J. Piro´ et al. / Tetrahedron: Asymmetry 13 (2002) 995–1004
1003
ester (17 mg, 0.104 mmol) compound 14 was obtained,
4.25. (3R,4R,5R)-5-Benzyloxy-N-[(1S)-1-(tert-butoxy-
after chromatography, as an oil (39 mg, 76%). [h]D=−
136 (c=1.0, CHCl3). IR (NaCl) 3325 (NH), 1722 (CO),
1663 (CO) cm−1. 1H NMR 0.73 (d, J=6 Hz, 3H,
CH(CH3)2), 0.82 (d, J=6 Hz, 3H, CH(CH3)%2), 1.44 (s,
9H, C(CH3)3), 1.50–1.70 (m, 3H, CH(CH3)2, CH2), 2.20
(br s, 1H, NH), 3.10–3.20 (m, 2H, H-3, H-4), 3.42 (dd,
J=15 and 3 Hz, 1H, H-6), 3.52 (dd, J=15 and 3 Hz,
1H, H-6%), 3.72 (s, 3H, CO2CH3), 4.23 (br s, 1H, H-5),
4.61 (s, 2H, CH2Ph), 4.64 (s, 1H, NCHPh), 5.12 (dd,
J=9 and 5 Hz, 1H, NCH), 7.20–7.40 (m, 11H, CH2Ph,
NCHPh, Ns-H4), 7.58 (td, J=8 and 1 Hz, 1H, Ns-H5),
7.77 (dd, J=8 and 1 Hz, 1H, Ns-H6), 7.98 (dd, J=8
and 1 Hz, 1H, Ns-H3); 13C NMR 21.5 (CH(CH3)2),
22.7 (CH(CH3)2%), 24.6 (CH(CH3)2), 28.0 (C(CH3)3),
38.0 (CH2), 42.9 (C6), 52.5 (CO2CH3), 54.6 (NCH),
58.8 (C4), 60.8 (NCHPh), 64.8 (C3), 71.6 (CH2Ph),
77.9 (C5), 82.1 (C(CH3)3), 124.9 (Ns-C3), 127.0–138.0
(NCHPh, CH2Ph, Ns-C1, Ns-C4, Ns-C5, Ns-C6), 148.1
(Ns-C2), 170.0 (CO), 170.7 (CO), 173.2 (CO). MS m/z
(%) 738 (M+, 1), 624 (7), 313 (63), 186 (20), 91 (100).
Anal. calcd for C37H46N4O10S: C, 60.15; H, 6.28; N,
7.58; S, 4.34. Found: C, 60.09; H, 6.38; N, 7.35; S,
4.78%.
carbonyl)-3-methylbutyl]-3,4-bis(o-nitrobenzensulfon-
amido)piperidin-2-one 16
Operating as for the preparation of compound 9, from
aziridine 1a (50 mg, 0.087 mmol) in THF:H2O (10:1 0.5
mL), KCN (7 mg, 0.096 mmol) and Bu4NCN (2 mg,
0.008 mmol) compound 16 (20 mg, 30%) was obtained,
after chromatography, as an oil,. [h]D=+6 (c=1.0,
CHCl3). IR (NaCl) 3335 (NH), 1730 (CO), 1678 (CO)
1
cm−1. H NMR 0.76 (br s, 6H, CH(CH3)2), 1.34 (s, 9H,
C(CH3)3), 1.40–1.60 (m, 3H, CH(CH3)2, CH2), 3.30
(dd, J=14 and 3 Hz, 1H, H-6), 3.54 (dd, J=14 and 4
Hz, 1H, H-6%), 3.86 (dd, J=10 and 5 Hz, 1H, H-4),
4.00–4.10 (m, 2H, H-3, H-5), 4.64 (s, 2H, CH2Ph), 4.83
(dd, J=9 and 5 Hz, 1H, NCH), 6.30 (br s, 1H, NH),
6.46 (d, J=6 Hz, 1H, NH), 7.20–7.40 (m, 5H, CH2Ph),
7.60–7.70 (m, 4H, Ns), 7.80–7.90 (m, 2H, Ns), 7.98 (dd,
J=6 and 3 Hz, 1H, Ns), 8.1 (m, 1H, Ns); 13C NMR
21.3 (CH(CH3)2), 23.0 (CH(CH3)2%), 24.3 (CH(CH3)2),
28.0 (C(CH3)3), 37.2 (CH2), 43.9 (C6), 55.0 (NCH),
57.2 (C4), 59.6 (C3), 72.0 (CH2Ph), 77.0 (C5), 82.2
(C(CH3)3), 125.6–134.5 (Ph, Ns), 136.9 (Ph-C1), 147.5
(Ns-C2, Ns-C2%), 166.5 (CO), 170.1 (CO). MS m/z (%):
776 (M+, 1), 675 (2), 223 (32), 186 (45), 91 (100).
4.24. (3R,4R,5R)-5-Benzyloxy-3-(ethoxycarbonyl)-
methylamino-N-[(1S)-1-(tert-butoxycarbonyl)-3-methyl-
butyl]-4-(o-nitrobenzensulfonamido)piperidin-2-one 15
4.26. (3R,4R,5R)-5-Benzyloxy-3-methyl-N-[(1S)-1-(tert-
butoxycarbonyl)-3-methylbutyl]-4-(p-toluensulfon-
amido)piperidin-2-one 19
Ammonia was bubbled through a suspension of Gly-
OEt.HCl (20 mg, 0.14 mmol) in dry THF (0.5 mL) for
15 min. The resulting suspension was filtered and the
clear filtrate was added to a solution of aziridine 1a (40
mg, 0.069 mmol) in dry THF (0.5 mL). Operating as
above, compound 15 was obtained, after chromatogra-
phy, as an oil (35 mg, 76%). [h]D=−40 (c=1.0, CHCl3).
To a suspension of CuI (111 mg, 0.58 mmol) in dry
Et2O (2 mL) cooled at 0°C, MeLi (1.6 M in Et2O, 0.725
mL, 1.16 mmol) was added. The mixture was stirred at
0°C for 15 min after which, a yellow solid had
appeared. A solution of aziridine 1b (158 mg, 0.29
mmol) in dry Et2O (4 mL) was then added dropwise.
The mixture was stirred at 0°C for 2 h, and the reaction
was quenched by adding 1 M aqueous NH4Cl. The
layers were separated, and the aqueous layer was
extracted with CH2Cl2. The combined organic extracts
were dried and evaporated. The resulting residue was
chromatographed (AcOEt:hexane=1:4) to yield com-
pound 19 as an oil (25 mg, 15%). [h]D=+3 (c=1.0,
CHCl3). IR (NaCl) 3262 (NH), 1729 (CO), 1646 (CO)
1
IR (NaCl) 3337 (NH), 1722 (CO), 1662 (CO) cm−1. H
NMR 0.78 (d, J=6 Hz, 3H, CH(CH3)2), 0.85 (d, J=6
Hz, 3H, CH(CH3)2%), 1.27 (t, J=7 Hz, 3H, CH2CH3),
1.43 (s, 9H, C(CH3)3), 1.45–1.65 (m, 3H, CH(CH3)2,
CH2), 2.10 (br s, 1H, NH), 3.17 (d, J=11 Hz, 1H, H-3),
3.23 (dd, J=11 and 4 Hz, 1H, H-4), 3.36 (dd, J=14
and 3 Hz, 1H, H-6), 3.37 (d, J=18 Hz, 1H, NHCH2),
3.50 (dd, J=14 and 3 Hz, 1H, H-6%), 3.53 (d, J=18 Hz,
1
cm−1. H NMR 0.88 (d, J=7 Hz, 6H, CH(CH3)2), 1.23
1H, NHCH%), 4.11 (dd, J=7 and 3 Hz, H-5), 4.18 (q,
2
(d, J=7 Hz, 3H, CH3), 1.43 (s, 9H, C(CH3)3), 1.50–1.70
(m, 3H, CH(CH3)2, CH2), 2.33 (quintuplet, J=7 Hz,
1H, H-3), 2.38 (s, 3H, CH3Ph), 3.10 (dd, J=13 and 6
Hz, 1H, H-6), 3.40–3.50 (m, 2H, H-4, H-6%), 3.72 (q,
J=6 Hz, 1H, H-5), 4.44 (s, 2H, CH2Ph), 4.89 (d, J=8
Hz, 1H, NH), 5.16 (dd, J=10 and 5 Hz, 1H, NCH),
7.20–7.40 (m, 5H, Ph), 7.22 (d, J=8 Hz, 2H, Ts-H3),
7.74 (d, J=8 Hz, 2H, Ts-H2); 13C NMR 16.2 (CH3),
21.3 (CH(CH3)2), 21.6 (CH3Ph), 23.2 (CH(CH3)%2), 24.9
(CH(CH3)2), 28.1 (C(CH3)3), 37.2 (CH2), 42.9 (C3),
44.4 (C6), 54.4 (NCH), 58.3 (C4), 71.7 (CH2Ph), 75.8
(C5), 82.0 (C(CH3)3), 127.0–128.4 (Ph-C2, Ph-C3, Ph-
C4, Ts-C3), 129.5 (Ts-C2), 137.4 and 138.0 (Ts-C4 and
Ph-C1), 143.4 (Ts-C1), 171.0 (CO), 171.2 (CO). MS m/z
(%) 559 (M+, 1), 457 (36), 91 (100), 57 (15). Anal. calcd
for C30H42N2O6S: C, 64.49; H, 7.58; N, 5.01; S, 5.74.
Found: C, 64.36; H, 7.63; N, 5.35; S, 5.78%.
J=7 Hz, 2H, CH2CH3), 4.56 (s, 2H, CH2Ph), 5.09 (dd,
J=9 and 5 Hz, 1H, NCH), 6.70 (br s, 1H, NH),
7.20–7.40 (m, 5H, CH2Ph), 7.45 (td, J=8 and 1 Hz,
1H, Ns-H4), 7.60 (td, J=8 and 1 Hz, 1H, Ns-H5), 7.78
(dd, J=8 and 1 Hz, 1H, Ns-H6), 8.01 (dd, J=8 and 1
Hz, 1H, Ns-H3); 13C NMR 14.1 (CH2CH3), 21.4
(CH(CH3)2), 22.8 (CH(CH3)2%), 24.5 (CH(CH3)2), 28.0
(C(CH3)3), 37.8 (CH2), 43.4 (C6), 49.3 (NHCH2), 54.5
(NCH), 60.3 (C3, C4), 61.0 (CH2CH3), 71.6 (CH2Ph),
77.6 (C5), 82.1 (C(CH3)3), 125.1 (Ns-C3), 127.7 (Ph-
C2), 127.8 (Ph-C4), 128.3 (Ph-C3), 131.2-133.4 (Ns-C1,
Ns-C4, Ns-C5, Ns-C6), 137.4 (Ph-C1), 147.8 (Ns-C2),
169.8 (CO), 170.7 (CO), 171.8 (CO). MS m/z (%) 678
(M++2, 1), 575 (1), 547 (5), 310 (15), 91 (100), 57 (36).
Anal. calcd for C32H44N4O10S: C, 56.79; H, 6.55; N,
8.28; S, 4.74. Found: C, 57.06; H, 6.76; N, 7.78; S,
5.01%.