PAPER
Convergent Approaches to Carbocyclic C-Nucleosides
4127
H-5), 3.92 (s, 3 H, 2¢-OCH3), 3.94 (s, 3 H, 6¢-OCH3), 4.35 (d,
J = 11.0 Hz, 1 H, CH2O), 4.38 (d, J = 11.0 Hz, 1 H, CH2O), 4.44 (d,
J = 11.3 Hz, 1 H, CH2O), 4.60 (d, J = 11.3 Hz, 1 H, CH2O), 5.73
(dm, J = 10.1 Hz, 1 H, H-4), 5.83 (dm, J = 10.1 Hz, 1 H, H-3), 7.40–
7.45 (m, 4 H, H-3¢¢), 7.53–7.58 (m, 2 H, H-4¢¢), 8.00–8.05 (m, 4 H,
H-2¢¢).
13C NMR (125.70 MHz, CDCl3): d = 9.4, 29.8, 31.2, 36.3, 37.1,
53.9, 54.3, 65.1, 69.7, 107.4, 124.6, 127.9, 128.4, 128.4, 129.5,
129.8, 129.9, 133.0, 133.1, 163.0, 166.3, 166.5, 169.8, 170.0.
HRMS-ESI: m/z [M + Na]+ calcd for C28H26N2O7 + Na: 525.1632;
found: 525.1628.
Hydrogenation of the Coupling Products; General Procedure
Pd(OH)2/C (150 mg) was added to a solution of the substrate (1.5
mmol) in MeOH (75 mL) and the mixture was stirred under H2 at-
mosphere for 20 h. The catalyst was removed by filtration through
a Celite pad and the filtrate was evaporated. Products were purified
by column chromatography.
HRMS-ESI: m/z [M + H]+ calcd for C29H30N2O6: 503.21766; found:
503.21772.
[3-(2,6-Dimethoxypyrimidin-4-yl)cyclohexane-1,1-diyl]bis-
methylene Dibenzoate (41)
Prepared from 37. Chromatography: hexanes–EtOAc (5:1); yield:
95%; colorless oil.
[4-(2,6-Dimethoxypyrimidin-4-yl)cyclohex-2-ene-1,1-diyl]bis-
methylene Dibenzoate (38)
Prepared from 27 and 33. Chromatography: hexanes–EtOAc (4:1);
yield: 60%; air-sensitive colorless oil.
1H NMR (600.13 MHz, DMSO-d6): d = 1.72 (m, 1 H, H-6¢a), 1.89
(m, 2 H, H-5¢a and H-6¢b), 2.05 (m, 1 H, H-5¢b), 3.43 (m, 1 H, H-
4¢), 3.87 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3), 4.29 (d, J = 10.9 Hz,
1 H, OCH2), 4.32 (d, J = 11.0 Hz, 1 H, OCH2), 4.38 (d, J = 10.9 Hz,
1 H, OCH2), 4.42 (d, J = 11.0 Hz, 1 H, OCH2), 5.88 (dd, J = 10.2,
2.3 Hz, 1 H, H-2¢), 6.03 (dd, J = 10.2, 3.1 Hz, 1 H, H-3¢), 6.40 (s, 1
H, H-5), 7.51 (m, 4 H, H-3¢¢), 7.66 (m, 2 H, H-4¢¢), 7.95 (m, 2 H, H-
2¢¢), 7.99 (m, 2 H, H-2¢¢).
13C NMR (150.92 MHz, DMSO-d6): d = 24.2, 25.4, 39.2, 42.1,
53.9, 54.5, 67.3, 67.8, 99.0, 129.0, 129.1, 129.2, 129.4, 129.4,
129.6, 129.7, 131.8, 133.7, 133.7, 165.1, 165.8, 171.8, 174.6.
HRMS-ESI: m/z [M + Na]+ calcd for C28H28N2O6 + Na: 511.1840;
found: 511.1836.
IR (CHCl3): 3092, 3065, 3027, 1718, 1596, 1585, 1568, 1494, 1480,
1453, 1386, 1316, 1280, 1269, 1177, 1111, 1070, 1027, 985, 838,
713, 687, 617 cm–1.
1H NMR (600.13 MHz, CDCl3): d = 1.43 (td, J = 13.6, 4.4 Hz, 1 H,
H-6ax), 1.56 (m, 1 H, H-4ax), 1.67 (qt, J = 13.7, 3.6 Hz, 1 H, H-6ax),
1.68 (dd, J = 13.6, 12.9 Hz, 1 H, H-2ax), 1.82 (dm, J = 14.0 Hz, 1 H,
H-5eq), 1.92 (dm, J = 13.7 Hz, 1 H, H-6eq), 1.98 (dm, J = 12.7 Hz, 1
H, H-4eq), 2.06 (dm, J = 13.6 Hz, 1 H, H-2eq), 2.83 (m, 1 H, H-3),
3.93 (s, 3 H, 2¢-OCH3), 3.94 (s, 3 H, 6¢-OCH3), 4.27 (d, J = 10.9 Hz,
1 H, CH2O), 4.32 (d, J = 10.9 Hz, 1 H, CH2O), 4.58 (s, 2 H, CH2O),
6.21 (s, 1 H, H-5¢), 7.40–7.44 (m, 4 H, H-3¢¢), 7.53–7.57 (m, 2 H, H-
4¢¢), 8.01–8.04 (m, 4 H, H-2¢¢).
13C NMR (150.92 MHz, CDCl3): d = 21.0, 29.3, 31.2, 34.9, 38.2,
40.1, 53.7, 54.5, 64.0, 70.8, 98.4, 128.3, 128.4, 129.6, 129.6, 129.1,
130.0, 133.0, 133.1, 165.2, 166.4, 166.4, 172.0, 175.6.
HRMS-FAB: m/z [M + Na]+ calcd for C28H30N2O6 + Na:
513.19961; found: 513.19922.
[4-(2,6-Dimethoxy-5-methylpyrimidin-4-yl)cyclohex-2-ene-1,1-
diyl]bismethylene Dibenzoate (47)
Prepared from 27 and 34. Chromatography: hexanes–EtOAc (11:2);
[3-(2,6-Dimethoxy-5-methylpyrimidin-4-yl)cyclohexane-1,1-
diyl]bismethylene Dibenzoate (42)
Prepared from 40. Chromatography: hexanes–EtOAc (5:1); yield:
93%; colorless oil.
yield: 52%; air-sensitive colorless oil.
1H NMR (600.13 MHz, CDCl3): d = 1.75 (ddd, J = 13.6, 11.9 Hz,
3.6 Hz, 1 H, H-6a), 1.96 (m, 1 H, H-5a), 2.02 (m, 1 H, H-5b), 2.10
(s, 3 H, 5¢-CH3), 2.12 (m, 1 H, H-6b), 3.72 (m, 1 H, H-4), 4.33 (d,
J = 10.8 Hz, 1 H, CH2O), 4.40 (d, J = 11.1 Hz, 1 H, CH2O), 4.45 (d,
J = 10.8 Hz, 1 H, CH2O), 4.54 (d, J = 11.1 Hz, 1 H, CH2O), 5.85
(ddd, J = 10.2, 2.5, 1.1 Hz, 1 H, H-2), 5.93 (ddd, J = 10.2, 2.5, 0.8
Hz, 1 H, H-3), 7.41–7.46 (m, 4 H, H-3¢¢), 7.54–7.58 (m, 2 H, H-4¢¢),
8.02–8.06 (m, 4 H, H-2¢¢).
13C NMR (150.92 MHz, CDCl3): d = 9.6, 23.8, 26.7, 38.9, 39.6,
54.0, 54.4, 66.8, 68.3, 107.4, 127.6, 128.4, 128.4, 129.6, 130.0,
132.5, 133.0, 133.1, 162.9, 166.3, 166.4, 169.9, 169.9.
HRMS-ESI: m/z [M + H]+ calcd for C29H30N2O6: 503.21766; found:
503.21760.
IR (CHCl3): 3065, 3029, 3027, 1718, 1602, 1584, 1575, 1492, 1475,
1391, 1380, 1371, 1316, 1284, 1269, 1177, 1113, 1082, 1071, 1027,
1009, 978, 937, 713, 687, 617, 532 cm–1.
1H NMR (600.13 MHz, CDCl3): d = 1.50 (td, J = 13.5, 4.5 Hz, 1 H,
H-6ax), 1.68 (m, 1 H, H-4ax), 1.70–1.86 (m, 5 H, H-2, H-5 and H-
4eq), 1.92 (dm, J = 14.0 Hz, 1 H, H-6eq), 2.01 (s, 3 H, 5¢-CH3), 3.14
(m, 1 H, H-3), 3.94 (s, 3 H, 2¢-OCH3), 3.94 (s, 3 H, 6¢-OCH3), 4.28
(d, J = 10.9 Hz, 1 H, CH2O), 4.32 (d, J = 10.9 Hz, 1 H, CH2O), 4.54
(d, J = 11.4 Hz, 1 H, CH2O), 4.70 (d J = 11.4 Hz, 1 H, CH2O), 7.39–
7.43 (m, 4 H, H-3¢¢), 7.53–7.57 (m, 2 H, H-4¢¢), 8.01–8.04 (m, 4 H,
H-2¢¢).
13C NMR (150.92 MHz, DMSO-d6): d = 9.2, 21.1, 29.5, 30.4, 33.9,
35.5, 38.2, 53.9, 54.2, 64.0, 70.9, 106.8, 128.3, 128.4, 129.5, 129.5,
129.8, 130.0, 133.0, 133.1, 165.9, 166.3, 166.4, 169.7, 171.1.
HRMS-ESI: m/z [M + H]+ calcd for C29H32N2O6: 505.23331; found:
505.23339.
[4-(2,6-Dimethoxypyrimidin-4-yl)-2-oxocyclohex-3-ene-1,1-
diyl]bismethylene Dibenzoate (39)
The compound 38 (300 mg, 0.6 mmol) was exposed to sunlight in a
glass vessel for 1 month. The mixture of products was chromato-
graphed (hexanes–EtOAc, 3:1) on a silica gel column to afford the
product 39 (154 mg, 50%).
1H NMR (600.13 MHz, DMSO-d6): d = 2.39 (t, J = 6.3 Hz, 2 H, H-
6¢), 2.98 (td, J = 6.3, 1.7 Hz, 2 H, H-5¢), 3.94 (s, 3 H, 6-OCH3), 3.94
(s, 3 H, 2-OCH3), 4.59 (d, J = 11.3 Hz, 2 H, CH2O), 4.61 (d,
J = 11.3 Hz, 2 H, CH2O), 7.00 (s, 2 H, H-5 and H-3¢), 7.50 (m, 4 H,
H-3¢¢), 7.66 (m, 2 H, H-4¢¢), 7.93 (m, 4 H, H-2¢¢).
13C NMR (150.92 MHz, DMSO-d6): d = 22.3, 26.8, 48.2, 54.4,
54.8, 64.9, 99.7, 126.5, 129.1, 129.4, 129.4, 133.8, 155.3, 163.6,
164.9, 165.6, 172.7, 199.3.
[4-(2,6-Dimethoxypyrimidin-4-yl)cyclohexane-1,1-diyl]bis-
methylene Dibenzoate (48)
Prepared from 38. Chromatography: hexanes–EtOAc (4:1); yield:
89%; colorless oil.
IR (CHCl3): 3092, 3072, 3065, 1718, 1596, 1585, 1567, 1494, 1480,
1452, 1386, 1315, 1287, 1272, 1177, 1108, 1071, 1027, 964, 839,
712, 687, 618 cm–1.
1H NMR (600.13 MHz, CDCl3): d = 1.57 (td, J = 13.6, 4.1 Hz, 2 H,
H-2¢ax), 1.80 (dm, J = 3.2 Hz, 2 H, H-3¢ax), 1.92 (dm, J = 13.9 Hz, 2
H, H-3¢eq), 2.01 (dm, J = 14.1 Hz, 2 H, H-2¢eq), 2.58 (tt, J = 11.9, 3.7
Synthesis 2010, No. 23, 4119–4130 © Thieme Stuttgart · New York