M. J. Alves et al. / Tetrahedron 62 (2006) 3095–3102
3099
were run as DCM mulls, and oils as thin films. Mass spectra
were recorded on a VG Autospec M. spectrometer.
Microanalyses were performed in a LECO-CHNS-932
analyser. Melting points (mp) were determined on a
Gallenkamp block. Dry flash chromatography was per-
formed on silica gel 60!0.063 mm for column chromato-
graphy. Petroleum ether 40–60 8C was distilled before use.
Toluene was distilled over sodium.
2H-azirine 2c (420 mg, 1.72 mmol) in toluene (10 mL) was
added 3-(3-(tert-butyldimethylsilyloxy)buta-1,3-dienyl)-
oxazolidin-2-one 3 (0.85 g; 3.16 mmol) dissolved in toluene
(10 mL). The reaction mixture was stirred under N2 at rt
over 4 days. After that the solvent was evaporated and a
white solid 5c was formed (mp 190.5–191.0 8C). Yield
(865 mg; 1.69 mmol, 58%). 1H NMR, (300 MHz, CDCl3, J
Hz), dZ0.22 (s, 3H, Me), 0.23 (s, 3H, Me), 0.96 (s, 9H, 3!
Me), 2.85 (dt, JZ18.6, 2.1 Hz, 1H, H-5), 3.00 (dd, JZ18.6,
1.2 Hz, 1H, H-5), 3.38 (s, 3H, OMe), 3.64 (s, 1H, H-7), 3.77
(t, JZ8.1 Hz, 2H, ox), 4.37 (m, 2H, ox), 4.61 (t, JZ2.1 Hz,
1H, H-3), 5.80 (br s, 1H, H-2), 7.08–7.15 (m, 1H, Ar), 7.25–
7.30 (m, 2H, Ar). 13C NMR, (75.5 MHz, CDCl3), dZK4.3
(Me), K4.4 (Me), 17.9 (C), 25.5 (Me), 27.7 (C-5), 41.9
(C-7), 42.3 (ox), 43.5 (C-6), 52.2 (Me), 61.9 (ox), 66.5
(C-2), 96.9 (C-3), 128.4, 128.9, 130.8, 135.6, 150.3 (C-4),
157.4 (CO, ox), 170.1 (CO). C23H28Cl2N2O5Si (511.09):
calculated C 54.00, H 5.48, N 5.48; found C 53.80, H 5.85,
N 5.66.
4.2. Synthesis of cycloadducts
4.2.1. 3-(6-Benzoyl-4-(tert-butyldimethylsilyloxy)-7-
methyl-1-aza-bicyclo[4.1.0]hept-3-en-2-yl)oxazolidin-2-
one 5a. The a-azide 1a (0.25 g; 1.33 mmol) was dissolved
in toluene (10 mL) and the solution refluxed for 2.5 h. After
cooling the solution to rt 3-(3-(tert-butyldimethylsilylox-
y)buta-1,3-dienyl)oxazolidin-2-one 3 (0.34 g; 1.26 mmol)
in toluene (10 mL) was added. The reaction mixture was
stirred under N2 at rt for 5 days. After that the solvent was
evaporated leaving an oil that was subjected to dry flash
chromatography (pet. ether/ether; 2:5). A white solid was
obtained and recrystallized from ether/pet. ether (mp 152.5–
154.0 8C) to give compound 5a. Yield (304 mg; 0.71 mmol,
4.2.4. Benzyl 4-(tert-butyldimethylsilyloxy)-2-(2-oxooxa-
zolidin-3-yl)-1-aza-bicyclo[4.1.0]hept-3-ene-6-carboxylate
5d. The a-azide 1d (1.80 g; 8.86 mmol) was dissolved in
toluene (200 mL) and heated under reflux for 5 h. After
cooling the solution to rt 3-(3-(tert-butyldimethylsilyloxy)-
buta-1,3-dienyl)oxazolidin-2-one 3 (1.25 g; 4.64 mmol) was
added,dissolvedintoluene(15 mL). Thereactionmixturewas
stirred under N2 at rt, for 4.5 days. After that the solvent was
evaporated to give a brown oil that was purified by dry flash
chromatography (pet. ether/ether; gradient polarity). The
product 5d was obtained as an oil. Yield (768 mg;
1
63%). H NMR, (300 MHz, CDCl3, J Hz), dZ0.16 (s, 3H,
Me), 0.18 (s, 3H, Me), 0.91 (s, 9H, 3!Me), 1.12 (d, JZ
5.7 Hz, 3H, Me), 2.44 (dm, JZ17.7 Hz, 1H, H-5), 2.52 (q,
JZ5.7 Hz, 1H, H-7), 2.82 (d, JZ17.7 Hz, 1H, H-5), 3.64 (t,
JZ8.1 Hz, 2H, ox), 4.63 (t, JZ2.1 Hz, 1H, H-3), 4.37 (dt,
JZ8.1 Hz, 3.3, 2H, ox), 5.90 (br s, 1H, H-2), 7.46–7.63 (m,
3H, Ar), 7.98–8.06 (m, 2H, Ar). 13C NMR, (75.5 MHz,
CDCl3), dZK4.6 (Me), K4.4 (Me), 15.2 (Me), 17.8 (C),
25.4 (Me), 29.3 (C-5), 34.4 (C-7), 41.4 (ox), 47.3 (C-6), 62.1
(ox), 65.6 (C-2), 98.2 (C-3), 128.6, 129.4, 133.4, 135.2, 149.4
(C-4), 157.4 (CO, ox), 197.4 (CO). C23H32N2O4Si (428.05):
calcd C 64.47, H 7.47, N 6.54; found C 64.20, H 7.56, N 6.47.
1
1.73 mmol; 37%). H NMR, (300 MHz, CDCl3, J Hz), dZ
0.19 (s, 6H, 2!Me); 0.94 (s, 9H, 3!Me); 2.27 (s, 1H, H-7);
2.28 (s, 1H, H-7); 2.60 (d, JZ18.0 Hz, 1H, H-5); 2.85 (br d,
JZ18.0 Hz, 1H, H-5), 3.60 (q, JZ8.4 Hz, 1H, ox), 3.75 (q,
JZ8.4 Hz, 1H, ox), 4.35–4.42 (m, 2H, ox), 4.50 (t, JZ2.1 Hz,
1H, H-3), 5.14 (d, JZ12.3 Hz, 1H, OCH2), 5.31 (d, JZ
12.3 Hz, 1H, OCH2), 5.67 (br s, 1H, H-2), 7.39 (br s, 5H, Ar).
13C NMR, (75.5 MHz, CDCl3), dZK4.6 (Me), K4.4 (Me),
17.8 (C), 25.4 (Me), 27.3 (C-5), 29.5 (C-7), 36.7 (C-6), 41.1
(ox), 62.0 (ox), 65.8 (C-2), 67.2 (CH2), 96.7 (C-3), 128.3,
128.32, 128.5, 135.5, 150.1(C-4), 157.3 (CO, ox), 171.2(CO).
HRMS (FAB): calcd 445.2159 [MC1]; found 445.2158.
4.2.2. 3-(6-Benzoyl-4-(tert-butyldimethylsilyloxy)-7-ethyl-
1-aza-bicyclo[4.1.0]hept-3-en-2-yl)oxazolidin-2-one 5b. To
a solution of 2H-azirine 2b (420 mg; 2.42 mmol) in toluene
(10 mL) was added 3-(3-(tert-butyldimethylsilyloxy)buta-
1,3-dienyl)oxazolidin-2-one 3 (0.45 g; 1.68 mmol) dissolved
in toluene (10 mL). The reaction mixture was stirred under N2
at rt for 4 days. After that the solvent was evaporated and the
crude subjected to dry flash chromatography (pet. ether/
diethyl ether; 1:2). A white solid 5b was obtained (mp 141.0–
143.5 8C). Yield (434 mg; 0.98 mmol; 58%). 1H NMR,
(300 MHz, CDCl3, J Hz), dZ0.15 (s, 3H, Me), 0.18 (s, 3H,
Me), 0.90 (s, 9H, 3!Me), 0.97 (t, JZ7.2 Hz, 3H, Me), 1.17–
1.30 (m, 1H, CHH), 1.37–1.48 (m, 1H, CHH), 2.36–2.44 (m,
2H, H-5CH-7), 2.84 (d, JZ18.0 Hz, 1H, H-5), 3.70 (m, 2H,
ox), 4.34 (t, JZ7.5 Hz, 2H, ox), 4.69 (t, JZ1.8 Hz, 1H, H-3),
5.79 (br s, 1H, H-2), 7.43–7.57 (m, 3H, Ar), 8.03 (d, JZ
7.2 Hz, 2H, Ar). 13C NMR, (75.5 MHz, CDCl3), dZK4.6
(Me), K4.5 (Me), 11.4 (Me), 17.8 (C), 23.5 (Me), 25.4 (Me),
29.3 (C-5), 40.9 (C-7), 42.1 (ox), 47.5 (C-6), 62.0 (ox), 65.7
(C-2), 98.2 (C-3), 128.5, 129.4, 133.3, 135.3, 149.0 (C-4),
157.3 (CO, ox), 197.7 (CO). C24H34N2O4Si (442.62):
calculated C 65.12, H 7.74, N 6.33; found C 64.78, H
7.63, N 6.39.
4.2.5. Ethyl 4-(tert-butyldimethylsilyloxy)-2-(2-oxooxa-
zolidin-3-yl)-6-(pyridin-2-yl)-1-aza-bicyclo[4.1.0]hept-3-
en-7-carboxylate 5e. To the 2H-azirine 2e (0.36 g;
1.87 mmol) solubilized in toluene (10 mL) was added 3-
(3-(tert-butyldimethylsilyloxy)buta-1,3-dienyl)oxazolidin-
2-one 3 (0.35 g; 1.87 mmol) solubilized in toluene (10 mL).
The reaction mixture was stirred under N2 at 75–80 8C for
2.5 days. After that the solvent was evaporated and the crude
obtained was purified by dry flash-cromatography (pet.
ether/diethyl ether; gradient polarity), to give compound 5e
as an oil. Yield (248 mg; 0.54 mmol; 29%). 1H NMR,
(300 MHz, CDCl3, J Hz), dZ0.15 (s, 3H, Me), 0.18 (s, 3H,
Me), 0.91 (s, 9H, 3!Me), 2.46 (dt, JZ18.0, 2.4 Hz, 1H,
H-5), 3.27 (dd, JZ18.0, 0.9 Hz, 1H, H-5), 3.27 (s, 1H, H-7),
3.60–3.75 (m, 2H, ox), 3.88–4.00 (m, 2H, CH2), 4.33–4.41
(m, 2H, ox), 4.58 (t, JZ2.1 Hz, 1H, H-3), 5.82 (br s, 1H, H-
2), 7.14–7.19 (m, 1H, Ar), 7.62–7.66 (m, 2H, Ar), 8.48–8.51
(m, 1H, Ar). 13C NMR, (75.5 MHz, CDCl3), dZK4.7 (Me),
K4.4 (Me), 13.8 (Me), 17.8 (C), 25.4 (Me), 31.2 (C-5), 40.1
4.2.3. Methyl 4-(tert-butyldimethylsilyloxy)-7-(2,
6-dichlorophenyl)-2-(2-oxooxazolidin-3-yl)-1-azabi-
cyclo[4.1.0]hept-3-en-6-carboxylate 5c. To a solution of