Novel Synthesis of 40C-Aryl-Branched Acyclic Nucleoside
1785
temperature for 3 h, and the resulting solid was filtered through a Celite pad. The
filtrate was concentrated under vacuum and the residue was purified by silica gel
column chromatography (EtOAc=hexane, 1:4) to give the allylic alcohol 4 (3.6 g,
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83%) as a colorless oil: H NMR (CDCl3, 300 MHz) d 7.32–7.07 (m, 5H), 5.99,
5.91 (dt, J ¼ 6.6, 6.6 Hz, 1H), 4.31 (d, J ¼ 6.6 Hz, 1H), 4.27 (s, 1H), 0.85, 0.81 (s, s,
9H), 0.02 (m, 6H); Anal calc for C16H26O2Si: C, 69.01; H, 9.41. Found: C, 69.18;
H, 9.26.
( )-3-(t-Butyldimethylsilyloxymethyl)-3-phenyl-pent-4-enoic acid ethyl ester (5).
A
solution of the allylic alcohol 4 (12 g, 43.09 mmol) in triethyl orthoacetate
(200 mL) and 0.5 mL of propionic acid was heated at 130–135ꢁC overnight. An
excess of triethyl orthoacetate was distilled off and the residue was purified by silica
gel column chromatography (EtOAc=hexane, 1:15) to give 5 (12.16 g, 81%) as a
colorless oil: 1H NMR (CDCl3, 300 MHz) d 7.36–7.25 (m, 5H), 6.26 (dd,
J ¼ 18.0, 11.1 Hz, 1H), 5.31 (dd, J ¼ 11.4, 1.2 Hz, 1H), 5.16 (dd, J ¼ 17.7, 0.6 Hz,
1H), 4.10–3.99 (m, 4H), 3.00 (s, 2H), 1.18 (t, J ¼ 6.9 Hz, 3H), 0.99 (s, 9H), 0.02
(d, J ¼ 8.1, 6H); 13C NMR (CDCl3) d 171.51, 143.17, 142.33, 127.82, 127.34,
126.30, 114.34, 67.73, 59.94, 48.70, 39.74, 25.76, 18.19, 14.07, ꢀ5.71; Anal calc
for C20H32O3Si: C, 68.92; H, 9.25. Found: C, 68.69; H, 9.05.
( )-3-(t-Butyldimethylsilyloxymethyl)-3-phenyl-pent-4-en-1-ol (6). To a solution
of 5 (3.2 g, 9.18 mmol) in CH2Cl2 (50 mL), DIBALH (20.1 mL, 1.0 M solution in
hexane) was added slowly at ꢀ78ꢁC, and stirred for 2 h at the same temperature.
To the mixture, methanol (10 mL) was added. The mixture was stirred at room tem-
perature for 2 h, and the resulting solid was filtered through a Celite pad. The filtrate
was concentrated under vacuum and the residue was purified by silica gel column
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chromatography (EtOAc=hexane, 1:4) to give 6 (2.5 g, 89%) as a colorless oil: H
NMR (CDCl3, 300 MHz) d 7.33–7.28 (m, 5H), 5.82 (dd, J ¼ 17.4, 10.8 Hz, 1H),
5.33 (d, J ¼ 10.7 Hz, 1H), 5.13 (d, J ¼ 10.5 Hz, 1H), 4.24 (t, J ¼ 6.9 Hz, 2H), 3.80
(s, 2H), 1.72 (m, 2H), 0.90 (s, 9H), ꢀ0.02 (s, 6H); 13C NMR (CDCl3) d 142.48,
141.65, 128.20, 127.32, 126.60, 115.09, 68.80, 67.72, 48.59, 34.18, 25.74, 18.13,
ꢀ5.71; Anal calc for C18H30O2Si: C, 70.53; H, 9.87. Found: C, 70.26; H, 9.66.
( )-1-O-Methanesulfonic acid-3-(t-butyldimethylsilyloxymethyl)-3-phenyl-pent-4-
enyl ester (7). To a solution of alcohol 6 (2.5 g, 8.15 mmol) in anhydrous CH2Cl2
(30 mL), anhydrous triethyl amine (2.27 mL, 16.3 mmol) and MsCl (1.39 g,
12.2 mmol) was added at 0ꢁC. The mixture was stirred at the same temperature
for 1 h, and quenched by adding a cold saturated NaHCO3 solution (2 mL). The mix-
ture was extracted with CH2Cl2 (100 mL) and water (50 mL). The organic layer was
dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated
under vacuum, and the residue was purified by silica gel column chromatography
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(EtOAc=hexane, 1:3) to give 7 (2.6 g, 83%) as a colorless oil: H NMR (CDCl3,
300 MHz) d 7.35–7.29 (m, 5H), 6.02 (dd, J ¼ 17.4, 10.8 Hz, 1H), 5.34 (d, J ¼ 9.9 Hz,
Hz, 1H), 5.17 (d, J ¼ 17.7 Hz, 1H), 4.25 (t, J ¼ 6.9 Hz, 2H), 3.83 (s, 2H), 2.93 (s, 3H,
mesyl), 2.44 (m, 2H), 0.95 (s, 9H), ꢀ0.02 (s, 6H); Anal calc for C19H32O4SSi: C,
59.33; H, 8.39. Found: C, 59.68; H, 8.54.