1.49–1.60 (3H, m, 5 -
3 ax,4 eq
rified by flash chromatography using 8% MeOH in CH Cl2
2
13.6 and J
0
0
0
0
0
0
to afford the title compound 8 (120 mg, 75%) as colourless
ꢁ
CH and 4 -H or 4 -H ), 1.71–1.79 (1H, m, 4 -H or 4 -
2
A
B
A
+
needles mp 62–65 C. Found (EI): M , 276.15725.
C H O requires M, 276.15729; nmax(film)/cm 3628–
H ), 1.97 (1H, ddd, J
B
14.8, J22ax,18 3.7 and J22ax,1
3.7 Hz, 22-Hax), 2.07 (1H, dddd, J22eq,22ax 14.8, J22eq,1
22ax,22eq
ꢀ1
1
3 24 6
3
J11ax,11eq 13.6, J11ax,10ax 13.6 and J11ax,10eq 4.5 Hz, 11-
290 (br s, OH); dH (400 MHz; CDCl ) 1.31 (1H, ddd,
3.7, J22eq,18 3.7 and J22eq,19eq 1.9 Hz, 22-Heq), 2.12 (1H,
3
0
0
2.8 Hz, 3 -Heq), 2.72–2.82
3 eq,4
dt, J
0
0
13.6 and J
0
3 eq,3 ax
Hax), 1.49–1.62 (3H, m, 9-CH , 10-HA or 10-H ), 1.73–
B
(16H, m, 8ꢂCH S), 3.09 (1H, t, J
3.7 Hz, 1-H), 3.37
1,22
2
2
1
1
.82 (1H, m, 10-HA or 10-H ), 1.98 (1H, ddd, J
B
5.1, J4ax,5 3.6 and J4ax,3 3.6 Hz, 4-Hax), 2.11–2.29 (2H,
(1H, dddd, J
J18eq,19eq 3.7 Hz, 18-H), 3.55–3.78 (8H, m, 6 -CH , 19-
3.7, J
3.7, J
3.7 and
4ax,4eq
18eq,22ax
18eq,22eq
18eq,19ax
0
CH , 16-CH and 3-CH ); d (100 MHz; CDCl ) 17.9
2
m, 4-Heq and 11-Heq), 3.11 (1H, t, J5,4 3.6 Hz, 5-H),
.37–3.41 (1H, m, 3-H), 3.47–3.84 (12H, m, 2-CH , 8-
2
2
2
C
3
0
0
0
3
(CH , C-4 ), 25.2 (CH , C-5 ), 26.4 (CH , C-22), 30.2
2
2
2
2
0
8.1 (CH , C-10), 25.1 (CH , C-9), 26.0 (CH , C-4),
CH , 2ꢂ1 -CH and 2ꢂCH OH); d (75 MHz; CDCl3)
(CH , C-3 ), 32.01, 32.04, 32.41, 32.46, 32.49, 32.52,
2
2
2
2
C
0
1
3
6
33.15, 33.18 (CH , 8ꢂCH S), 61.0 (CH , C-6 ), 62.1
2
2
2
2
2
2
1.1 (CH , C-11), 60.9 (CH , C-8), 61.0 (CH , C-2), 61.5,
2
1.6 (CH , 2ꢂC-1 ), 70.9, 71.3 (CH , 2ꢂCH OH), 72.2
(CH , C-19), 69.2 (CH , C-16), 70.5 (CH , C-3), 71.9
2 2 2
2
2
0
(CH, C-18), 77.2 (CH, C-1), 96.5 (quat, C-21); m/z (EI)
454 (M , 19%), 131 (42), 120 (71), 87 (100), 61 (74), 41
(35).
2
2
2
+
(
CH, C-3), 77.2 (CH, C-5), 96.1 (quat, C-6); m/z (EI) 276
M , 0.4%), 158 (10), 101 (41), 88 (95), 73 (42), 69 (23),
+
(
4
5 (100).
4
.1.7. [1S*,21R*,24S*]-Spiro[2,20,23-trioxa-5,8,11,14,17-
0
4.1.5. [1S*,15R*,18S*]-Spiro[2,14,17-trioxa-5,8,11-tri-
thiabicyclo[13.3.1]-nonadecane-18,2 -tetrahydropyran]
pentathiabicyclo[19.3.1]-pentacosane-24,2 -tetrahydro-
pyran] 10c. The title compound 10c was prepared from the
spiroacetal ditosylate 5 (0.27 g, 0.46 mmol), 3,6,9-trithiaun-
decane-1,11-dithiol 9c (0.13 g, 0.46 mmol) and caesium car-
bonate (0.45 g, 1.4 mmol) using a similar procedure to that
described above for crown ether 10a. The crude product
was purified by flash chromatography using hexane–ethyl
acetate (4:1) as eluent to afford the title compound 10c
0
0a. A solution of the spiroacetal ditosylate 5 (100 mg,
1
0
.17 mmol) in dimethylformamide (5 mL) and a solution
of the 2-mercaptoethyl sulfide 9a (220 mg, 0.17 mmol) in di-
methylformamide (5 mL) were added from separate addi-
tion funnels over 2.5 h to a vigorously stirred suspension
of caesium carbonate (170 mg, 0.51 mmol) in dimethylfor-
ꢁ
+
mamide (20 mL) at 60 C. The mixture was left to stir for
1
(0.15 g, 64%) as a pale yellow oil; found (EI): M ,
514.13764. C H O S requires M, 514.13737; dH
6 h. The reaction mixture was then filtered through a short
2
1 38 4 5
pad of Celite and the filter cake washed with dichlorome-
thane (3ꢂ15 mL). The solvent was removed under reduced
pressure to yield a yellow oil that was purified by flash chro-
matography using hexane–ethyl acetate (4:1) as eluent to af-
ford the title compound 10a (58 mg, 86%) as a pale yellow
(400 MHz; CDCl ) 1.32 (1H, ddd, J
3
0
0
13.3, J
4.3 Hz, 3 -Hax), 1.46–1.60 (3H, m, 5 -
0
0
3 ax,3 eq
3 ax,4 ax
0
CH and 4 -H or 4 -H ), 1.66-1.82 (1H, m, 4 -H or 4 -
0
13.3 and J
0
0
3
0
ax,4 eq
0
H ), 1.95 (1H, ddd, J
0
0
3.8 and J25ax,1
2
A
B
A
14.8, J
B
25ax,25eq
25ax,21
0
3.8 Hz, 25-Hax), 2.05–2.14 (2H, m, 3 -Heq and 25-Heq),
2.69–2.84 (20H, m, 10ꢂCH S), 3.08 (1H, t, J
+
oil; found (EI): M , 394.13104. C H O S requires M,
3
3.8 Hz,
1,25
1
7
30
4
2
0
CH , 3-CH and 19-CH ); d (100 MHz; CDCl ) 17.9
3
1
94.13063; d (400 MHz; CDCl ) 1.26 (1H, ddd, J
H
0
0
1-H), 3.53 (1H, br s, 21-H), 3.55–3.79 (8H, m, 6 -CH , 22-
2
3
3 ax,3 eq
0
3.6, J3
0
0
13.6 and J
0
0
0
4.4 Hz, 3 -Hax), 1.51–1.57
ax,4 ax
0
3 ax,4 eq
0
2
2
2
C
3
0
15.2, J19ax,15 3.4
0
0
0
(CH , C-3 ), 31.9, 32.1, 32.30, 32.32, 32.4, 32.5, 32.6,
(
HA or 4 -H ), 1.91 (1H, ddd, J
3H, m, 5 -CH and 4 -H or 4 -H ), 1.73–1.81 (1H, m, 4 -
B
(CH , C-4 ), 25.2 (CH , C-5 ), 26.1 (CH , C-25), 30.3
2
2
a
2
2
0
and J19ax,1 3.4 Hz, 19-Hax), 2.15–2.25 (2H, m, 19-Heq and
B
19ax,19eq
2
0
32.7, 32.9, 33.0 (CH , 10ꢂCH S), 61.0 (CH , C-6 ),
2
2
2