Debarge et al.
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2.06 (d, 1.65H, J = 1.2 Hz, CH3, major epimer). δc (100 MHz;
CDCl3): 168.7 (C, CO2Me, major epimer), 168.6 (C, CO2Me,
minor epimer), 167.1 (C, NCOPh, minor epimer), 166.9 (C,
NCOPh, major epimer), 165.6 (C, OCOPh, 2 epimers), 165.3 (C,
OCOPh, 2 epimers), 162.8 (C, C-4, major epimer), 162.7 (C, C-4,
minor epimer), 150.0 (C, C-2, 2 epimers), 135.6 (CH, C-6, major
epimer), 135.2 (CH, C-6, minor epimer), 134.7 (CH, 2 epimers),
133.7 (CH, 2 epimers), 133.6 (CH, 2 epimers), 131.6 (C, 2 epimers),
130.4 (CH, 2 epimers), 129.9 (CH, 2 epimers), 129.8 (CH,
2 epimers), 129.0 (CH, 2 epimers), 128.9 (C, 2 epimers), 128.6
(CH, 2 epimers), 128.5 (CH, 2 epimers), 112.6 (C, C-5, minor
epimer), 112.4 (C, C-5, major epimer), 85.4 (CH, C-10, major
epimer), 85.0 (CH, C-10, minor epimer), 82.6 (CH, C-40, major
epimer), 82.4(CH, C-40, minor epimer), 76.4 (CH, d, J= 156.5 Hz,
PCH, minor epimer), 75.9 (CH, d, J = 157.8 Hz, PCH, major
epimer), 73.6, 73.1 (2 ꢀ CH, C-20, C-30, major epimer), 72.9, 72.7
(2 ꢀ CH, C-20, C-30, minor epimer), 72.1 (CH2, d, J = 12.0 Hz,
C-50, major epimer), 71.7 (CH2, d, J = 12.0 Hz, C-50, minor
epimer), 54.5-53.9 (CH3, m, (CH3O)2PO, 2 epimers), 53.23 (CH3,
CO2CH3, minor epimer), 53.17 (CH3, CO2CH3, major epimer),
12.1 (CH3, CH3-C-5, minor epimer), 12.0 (CH3, CH3-C-5, major
epimer). One aromatic C not seen. δP (121 MHz; CDCl3): 16.12
(minor epimer), 16.07 (major epimer). HRMS (ESþ) m/z calcd for
C36H35N2O14P [M þ H]þ 751.1904, found 751.1876. [R]D -104.6
(c 1, CHCl3, 20 °C). νmax cm-1 (film) 2958, 1732, 1665, 1600, 1449,
1374, 1267, 1125, 1046, 714.
OH-Insertion Reaction of 3-N,30-O-Dibenzoyl-20deoxy-
uridine (30b) and Trimethyl Phosphonodiazoacetate (20) to Give
Phosphonate 48b. Treatment of 30b (780 mg, 1.79 mmol) and 20
(484 mg, 2.32 mmol) with rhodium(II) acetate (∼1 mol %) by
procedure D (chromatography using CH2Cl2/MeOH, 99:1) af-
forded the title product 48b as a white solid (860 mg, 78%). mp:
51-52 °C. NMR shows roughly a 1:1 mixture of two epimers. δH
(300 MHz; CDCl3): 8.44 (d, 0.5H, J = 8.4 Hz, H-6, one epimer),
8.25 (d, 0.5H, J = 8.1 Hz, H-6, one epimer), 8.02-7.94 (m, 4H,
ArHortho), 7.67-7.55 (m, 2H, ArHpara), 7.52-7.41 (m, 4H,
ArHmeta), 6.59-6.52 (m, 1H, H-10), 5.98 (d, 0.5H, J = 8.1 Hz,
H-5, one epimer), 5.95 (d, 0.5H, J = 8.1 Hz, H-5, one epimer),
5.80-5.76 (m, 0.5H, H-30, one epimer), 5.68-5.64 (m, 0.5H, H-30,
one epimer), 4.47 (d, 0.5H, J= 18.6 Hz, PCH, one epimer), 4.46 (d,
0.5H, J = 18.3 Hz, PCH, one epimer), 4.37-4.31 (m, 1H, H-40),
4.04-3.79 (m, 11H, 2 H-50, 9CH3), 2.68-2.44 (m, 2H, H-20). δc (75
MHz; CDCl3): 168.9 (C, CO2Me, one epimer), 168.8 (C, CO2Me,
one epimer), 167.0 (C, NCOPh, 2 epimers), 166.0 (C, OCOPh,
2 epimers), 162.2 (C, C-4, one epimer), 162.1 (C, C-4, one epimer),
149.6 (C, C-2, 2 epimers), 141.0 (CH, C-6, one epimer), 140.7 (CH,
C-6, one epimer), 135.0 (CH, 2 epimers), 133.6 (CH, 2 epimers),
131.6 (C, 2 epimers), 130.4 (CH, 2 epimers), 129.7 (CH, 2 epimers),
129.2 (C, 2 epimers), 129.1 (CH, 2 epimers), 128.5 (CH, 2 epimers),
103.2 (CH, C-5, one epimer), 102.8 (CH, C-5, one epimer), 85.5
(CH, C-10, one epimer), 85.1 (CH, C-10, one epimer), 84.1 (CH,
C-40, one epimer), 84.0 (CH, C-40, one epimer), 76.3 (CH, C-30, one
epimer), 76.2 (CH, C-30, one epimer), 75.9 (CH, d, J = 158.0 Hz,
PCH, one epimer), 75.8 (CH, d, J = 158.0 Hz, PCH, one epimer),
72.6 (CH2, d, J = 10.5 Hz, C-50, one epimer), 72.4 (CH2, d, J =
11.5 Hz, C-50, one epimer), 54.0-53.8 (CH3, m, (CH3O)2PO,
2 epimers), 53.1 (CH3, CO2CH3, 2 epimers), 38.0 (CH2, C-20,
one epimer), 37.7 (CH2, C-20, one epimer). δP (121 MHz; CDCl3):
16.52 (one epimer), 16.50 (one epimer). HRMS (ESþ) m/z calcd for
C28H30N2O12P [M þ H]þ 617.1536, found 617.1525. [R]D -16.69
(c 0.8, CHCl3, 20 °C). νmax cm-1 (film) 1749, 1707, 1669, 1450, 1271,
1028, 716.
roughly a 1:1 mixture of two epimers. δH (300 MHz; CDCl3):
9.15 (bs, 1H, NH), 8.82 (d, 0.5H, J = 7.8 Hz, H-6, 1 epimer), 8.61
(d, 0.5H, J = 7.8 Hz, H-6, 1 epimer), 8.00-7.88 (m, 6H, ArHortho),
7.59-7.30 (m, 10H, H-5, ArHpara, ArHmeta), 6.84 (d, 0.5H, J = 6.6
Hz, H-10, 1 epimer), 6.83 (d, 0.5H, J = 6.6 Hz, H-10, 1 epimer), 6.02
(dd, 0.5H, J = 5.4, 2.4 Hz, H-30, 1 epimer), 5.92 (dd, 0.5H, J = 5.4,
2.4 Hz, H-30, 1 epimer), 5.83 (dd, 0.5H, J = 6.6, 5.7 Hz, H-20,
1 epimer), 5.76 (dd, 0.5H, J = 6.6, 5.7 Hz, H-20, 1 epimer), 4.65 (d,
0.5H, J = 18.6 Hz, PCH, 1 epimer), 4.63 (d, 0.5H, J = 18.6 Hz,
PCH, 1 epimer), 4.57-4.53 (m, 1H, H-40), 4.03-3.83 (m, 11H, 2H-
50, 9CH3). δc (75 MHz; CDCl3): 167.0 (C, NCOPh, 2 epimers),
165.5 (C, 2 ꢀ OCOPh, 1 epimer), 165.1 (C, 2 ꢀ OCOPh, 1 epimer),
162.6 (C, C-4, 2 epimers), 145.8 (CH, C-6, 1 epimer), 145.6 (CH,
C-6, 1 epimer), 133.6 (CH), 133.5 (CH), 133.2 (C), 133.0 (CH),
130.0 (CH), 129.8 (CH), 128.9 (CH), 128.8 (C), 128.7 (C), 128.5
(CH), 128.4 (CH), 127.7 (CH), 98.0 (CH, C-5, 2 epimers), 87.2 (CH,
C-10, 1 epimer), 86.8 (CH, C-10, 1 epimer), 82.7 (CH, C-40,
1 epimer), 82.6 (CH, C-40, 1 epimer), 76.0 (d, CH, J = 156.5 Hz,
PCH, 1 epimer), 75.9 (d, CH, J = 156.7 Hz, PCH, 1 epimer), 75.3
(CH, C-20, 1 epimer), 74.7 (CH, C-20, 1 epimer), 72.6 (CH, C-30,
2 epimers), 71.7-71.4 (m, CH2, C-50, 2 epimers), 54.4-54.1 [m,
CH3, (CH3O)2PO, 2 epimers], 53.24, 53.19 (CH3, CO2CH3, 2
epimers). C-2 could not be detected. δP (121 MHz; CDCl3): 16.47
(one epimer), 16.20 (one epimer). HRMS (ESþ) m/z calcd for
C35H35N3O13P[Mþ H]þ 736.1908, found 736.1920. [R]D -58.80 (c
0.5, CHCl3, 20 °C).
OH-Insertion Reaction of 30-O,4-N-Dibenzoyl-20-deoxycyti-
dine 34b and Trimethyl Phosphonodiazoacetate 20 to Give Phos-
phonate 49b. Treatment of 34b (490 mg, 1.12 mmol) and 20 (258 mg,
1.24 mmol) with rhodium(II) acetate (∼1 mol %) by procedure D
(chromatography using neat EtOAc) afforded the product 49b as
a solid (310 mg, 45%). NMR shows roughly a 1:1 mixture of
two epimers. δH (400 MHz; CDCl3): 8.21 (d, 0.5H, J = 8.1 Hz,
H-6, 1 epimer), 8.08 (bd, 2H, J = 7.5 Hz, ArHortho, 2 epimers), 8.02
(d, 0.5H, J = 7.8 Hz, H-6, 1 epimer), 7.84 (bd, 2H, J = 7.5 Hz,
ArHortho, 2 epimers), 7.65-7.35 (m, 6H, ArHpara, ArHmeta),
6.81-6.73 (m, 2H, H-5, H-10, 2 epimers), 5.82 (bd, 0.5H, J = 5.7
Hz, H-30, 1 epimer), 5.69 (bd, 0.5H, J = 5.7 Hz, H-30, 1 epimer),
4.48 (d, 0.5H, J = 18.6 Hz, PCH, 1 epimer), 4.46 (d, 0.5H, J = 18.3
Hz, PCH, 1 epimer), 4.42-4.39 (bs, 0.5H, H-40, 1 epimer), 4.38-
4.36 (bs, 0.5H, H-40, 1 epimer), 3.98-3.82 (m, 11H, 2H-50, 9CH3),
2.76-2.63 (m, 1H, one of H-20, 1 epimer), 2.59-2.44 (m, 1H, one of
H-20, 1 epimer). δc (100 MHz; CDCl3): 167.08 (C, CO2Me, 1 epimer),
167.06 (C, CO2Me, 1 epimer), 166.99 (NCOPh, 1 epimer), 166.96
(NCOPh, 1 epimer), 166.1 (C, OCOPh, 2 epimers), 162.8 (C, C-4,
2 epimers), 145.6 (C, C-2, 1 epimer), 145.5 (C, C-2, 1 epimer), 133.65
(CH), 133.60 (CH), 132.13 (C), 132.10 (C), 130.0 (CH), 129.8
(CH), 129.7 (CH), 129.24 (C), 129.18 (C), 128.9 (CH), 128.6 (CH),
128.5 (CH), 127.94 (CH), 127.92 (CH), 99.5 (CH, C-5, 1 epimer),
99.1 (CH, C-5, 1 epimer), 86.3 (CH, C-10, 1 epimer), 85.9 (CH, C-10,
1 epimer), 84.23 (CH, C-40, 1 epimer), 84.18 (CH, C-40, 1 epimer),
76.4 (CH, C-30, 1 epimer), 76.3 (CH, C-30, 1 epimer), 76.0 (d, CH,
J=157.6 Hz, PCH, 1 epimer), 75.8 (d, CH, J=157.6 Hz, PCH,
1 epimer), 72.6 (d, CH2, J=22.1 Hz, C-50, 1 epimer), 72.5 (d, CH2,
J = 22.1 Hz, C-50, 1 epimer), 54.1-53.8 [m, CH3, (CH3O)2PO,
2 epimers], 53.15-53.08 (m, CH3, CO2CH3, 2 epimers), 38.3 (CH2,
C-20, 1 epimer), 38.1 (CH2, C-20, 1 epimer). C-2 could not be
detected. δP (121 MHz; CDCl3): 16.53 (one epimer), 16.50 (one
epimer). HRMS (ESþ) m/z calcd for C28H31N3O11P [M þ H]þ
616.1696, found 616.1669. [R]D -20.50 (c 0.5, CHCl3, 20 °C).
OH-Insertion Reaction of 20-O,30-O,6-N,N-Tetrabenzoylade-
nosine 38a and Trimethyl Phosphonodiazoacetate 20 to Give
Phosphonate 50a. Treatment of 38a (3.50 g, 5.12 mmol) and 20
(1.60 g, 7.68 mmol) with rhodium(II) acetate (∼1 mol %) by
procedure D (chromatography using EtOAc/hexane, 80:20) af-
forded the title product 50a as a solid (2.90 g, 66%). mp: 98-99 °C.
NMR shows roughly a 1:1 mixture of two epimers. δH (300 MHz;
CDCl3): 8.99 (s, 0.5H, H-2 or H-8, 1 epimer), 8.94 (s, 0.5H, H-2 or
OH-Insertion Reaction of 20-O,30-O,4-N-Tribenzoylcytidine
34a and Trimethyl Phosphonodiazoacetate 20 to Give Phospho-
nate 49a. Treatment of 34a (3.50 g, 6.30 mmol) and 20 (1.57 g,
7.56 mmol) with rhodium(II) acetate (∼1 mol %) by procedure
D (chromatography using EtOAc/hexane, 80:20 to neat EtOAc)
afforded the product 49a as a solid (2.40 g, 52%). NMR shows
120 J. Org. Chem. Vol. 76, No. 1, 2011