CDCl3) d 15.8 (C-2¢), 63.9 (dt, J = 17.7, 2.7 Hz, Hz, C-1¢), 82.78
(dt, J = 192.0, 157.1 Hz, C-1), 31P NMR (202.46 MHz, CDCl3) d
11.08 (d, J = 74.6 Hz); HRMS (ESI) calcd for (C9H21O6P2F) [M +
Na]+: 329.0695; found 329.0697.
(500.13 MHz, CDCl3) d 0.88 (t, J = 6.9 Hz, 3H, H-7), 1.30 (m,
6H, H-4, H-5, H-6), 1.36 (t, J = 7.1 Hz, 12H, H-2¢), 1.64 (m, 2H,
H-3), 2.15 (m, 2H, H-2), 4.26 (m, 8H, H-1¢); 13C NMR (125.77
MHz, CDCl3) d 13.98 (C-7), 16.38 (p, J = 2.7 Hz, C-2¢), 22.45
(C-6), 22.84 (q, J = 5.4 Hz, C-3), 29.59 (C-5), 31.38 (C-4), 33.21
(d, J = 20.1 Hz, C-2), 63.78 (dt, J = 27.2, 3.2 Hz, C-1¢), 95.84 (dt, J
= 188.0, 156.2 Hz, C-1); 31P NMR (202.46 MHz, CDCl3) d 14.76
(d, J = 75.1 Hz). Calcd for (C15H34FO6P2) [M + Na]+: 413.1634;
found: 413.1635.
Tetraethyl 1-(fluoroethylidene)-1,1-bisphosphonate (26). 43%
yield; colorless oil; IR (film, cm-1) 2984, 2935, 2874, 1445, 1393,
1369, 1256, 1165, 1024, 970, 845, 816, 793, 536; 1H NMR (500.13
MHz, CDCl3) d 1.37 (d, J = 7.1 Hz, 12H, H-2¢), 1.83 (dt, J =
25.7, 15.4 Hz, 3H, H-2), 4.28 (m, 8H, H-1¢);13C NMR (125 MHz,
CDCl3) d 16.4 (dd, J = 7.1, 2.9 Hz, C-2), 19.1 (d, J = 20.9 Hz,
C-2¢), 64.0 (dt, J = 28.0, 3.2 Hz, C-1¢), 93.0 (dt, J = 183.9, 160.5
Hz, C-1); 31P NMR (202.46 MHz, CDCl3) d 14.92 (d, J = 72.1
Hz). HRMS (ESI) calcd for (C10H24O6P2F) [M + H]+: 321.1032;
found 321.1022.
Tetraethyl 1-(fluoro-n-octylidene)-1,1-bisphosphonate (32).
48% yield; colorless oil; IR (film, cm-1) 2982, 2959, 2930, 2858,
2358, 1452, 1393, 1258, 1165, 1026, 970, 797, 580, 538; 1H NMR
(500.13 MHz, CDCl3) d 0.90 (t, J = 7.0 Hz, 3H, H-8), 1.30 (t, J
= 7.1 Hz, 12H, H-2¢), 2.15 (dtt, J = 23.8, 15.3, 8.4 Hz, 2H, H-2),
4.27 (m, 8H, H-1¢); 13C NMR (125.77 MHz, CDCl3) d 14.06
(C-8), 16.46 (p, J = 3.1 Hz, C-2¢), 22.59 (C-7), 22.96 (q, J = 5.3
Hz, C-3), 28.90 (C-6), 29.93 (C-5), 31.70 (C-4), 33.27 (d, J = 19.8
Hz, C-2), 63.87 (dt, J = 27.3, 2.8 Hz, C-1¢), 95.84 (dt, J = 188.0,
156.2 Hz, C-1); 31P NMR (202.46 MHz, CDCl3) d 14.58 (d, J =
74.6 Hz). (F8OEt) HRMS (ESI) calcd for (C16H36O6P2F) [M +
H]+: 405.1971; found 405.1977.
Tetraethyl 1-(fluoro-n-propylidene)-1,1-bisphosphonate (27).
36% yield; colorless oil; IR (film, cm-1) 2981, 2933, 1444, 1394,
1
1369, 1263, 1164, 1022, 972, 784, 769; H NMR (500.13 MHz,
CDCl3) d 1.17 (t, J = Hz, 3H, H-3), 1.37 (t, J = Hz, 12H, H-2¢),
2.24 (m, 2H, H-2), 4.29 (m, 8H, H-1¢); 13C NMR (125.77 MHz,
CDCl3) d 7.8 (dd, J = 12.7, 4.6 Hz), 16.4 (dt, J = 5.9, 3.0 Hz), 26.5
(d, J = 20.9 Hz, C-2¢), 63.8 (dt, J = 28.2, 3.2 Hz, C-1¢); 31P NMR
(202.46 MHz, CDCl3) d 15.00 (d, J = 74.6 Hz). HRMS (ESI)
calcd for (C11H25FO6P2Na) [M + Na]+: 357.1008; found 357.1013.
Tetraethyl 1-(fluoro-n-nonylidene)-1,1-bisphosphonate (33).
24% yield; colorless oil; IR (film, cm-1) 2981, 2959, 2928, 2856,
1
1467, 1392, 1369, 1261, 1163, 1024, 974, 797, 663, 577, 540; H
Tetraethyl 1-(fluoro-n-butylidene)-1,1-bisphosphonate (28).
47% Yield; Colorless oil; IR (film, cm-1) 2981, 2935, 2875, 1649,
1444, 1392, 1369, 1261, 1164, 1022, 972, 794, 746; 1H NMR
(500.13 MHz, CDCl3) d 0.97 (t, J = 7.3 Hz, 3H, H-4), 1.38 (t,
J = 7.0 Hz, 12H, H-2¢), 1.68 (m, 2H, H-3), 2.14 (dtt, J = 47.0,
15.1, 8.6 Hz, 2H, H-2), 4.25 (m, 8H, H-1¢); 13C NMR (125.77
MHz, CDCl3) d 14.52 (C-4), 16.43 (p, J = 2.9 Hz, C-2¢), 16.54
(q, J = 5.4 Hz), 35.29 (d, J = 20.0 Hz), 63.87 (dt, J = 27.4, 2.4
Hz, C-1¢), 95.86 (dt, J = 187.3, 156.2 Hz, C-1); 31P NMR (202.46
MHz, CDCl3) d 14.52 (d, J = 74.6 Hz). HRMS (ESI) calcd for
(C12H28FO6P2) [M + H]+: 349.1345; found: 349.1348.
NMR (500.13 MHz, D2O) d 0.88 (t, J = 7.0 Hz, 3H, H-9), 1.30
(m, 10H), 1.37 (t, J = 7.1 Hz, 12H, H-2¢), 1.64 (p, J = 7.3 Hz,
2H, H-3), 2.15 (dtt, J = 47.3, 15.3, 8.3 Hz, 2H, H-2), 4.27 (m,
8H, H-1¢); 13C NMR (125.77 MHz, CDCl3) d 14.06 (C-9), 16.43
(p, J = 2.7 Hz, C-2 ), 22.62 (C-8), 22.93 (q, J = 5.4 Hz, C-3),
29.15 (C-7), 29.19 (C-6), 29.98 (C-5), 31.80 (C-4), 33.25 (d, J =
20.1 Hz, C-2), 63.83 (dt, J = 27.3, 2.7 Hz, C-1¢); 31P NMR (202.46
MHz, CDCl3) d 15.01 (d, J = 74.6 Hz). HRMS (ESI) calcd for
(C17H38O6P2F) [M + H]+: 419.2128; found 419.2131.
Tetraethyl 1-(fluoro-n-decylidene)-1,1-bisphosphonate (34).
33% yield; colorless oil; IR (film, cm-1) 2982, 2961, 2926, 2856,
Tetraethyl 1-(fluoro-n-pentylidene)-1,1-bisphosphonate (29).
1
1468, 1450, 1393, 1369, 1261, 1165, 1024, 976, 797, 663, 540; H
49% yield; colorless oil; IR (film, cm-1) 2964, 2934, 2874, 1445,
NMR (500.13 MHz, CDCl3) d 0.90 (t, J = 6.9 Hz, 3H, H-10), 1.32
(m, 6H, CH2), 1.39 (t, J = 7.1 Hz, 8H, H-2¢), 1.63 (m, 2H, H-3),
2.12 (dtt, J = 47.4, 15.4, 8.4 Hz, 2H, H-2), 4.26 (m, 8H, H-1¢);13C
NMR (125.77 MHz, CDCl3) d 14.1 (C-10), 16.5 (p, J = 2.9 Hz,
C-2¢), 22.6 (C-9), 23.0 (q, J = 5.5 Hz, C-3), 29.2 (C-6), 29.5 (C-7),
30.0 (C-5), 31.9 (C-4), 33.3 (d, J = 19.6 Hz, C-2), 63.9 (dt, J =
27.9, 3.2 Hz, C-1¢); 31P NMR (202.46 MHz, CDCl3) d 14.78 (d, J
= 74.6 Hz). HRMS (ESI) calcd for (C10H39O6P2FNa) [M + Na]+:
455.2104; found 455.2105.
1
1393, 1261, 1165, 1024, 975, 797, 540; H NMR (500.13 MHz,
CDCl3) d 0.93 (t, J = 7.4 Hz, 3H, H-5), 1.37 (t, J = 7.1 Hz, 12H,
H-2¢), 1.70 (br s, 2H), 2.17 (m, 2H, H-2), 4.27 (m, 8H, H-1¢); 13
C
NMR (125.77 MHz, CDCl3) d 13.76, 14.43 (q, J = 2.9 Hz, C-2¢),
23.09, 25.04 (t, J = 5.5. Hz), 32.99 (d, J = 20.1 Hz), 63.86 (dt, J =
27.2, 3.2 Hz, C-1¢); 31P NMR (202.46 MHz, CDCl3) d 15.79 (d,
J = 74.6 Hz). HRMS (ESI) calcd for (C13H30O6P2F) [M + H]+:
363.1502; found 363.1508.
Tetraethyl 1-(fluoro-n-hexylidene)-1,1-bisphosphonate (30).
57% yield; colorless oil; 1H NMR (500.13 MHz, CDCl3) d 0.90 (t,
J = 7.1 Hz, 3H, H-5), 1.30 (m, 8H, H-4, H-5, H-6, H-7), 1.37 (t, J
= 7.1 Hz, 12H, H-2¢),1.64 (p, J = 7.2 Hz, 2H, H-3), 2.15 (dt, J =
22.3, 15.3 Hz, H-2), 4.28 (m, 8H, H-1¢); 13C NMR (125.77 MHz,
CDCl3) d 13.88 (C-6), 16.39 (p, J = 3.0 Hz, C-2¢), 22.23 (C-5),
22.57 (q, J = 5.4 Hz, C-3), 32.09 (C-4), 33.17 (d, J = 20.0 Hz, C-2),
63.81 (dt, J = 27.2, 3.2 Hz, C-1¢), 95.85 (dt, J = 187.1, 156.2 Hz,
C-1); 31P NMR (202.46 MHz, CDCl3) d 15.02 (d, J = 74.6 Hz).
Silylation/methanolysis: general procedure
To a solution of the resulting tetraethyl ester (14, 26–34; 1
equivalent) in anhydrous methylene chloride was added dropwise
trimethylsilyl bromide (10 equivalents) in an argon atmosphere.
The reaction mixture was stirred at room temperature for 48 h.
After cooling at 0 ◦C, anhydrous methanol (10 mL) was added
and the resulting mixture was allowed to reach room temperature.
The solution was then concentrated under reduced pressure. The
residue was dissolved in dry methanol (10 mL) and subsequently
concentrated twice under reduced pressure. The solvent was
evaporated and the residue was purified by reverse phase column
Tetraethyl 1-(fluoro-n-heptylidene)-1,1-bisphosphonate (31).
35% yield; colorless oil; IR (film, cm-1) 2984, 2961, 2932, 2872,
2858, 1456, 1393, 1369, 1261, 1164, 1022, 976, 794, 576; 1H NMR
1430 | Org. Biomol. Chem., 2012, 10, 1424–1433
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