O. Tamura et al. / Tetrahedron 60 (2004) 9997–10003
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4.1.2. (2S)-N-[[(3R,5S)-2-(Diphenylmethyl)-3-(3-pyridyl)-
isoxazolidin-5-yl]carbonyl]bornane-10,2-sultam, 12. To
a stirred mixture of (2S)-8 (380 mg, 1.41 mmol) and MgBr2
(318 mg, 1.41 mmol) in CH2Cl2 (15 mL) was added nitrone
3c (80 mg, 0.282 mmol) in CH2Cl2 (2 mL), and the mixture
was heated at reflux for 3 days. After cooling, the mixture
was successively washed with a saturated solution of
NaHCO3 and brine, dried (Na2CO3), and evaporated under
reduced pressure. The residue was chromatographed on
silica gel (CHCl3–AcOEt, 30:1) to give 12 (94 mg, 60%) as
colorless crystals: mp 224–226 8C (n-hexane–AcOEt);
[a]2D0ZC89.8 (c 0.32, CHCl3); IR (CHCl3) 1700,
The mixture was subjected to preparative TLC on silica gel
(Et2O–AcOEt, 10:1) to give 16 (101 mg, 80%): mp 85–
88 8C; [a]2D6ZC72.3 (c 0.32, CHCl3); IR (CHCl3) 1700,
1
1340 cmK1; H NMR (270 MHz, CDCl3) d 0.98 (3H, s),
1.19 (3H, s), 127 (3H, s), 1.28 (3H, s), 1.32 (3H, s), 1.44
(3H, s), 1.2–1.3 (2H, m), 1.8–2.15 (4H, m), 2.24–2.26 (1H,
m), 2.70 (1H, ddd, JZ12.7, 8.3, 4.4 Hz), 3.02 (1H, dt, JZ
12.7, 6.4 Hz), 3.43 (1H, d, JZ13.7 Hz), 3.52 (1H, d, JZ
13.7 Hz), 3.61 (1H, dd, JZ8.3, 6.4 Hz), 3.86 (1H, dd, JZ
8.3, 4.4 Hz), 3.92 (1H, dd, JZ7.8, 4.9 Hz), 4.13 (1H, dd,
JZ8.3, 6.4 Hz), 4.26 (1H, dt, JZ8.3, 6.8 Hz), 4.66 (1H, dd,
JZ6.4, 4.4 Hz), 4.85 (1H, dd, JZ6.9, 4.4 Hz), 4.86 (1H, s),
5.06 (1H, d, JZ6.4 Hz), 5.15 (1H, dd, JZ8.3, 6.4 Hz), 7.24
(1H, dd, JZ7.8, 4.9 Hz), 7.71 (1H, br d, JZ7.8 Hz), 8.50
(1H, br d, JZ4.9 Hz), 8.61 (1H, br s); 13C NMR (67.8 MHz,
CDCl3) d 19.8, 20.9, 24.8, 25.2, 26.0, 26.426.6, 32.9, 38.1,
39.4, 44.7, 47.8, 48.9, 53.0, 62.8, 65.5, 65.8, 75.6, 76.6,
80.2, 83.8, 84.2, 97.3, 109.5, 112.5, 123.4, 134.3, 135.8,
148.7, 148.8, 170.1. HRMS (EI) m/z Calcd for
C31H43N3O9S 633.2720, found: 633.2717. (b) (Table 1,
entry 3). A solution of (2S)-8 (185 mg, 0.686 mmol) and 15
(50.0 mg, 0.137 mmol) in (CH2Cl)2 (5 mL) was heated at
reflux for 12 h. A work-up similar to that for the reaction in
CH2Cl2 gave 16 (61.2 mg, 71%) and a mixture of isomers
(6.7 mg, 7.7%)
1
1340 cmK1; H NMR (270 MHz, CDCl3) d 0.93 (3H, s),
1.08 (3H, s), 1.1–1.3 (2H, m), 1.75–1.9 (3H, m), 1.9–2.1
(1H, m), 2.1–2.2 (1H, m), 2.7–3.0 (2H, m), 3.35 (1H, d, JZ
13.8 Hz), 3.44 (1H, d, JZ13.8 Hz), 3.76 (1H, br t, JZ
6.1 Hz), 3.95 (1H, t, JZ7.9 Hz), 4.88 (1H, s), 5.01 (1H, br),
7.05–7.10 (3H, m) 7.1–7.35 (6H, m), 7.45 (2H, d, JZ
7.2 Hz), 7.90 (1H, br d, JZ7.8 Hz), 8.23 (1H, br s), 8.39
(1H, dd, JZ4.4, 1.5 Hz); 13C NMR (67.8 MHz, CDCl3) d
20.4, 21.5, 26.7, 33.3, 38.9, 45.4, 48.1, 49.4, 53.2, 65.2,
65.5, 73.0, 75.4, 77.7, 124.1, 127.8, 127.9, 128.6, 128.7,
128.9, 129.5, 136.1, 136.5, 140.4, 140.7, 149.1, 149.8,
169.8; MS m/z 557 (MC); HRMS calcd for C32H35N3O4S
557.2349, found: 557.2344.
4.1.3. (2R)-N-[[(3S,5R)-2-(Diphenylmethyl)-3-(3-pyridyl)
isoxazolidin-5-yl]carbonyl]bornane-10,2-sultam, ent-12.
Mp 224–226 8C (n-hexane–AcOEt); [a]2D0ZK89.8 (c 0.31,
CHCl3).
4.1.6. (2S)-N-[[(3S,5S)-3-(3-Pyridyl)isoxazolidin-5-
yl]carbonyl]bornane-10,2-sultam, 17. A solution of 16
(39.9 mg, 63.0 mmol) in concentrated HCl–EtOH (1:6,
1 mL) was stirred at room temperature for 5 h. After
concentration, the residue was diluted with CHCl3, washed
with a saturated solution of NaHCO3, dried (MgSO4), and
concentrated. The residue was chromatographed on silica
gel (CHCl3–AcOEt, 20:1) to give 17 (18.7 mg, 76%): mp
218–219 8C (AcOEt–MeOH); [a]2D5ZC175.2 (c 0.36,
4.1.4. (Z)-3-Pyridyl-N-(20,30:50,60-O-diisopropylidene-a-
L-gulofuranosyl)methylideneamine N-oxide, 15. A mix-
ture of 3-pyridinecarbaldehyde (0.70 mL, 8.72 mmol) and
2,3:5,6-O-diisopropylidene-L-gulofuranose
oxime11d
CHCl3); IR (CHCl3) 1690, 1340 cmK1
;
1H NMR
(2.00 g, 7.26 mmol) in toluene (30 mL) was heated at reflux
with azeotropic removal of water by a Dean–Stark trap for
20 h. After cooling to room temperature, precipitated
crystals were collected by filtration to give 15 (1.88 g,
71%). The mother liquor was concentrated to give the
residue, which was chromatographed on silica gel (AcOEt)
to give additional 15 (611 mg, total 94%): mp 177–180 8C
(toluene); [a]2D6ZC42.3 (c 2.37, CHCl3); IR (CHCl3) 2990,
(270 MHz, CDCl3) d 0.99 (3H, s), 1.18 (3H, s), 1.3–1.5
(2H, m), 1.8–2.0 (3H, m), 2.0–2.3 (2H, m), 2.6–2.8 (1H, m),
2.95 (ddd, JZ13.2, 8.8, 4.4 Hz), 3.44 (1H, d, JZ13.8 Hz),
3.53 (1H, d, JZ13.8 Hz), 3.90 (1H, dd, JZ7.8, 4.9 Hz),
4.73 (1H, m), 5.26 (1H, dd, JZ8.3, 4.4 Hz), 7.26 (1H, m),
6.60 (1H, br), 7.76 (1H, d, JZ7.8 Hz), 8.50 (1H, d, JZ
4.9 Hz), 8.59 (1H, br s); 13C NMR (67.8 MHz, CDCl3) d
19.8, 20.8, 26.3, 32.8, 38.2, 38.4, 42.8, 44.4, 44.6, 47.8,
49.0, 53.0, 60.0, 65.1, 123.4, 133.8, 148.2, 148.5, 172.4;
HRMS (EI) m/z Calcd for C19H25N3O4S 391.1566, found:
391.1557. Anal. Calcd for C19H15NO2: C, 58.29; H, 6.44; N,
10.73, found: C, 58.03; H, 6.39; N, 10.66.
1
1560 cmK1; H NMR (270 MHz, CDCl3) d 1.34 (3H, s),
1.41 (3H, s), 1.47 (3H, s), 1.52 (3H, s), 3.74 (1H, dd, JZ8.3,
7.1 Hz), 4.23 (1H, dd, JZ8.3, 6.6 Hz), 4.40 (1H, dt, JZ8.3,
6.6 Hz), 4.60 (1H, dd, JZ8.3, 4.3 Hz), 4.90 (1H, dd, JZ5.9,
4.3 Hz), 5.33 (1H, d, JZ5.9 Hz), 5.60 (1H, s), 7.36 (1H, dd,
JZ8.3, 5.0 Hz), 7.68 (1H, s), 8.63 (1H, dd, JZ4.6, 1.7 Hz),
8.93 (1H, dt, JZ8.3, 1.7 Hz), 9.00 (1H, d, JZ2.0 Hz); 13C
NMR (67.8 MHz, CDCl3) d 24.5, 25.4, 25.9, 26.7, 65.8,
75.8, 80.2, 84.4, 87.6, 103.5, 109.9, 113.5, 123.5, 126.0,
130.7, 134.8, 150.1, 151.1. Anal. Calcd for C18H24N2O6: C,
59.33; H, 6.64; N, 7.69, found: C, 59.61; H, 6.77; N, 7.51.
4.1.7. (2S)-N-[[(3S,5S)-2-Methyl-3-(3-pyridyl)isoxazoli-
din-5-yl]carbonyl]bornane-10,2-sultam, 19. A mixture
of 17 (10.8 mg, 27.6 mmol) and a 36% aqueous solution of
formaldehyde (0.07 mL) in EtOH (1.5 mL) was stirred at
room temperature for 2 h, and then the mixture was
concentrated to give crude (2S)-N-[[(3S,5S)-2-ethoxy-
methyl-3-(2-pyridyl)isoxazolidin-5-yl]carbonyl]bornane-
10,2-sultam (18). The crude 18 was diluted with a 1:1
mixture of CF3CO2H and CH2Cl2 (3 mL). To the solution
was added Et3SiH (36 mL, 0.41 mmol), and the mixture was
heated at reflux for 30 min. After concentration, the residue
was diluted with CHCl3, washed with a saturated aqueous
solution of NaHCO3, dried (MgSO4), and concentrated. The
residue was chromatographed on silica gel (AcOEt–MeOH,
4.1.5. (2S)-N-[[(3S,5S)-2-(20,30:50,60-O-Diisopropylidene-
a-L-gulofuranosyl)-3-(3-pyridyl)isoxazolidin-5-yl]carbo-
nyl]bornane-10,2-sultam, 16. (a) (Table 1, entry 2). A
solution of (2S)-8 (269 mg, 1.00 mmol) and 15 (73 mg,
0.20 mmol) in CH2Cl2 (5 mL) was heated at reflux for 7
days. After concentration of the mixture, the residue was
chromatographed on silica gel (CHCl3–AcOEt, 30:1) to
give a 9.3:1 mixture (111.5 mg) of 16 and other isomers.