1,4-Addition of tetraethyl fluoromethylenebisphosphonate to α,β-unsaturated compounds

Article abstract of DOI:10.1016/j.jfluchem.2011.03.011

Tetraethyl fluoromethylenebisphosphonate in the presence of cesium carbonate in DMF undergoes efficient 1,4-addition to Michael acceptors having terminal double bond such as α,β-unsaturated ketones, esters, sulfones, sulfoxides, and phosphonates to yield

Full text of DOI:10.1016/j.jfluchem.2011.03.011

Journal of Fluorine Chemistry 132 (2011) 363–366
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Short communication
1,4-Addition of tetraethyl fluoromethylenebisphosphonate to
compounds
a,b-unsaturated
*
Stanislav Opekar, Petr Beier
´
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 166 10 Prague 6, Czech Republic
A R T I C L E I N F O
A B S T R A C T
Article history:
Tetraethyl fluoromethylenebisphosphonate in the presence of cesium carbonate in DMF undergoes
efficient 1,4-addition to Michael acceptors having terminal double bond such as -unsaturated
-alkyl-a-
Received 11 January 2011
Received in revised form 11 March 2011
Accepted 12 March 2011
Available online 21 March 2011
a,b
ketones, esters, sulfones, sulfoxides, and phosphonates to yield the corresponding adducts (
fluoromethylenebisphosphonates) in good to excellent yields.
a
ß 2011 Elsevier B.V. All rights reserved.
Keywords:
1,4-Addition
Phosphonates
Fluorine
1. Introduction
of lithium salt of diethyl fluoromethylenebisphosphonate (1) with
methylating agents such as iodomethane or dimethylsulfate (other
alkylating reagents such as iodoethane fail in this reaction) [7].
Bisphosphonates are compounds of interesting biological
properties. Currently, there is a number of drugs based on
bisphosphonates that are used for the treatment of various bone
diseases (such as osteoporosis, Paget’s disease, tumor-induced
osteolysis, and hypercalcemia) [1]. Bisphosphonates have also
been found to have anticancer [2], antiparasitic [3], and herbicidal
[4] properties. They are non-hydrolyzable analogues of the
endogenous pyrophosphate in which the oxygen bridge is replaced
by a carbon atom. The most potent bisphosphonates currently in
use as anti-resorptive agents such as ibandronate, alendronate,
risedronate and zoledronate consist of hydroxyl group and
nitrogen-containing side chain attached to the bridging carbon
atom. It was found recently by McKenna and co-workers that the
replacement of hydroxyl group in risedronate for fluorine atom
retains the biological activity but leads to reduced bone affinity,
which can be useful therapeutically in certain situations [5]. These
Very recently, we have reported a general methodology towards
a-
alkyl- -fluoromethylenebisphosphonates starting from and
a
1
employing alkylation with various alkyl halides using either
cesium carbonate in DMF or sodium dimsyl [8]. Also it was shown
by us that 1 undergoes Horner–Wadsworth–Emmons reactions
with aromatic aldehydes in the presence of excess of cesium
carbonate to provide
a-fluorovinylphosphonates in excellent
yields, however, with only moderate E:Z selectivity [9]. These
results demonstrated that sodium or cesium salt of 1 is stable in
polar aprotic solvents at room temperature and nucleophilic
enough to affect the desired alkylation reaction, and prompted us
to investigate 1,4-addition of carbanion of 1 to
a
,b
-unsaturated
compounds as a new method towards
nebisphosphonates.
a-alkyl-a-fluoromethyle-
Fluorinated carbanions often react as ‘‘hard’’ nucleophiles
giving the products of 1,2-addition instead of 1,4-addition with
Michael type acceptors. This is the general reactivity observed for
the trifluoromethyl group transfer using the Ruppert–Prakash
reagent (TMSCF3) [10] unless a special reaction design is used such
as protection of carbonyl function with a bulky Lewis acid [11].
However, electron deficient arylidenemalonitriles undergo effi-
cient Michael additions [12] and 1,4-addition is also observed with
2-perfluoroalkylchromones [13], 3-arylchromones [14], quino-
lones [13] and coumarins [11]. Investigations of 1,2- and 1,4-
findings make
a-alkyl-a-fluoromethylenebisphosphonates par-
ticularly interesting targets in the search for new biologically
active bisphosphonates.
Previously,
a-alkyl-a-fluoromethylenebisphosphonates have
been prepared by one of these methods: (a) addition of carbon or
nitrogen nucleophiles to bis(diethylphosphono)ethylene, followed
by electrophilic fluorination [6], (b) alkylation of methylenebis-
phosphonate followed by electrophilic fluorination [5], (c) reaction
additions to
a,b-unsaturated ketones, esters and nitroolefins
carried out by Hu and co-workers have shown that the order of soft
to hard character of fluorinated sulfone-containing carbanions is as
* Corresponding author. Tel.: +420 220 183 409; fax: +420 233 331 733.
E-mail address: beier@uochb.cas.cz (P. Beier).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.03.011

364
S. Opekar, P. Beier / Journal of Fluorine Chemistry 132 (2011) 363–366
follows: (PhSO2)2CFÀ > PhSO2CHFÀ > PhSO2CF2 [15]. 1,4-Addi-
tions of monofluoromethylene moieties are known. For example,
Prakash and co-workers have described efficient conjugate
À
Table 1
Optimization of the 1,4-addition of tetraethyl fluoromethylenebisphosphonate (1)
to methyl vinyl ketone (2a)a
O
additions of PhSO2CHFR (R = NO2, CN, CO2Et, SO2Ph) to
a,b-
unsaturated compounds using either trimethylphosphine or
potassium carbonate at room temperature [16]. Michael addition
P
P
P
P
P
P
base
DMF
+
+
reactions between
ketones or esters proceed at room temperature in the presence of
spray-dried potassium fluoride [17]. Using the same base
a-fluoro-b-keto esters and a,b-unsaturated
F
F
F
O
O
O
a
-
1
2a
3a
4a
fluoronitroalkanes undergo 1,4-addition to methyl vinyl ketone or
acrylonitrile [18]. Some enantioselective Michael additions of
monofluoromethylene moieties have been published recently.
Enantioselective Michael addition of 1-fluoro-bis(phenylsulfonyl)-
P = P(O)(OEt)
2
.
Entry
Base (eq.)
Temp.
Time
(h)
3a, Yield
4a, Conv.
(%)b
methane to
a,b-unsaturated ketones catalyzed by ammonium
( 8C)
(%)
salts of cinchona alkaloids in the presence of excess of cesium
carbonate have been reported by Shibata and co-workers [19] and
1
2
3
4
5
6
K2CO3 (2)
K2CO3 (2)
Cs2CO3 (1)
Cs2CO3 (2)
Cs2CO3 (3)
Cs2CO3 (2)
rt
rt
rt
rt
rt
50
21
49
19
6
17b
0
4
0
2
2
9
45b
44c
highly efficient stereoselective Michael addition of
a-fluoro-a-
88c, 67d
61c, 48d
74b
nitro(phenylsulfonyl)methane to chalcones catalyzed by cinchona
alkaloid-derived chiral bifunctional triourea organocatalysts have
been reported by Prakash and co-workers [20].
6
0.75
a
Reactions were carried out using 1 (0.3 mmol, 1 eq.), 2a (0.75 mmol, 2.5 eq.),
base (0.3–0.9 mmol, 1–3 eq.) in DMF (2 mL).
2. Results and discussion
b
Conversion estimated by GC–MS analysis.
19F NMR yield using 4-fluoroanisole as internal standard (20 s relaxation time).
c
d
First, 1,4-addition of tetraethyl fluoromethylenebisphospho-
nate (1) to model Michael acceptor – methyl vinyl ketone (2a) was
tested in the presence of equimolar amounts of triphenylpho-
sphine as nucleophilic initiator in THF. However, even after 24 h at
ambient temperature, no addition product 3a was observed. The
use of two-fold excess of potassium carbonate in DMF was more
successful and low conversions of the desired adduct 3a were
observed accompanied by small amounts of double addition
product 4a after prolonged reaction time (Table 1, entries 1 and 2).
Employment of cesium carbonate led to considerable improve-
ments in the reaction outcome. Further optimization experiments
revealed that conducting the reaction at room temperature with
two equivalents of cesium carbonate provided good yield of the
desired product 3a while the formation of the double addition side
product 4a was negligible (Table 1, entry 4).
Isolated yield.
Table 2
1,4-Addition of tetraethyl fluoromethylenebisphosphonate (1) to
compounds (2)a
a
,b
-unsaturated
R
P
P
R
R
R
Cs2CO3 (2 eq.)
DMF, rt
P
P
or
+
R
R
F
F
R
1
2
3
P = P(O)(OEt)2
.
Optimized reaction conditions were used in the scope and
limitation study of the 1,4-addition of 1 to various a,b-unsaturated
Entry 2 Michael acceptor
Time 3
Product
Yield (%)b
(eq.)
(h)
compounds (Table 2). Addition to methyl vinyl ketone proceeded
smoothly to give the addition adduct 3a in 67% isolated yield (Table
2, entry 1). The use of methyl acrylate gave 3b in 81% yield in 22 h
(Table 2, entry 2). Diethyl vinylphosphonate 2c provided the
corresponding adduct 3c in a good yield (Table 2, entry 3) and it
was found that the long reaction time could be shortened to 48 h
by conducting the reaction at 50 8C with similar product
conversion. Very good 80% yield was obtained by using phenyl
vinyl sulfoxide (2d). Phenyl vinyl sulfone represented the most
reactive Michael acceptor tested; the corresponding adduct 3e was
obtained in 90% isolated yield. Addition to the triple bond of ethyl
propiolate (2f) gave the adducts in combined 48% yield. Each
stereoisomer was isolated by column chromatography and the
P
P
1
2a
2.5 6
3a
3b
67
O
F
O
P
P
CO2Me
2
3
4
2b
2c
2d
1.5 22
81
77
80
F
CO Me
2
P
P
P
2.0 144 3c
F
P
major Z-isomer was obtained in 35% yield (Table 2, entry 6).
a-
Alkyl substitution on the Michael acceptor dramatically slows
down the reaction as observed for methyl methacrylate (2g).
P
P
Ph
S
2.5 18
3d
3e
Unfortunately,
b-substituted Michael acceptors were not reactive
Ph
S
F
as judged by 19F and 31P NMR of reaction mixtures, which showed
only signals corresponding to starting bisphosphonate 1. This was
the case for 2-cyclohexenone, chalcone and even strongly activated
acceptors such as nitrostyrene or benzylidenemalononitrile (Table
2, entries 8–11). As shown by Dilman and co-workers [12] the
trifluoromethyl, pentafluoroethyl and pentafluorophenyl group
could be efficiently transferred to 2k using corresponding silanes
in the presence of sodium acetate as a nucleophilic initiator. Highly
sterically demanding character of the carbanion of fluoromethy-
O
O
Ph
S
O O
P
P
5
2e
1.2 3
90
Ph
S
O O
F

S. Opekar, P. Beier / Journal of Fluorine Chemistry 132 (2011) 363–366
365
Table 2 (Continued )
recorded on a LTQ Orbitrap XL instrument using electrospray (ESI)
ionization. Reactions were conducted under Ar. DMF was dried by
refluxing with calcium hydride followed by distillation and kept
Entry 2 Michael acceptor
Time 3
Product
Yield (%)b
(eq.)
(h)
˚
over molecular sieves (3 A). All other chemicals were used as
received.
CO Et
CO2Et
P
P
2
6
2f
2.5 18
(Z)-3f
35
F
4.1. General preparation of tetraethyl
a-alkyl-a-
fluoromethylenebisphosphonates 3
P
P
(E)-3f
13
Tetraethyl fluoromethylenebisphosphonate (1) (92 mg,
0.3 mmol, 1 eq.) and Michael acceptor 2 (0.36–0.75 mmol, 1.2–
2.5 eq.) were added to a mixture of cesium carbonate (195 mg,
0.6 mmol, 2 eq.) in dry DMF (2.0 mL) in a Shlenk flask. The reaction
mixture was stirred at rt for appropriate time and then poured into
saturated aqueous solution of ammonium chloride (25 mL). The
product was extracted into diethyl ether (3 Â 25 mL), dried
(MgSO4) and concentrated under reduced pressure. Column
chromatography using silica gel gave pure products 3 (new
compounds).
F
CO Et
2
P
P
7
8
2g
2h
2.5 168 3g
25c
F
CO Me
CO Me
2
2
P
P
2.5 72
3h
0
O
O
F
4.1.1. Diethyl [1-(diethoxy-phosphoryl)-1-fluoro-4-oxo-pentyl]-
phosphonate, 3a
P
P
Ph
Ph
Ph
1.3 168 3i
Prepared according to the general procedure using 2a (53 mg,
9
2i
0
0
0
Ph
O
0.75 mmol, 2.5 eq.) in 6 h at rt giving 3a (76 mg, 67%) as a colorless
F
O
3
liquid: Rf = 0.17 (EtOAc); 1H NMR:
d
1.38 (t, 12H, JHH = 7.1 Hz,
Ph
4 Â OCH2CH3), 2.18 (s, 3H, COCH3), 2.39–2.57 (m, 2H, CH2), 2.86–
2.92 (m, 2H, CH2), 4.23–4.34 (m, 8H, 4 Â OCH2); 13C NMR:
d 16.3–
P
P
10
2j
2.5 72
3j
16.5 (m), 26.6 (d, 2JCF = 20.3 Hz, CFCH2), 29.9, 37.1–37.3 (m), 64.0–
64.2 (m), 94.8 (dt, 1JCF = 187.6 Hz, 1JCP = 157.2 Hz, CF), 206.7 (C55O);
NO
2
F
NO2
2
3
19F NMR:
d
À193.4 (tt, JFP = 75.0 Hz, JFH = 22.5 Hz); 31P NMR:
d
Ph
2
14.1 (d, JPF = 75.0 Hz); GC–MS (EI) m/z 334 (16%), 306 (100), 291
(15), 279 (35), 251 (17), 239 (38), 219 (17), 207 (44), 197 (49), 183
(38), 170 (42), 127 (35), 43 (32); HRMS (ESI+) m/z calcd. for
13H28FO7P2 (M + H)+: 377.1289, found: 377.1286.
CN
CN
CN
CN
P
P
11
2k
2.5 72
3k
Ph
C
F
Ph
4.1.2. Methyl 4,4-bis-(diethoxy-phosphoryl)-4-fluoro-butyrate, 3b
Prepared according to the general procedure using 2b (39 mg,
0.45 mmol, 1.5 eq.) in 22 h at rt giving 3b (95 mg, 81%) as a
a
Reactions were carried out using 1 (0.3 mmol, 1 eq.), 2 (0.36–0.75 mmol, 1.2–
2.5 eq.), Cs2CO3 (0.6 mmol, 2 eq.) in DMF (1 mL) at rt.
b
Isolated yield.
19F NMR yield using 4-fluoroanisole as internal standard (20 s relaxation time).
c
colorless liquid: Rf = 0.22 (EtOAc); 1H NMR:
d 1.38 (t, 12H,
3JHH = 7.1 Hz, 4 Â OCH2CH3), 2.45–2.62 (m, 2H, CH2), 2.70 c
À2.78 (m, 2H, CH2), 3.69 (s, 3H, CO2CH3), 4.22–4.35 (m, 8H,
4 Â OCH2); 13C NMR:
d 16.2–16.4 (m), 27.8–28.1 (m), 28.0 (d,
lenebisphoshonate 1 explains the observed lack of reactivity with
2k.
2JCF = 20.1 Hz, CFCH2), 51.6, 63.8–64.3 (m), 94.5 (dt,
1
1JCF = 188.9 Hz, JCP = 156.7 Hz, CF), 172.9 (C55O); 19F NMR:
d
2
3
À194.5 (tt, JFP = 74.0 Hz, JFH = 22.3 Hz); 31P NMR:
d
14.0 (d,
2JPF = 74.0 Hz); GC–MS (EI) m/z 361 (16%), 319 (59), 306 (31),
3. Conclusion
291 (93), 263 (58), 255 (41), 235 (52), 207 (100), 183 (39), 127
(34); HRMS (ESI+)
393.12380, found: 393.12367.
m/z calcd. for C13H28FO8P2 (M + H)+:
In conclusion, tetraethyl fluoromethylenebisphosphonate (1) in
the presence of two-fold excess of cesium carbonate in DMF reacts
with Michael acceptors having terminal double or triple bond in
4.1.3. Diethyl [1,3-dis-(diethoxy-phosphoryl)-1-fluoro-propyl]-
phosphonate, 3c
1,4-addition fashion to provide
methylenebisphosphonates 3 in moderate to excellent yields.
a-alkyl or a-alkenyl-a-fluoro-
Prepared according to the general procedure using 2c (98 mg,
0.6 mmol, 2.0 eq.) in 144 h at rt giving 3c (109 mg, 77%) as a
Michael acceptors with substituted double bond in
found to be unreactive.
b position were
colorless liquid: Rf = 0.27 (EtOAc–MeOH, 9:1); 1H NMR:
d = 1.32–
1.40 (m, 18H, 6 Â OCH2CH3), 2.03–2.22 (m, 2H, CH2), 2.35–2.57 (m,
4. Experimental
2H, CH2), 4.05–4.16 (m, 4H, 2 Â OCH2), 4.18–4.35 (m, 8H,
1H, 13C {1H}, 19F and 31P {1H} NMR spectra were recorded in
CDCl3 on a Bruker 400 MHz instrument at 400, 100.6, 376, and
162 MHz, respectively. Chemical shifts (
relative to Me4Si (0 ppm, for 1H NMR), residual CHCl3 (7.26 ppm for
1H NMR and 77.0 ppm for 13C NMR), internal CFCl3 (0 ppm for 19
NMR), and external H3PO4 in water (0 ppm for 31P NMR). GC–MS
spectra were recorded on an Agilent 7890A gas chromatograph
coupled with 5975C quadrupole mass selective electron impact
(EI) detector (70 eV). High resolution mass spectra (HRMS) were
4 Â OCH2); 13C NMR:
d 16.1–16.2 (m), 16.2–16.3 (m), 19.5 (dq,
1JCP = 142.4 Hz, 3JCF = 3JCP = 5.8 Hz, CH2PO), 26.3 (dd, 2JCF = 21.0 Hz,
2
d
) are reported in ppm
2JCP = 2.7 Hz CFCH2), 61.6 (d, JCP = 6.4 Hz, 2 Â OCH2), 63.8–64.2
1
1
3
(m), 94.2 (ddt, JCF = 190.0 Hz, JCP = 156.7 Hz, JCP = 18.6 Hz, CF);
2
3
F
19F NMR:
d
À194.0 (tt, JFP = 74.1 Hz, JFH = 21.7 Hz); 31P NMR:
d
= 13.7 (d, 2P, 2JPF = 74.1 Hz, CFP2), 30.6 (s, 1P, CH2P); GC–MS (EI)
m/z 425 (16%), 333 (97), 319 (26), 306 (100), 285 (28), 261 (26), 221
(25), 207 (23), 170 (20), 165 (22), 109 (21); HRMS (ESI+) m/z calcd.
for C15H35FO9P3 (M + H)+: 471.14725, found: 471.14699.

366
S. Opekar, P. Beier / Journal of Fluorine Chemistry 132 (2011) 363–366
4.1.4. Diethyl [3-benzenesulfinyl-1-(diethoxy-phosphoryl)-1-fluoro-
propyl]-phosphonate, 3d
Acknowledgement
Prepared according to the general procedure using 2d
(114 mg, 0.75 mmol, 2.5 eq.) in 18 h at rt giving 3d (110 mg,
80%) as a colorless liquid: Rf = 0.43 (EtOAc–MeOH, 9:1); 1H NMR:
This work was supported by Research Plan AVZ40550506 from
the Academy of Sciences of the Czech Republic and the Grant
Agency of the Czech Republic (203/08/P310).
d
= 1.38–1.49 (m, 12H, 4 Â CH3), 2.31–2.53 (m, 1H, CHaHb), 2.63–
2.87 (m, 1H, CHaHb), 3.15–3.23 (m, 1H, CHaHb), 3.42–3.53 (m,
1H, CHaHb), 4.26–4.42 (m, 8H, 4 Â OCH2), 7.59–7.67 (m, 3H,
Appendix A. Supplementary data
C
ArH), 7.72–7.76 (m, 2H, CArH); 13C NMR:
d
16.3–16.5 (m), 25.2
2
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jfluchem.2011.03.011.
(d, JCF = 20.8 Hz, CFCH), 49.7–49.9 (m), 64.0–64.5 (m), 94.3 (dt,
1JCF = 189.7 Hz, JCP = 156.9 Hz, CF), 124.2, 129.2, 131.0, 143.2;
1
19F NMR:
d
d
= –193.0 (tt, JFP = 73.9 Hz, JFH = 22.0 Hz); 31P NMR:
2
3
13.3 (d, 2JPF = 73.9 Hz); HRMS (ESI+) m/z calcd. for
17H30FO7P2S (M + H)+: 459.1166, found: 459.1166.
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d 12.9
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[11] D.V. Sevenard, V.Ya. Sosnovskikh, A.A. Kolomeitsev, M.H. Ko¨nigsmann, G.-V.
Ro¨schenthaler, Tetrahedron Lett. 44 (2003) 7623–7627.
[12] A.D. Dilman, V.V. Levin, P.A. Belyakov, M.I. Struchkova, V.A. Tartakovsky, Tetra-
hedron Lett. 49 (2008) 4352–4354.
[13] (a) V.Ya. Sosnovskikh, B.I. Usachev, D.V. Sevenard, G.-V. Ro¨schenthaler, J. Fluorine
Chem. 126 (2005) 779–784;
(d, 2JPF = 73.2 Hz); GC–MS (EI) m/z 382 (20%), 333 (82), 317 (74),
306 (91), 291 (81), 277 (40), 263 (46), 249 (43), 235 (43), 221
(100), 207 (73), 183 (41), 125 (73), 99 (50), 77 (73), 65 (47); HRMS
(ESI+) m/z calcd. for C17H30FO8P2S (M + H)+: 475.1115, found:
475.1115.
4.1.6. Ethyl 4,4-bis-(diethoxy-phosphoryl)-4-fluoro-but-2-enoate, 3f
Prepared according to the general procedure using 2f (74 mg,
0.75 mmol, 2.5 eq.) in 18 h at rt giving (Z)-3f (43 mg, 35%) as a
colorless liquid: Rf = 0.24 (EtOAc); 1H NMR:
d 1.26–1.39 (m, 15H,
5 Â CH3), 4.18–4.24 (m, 2H, CO2CH2), 4.27–4.36 (m, 8H, 4 Â OCH2),
6.03–6.07 (m, 1H, CH55), 6.07–6.16 (m, 1H, CH55); 13C NMR:
16.2–16.4 (m), 60.8, 64.8–65.1 (m), 97.1 (dt, JCF = 202.8 Hz,
1JCP = 154.1 Hz, CF), 122.8 (dt, 3JCF = 10.5 Hz, 3JCP = 5.4 Hz,
d
14.0,
1
2
2
CFCH = CH), 126.8 (dt, JCF = 13.6 Hz, JCP = 4.9 Hz, CFCH = ), 166.3
2
3
(C = O); 19F NMR:
NMR:
d
À193.7 (dt, JFP = 68.0 Hz, JFH = 27.6 Hz); 31P
d
8.8 (d, 2JPF = 68.0 Hz); GC–MS (EI) m/z 359 (15%), 246 (21),
223 (28), 222 (96), 194 (78), 166 (100), 138 (51); HRMS (ESI+) m/z
calcd. for C14H28FO8P2 (M + H)+: 405.12380, found: 405.12375;
and (E)-3f (17 mg, 13%) as a colorless liquid: Rf = 0.38 (EtOAc); 1H
(b) V.Ya. Sosnovskikh, B.I. Usachev, D.V. Sevenard, G.-V. Ro¨schenthaler, J. Org.
Chem. 68 (2003) 7747–7754;
(c) V.Ya. Sosnovskikh, D.V. Sevenard, B.I. Usachev, G.-V. Ro¨schenthaler, Tetrahe-
dron Lett. 44 (2003) 2097–2099.
NMR:
d
1.29–1.39 (m, 15H, 5 Â CH3), 4.15–4.35 (m, 10H,
3 4
5 Â OCH2), 6.20 (dt, 1H, JHH = 15.6 Hz, JHP = 4.9 Hz, CH), 7.15
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4456–4458.
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Chem. 4 (2008) 17.
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Int. Ed. 47 (2008) 8051–8054.
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U.S.A. 106 (2009) 4090–4094.
(ddt, 1H, 3JHF = 25.5 Hz, 3JHH = 15.6 Hz, 3JHP = 3.6 Hz, CH); 13C NMR:
d
14.2, 16.3–16.4 (m), 60.9, 64.8–65.0 (m), 122.1 (dt, 3JCF = 12.1 Hz,
3JCP = 9.3 Hz, CFCH55CH), 137.9 (dt, JCF = 14.2 Hz, JCP = 4.9 Hz,
2
2
CFCH55), 165.0 (C55O); 19F NMR:
d
3JFH = 25.5 Hz); 31P NMR: = 9.3 (d, 2JPF = 69.2 Hz); GC–MS (EI) m/z
d
À192.6 (dt, JFP = 69.2 Hz,
2
359 (16%), 246 (21), 223 (28), 222 (96), 194 (79), 166 (100), 138
(50); HRMS (ESI+) m/z calcd. for C14H28FO8P2 (M + H)+: 405.12380,
found: 405.12382.