Majewski et al.
1797
the solvent was evaporated. The ratio of 7:8 (18:82) was
measured by H NMR. The crude mixture was purified by
140.9, 135.3, 129.9, 128.8, 127.9, 117.6, 116.5, 48.8, 44.4,
44.0, 40.0, 34.5.
1
dry flash chromatography (dichloromethane J dichloro-
methane–ethyl acetate, 1:1), which yielded pure 8 as a white
solid (0.217 g, 61%) and pure 7 (0.038 g, 13%).
2,7
5
,5-Dimethyl-6-oxa-12-thia-tricyclo[7.2.1.0 ]dodec-2(7)-
en-3-one (17)
Properties of 8: mp 162–164°C. R = 0.59 (hexane–ethyl
f
Lithium enolate of 1 (0.5 mmol) was prepared according
to procedure B (base 11d). Senecioyl cyanide (0.055 mL,
.72 mmol) in THF (1 mL) was added, and the resulting
mixture was stirred at –78°C for 30 min, followed by
quenching with 40% K CO (2 mL). After warming up to rt
the reaction mixture was extracted with ether (3 × 10 mL).
The combined extracts were dried over MgSO and the sol-
vent was removed under vacuum to give the crude product
6. Compound 16 was subjected to cyclization without puri-
acetate, 1:1). CI-MS (NH ) m/z (%): 304 (27), 232 (17), 231
3
(
(
(
87), 162 (63), 160 (19), 143 (16), 142 (80), 124 (20), 114
50), 109 (15), 106 (24), 105 (100), 94 (29), 91 (14), 81
0
–
1
15), 78 (23), 77 (24), 74 (19), 61 (65). IR (cm ): 3510,
2
3
1
1
701, 1190, 1050. H NMR d: 7.50–7.28 (m, 10H), 5.45 (d,
J = 9.5 Hz, 2H), 3.20–3.10 (m, 2H), 2.85 (d, J = 8.0 Hz,
4
2
1
H), 2.07–1.80 (m, 6H). 13C NMR d: 210.5, 141.2, 128.8,
28.5, 127.0, 75.9, 68.0, 48.9, 33.4.
1
fication: the entire sample was dissolved in EtOH (7 mL),
anhydrous Na CO (0.14 g) was added, and the mixture was
heat at reflux for 1 h. The solvent was then removed under
vacuum, the residue was taken in ether and the carbonate
was filtered off. Column chromatography (hexane–EtOAc,
2
3
Compound 9
8
-Thiabicyclo[3.2.1]oct-2-en-3-yl trimethylsilane (5a)
(
(
(
0.320 g, 1.50 mmol) was dissolved in dichloromethane
10 mL), the solution was cooled down to –78°C, and TiCl4
0.17 mL, 1.50 mmol) was added. The mixture was stirred
4
:1) afforded the product 17 as a white solid (91 mg, 81%).
This sample had 92% ee as determined by HPLC using a
ChiraDex 250–4 column (Merck), an UV detector (at
for 1 h at –78°C and then for 2 h at 0°C. The reaction was
then quenched with saturated solution of NaHCO (10 mL).
Diethyl ether (100 mL) was added, and the organic phase
was separated and washed with saturated NaHCO (2 ×
3
2
0
54 nm) in 50% MeOH – phosphate buffer (pH = 6.8, c =
–
1
.025 M), flow: 0.4 mL min . mp 90–92°C (note: racemate
3
25
mp 75–77°C). [a]D –94.1 (c 1.03, MeOH). R = 0.20 (hex-
f
2
5 mL), brine (25 mL), and dried with MgSO . The solvent
4
ane–EtOAc, 4:1). EI-MS m/z (%): 224 (100), 209 (76), 168
was evaporated under vacuum and the product was subjected
to dry flash chromatography (hexane J hexane–ethyl ace-
tate, 4:1), which yielded two products: 1 (0.037 g, 17%) and
(
26), 155 (13), 140 (44), 135 (11), 97 (12), 85 (10), 83 (10),
9 (17), 71 (23). IR (cm ): 1652, 1603. H NMR d: 1.35 (s,
H), 1.37 (s, 3H), 1.80–1.88 (m, 1H), 2.10–2.31 (m, 4H),
–
1
1
7
3
2
9
(0.150 g, 70%).
.42 (d, J = 16.6 Hz, 1H), 2.49 (d, J = 16.6 Hz, 1H), 2.79
Properties of 9: mp 135–137°C. R = 0.19 (hexane–ethyl
acetate, 4:1). EI-MS m/z (%): 284 (M , 8), 266 (60), 233
13
f
(
dq, J = 18.6, 2.1 Hz, 1H), 3.87(m, 1H), 4.55 (m,1H).
C
+
NMR d: 25.8, 27.2, 34.4, 40.1, 40.6, 42.3, 45.0, 47.3, 80.5,
(
28), 142 (100), 114 (35), 99 (24), 85 (68), 69 (82).
1
7
19.5, 168.4, 188.3. Anal. calcd. for C H O S: C 64.26, H
.19; found: C 64.47, H 7.17.
12
16
2
HRMS calcd. for C H O S : 284.0905; found: 284.0909.
IR (cm ): 3435, 1696, 1052. H NMR d: 4.18–4.05 (br s,
1
4
20
2 2
–
1
1
1
1
1
4
H), 3.96–3.87 (m, 1H), 3.83–3.75 (m, 1H), 3.71–3.63 (m,
H), 3.61–3.52 (m, 1H), 2.88–2.77 (m, 1H), 2.66–1.77 (m,
4H). C NMR d: 208.7, 72.9, 68.7, 53.3, 46.8, 46.5, 46.3,
2
,7
5
-Methyl-6-oxa -12-thia-tricyclo[7.2.1.0 ]dodeca-2(7)-4-
1
3
dien-3-one (15)
Lithium enolate of 1 (0.5 mmol) was generated according
to procedure B (base 11d). 2-Bromo-2-butenoyl cyanide (95 mg,
5.9, 45.8, 45.5, 33.8, 33.4, 33.0, 32.9.
9
7%, 0.53 mmol) in THF (1 mL) was then added and the re-
(
–)-2-Cinnamoyl-8-thiabicyclo[3.2.1]octan-3-one (13)
Lithium enolate of 1 (0.5 mmol) was prepared as de-
sulting mixture was stirred at –78°C for 30 min. followed by
quenching with 40% K CO (2 mL). After warming up to rt
2
3
scribed in procedure B (base 11d). After stirring at –78°C
for 3 h, cinnamoyl cyanide (100 mg, 0.60 mmol) in THF
the reaction mixture was extracted with ether (3 × 10 mL).
The combined extracts were dried over MgSO and the sol-
4
(
1 mL) was added to the enolate, and the resulting mixture
was stirred at –78°C for 30 min, followed by quenching with
0% K CO (2 mL). After warming up to rt, the reaction
vent was removed under vacuum to give the crude product
14 that was refluxed over 3 h in triethylamine (5 mL). The
4
solvent (Et N) was then removed under vacuum. The resi-
2
3
3
mixture was extracted with CHCl (3 × 10 mL). The com-
dues were basified with 40% K CO (10 mL) and extracted
with ether (3 × 10 mL). The extracts were dried over MgSO4.
After removal of the solvent, column chromatography af-
3
2
3
bined extracts were dried over MgSO and the solvent was
4
removed under vacuum. Column chromatography (SiO2,
hexane–ethyl acetate, 4:1) afforded the pure product 13 as a
yellow oil (83 mg, 61%). This product had 87% ee as deter-
forded the product as oil (53 mg, 51%). This sample had
1
87% ee as determined by H NMR with (S)-(+)-TFAE. R =
f
2
5
mined by NMR with (S)-(+)-TFAE. [a] –330 (c 0.99,
0.50 (CH Cl –MeOH, 9:1). EI-MS m/z (%): 208 (100), 180
D
2
2
MeOH). R = 0.40 (hexane–ethyl acetate, 4:1). HRMS calcd.
(65), 179 (34), 175 (55), 161 (13), 91 (9),77 (5). HRMS
f
–1
+
for C H O S: 272.0871; found: 272.0866. IR (cm ): 1626,
calcd. for C H O S: 208.0557 (M ); found: 208.0558. IR
16
16
2
11 12
2
1
–1
1
1
7
1
1
576, 1558, 1540. H NMR d: 7.67 (d, J = 15.5 Hz, 1H),
.60–7.54 (m, 2H), 7.43–7.33 (m, 3H), 7.01 (d, J = 15.5 Hz,
H), 4.56–4.49 (m, 1H), 3.92–3.78 (m, 1H), 3.00 (dd, J =
9.0, 6.0 Hz, 1H), 2.58 (dd, J = 19.0, 2.0 Hz, 1H), 2.40–2.20
(cm ): 1659, 1611, 1596. H NMR d: 1.82–1.93 (m, 1H),
2.16 (s, 3H), 2.10–2.40 (m, 3H), 2.52 (dd, J = 18.1, 2.3 Hz,
1H), 3.08 (dq, J = 18.1, 2.1 Hz, 1H), 3.95 (m, 1H), 4.67 (d,
1
3
J = 4.9 Hz, 1H), 6.03 (s, 1H). C NMR d: 20.0, 34.6, 39.8,
1
3
(
m, 4H), 2.10–1.93 (m, 1H). C NMR d: 199.3, 169.8,
40.4, 40.5, 44.9, 113.5, 129.6, 162.3, 165.1, 176.1. Note:
©
2001 NRC Canada