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L. Araki et al. / Tetrahedron 61 (2005) 11976–11985
NMR (500 MHz, CDCl3) d 1.13 (s, 12H), 1.26 (s, 9H),
2.27–2.30 (m, 2H), 2.45 (dt, 2H, JZ6.5, 2.8 Hz), 3.23 (d,
2H, JZ5.0 Hz), 3.57–3.63 (m, 2H), 3.66–3.74 (m, 2H), 3.79
(s, 6H), 4.15–4.19 (m, 1H), 4.50–4.56 (m, 1H), 5.15 (dd, 1H,
JZ9.2, 5.8 Hz), 5.75 (d, 2H, JZ2.6 Hz), 6.81 (d, 4H, JZ
8.4 Hz), 7.04–7.06 (m, 1H), 7.17–7.22 (m, 1H), 7.23–7.29
(m, 3H), 7.30–7.36 (m, 4H), 7.43–7.47 (m, 2H), 7.61 (d, 1H,
JZ1.0 Hz); 13C NMR (CDCl3) d 20.2, 24.5, 24.7, 26.8,
29.7, 38.7, 43.3, 55.2, 59.4, 64.2, 67.7, 75.1, 76.5, 86.1,
97.5, 113.0, 116.6, 126.7, 127.7, 128.3, 130.2, 136.2, 138.0,
143.4, 158.4, 177.6; 31P NMR (202 MHz, CD3CN) d: 148.7;
HRMS (LSIMS)19 calcd for C44H57N4O8PCNa [(MC
Na)C] 823.3809, found 823.3801.
resulting mixture was stirred at 0 8C for 30 min and then at rt
for 2.5 h. The solvent was evaporated to give a residue,
which was subsequently purified by flash column chroma-
tography (5–15% MeOH in EtOAc) to obtain 19 (86 mg,
1
74%) as a colorless oil; H NMR (CDCl3) d 1.17 (s, 9H),
3.62 (dd, 1H, JZ12.6, 4.2 Hz), 3.77 (dd, 1H, JZ12.6,
3.1 Hz), 3.90–3.97 (m, 2H), 3.98 (ddt, 1H, JZ13.1, 5.3,
1.6 Hz), 4.08 (ddt, 1H, JZ13.1, 5.3, 1.6 Hz), 4.19 (dd, 1H,
JZ5.2, 4.5 Hz), 4.77 (d, 1H, JZ6.6 Hz), 5.07 (ddt, 1H, JZ
10.3, 1.6, 1.2 Hz), 5.16 (dq, 1H, JZ17.4, 1.6 Hz), 5.82 (ddt,
1H, JZ17.4, 10.3, 5.3 Hz), 5.94 (s, 2H), 7.32 (s, 1H), 7.84
(s, 1H); HRMS(EIMS) calcd for C17H27N2O6 [(MCH)C]
355.1867, found 355.1869.
4.1.13. {4-[3,5-O-(1,1,3,3-Tetraisopropyldisiloxane-1,3-
diyl)-b-D-ribofuranosyl]imidazolyl}methyl 2,2-dimethyl-
propiolate (17). A mixture of 5c (755 mg, 1.29 mmol), 20%
Pd(OH)2–C23 (453 mg), and cyclohexene (3.9 ml,
38.80 mmol) in EtOH (30 ml) was refluxed for 3 h. After
filtration through Celite, the filtrate was evaporated to give
triol 8 (437 mg), which was subsequently dissolved with dry
pyridine (18 ml). 1,3-Dichloro-1,1,3,3-tetraisopropyl-
disiloxane (0.4 ml) was added dropwise to the pyridine
solution of 8 at 0 8C. The resulting mixture was stirred for
1 h at the same temperature and then at rt for 3 h. After
evaporation, the crude product was purified by flash column
chromatography (30–50% EtOAc in hexanes) to obtain 17
(481 mg, 67%) as a colorless oil; 1H NMR (CDCl3) d 0.94–
1.12 (m, 28H), 1.18 (s, 9H), 3.00 (br s, 1H), 3.94–4.10 (m,
3H), 4.27 (dd, 1H, JZ12.0, 7.7 Hz), 4.46 (t, 1H, JZ
12.0 Hz), 4.77 (d, 1H, JZ7.7 Hz), 5.78 (s, 2H), 7.10 (s, 1H),
7.66 (s, 1H); HRMS(EIMS) calcd for C26H48N2O7Si2
[(M)C] 556.2997, found 556.2988.
4.1.16. [4-(2-O-Allyl-5-O-DMT-D-b-ribofuranosyl)imi-
dazolyl]methyl 2,2-dimethylpropiolate (20). By the
same procedure as used for the preparation of 9, a mixture
of allyl compound 19 (43 mg, 0.12 mmol), DMTCl (66 mg,
0.18 mmol), Et3N (0.03 ml, 0.18 mmol), and DMAP
(0.4 mg, 0.003 mmol) was stirred at rt for 19 h to give 20
(81 mg, quant) as an amorphous product; 1H NMR (CDCl3)
d 1.12 (s, 9H), 3.28 (dd, 1H, JZ10.0, 4.8 Hz), 3.38 (dd, 1H,
JZ10.0, 3.9 Hz), 3.78 (s, 6H), 4.00–4.28 (m, 5H), 4.97 (d,
1H, JZ3.8 Hz), 5.17 (dd, 1H, JZ10.3, 1.4 Hz), 5.26 (dd,
1H, JZ17.1, 3.0, 1.4 Hz), 5.69 (q, 2H, JZ10.8 Hz), 5.90
(ddt, 1H, JZ17.1, 15.7, 5.4 Hz), 6.81 (d, 4H, JZ9.0 Hz),
7.07 (br s, 1H), 7.14–7.50 (m, 9H), 7.62 (br d, 2H, JZ
1.3 Hz); 13C NMR (CDCl3) d 27.1, 55.3, 64.2, 67.7, 71.2,
71.4, 78.2, 82.1, 82.9, 86.0, 112.7, 117.2, 126.2, 127.3,
127.9, 129.8, 133.5, 135.6, 137.7, 141.6, 144.5, 157.8, 176.8
(CO); HRMS(EIMS) calcd for C38H44N2O8 [(M)C]
656.3095, found 656.3091.
4.1.14. {4-[2-O-Allyl-3,5-O-(1,1,3,3-tetraisopropyldi-
siloxane-1,3-diyl)-b-D-ribofuranosyl]imidazolyl}methyl
2,2-dimethylpropiolate (18). Compound 17 (481 mg,
0.87 mmol) was rendered anhydrous by coevaporation
with dry pyridine three times. The residue was repeated
coevaporated with dry toluene and finally dissolved in dry
THF (9 ml). Triphenylphosphine (45 mg, 0.17 mmol) and
tris(dibenzylideneacetone)-dipalladium (0) (16 mg,
0.017 mmol) were added. Finally, allyl ethyl carbonate
(0.2 ml, 1.74 mmol) was added dropwise with stirring, and
the reaction mixture was refluxed for 15 h and then
evaporated. The residue was purified by flash column
chromatography (10–30% EtOAc in hexanes) to obtain 18
(197 mg, 38%) as a colorless oil; 1H NMR (CDCl3) d 0.92–
1.12 (m, 28H), 1.16 (s, 9H), 3.97 (dd, 1H, JZ12.7, 2.4 Hz),
4.00–4.06 (m, 3H), 4.11 (dd, 1H, JZ12.7, 2.4 Hz), 4.16–
4.43 (m, 2H), 4.97 (s, 1H), 5.15 (dq, 1H, JZ10.1, 1.9 Hz),
5.32 (dq, 1H, JZ17.5, 1.9 Hz), 5.76 (dd, 1H, JZ15.9,
10.6 Hz), 5.87–6.01 (ddt, 1H, JZ17.5, 10.1, 5.0 Hz), 7.10
(s, 1H), 7.62 (s, 1H); HRMS(EIMS) calcd for
C29H52N2O7Si2 [(M)C] 596.3310, found 596.3308.
4.1.17. {4-[2-O-Allyl-5-O-DMT-3-O-(2-CE-N,N-diiso-
propylphosphoramidite)-b-D-ribofuranosyl]imidazolyl}-
methyl 2,2-dimethylpropiolate (1c). By the same
procedure for 1a, compound 20 (43 mg, 0.07 mmol) was
dissolved in dichloromethane (0.3 ml). To the solution was
added a solution of DCI (6 mg, 0.05 mmol) in CH3CN
(0.05 ml) followed by CETPA (21 ml, 0.07 mmol). After the
mixture was stirred at rt for 12 h, DCI (6 mg, 0.050mmol) in
CH3CN (0.05 ml) and 2-cyanoethyl N,N,N0,N -tetraiso-
propylphosphodiamidite (21 ml, 0.07 mmol) were added.
The resulting mixture was further stirred for 12 h at rt and
then evaporated. The residual oil was chromatographed
using benzene by NH-silica gel chromatography to give
partially purified 1c (33 mg, 60%). The semi-purified 1c was
further purified by NH-silica gel (35% EtOAc in hexane) to
give 1c (15 mg, 27%) as a colorless oil; 1H NMR (500 MHz,
CDCl3) d 1.00 (s, 2H), 1.08–1.40 (m, 19H), 2.32 (t, 1H, JZ
6.5 Hz), 2.61 (q, 1H, JZ5.9 Hz), 3.20 (td, 2H, JZ8.8,
3.8 Hz), 3.33–3.65 (m, 5H), 3.78 (s, 6H), 4.00–4.45 (m, 5H),
4.98 (t, 1H, JZ5.3 Hz), 5.11 (br d, 1H, JZ9.5 Hz), 5.23 (d,
1H, JZ17.3 Hz), 5.60–5.77 (m, 2H), 5.80–5.95 (m, 1H),
6.80 (dd, 4H, JZ8.3, 6.4 Hz), 7.10 (br d, 1H, JZ3.7 Hz),
7.16–7.30 (m, 3H), 7.31–7.39 (m, 4H), 7.44–7.50 (m, 2H),
7.61 (s, 1H); 31P NMR (202 MHz, CDCl3) d 149.7, 150.4;
HRMS(LSIMS)19 calcd for C47H62N4O9P [(MCH)C]
857.4251, found 857.4252; calcd for C47H61N4O9PNa
[(MCNa)C] 879.4070, found 879.4069; calcd for
C47H61N4O9PK [(MCK)C] 895.3810, found 895.3811.
4.1.15. [4-(2-O-Allyl-b-D-ribofuranosyl)imidazolyl]
methyl 2,2-dimethylpropiolate (19). A solution of
TMEDA (0.3 ml, 1.98 mmol) in CH3CN (0.3 ml) and HF
(46% aqueous solution, 57 ml) was added to a small round-
bottom flask at 0 8C. The HF/TMEDA mixture was stirred at
0 8C for 10 min, and a solution of 18 (197 mg, 0.33 mmol)
in CH3CN (2.3 ml) was added dropwise over 5 min. The