Radical conjugated addition: Addition of dialkyl phosphonodifluoromethyl radical onto unsaturated ketones

Article abstract of DOI:10.1055/s-0028-1088207

The free radical addition of phosphonodifluoromethyl radical is reported from iodophosphonate and sodium dithionite, triethylborane, or dilauroyl peroxide as initiator. Triethylborane promoted the radical conjugated addition onto enones.

Full text of DOI:10.1055/s-0028-1088207

LETTER
981
Radical Conjugated Addition: Addition of Dialkyl Phosphonodifluoromethyl
Radical onto Unsaturated Ketones
Radical
C
onjugate
b
d
A
ddition oubacary Sène,a Sonia Diab,a Antje Hienzsch,a Dominique Cahard,b Thierry Lequeux*a
a
Laboratoire de Chimie Moléculaire et Thioorganique, CNRS UMR 6507 & FR3038, Université de Caen Basse-Normandie, ENSICAEN
6 Boulevard du Maréchal Juin, 14050 Caen Cedex, France
Fax +33(2)31452865; E-mail: Thierry.Lequeux@ensicaen.fr
Chimie Organique et Bioorganique: Réactivité et Analyse, CNRS UMR 6014 & FR3038, Université de Rouen, INSA de Rouen,
Rue Tesnière, 76130 Mont Saint Aignan, France
b
Received 22 December 2008
The formal liberation of the phosphonodifluoromethyl
free radical I has been realized from halo- and chalco-
geno-phosphonates in the presence of radical initiator
(Scheme 2). Tin- or light-promoted free-radical addition
from O,O-dialkyl alkylsulfanyl- or alkylselanyldifluoro-
methylphosphonates for the preparation of secondary and
primary difluoromethylphosphonates by trapping the
free-radical species liberated in situ.5
Abstract: The free radical addition of phosphonodifluoromethyl
radical is reported from iodophosphonate and sodium dithionite, tri-
ethylborane, or dilauroyl peroxide as initiator. Triethylborane pro-
moted the radical conjugated addition onto enones.
Key words: radical reaction, fluorine, enone, phosphonate, alkene
Due to the limitation of methylenephosphonates as bio-
logical models of phosphates, difluoromethylenephos-
phonates have, and still arouse, interest as stable isopolar
phosphate mimics.1 It is generally assumed that the phos-
phate unit will be fully ionized on protein binding, and di-
fluoromethylenephosphonates represent a new class of
analogues of phosphates, which provide a powerful arse-
nal of biological probes for examination or perturbation of
the mechanisms of phosphoryl-transfer enzymes. Their
efficiency has been established through many examples of
high affinity enzyme inhibitors, and difluoromethylene-
phosphonates emerge as excellent pyrophosphate and
phosphate surrogates.
R
H2C = CHR, Pd(Ph3P)4, 20 °C
63–91%
CF2P(O)(OEt)2
R = Alk
I
O
O
XCF2P(O)(OEt)2
X = I, Br
EtOH, 20 °C
BrCo(dmgH)2Py cat., Zn
CF2P(O)(OEt)2
18%
CF2P(O)(OEt)2
HCF2P(O)(OEt)2
CF2P(O)(OEt)2
CF2P(O)(OEt)2
I
II
III
Scheme 1 Transition-metal-promoted coupling reaction
Although the addition of alkyl carbethoxydifluoromethyl
free radical onto alkenes has been largely applied,2 the in-
troduction of the dialkyl phosphonodifluoromethyl group Adducts were obtained from electron-rich alkenes, in-
by free-radical addition has been partially studied. It has cluding 1,2-disustituted alkenes or alkynes. The reaction
been found that Pd0 and CoII promoted the coupling reac- was limited by a competitive reaction due to the presence
tion from the diethyl iodo- or bromodifluoromethylphos- of hydrogen donor [Bu3SnH or (Me3Si)3SiH]. A competi-
phonates and alkenes (Scheme 1). The reaction proceeds tive formation of reduction product II or homocoupling
through a radical process in the presence of catalytic product III was observed from electron-deficient alkenes
amount of Pd(PPh3)4,3 or bromo(pyridine)cobaloxime.4 In as free-radical acceptors, dramatically influenced the
the presence of Pd0 a group-transfer reaction was ob- course of the radical addition. It has been assumed that
served with alkenes affording iodoalkanes in high yields. this radical presented rather an electrophilic character and
In contrast, in the presence of CoIII/Zn corresponding de- better results were observed from electron-rich alkenes.
halogenated phosphonates were obtained. In addition, the Sodium hydrosulfite (or sodium dithionite) radical initia-
first method is efficient from terminal electron-rich ole- tor has been largely used to generate fluorinated radicals.6
fins, while the second allowed the addition onto electron-
deficient and -rich alkenes. This reaction could be consid-
ered as the first report of the radical-conjugated addition
O
Bu3SnH, AIBN,
toluene, 110 °C
CF2P(O)(OR2)2
O
(RCA) of the phosphonodifluoromethyl radical onto al-
kenes, although this reaction involved a transition metal.
49–68%
R1
H
XCF2P(O)(OR2)2
H
Na2S2O4, NaHCO3,
MeCN, H2O, 20 °C
R1
X = I, SMe, SePh
R2 = Et, i-Pr
CF2P(O)(OEt)2
56–79%
SYNLETT 2009, No. 6, pp 0981–0985
x
x.
x
x.
2
0
0
9
I
Advanced online publication: 16.03.2009
Scheme 2 Formal free-radical addition
DOI: 10.1055/s-0028-1088207; Art ID: G39908ST
© Georg Thieme Verlag Stuttgart · New York

982
A. Sène et al.
LETTER
Few examples concern the phosphonodifluoromethyl rad- duced radical II or the homodimer III. The last method
ical, and among them, the free-radical addition onto employed dilauroyl peroxide as free-radical initiator. This
alkynes was noted first (Scheme 2). The reaction involved later required elevated temperature (80 °C) to initiate the
the sulfinatodehalogenation of the iododifluoromethyl- reaction, and was conducted by a slow addition of a solu-
phosphonate,7 proceeding through an electron-transfer tion of the initiator to a solution of alkene and iodophos-
process leading to the free phosphonodifluoromethyl rad- phonate in refluxed DCE. The starting phosphonate was
ical, which was then trapped by alkynes. The second rad- consumed within 3 hours, and the product 3 was isolated
ical ensured the propagation of the reaction by a in a lower yield (45%) due probably to its moderate stabil-
radicophile attack of the iodine atom of the starting pre- ity in refluxed solvent.
cursor, giving to this reaction a group-transfer reaction
character. Recently, the method has been extended to the
synthesis of g-butyrolactones through the addition of the
phosphonodifluoromethyl radical onto 4-pentenoic ac-
ids.8 Except this example, no general study of the addition
of the phosphonodifluoromethyl radical, generated from
the iodophosphonate, onto alkenes has been reported in
the literature.
C6H13
C6H13
methoda
CF2P(O)(Oi-Pr)2
ICF2P(O)(Oi-Pr)2
I
(A) 75%; (B) 76%;
(C) 45%
2
3
a
Scheme 4 Reagents and conditions:
method A: Na2S2O4,
NaHCO3, MeCN–H2O (5:3), r.t, 18 h; method B: Et3B, (0.3 equiv, 1
M in n-hexane), CH2Cl2, r.t, 1 h; method C: dilauroyl peroxide (0.3
equiv), DCE, 80 °C, 3 h.
In this paper we report our results in this field involving
the dialkyl iododifluoromethylphosphonate and electron-
rich and -deficient alkenes in the presence of a variety of
free-radical initiators.
Table 1 Sodium Dithionite Promoted Free-Radical Addition
Entry Product
Methoda Time (h) Yield (%)
The iodophosphonate 2 can be easily prepared from the
dialkyl bromodifluoromethylphosphonate through the
formation of the organozinc reagent and subsequent trap-
ping with iodine,9 instead of the use of CF2I2.7 Alternative
preparation consists in trapping the lithiated anion pre-
pared from the sulfide 1 with iodine (Scheme 3).10 This
latter approach, based on a nucleophilic fluorination of
phosphonates, is sustainable; the use of regulated chemi-
cals such as difluorodihalomethane derivatives is not
needed anymore.
I
1
A
12
65
CF2P(O)(Oi-Pr)2
CF2P(O)(Oi-Pr)2
4
5a
A
B
12
3
60
2:3 ratio
2
CF2P(O)(Oi-Pr)2
CF2(O)P(Oi-Pr)2
I
1) t-BuLi, THF, –78 °C
2) I2, 1 h, –78 °C
5b
5a
ICF2P(O)(Oi-Pr)2
MeSCF2P(O)(Oi-Pr)2
81%
1
2
3
4
A
A
24
12
47
74
Scheme 3 Iodophosphonate synthesis
I
Having in hand iodofluorophosphonate 2, three initiators
were tested to generate the free radical for reaction with
alkenes (Scheme 4). Initially, the reaction was performed
from iodophosphonate 2 (1 equiv) and n-octene (1.3
equiv). The three initiator systems tested were: (A)
Na2S2O4/NaHCO3 in MeCN–H2O, (B) Et3B in CH2Cl2,
and (C) dilauroyl peroxide in refluxing DCE. In the pres-
ence of sodium dithionite (2 equiv) and sodium hydro-
genocarbonate (1 equiv) in MeCN–H2O (5:3), the reaction
was slow and required 18 hours at room temperature to be
completed. Iodoalkane 3 was the exclusive product ob-
served by analysis of the crude mixture (19F NMR) and
was isolated in 75% yield by flash column chromatogra-
phy. The reaction was faster with Et3B and reached com-
pletion after 1 hour of stirring at room temperature. Best
results were observed when the addition of a solution of
triethylborane (0.3 equiv, 1 M in n-hexane) was realized
in three portions to a mixture of alkene and iodophospho-
nate. The product was also isolated in good yield (76%),
and no trace of byproduct was observed, such as the re-
BnO
CF2P(O)(Oi-Pr)2
6
OH
O
5
6
A
A
12
12
89
45
CF2P(O)(Oi-Pr)2
7
8
O
OH
CF2P(O)(Oi-Pr)2
a Method A: Na2S2O4, NaHCO3, MeCN–H2O (5:3), r.t.; method B:
Et3B, (0.3 equiv, 1 M in n-hexane), CH2Cl2, r.t.
Other alkenes reacted with the radical precursor 2 under
these experimental conditions (Table 1). From 1,1-disub-
stituted alkenes such as methylenecyclobutane the reac-
tion reached completion after 12 hours at room
temperature and lead to the iodoalkane 4 in 65%. How-
Synlett 2009, No. 6, 981–985 © Thieme Stuttgart · New York

LETTER
Radical Conjugated Addition
983
ever, a competitive elimination reaction took place from served when the iodophosphonate 2 and 2,3-dihydro-
methylenecyclopentane and a mixture of alkene 5a and iodo- furane were submitted to methods B and C. The starting
alkane 5b was obtained in a 2:3 ratio, after 12 hours at materials were recovered. Finally, the group-transfer reac-
room temperature.11
tion was attempted from 2,3-dihydropyrane. The addition
proceeded smoothly and a mixture of cis/trans lactol iso-
mers 8 was obtained in a 1:1 ratio. The products were iso-
lated in a lower yield (45%). The formation of the
hemiacetals from vinyl ethers as radical acceptors was is-
sued from a substitution reaction by water of the reactive
intermediate gem-iodoether.
This alkene 5a was obtained exclusively and isolated in
47% yield when the reaction was conducted over 24 hours
instead of the initial 12 hours. No success to obtain exclu-
sively the iodoalkane 5b was observed when using Et3B
as radical initiator (method B), and no reaction occurred
with dilauroyl peroxide (method C). The reaction condi-
tions supported the presence of other functionalities, and In order to explore the limits of this group-transfer reac-
from the O-benzylallyl ether the corresponding iodoal- tion, the addition was realized from electron-deficient al-
kane 6 was isolated in good yield (74%). However, the kenes. From ethyl acrylate no addition occurred whatever
corresponding iodohydrin cannot be obtained directly;12 the free-radical initiator used, probably due to a competi-
from the allylic alcohol no radical addition was observed tive polymerization of the free-radical acceptor. From less
whatever the method used.
sensitive to polymerization free-radical acceptors, such as
enones, the reaction took place in the presence of Et3B
(0.3 equiv). However, a mixture of iodophosphonate 2
and adduct 12 was obtained after 3 hours at 20 °C. Opti-
mization of the experimental conditions allowed to reach
completion from cyclic enones and Et3B (0.6 equiv) after
6 hours under stirring (Scheme 6). In this case, addition of
10% of the radical initiator every hour was required to
observe reproducible results. From cyclohexenone and
cyclopentenone, secondary difluoromethylphosphonates
were obtained. The corresponding cycloalkanones 12a19
and 12b were isolated in 69% and 62% yields, respective-
ly. Traces of 2-iodo cycloalkanone were observed in the
crude mixture (19F NMR). In contrast to nonactivated al-
kenes, the expected a-iodoketone was presumably too
reactive and gave back the intermediate radical. The re-
duction of this intermediate radical occurred probably
through a hydrogen transfer reaction from the n-hexane
coming from the added Et3B solution (1 M in n-hexane).
This kind of reduction was previously reported in the lit-
erature from xanthates.15 From alicyclic enones, such as
the ethylvinyl ketone, a mixture of alkanone 13 and io-
doalkanone 14 was produced in a 9:1 ratio. The corre-
sponding phosphonate 13 was obtained in 77% yield. In
all cases no reaction occurred when the alkenone and the
iodophosphonate were reacted in the presence of sodium
dithionite or lauroyl peroxide
The addition reaction was then extended to electron-rich
alkenes such as alkylvinyl ethers. From n-butyl vinyl
ether, the reaction afforded a mixture of products identi-
fied as the hemiacetal 9 and the corresponding aldehyde
10 in 4:6 ratio in the crude (Scheme 5). The methods B
(Et3B),13 or C (dilauroyl peroxide) did not allow to obtain
any addition products. The presence of water seems to be
necessary to convert in situ the expected unstable iodo-
ether into the corresponding hemiacetal. Indeed, traces of
hemiacetal were observed when the reaction was initiated
by Et3B in CH2Cl2 containing 5–10% of water. However,
during the separation of 9 and 10 by flash chromatogra-
phy, conversion of the acetal 9 in 10 followed by elimina-
tion of a fluorine atom from the aldehyde 10 occurred.14
In this case, only a mixture of alkene stereoisomers 11
was isolated in low yield (32%). The addition of a catalyt-
ic amount of HClaq (1%) in THF at room temperature to
the crude mixture afforded exclusively the aldehyde 10 in
65% yield. This aldehyde was obtained after 1 hour under
stirring followed by a short filtration on a silica pad.
BuO
OH
Na2S2O4, NaHCO3,
CF2P(O)(Oi-Pr)2
MeCN–H2O (5:3),
BuO
12 h, 20 °C
HCl,
THF
9
+
ICF2P(O)(Oi-Pr)2
CF2P(O)(Oi-Pr)2
2
O
F
10
65%
SiO2
4:6
P(O)(Oi-Pr)2
O
O
32%
11
O
n
Z/E = 1:1
Et3B (0.6 equiv),
CH2Cl2, 6 h, 20 °C
Scheme 5 Vinyl ether as free-radical trap
69%, n = 1
62%, n = 0
CF2P(O)(Oi-Pr)2
n
In contrast, from cyclic vinyl ethers the hemiacetal was
obtained exclusively under the method A (Table 1, entries
5 and 6). From 2,3-dihydrofurane, the trans-hemiacetal 7
was formed as major product in a 9:1 ratio. The mixture
of isomers was isolated in excellent yield (89%). The
trans configuration was deduced from NMR data and con-
firmed by 1H{19F} HOESY experiment, which showed a
correlation between the hydrogen atom H2 and the two
fluorine atoms of the CF2 group. Again, no result was ob-
12a n = 1
12b n = 0
O
ICF2P(O)(Oi-Pr)2
O
2
Et3B (0.6 equiv),
CH2Cl2, 6 h, 20 °C
CF2P(O)(Oi-Pr)2
+
I
13
14
9:1
O
77%
CF2P(O)(Oi-Pr)2
Scheme 6 Radical-conjugated addition
Synlett 2009, No. 6, 981–985 © Thieme Stuttgart · New York

984
A. Sène et al.
LETTER
L. J. Fluorine Chem. 2005, 126, 63. (f) Ghattas, W.; Hess,
C. R.; Iacazio, G.; Hardré, R.; Klinman, J. P.; Réglier, M.
J. Org. Chem. 2006, 71, 8618. (g) Moreno, B.; Quehen, C.;
Rose-Hélène, M.; Leclerc, E.; Quirion, J.-C. Org. Lett. 2007,
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However, this radical-conjugated addition was limited
since no addition was observed, neither from (E)-cinnam-
aldehyde nor from (E)-4-phenyl-butenone. The substitu-
tion of the double bond appeared as a limiting parameter.
These unexpected results raise the question concerning
the electronic character of the phosphonodifluoromethyl
radical. As speculated earlier, the electronic character of
the difluoroalkyl radical should be dominated by the in-
ductive effect of the fluorine atoms, but the influence of
the fluorine lone pairs adjacent to the carbon-centered rad-
ical play a major role, giving it rather a nucleophilic char-
acter.16 Although no theoretical data are available, it
might be tempting to speculate that the phosphonodifluo-
roalkyl radical exhibit an electrophilic/nucleophilic char-
acter. The phosphonoester function play a crucial role
since traces of adduct were detected in the crude mixture
when the reaction was realized from BrCF2CO2Et in the
presence of Et3B (18 h at 20 °C).
In conclusion, this radical-conjugated addition17 opened a
new and attractive alternative to prepare secondary phos-
phonates taking into account that only few examples of
the anionic version of this reaction are known.18 This re-
sult comes to complement the panel of addition of fluori-
nated free radicals onto electron-deficient alkenes
reported in the literature.16 Investigations to prepare im-
portant analogues of nucleotides and cyclitols from func-
tionalized cyclic enones are under way.
(3) (a) Yang, Z.; Burton, D. J. Tetrahedron Lett. 1991, 32,
1019. (b) Yang, Z.; Burton, D. J. J. Org. Chem. 1992, 57,
4676.
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G.; Piettre, S. Org. Lett. 2001, 3, 185. (b) Pignard, S.;
Lopin, C.; Gouhier, G.; Piettre, S. R. J. Org. Chem. 2006, 71,
31. (c) Murakami, S.; Kim, S.; Ishii, H.; Fuchigami, T.
Synlett 2004, 815.
(6) (a) Huang, B.; Wu, F.; Zhou, C. J. Fluorine Chem. 1995, 75,
1. (b) Wu, F.; Huang, B.; Lu, L.; Huang, W. J. Fluorine
Chem. 1996, 80, 91. (c) Petrik, V.; Cahard, D. Tetrahedron
Lett. 2007, 48, 3327. (d) Li, Y.; Li, H.; Hu, J. Tetrahedron
2009, 65, 478.
(7) Li, A.; Chen, Q. Synthesis 1996, 606.
(8) Yang, X.; Zhu, Y.; Fang, X.; Yang, X.; Wu, F.; Shen, Y.
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(9) Nair, K. D.; Guneratne, R. D.; Modak, A. S.; Burton, D. J.
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(10) Henry-dit-Quesnel, A.; Toupet, L.; Pommelet, J.-C.;
Lequeux, T. Org. Biomol. Chem. 2003, 1, 2486.
(11) The elimination of HI was also observed when crude 5b was
treated with DBU in CH2Cl2 over 2 h at 20 °C.
(12) Xu, Y.; Prestwich, G. D. Org. Lett. 2002, 4, 4021.
(13) Li, Y.; Liu, J.; Zhang, L.; Zhu, L.; Hu, J. J. Org. Chem. 2007,
72, 5824.
(14) Chambers, R. D.; Jaouhari, R.; O’Hagan, D. Tetrahedron
1989, 45, 5101.
(15) (a) Quiclet-Sire, B.; Zard, S. Z. J. Am. Chem. Soc. 1996, 118,
9190. (b) Studer, A.; Amrein, S. Synthesis 2002, 835.
(c) Jean-Baptiste, L.; Yemets, S.; Legay, R.; Lequeux, T.
J. Org. Chem. 2006, 71, 2352.
Acknowledgment
This work has been performed through the interregional Norman
Chemistry Network (CRUNCh), the ‘Région Haute-Normandie’,
the ‘Region Basse-Normandie’, European funding (Erasmus pro-
gram of the University of Chemnitz) and the ‘Ministère de l’Enseig-
nement Supérieur et de la Recherche’ are gratefully thanks for their
financial support.
(16) (a) Buttle, L. A.; Motherwell, W. B. Tetrahedron Lett. 1994,
35, 3995. (b) Dolbier, W. R. Chem. Rev. 1996, 96, 1557.
(17) Srikanth, G. S. C.; Castle, S. L. Tetrahedron 2005, 61,
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(18) (a) Lequeux, T. P.; Percy, J. M. J. Chem. Soc., Chem.
Commun. 1995, 2111. (b) Kawamoto, A. M.; Campbell,
M. M. J. Chem. Soc., Perkin Trans. 1 1997, 1249.
(c) Murano, T.; Muroyama, S.; Yokomatsu, T.; Shibuya, S.
Synlett 2002, 1657. (d) Hikishima, S.; Isobe, M.; Koyanagi,
S.; Soeda, S.; Shimeno, H.; Sibuya, S.; Yokomatsu, T.
Bioorg. Med. Chem. 2006, 14, 1660.
(19) Typical Procedure for the Synthesis of Phosphonate 12a
To a solution of the 2-cyclohexenone (0.073 mL, 0.76
mmol) and iodo-difluoromethylphosphonate 2 (200 mg,
0.58 mmol) in CH2Cl2 (5 mL) at 20 °C under N2 was slowly
added a solution of Et3B (0.058 mL, 1 M in n-hexane).
Addition of Et3B (5 × 0.058 mL) was realized every 1 h until
complete consumption of the iodophosphonate. After 6 h
under stirring, the solvents were evaporated under reduced
pressure, and the crude mixture was purified by flash column
chromatography (n-C5H12–EtOAc, 3:2) to afford the
phosphonoketone 12a (125 mg, 69%). 1H NMR (250 MHz,
CDCl3): d = 1.30 (d, 3JHH = 6.2 Hz, 12 H), 1.53–1.67 (m, 2
H), 2.05–2.61 (m, 7 H), 4.78 (dsept, 3JHH = 3JHP = 6.2 Hz, 2
H). 19F NMR (235 MHz, CDCl3): d = –115.7 (ddd, 2JFF = 299
Hz, 2JFP = 108 Hz, 3JFH = 13 Hz), –118.14 (ddd, 2JFF = 299
References and Notes
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Chem. Commun. 1990, 1053. (e) Kim, C. U.; Luh, B. Y.;
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(b) Julià, L.; Bosch, M. P.; Rodriguez, S.; Guerrero, A.
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Synlett 2009, No. 6, 981–985 © Thieme Stuttgart · New York

LETTER
Hz, 2JFP = 108 Hz, 3JFH = 13 Hz). 31P NMR (101 MHz,
Radical Conjugated Addition
985
CDCl3): d = –119.04 (ddd,2JFF = 298 Hz, 2JFP = 101 Hz,
CDCl3): d = 4.64 (t, 2JPF = 108 Hz). 13C (63 MHz, CDCl3):
d = 23.7 (m, i-Pr and CH2), 24.0 (d, 3JCP = 2.5 Hz, i-Pr), 24.2
(s, CH2), 39.8 (dt, 3JCF = 3JCP = 4.6 Hz, CH2), 40.9 (s, CH2),
42.8 (dt, 2JCF = 20.6 Hz, 2JCP = 15.3 Hz, CH), 73.8 (d,
2JCP = 3.0 Hz, i-Pr), 73.9 (d, 2JCP = 3.0 Hz, i-Pr), 121.9
(dt, 1JCF = 263.0 Hz, 1JCP = 214.0 Hz, CF2), 208.9 (s, CO).
HRMS (ESI): m/z [M + H]+ calcd for C13H24F2O4P:
313.1380; found: 313.1366.
3JFH = 15 Hz), –117.10 (ddd, 2JFF = 298 Hz, 2JFP = 101 Hz,
3JFH = 17 Hz). 31P NMR (101 MHz, CDCl3): d = 4.79 (t,
2JPF = 108 Hz). 13C (63 MHz, CDCl3): d = 22.1 (dt, 3JCF
=
3JCP = 5.1 Hz, CH2), 23.7 (d, 3JCP = 4.2 Hz, i-Pr), 24.0 (d,
3JCP = 3.3 Hz, i-Pr), 37.5 (s, CH2), 38.1 (dt, 3JCF = 3JCP = 3.0
Hz, CH2), 40.5 (dt, 2JCF = 21.4 Hz, 2JCP = 15.2 Hz, CH), 73.8
(d, 2JCP = 7.2 Hz, i-Pr), 73.81 (d, 2JCP = 7.1 Hz, i-Pr), 119.9
(dt, 1JCF = 262.0 Hz, 1JCP = 217.0 Hz, CF2), 215.8 (s, CO).
ESI-HRMS: m/z [M + H]+ calcd for C12H22F2O4P: 299.1224;
found: 299.1213.
Phosphonate 12b: 1H NMR (250 MHz, CDCl3): d = 1.31 (d,
3JHH = 6.2 Hz,12 H), 1.97–2.38 (m, 6 H), 2.84–2.91 (m, 1 H),
4.80 (dsp, 3JHH = 3JHP = 6.2 Hz, 2 H). 19F NMR (235 MHz,
Synlett 2009, No. 6, 981–985 © Thieme Stuttgart · New York