A. E. Wro´blewski, K. B. Balcerzak / Tetrahedron: Asymmetry 13 (2002) 845–850
849
1
1230, 1026, 752 and 701 cm−1; H NMR (300 MHz,
CDCl3): l=7.35–7.14 (m, 15H), 4.70 (d, J=11.1 Hz,
1H); 4.25–4.10 (m, 5H), 4.11 (d, J=11.1 Hz, 1H), 3.78
(dd, J=7.1 Hz, J=2.4 Hz, 1H, H-1), 3.60 and 3.55 (AB,
In a similar fashion, from (1S,2R)-8b (250 mg, 0.502
mmol), the acetate (1S,2R)-9b was obtained as a colorless
oil (219 mg, 80%). [h]D=+37.5 (c=0.841, CHCl3); IR
(film): w=3086, 2982, 2931, 2910, 2799, 1738, 1240, 1039,
1
J
AB=13.5 Hz, 4H), 2.66 (ddAB, JAB=12.8 Hz, J=7.2
968, 747 and 699 cm−1; H NMR (300 MHz, CDCl3):
Hz, J=1.2 Hz, 1H, H-3a), 2.58 (dAB, JAB=12.8Hz,
J=6.4 Hz, 1H, H-3b), 1.32 and 1.30 (2t, J=6.9 Hz, 6H):
13C NMR (75.5 MHz, CDCl3): l=138.74, 137.41,
129.30, 128.45, 128.38, 128.33, 127.94, 127.30, 75.29 (d,
J=164.0 Hz, C-1), 74.67 (d, J=2.0 Hz), 67.92 (d, J=2.0
Hz, C-2), 62.80 and 62.60 (2d, J=6.9 Hz), 58.65, 56.04
(d, J=12.0 Hz, C-3), 16.83 (d, J=5.7 Hz); 31P NMR
(121.5 MHz, CDCl3): l=23.18. Anal. calcd for
C28H36NO5P: C, 67.58; H, 7.31; N, 2.81. Found: C, 67.58;
H, 7.36; N, 2.95%.
l=7.35–7.19 (m, 15H), 5.42 (dddd, J=10.7 Hz, J=7.7
Hz, J=4.8 Hz, J=2.7 Hz, 1H, H-2), 4.66 and 4.54 (AB,
J=11.7 Hz, 2H), 4.15–4.00 (m, 4H), 3.85 (dd, J=12.8
Hz, J=2.7 Hz, 1H, H-1), 3.75 and 3.43 (AB, J=13.7 Hz,
4H), 2.92 (dAB, J=14.4 Hz, J=4.8 Hz, 1H, H-3a), 2.88
(dAB, J=14.4 Hz, J=7.7 Hz, 1H, H-3b), 1.98 (s, 3H),
1.29 and 1.27 (2t, J=7.0 Hz, 6H); 13C NMR (75.5 MHz,
CDCl3): l=170.13, 139.40, 137.12, 129.08, 128.41,
128.37, 128.19, 128.02, 126.94, 76.05 (d, J=164.0 Hz,
C-1), 74.47 (d, J=6.3 Hz, OCH2Ph), 71.40 (d, J=9.4 Hz,
C-2), 62.91 and 62.75 (2d, J=7.0 Hz), 58.88, 53.44 (s,
C-3), 21.46, 16.81 and 16.73 (2d, J=5.6 Hz); 31P NMR
(121.5 MHz, CDCl3): l=19.73. Anal. calcd for
C30H38NO6P: C, 66.77; H, 7.11; N, 2.59. Found: C, 66.98;
H, 7.15; N, 2.89%.
In a similar fashion, from (1S,2R)-2b (299 mg, 0.996
mmol) and dibenzylamine (0.201 mL, 1.045 mmol),
(1S,2R)-8b (360 mg, 73%) was obtained as a white solid
after crystallisation from heptane–ether. Mp 56–57°C;
[h]D=+45.4 (c=0.82, CHCl3); IR (KBr): w=3314, 3030,
2977, 2926, 2866, 1226, 1059, 750 and 700 cm−1; 1H NMR
(300 MHz, CDCl3): l=7.40–7.20 (m, 13H), 7.18–7.10
(m, 2H), 4.59 and 4.52 (AB, JAB=11.3 Hz, 2H), 4.16–
4.02 (m, 5H), 3.90 (dd, J=12.0 Hz, J=3.4 Hz, 1H, H-1),
3.85 (d, J=13.5 Hz, 2H), 3.75 (brs, 1H), 3.44 (d, J=13.5
Hz, 2H), 2.88 (dAB, JAB=13.0 Hz, J=10.0 Hz, 1H,
H-3a), 2.77 (dAB, J=13.0 Hz, J=3.8 Hz, 1H, H-3b),
1.28 (t, J=7.0 Hz, 6H); 13C NMR (75.5 MHz, CDCl3);
l=138.53, 137.56, 129.26, 128.67, 128.49, 128.26, 127.79,
127.33, 77.06 (d, J=163.2 Hz, C-1), 75.40 (d, J=7.2 Hz),
67.92 (d, J=10.6 Hz, C-2), 63.07 and 62.45 (2d, J=6.9
Hz), 58.67, 54.36 (d, J=3.7 Hz, C-3), 16.82 and 16.77 (2d,
J=5.4 Hz); 31P NMR (121.5 MHz, CDCl3): l=21.60.
Anal. calcd for C28H36NO5P: C, 67.58; H, 7.31; N, 2.81.
Found: C, 67.48; H, 7.24; N, 3.08%.
4.6. Diethyl (1R,2R)-3-acetamido-1,2-dihydroxypropyl-
phosphonate 10a
A solution of (1R,2R)-9a (0.442 g, 0.819 mmol) in
anhydrous ethanol (5 mL) was hydrogenated over
Pd(OH)2/C (20%, 136 mg) at room temperature for 6
days. The catalyst was removed by filtration, the solu-
tion was concentrated, and the residue was chro-
matographed on
a
silica gel column with
chloroform:methanol (20:1, v/v) to give (1R,2R)-10a as
a colorless oil (0.170 g, 77%). [h]D=+19.0 (c=0.98,
CHCl3); IR (film): w=3285, 2984, 2921, 2852, 1648,
1559, 1218, 1045, 971 cm−1; 1H NMR (300 MHz,
CDCl3): l=6.40 (brt, J=5.5 Hz, 1H), 4.23 (qu, J=7.1
Hz, 2H), 4.19 (dq, J=7.3 Hz, J=7.1 Hz, 2H), 4.3–4.1
(brs, 2H), 4.01 (dddd, J=7.1 Hz, J=6.1 Hz, J=3.5 Hz,
J=3.0 Hz, 1H, H-2), 3.85 (dd, J=11.0 Hz, J=3.0 Hz,
1H, H-1), 3.65 (ddd, J=14.0 Hz, J=7.1 Hz, J=5.5 Hz,
1H, H-3b), 3.32 (ddd, J=14.0 Hz, J=6.1 Hz, J=5.5
Hz, 1H, H-3a), 2.02 (s, 3H), 1.36 (t, J=7.1 Hz, 6H);
13C NMR (75.5 MHz, CDCl3): l=171.92, 69.82 (d,
J=2.0 Hz, C-2), 68.99 (d, J=163.8 Hz, C-1), 63.64 and
62.99 (2d, J=7.2 Hz), 42.57 (d, J=12.9 Hz, C-3), 16.73
and 16.69 (2d, J=5.7 Hz); 31P NMR (121.5 MHz,
CDCl3): l=23.09. Anal. calcd for C9H20NO6P: C,
40.14; H, 7.50; N, 5.20. Found: C, 39.87; H, 7.19; N,
5.02%.
4.5. Diethyl (1R,2R)-2-acetyloxy-3-(N,N-dibenzyl-
amino)-1-benzyloxypropyl-phosphonate 9a
Standard acetylation of (1R,2R)-8a (88 mg, 0.18 mmol)
with acetic anhydride (20.0 mL, 0.22 mmol) in the
presence of NEt3 (38.0 mL, 0.27 mmol) and DMAP (one
crystal) in CH2Cl2 (1 mL) gave after chromatography on
a silica gel column (1R,2R)-9a as a colorless oil (70 mg,
73%). [h]D=−11.3 (c=1.42, CHCl3); IR (film): w=2982,
2915, 2836, 1738, 1239, 1045, 1026, 969, 739, 698 cm−1;
1H NMR (300 MHz, CDCl3): l=7.38–7.17 (m, 15H),
5.37 (dddd, J=7.3 Hz, J=6.8 Hz, J=5.7 Hz, J=2.5 Hz,
1H, H-2), 4.74 (d, J=11.5 Hz, 1H), 4.23–4.04 (m, 4H),
4.02 (d, J=11.5 Hz, 1H), 3.96 (dd, J=8.5 Hz, J=2.5 Hz,
1H, H-1), 3.64 and 3.49 (AB, J=13.1 Hz, 4H), 2.83 (dd,
J=13.1 Hz, J=7.3 Hz, 1H, H-3a), 2.58 (ddd, J=13.1 Hz,
J=5.7 Hz, J=3.2 Hz), (1H, H-3b), 2.05 (s, 3H), 1.28 (t,
J=7.0 Hz, 6H); 13C NMR (75.5 MHz, CDCl3): l=
170.13, 139.01, 137.50, 129.25, 128.36, 128.28, 128.27,
127.86, 127.19, 74.93 (d, J=1.7 Hz, OCH2Ph), 74.38 (d,
J=167.5 Hz, C-1), 70.12 (s, C-2), 63.16 and 62.39 (2d,
J=7.1 Hz), 58.76, 53.82 (d, J=9.7 Hz, C-3), 21.43, 16.85
and 16.77 (2d, J=5.5 Hz); 31P NMR (121.5 MHz,
CDCl3): l=20.77. Anal. calcd for C30H38NO6P: C,
66.77; H, 7.11; N, 2.59. Found: C, 67.01; H, 7.35; N,
2.32%.
In a similar manner, from (1S,2R)-9b (0.260 g, 0.491
mmol), the acetamide (1S,2R)-10b (0.098 g, 74%) was
obtained as an almost colorless oil. [h]D=−77.2 (c=
1.01, CHCl3); IR (film): w=3304, 2985, 2913, 1643,
1556, 1226, 1044, 970 cm−1; 1H NMR (300 MHz,
CDCl3): l=6.29 (brt, J=4.8 Hz, 1H), 5.33 (dd, J=27.0
Hz, J=5.3 Hz, 1H, HOC-1), 4.35–4.15 (m, 5H), 4.05–
3.90 (m, 2H, H-2, H-3b), 3.58 (dt, J=10.0 Hz, J=10.0
Hz, J=5.3 Hz, 1H, H-1), 3.19 (dddd, J=14.7 Hz,
J=4.8 Hz, J=3.0 Hz, J=3.0 Hz, 1H, H-3a), 2.08 (s,
3H), 1.38 and 1.37 (2t, J=7.0 Hz, 6H); 13C NMR (75.5
MHz, CDCl3): l=172.0, 69.25 (d, J=2.9 Hz, C-2),
66.25 (d, J=164.0 Hz, C-1), 62.40 and 62.08 (2d, J=7.0
Hz), 40.21 (d, J=13.5 Hz, C-3), 21.77, 15.45 and 15.37