PAPER
Synthesis and Reactions of gem-Bis(phosphono)ethylenes
1975
Anal. Calcd for C17H31NO8P2S: C, 43.31; H, 6.63; N, 2.97; found:
C, 42.92; H, 6.67; N, 2.86.
agent. After a similar work-up as given above, the residue was chro-
matographed on silica gel (acetone) to give 9 in 66% yield.
IR (neat): 3544, 3486, 2996, 2939, 1581, 1481, 1388, 1253, 1047,
981, 948, 926, 817, 790, 640 cm–1.
[1-Halo-2-(1-imidazolyl)ethyl]-1,1-bis(diethylphosphonates) 7;
General Procedure
1H NMR (400 MHz, CDCl3): d = 1.27 (12 H, td, J = 7.1 Hz,
3JP-H = 10.2 Hz), 2.61 (1 H, td, J = 6.4 Hz, 1JP-H = 23.8 Hz), 3.25 (2
H, dd, J = 6.5 Hz, 2JP-H = 16.2 Hz), 4.07–4.31 (8 H, m), 7.22 (1 H,
dd, J = 4.8 Hz, 4JP-H = 7.8 Hz), 7.63 (1 H, td, J = 1.8 Hz, 4JP-H = 7.8
Hz), 8.47 (1 H, dd, J = 1.5 Hz, 5JP-H = 4.8 Hz), 8.52 (1 H, d, J = 2.0
Hz).
13C NMR (101 MHz, CDCl3): d = 16.1, 28.6, 38.8 (t, 3JP-C = 134.4
Hz), 62.4 (d, 3JP-C = 20.9 Hz), 62.6 (d, 3JP-C = 20.9 Hz), 122.8, 134.9
(m), 136.4, 147.6 (m), 150.1 (m).
To a suspension of KH or NaH (3.33 mmol) in THF (30 mL) was
added a solution of imidazole (227 mg, 3.33 mmol) in THF (5 mL)
at 0 °C under N2. After stirring the reaction mixture for 1 h at 0 °C
and then for 30 min at r.t., a solution of 2a (1.00 g, 3.33 mmol) in
THF (5 mL) was added to the cooled mixture at 0 °C. The reaction
mixture was stirred for 30 min, and then a solution of 18-crown-6
(176 g, 0.666 mmol) in THF (2 mL) was added. After stirring the
mixture for 30 min, a halogenating agent (Selectfluor or NCS, 5.00
mmol) was added. The mixture was stirred for 10 h, and the reaction
was quenched by the addition of a phosphate buffer (pH 7). The or-
ganic layer was extracted with EtOAc, and the extract was washed
with brine, dried (Na2SO4), and evaporated in vacuo. The residue
was chromatographed on silica gel (acetone–MeOH, 20:1) to give
7a,b.
MS (FAB+, 70 eV): m/z = 380 (M+ + H).
HRMS (FAB+): m/z calcd for C15H28NO6P2 (M+ + H): 380.1393;
found: 380.1405.
Halogenation of 9; General Procedure
To a suspension of KH (60 mg, 35wt% in mineral oil) in THF (4
mL) was added a solution of 9 (200 mg, 0.527 mmol) in THF (1 mL)
at 0 °C under N2. After stirring the reaction mixture at this temper-
ature for 1 h, and at r.t. for 30 min, a solution of 18-crown-6 (28 mg,
0.11 mmol) in THF (1 mL) was added followed by a halogenating
agent (Selectfluor or NCS, 0.791 mmol). The mixture was stirred at
0 °C for 10 h. After a similar work-up as given above for the one-
step preparation of 8, the residue was chromatographed on silica gel
(acetone) to give 8a,b.
[1-Chloro-2-(1-imidazolyl)ethyl]-1,1-bis(diethylphosphonate)
(7a)
IR (neat): 3459, 2969, 2917, 1267, 1066, 1051, 798 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.19–1.46 (12 H, m), 4.19–4.29 (8
H, m), 4.71 (2 H, dd, 2JP-H = 11 Hz), 7.00 (1 H, s), 7.11 (1 H, s), 7.62
(1 H, s).
13C NMR (101 MHz, CDCl3): d = 16.3 (dd, 3JP-C = 24.9, 36.1 Hz),
1
2
50.8, 61.0 (t, JP-C = 140.0 Hz), 64.7 (d, JP-C = 47.5 Hz), 121.2,
127.7, 138.9.
MS (FAB+, 70 eV): m/z = 403 (M+ + H).
[1-Chloro-2-(3-pyridyl)ethyl]-1,1-bis(diethylphosphonate) (8a)
IR (neat): 3513, 2987, 2931, 2910, 1637, 1585, 1479, 1427, 1392,
1263, 1162, 1004, 952, 813, 711 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.24 (6 H, dd, 3JP-H = 7.1 Hz), 1.33
(6 H, dd, 3JP-H = 7.1 Hz), 3.56 (2 H, dd, 3JP-H = 12.8 Hz), 4.17–4.27
(8 H, m), 7.23 (1 H, dd, J = 7.8 Hz), 7.78 (1 H, dd, td, J = 1.9, 7.9
Hz), 8.50 (1 H, dd, J = 4.8 Hz, 8.61 (1 H, d, J = 1.8 Hz).
Anal. Calcd for C13H25ClN2O6P2: C, 38.77; H, 6.26; N, 6.96; found:
C, 38.44; H, 6.35; N, 7.14.
[1-Fluoro-2-(1-imidazolyl)ethyl]-1,1-bis(diethylphosphonate)
(7b)
IR (neat): 3488, 2993, 1702, 1392, 1253, 1022, 970 cm–1.
3
13C NMR (101 MHz, CDCl3): d = 16.0 (dd, JP-C = 3.5, 6.2 Hz),
1H NMR (400 MHz, CDCl3): d = 1.30–1.38 (12 H, m), 4.15–4.26 (8
H, m), 4.64–4.76 (2 H, m), 7.01 (1 H, s), 7.03 (1 H, s), 7.56 (1 H, s).
1
2
37.6, 61.65 (t, JP-C = 143.0 Hz), 64.2 (dd, JP-C = 3.5 Hz), 122.1,
129.9 (dd, J = 8.0 Hz), 138.7, 147.9 (d, J = 10.3 Hz), 151.9.
13C NMR (101 MHz, CDCl3): d = 16.1 (m), 48.5 (d, JF-C = 19.2
2
MS (FAB+, 70 eV): m/z = 414 (M+ + H).
HRMS (FAB+): m/z calcd for C15H27ClNO6P2 (M+ + H) 414.1004;
1
1
Hz), 64.5 (m), 93.5 (td, JP-C = 153.1 Hz, JF-C = 195.6 Hz), 120.8
(m), 128.5 (m), 138.3 (m).
19F NMR (470 MHz, CDCl3): d = –31.5 (dt, JP-F = 69.6 Hz,
JH-F = 25.4 Hz).
found: 414.1014.
[1-Fluoro-2-(3-pyridyl)ethyl]-1,1-bis(diethylphosphonate) (8b)
IR (neat): 3455, 2981, 2935, 2912, 1637, 1577, 1481, 1427, 1390,
1268, 960, 852, 806, 748, 721 cm–1.
MS (FAB+, 70 eV): m/z = 387 (M+ + H).
HRMS (FAB+): m/z calcd for C13H26FN2O6P2 (M+ + H): 387.1252;
found: 387.1275.
1H NMR (400 MHz, CDCl3): d = 1.23–1.37 (12 H, m), 3.51 (2 H,
dd, 2JP-H = 12.4 Hz, 1JF-H = 27.4 Hz), 4.14–4.24 (8 H, m), 7.22 (1 H,
dd, J = 4.8, 7.7 Hz), 7.67 (1 H, d, J = 7.1 Hz), 8.50 (1 H, dd, J = 1.2,
4.7 Hz), 8.55 (1 H, s).
[1-Halo-2-(3-pyridyl)ethyl]-1,1-bis(diethylphosphonates) 8;
General Procedure
According to the established procedure,12 3-pyridyllithium was pre-
pared from 3-bromopyridine (1.05 g, 6.66 mmol, 0.64 mL) using n-
BuLi (6.66 mmol, 4.2 mL, 1.57 M in hexane) in THF (6 mL) and
toluene (65 mL). To a cooled solution of 3-pyridyllithium at –60 °C
in toluene–THF was added a solution of 2a (2 g, 6.66 mmol) in THF
(10 mL). After stirring the mixture for 1 h, a halogenating agent
(NCS or Selectfluor) was added. The reaction mixture was stirred at
this temperature for 15 min and at r.t. for 3 h. A similar work-up as
that given for the preparation of 7 afforded a residue that was chro-
matographed on silica gel (acetone) to give the compounds 8a,b
(see below for spectral data).
13C NMR (101 MHz, CDCl3): d = 16.1 (dd, 3JP-C = 27.4, 28.6 Hz),
2
2
35.6 (d, JP-C = 19.3 Hz), 63.7 (d, JP-C = 39.4 Hz), 94.3 (dd,
1JP-C = 155.9 Hz, 1JF-C = 192.8 Hz), 122.6 (d, J = 10.6 Hz), 129.8 (d,
J = 9.0 Hz), 138.4 (d, J = 15.2 Hz), 147.9 (d, J = 26.7 Hz), 151.5 (d,
J = 28.6 Hz).
19F NMR (470 MHz, CDCl3): d = –31.6 (dt, JP-F = 72.5 Hz,
JH-F = 26.8 Hz).
MS (FAB+, 70 eV): m/z = 387 (M+ + H).
HRMS (FAB+): m/z Calcd for C15H27FNO6P2 (M+ + H): 387.1252;
found: 387.1275.
[2-(3-Pyridyl)ethyl]-1,1-bis(diethylphosphonate) (9)
The reaction was carried out in a similar manner as for the prepara-
tion of 8 using phosphate buffer (pH 7) instead of a halogenating
Anal. Calcd for C15H26FNO6P2: C, 45.34; H, 6.60; N, 3.53. Found:
C, 45.04; H, 6.73; N, 3.54.
Synthesis 2003, No. 13, 1971–1976 © Thieme Stuttgart · New York