R. S. Coleman et al. / Tetrahedron 63 (2007) 3450–3456
3455
ꢂ1
1662, 1601, 1556, 1518, 1431, 1370, 1311 cm . EI-HRMS,
m/z calcd for C H NO : 399.1682; found: 399.1696.
5.8. Coumarin dimethoxytrityl ether
2
2
25
6
A solution of 1 (100 mg, 0.28 mmol), co-evaporated with
pyridine (2ꢁ3 mL), dissolved in dry pyridine (4 mL) under
5
.5. C-Riboside 6c
ꢀ
methyl chloride (114 mg, 0.34 mmol, 1.2 equiv). After 3 h at
N at 25 C was treated with bis-(4-methoxyphenyl)phenyl-
2
A solution of triflate 3c (375 mg, 1 mmol) in dry CH CN
3
ꢀ
(
(
20 mL) in a Teflon-capped vial was treated with glycal 2c
700 mg, 3 mmol, 3 equiv), Pd(OAc) (90 mg, 0.4 mmol,
25 C, the reaction mixture was diluted with saturated
aqueous NaHCO3 (10 mL) and extracted with CH Cl
2
2
2
0
0
3
.4 equiv), 1,3-bis(diphenylphosphino)propane (20.6 mg,
.050 mmol, 0.05 equiv), and NaHCO (252 mg, 3 mmol,
equiv). The reaction mixture was stirred for 5 h at 24 C.
(3ꢁ10 mL). The combined organic extracts were dried
(Na SO ), concentrated, and the residue was purified by
2
3
4
ꢀ
flash chromatography (2.5ꢁ15 cm Et N deactivated silica,
3
The mixture was concentrated in vacuo and the residue
was purified by flash chromatography (silica gel, 4:1 ether/
hexane) to afford 6c as a yellow oil (227 mg, 79%): H
Et O) to afford the corresponding DMT ether (164 mg,
2
1
89%) as a yellow foam: H NMR (300 MHz, CDCl3)
d 7.25 (m, 9H, ArH), 6.91 (s, 1H, ArH), 6.83 (m, 4H,
ArH), 6.26 (s, 1H, ArH), 5.34 (dd, J¼6.4, 9.5 Hz, 1H,
1
NMR (250 MHz, CDCl ) d 7.06 (s, 1H), 6.23 (s, 1H), 5.95
3
0
(s, 6H, 2 OCH ), 3.35 (m, 1H, C5 –H), 3.15 (m, 5H, 2
0
0
(
d, J¼3.7 Hz, 1H), 4.87 (dd, J¼2.0, 1.7 Hz, 1H), 4.66 (m,
C1 –H), 4.33 (m, 1H, C3 –H), 4.11 (m, 1H, C4 –H), 3.71
0
CH +C5 –H), 2.85 (m, 2H, CH ), 2.71 (m, 2H, CH ), 2.40
1
2
H), 3.72 (m, 2H), 3.25 (m, 4H), 2.86 (m, 2H), 2.78 (m,
H), 1.97 (m, 4H), 0.93 (s, 9H), 0.11 (s, 3H), 0.09 (s, 3H);
C NMR (75 MHz, CDCl ) d 163.0, 155.6, 152.3, 151.4,
3
0
(m, 1H, C2 –H), 1.85 (m, 5H, 2 CH +C2 –H); C NMR
2
2
2
1
3
0
(75 MHz, CDCl ) d 162.8, 158.5, 156.3, 151.2, 145.6,
0
13
3
2
1
6
45.7, 121.2, 118.1, 106.9, 106.6, 104.8, 98.3, 83.6, 79.7,
3.4, 49.8, 49.4, 27.7, 25.3, 21.4, 20.5, 20.4, 17.9, ꢂ4.9,
3
144.7, 135.7, 130.0, 129.9, 128.1, 127.8, 126.8, 120.9,
117.9, 113.1, 106.9, 106.2, 104.0, 103.4, 86.3, 85.9, 75.2,
64.3, 58.5, 55.2, 49.8, 49.4, 21.5, 20.6, 20.4; FABMS, m/z
ꢂ5.1; IR (neat) n
3444, 2932, 2856, 1703, 1654, 1600,
556, 1518, 1431, 1370, 1311 cm . EI-HRMS, m/z calcd
max
ꢂ1
1
for C H NO Si: 469.2284; found: 469.2284.
+
659 (M ): 303, 118.
26
35
5
0
0
5
.6. 3 -Keto-2 -deoxy C-riboside 7
5.9. Coumarin phosphoramidite 8
Enol ether 6c (235 mg, 0.5 mmol) was dissolved in dry THF
(
A solution of the above ether (100 mg, 0.15 mmol) in
ꢀ
13 mL) under argon and was treated with HF$pyridine
70% HF by weight, 0.25 mL, 17.5 equiv). The reaction
anhydrous CH Cl (3 mL) under N at 25 C was treated se-
2
2
2
(
quentially with tetrazole (6 mg, 75 mmol, 0.5 equiv), dry
diisopropylamine (11 mL, 75 mmol, 0.5 equiv), and (2-
ꢀ
mixture was stirred for 14 h at 24 C. Concentration in vacuo
and purification of the residue by flash chromatography (sil-
ica gel, ether) afforded 7 as a bright yellow solid (135 mg,
7
1
3
6
1
0
(55 mg, 0.18 mmol, 1.2 equiv). After 3 h at 25 C, the reac-
0
cyanoethyl)-N,N,N ,N -tetraisopropyl phosphorodiamidite
ꢀ
tion mixture was diluted with CH Cl (10 mL) and dried
1
6%): H NMR (300 MHz, CDCl ) d 6.79 (s, 1H), 6.43 (s,
3
2
2
H), 5.36 (dd, J¼11.0, 6.1 Hz, 1H), 4.08 (dd, J¼3.4,
.3 Hz, 1H), 3.94 (m, 2H), 3.20 (m, 4H), 2.97 (dd, J¼18.0,
.1 Hz, 1H), 2.81 (m, 2H), 2.70 (m, 2H), 2.38 (dd, J¼18.0,
(Na SO ). The solvent was removed in vacuo and the residue
2 4
was purified by flash chromatography (2ꢁ12 cm Et N deac-
3
tivated silica, 5% CH OH/CH Cl ) to afford 8 (85 mg, 71%)
2
3
2
1
3
1
1.0 Hz, 1H), 1.91 (m, 4H); C NMR (75 MHz, CDCl )
as a yellow foam: H NMR (300 MHz, CDCl ) d 7.30 (m, 9H,
3
3
d 212.2, 162.9, 154.3, 151.1, 145.8, 120.5, 118.3, 106.8,
ArH), 6.9 (s, 1H, ArH), 6.8 (m, 4H, ArH), 6.32 (s, 1H, ArH),
5.3 (dd, J¼6.2, 9.5 Hz, 1H, C1 –H), 4.45 (m, 1H, C3 –H),
0
4.10 (m, 1H, C4 –H), 3.80 (s, 6H, 2 OCH ), 3.65 (m, 6H,
0
1
2
1
05.5, 103.6, 82.2, 72.6, 61.3, 49.7, 49.3, 44.4, 27.6, 21.3,
0.4, 20.3; IR (neat) nmax 3412, 2921, 2845, 1758, 1698,
616, 1600, 1556, 1518, 1436, 1311 cm . EI-HRMS, m/z
0
3
ꢂ1
CH CH CN and 2 CH(CH ) ), 3.4 (dd, J¼5.2, 9.8 Hz, 1H,
2
2
3 2
0 0
C5 –H), 3.2 (m, 5H, CH +C5 –H), 2.8 (m, 2H, CH ), 2.7
2 2
calcd for C H NO : 355.1420; found: 355.1429.
0
2
21
5
0
(
m, 2H, CH ), 2.40 (ddd, J¼2.4, 6.2, 13.1 Hz, 1H, C2 –H),
2
0
0
5
.7. 2 -Deoxy C-riboside 1
1.9 (m, 5H, 2 CH +C2 –H) 1.19 (d, J¼3.1 Hz, 6H,
2
1
3
CH(CH ) ) 1.17 (d, J¼3.1 Hz, 6H, CH(CH ) ); C NMR
3
2
3 2
Ketone 7 (135 mg, 0.38 mmol) was dissolved in dry CH CN
3
(75 MHz, CDCl ) d 162.7, 158.5, 156.1, 151.2, 145.6,
3
(
10 mL) and glacial acetic acid (10 mL) under argon. The
ꢀ
144.7, 135.7, 130.0, 129.9, 128.1, 127.8, 126.8, 120.9,
117.9, 117.6, 113.2, 106.9, 106.2, 103.5, 86.3, 85.8, 75.1,
74.1, 64.3, 59.2, 58.2, 51.2, 49.8, 49.4, 42.9, 42.1, 24.6,
24.5, 21.5, 20.6, 20.4, 20.3, 20.2, 16.9, 16.8.
reaction mixture was cooled to 0 C and sodium triacetoxy-
borohydride (106 mg, 0.5 mmol, 1.3 equiv) was added.
ꢀ
and the orange-brown residue was purified by flash chroma-
After 10 min at 0 C, the volatiles were removed in vacuo
tography (silica gel, 4:1 CHCl /MeOH) to afford 1 as a yel-
3
1
low solid (105 mg, 77%): H NMR (250 MHz, CDCl )
3
Acknowledgements
d 6.90 (s, 1H), 6.29 (s, 1H), 5.36 (dd, J¼9.6, 6.1 Hz, 1H),
4
2
2
.44 (m, 1H), 4.08 (m, 1H), 3.72 (m, 2H), 3.23 (m, 4H),
.85 (m, 2H), 2.73 (m, 2H), 2.46 (ddd, J¼13.2, 6.1,
This work was funded by a grant from the National Institutes
of Health (R01GM61292).
1
3
.4 Hz, 1H), 1.94 (m, 5H); C NMR (125 MHz, CDCl )
3
d 163.4, 156.7, 151.2, 145.8, 120.9, 118.3, 106.9, 106.1,
1
2
1
02.8, 87.2, 75.2, 73.2, 63.1, 49.9, 49.5, 42.6, 27.7, 21.5,
0.6, 20.4; IR (neat) nmax 3401, 2943, 2556, 1687, 1605,
551, 1519, 1438, 1301 cm . EI-HRMS, m/z calcd for
References and notes
ꢂ1
1. Crespo-Hern ꢀa ndez, C. E.; Cohen, B.; Hare, P. M.; Kohler, B.
Chem. Rev. 2004, 104, 1977.
C H NO : 357.1576; found: 357.1568.
2
0
23
5