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V. Vanek et al. / Tetrahedron 65 (2009) 862–876
873
J(40aA,40aB)¼13.2, J(40aA,40)¼8.7 (H-40aA); 2.07 ddd, 1H,
J(40aB,10)¼8.7, J(40aB,40aA)¼13.2, J(40aB,40)¼5.8 (H-40aB). 13C NMR
(DMSO-d6): 160.21 (C-2); 156.24 (C-6); 151.84 (C-4); 135.70 (C-8);
113.53 (C-5); 70.01 d, J(C,P)¼6.8, 69.79 d, J(C,P)¼6.4, w24.00 4ꢁd,
J(C,P)¼3.9 (P(OiPr)2); 64.76 d, J(40,P)¼14.2 (C-40); 63.55 (C-50); 59.85
(C-20); 51.15 (C-10); 49.26 d, J(C,P)¼164.1 (N–CH2–P); 33.81 (C-40a).
(DMSO-d6): 165.49 (C-4); 158.25, 158.24, 145.10, 135.86, 135.79,
129.90 (2), 129.87 (2), 128.00 (2), 127.9 (2), 126.86, 113.35 (2) and
113.33 (2) (2ꢁC6H4 and C6H5 (ODMTr)); 155.83 (C-2); 142.62 (C-
6); 93.55 (C-5); 85.79 (pCo (ODMTr)); 70.04 d, J(C,P)¼6.3, 69.82 d,
J(C,P)¼7.5, 24.06 d, J(C,P)¼5.0, 24.01
d
J(C,P)¼5.0, 24.00 d,
J(C,P)¼5.0 and 23.90 d, J(C,P)¼5.0 (P(OiPr)2); 64.50 d, J(40,P)¼18.9
(C-40); 63.73 (C-50); 60.03 (C-20); 55.22 (2ꢁOMe (ODMTr)); 52.26
(C-10); 49.50 d, J(C,P)¼170.5 (N–CH2–P); 35.43 (C-40a). Compound
23c: HRMS (FAB) calcd for C37H48N4O7P [MþH]þ 691.3261, found:
691.3270. IR nmax/cmꢂ1 (CHCl3): 1633, 1615, 1303, 1589, 1565, 1413,
1374 (cytosine); 2838, 1509, 1178, 1071 (–ODMTr); 2982, 1465,
1386, 1374, 1250, 1012, 993 (–CH2PO(OiPr)2). 1H NMR (DMSO-d6):
7.81 d, 1H, J(6,5)¼5.7 (H-6); 7.37 m, 2H, 7.30 m, 2H, 7.24 m, 4H,
7.22 m, 1H and 6.88 m, 4H (2ꢁC6H4 and C6H5 (ODMTr)); 6.87 br s,
1H and 6.76 br s, 1H (NH2); 6.04 d, 1H, J(5,6)¼5.7 (H-5); 5.15 m, 1H,
J(10,20A)¼1.6, J(10,20B)¼5.5, J(10,40aA)¼7.7, J(10,40aB)¼3.6 (H-10); 4.48
m, 2H, 1.185 d, 3H, J¼6.2, 1.15 d, 6H, J¼6.2 and 1.105 d, 3H, J¼6.2
(P(OiPr)2); 3.73 s, 6H (2ꢁOMe (ODMTr)); 3.35 dd, 1H, J(20A,10)¼1.6,
J(20A,20B)¼11.2 (H-20A); 3.33 dd, 1H, 1H, J(gem)¼15.5 and 2.57 dd,
1H, J(gem)¼15.5, J(H,P)¼4.8 (N–CH2–P); 3.09 dd, 1H, J(50A,40)¼6.2,
J(50A,50B)¼9.6 (H-50A); 3.04 dd, 1H, J(50B,40)¼5.0, J(50B,50A)¼9.6
(H-50B); 2.72 m, 1H, J(40,40aA)¼7.7, J(40,40aB)¼8.2, J(40,50A)¼6.2,
J(40,50B)¼5.0 (H-40); 2.61 dd, 1H, J(20B,10)¼5.5, J(20B,20A)¼11.2 (H-
20B); 2.26 dt, 1H, J(40aA,10)¼7.7, J(40aA,40aB)¼13.8, J(40aA,40)¼7.7
(H-40aA); 1.46 ddd, 1H, J(40aB,10)¼3.6, J(40aB,40aA)¼13.8,
J(40aB,40)¼8.2 (H-40aB). 13C NMR (DMSO-d6): 165.51 (C-4); 164.65
(C-2); 158.24 (2), 145.21, 135.88, 135.87, 129.88 (4), 128.03 (2),
127.87 (2), 126.85, 113.37 (2) and 113.36 (2) (2ꢁC6H4 and C6H5
(ODMTr)); 156.30 (C-6); 99.45 (C-5); 85.92 (pCo (ODMTr)); 73.96
(C-10); 70.16 d, J(C,P)¼6.3, 69.54 d, J(C,P)¼6.3, 24.08 d, J(C,P)¼3.8,
24.00 d, J(C,P)¼3.8, 23.94 d, J(C,P)¼5.0 and 23.85 d, J(C,P)¼5.0
(P(OiPr)2); 66.96 (C-50); 64.18 d, J(40,P)¼17.6 (C-40); 61.81 (C-20);
55.21 (2ꢁOMe (ODMTr)); 50.62 d, J(C,P)¼163.4 (N–CH2–P); 35.81
(C-40a).
5.2.8. Diisopropyl 1-(adenin-9-yl)-5-O-dimethoxytrityl-1,2,3-
trideoxy-3-aza-4a-carba-b-L-glycero-pentofuranos-3-
ylmethylphosphonate (23a)
The general procedure A was followed using mesylate 14a
(1.34 g,1.98 mmol), Cs2CO3 (0.78 g, 2.38 mmol) and adenine (0.40 g,
2.98 mmol). The reaction was complete after 4 h. White foam
(0.530 g, 37%). HRMS (FAB) calcd for C38H48N6O6P [MþH]þ
715.3373, found: 715.3365. IR nmax/cmꢂ1 (CHCl3): 1630, 1608, 1301
(adenine); 1608, 1509, 1178, 1035 (–ODMTr); 2983, 1467, 1250, 1178,
1010, 991 (–CH2PO(OiPr)2). 1H NMR (DMSO-d6): 8.26 s, 1H (H-8);
8.12 s, 1H (H-2); 7.30 m, 2H, 7.26 m, 2H, 7.19 m, 1H, 7.17 m, 2H, 7.16
m, 2H and 6.83 m, 4H (2ꢁC6H4 and C6H5 (ODMTr)); 7.22 br s, 2H
(NH2); 4.97 m, 1H, J(10,20A)w1.0, J(10,20B)¼5.7, J(10,40aA)¼8.4,
J(10,40aB)¼2.4 (H-10); 4.56 m, 2H, 1.24 d, 3H, J¼6.1, 1.20 d, 3H, J¼6.1,
1.195 d, 3H, J¼6.1 and 1.16 d, 3H, J¼6.1 (P(OiPr)2); 3.72 s, 6H (2ꢁOMe
(ODMTr)); 3.63 br d, 1H, J(20A,10)w1.0, J(20A,20B)¼10.8 (H-20A); 3.41
dd, 1H, J(gem)¼14.8, J(H,P)¼18.8 and 2.66 dd, 1H, J(gem)¼14.8,
J(H,P)¼4.6 (N–CH2–P); 3.03 d, 2H, J(50A,40)wJ(50B,40)w5.2 (H-
50AþH-50B); 2.84 dd, 1H, J(20B,10)¼5.7, J(20B,20A)¼10.8 (H-20B); 2.81
m, 1H, J(40,40aA)¼8.8, J(40,40aB)¼7.0, J(40,50A)wJ(40,50B)w5.2 (H-40);
2.53 ddd, 1H, J(40aA,10)¼8.4, J(40aA,40aB)¼13.8, J(40aA,40)¼8.8 (H-
40aA); 1.71 ddd, 1H, J(40aB,10)¼2.4, J(40aB,40aA)¼13.8, J(40aB,40)¼7.0
(H-40aB).13C NMR (DMSO-d6): 158.28,158.20,144.97,135.85,135.77,
129.83 (2), 129.80 (2), 127.97 (2), 127.90 (2), 126.84 and 113.31 (4)
(2ꢁC6H4 and C6H5 (ODMTr)); 156.12 (C-4); 152.20 (C-2); 149.36 (C-
6); 138.73 (C-8); 118.83 (C-5); 85.55 (pCo (ODMTr)); 70.06 d,
J(C,P)¼6.3, 69.88 d, J(C,P)¼7.5, 24.05 d, J(C,P)¼3.8, 24.02 (2) d,
J(C,P)¼3.8 and 23.94 d, J(C,P)¼3.8 (P(OiPr)2); 65.0 (C-50); 64.10 d,
J(40,P)¼18.9 (C-40); 60.33 (C-20); 55.21 (2ꢁOMe (ODMTr)); 51.70 (C-
10); 49.92 d, J(C,P)¼162.2 (N–CH2–P); 35.56 (C-40a).
5.2.10. Diisopropyl 1-(thymin-1-yl)-5-O-dimethoxytrityl-1,2,3-
trideoxy-3-aza-4a-carba-b-L-glycero-pentofuranos-3-
ylmethylphosphonate (23d)
5.2.9. Diisopropyl 1-(cytosin-1-yl)-5-O-dimethoxytrityl-1,2,3-
The general procedure A was followed using mesylate 14a
(1.35 g, 2.00 mmol), Cs2CO3 (0.78 g, 2.40 mmol) and thymine
(0.38 g, 3.00 mmol). The reaction was complete after 3 h. White
foam (0.554 g, 39%). HRMS (FAB) calcd for C38H49N3O8P [MþH]þ
706.3257, found: 706.3269. IR nmax/cmꢂ1 (CHCl3): 1697, 1680 (thy-
mine); 1509, 1178, 1154, 1035 (–ODMTr); 1251, 1178, 1011, 991
(–CH2PO(OiPr)2). 1H NMR (DMSO-d6): 11.20 br s, 1H (NH); 7.76 q,
1H, J(6,Me)¼1.2 (H-6); 7.35 m, 2H, 7.28 m, 2H, 7.24 m, 2H, 7.22 m,
4H, 6.87 m, 2H and 6.86 m, 2H (2ꢁC6H4 and C6H5 (ODMTr)); 4.83 m,
1H, J(10,20A)ꢃ1.0, J(10,20B)¼6.6, J(10,40aA)¼9.2, J(10,40aB)¼3.0 (H-10);
4.55 m, 2H, 1.22 d, 3H, J¼6.1, 1.21 d, 3H, J¼6.2, 1.19 d, 3H, J¼6.2 and
1.14 d, 3H, J¼6.2 (P(OiPr)2); 3.72 s, 6H (2ꢁOMe (ODMTr)); 3.36 dd,
1H, 1H, J(gem)¼14.8, J(H,P)¼10.0 and 2.52 dd, 1H, J(gem)¼14.8,
J(H,P)¼5.0 (N–CH2–P); 3.33 br d, 1H, J(20A,10)ꢃ1.0, J(20A,20B)¼11.2
(H-20A); 3.05 d, 2H, J(50A,40)wJ(50B,40)w4.8 (H-50AþH-50B); 2.70 m,
1H, J(40,40aA)¼8.2, J(40,40aB)¼7.5, J(40,50A)wJ(40,50A)w4.8 (H-40);
2.65 dd, 1H, J(20B,10)¼6.6, J(20B,20A)¼11.2 (H-20B); 2.39 ddd, 1H,
J(40aA,10)¼9.2, J(40aA,40aB)¼14.0, J(40aA,40)¼8.2 (H-40aA); 1.50 ddd,
1H, J(40aB,10)¼3.0, J(40aB,40aA)¼14.0, J(40aB,40)¼7.5 (H-40aB); 1.62 d,
3H, J(Me,6)¼1.2 (5-Me). 13C NMR (DMSO-d6): 163.95 (C-2); 158.26,
158.22, 145.08, 135.76 (2), 129.90 (2), 129.87 (2), 128.00 (2), 127.89
(2), 126.89, 113.35 (2) and 113.32 (2ꢁC6H4 and C6H5 (ODMTr));
151.06 (C-4); 137.94 (C-6); 108.95 (C-5); 85.85 (pCo (ODMTr));
70.06 d, J(C,P)¼6.3, 69.84 d, J(C,P)¼6.3, 24.02 d, 3H, J(C,P)¼3.8,
23.96 d, 6H, J(C,P)¼3.8, 23.92 d, 3H, J(C,P)¼3.8 (P(OiPr)2); 64.55 (C-
50); 64.39 d, J(40,P)¼17.6 (C-40); 59.69 (C-20); 55.20 (2ꢁOMe
(ODMTr)); 52.22 (C-10); 49.83 d, J(C,P)¼163.5 (N–CH2–P); 35.19 (C-
40a); 12.57 (5-Me).
trideoxy-3-aza-4a-carba-b-L-glycero-pentofuranos-3-ylmethyl-
phosphonate (23b) and diisopropyl 1-(cytosin-2-O-yl)-5-O-
dimethoxytrityl-1,2,3-trideoxy-3-aza-4a-carba-b-L-glycero-
pentofuranos-3-ylmethylphosphonate (23c)
The general procedure A was followed using mesylate 14a
(1.41 g, 2.09 mmol), Cs2CO3 (0.82 g, 2.51 mmol) and cytosine
(0.35 g, 3.13 mmol). The reaction was complete after 4 h. Purifi-
cation by flash chromatography afforded N-alkylated 23b (white
foam, 0.388 g, 27%) and O-alkylated 23c (white foam, 0.475 g,
33%). Compound 23b: HRMS (FAB) calcd for C37H48N4O7P [MþH]þ
691.3261, found: 691.3259. IR nmax/cmꢂ1 (CHCl3): 1650, 1599, 1482,
1295 (cytosine); 1608, 1509, 1178, 1035 (–ODMTr); 2985, 1251,
1011, 990 (–CH2PO(OiPr)2). 1H NMR (DMSO-d6): 7.99 d, 1H,
J(6,5)¼7.4 (H-6); 7.36 m, 2H, 7.30 m, 2H, 7.23 m, 2H, 7.22 m, 3H
and 6.87 m, 4H (2ꢁC6H4 and C6H5 (ODMTr)); 7.04 br s, 1H and 6.96
br s, 1H (NH); 5.62 d, 1H, J(5,6)¼7.4 (H-5); 4.89 m, 1H, J(10,20A)w0,
J(10,20B)¼6.7, J(10,40aA)¼8.8, J(10,40aB)¼2.8 (H-10); 4.56 m, 2H, 1.23
d, 3H, J¼6.3, 1.22 d, 3H, J¼6.3, 1.20 d, 3H, J¼6.3 and 1.16 d, 3H,
J¼6.3 (P(OiPr)2); 3.73 s, 6H (2ꢁOMe (ODMTr)); 3.34 dd, 1H,
J(20A,10)w0, J(20A,20B)¼11.0 (H-20A); 3.30 dd, 1H, 1H, J(gem)¼14.9,
J(H,P)¼19.3 and 2.47 dd, 1H, J(gem)¼14.8, J(H,P)¼4.8 (N–CH2–P);
3.09 dd, 1H, J(50A,40)¼3.9, J(50A,50B)¼10.2 (H-50A); 2.95 dd, 1H,
J(50B,40)¼4.8, J(50B,50A)¼10.2 (H-50B); 2.63 m, 1H, J(40,40aA)¼9.0,
J(40,40aB)¼3.9, J(40,50A)¼3.9, J(40,50B)¼4.8 (H-40); 2.62 dd, 1H,
J(20B,10)¼6.7, J(20B,20A)¼11.0 (H-20B); 2.36 ddd, 1H, J(40aA,10)¼8.8,
J(40aA,40aB)¼14.0, J(40aA,40)¼9.0 (H-40aA); 1.47 ddd, 1H,
J(40aB,10)¼2.8, J(40aB,40aA)¼14.0, J(40aB,40)¼7.8 (H-40aB). 13C NMR