S. Doherty et al. / Tetrahedron: Asymmetry 20 (2009) 1437–1444
1441
MeOH (100:4). 31P{1H} NMR (202.5 MHz, CDCl3, d): 28.8; 1H NMR
(300.0 MHz, CDCl3, d): 7.48 (d, J = 8.5 Hz, 2H, C6H4), 7.36 (d,
J = 8.5 Hz, 2H, C6H4), 5.86 (s, 2H, NH2), 4.06 (d, J = 11.9 Hz, 1H,
@CH), 3.70 (d, J = 11.3 Hz, 6H, OCH3); 13C{1H} NMR (75.8 MHz,
CDCl3, d): 161.8 (d, J = 7.0 Hz, @CNH2), 137.5 (d, J = 21.1 Hz,
C6H4), 136.2 (C6H4), 129.0 (C6H4), 127.5 (C6H4), 74.1 (d,
J = 193 Hz, PC@C), 51.8 (d, J = 5.1 Hz, OCH3); LRMS (ESI+) m/z 262
[M+H]+; HRMS (ESI+) exact mass calcd for C10H14ClNO3P [M+H]+ re-
quires m/z 262.0400, found m/z 262.0397.
m/z 284.1052, found m/z 284.1049. (Z)-4a. 31P{1H} NMR
(202.5 MHz, CDCl3, d): 22.1; 1H NMR (300.0 MHz, CDCl3, d): 9.89
(s, 1H, NH), 7.16 (d, J = 7.9 Hz, 2H, C6H4), 7.01 (d, J = 7.6 Hz, 2H,
C6H4), 4.75 (d, J = 11.7 Hz, 1H, @CH), 3.58 (d, J = 11.4 Hz, 6H,
OCH3), 2.22 (s, 3H, CH3), 1.98 (s, 3H, C6H4CH3); 13C{1H} NMR
(75.8 MHz, CDCl3, d): 168.1 (C@O), 157.3 (d, J = 3.0 Hz, C@CP),
140.3 (C6H4), 134.7 (d, J = 18.9 Hz, C6H4), 129.3 (C6H4), 127.0
(C6H4), 94.1 (d, J = 185 Hz, C@CP), 51.9 (d, J = 5.4 Hz, OCH3), 23.9
(CH3), 20.8 (C6H4CH3); LRMS (ESI+) m/z 284 [M+H]+; HRMS (ESI+)
exact mass calcd for C13H19NO4P [M+H]+ requires m/z 284.1052,
found m/z 284.1049. Anal. Calcd for C13H18NO4P: C, 55.12; H,
6.41; N, 4.94. Found: C, 55.32; H, 6.69; N, 5.12.
4.2.4. Dimethyl 2-amino-2-p-bromophenylvinylphosphonate
3e
Enamino phosphonate 3e was prepared according to the proce-
dure described above for 3a on the same scale and isolated as an
analytically and spectroscopically pure solid in 66% yield (7.07 g)
after purification by column chromatography eluting with CHCl3/
MeOH (100:4). 31P{1H} NMR (202.5 MHz, CDCl3, d): 28.6; 1H NMR
(300.0 MHz, CDCl3, d): 7.43 (d, J = 8.1 Hz, 2H, C6H4), 7.35 (d,
J = 8.5 Hz, 2H, C6H4), 5.94 (s, 2H, NH2), 3.95 (d, J = 12.0 Hz, 1H,
@CH), 3.61 (d, J = 11.3 Hz, 6H, OCH3); 13C{1H} NMR (75.8 MHz,
CDCl3, d): 161.7 (d, J = 6.9 Hz, @CNH2), 137.6 (d, J = 21.1 Hz, C6H4),
131.7 (C6H4), 127.6 (C6H4), 124.0 (C6H4), 73.3 (d, J = 195.0 Hz,
PC@C), 51.5 (d, J = 5.1 Hz, OCH3); LRMS (ESI+) m/z 306 [M+H]+;
HRMS (ESI+) exact mass calcd for C10H14BrNO3P [M+H]+ requires
m/z 305.9895, found m/z 305.9898.
4.3.2. (E)- and (Z)-Dimethyl 2-acetylamino-2-
phenylvinylphosphonate 4b
(E)- and (Z)-4b were prepared according to the procedure de-
scribed above for 4a on the same scale and isolated as an analyti-
cally and spectroscopically pure oil after purification by column
chromatography eluting with CHCl3/MeOH (100:4). (E)-4b: Rf-va-
lue 0.3; 1.13 g (42%). 31P{1H} NMR (202.5 MHz, CDCl3, d): 22.7;
1H NMR (300.0 MHz, CDCl3, d): 7.90 (s, 1H, NH), 7.38 (m, 5H,
C6H5), 6.74 (d, J = 12.0 Hz, 1H, @CH), 3.33 (d, J = 11.2 Hz, 6H,
OCH3), 2.01 (s, 3H, CH3); 13C{1H} NMR (75.8 MHz, CDCl3, d):
167.9 (C@O), 149.6 (d, J = 16.7 Hz, C@CP), 134.7 (d, J = 6.2 Hz,
C6H5), 129.5 (C6H5), 128.5 (C6H5), 128.1 (C6H5), 95.2 (d,
J = 202 Hz, C@CP), 50.1 (d, J = 6.1 Hz, OCH3), 24.6 (CH3); LRMS
(ESI+) m/z 270 [M+H]+; HRMS (ESI+) exact mass calcd for
C12H17NO4P [M+H]+ requires m/z 270.0895, found m/z 270.0898.
(Z)-4b: Rf-value 0.3; 0.59 g (22%). 31P{1H} NMR (202.5 MHz, CDCl3,
d): 22.6; 1H NMR (300.0 MHz, CDCl3, d): 10.1 (s, 1H, NH), 7.35 (m,
5H, C6H5), 4.81 (d, J = 11.6 Hz, 1H, @CH), 3.73 (d, J = 11.4 Hz, 6H,
OCH3), 2.12 (s, 3H, CH3); 13C{1H} NMR (75.8 MHz, CDCl3, d):
168.3 (C@O), 157.8 (d, J = 3.1 Hz, C@CP), 137.1 (d, J = 18.9 Hz,
C6H5), 129.4 (C6H5), 128.0 (C6H5), 126.7 (C6H5), 94.7 (d,
J = 184 Hz, C@CP), 52.2 (d, J = 5.3 Hz, OCH3), 24.2 (CH3); LRMS
(ESI+) m/z 270 [M+H]+; HRMS (ESI+) exact mass calcd for
C12H16NO4PNa [M+H]+ requires m/z 270.0895, found m/z
270.0903. Anal. Calcd for C12H16NO4P: C, 53.53; H, 5.99; N, 5.20.
Found: C, 53.91; H, 6.22; N, 5.51.
4.2.5. Dimethyl 2-amino-2-p-methoxyphenylvinylphosphonate
3f
Enamino phosphonate 3f was prepared according to the proce-
dure described above for 3a on the same scale and isolated as an
analytically and spectroscopically pure solid in 54% yield (4.86 g)
after purification by column chromatography eluting with CHCl3/
MeOH (100:4). 31P{1H} NMR (202.5 MHz, CDCl3, d): 28.8; 1H NMR
(300.0 MHz, CDCl3, d): 7.47 (d, J = 6.7 Hz, 2H, C6H4), 6.88 (d,
J = 7.7 Hz, 2H, C6H4), 5.85 (s, 2H, NH2), 4.01 (d, J = 12.3 Hz, 1H,
@CH), 3.83 (s, 3H, CH3O), 3.69 (d, J = 11.3 Hz, 6H, OCH3); 13C{1H}
NMR (75.8 MHz, CDCl3, d): 162.7 (d, J = 6.7 Hz, @CNH2), 161.4
(C6H4), 131.3 (d, J = 20.8 Hz, C6H4), 127.5 (C6H4), 114.1 (C6H4),
72.1 (d, J = 194.2 Hz, PC@C), 55.3 (p-OMe) 51.7 (d, J = 5.0 Hz,
OCH3); LRMS (ESI+) m/z 258 [M+H]+; HRMS (ESI+) exact mass calcd
for C11H17NO4P [M+H]+ requires m/z 258.0895, found m/z
258.0899.
4.3.3. (E)- and (Z)-Dimethyl 2-acetylamino-2-p-
fluorophenylvinylphosphonate 4c
4.3. Synthesis of (E)- and (Z)-dimethyl 2-acetylamino-2-
arylvinylphosphonate 4a–f
(E)- and (Z)-4c were prepared according to the procedure de-
scribed above for 4a on the same scale and isolated as an analyti-
cally and spectroscopically pure oil after purification by column
chromatography eluting with CHCl3/MeOH (100:4). (E)-4c: Rf-va-
lue 0.3; 1.49 g (52%). 31P{1H} NMR (202.5 MHz, CDCl3, d): 22.3;
1H NMR (300.0 MHz, CDCl3, d): 7.85 (s, 1H, NH), 7.38 (m, 2H,
C6H4), 7.04 (m, 2H, C6H4), 6.72 (d, J = 11.9 Hz, 1H, @CH), 3.39 (d,
J = 11.2 Hz, 6H, OCH3), 2.04 (s, 3H, CH3); 13C{1H} NMR (75.8 MHz,
CDCl3, d): 170.0 (C@O), 163.6 (d, J = 250 Hz, C6H4), 150.1 (d,
J = 16.3 Hz, C@CP), 132.7 (C6H4), 130.7 (d, J = 8.8 Hz, C6H4), 115.2
(d, J = 21.9 Hz, C6H4), 98.3 (d, J = 202 Hz, PC@C), 51.8 (d,
J = 5.9 Hz, OCH3), 24.9 (CH3); LRMS (ESI+) m/z 288 [M+H]+; HRMS
(ESI+) exact mass calcd for C12H15FNO4P [M+H]+ requires m/z
288.0801, found m/z 288.0804. (Z)-4c: Rf-value 0.3; 0.48 g (17%).
31P{1H} NMR (202.5 MHz, CDCl3, d): 22.3; 1H NMR (300.0 MHz,
CDCl3, d): 10.5 (s, 1H, NH), 7.30 (m, 2H, C6H4), 6.97 (m, 2H, C6H4),
4.79 (d, J = 11.2 Hz, 1H, @CH), 3.77 (d, J = 11.3 Hz, 6H, OCH3), 2.08
(s, 3H, CH3); 13C{1H} NMR (75.8 MHz, CDCl3, d): 167.5 (C@O),
162.7 (d, J = 250 Hz, C6H4), 155.7 (d, J = 3.2 Hz, C@CP), 132.3 (d,
J = 19.3 Hz, C6H4), 127.9 (d, J = 8.4 Hz, C6H4), 114.2 (d, J = 22.0 Hz,
C6H4), 93.9 (d, J = 185 Hz, PC@C), 51.9 (d, J = 5.4 Hz, OCH3), 24.3
4.3.1. (E)- and (Z)-Dimethyl 2-acetylamino-2-p-
tolylvinylphosphonate 4a
Enamino phosphonate 4a (1.96 g, 10 mmol) was dissolved in a
mixture of dichloromethane (20 mL) and pyridine (3.96 mL,
50 mmol) and cooled to ꢀ78 °C. Acetyl chloride (2.36 g, 30 mmol)
was added dropwise with vigorous stirring and the resulting solu-
tion stirred for 2 h. The suspension was filtered through a pad of
Celite, washed with CuSO4(aq) (3 ꢂ 50 mL) and brine (3 ꢂ 50 mL),
and dried over sodium sulfate. The solvent was removed in vacuo
and the residue purified by column chromatography by eluting
with CHCl3/MeOH (100:4). (E)-4a: Rf-value 0.3; 1.53 g (54%) pale
yellow oil. 31P{1H} NMR (202.5 MHz, CDCl3, d): 22.3; 1H NMR
(300.0 MHz, CDCl3, d): 8.03 (s, 1H, NH), 7.27 (d, J = 7.9 Hz, 2H,
C6H4), 7.13 (d, J = 7.9 Hz, 2H, C6H4), 6.66 (d, J = 12.1 Hz, 1H, @CH),
3.33 (d, J = 11.2 Hz, 6H, OCH3), 2.32 (s, 3H, CH3), 1.98 (s, 3H,
C6H4CH3); 13C{1H} NMR (75.8 MHz, CDCl3, d): 169.5 (C@O), 151.3
(d, J = 16.7 Hz, C@CP), 139.7 (C6H4), 133.5 (d, J = 6.2 Hz, C6H4),
128.7 (C6H4), 128.4 (C6H4), 97.4 (d, J = 202 Hz, C@CP), 51.6 (m,
OCH3), 24.5 (CH3), 21.1 (C6H4CH3); LRMS (ESI+) m/z 284 [M+H]+;
HRMS (ESI+) exact mass calcd for C13H19NO4P [M+H]+ requires