Tamura et al.
1
(CHCl3) 2968, 3013 cm-1; H NMR (270 MHz, CDCl3) δ 3.24
(3aR*,6aR*)-Hexahydro-3,3-dimethyl-5-tosyl-1H-pyr-
rolo[3,4-c]isoxazole (16f). Oxime 11a (654 mg, 2.61 mmol)
was treated with BF3‚OEt2 (0.45 mL, 5.3 mmol) in (CH2Cl)2
(5 mL) at room temperature for 21 h. After workup, the crude
material was chromatographed on silica gel (AcOEt-CHCl3,
1:10) to give 16f (278 mg, 68%): mp 172-175 °C (hexane-
(1H, br dtd, J ) 2.7, 6.0, 8.5 Hz), 3.75 (1H, dd, J ) 5.1, 10.0
Hz), 3.83 (1H, dd, J ) 6.5, 9.2 Hz), 3.87 (1H, dd, J ) 2.2, 10.0
Hz), 3.97 (1H, dd, J ) 2.7, 9.2 Hz), 4.27 (1H, m), 4.65 (1H, d,
J ) 5.3 Hz), 7.37 (5H, br s); the NH was not observed; 13C
NMR (67.8 MHz, CDCl3) δ 58 (br), 68.8 (br), 72.5 (br), 92 (br),
127.0, 128.8, 129.2, 138.7; HRMS calcd for C11H13NO2 191.0946,
found 191.0936.
Table 1, Entry 5: General Procedure for the BF3‚OEt2-
Mediated Cycloaddition of O-TBS Oximes 16. To a
stirred solution of 9a (61 mg, 0.2 mmol) in CH2Cl2 was added
BF3‚OEt2 (53 µL, 0.42 mmol) at 0 °C, and the mixture was
stirred at room temperature for 1 h. Saturated aqueous
NaHCO3 was added, and the whole was extracted with CHCl3,
washed successively with water and brine, dried (MgSO4), and
concentrated under reduced pressure. The residue was chro-
matographed on silica gel (hexane-AcOEt, 4:1-1:1) to give
16a (37 mg, 97%).
1
AcOEt); IR (CHCl3) 1348 cm-1; H NMR (270 MHz, CDCl3) δ
1.21 (3H, s), 1.26 (3H, s), 2.44 (3H, s), 2.71 (1H, br q, J ) 6.9
Hz), 2.92-3.49 (4H, m), 4.10 (1H, dt, J ) 4.6, 7.6 Hz), 7.34
(2H, d, J ) 7.9 Hz), 7.69 (2H, d, J ) 7.9 Hz); 13C NMR (67.8
MHz, CDCl3) δ 20.4, 21.5, 29.7, 43.2, 50.1, 54.9, 53.3, 127.5,
129.6, 134.5, 143.5. Anal. Calcd for C14H20N2O3S: C, 56.73;
H, 6.80; N, 9.45. Found: C, 56.59; H, 6.95; N, 9.38.
(3aR*,6aR*)-Hexahydro-5-tosyl-1H-pyrrolo[3,4-c]isox-
azole (16g) and (1R*,5S*)-3-(Toluene-4-sulfonyl)-3,7-diaza-
6-oxabicyclo[3,2,1]octane (18a). Oxime 11b (77 mg, 0.2
mmol) was treated with BF3‚OEt2 (53 µL, 0.42 mmol) in
(CH2Cl)2 (2 mL) at 50 °C for 40 h. After workup, the crude
material was chromatographed on silica gel (hexane-AcOEt,
1:2-1:4) to give 16g (18 mg, 32%) and 18a (19 mg, 33%). 16g:
IR (CHCl3) 1348 cm-1; 1H NMR (270 MHz, CDCl3) δ 2.44 (3H,
s), 2.83 (2H, br), 3.15 (1H, m), 3.26-3.90 (4H, br), 4.08 (1H,
m), 5.07 (1H, br), 7.35 (2H, d, J ) 7.9 Hz), 7.68 (2H, d, J ) 8.2
Hz); 13C NMR (67.8 MHz, CDCl3) δ 21.6, 47.6, 52.8, 64.8, 77.2,
128.1, 129.8, 131.4, 144.1. Anal. Calcd for C12H16O3N2S: C,
53.71; H, 6.01; N, 10.44. Found: C, 53.77; H, 6.25; N, 10.05.
18a: IR (CHCl3) 1336 cm-1; 1H NMR (270 MHz, CDCl3) δ 2.04
(2H, m), 2.43 (3H, s), 2.85 (1H, br d, J ) 11.9 Hz), 3.03 (1H,
br d, J ) 11.9 Hz), 3.62 (1H, br d, J ) 11.9 Hz), 3.77 (1H, br
s), 4.48 (1H, br s), 7.31 (2H, d, J ) 8.3 Hz), 7.71 (2H, d, J )
8.3 Hz); the NH was not observed; 13C NMR (67.8 MHz, CDCl3)
δ 21.5, 37.2, 50.7, 51.1, 53.3, 71.3, 127.5, 129.6, 134.5, 143.6;
HRMS calcd for C12H16O3N2S 268.0882, found 268.0886. Anal.
Calcd for C12H16O3N2S: C, 53.71; H, 6.01; N, 10.44. Found:
C, 53.96; H, 6.18; N, 10.06.
(1R*,5S*)-5-Methyl-3-tosyl-3,7-diaza-6-oxabicyclo[3,2,1]-
octane (18b). Oxime 11c (62 mg, 0.16 mmol) was treated with
BF3‚OEt2 (43 µL, 0.32 mmol) in CH2Cl2 (1.6 mL) at room
temperature for 20 h. After workup, the crude material was
chromatographed on silica gel (hexane-AcOEt, 1:5) to give 17b
(26 mg, 58%): IR (CHCl3) 1340 cm-1; 1H NMR (270 Mz, CDCl3)
δ 1.35 (3H, s), 1.92 (2H, m), 2.43 (3H, s), 2.71 (1H, d, J ) 11.6
Hz), 2.86 (1H, d, J ) 11.6 Hz), 3.66-3.77 (2H, m), 7.30 (2H, d,
J ) 8.3 Hz), 7.72 (2H, d, J ) 8.3 Hz); 13C NMR (67.8 Mz,
CDCl3) δ 20.4, 21.5, 29.7, 43.2, 50.1, 54.9, 55.3, 127.5, 129.6,
134.4, 143.5; HRMS (FAB) calcd for C13H19N2O3S (MH+)
283.1116, found 283.1127.
(3R*,3aR*,6aS*)-Hexahydro-3-phenylfuro[3,4-c]isox-
azole (16b) (Table 2, Entry 1). Oxime 9b (61 mg, 0.2 mmol)
was treated with BF3‚OEt2 (53 µL, 0.42 mmol) in CH2Cl2 (2
mL) at room temperature for 1 h. After workup, the crude
material was chromatographed on silica gel (hexane-AcOEt,
1:1) to give 16b (33 mg, 87%): IR (CHCl3) 3013, 2862 cm-1
;
1H NMR (270 MHz, CDCl3) δ 3.27-3.42 (2H, m), 3.51 (1H,
dd, J ) 6.9, 9.2 Hz), 3.79 (1H, dd, J ) 4.4, 9.6 Hz), 4.01 (1H,
dd, J ) 6.9, 9.6 Hz), 4.30 (1H, dt, J ) 4.4, 8.2 Hz), 4.88 (1H,
d, J ) 6.3 Hz), 5.64 (1H, br s), 7.24-7.39 (5H, m); 13C NMR
(67.8 MHz, CDCl3) δ 53.0, 67.3, 69.9, 75.1, 88.0, 126.8, 128.1,
128.8, 136.4; HRMS calcd for C11H13NO2 191.0946, found
191.0939.
(3aR*,6aS*)-Hexahydro-3,3-dimethylfuro[3,4-c]isox-
azole (16c) (Table 2, Entry 2). Oxime 9c (51 mg, 0.2 mmol)
was treated with BF3‚OEt2 (53 µL, 0.42 mmol) in CH2Cl2 (2
mL) at room temperature for 1 h. After workup, the crude
material was chromatographed on silica gel (hexane-AcOEt,
1:4) to give 16c (23 mg, 80%) as an oil: IR (CHCl3) 3013, 2980,
2866 cm-1; 1H NMR (270 MHz, CDCl3) δ 1.28 (3H, s), 1.32 (3H,
s), 2.74 (1H, dt, J ) 4.0, 7.6 Hz), 3.64 (1H, dd, J ) 7.6, 9.5
Hz), 3.75 (1H, dd, J ) 4.1, 9.5 Hz), 3.79 (1H, dd, J ) 5.6, 9.5
Hz), 3.88 (1H, dd, J ) 4.0, 7.6 Hz), 4.16 (1H, br td, J ) 4.5,
7.6 Hz); the NH was not observed; 13C NMR (67.8 MHz, CDCl3)
δ 21.0, 26.2, 57.1, 67.4, 69.6, 73.0, 84.7; HRMS calcd for
C7H13NO2 143.0946, found 143.0933.
(3R*,3aR*,6aR*)-Benzyl Tetrahydro-3-phenyl-1H-pyr-
rolo[3,4-c]isoxazole-5-(3H)-carboxylate (16d) (Table 2,
Entry 3). Oxime 10 (88 mg, 0.2 mmol) was treated with
BF3‚OEt2 (53 µL, 0.42 mmol) in CH2Cl2 (2 mL) at room
temperature for 1 h. After workup, the crude material was
chromatographed on silica gel (hexane-AcOEt, 1:1) to give 16d
(60 mg, 92%) as an oil: IR (CHCl3) 3013, 1697 cm-1; 1H NMR
(270 MHz, CDCl3) δ 3.24 (1H, br s), 3.54 (2H, br s), 3.72 (2H,
br s), 4.22 (1H, td, J ) 4.8, 7.9 Hz), 4.74 (1H, br s), 5.42 (1H,
br s), 7.27-7.44 (10H, m); 13C NMR (67.8 MHz, CDCl3) δ 50.5,
55 (br), 66 (br), 67.5, 91 (br), 126.6, 128.4, 128.5, 128.7, 128.9,
129.2, 136.9, 138.9, 155.2; HRMS calcd for C19H20N2O3 324.1474,
found 324.1476.
2-(Oxo-2-phenylethyl)-1,2,3,4-tetrahydropyridine N-
Oxide (19). Oxime 15 (77 mg, 0.2 mmol) was treated with
BF3‚OEt2 (53 µL, 0.42 mmol) in CH2Cl2 (2 mL) at 0 °C for 30
min. After workup, the crude material was triturated with
Et2O, and the resulting precipitates were collected to give 19
(24 mg, 56%) as colorless powder. This material was too
unstable to be recrystallized: IR (CHCl3) 2361, 1686 cm-1; 1H
NMR (270 MHz, CDCl3) δ 1.69-2.33 (4H, m), 2.47 (2H, m),
3.19 (1H, dd, J ) 9.2, 17.5 Hz), 4.23 (1H, dd, J ) 3.3, 17.5
Hz), 4.43 (1H, m), 7.22 (1H, t, J ) 3.9 Hz), 7.38-7.66 (3H, m),
7.94-8.05 (2H, m); 13C NMR (67.8 MHz, CDCl3) δ 16.3, 26.4,
28.5, 41.7, 64.1, 128.6, 129.1, 129.1, 133.5, 133.8, 180.4; HRMS
calcd for C13H15NO2 217.1103, found 217.1103.
(3aR*,6aS*)-Hexahydro-3-phenyl-1H-cyclopenta[c]-
isoxazole (16e) (Table 2, Entry 4). Oxime 12 (60 mg, 0.2
mmol) was treated with BF3‚OEt2 (53 µL, 0.42 mmol) in
CH2Cl2 (2 mL) at room temperature for 5 days. After work-
up, the crude material was chromatographed on silica gel
(hexane-AcOEt, 1:1) to give 16e (28 mg, 73%) as a 1:1 mix-
(3aR,6S,6aR)-Hexahydro-3,3,6-trimethyl-5-tosyl-1H-
pyrrolo[3,4-c]isoxazole (16h). Oxime 11d (85 mg, 0.2 mmol)
was treated with BF3‚OEt2 (53 µL, 0.42 mmol) in CH2Cl2 (2
mL) at 0 °C for 6 h. After workup, the crude material was
chromatographed on silica gel (hexane-AcOEt, 1:1) to give an
11:1 mixture of 16h and 16i (57 mg, 92%). An analytical
sample of 16h was obtained by preparative TLC on silca gel
ture of diastereomers: IR (CHCl3) 3011, 2961, 2870 cm-1
;
1H NMR (270 MHz, CDCl3) δ 1.10-2.01 (6H, m), 3.02 (1H ×
1/2, m), 3.12 (1H × 1/2, td, J ) 6.6, 8.1 Hz), 4.00-4.13
(1H, m), 4.51 (1H × 1/2, br s), 4.82 (1H, d, J ) 6.6 Hz),
4.90-5.90 (1H, br), 7.22-7.42 (5H, m); 13C NMR (67.8
MHz, CDCl3) δ 24.8, 26.5, 28.6, 31.3, 32.1, 35.5, 52.3, 56.6,
67.3, 67.9, 88.8, 91.3, 126.4, 126.7, 127.4, 128.2, 128.4, 128.9,
137.9, 140.1; HRMS calcd for C12H15NO 189.1154, found
189.1155.
1
(hexane-AcOEt, 2:3): IR (CHCl3) 2980, 1344 cm-1; H NMR
(270 MHz, C6D6) δ 0.67 (3H, s), 0.81 (3H, s), 1.43 (3H, d, J )
6.3 Hz), 1.84 (3H, s), 2.03 (1H, br q, J ) 7.5 Hz), 2.92 (1H, dd,
J ) 6.9, 10.1 Hz), 2.99 (1H, dd, J ) 5.5, 7.5 Hz), 3.20 (1H, br
quint, J ) 6.0 Hz), 3.43 (1H, dd, J ) 8.5, 10.1 Hz), 6.78 (2H,
10724 J. Org. Chem., Vol. 70, No. 26, 2005