V.R. Doddi et al. / Tetrahedron 64 (2008) 9117–9122
9121
(m,1H, minor),4.32(m,1H,bothisomers),3.81(dd,1H, J¼8.0, 5.1 Hz),
(400 MHz, CDCl3):
d
5.83–5.74 (m, 2H), 5.39–5.35 (m, 2H), 5.23 (d,
3.75 (dd, 1H, minor, J¼8.1, 3.1 Hz), 2.46–2.36 (m, 2H, both isomers),
1H, J¼10.2 Hz), 5.13 (d, 1H, J¼3.8 Hz), 5.09 (s, 1H), 4.33 (dd, 1H,
J¼7.8, 7.5 Hz), 4.24–4.21 (m, 1H), 3.66 (dd, 1H, J¼7.6, 7.0 Hz), 2.46–
2.43 (m, 1H), 2.33–2.27 (m, 1H), 1.92 (s, 3H), 1.43 (s, 3H), 1.41 (s, 3H).
2.42 (s, 3H), 1.34 (s, 3H, minor), 1.33 (s, 3H, major), 1.30 (s, 3H,
minor), 1.27 (s, 3H, major). 13C NMR (400 MHz, CDCl3):
d 144.7,
135.3, 134.4, 134.2, 132.2, 131.5, 129.6, 127.9, 119.2, 109.6, 80.8, 79.6,
79.0, 78.6, 35.5, 26.8, 26.6, 21.6. nmax (neat film): 2987, 2933, 1644,
1598, 1368, 1216, 1176, 1096, 815 cmꢀ1. ESMS: m/z 375 [MþNa]þ.
Anal. Calcd for C18H24O5S: C, 61.34; H, 6.86; O, 22.70; S, 9.10. Found:
C, 61.46; H, 6.84.
13C NMR (100 MHz, CDCl3):
d 169.53, 135.44, 133.82, 118.95, 118.25,
109.18, 81.87, 80.36, 49.39, 35.27, 29.65. nmax (neat film): 3283,
3079, 2986, 2931, 2856, 1650, 1553, 1438, 1372, 1244, 1215, 1063,
989, 924, 877, 695 cmꢀ1. ESMS: m/z 306 [MþNa]þ. Anal. Calcd for
C13H21NO3: C, 65.25; H, 8.84; N, 5.85; O, 20.06. Found: C, 65.28; H,
8.82; N, 5.83.
4.1.9. (4R,5R)-4-(1-Azidobut-3-enyl)-2,2-dimethyl-5-vinyl-1,3-
dioxolane (15)
4.1.11. (3R,4R,5S)-5-Acetamidoocta-1,7-diene-3,4-diyl
diacetate (18)
The same experimental procedure was followed for converting
17 (200 mg, 0.835 mmol) to 18 as was followed for the conversion
of 5 to 6. Purification was done by using SiO2 column chromatog-
To a stirred solution of tosylate 14 in dry DMF (4 mL) was added
NaN3 (1.106 g, 17.023 mmol). This heterogeneous mixture was stir-
red at 90 ꢁC for 6 h, and then it was cooled to room temperature
followed by addition of water (5 mL), and extraction with ether
(3ꢂ10 mL). The combined organic layer was washed with brine so-
lution and dried over Na2SO4. Removal of the solvent under reduced
pressure gave a residue, which was purified by column chroma-
tography (hexane/EtOAc, 95:5) to give azide 15 (819 mg, 86% overall
yield for two steps) as a pale yellow liquid. Rf¼0.7 (hexane/EtOAc,
9:1); 1H NMR (400 MHz, CDCl3) of the mixture of diastereomers
raphy (hexane/EtOAc, 2:3). Colorless oil (174 mg, 73% yield over two
28
steps). [
a]
ꢀ30.9 (c 1.1, CH2Cl2). Rf¼0.5 (hexane/EtOAc, 2:3); 1H
D
NMR (400 MHz, CDCl3):
d 5.84–5.64 (m, 3H), 5.39–5.31 (m, 3H),
5.10–5.05 (m, 3H), 4.35–4.30 (m, 1H), 2.12–2.02 (m, 2H), 2.11 (s, 3H),
2.06 (s, 3H), 2.03 (s, 3H). 13C NMR (100 MHz, CDCl3):
d
169.8, 169.4,
132.8, 131.5, 120.2, 118.6, 74.1, 73.2, 48.0, 37.1, 23.3, 20.8, 20.6. nmax
(neat film): 3289, 3078, 2927, 2853, 1746, 1659, 1539, 1434, 1373,
1224, 1026, 938, 737 cmꢀ1. ESMS: m/z 306 [MþNa]þ. Anal. Calcd for
(80:20): d 6.34–6.27 (m, 2H, minor), 5.84–5.71 (m, 2H, both isomers),
5.43–5.09 (m, 5H, both isomers), 4.39 (dd, 1H, major, J¼8.3, 7.6 Hz),
4.12–4.04 (m, 2H, minor), 3.77(dd,1H, minor, J¼7.8, 5.1 Hz), 3.71 (dd,
1H, major, J¼8.2, 2.9 Hz), 3.63–3.58 (m,1H, minor), 3.10–3.05 (m,1H,
major), 2.54 (m,1H, major), 2.42 (m,1H, major), 2.29 (m,1H, minor),
2.19 (m,1H, minor),1.46 (s, 3H, major),1.44 (s, 3H, minor),1.42 (s, 3H,
C14H21NO5: C, 59.35; H, 7.47; N, 4.94; O, 28.24. Found: C, 59.37; H,
7.50; N, 4.96.
4.1.12. (1R,2R,6S)-6-Acetamidocyclohex-3-ene-1,2-diyl
diacetate (19)
major),1.39 (s, 3H, minor).13C NMR (100 MHz, CDCl3):
d 135.6,135.6,
134.8,134.7,133.4,133.3,119.8,119.1,118.5,118.4, 91.7, 82.2, 82.1, 81.7,
79.4, 79.3, 62.8, 59.2, 59.1, 35.3, 27.0, 26.5. nmax (neat film): 3082,
2987, 2934, 2114, 1643, 1376, 1241, 1057, 927, 876, 510 cmꢀ1. ESMS:
m/z 246 [MþNa]þ. Anal. Calcd for C11H17N3O2: C, 59.17; H, 7.67; N,
18.82; O, 14.33. Found: C, 59.38; H, 7.70; N, 18.78.
The same experimental procedure was followed for converting
18 (150 mg, 0.529 mmol) to 19 as was followed for the conversion
of 6 to 8. Purification was done by using SiO2 column chromatog-
28
raphy (hexane/EtOAc, 1:4). Viscous liquid (110 mg, 81% yield). [a]
D
ꢀ45.16 (c 1.55, CH2Cl2). Rf¼0.5 (hexane/EtOAc, 1:4); 1H NMR
(400 MHz, CDCl3):
d 5.81–5.71 (m, 1H, H-1), 5.72 (d, 1H, NH,
4.1.10. Procedure for the reduction of azide 15
J¼8.7 Hz), 5.58–5.55 (m, 2H, H-2, H-3), 5.04 (dd, 1H, H-4, J¼11.0,
7.3 Hz), 4.39–4.30 (m, 1H, H-5), 2.64–2.58 (m, 1H, H-6), 2.07–2.05
(m, 1H, H-60), 2.08 (s, 3H, COCH3), 2.06 (s, 3H, COCH3), 1.94 (s, 3H,
To a stirred solution of azide 15 (1 g, 4.478 mmol) in dry THF
(3 mL) at room temperature, were added triphenylphosphine
(1.408 g, 5.37 mmol) and water (0.32 ml, 17.952 mmol). The mix-
ture was stirred for 10 h, diluted with ethyl acetate, and washed
with brine. The organic layer was dried over Na2SO4 and then
concentrated to give the crude amine. The crude amine was dis-
solved in CH2Cl2 (3 mL), treated with excess of Et3N (2 mL) and
Ac2O (2 mL) at room temperature, and the mixture stirred for 4 h.
The reaction mixture was extracted with CH2Cl2 (2ꢂ25 mL) and the
organic layer washed with water, brine, and then dried over
Na2SO4. Evaporation of the solvent followed by purification using
SiO2 column chromatography (hexane/EtOAc, 7:3) gave a mixture
of diastereomers (16/17, 19:81 ratio) (749 mg, 70% yield).
COCH3). 13C NMR (100 MHz, CDCl3):
d 172.1, 170.2, 169.7, 127.9,
124.9, 73.3, 72.0, 48.0, 31.6, 23.3, 21.0, 20.9. nmax (neat film): 3463,
2963, 2926, 2853, 1744, 1649, 1412, 1370, 1241, 1048, 943, 890,
530 cmꢀ1. ESMS: m/z 278 [MþNa]þ. Anal. Calcd for C12H17NO5: C,
56.46; H, 6.71; N, 5.49; O, 31.34. Found: C, 56.48; H, 6.70; N, 5.52.
4.1.13. (1S,2S,3S,4R,5S)-5-Acetamidocyclohexane-1,2,3,4-tetrayl
tetraacetate (20)
The same experimental procedure was followed for converting
19 (100 mg, 0.39 mmol) to 20 as was followed for the conversion of
8 to 10. Purification was done by using SiO2 column chromatogra-
28
phy (hexane/EtOAc, 1:9). Colorless oil (98 mg, 67% yield). [a]
D
4.1.10.1. N-((S)-1-((4R,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-
þ9.66 (c 6.5, CHCl3). Rf¼0.5 (hexane/EtOAc, 1:9); 1H NMR
28
but-3-enyl)acetamide (17). Viscous liquid (607 mg, 57% yield). [
a
]
(400 MHz, CDCl3):
d
5.66 (d, 1H, NH, J¼8.8 Hz), 5.51 (t, 1H, H-3,
D
ꢀ20.64 (c 1.55, CH2Cl2). Rf¼0.45 (hexane/EtOAc, 3:2); 1H NMR
J¼10.0 Hz), 5.43 (dd, 1H, H-1, J¼5.8, 3.2 Hz), 4.94–489 (m, 2H, H-2,
H-4), 4.50–4.41 (m, 1H, H-5), 2.28–2.23 (m, 1H, H-6), 2.16 (s, 3H,
COCH3), 2.06 (s, 3H, COCH3), 2.02 (s, 3H, COCH3), 1.99 (s, 3H,
COCH3), 1.62–1.54 (ddd, 1H, H-60, J¼14.6, 12.7, 2.2 Hz). 13C NMR
(400 MHz, CDCl3):
d
5.83–5.67 (m, 3H), 5.42 (dd, 1H, J¼17.0, 1.2 Hz),
5.27 (dd, 1H, J¼10.2, 1.0 Hz), 5.12–5.06 (m, 2H), 4.16–4.10 (m, 1H),
4.04 (dd, 1H, J¼8.5, 7.3 Hz), 3.74 (dd, 1H, J¼8.5, 1.2 Hz), 2.35–2.31
(m, 2H), 2.02 (s, 3H), 1.42 (s, 3H), 1.41 (s, 3H). 13C NMR (100 MHz,
(100 MHz, CDCl3):
d 169.9, 169.7, 73.9, 71.6, 69.5, 66.8, 46.7, 31.9,
CDCl3):
d
170.0, 132.0, 131.5, 119.9, 118.9, 72.9, 70.6, 35.4, 20.9, 20.6.
23.2, 20.9, 20.5. nmax (neat film): 3288, 3074, 2925, 2853,1745, 1665,
1605, 1555, 1433, 1371, 1232, 1160, 1046, 932, 736 cmꢀ1. ESMS: m/z
396 [MþNa]þ. Anal. Calcd for C16H23NO9: C, 51.47; H, 6.21; N, 3.75;
O, 38.57. Found: C, 51.83; H, 6.20; N, 3.73.
nmax (neat film): 3436, 3282, 2981, 2929, 2854, 1646, 1556, 1443,
1375, 1296, 1236, 1175, 1097, 1065, 915, 741 cmꢀ1. [MþNa]þ. Anal.
Calcd for C13H21NO3: C, 65.25; H, 8.84; N, 5.85; O, 20.06. Found: C,
65.32; H, 8.83; N, 5.83.
Acknowledgements
4.1.10.2. N-((R)-1-((4R,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-
28
but-3-enyl)acetamide (16). Viscous liquid (142 mg, 13% yield). [
a
]
We thank Dr. J. K. Bera for solving the crystal structure of
compound 10. We thank the Department of Science and
D
þ0.41 (c 3.85, CH2Cl2). Rf¼0.44 (hexane/EtOAc, 3:2); 1H NMR