H. Hakala et al. / Tetrahedron 58 (2002) 8771–8777
8775
S-solketal (12.0 mL, 96 mmol) and triphenylphosphine
(23.3 g, 89 mmol) were dissolved in dry THF (160 mL).
Diethylazodicarboxylate (DEAD; 14.0 mL, 89 mmol) was
added in five portions during 15 min, and the mixture was
stirred at rt for an additional 2 h. After concentration in
vacuo the product was purified on silica gel (eluent: diethyl
ether). Pure fractions were pooled and concentrated to give
trityl chloride (8.3 g, 24.5 mL; dissolved in 25 mL of dry
dichloromethane) was added dropwise, and the mixture was
stirred for 3 h at rt, after which all volatile materials were
removed in vacuo. The residue was dissolved in dichloro-
methane, washed with sat. NaHCO3 and dried over Na2SO4.
Purification on silica gel using diethyl ether as the eluent
yielded 9.3 g (82 %) of compound 5 as a solid. Mp 468C. 1H
NMR (CDCl3): d 7.30 (9H, m); 7.22 (1H, d, J¼7.9 Hz); 7.17
(4H, d, J¼9.0 Hz); 5.74 (1H, d, J¼7.9 Hz); 3.98 (4H, m);
3.94 (1H, m); 3.80 (6H, s); 2.45 (1H, br); 2.23 (2H, dt,
J¼2.7 and 7.2 Hz); 1.95 (1H, t, J¼2.7 Hz); 1.76 (2H, m);
1.57 (2H, m). IR (KBr): 3293 cm21 (CuCH). [MþNa]þ
obs 591.2467 calcd for C34H36N2NaOþ6 : 591.2466.
1
21.0 g (86%) of the title compound as an oil. H NMR
(CDCl3): d 7.94 (1H, d, J¼7.5 Hz); 7.66 (1H, m); 7.45 (2H,
m); 7.35 (2H, d, J¼8.1 Hz); 5.82 (1H, d, J¼7.5 Hz); 4.38
(1H, m); 4.07 (2H, m); 3.71 (2H, m); 1.46 (3H, s); 1.35 (3H,
s). [MþH]þ obs 331.1295 calcd for C17H19N2Oþ5 :
331.1288.
3.1.2. (S)-1-(2,3-O-Isopropylidene-2,3-dihydroxypropyl)-
uracil (2). Compound 1 (20.5 g, 62.2 mmol) was suspended
in the mixture of 25% aq. ammonia and methanol (200 mL,
1:1, v/v), and stirred at ambient temperature for 2 h,
concentrated in vacuo and purified on silica gel (eluent:
20% methanol in dichloromethane, v/v) to give the title
compound as a solid. Yield was 13.8 g (98%). Mp 150–28C.
1H NMR (CDCl3): d 9.28 (1H, br); 7.30 (1H, d, J¼5 Hz);
5.71 (1H, d, J¼5 Hz); 4.38 (1H, m); 4.11 (2H, m); 3.68 (2H,
m); 1.41 (3H, s); 1.33 (3H, s). [MþH]þ obs 277.1035 calcd
for C10H15N2Oþ4 : 227.1032.
3.1.6. (S)-1-[3-(4,40-Dimethoxytrityl-2,3-dihydroxypro-
pyl)]-3-{tetramethyl 2,20,200, 2000-[(4-(5-hexyn-1-yl)-pyri-
dine-2,6-diyl)bis(methylenenitrilo)]tetrakis-(acetato)}-
uracil (8). A mixture of tetramethyl 2,20,200,2000-[(4-bromo-
pyridine-2,6-diyl)bis-(methylenenitrilo)]tetrakis(acetate)
(6; 3.2 g, 6.3 mmol) and compound 5 (4.7 g, 8.2 mmol) in
dry THF (14 mL) and triethylamine (24 mL) was deaerated
with argon. Bis(triphenylphosphine)palladium(II) chloride
(88 mg, 0.126 mmol) and CuI (48 mg, 0.252 mmol) were
added and the mixture was stirred for 7 h at 558C. The
cooled solution was filtered, the filtrate was evaporated and
redissolved in dichloromethane. The solution was washed
with water, dried (Na2SO4) and concentrated. Purification
on silica gel (eluent petroleum ether, bp 40–608C/ethyl
acetate/triethylamine, 2:5:1, v/v/v) yielded the title com-
pound as a solid (5.3 g, 85%). Mp 408C. 1H NMR (CDCl3):
d 7.39 (2H, s); 7.27 (9H, m); 7.12 (1H, d, J¼7.9 Hz); 6.83
(4H, d, J¼8.8 Hz); 5.61 (1H, d, J¼7.9 Hz); 4.11 (2H, m);
3.98 (4H, s); 3.94 (1H, m); 3.79 (6H, s); 3.70 (12H, s); 3.61
(8H, s); 3.17 (2H, d, J¼4.9 Hz); 2.74 (1H, br); 2.44 (2H, t,
J¼7.1 Hz); 1.72 (2H, m); 1.65 (2H, m). IR (KBr):
2236 cm21 þ(CuC). [MþH]þ obs 992.4245 calcd for
C53H62N5O14: 992.4288.
3.1.3. (S)-1-(2,3-O-Isopropylidene-2,3-dihydroxypropyl)-
3-(5-hexyn-1-yl)uracil (3). Compound 2 (15.3 g, 68 mmol),
5-hexyn-1-ol (8.9 mL; 81 mmol) and triphenylphosphine
(21.0 g, 81 mmol) were suspended in dry THF (250 mL).
DEAD (12.8 mL, 81 mmol) was added in four portions
during 15 min, and the mixture was allowed to stir overnight
at ambient temperature. After concentration, purification
was performed on silica gel (eluent: 3% methanol in
dichloromethane, v/v) to give the title compound as an oil.
Yield was 13.4 g (64 %). 1H NMR (CDCl3): d 7.26 (1H, d,
J¼8.1 Hz); 5.73 (1H, d, J¼8.1 Hz); 4.38 (1H, m); 4.11 (2H,
m); 3.96 (2H, t, J¼7.0 Hz); 3.69 (2H, m); 2.80 (2H, br); 2.25
(2H, td, J¼2.7 and 7.1 Hz); 1.95 (1H, t, J¼2.7 Hz); 1.76
(2H, m); 1.61 (2H, m); 1.42 (3H, s); 1.34 (3H, s). IR (film):
3290 cm21 (CuCH). [MþH]þ obs 307.1659 calcd for
C16H23N2Oþ4 : 307.1658.
3.1.7. (S)-1-[3-(4,40-Dimethoxytrityl-2,3-dihydroxy-pro-
pyl)]-3-(2,20,200,2000-{[40-(400-(5-hexyn-1-yl)-phenyl)-2,20:
60,200-terpyridine-6,600-diyl]bis (methylene-nitrilo)tetra-
kis(acetato)}uracil (9). Synthesis, work up and purification
was performed as described in Section 3.1.6 but using
tetramethyl 2,20,200,2000-{[40-(400-bromophenyl)-2,20:60,200-ter-
pyridine-6,600-diyl]bis-(methylenenitrilo)}tetrakis(acetate)
(7; 1.5 g, 2.0 mmol) and compound 5 (1.5 g, 2.5 mmol).
Yield was 1.9 g (75%, an oil). 1H NMR (DMSO-d6): d 8.63
(2H, s); 8.55 (2H, d, J¼7.7 Hz); 8.02 (2H, t J¼7.7 Hz); 7.86
(2H, t, J¼8.5 Hz); 7.62 (4H, t, J¼7.3 Hz); 7.53 (1H, d,
J¼8.1 Hz); 7.42 (2H, d, J¼7.4 Hz); 7.28 (4H, m); 6.88 (4H,
d, J¼8.8 Hz); 5.64 (1H, d, J¼7.7 Hz); 5.32 (1H, d, J¼
5.5 Hz); 4.10 (4H, s); 3.86 (2H, m); 3.72 (8H, s); 3.68 (6H,
s); 3.51 (1H, m); 2.97 (2H, m); 2.88 (2H, m); 2.51 (6H, m).
IR (film): 2227 cm21 (CuC). [MþH]þ obs 1222.5059
calcd for C69H72N7Oþ14: 1222.5132.
3.1.4. (S)-1-(2,3-Hydroxypropyl)-3-(5-hexyn-1-yl)uracil
(4). Compound 3 (13.3 g, 43.4 mmol) was dissolved in
methanol (500 mL) containing iodine (1%, w/v), and stirred
overnight at ambient temperature. Sodium bisulfite was
added and the mixture was stirred until the color of iodine
disappeared. Solid material was removed by filtration, and
the filtrate was concentrated in vacuo. Purification was
performed on silica gel (eluent MeOH/CH2Cl2 1:9, v/v) to
give the title compound as a solid. Yield was 9.83 g (85%).
Mp 101–38C. 1H NMR (CDCl3): d 7.27 (1H, d, J¼7.9 Hz);
5.74 (1H, d, J¼7.9); 3.99 (2H, m); 3.96 (2H, t, J¼7.3 Hz);
3.84 (1H, m); 3.61 (2H, m); 2.84 (2H, br); 2.25 (2H dt,
J¼2.7 and 7.0 Hz); 1.95 (1H, t, J¼2.7 Hz); 1.75 (2H, m);
1.60 (1H, m). IR (KBr): 3265 cm21 (CuCH). [MþH]þ obs
267.1339 calcd for C13H19N2Oþ4 : 267.1325.
3.1.8. (S)-1-(2,3-Dihydroxypropyl)uracil (12). Iodolysis
of compound 2 (2.4 g, 10.6 mmol) as described in Section
3.1.4 yielded the title compound as an oil after silica gel
column chromatography (eluent MeOH/CH2Cl2, 1:5, v/v).
Yield was 1.63 g (82%). 1H NMR (DMSO-d6): d 11.21 (1H,
br); 7.50 (1H, d, J¼7.8 Hz); 5.50 (1H, d, J¼7.8 Hz); 5.03
(1H, br); 4.72 (1H, br); 3.93 (1H, m); 3.66 (2H, m); 3.35
3.1.5. (S)-1-[3-(4,40-Dimethoxytrityl-2,3-dihydroxypro-
pyl)]-3-(5-hexyn-1-yl)uracil (5). Compound 4 (5.44 g,
20 mmol) was dried by coevaporations with0 dry pyridine
and dissolved in the same solvent (40 mL). 4,4 -Dimethoxy-