Y. Taniguchi et al. / Tetrahedron 69 (2013) 600e606
605
same temperature, the reaction mixture was warmed up to room
temperature. After stirring for 2 h, the reaction mixture was
quenched by a satd NaHCO3 solution and extracted with CHCl3. The
organic layer was continuously washed with water and a satd NaCl
solution, dried over Na2SO4, then evaporated under reduced pres-
sure. The residue was purified by flash column chromatography
(CHCl3:MeOH¼20/1) to give compound 15 as a colorless oil
24.1 mmol) was added BF3$Et2O (3.8 mL, 30.1 mmol) at ꢁ78 ꢀC.
After stirring for 40 min at ꢁ40 ꢀC, the reaction mixture was diluted
with EtOAc, washed with a satd NaCl solution, dried over Na2SO4,
then evaporated under reduced pressure. The residue was purified
by flash column chromatography (Hexane:EtOAc¼30/1) to give the
a
-phenyl compound as a colorless oil (1.08 g, 2.2 mmol, 11%), and
the
b
-phenyl compound as a colorless oil (6.48 g, 13.3 mmol, 66%).
-phenyl compound (4.93 mmol, 10.1 mmol) was dis-
(400 mg, 0.79 mmol, 74%). lmax (neat) 2944, 2868, 1465 cmꢁ1
;
dH
The desired b
(400 MHz, CDCl3) 7.19e7.32 (5H, m), 4.52e4.58 (1H, m), 4.12 (1H, d J
4.1 Hz), 3.68 (1H, d, J 4.0 Hz), 3.33 (3H, s), 3.18 (1H, s), 2.67e2.70
(1H, m), 2.56e2.60 (1H, m), 2.10 (1H, dd, J 7.0, 14.3 Hz), 1.88 (1H, dd,
J 7.0, 14.3 Hz), 0.86e1.24 (30H, m); dC (125 MHz, CDCl3) 144.3, 128.1,
126.8,125.4, 88.6, 87.1, 80.2, 70.4, 60.8, 60.4, 37.8, 37.1,17.5,17.4,17.3,
17.1, 17.0, 13.4, 13.1, 12.8, 12.7; HRMS (ESI-TOF): MþHþ, found
510.3033. C26H48NO5Si2 requires 510.3066.
solved in THF (40 mL), and then TBAF$3H2O (3.82 g, 12.1 mmol) was
added to the reaction mixture. After stirring for 2 h, the reaction
mixture was evaporated under reduced pressure. The residue was
dissolved in MeOH (37 mL), and then DOWEX-50WX8-100 (3.12 g)
was added to the reaction mixture. After stirring for 40 h, the re-
action mixture was filtered off, and the filtrate was evaporated
under reduced pressure. The residue was purified by flash column
chromatography (Hexane:EtOAc¼1/1) to give compound 17 as
a colorless foam (1.42 g, 6.76 mmol, 82% for two steps). lmax (neat)
4.3.5. (10S,20R,30R,40R)-10-[(N-3-Methoxy-2-methylacryoyl)-ureido]-
20-methoxy-10-phenyl-30,50-O-tetraisopropyldisiloxy-ribose (16). To
a solution of 15 (370 mg, 0.73 mmol) in benzene (15 mL) was added
a solution of 7 in benzene (excess amount). After stirring for 5 h, the
reaction mixture was quenched by a satd NH4Cl solution and
extracted with EtOAc. The organic layer was continuously washed
with water and a satd NaCl solution, dried over Na2SO4, then
evaporated under reduced pressure. The residue was purified by
flash column chromatography (CHCl3:MeOH¼99/1) to give com-
pound 16 as a colorless oil (463 mg, 0.71 mmol, 90%). lmax (neat)
3346, 3272, 3201 cmꢁ1
; dH (400 MHz, CD3OD) 7.44e7.25 (5H, m),
4.70 (1H, d, J 7.2 Hz), 4.03 (1H, d, J 4.0 Hz), 3.98 (1H, q, J 4.0 Hz), 3.87
(1H, t, J 6.0 Hz), 3.80 (1H, dd, J 3.6, 12.0), 3.74 (1H, dd, J 5.2, 12.0 Hz);
dC (125 MHz, CDCl3) 141.9, 129.2, 128.7, 127.4, 86.3, 85.6, 79.1, 72.9,
63.7; HRMS (ESI-TOF): MþNaþ, found 233.0804. C11H14O4Na re-
quires 233.0784.
4.4.2. (1S,2R,3S,4R)-1-Deoxy-3,5-O-(1,3-disiloxanediyl-1,1,3,3-
tetraisopropyl)-1-phenylribose (18). To a solution of 17 (1.0 g,
4.76 mmol) in pyridine (48 mL) was added TIPDSCl2 (1.8 mL,
5.72 mmol) at 0 ꢀC. After stirring for 1 h at room temperature, the
reaction mixture was diluted with EtOAc, washed with a satd NaCl
solution, dried over Na2SO4, then evaporated under reduced pres-
sure. The residue was purified by flash column chromatography
(Hexane:EtOAc¼15/1 to 10/1) to give compound 18 as a colorless oil
2943, 2865, 1684, 1543 cmꢁ1
; dH (400 MHz, CDCl3) 8.67 (1H, s), 8.06
(1H, s), 7.46 (1H, d, J 7.3 Hz), 7.24 (1H, t, J 7.1 Hz), 7.17 (1H, t, J 7.2 Hz),
4.58 (1H, dd, J 2.0, 13.0 Hz), 4.48 (1H, dd, J 2.0, 13.0 Hz), 4.10e4.15
(1H, m), 3.90e4.00 (1H, m), 3.78 (1H, d, J 4.0 Hz), 3.40 (3H, s), 3.00
(1H, dd, J 5.2,16.2 Hz), 2.81 (1H, dd, J 5.2, 16.2 Hz), 2.70 (1H, dd, J 3.7,
16.8 Hz), 2.90e3.30 (1H, m), 2.18e2.38 (1H, m), 0.85e1.25 (30H, m);
dC (125 MHz, CDCl3) 168.8, 157.9, 154.0, 144.2, 128.1, 126.7, 125.4,
107.4, 88.7, 86.5, 80.4, 70.5, 61.3, 61.1, 60.2, 35.4, 35.1, 17.6, 17.4, 17.3,
17.2, 17.1, 17.0, 13.4, 13.1, 12.8, 12.7, 8.8; HRMS (ESI-TOF): MþNaþ,
found 673.3286. C32H54N2NaO8Si2 requires 673.3311.
(1.99 g, 4.40 mmol, 92%). lmax (neat) 3518, 2945, 2868 cmꢁ1
; dH
(400 MHz, CDCl3) 7.40 (2H, d, J 7.3 Hz), 7.32 (2H, t, J 7.3 Hz), 7.25 (1H,
t, J 7.3 Hz), 4.82 (1H, d, J 3.7 Hz), 4.36 (1H, d, J 6.1 Hz), 4.13e3.92 (3H,
m), 2.93 (1H, t, J 3.7 Hz), 1.10e0.93 (28H, m); dC (125 MHz, CDCl3)
140.1, 128.4, 127.62, 125.8, 85.5, 82.4, 71.7, 62.6, 17.5, 17.4, 17.3, 17.1,
17.1, 17.0, 13.4, 13.2, 12.9, 12.7; HRMS (ESI-TOF): MþHþ, found
453.2531. C23H41O5Si2 requires 453.2487.
4.3.6. (10S,20R,30R,40R)-10-[(3,4-Dihydro-2,4-dioxo-5-methyl-1(2H)
pyrimidinyl)]-20-methoxy-10-phenylribose (2). To a solution of 16
(430 mg, 0.66 mmol) in THF (5 mL) was added a solution of TBAF in
THF (1.59 mL, 1.59 mmol). After stirring for 2 h, the reaction mixture
was diluted with EtOAc. The organic layer was continuously washed
with water and a satd NaCl solution, dried over Na2SO4, then evap-
orated under reduced pressure. The residue was purified by flash
column chromatography (CHCl3:MeOH¼99/1) to give a colorless oil
(244 mg, 0.60 mmol, 90%). This colorless oil (220 mg, 0.54 mmol) was
dissolved in a solution of H2SO4 (1 M, 8 mL), then the mixture was
stirred for 3 h at 90 ꢀC. The reaction mixture was neutralized bya satd
NaHCO3 solution and extracted with EtOAc. The organic layer was
continuously washed with water and a satd NaCl solution, dried over
Na2SO4, then evaporated under reduced pressure. The residue was
purified by flash column chromatography (CHCl3:MeOH¼99/1) to
give compound 2 as a colorless foam (127 mg, 0.34 mmol, 72%). lmax
4.4.3. (1S,2R,3S,4R)-1-Deoxy-3,5-O-(1,3-disiloxanediyl-1,1,3,3-
tetraisopropyl)-2-O-methyl-1-phenylribose (19). To a solution of 18
(1.98 g, 4.37 mmol) in THF (44 mL) was added MeI (2.7 mL,
43.7 mmol) and NaHMDS (2.07 M in THF, 6.4 mL,13.1 mmol) at 0 ꢀC.
After stirring for 1 h, the reaction was quenched by a satd NH4Cl
solution, extracted with EtOAc, and then the organic layer was
washed with a satd NaCl solution, dried over Na2SO4, then evapo-
rated under reduced pressure. The residue was purified by flash
column chromatography (Hexane:EtOAc¼20/1) to give compound
19 as a colorless oil (1.57 g, 3.36 mmol, 77%). lmax (neat) 2946,
2866 cmꢁ1
; dH (400 MHz, CDCl3) 7.42 (2H, d, J 7.3 Hz), 7.31 (2H, t, J
7.6 Hz), 7.23 (1H, t, J 7.3 Hz), 4.95 (1H, s), 4.36 (1H, dd, J 3.6, 4.9 Hz),
4.19 (1H, dd, J 13.1, 2.4 Hz), 3.57 (3H, s), 3.56 (1H, t, J 4.9 Hz),
1.10e0.88 (28H, m); dC (125 MHz, CDCl3) 141.1, 128.3, 127.4, 125.7,
87.2, 84.6, 80.9, 70.6, 60.7, 58.9, 17.5, 17.4, 17.4, 17.3, 17.2, 17.0, 13.5,
13.1, 12.9, 12.6; HRMS (ESI-TOF): MþHþ, found 467.2660.
(neat) 3414, 2931, 2836, 1673, 1471, 1447 cmꢁ1
; dH (400 MHz, CDCl3)
8.86 (1H, s), 7.43 (2H, d, J 7.3 Hz), 7.32 (2H, t, J 7.3 Hz), 7.23 (1H, t, J
7.5 Hz), 6.63 (1H, s), 4.12 (2H, d J 3.6 Hz), 3.87e3.93 (1H, m),
3.66e3.81 (3H, m), 3.61 (1H, d J 3.6 Hz), 3.56 (3H, s), 3.35e3.45 (1H,
m), 2.44e2.51 (1H, m), 2.32e2.39 (1H, m), 2.12 (2H, s), 1.75 (3H, m);
dC (125 MHz, CDCl3) 164.1,150.7, 143.5,141.0, 128.6,127.4,109.8, 89.1,
85.4, 83.8, 70.5, 63.4, 60.2, 44.9, 33.0, 12.1; HRMS (ESI-TOF): MþNaþ,
found 399.1522. C19H24N2NaO6 requires 399.1527.
C24H43O5Si2 requires 467.2644.
4.4.4. (1S,2R,3S,4R)-1-Deoxy-2-O-methyl-1-phenylribose (3). To a so-
lution of 19 (1.54 g, 3.30 mmol) in THF (33 mL) was added a solution
of TBAF in THF (8.25 mL, 8.25 mmol). After stirring for 1 h, the re-
action mixture was diluted with EtOAc. The organic layer was con-
tinuously washed with water and a satd NaCl solution, dried over
Na2SO4, then evaporated under reduced pressure. The residue was
purified by flash column chromatography (Hexane:EtOAc¼2/1) to
give the compound 3 as a colorless oil (505.6 mg, 2.25 mmol, 68%).
4.4. Synthesis of 3
4.4.1. (1S,2R,3S,4R)-1-Deoxy-1-phenylribose (17). To a mixture of 4
(10.1 g, 20.1 mmol) in CH2Cl2 (67 mL) and Et3SiH (3.9 mL,