11584
A. Viso et al. / Tetrahedron 64 (2008) 11580–11588
2.41 (d, 1H, J¼10.4 Hz), 2.84 (ap d, 1H, J¼12.1 Hz), 3.24 (dd, 1H,
J¼7.0, 5.1 Hz), 3.53 (dd, 1H, J¼10.3, 2.9 Hz), 3.73 (dd, 1H, J¼9.8,
4.7 Hz), 3.79 (d, 1H, J¼14.5 Hz), 3.84 (dd, 1H, J¼9.8, 7.8 Hz), 4.78 (s,
1H), 4.83 (s, 1H), 5.46 (d, 1H, J¼14.1 Hz), 7.28 (m, 5H). 13C NMR
3.59 (dd, 1H, J¼10.5, 3.9 Hz), 3.60 (ap d, 1H, J¼15.2 Hz), 4.03 (d, 1H,
J¼15.2 Hz), 5.19 (s, 1H), 5.29 (d, 1H, J¼15.2 Hz), 5.35 (s, 1H), 7.21–
7.33 (m, 8H), 7.43 (ap d, 2H). IR (film): 3353, 2949, 2925, 2855,1653,
1462, 1449, 1254, 1106, 835, 776 cmꢁ1. MS (ES): 1007 [2MþNa]þ,
515 [MþNa]þ, 493 [Mþ1]þ (100%).
(CDCl3, 75 MHz)
d
ꢁ5.4, ꢁ5.3, 18.2, 19.2, 19.5, 21.8, 25.4, 25.9 (3C),
41.9, 48.7, 51.3, 56.8, 57.2, 63.7, 113.3, 127.6, 128.5 (2C), 128.8 (2C),
137.6, 142.5, 170.8. IR (film): 3372, 2955, 2929, 2854, 1646, 1471,
1461, 1453, 1387, 1375, 1361, 1257, 1101, 837, 776, 696 cmꢁ1. MS (ES):
453 [MþNa]þ, 431 [Mþ1]þ (100%). Anal. Calcd for C25H42N2O2Si: C,
69.72; H, 9.83; N, 6.50. Found: C, 69.55; H, 9.41; N, 6.79.
3.4.4. (þ)-(3R,5R,6S)-1-Benzyl-3-[2-(benzyloxymethyl)prop-2-en-
1-yl]-6-(tert-butyldiphenylsilyloxymethyl)-5-(iso-propyl)piperazin-
2-one, 7f
From 5b (90 mg, 0.181 mmol), benzyl 2-(bromomethyl)prop-2-
en-1-yl ether7 (23
m
L, 0.235 mmol), Zn (16 mg, 0.235 mmol), and
3.4.2. (þ)-(3R,5R,6S)-1-Benzyl-6-(tert-butyldiphenylsilyloxy-
methyl)-5-(iso-propyl)-3-(2-methylprop-2-en-1-yl)piperazin-2-
one, 7d
TMSCl (4 mg, 5 mL, 0.04 mmol) in DMF, following procedure B and
after 16 h adding the same amounts of reagents (46 h total), 7f
(80 mg, 0.121 mmol, 70%) was obtained after chromatography (5–
From 5b (91 mg, 0.183 mmol), 3-bromo-2-methylpropene (97%,
50% EtOAc–hexane) as a colorless oil. Data for 7f: Rf 0.22 (20%
20
24
mL, 0.245 mmol), Zn (16 mg, 0.238 mmol), and TMSCl (4 mg,
AcOEt–hexane). [
a]
þ49.1 (c 1.40). 1H NMR (CDCl3, 300 MHz)
D
5
m
L, 0.04 mmol) in DMF, following procedure B (16 h), 7d (85 mg,
d
0.33 (d, 3H, J¼6.4 Hz), 0.74 (d, 3H, J¼6.8 Hz), 1.03 (s, 9H), 1.51 (m,
0.153 mmol, 84%) was obtained after chromatography (10–20%
1H), 1.73 (br s, 1H), 2.14 (dd, 1H, J¼13.9, 10.0 Hz), 2.50 (d, 1H,
J¼10.5 Hz), 2.87 (d, 1H, J¼13.7 Hz), 3.24 (dd, 1H, J¼8.1, 4.6 Hz), 3.47
(d, 1H, J¼14.4 Hz), 3.55 (m, 1H), 3.75 (dd, 1H, J¼4.5, 10.0 Hz), 3.91
(m, 3H), 4.48 (ap q, 2H, J¼12.0 Hz), 4.99 (s, 1H), 5.16 (s, 1H), 5.33 (d,
1H, J¼14.4 Hz), 7.10 (m, 2H), 7.27 (m, 8H), 7.41 (m, 6H), 7.64 (m, 4H).
EtOAc–hexane) as a colorless oil. Data for 7d: Rf 0.32 (20% AcOEt–
20
hexane). [
a
]
þ57.1 (c 1.80). 1H NMR (CDCl3, 300 MHz), COSY
d 0.36
D
(3H, d, J¼6.6 Hz, CH3), 0.83 (3H, d, J¼6.6 Hz, CH3), 1.03 (9H, s, 3CH3
tBu), 1.58 (1H, m, CH iPr), 1.67 (1H, br s, NH), 1.71 (3H, s, CH3 allyl),
2.10 (1H, dd, J¼13.4, 10.5 Hz, CH2 allyl), 2.53 (1H, d, J¼10.5 Hz, H-5),
2.79 (1H, d, J¼12.5 Hz, CH2 allyl), 3.27 (1H, dd, J¼8.2, 4.5 Hz, H-6),
3.49 (2H, dm, J¼14.4 Hz, NBn and H-3), 3.77 (1H, dd, J¼4.5, 9.9 Hz,
CH2O), 3.93 (1H, dd, J¼9.9, 8.2 Hz, CH2O), 4.74 (1H, s, CH2]C), 4.81
(1H, s, CH2]C), 5.35 (1H, d, J¼14.2 Hz, NBn), 7.11 (2H, m, Ar–H),
7.25 (3H, m, Ar–H), 7.41 (6H, m, Ar–H), 7.64 (4H, m, Ar–H). 13C NMR
13C NMR (CDCl3, 75 MHz)
d 19.1,19.2,19.5, 25.3, 26.8 (3C), 38.0, 48.5,
52.0, 56.5, 57.1, 63.9, 72.3, 72.7, 114.5, 127.5, 127.6, 127.8 (5C), 128.3
(2C), 128.4 (2C), 128.7 (2C), 129.8 (2C), 129.9, 133.2 (2C), 135.5 (4C),
137.5, 138.2, 142.8, 170.3. IR (film): 3555, 3070, 2960, 2931, 2858,
1643, 1471, 1453, 1428, 1389, 1362, 1265, 1240, 1112, 823, 739,
701 cmꢁ1. MS (ES): 683 [MþNa]þ, 661 [MþH]þ.
(CDCl3, 75 MHz)
d 19.1, 19.2, 19.6, 21.8, 25.4 (3C), 26.8, 41.8, 48.6,
51.2, 56.4, 57.2, 63.8, 113.2, 127.5, 127.8 (4C), 128.4 (2C), 128.7 (2C),
129.8, 129.9, 133.1, 133.2, 135.5 (4C), 137.5, 142.4, 170.6. 2D-NOESY
show cross-points between: CH3 (0.83)/CH3 (0.36), CH3 (0.83)/iPr,
CH3 (0.83)/H-5, CH3 (0.83)/H-3. IR (film): 3400, 3052, 2960, 1646,
1428, 1264, 1113, 896, 823, 740, 701 cmꢁ1. MS (ES): 555 [MþH]þ,
577 [MþNa]þ, 1131 [2MþNa]þ. Anal. Calcd for C35H46N2O2Si$HCl: C,
71.09; H, 8.01; N, 4.74; Cl, 6.00. Found: C, 70.84; H, 8.25; N, 4.96.
3.4.5. Ethyl (þ)-2-((2R,5S,6R)-4-benzyl-5-(tert-butyldimethyl
silyloxymethyl)-6-(iso-propyl)-3-oxopiperazin-2-yl)methyl-
acrylate, 7b and ethyl 2-((2R,5S,6R)-4-benzyl-5-(tert-
butyldimethylsilyloxymethyl)-1-(2-ethoxycarbonylallyl)-6-(iso-
propyl)-3-oxopiperazin-2-yl)methylacrylate, 9a
From 5a (20 mg, 0.054 mmol), ethyl 2-(bromomethyl)acrylate
(95%, 12 mL, 0.084 mmol), Zn (7 mg, 0.107 mmol), and CeCl3$7H2O
(2 mg, 0.005 mmol) following general procedure A (22 h), 7b
(21 mg, 0.043 mmol, 80%) was obtained after chromatography (5–
10% EtOAc–hexane) as a colorless oil. Alternatively, from 5a (13 mg,
3.4.3. (þ)-(3R,5R,6S)-1-Benzyl-6-(tert-butyldimethylsilyloxy-
methyl)-5-(iso-propyl)-3-(2-phenylprop-2-en-1-yl)piperazin-2-
one, 7e and (3S,5R,6S)-1-benzyl-6-(tert-butyldimethyl-
silyloxymethyl)-5-(iso-propyl)-3-(2-phenylprop-2-en-1-
yl)piperazin-2-one, 8e
0.035 mmol), ethyl 2-(bromomethyl)acrylate (95%, 14 mg, 10
0.073 mmol), Zn (5 mg, 0.070 mmol), and TMSCl (2 mg, 2
m
m
L,
L,
0.017 mmol) in DMF (procedure B) adding an equal amount of re-
agents after 16 h and 40 h (88 h total) a mixture (87:13) of 7b and
9a was obtained. After chromatography (2–5% EtOAc–CH2Cl2), 7b
(11 mg, 0.023 mmol, 64%) and 9a (2 mg, 0.003 mmol, 10%) were
From 5a (22 mg, 0.059 mmol), 3-bromo-2-phenylpropene10
(15 mg, 0.076 mmol), Zn (4 mg, 0.076 mmol), and TMSCl (2 mg,
2 mL, 0.012 mmol) in DMF, following procedure B (18 h), a mixture
(79:21) of 7e and 8e was obtained. After chromatography (5–10%
EtOAc–hexane) 7d (18 mg, 0.037 mmol, 63%) and 8e (4 mg,
0.008 mmol, 14%) were isolated as colorless oils. Data for 7e: Rf 0.34
isolated as colorless oils. Data for 7b: Rf 0.26 (20% EtOAc–hexane).
20
[a
]
þ86.6 (c 0.56). 1H NMR (CDCl3, 400 MHz)
d 0.03 (s, 6H), 0.32
D
(d, 3H, J¼6.4 Hz), 0.79 (d, 3H, J¼6.8 Hz), 0.86 (s, 9H), 1.28 (t, 3H,
J¼7.1 Hz), 1.47 (m, 1H), 1.67 (br s, 1H), 2.36 (d, 1H, J¼10.4 Hz), 2.55
(dd, 1H, J¼13.9, 7.5 Hz), 3.10 (dd, 1H, J¼13.8, 3.6 Hz), 3.20 (dd, 1H,
J¼6.6, 4.9 Hz), 3.67 (dd, 1H, J¼7.4, 4.3 Hz), 3.70 (dd, 1H, J¼9.9,
4.6 Hz), 3.79 (d, 1H, J¼14.5 Hz), 3.81 (dd, 1H, J¼9.9, 7.5 Hz), 4.19 (qd,
2H, J¼7.1, 2.2 Hz), 5.45 (d, 1H, J¼14.5 Hz), 5.63 (s, 1H), 6.18 (s, 1H),
20
(20% EtOAc–hexane). [
d
a]
þ37.0 (c 0.83). 1H NMR (CDCl3, 400 MHz)
D
0.07 (s, 6H), 0.28 (d, 3H, J¼6.6 Hz), 0.46 (d, 3H, J¼6.6 Hz), 0.89 (s,
9H), 1.41–1.50 (m, 1H), 1.62 (br s, 1H), 2.36 (ap d, 1H, J¼10.2 Hz),
2.48 (dd, 1H, J¼14.1, 10.9 Hz), 3.20 (dd, 1H, J¼7.4, 4.7 Hz), 3.40 (dd,
1H, J¼10.9, 2.7 Hz), 3.61 (ap d, 1H, J¼14.1 Hz), 3.75 (dd, 1H, J¼9.8,
4.7 Hz), 3.80 (d, 1H, J¼14.4 Hz), 3.89 (dd, 1H, J¼9.8, 7.8 Hz), 5.19 (s,
1H), 5.49 (s, 1H), 5.47 (d, 1H, J¼14.4 Hz), 7.25–7.37 (m, 8H), 7.48 (dd,
7.22–7.32 (m, 5H). 13C NMR (CDCl3, 75 MHz)
d
ꢁ5.4 (2C), 14.2, 18.2,
19.1,19.5, 25.3, 25.9 (3C), 35.4, 48.6, 53.4, 57.0, 57.3, 60.7, 63.9, 126.8,
127.6,128.5 (2C),128.8 (2C),137.6,138.1,167.4,169.9. IR (film): 3355,
2961, 2929, 2853, 1716, 1647, 1450, 1387, 1248, 1176, 1096, 837, 774,
700 cmꢁ1. MS (ES): 999 [2MþNa]þ, 511 [MþNa]þ, 489 [Mþ1]þ
(100%). Anal. Calcd for C27H44N2O4Si: C, 66.35; H, 9.07; N, 5.73.
Found: C, 66.02; H, 9.30; N, 5.84. Partial data for 9a: Rf 0.26 (5%
2H, J¼8.0, 1.4 Hz). 13C NMR (CDCl3, 75 MHz)
ꢁ5.4, ꢁ5.3, 18.2, 18.5,
d
19.4, 25.0, 25.9 (3C), 39.8, 48.5, 51.5, 56.8, 57.3, 63.7, 115.3, 126.5
(2C), 127.5, 127.7, 128.4 (2C), 128.5 (2C), 128.7 (2C), 137.6, 139.7,
145.6, 170.4. IR (film): 3473, 2949, 2925, 2854, 1647, 1470, 1438,
1251, 1236, 1092, 834, 776 cmꢁ1. MS (ES): 1007 [2MþNa]þ, 515
[MþNa]þ, 493 [Mþ1]þ (100%). Anal. Calcd for C30H44N2O2Si: C,
73.12; H, 9.00; N, 5.68. Found: C, 72.95; H, 9.34; N, 5.41. Partial data
for 8e: Rf 0.20 (20% EtOAc–hexane). 1H NMR (CDCl3, 400 MHz)
EtOAc–CH2Cl2). 1H NMR (CDCl3, 300 MHz)
d
ꢁ0.02 (s, 3H, Me), 0.01
(s, 3H), 0.26 (d, 3H, J¼6.6 Hz), 0.79 (d, 3H, J¼6.8 Hz), 0.85 (s, 9H),
1.26 (t, 3H, J¼7.1 Hz), 1.29 (t, 3H, J¼7.2 Hz), 2.52 (d, 1H, J¼10.5 Hz),
2.85 (m, 2H), 3.45 (m, 1H), 3.50 (m, 2H), 3.64 (d,1H, J¼13.2 Hz), 3.65
(m,1H), 3.85 (d,1H, J¼13.7 Hz), 4.16 (m, 5H), 5.04 (d, 1H, J¼14.4 Hz),
5.63 (s, 1H), 5.75 (s, 1H), 6.16 (d, 1H, J¼1.7 Hz), 6.22 (s, 1H), 7.27 (m,
d
ꢁ0.09 (s, 3H), ꢁ0.08 (s, 3H), 0.69 (d, 3H, J¼6.6 Hz), 0.72 (d, 3H,
J¼6.6 Hz), 0.77 (s, 9H), 1.53 (m, 2H), 2.56 (m, 2H), 3.13 (dt, 1H, J¼6.5,
3.3 Hz), 3.23 (dd, 1H, J¼10.4, 2.7 Hz), 3.35 (dd, 1H, J¼10.7, 3.3 Hz),