S. Laabs et al. / Tetrahedron 58 32002) 1317±1334
1331
[a]D 251.94 c1.8, CHCl3). 1H NMR 4500 MHz):
7.21 4m, 5H, Ar-H) ppm. 13C NMR 468 MHz): d25.5
23
d20.01 4s, 6H, 70-H); 0.82 4s, 9H, 90-H); 1.17 4m, 1H,
4C-70); 17.1 4C-80); 22.7 4C-40); 25.5 4C-90); 25.94C-3 );
0
1
1
2
0
0
4 -H); 1.30 4m, 1H, 3 -H); 1.694m, 1H, 4 0-H); 1.77 4m,
35.2 4C-4); 46.2 4C-5); 46.0 4C-50); 49.5 4C-3); 58.4
4C-20); 62.1 4C-2); 63.3 4C-60); 126.7 4C-10); 127.7 4C-9
and C-11); 128.1 4C-8 and C-12); 139.3 4C-7); 169.7
4C-6) ppm. IR 4®lm): nmax3293 4w, br, NH), 2955 s,
2928 4s, CH), 1639 4s, CCvO), 1103 s, br, 837 4s, br,
OTBS). MS 480 eV, 1008C): m/z388 4M1), 373
4M2CH3), 346 4M2C2H4N), 331 4M2C4H9), 284, 227,
214, 200, 192, 186 4M2C4H7N±CH2OTBS), 146 4100,
2
1
0
1H, 3 -H); 2.24 4ddt, 1H, J7.5, 12.0, 12.0 Hz, 4 -H); 2.32
2
1
0
4m, 1H, 4 -H); 2.57 4dt, 1H, J7.6, 10 Hz, 5 -H); 3.21 4ddd,
2
0
1H, J4.9, 8.7, 10 Hz, 5 -H); 3.394dd, 1H, J7.4, 10 Hz,
1
1
0
6 -H); 3.51 4ddd, 1H, J6.6, 11.4, 11.4 Hz, 5 -H); 3.70 4dd,
1H, J3.4, 10 Hz, 62-H); 3.80 4m, 3H, 3-H, 52-H and 20-H);
4.73 4d, 1H, J9.5 Hz, 2-H); 5.91 4s, 2H, 13-H); 6.72 4m,
3H, 8-H, 11-H and 12-H) ppm. 13C NMR 468 MHz):
d25.4 4C-70); 18.1 4C-80); 23.0 4C-40); 25.8 4C-90); 26.4
4C-30); 32.3 4C-4); 45.7 4C-5); 46.8 4C-50); 47.7 4C-3); 59.8
4C-20); 61.3 4C-2); 62.0 4C-60); 101.3 4C-13); 108.2 4C-8);
108.3 4C-11); 122.3 4C-12); 129.0 4C-7); 147.5 4C-10);
147.94C-9); 165.4 4C-6) ppm. IR 4®lm): nmax3426 4w,
br, NH), 2955 s, 2928 4s, CH), 1649 4s, CCvO), 1254 4s,
Ar-O), 1098 4s, OTBS), 1031 4s, C-O), 836 4s, OTBS). MS
4EI, 80 eV, 958C): m/z432 4M1), 417 4M2CH3), 390
4M2C2H4N), 375 4M2C4H9), 227, 190 4100, Ar-C4H7N),
131, 84, 70. HRMS 4EI, 80 eV, 1108C) [C23H36N2O4Si]
Calcd: 432.24442. Found: 432.24518.
Ph-C4H7N1),
70.
HRMS
4EI,
80 eV,
[C22H36N2O2Si] Calcd: 388.254607. Found: 388.25833.
1008C)
5.6.4. 03R,4R,9S)-003,4-Methylenedioxy)-phenyl)-octa-
hydro-dipyrrolo[1,2-a;10,20-d]-pyrazine-2,8-dione 020).
Reaction with 0.6 g 41.61 mmol) a-azidoamide 15a follow-
ing the standard procedure. Before drying with MgSO4, the
clear yellow solution was stirred for another 12 h to
complete the formation of the pyrazinedione 20. Puri®cation
by column chromatography on silica gel 4n-hexane/EtOAc
1:1, Rf0.2). Yield: 0.31 g 41.0 mmol, 62%) of 20 as a pale
yellow oil, which crystallized from Et2O/hexanes, mp 208±
23
5.6.2. 02R,3R)-3-04-Methoxyphenyl)-proline 02S-0t-butyl-
dimethylsiloxymethyl)-pyrrolidinyl) amide 019b). Reac-
tion with 0.12 g 40.27 mmol) a-azidoamide 16b following
the standard procedure. Puri®cation by column chromato-
graphy on silica gel 4MeOH/EtOAc 1:10, Rf,0.05,
Rf0.1 in MeOH/EtOAc 41:10)11% Et3N). Yield: 0.07 g
2098C. [a]D 230.7 4c1.1, CHCl3). 1H NMR 4500 MHz,
CD2Cl2): d1.68 4m, 3H, 101-H and 111-H); 1.87 4m, 1H,
112-H); 2.12 4ddd, 1H, J3.2, 9.6, 12.8 Hz, 51-H); 2.22 4m,
1H, 102-H); 2.36 4m, 1H, 52-H); 3.05 4ddd, 1H, J3.5, 9.6,
12.1 Hz, 121-H); 3.34 4ddd, 1H, J3.9, 12.6, 11.3 Hz,
61-H); 3.37 4dd, br, J5.9, 10.6 Hz, 1H, 9-H); 3.66 4ddd,
1H, J8.4, 8.4, 12.1 Hz, 122-H); 3.70 4dd, 1H, J5.4,
7.6 Hz, 4-H); 4.22 4dd, 1H, J1.7, 5.4 Hz, 3-H); 4.28
4ddd, 1H, J7.4, 9.6, 12.6 Hz, 62-H); 5.92 4s, 2H, 70-H);
6.48 4dd, 1H, J1.7, 8.1 Hz, 60-H); 6.54 4d, 1H,
J1.7 Hz, 20-H); 6.71 4d, 1H, J8.1 Hz, 50-H) ppm. NOE
analysis: 2.12)2.36 423.5); 3.34 41.0); 3.70 42.0); 4.28
44.0); 6.48, 6.54 47.0); 2.36)2.12 425.5); 3.34 48.0); 3.70
410.0); 4.22 44.0); 3.34)2.36 45.0); 4.28 426.0); 3.70)2.36
42.0); 4.22 410.5); 6.48, 6.54 45); 4.22)3.70 412.0); 4.28
44.0); 4.28)2.12 44.0); 2.36 41.0); 3.34 430); 6.48, 6.54
43.0); 6.48, 6.54)2.12 42.5); 3.70 45.0); 4.28 45.0). 13C
NMR 468 MHz, CD2Cl2): d21.3 4C-11); 29.0 4C-10);
29.9 4C-5); 43.8 4C-4); 44.4 4C-6); 45.4 4C-12); 60.1
4C-9); 66.6 4C-3); 101.0 4C-70); 108.2 4C-50); 108.3
4C-20); 120.4 4C-60); 133.3 4C-10); 146.7 4C-40); 147.7 4C-
30); 162.2 4C-2); 165.5 4C-8) ppm. IR 4®lm): nmax2991 m,
2961 4m, CH), 1665 4s, CCvO), 1648 4s, CCvO), 1237 4s,
Ar-O), 1034 4s, C±O). MS 4EI, 80 eV, 608C): m/z314
4M1, 100%), 297 4M2OH), 244 4M2C4H8N), 217
4M2C5H7NO), 127, 189, 175, 166, 162, 138, 131, 122
4Ar-H1), 103, 70. HRMS 4EI, 80 eV, 1258C)
[C17H18N2O4] Calcd: 314.126657. Found: 314.12378.
23
40.17 mmol, 62%) of a clear oil. [a]D 282 4c1.4,
1
CHCl3). H NMR 4250 MHz) d20.04 4s, 6H, 70-H);
1
0
3 -H); 1.63 4m, 2H, 3 -H and 4 -H); 1.94 4m, 1H, 4 -H);
0.77 4s, 9H, 90-H); 1.04 4m, 1H, 4 -H); 1.18 4m, 1H,
1
2
2
1
0
2.11 4m, 1H, 4 -H); 2.74 4m, 1H, 5 -H); 2.91 4m, 1H,
0
0
2
1
0
2
1
0
0
5 -H); 3.13 4m, 2H, NH and 6 -H); 3.35±3.67 4m, 5H,
20-H, 3-H, 51-H, 52-H, 62-H); 3.72 4s, 3H, 13-H); 4.16 4d,
1H, J8.8 Hz, 2-H); 4.76 4s, br, 1H, NH); 6.74 4d, 2H,
J7.4 Hz, 8-H and 12-H); 7.10 4d, 2H, J7.4 Hz, 9-H
13
and 11-H) ppm. C NMR 468 MHz): d25.5 4C-70);
18.1 4C-80); 23.1 4C-40); 25.8 4C-90); 26.3 4C-30); 35.3
4C-4); 46.04 4C-5); 47.0 4C-50); 48.94C-3); 55.3 4C-13);
58.94C-2 ); 62.4 4C-2); 63.3 4C-60); 113.5 4C-9, C-11);
129.4 4C-8, C-12); 131.1 4C-7); 158.7 4C-10); 169.6
4C-6) ppm. IR 4®lm): nmax3291 4w, br, NH), 2952 s,
1644 4s, br, CCvO), 12494s, br, Ar-O), 1101 4s, br,
OTBS), 1035 4s, C±O), 834 4s, OTBS). MS 4EI, 80 eV,
1308C): m/z418 4M1), 403 4M2CH3), 3894M 2CHO),
376 4M2C2H4N), 361 4M2C4H9), 218, 176 4100%,
Ar-C4H7N), 134, 106, 70. HRMS 4EI, 80 eV, 1008C
[C22H38N2O3Si] Calcd: 418.265172. Found: 418.26172.
5.6.3. 02R,3R)-3-0Phenyl)-proline-02S-0t-butyl-dimethyl-
siloxymethyl)-pyrrolidinyl) amide 019c). Reaction with
0.53 g 41.28 mmol) a-azidoamide 16c following the
standard procedure. Puri®cation by column chromatography
on silica gel 4MeOH/EtOAc 1:10, Rf,0.05, 0.1 in MeOH/
EtOAc 41:10)11% Et3N). Yield: 0.35 g 40.9mmol, 71%) of
5.6.5. N-t-Butyloxycarbonyl-3R-003,4-methylenedioxy)-
02S-0hydroxymethyl)-pyrrolidinyl)
phenyl)-R-proline
amide 022). Acetyl chloride 41 mL) was cleaved with dry
MeOH 415 mL) at 08C to generate methanolic HCl. The
cooling bath was removed and proline amide 19a 40.14 g,
0.32 mmol) in dry MeOH 415 mL) was added dropwise. The
solution was stirred for about 30 min until the silylether was
found to be completely consumed. Then, aqueous NaHCO3
and a small amount of solid K2CO3 was added to raise the
pH to about 10. BOC2O 476 mg, 0.35 mmol) was injected by
means of a syringe and the mixture was stirred at rt for 12 h.
Work-up started by extraction with CH2Cl2 44£10 mL). The
a clear oil. [a]D 272 4c0.7, CHCl3). 1H NMR
23
4250 MHz) d20.02 4s, 6H, 70-H); 0.82 4s, 9H, 90-H);
1
0.97 4m, 1H, 4 -H); 1.14 4m, 1H, 3 -H); 1.62 4m, 2H,
1
0
0
2
2
0
4 -H); 2.15 4m, 1H, 4 -H); 2.77 4m, 1H, 5 -H); 2.88 4m,
0
3 -H and 4 -H); 1.96 4ddt, 1H, J7.0, 11.5, 11.5 Hz,
1
2
1
0
2
1
0
0
1H, 5 -H); 3.16 4m, 2H, NH and 6 -H); 3.38±3.64 4m, 5H,
20-H, 3-H, 51-H, 52-H, 62-H); 4.13 4d, 1H, J8.83 Hz, 2-H);