suspension was filtered and the filtrate concentrated in vacuo
to leave a yellow oil (0.24 g) which was purified by column
chromatography (silica gel, 40% ethyl acetate–light petroleum)
to afford the ester 7 (0.24 g, 100%) as a colourless oil; Rf (40%
ethyl acetate–light petroleum) 0.11; δH (300 MHz; CDCl3) 5.85
(1H, tdd, J 17.3, 10.7, 5.5, H-2Ј), 5.29 (1H, d, J 17.3, H-3Јa),
5.18 (1H, d, J 10.7, H-3Јb), 4.56 (2H, d, J 5.5, H-1Ј), 4.16–4.04
m, H-1, H-2), 4.38–4.12 (4H, m, OCH2CH3), 1.25 (6H, t, J 7.3,
OCH2CH3); δC (75 MHz; CDCl3) 138.4, 137.8, 134.4, 132.2 (dt,
2
1
1
2JC–P 13.8, JC–F 23.1), 129.6, 128.1, 115.4 (dt, JC–P 215, JC–F
3
262), 65.3, 16.2; δF (282 MHz; CDCl3) Ϫ112.1 (dd, JF–H 9.1,
2JF–P 106); δP (121 MHz; CDCl3) 12.7 (t, 2JP–F 106); m/z (CI) 372
(100%, M[NH4]ϩ), 355 (80, M ϩ 1).
2
(4H, m, OCH2CH3), 2.93 (2H, d, JH–P 21.7, H-1), 1.27 (6H, t,
Ethyl 4-diethoxyphosphoryl-4,4-difluoro-2-ethoxycarbonyl-3-
hydroxybutanoate
J 7.0, OCH2CH3); δC (75 MHz; CDCl3) 165.3, 131.5, 118.6,
2
1
66.0, 62.6 (d, JC–P 5.7), 32.4 (d, JC–P 134), 16.2; δP (121 MHz;
Potassium fluoride (0.1 g, 2.0 mmol) was added to a cool (0 ЊC)
solution of 5 (1.00 g, 4.3 mmol) and diethyl malonate (1.94 ml,
12.82 mmol) in propan-2-ol (25 ml). The reaction mixture was
stirred at 0 ЊC for 1 hour before being warmed to room tem-
perature and stirred for a further 18 hours. The resulting yellow
solution was diluted with diethyl ether (30 ml), washed with
brine (30 ml) and re-extracted with diethyl ether (3 × 40 ml).
The combined organic extracts were dried (MgSO4) and the
solvent removed in vacuo to afford a yellow oil. Column
chromatography (40% ethyl acetate in light petroleum) afforded
the alcohol adduct (1.41 g, 88%) as a slightly yellow oil; Rf (40%
ethyl acetate in light petroleum) 0.43 (Found: C, 41.9; H, 6.2;
C13H23F2O8P requires: C, 41.5; H, 6.1%); δH (300 MHz; CDCl3)
4.88 (1H, br s, OH), 4.71–4.59 (1H, m, H-3), 4.25–4.04 (8H, m,
POCH2CH3, CO2CH2CH3), 3.73 (1H, d, J 6.0, H-2), 1.25 (6H,
t, J 7.3, OCH2CH3), 1.17 (3H, t, J 7.3, CO2CH2CH3), 1.15 (3H,
t, J 7.3, CO2CH2CH3); δC (75 MHz; CDCl3) 168.0, 166.1, 118.6
CDCl3) 19.8 (s).
Allyl (2E)-4-(diethoxyphosphoryl)-4,4-difluorobut-2-enoate 8
The allyl ester was prepared in an identical manner to 6a from
triethylamine (1.12 mmol, 0.16 cm3), 7 (1.02 mmol, 0.24
g), LiBr (1.22 mmol, 0.11 g) and 5 (1.12 mmol, 0.26 g) in THF
(5 cm3). The yellow oil (0.28 g) was purified by column chrom-
atography (silica gel, 40% ethyl acetate in light petroleum) to
afford the allyl ester (0.24 g, 79%) as a colourless oil; Rf (40%
ethyl acetate in light petroleum) 0.13 (Found: C, 44.6; H, 5.7.
C11H17F2O5P requires: C, 44.3; H, 5.8%); δH (300 MHz; CDCl3)
6.89 (1H, dt, J 12.9, 3JH–F 12.7, H-3), 6.40 (1H, dd, J 12.9, 4JH–F
2.2, H-2), 5.91 (1H, tdd, J 17.3, 10.7, 5.5, H-2Ј), 5.32 (1H, d,
J 17.3, H-3Јa), 5.25 (1H, d, J 10.7, H-3Јb), 4.66 (2H, d, J 5.5,
H-1Ј), 4.30–4.13 (4H, m, OCH2CH3), 1.35 (6H, t, J 7.0,
2
OCH2CH3); δC (75 MHz; CDCl3) 164.0, 135.7 (dt, JC–F 22.0,
2JC–P 13.0), 131.5, 127.6 (dt, JC–F 14.7, JC–P 5.7), 118.9, 116.1
(dt, JC–P 209, JC–F 266), 70.6 (dt, JC–P 17.1, JC–F 25.3), 64.8,
62.1, 50.4, 16.2, 13.8; δF (282 MHz; CDCl3) Ϫ114.5 (1F, dd,
3
3
1
1
2
2
1
1
2
(dt, JC–F 260.0, JC–P 217.0), 65.9, 65.1 (d, JC–P 6.5), 16.2;
2
3
2
δF (282 MHz; CDCl3) Ϫ112.0 (ddd, 2JF–P 109.1, 3JF–H 12.7, 4JF–H
2JF–P 97.6, JF–F 305), Ϫ125.95 (1F, ddd, JF–H 21.0, JF–P 97.6,
2
2
2.2); δP (121 MHz; CDCl3) 5.27 (t, JF–P 109.1) [HRMS
2JF–F 305); δP (121 MHz; CDCl3) 5.38 (t, JP–F 97.6); m/z (CI)
(CI, M ϩ 1) Found: 299.086839. Calc. for C11H18F2O5P
299.085994]; m/z (CI) 316 (20%, M ϩ 18), 299 (30, M ϩ 1), 174
(50), 157 (64), 70 (100).
394 (55%, M[NH4]ϩ), 377 (90, M ϩ 1).
Ethyl 4-diethoxyphosphoryl-4,4-difluoro-2-ethoxycarbonylbut-2-
enoate 6c
(2E)-4-(Diethoxyphosphoryl)-4,4-difluorobut-2-enoic acid 6b
Methanesulfonyl chloride (0.86 ml, 11.17 mmol) was added in
one portion to a cooled (0 ЊC) solution of the alcohol (1.40 g,
3.72 mmol) in DCM (25 ml) under a nitrogen atmosphere. The
mixture was stirred for 30 minutes at 0 ЊC, before the addition
of freshly distilled triethylamine (1.53 ml, 11.17 mmol). After
stirring for 1 hour, water (20 ml) was added. The mixture was
extracted with diethyl ether (3 × 25 ml), washed with brine (15
ml) and re-extracted with diethyl ether (3 × 25 ml). The com-
bined organic extracts were dried (MgSO4) and concentrated
in vacuo to afford a yellow oil. Purification by column chrom-
atography (40% ethyl acetate in light petroleum) afforded the
enedioate 6c (0.91 g, 68%) as a clear oil; Rf (40% ethyl acetate in
light petroleum) 0.35 (Found: C, 48.2; H, 6.5; C13H21F2O7P
Triphenylphosphine (3.38 mmol, 0.89 g) was added to a stirred
solution of the allyl butenoate (2.11 mmol, 0.63 g), palladium
acetate (0.10 mmol, 0.02 g) and morpholine (2.54 mmol, 0.22
cm3) in THF (6 cm3) under an atmosphere of nitrogen. After
stirring overnight the solvent was concentrated in vacuo. The
residue was redissolved in DCM (20 cm3), washed with HCl
(2 × 2 cm3 of a 3.0 M aqueous solution), dried (MgSO4) and
concentrated in vacuo to leave a golden oil (1.03 g) which was
purified by column chromatography (silica gel, 1% acetic acid
and 4% methanol in chloroform) to afford acid 6b (0.54 g, 99%)
as a clear oil; Rf (1% acetic acid and 4% methanol in chloro-
form) 0.20; δH (300 MHz; CDCl3) 10.42 (br s, CO2H), 6.92 (1H,
tdd, J 15.8, 3JH–F 12.7, 3JH–P 1.9, H-3), 6.40 (1H, tdd, JH–H 15.8,
requires: C, 47.9; H, 6.4%); νmax/cmϪ1 2986s, 1738vs (C᎐O),
᎐
4JH–P 5.3, JH–F 2.5, H-2), 4.36–4.23 (4H, m, OCH2CH3), 1.38
1666w; δH (300 MHz; CDCl3) 6.76 (1H, dt, 3JH–P 2.5, 3JH–F 15.0,
H-3), 4.38–4.12 (8H, m, POCH2CH3, CO2CH2CH3), 1.37–1.33
(12H, m, POCH2CH3, CO2CH2CH3); δC (75 MHz; CDCl3)
4
(6H, t, JH–H 7.0, OCH2CH3); δC (75 MHz; CDCl3) 166.9, 135.8
2
2
3
3
(dt, JC–F 21.5, JC–P 13.0), 128.3 (dt, JC–F 7.0, JC–P 7.0), 116.2
1
1
2
2
2
(dt, JC–F 260.3, JC–P 218.2), 65.7 (d, JC–P 6.6), 16.4; δF (282
163.5, 161.9, 135.9, 130.9 (dt, JC–P 14.1, JC–F 21.0), 116.0 (dt,
2
3
4
1
MHz; CDCl3) Ϫ112.1 (ddd, JF–P 108.7, JF–H 12.7, JF–H 2.5);
δP (121 MHz; CDCl3) 5.19 (t, 2JF–P 108.7). These spectroscopic
data were in agreement with those reported by Kawamoto and
Campbell.34
1JC–P 216, JC–F 261), 65.3, 62.5, 62.0, 16.3, 13.8; δF (282 MHz;
CDCl3) Ϫ112.1 (dd, 3JF–H 15.0, 2JF–P 103); δP (121 MHz; CDCl3)
2
3.6 (t, JP–F 103); m/z (CI) 376 (100%, M[NH4]ϩ), 359 (80,
M ϩ 1), 174 (38).
(2E)-3-Diethoxyphosphoryl-3,3-difluoro-1-phenylsulfonylprop-1-
3-Diethoxyphosphoryl-3,3-difluoro-1-nitropropan-2-ol
ene 6d
Prepared as for 6c from potassium fluoride (0.5 g, 10 mmol), 5
(6.00 g, 25.6 mmol) and nitromethane (4.16 ml, 77.0 mmol) in
propan-2-ol (100 ml). Column chromatography (40% ethyl
acetate in light petroleum) afforded pure nitroalcohol (6.00 g,
84%) as a slightly yellow oil; Rf (40% ethyl acetate in light pet-
roleum) 0.44 (Found: C, 30.4; H, 5.1; N, 5.1; C7H14F2NO6P
requires C, 30.3; H, 5.1; N, 5.1%); δH (300 MHz; CDCl3) 5.30
(1H, br s, OH), 4.95–4.75 (1H, m, H-2), 4.63 (1H, dd, J 14.0,
2.5, H-1a), 4.55 (1H, dd, J 14.0, 9.2, H-1b), 4.28 (2H, q, J 7.3,
Vinyl sulfone 6d was prepared in an identical manner to 6a from
anhydrous lithium bromide (1.40 g, 16.32 mmol), 942 (4.39 g,
15.00 mmol), triethylamine (2.05 ml, 15.00 mmol) and 5 (3.00 g,
13.6 mmol) in THF (25 ml). Column chromatography (40%
ethyl acetate in light petroleum) afforded vinyl sulfone 6d (3.01
g, 66%) as a pale yellow oil; Rf (40% ethyl acetate in light petrol-
eum) 0.24 (Found: C, 44.1; H, 4.9; C13H17F2O5PS requires: C,
44.0; H, 4.8%); δH (300 MHz; CDCl3) 7.82 (2H, d, J 8.0, ArH),
7.61 (1H, t, J 8.0, ArH), 7.58 (2H, t, J 8.0, ArH), 6.90–6.86 (2H,
3
OCH2CH3), 4.26 (2H, q, J 7.3, OCH2CH3), 1.36 (6H, t, JH–H
3612
J. Chem. Soc., Perkin Trans. 1, 1999, 3609–3614