10550
G. Tang et al. / Tetrahedron 60 (2004) 10547–10552
xylene was rotary evaporated in vacuum. Flash chromato-
graphy of the residue afforded cyclization products.
307.1208, found 307.1201; FT-IR (KBr) 3031, 1745,
1707 cmK1
.
4.1.7. (4S,8aR)-8a-Benzyloxymethyl-4-phenyl-tetra-
hydropyrrolo[2,1-c][1,4]oxazine-1,6-dione 11d. [a]2D0Z
C70.9 (c 0.9, CHCl3); 1H NMR (300 MHz, CDCl3) d
7.36–7.28 (m, 8H), 7.25–7.20 (m, 2H), 5.13 (dd, JZ10.4,
6.6 Hz, 1H), 4.72 (dd, JZ11.9, 10.4 Hz, 1H), 4.51 (dd, JZ
12.0, 6.6 Hz, 1H), 4.52 and 4.46 (AB q, JZ11.7 Hz, 2H),
3.75 and 3.68 (AB q, JZ9.6 Hz, 2H), 2.70–2.45 (m, 2H),
2.39–2.27 (m, 2H); EI-MS m/z 352 (MCH)C, 230, 91, 77
55; FT-IR (KBr) 3064, 1755, 1705 cmK1. Anal. Calcd for
C21H21NO4 C, 71.78, H, 6.02, N, 3.99; found C, 71.84, H,
6.04, N, 4.06.
4.1.1. (4S,8aR)-8a-Methyl-4-phenyltetrahydro-pyr-
rolo[2,1-c][1,4]oxazine-1,6-dione 11a. [a]2D0ZC11.7 (c
1.2, CHCl3); H NMR (300 MHz, CDCl3) d 7.37–7.29 (m,
1
3H), 7.10–7.07 (m, 2H), 5.04 (d, JZ3.9 Hz, 1H), 4.91 (dd,
JZ12.2, 4.0 Hz, 1H), 4.40 (d, JZ12.2 Hz, 1H), 2.68–2.55
(m, 2H), 2.47–2.37 (m, 1H), 2.33–2.28 (m, 1H), 1.67 (s,
3H); EI-MS m/z 245 (MC), 230, 201, 187, 174, 159, 131,
104, 77, 51. HRMS Calcd for C14H15NO3 (MC) 245.1052,
found 245.1030; FT-IR (KBr) 1759, 1697 cmK1
.
4.1.2. (4S,8aS)-8a-Methyl-4-phenyltetrahydro-pyr-
rolo[2,1-c][1,4]oxazine-1,6-dione 12a. [a]2D0ZC104.3 (c
6.4, CHCl3); H NMR (300 MHz, CDCl3) d 7.42–7.31 (m,
1
4.1.8. (4S,8aS)-8a-Benzyloxymethyl-4-phenyl-tetra-
hydropyrrolo[2,1-c][1,4]oxazine-1,6-dione 12d. [a]2D0Z
C116.0 (c 1.6, CHCl3); H NMR (300 MHz, CDCl3) d
5H), 5.19 (dd, JZ10.2, 6.5 Hz, 1H), 4.63 (dd, JZ12.4,
6.4 Hz, 1H), 4.49 (dd, JZ12.4, 10.2 Hz, 1H), 2.76–2.58 (m,
2H), 2.46–2.34 (m, 1H), 2.26–2.17 (m, 1H), 1.64 (s, 3H);
EI-MS m/z 246 (MCH)C, 232, 218, 201, 187, 158, 130,
104, 98, 43. HRMS Calcd for C14H15NO3 (MC) 245.1052,
1
7.39–7.23 (m, 8H), 7.07–7.04 (m, 2H), 5.09 (dd, JZ11.7,
4.2 Hz, 1H), 4.94 (d, JZ4.1 Hz, 1H), 4.56 (s, 2H), 4.21 (d,
JZ11.6 Hz, 1H), 3.76 and 3.72 (AB q, JZ9.7 Hz, 2H),
2.61–2.28 (m, 4H); EI-MS m/z 352 (MCH)C, 260, 230,
184, 82, 55; FT-IR (KBr) 3032, 1759, 1706 cmK1. Anal.
Calcd for C21H21NO4 C, 71.78, H, 6.02, N, 3.99; found C,
71.41, H, 5.86, N, 3.89.
found 245.1023; FT-IR (KBr) 1745, 1698 cmK1
.
4.1.3. (4S,8aS)-8a-Ethyl-4-phenyltetrahydropyrrolo[2,1-
c][1,4]oxazine-1,6-dione 11b. [a]2D0ZC22.7 (c 19.2,
CHCl3); 1H NMR (300 MHz, CDCl3) d 7.42–7.31 (m,
5H), 5.17 (dd, JZ10.8, 6.6 Hz, 1H), 4.62 (dd, JZ12.5,
6.7 Hz, 1H), 4.50 (dd, JZ12.4, 11.0 Hz, 1H), 2.71–2.52 (m,
2H), 2.44–2.26 (m, 2H), 2.05 (m, JZ7.1 Hz, 1H), 1.94 (m,
JZ7.1 Hz, 1H), 1.05 (t, JZ7.4 Hz, 3H); EI-MS m/z 259
(MC), 229, 215, 201, 174, 158, 145. HRMS Calcd for
C15H17NO3 (MC) 259.1209, found 259.1204; FT-IR (KBr)
1741, 1705, 1454 cmK1. Anal. Calcd for C15H17NO3 C,
69.48, H, 6.61, N, 5.40; found C, 69.39, H, 6.63, N, 5.26.
4.1.9. (4S,8aS)-8a-Cyclopropyl-4-phenyl-tetrahydro-
pyrrolo[2,1-c][1,4]oxazine-1,6-dione 11e. [a]2D0ZK8.1 (c
1.6, CHCl3); H NMR (300 MHz, CDCl3) d 7.40–7.35 (m,
1
3H), 7.34–7.31 (m, 2H), 5.10 (dd, JZ11.7, 7.0 Hz, 1H),
4.76 (t, JZ12.0 Hz, 1H), 4.56 (dd, JZ12.2, 6.9 Hz, 1H),
2.69–2.59 (m, 2H), 2.36–2.30 (m, 2H), 1.44 (dt, JZ8.4,
2.8 Hz, 1H), 0.81 (m, 2H), 0.67 (t, JZ5.0 Hz, 1H), 0.50 (t,
JZ5.0 Hz, 1H); EI-MS m/z 272 (MCH)C, 227, 213, 156,
104, 91, 77. HRMS Calcd for C16H17NO (MCKCO2)
227.13101, found 227.13101.
4.1.4. (4S,8aR)-8a-Ethyl-4-phenyltetrahydropyrrolo[2,1-
c][1,4]oxazine-1,6-dione 12b. [a]2D0ZC103.0 (c 4.4,
CHCl3); 1H NMR (300 MHz, CDCl3) d 7.30–7.21 (m,
3H), 7.02–7.00 (m, 2H), 4.97 (d, JZ4.0 Hz, 1H), 4.87 (dd,
JZ12.1, 4.0 Hz, 1H), 4.30 (d, JZ12.1 Hz, 1H), 2.55–2.43
(m, 2H), 2.35 (m, 2H), 1.91 (m, 2H), 1.01 (t, JZ7.6 Hz,
3H); EI-MS m/z 259 (MC), 229, 215, 104, 42. HRMS Calcd
for C15H17NO3 (MC) 259.1208, found 259.1232; FT-IR
(KBr) 1755, 1695, 1452 cmK1. Anal. Calcd for C15H17NO3
C, 69.48, H, 6.61, N, 5.40; found C, 69.38, H, 6.65, N, 5.40.
4.1.10. 5-Hydroxy-4-oxopentanoic acid methyl ester 14.
To a stirred solution of methyl 5-bromo-4-oxo-pentanate 13
(1.99 g, 11.4 mmol) in 85% ethanol (20 mL) was added
sodium formate dihydrate (1.25 g, 12.0 mmol). The result-
ing mixture was refluxed overnight, and then concentrated
in vacuum and diluted with water. To this solution was
added 0.1 M HCl to adjust the pH to 6. EtOAc-extractive
work-up followed by chromatography eluting with
n-hexane/EtOAc (3:2) gave 1.59 g (95%) of 25 as colorless
1
liquid. H NMR (300 MHz, CDCl3) d 4.29 (d, JZ4.5 Hz,
4.1.5. (4S,8aR)-8a-Phenyl-4-phenyltetrahydro-pyr-
rolo[2,1-c][1,4]oxazine-1,6-dione 11c. [a]2D0ZK5.5 (c
0.8, CHCl3); H NMR (300 MHz, CDCl3) d 7.45–7.15 (m,
2H), 3.65 (s, 3H), 3.05 (t, JZ4.5 Hz, 1H, OH), 2.67 (s, 4H);
EI-MS m/z 147 (MCH)C, 129, 115, 59, 55; IR (neat) 3448,
1728, 1440 cmK1. Anal. Calcd for C6H10O4 C, 49.31, H,
6.90; found C, 48.98, H, 6.90.
1
10H), 5.10 (d, JZ3.7 Hz, 1H), 4.32 (dd, JZ12.0, 3.9 Hz,
1H), 4.10 (d, JZ12.0 Hz, 1H), 2.95 (m, 1H), 2.51–2.36 (m,
3H); EI-MS m/z 308 (MCH)C, 263, 221, 193, 104. HRMS
Calcd for C19H17NO3 (MC) 307.1208, found 307.1220;
4.1.11. 5-Benzyloxy-4-oxo-pentanoic 3d. To a solution of
O-benzyl 2,2,2-trichloroacetimidate (3.79 g, 15.0 mmol)
and 14 (1.46 g, 10.0 mmol) in cyclohexane/dichloro-
methane (2:1) (60 mL) was added CF3SO2H (50 mL) at
0 8C. The resulting mixture was stirred overnight at room
temperature before saturated NaHCO3 was added. The
aqueous layer was extracted with EtOAc. The combined
organic layers were washed with brine, dried with Na2SO4
and concentrated. Flash chromatography eluting with 10:1
n-hexane/EtOAc afforded 2.17 g (92%) of benzyl ether as a
colorless liquid.
FT-IR (KBr) 3062, 1758, 1708 cmK1
.
4.1.6. (4S,8aS)-8a-Phenyl-4-phenyltetrahydro-pyr-
rolo[2,1-c][1,4]oxazine-1,6-dione 12c. [a]2D0ZK25.6 (c
1.2, CHCl3); H NMR (300 MHz, CDCl3) d 7.35–7.20 (m,
1
10H), 5.25 (dd, JZ12.5, 6.0 Hz, 1H), 4.35 (dd, JZ12.1,
6.0 Hz, 1H), 4.25 (d, JZ12.4 Hz, 1H), 3.25 (m, 1H), 2.60
(m, 1H), 2.45–2.20 (m, 2H); EI-MS m/z 307 (MC), 263,
249, 221, 193, 104. HRMS Calcd for C19H17NO3 (MC)