5004
M. E. Hediger / Bioorg. Med. Chem. 12 (2004) 4995–5010
1210, 1070, 855, 835cmꢀ1. H NMR (d-6 PhD refer-
enced to d 7.15) d 5.57–5.45 (m, 2H), 5.25 (d, 0.5H,
J=9.2), 5.20 (d, 0.5H, J=9.3), 4.72 (m, 1H), 4.20 (m,
2H), 4.02 (m, 2H), 3.90 (m, 2H), 2.74 (d, 0.5H,
J=17.4), 2.42 (d, 0.5H, J=14.3), 2.11–1.79 (m, 6H),
1.47 (m, 0.5H), 1.03 (m, 2H), 0.91 (m, 6H), ꢀ0.12 (bs,
9H). 13C NMR (50ꢁC in d-6 PhD referenced to d
128.00) d 177.58, 176.15, 175.48, 175.39, 156.23,
155.39, 126.61, 125.89, 125.26, 124.49, 63.29, 61.15,
60.61, 51.77, 51.54, 43.62, 43.21, 40.61, 38.65, 34.71,
32.16, 31.58, 27.97, 22.78, 22.48, 18.05, 12.40, ꢀ1.61.
Anal. Calcd for C20H35O6NSi: C, 58.08; H, 8.53; N,
3.39. Found: C, 58.05; H, 8.25; N, 3.32.
vigorously stirred a 0ꢁC until no color remained from
the bicyclic starting material. This cold, two-phase mix-
ture was poured into 300mL of vigorously refluxing
CCl4 and heated for 3min after returning to reflux.
The cooled solution was partitioned between Et2O
(400mL) and NaOH (1.0M, 3·50mL), H2SO4 (0.5M,
4·20mL), 50% saturated aqueous NaHCO3, and brine.
The solution was dried, filtered and solvents evaporated
to give a yellow oil. This material was purified by flash
chromatography (20% EtOAc/hexanes) to yield 3.140g
(93%) of the pale-yellow bicyclic aza nonene as a 1:1
mixture of diastereomers. IR (CDCl3 solution) 2970,
1730, 1690, 1530, 1420, 1300, 1255, 1215, 1110, 1070,
1
865, 845cmꢀ1 1H NMR 6.00–5.50 (m, 2H), 4.91 (d,
.
5.11. ( ) Diethyl (1R ,3R S ,5S ,7R )-2-(N-2-trimethyl-
* *
0.5H, J=7.2), 4.87 (m, 0.5H), 4.75–4.72 (m, 1H), 4.58
(bs 0.5H), 4.28–3.98 (m, 6.5H), 2.68 (dd, 0.5H,
J=14.2, 6.9), 2.44–2.34 (m, 1.5H), 2.21–2.08 (m, 1H),
2.06–1.95 (m, 2H), 1.90–1.72 (m, 2H), 1.27–1.17 (m,
6H), 1.07–0.91 (m, 2H), 0.40–0.00 (m, 9H). 13C NMR
(70ꢁC in d-6 PhD referenced to d 128.00) d 175.91,
175.82, 172.48, 171.82, 156.22, 155.82, 155.77, 129.92,
129.61, 129.29, 126.61, 125.95, 125.95, 125.47, 125.24,
124.57, 120.56, 63.69, 63.27, 61.11, 60.94, 60.63,
60.51,52.59, 51.28, 46.23,44.82,43.74, 43.37, 39.31,
38.49, 36.73, 35.22, 34.67, 33.00, 32.88, 32.33, 31.51,
30.69, 28.28, 22.83, 22.57, 18.22, 18.14, 14.12, 14.10,
14.08, 14.05, 14.02, ꢀ1.60. Anal. Calcd for C20H33O6N-
Si: C, 58.36; H, 8.08; N, 3.40. Found: C, 58.65; H, 7.94;
N, 3.15.
*
*
silylethoxycarbonyl)-8-phenylselenyl-2-aza-bicyclo-
*
[3.3.1]nonane-3,5-dicarboxylate (21)
In a dry 250-mL round-bottomed flask was placed
monocylic urethane, 20, (4.149g, 10.0mmol) and a mag-
netic stir bar. While sweeping with nitrogen, the flask
was charged with CH2Cl2 (50mL) followed by N-PSP
(4.546g, 15.1mmol)16 and ( )-camphorsulfonic acid
(0.466g, 2.01mmol).17 The flask was fitted with a reflux
condensor, additional CH2Cl2 (50mL) was added and
reflux initiated. Analysis of the reaction mixture by
TLC after 12h indicated no starting urethane remained.
The reaction mixture was cooled, poured into Et2O
(200mL), and evaporated to give a brown oil. This
material was purified by flash chromatorgraphy (20%
EtOAc/hexanes) to yield 4.676g (82%) of the deep or-
ange bicyclic adduct as an undetermined mixture of dia-
stereomers. IR (CDCl3 solution) 3065, 2965, 1725, 1690,
1460, 1405, 1315, 1295, 1255, 1200, 1080, 1025, 865,
5.13. ( ) Diethyl (1R ,2S ,4R ,6S ,8S )-9-(N-2-tri-
*
*
*
*
*
methylsilylethoxycarbonyl)-9-azaoxatricyclo-[4.3.1.02,4]-
decane-6, 8-dicarboxylate and ( ) diethyl (1R ,2S ,4R ,
*
*
*
6S ,8R )-9-(N-2-trimethylsilylethoxycarbonyl)-9-azaoxa-
*
*
840cmꢀ1
.
1H NMR (60ꢁC in d-6 PhD referenced to
tricyclo-[4.3.1.02,4]-decane-6,8-dicarboxylate (23a and
23b)
7.15) d 7.85–7.50 (m, 2H), 7.10–6.85 (m, 3H), 5.00–
4.85 (m, 1.5H), 4.43 (dd, 0.5H, J=9.8, 7.1), 4.30–3.70
(m, 6H), 3.60–2.80 (m, 1H), 2.65–2.45 (m, 2H), 2.40–
1.15 (m, 6H), 1.15–0.60 (m, 8H), 0.20 to ꢀ0.20 (m,
9H). 13C NMR (60ꢁC in d-6 PhD referenced to d
128.00) d 176.16, 175.96,173.24, 172.70, 172.40, 156.51,
156.40, 156.23, 135.31, 134.82, 133.23, 130.59, 130.45,
129.35, 129.23, 129.12, 129.07, 128.29, 127.91, 127.61,
127.42, 126.99, 66.35, 63.80, 61.18, 60.96, 60.72, 60.68,
53.30, 53.12, 52.63, 52.27, 45.79, 44.85, 43.79, 43.33,
39.02, 38.88, 32.92, 32.79, 32.65, 32.26, 32.09, 31.82,
28.93, 28.15, 28.01, 26.41, 24.33, 24.14, 22.88, 18.79,
18.27, 18.20, 18.09, 14.22, 14.12, 14.11, 14.07, 14.03,
ꢀ1.14, ꢀ0.43, ꢀ0.57, ꢀ1.61, ꢀ1.63, ꢀ1.82. Anal. Calcd
for C26H39O6NSiSe: C, 54.91; H, 6.91; N, 2.46. Found:
C, 55.16; H, 6.86; N, 2.22.
In a dry 100-mL round-bottomed flask was placed the
bicyclic olefin, 22, (632mg, 1.54mmol), mCPBA(ca.
85% purity, 663mg, 3.07mmol) and a magnetic stir
bar. The flask was sealed and CH2Cl2 (15.0mL) was
added. The reaction mixture was stirred for 10h at
ambient temperature, at which time TLC analysis
showed only a trace of the staring olefin. The reaction
suspension was cooled to 0ꢁC, and dimethyl sulfide
(1.13mL, 975mg, 15.7mmol) was added. After stirring
1h, hexanes (60mL) were added to the suspension.
The reaction mixture was filtered through a Celiteꢂ
pad, and the retained material washed with minimal
cold hexanes. The combined filtrate and washings were
evaporated and the residue purified by flash chromato-
graphy (20% EtOAc/hexanes, SiO2 (8cm·20cm; base-
rinsed and oven dried collection tubes) to give first
272mg (41%) of endo epoxide 23a followed by 291mg
(44%) of exo epoxide 23b.
5.12. ( ) Diethyl (1R ,3R S ,5S )-2-(N-2-trimethylsilyl-
* *
*
ethoxycarbonyl)-2-azabicyclo[3.3.1]non-7-ene-3, 5-dicarb-
*
oxylate (22)
In a 250-mL round-bottomed flask was placed the [3.3.1]
adduct, 21, (4.676, 8.22mmol), CH2Cl2 (10mL), pyr-
idine (10mL), and a large magnetic stir bar. The solu-
tion was cooled to 0ꢁC with stirring and cold tert-butyl
peroxide (10mL) and 30% hydrogen peroxide (100mL)
were added sequentially. The flask was sealed and
vented with a fine needle; the two-phase mixture was
endo Epoxide 23a: IR (CDCl3 solution) 2990, 2970,
1730, 1695, 1415, 1330, 1295, 1250, 1210, 1100, 1050,
1
1030, 860, 840cmꢀ1. H NMR (90ꢁC, d-8 PhMe refer-
enced to Me at d 2.09) d 4.87 (bs, 2H), 4.23 (m, 2H),
3.87 (m, 4H), 3.28 (dd, 1H, J=3.6, 3.6), 2.74 (dd, 1H,
J=3.9, 3.9), 2.49 (ddd, 1H, J=14.1, 2.3, 1.6), 2.30 (m,
1H), 2.11 (m, 1H), 1.91 (ddd, 1H, J=16.0, 4.4, 2.1),