A facile and efficient synthesis of diethyl α, α- chlorofluoroalkanephosphonates

Article abstract of DOI:10.1002/hc.20604

A facile and efficient synthetic methodology for the preparation of diethyl α, α-chlorofluoro- alkanephosphonates is described. A wide variety of diethyl α-hydroxyphosphonates were investigated by a two-step halogenation procedure, which includes nucleoph

Full text of DOI:10.1002/hc.20604

Heteroatom Chemistry
Volume 21, Number 4, 2010
A Facile and Efficient Synthesis of Diethyl
α,α-Chlorofluoroalkanephosphonates
Zhi Guan, Di Wu, Jian-Ping Fu, and Yan-Hong He
School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715,
People’s Republic of China
Received 5 January 2010; revised 14 March 2010
and electronic similarities to the parent phosphate
ABSTRACT: A facile and efficient synthetic methodo-
groups [12–21]. A number of methods for the intro-
logy for the preparation of diethyl α,α-chlorofluoro-
duction of a halogen and two same halogens at the
alkanephosphonates is described. A wide variety of
α-CH2 position of phosphonates by the nucleophilic
diethyl α-hydroxyphosphonates were investigated by
and electrophilic halogenations have been reported.
a two-step halogenation procedure, which includes
The nucleophilic halogenation is effectively achieved
nucleophilic chlorination with PPh3 and CCl4 and
usually starting with α-hydroxyphosphonates or
electrophilic fluorination with N-fluorobisbenzene-
α-ketophosphonates using nucleophilic halogenat-
sulfonimide. Aromatic and aliphatic α,α-chlorofluoro-
ing reagents, such as Et2N-SF3 (DAST) [22–
phosphonates could be prepared by this method with
24] for fluorination, PPh3/CCl4 [25] and SOCl2
ꢀ
C
acceptable yields.
2010 Wiley Periodicals, Inc. Het-
[26] for chlorination, SOBr2 [26], PPh3/CBr4 [27],
PPh3/Br2/pyridine [27], CH2 CHCH2Br/N,Nꢁ-car-
bonyldiimidazole (CDI) [28], and PPh3/DDQ/n-
Bu4NBr [29] for bromination, MeI/CDI [28], PI3 [26],
and PPh3/DDQ/n-Bu4NI [29] for iodination. Mean-
while, electrophilic halogenation is a more pow-
erful method to generate α-halogenated phospho-
nates and α,α-dihalogenated phosphonates, which
directly started with phosphonates. Electrophilic
halogenating reagents usually are N-fluorobisben-
zenesulfonimide (NFSI), selectfluor, and a lot of
other electrophilic fluorinating reagents for flu-
orination [30–33], hexachloroethane (C13C CC13)
[32], and CCl4[34] for chlorination, tetrachlorodi-
bromoethane (BrC12C CC12Br) [32] for bromina-
tion, and iodine [32] for iodination. However, little
attention has been given to explore more compli-
cated α,α-chlorofluorophosphonates as yet. As part
of our program to extend new potent and non-
peptidyl inhibitors of protein tyrosine phosphatases
(PTPs), it is necessary to synthesize a wide variety
of α,α-chlorofluorophosphonate molecules. Accord-
ing to the literature, the α-monobromophosphonates
[35], α-monofluorophosphonates [4,23], and α,α-
difluorophosphonates [36–38] as natural phosphate
mimetics can potentially target phosphate-binding
eroatom Chem 21:250–255, 2010; Published online in
Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20604
INTRODUCTION
In the past few years, the α-functionalized phospho-
nates have attracted considerable attention in the
field of biology, pharmacology, and organic chem-
istry [1–7]. In particular, α-halogenated phospho-
nates, which are widely utilized as synthetic reagents
and especially as good precursors for the synthesis
of symmetrical or unsymmetrical α-halogenoalkenes
and alkynes in mild conditions by the Wittig–Horner
reaction [8–11], are fascinating organophosphorus
compounds. Moreover, the α-monohalogenated and
α,α-dihalogenated phosphonates are often designed
as phosphate mimics to be used as enzyme inhibitors
and metabolite probes because of their structural
Correspondence to: Yan-Hong He; e-mail: heyh@swu.edu.cn.
Contract grant sponsor: State Personnel Ministry.
Contract grant sponsor: Natural Science Foundation Project of
CQ CSTC of 2009BA5051.
c
ꢀ
2010 Wiley Periodicals, Inc.
250

A Facile and Efficient Synthesis of Diethyl α,α-Chlorofluoroalkanephosphonates 251
pockets and are directed to an enzyme active site
Our initial approach to the introduction of flu-
orine atom relied on a nucleophilic fluorination to
prepare the α-fluorophosphonates (2) with Et2N-
SF3 (DAST), and this step worked quite well. How-
ever, the subsequent electrophilic chlorination of
α-monofluorophosphonates with C13C CC13 and
sodium hexamethyldisilazane (NaHMDS) did not
proceed as smoothly as expected. Thereby, the two-
step halogenation procedure that included a nucle-
ophilic fluorination and electrophilic chlorination is
not advisable, because of weak nucleophilicity of in-
termediate α-fluorophosphonate carbanions and the
weak electrophilicity of the C13C CC13.
The poor results led us to seek an alternate pre-
paration of α,α-chlorofluorophosphonates 3. We de-
cided to exchange the sequence of halogenations.
Therefore, the appropriate α-chlorophosphonates
were formed by treatment of α-hydroxyphospho-
nates with triphenylphosphine in CCl4 [25,39] at
80◦C in high yields (2a–2i, Table 1, Scheme 2).
In the last step, the diethyl α-chlorophosphonate
carbanions, the key intermediates in the synthesis
of α,α-chlorofluorophosphonates 3, were very selec-
tively formed from diethyl α-chlorophosphonates 2
by using sodium hexamethyldisilazane (NaHMDS,
1.5–2 equiv) as metallating agent at −78◦C
(Scheme 3). The fluorination step took place at low
temperature (−78◦ to −30◦C) using excess fluori-
nating reagents (NFSI, 1.3 equiv). After warming
to room temperature, the reaction was quenched
with dilute aqueous HCl (0.01 N) to neutralize excess
NaHMDS. The crude diethyl α,α-chlorofluorophos-
phonates 3 could be isolated through a silica
gel column with EtOAc/hexane (1:5). Fortunately,
this procedure worked well and a wide variety of
α,α-chlorofluoroalkylphosphonates and α,α-chloro-
fluorobenzylphosphonates (3a–3i, Table 2) were ob-
tained in reasonable to good yields except 3a and 3d.
All the structures were confirmed by the analytical
and spectral data.
for covalent modification in an activity-dependent
fashion. But these compounds have respective draw-
backs. For example, the radius of bromine atom is
much larger than hydrogen, which resulted in the
probes having a difficulty to approach target pock-
ets, and the fluorine atom is a poor leaving group.
On the basis of both electronic and steric consider-
ations, α,α-chlorofluorophosphonates as enzyme in-
hibitors and phosphate mimics will have their own
special advantages. Therefore, it is a desirable and
unfulfilled goal to develop a general method to ob-
tain a wide variety of α,α-chlorofluorophosphonates.
This paper reports a new and efficient approach
to synthesize diethyl α,α-chlorofluorophosphonates,
which includes a two-step halogenation procedure.
We found that a wide range of α,α-chlorofluorophos-
phonates could be prepared by this method with
acceptable yields. Diethyl α,α-chlorofluoroalkyl-
phosphonates can be easily synthesized, besides di-
ethyl α,α-chlorofluoro benzylphosphonates that we
reported recently [39].
RESULTS AND DISCUSSION
Since electrophilic monohalogenation at the α-CH2
position of phosphonates could directly form com-
plex mixtures of monohalogeno-, dihalogeno-, and
nonhalogenophonates, we started our preparation
with nucleophilic halogenation of α-hydroxyphos-
phonates (1) to give monohalogenophonates (2),
which underwent electrophilic halogenation to give
diethyl α,α-chlorofluorophosphonates (3). The strat-
egy is shown in Scheme 1.
A variety of starting diethyl α-hydroxyphos-
phonates, with different length of carbon alkyl
chains or substituted aromatic rings, were involved
in the reaction sequence. They could be easily pre-
pared in excellent yields from corresponding aldehy-
des and diethyl phosphite (the Pudovik reaction) on
a laboratory scale [40]. With these starting materials
in hand, the diethyl α,α-chlorofluorophosphonates
were prepared by a nucleophilic halogenation proce-
dure and then electrophilic halogenation procedure
(Scheme 1).
The compounds were stable at 4◦C for at least
several weeks. An array of electron-withdrawing or
electron-donating functional groups, such as ether,
halogen, and cyano, on aromatic rings could be tol-
erated. We also investigated the influence of steric
O
O
O
Nucleophilic
halogenation
Electrophilic
halogenation
R
P(OEt)2
R
P(OEt)2
R
P(OEt)2
F
Cl
OH
1
X
2
3
R = aryl or alkyl, X = Cl or F
SCHEME 1
Heteroatom Chemistry DOI 10.1002/hc

252 Guan et al.
TABLE 1 Diethyl α-Chlorophosphonates 2
2
R
1H NMR (CDCl ) δα
(2JPH
)
13C NMR (CDCl ) δα
(1JPC
CH
)
Yielda (%)
CH
3
3
a
b
c
d
e
f
g
h
i
2-CH3OC6H4-
3-CH3OC6H4-
3-NCC6H4-
2-ClC6H4-
3-ClC6H4-
Et-
i-Pr-
n-Pr-
i-Bu-
5.64 (d, 2JPH = 14.0)
4.87 (d, 2JPH = 14.1)
4.91 (d, 2JPH = 14.8)
5.58 (d, 2JPH = 14.8)
4.86 (d, 2JPH = 14.4)
3.78 (dt, 2JPH = 10.3)
3.86 (dd, 2JPH = 12.1)
3.86 (dt, 2JPH = 10.7)
3.92 (dt, 2JPH = 11.3)
45.5 (d, 1JPC = 162.5)
53.3 (d, 1JPC = 158.6)
52.3 (d, 1JPC = 157.6)
48.9 (d, 1JPC = 161.0)
52.7 (d, 1JPC = 158.2)
54.1 (d, 1JPC = 158.7)
59.0 (d, 1JPC = 156.6)
51.7 (d, 1JPC = 159.1)
50.3 (d, 1JPC = 159.7)
77
81
85
80
83
89
82
76
79
aIsolated yields.
O
O
phonates. Under these conditions, the step of de-
protonation to form diethyl α-chlorophosphonates
carbanions was slowed down because of a difficult
approach of NaHMDS in a highly crowded position.
α,α-Chlorofluoroalkylphosphonates (3f–3i) were ob-
tained in moderate yields.
PPh3, CCl4, 80°C
R
P(OEt)2
R
P(OEt)2
OH
1
X
2
X = Cl
SCHEME 2
CONCLUSION
hindrance of the substituents (R). The reaction was
general for substrates 2 with m-substituted aromatic
rings or with alkyl substituents. However, o-methoxy
derivative 3a and o-chloro derivative 3d were not
obtained by flash column chromatography of silica
gel, and only trace products were observed by TLC.
This decrease in yield could be attributed to the in-
creased steric demands of the o-substituted phos-
In conclusion, we have demonstrated that a wide
variety of diethyl α,α-chlorofluorophosphonates can
be synthesized by two steps from the correspond-
ing α-hydroxyphosphonates via nucleophilic chlo-
rination and then electrophilic fluorination. This
procedure is applicable to preparation of a wide
range of aromatic and aliphatic substituted α,α-
chlorofluorophosphonates. These compounds could
be potential inhibitor of PTPs. Attempts toward the
asymmetric version of the reaction, as well as the
extension of this method, are currently underway.
O
O
°
°
NFSI, NaHMDS, –78 C to –30 C
R
P(OEt)
2
R
P(OEt)
2
F
Cl
X
2
EXPERIMENTAL
General
3
X = Cl
NMR spectra were operated at 300 MHz for pro-
ton, 75 MHz for carbon, 121.5 MHz for phosphorus,
SCHEME 3
TABLE 2 Diethyl α,α-Chlorofluorophosphonate 3
3
R
19F NMR (CDCl ) δα
(2JFP
)
31P NMR (CDCl ) δα
(2JPF
CClF
)
Yield (%)a
CClF
3
3
a
b
c
d
e
f
g
h
i
2-CH3OC6H4-
3-CH3OC6H4-
3-NCC6H4-
2-ClC6H4-
3-ClC6H4-
Et-
i-Pr-
n-Pr-
i-Bu-
Trace
79
82
Trace
80
62
72
65
52
−132.04 (d, 2JFP = 93.1)
−128.38 (d, 2JFP = 90.2)
−130.60 (d, 2JFP = 93.1)
−127.94 (dq, 2JFP = 87.4)
−124.20 (d, 2JFP = 90.2)
−127.71 (dq, 2JFP = 90.2)
−126.78 (dq, 2JFP = 90.2)
2.23 (d, 2JPF = 90.6)
1.35 (d, 2JPF = 89.2)
4.10 (d, 2JPF = 90.3)
4.06 (d, 2JPF = 90.2)
3.74 (d, 2JPF = 90.2)
5.54 (d, 2JPF = 90.4)
4.73 (d, 2JPF = 90.5)
aIsolated yields.
Heteroatom Chemistry DOI 10.1002/hc

A Facile and Efficient Synthesis of Diethyl α,α-Chlorofluoroalkanephosphonates 253
and 282 MHz for fluorine. 31P downfield shifts (δ)
are expressed in ppm with a positive sign relative
to external 85% H3PO4 in H2O. 1H and 13C chemical
shifts (δ) are reported in ppm relative to CDCl3 as in-
ternal standard. 19F chemical shifts (δ) are reported
in ppm relative to CFCl3 as external standard. Cou-
pling constants (J) are given in hertz. The following
abbreviations are used: s, d, t, q, p, h, and m for
singlet, doublet, triplet, quadruplet, pentuplet, hep-
tuplet, and multiplet, respectively. High-resolution
electron microscopy (HRMS) spectra were recorded
on a high resolution ESI-FTICR mass spectrome-
try (Varian 7.0T). Organic solvents were purified by
standard procedures. Tetrahydrofuran (THF) was
distilled under an inert atmosphere from purple so-
lutions of sodiumbenzophenone ketyl. The synthesis
of all compounds was carried out under dry N2.
A solution of NFSI (1.31 mmol) in dry THF (5 mL)
was added over a period of 10 min. After addition,
the solution was stirred for 1 h and then allowed
to warm to −30◦C. The reaction was quenched with
0.01 N HC1, and the resulting solution was extracted
with CH2Cl2. The combined organic layer was dried
over MgSO4, and solvents were removed under re-
duced pressure. The crude material was purified via
flash column chromatography of silica gel [39].
Diethyl α,α-Chlorofluoro-3-methoxybenzylphos-
phonates (3b). 1H NMR (300 MHz, CDCl3): δ = 1.22
(t, J = 6.8 Hz, 3H), 1.39 (t, J = 6.7 Hz, 3H), 3.84
(s, 3H), 3.95–4.00 (m, 1H), 4.08–4.16 (m, 1H), 4.30–
4.34 (m, 2H), 6.96 (d, J = 7.4 Hz, 1H), 7.20 (s, 1H),
7.34 (d, J = 7.9 Hz, 1H), 7.38–7.93 (m, 1H) ppm; 13
C
3
NMR (75 MHz, CDCl3): δ = 16.2 (d, JPC = 5.6 Hz),
3
2
16.4 (d, JPC = 5.6 Hz), 55.4, 65.2 (d, JPC = 7.0 Hz),
2
1
65.6 (d, JPC = 6.9 Hz), 106.7 (dd, JPC = 195.8 Hz,
1 JFC = 258.6 Hz), 111.7, 116.0, 118.5, 129.4, 137.3,
159.4 ppm; 31P NMR (121.5 MHz, CDCl3): δ = 2.23
General Procedure for the Preparation of
α-Hydroxyphosphonates 1
To a solution of sodium ethoxide (1.0 mmol) in
CH2Cl2 (10 mL), diethyl phosphite (0.912 mmol) was
added via a syringe at −35◦C under argon. The re-
action was stirred for 30 min, and a solution of
aldehyde (0.76 mmol) in CH2Cl2 (5 mL) was added.
The mixture was stirred for 3–5 h. The reaction was
quenched with 0.1 N HC1, and the resulting solu-
tion was extracted with ethyl acetate. The organic
layer was dried with MgSO4, and the solvents were
removed in vacuo. The crude material was purified
via flash column chromatography [40].
(d, JFP = 90.6) ppm; 19F NMR (282 MHz, CDCl3):
2
2
δ = −132.04 (d, JPF = 93.1 Hz) ppm; HRMS for
C12H17ClFO4P [M + Na+]: calculated 333.0429; found
333.0425.
Diethyl α,α-Chlorofluoro-3-cyanobenzylphospho-
nates (3c). 1H NMR (300 MHz, CDCl3): δ = 1.26 (t,
J = 7.0 Hz, 3H), 1.40 (t, J = 7.0 Hz, 3H), 4.06–4.19
(m, 2H), 4.30–4.40 (m, 2H), 7.58 (t, J = 7.7 Hz, 1H),
7.73 (d, J = 7.6 Hz, 1H), 7.80 (d, J = 11.0 Hz, 2H)
ppm; 13C NMR (75 MHz, CDCl3): δ = 16.2 (d, 3 JPC
=
5.5 Hz), 16.4 (d, 3 JPC = 5.5 Hz), 65.4 (d, 2 JPC = 7.1 Hz),
2
1
General Procedure for the Preparation of
α-Chlorophosphonates 2 from
α-Hydroxyphosphonates 1
66.1 (d, JPC = 7.2 Hz), 105.7 (dd, JPC = 193.9 Hz,
1 JFC = 259.0 Hz), 112.8, 117.9, 129.3, 129.8, 130.7,
133.5, 137.8 ppm; 31P NMR (121.5 MHz, CDCl3): δ =
2
1.35 (d, JFP = 89.2 Hz) ppm; 19F NMR (282 MHz,
A solution of 1 (3.46 mmol) and triphenylposphine
(5.19 mmol) in dry CCl4 was refluxed for 8 h un-
der argon. Then, the mixture was evaporated under
reduced pressure, and the semisolid residue was ex-
tracted with petroleum ether. The combined extracts
were filtered, and the solvent was removed under re-
duced pressure. The crude material was purified by
flash column chromatography of silica gel [25,39].
CDCl3): δ = −128.38 (d, 2 JPF = 90.2 Hz) ppm; HRMS
for C12H14ClFNO3P [M + Na+]: calculated 328.0276;
found 328.0280.
Diethyl α,α-Chlorofluoro-3-chlorobenzylphospho-
nates (3e). 1H NMR (300 MHz, CDCl3): δ = 1.25
(t, J = 7.1 Hz, 3H), 1.39 (t, J = 7.0 Hz, 3H), 4.01–
4.19 (m, 2H), 4.30–4.38 (m, 2H), 736 (d, J = 7.8 Hz,
1H), 7.41 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 7.2 Hz,
1H), 7.65 (s, 1H) ppm; 13C NMR (75 MHz, CDCl3):
General Procedure for the Preparation of
α,α-Chlorofluorophosphonates 3 from
α-Chlorophosphonates 2
3
3
δ = 16.2 (d, JPC = 5.6 Hz), 16.4 (d, JPC = 5.6 Hz),
65.3 (d, 2 JPC = 7.1 Hz), 65.8 (d, 2 JPC = 7.2 Hz), 106.0
1
1
To a solution of the α-chlorophosphonates 2
(0.94 mmol) in dry THF (10 mL) at −78◦C, drop wise
a solution of NaHMDS (1.69 mmol, 2.0 M in THF) in
dry THF (5 mL) under argon was added. The result-
ing dark green solution was stirred for 1 h at −78◦C.
(dd, JPC = 195.6 Hz, JFC = 258.6 Hz), 124.6 (d,
3 JFC = 8.0 Hz), 126.4 (d, 3 JFC = 8.8 Hz), 129.6, 130.2,
134.4, 137.6 ppm; 31P NMR (121.5 MHz, CDCl3): δ =
4.10 (d, JFP = 90.3 Hz) ppm; 19F NMR (282 MHz,
2
CDCl3): δ = −130.60 (d, 2 JPF = 93.1 Hz) ppm; HRMS
Heteroatom Chemistry DOI 10.1002/hc

254 Guan et al.
for C11H14Cl2FO3P [M + Na+]: calculated 336.9934;
3
2 JPF = 90.2 Hz, JHF = 19.7 Hz) ppm; HRMS for
C9H19ClFO3P [M + Na+]: calculated 283.0637; found
found 336.9927.
283.0634.
Diethyl α,α-Chlorofluoroethylphosphonates (3f).
1H NMR (300 MHz, CDCl3): δ = 1.19 (t, J = 7.3 Hz,
3H), 1.36–1.42 (m, 6H), 2.05–2.37 (m, 2H), 4.24–4.38
(m, 4H) ppm; 13C NMR (75 MHz, CDCl3): δ = 6.6
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3
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2
2 JPC = 20.6 Hz), 64.6 (d, JPC = 7.0 Hz), 65.1 (d,
1
1
2 JPC = 7.0 Hz), 110.0 (dd, JPC = 195.9 Hz, JFC
=
255.4 Hz) ppm; 31P NMR (121.5 MHz, CDCl3): δ =
4.06 (d, JFP = 90.2 Hz) ppm; 19F NMR (282 MHz,
2
2
3
CDCl3): δ = −127.94 (dq, JPF = 87.4 Hz, JHF
=
11.3 Hz) ppm; HRMS for C7H15ClFO3P [M + Na+]:
calculated 255.0324; found 255.0325.
Diethyl α,α-Chlorofluoroisopropylphosphonates
(3g). 1H NMR (300 MHz, CDCl3): δ = 1.16 (dd,
J1 = 3.8 Hz, J2 = 6.4 Hz, 6H), 1.36–1.42 (m, 6H),
2.53–2.60 (m, 2H), 4.24–4.37 (m, 4H) ppm; 13C NMR
3
(75 MHz, CDCl3): δ = 15.7 (d, JPC = 6.8 Hz), 16.3
3
3
(d, JPC = 5.7 Hz), 17.4 (d, JPC = 6.0 Hz), 36.4 (d,
2 JPC = 19.2 Hz), 64.4 (d, JPC = 7.5 Hz), 65.0 (d,
2
2 JPC = 10.8 Hz), 113.5 (dd, JPC = 192.2 Hz, JFC
=
1
1
255.8 Hz) ppm; 31P NMR (121.5 MHz, CDCl3): δ =
3.74 (d, JFP = 90.2 Hz) ppm; 19F NMR (282 MHz,
2
CDCl3): δ = −124.20 (d, 2 JPF = 90.2 Hz) ppm; HRMS
for C8H17ClFO3P [M + Na+]: calculated 269.0480;
found 269.0483.
Diethyl
α,α-Chlorofluoropropylphosphonates
(3h). 1H NMR (300 MHz, CDCl3): δ = 1.00 (t, J =
7.4 Hz, 3H), 1.39 (t, J = 7.0 Hz, 3H), 1.40 (t, J =
7.0 Hz, 3H), 1.66–1.77 (m, 2H), 2.04–2.36 (m, 2H),
4.24–4.38 (m, 4H) ppm; 13C NMR (75 MHz, CDCl3):
3
3
δ = 13.6, 15.8 (d, JPC = 6.0 Hz), 16.4 (d, JPC
5.8 Hz), 40.4 (d, JPC = 7.0 Hz), 40.7 (d, JPC
=
=
=
2
2
2
2
7.0 Hz), 64.5 (d, JPC = 7.1 Hz), 65.1 (d, JPC
7.0 Hz), 109.6 (dd, 1 JPC = 195.5 Hz, 1 JFC = 255.4 Hz)
ppm; 31P NMR (121.5 MHz, CDCl3): δ = 5.54 (d,
2 JFP = 90.4 Hz) ppm; 19F NMR (282 MHz, CDCl3):
2
3
δ = −127.71 (dq, JPF = 90.2 Hz, JHF = 8.5 Hz)
ppm; HRMS for C8H17ClFO3P [M + Na+]: calculated
269.0480; found 269.0478.
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G. M. J Chem Soc, Perkin Trans 1 2000, 3, 421.
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Diethyl
α,α-Chlorofluoroisobutylphosphonates
(3i). 1H NMR (300 MHz, CDCl3): δ = 1.02–1.05
(m, 6H), 1.39 (dt, J1 = 2.9 Hz, J2 = 7.0 Hz, 6H),
2.08–2.28 (m, 3H), 4.26–4.51 (m, 4H) ppm; 13C NMR
3
(75 MHz, CDCl3): δ = 16.4 (d, JPC = 5.6 Hz), 23.0,
3
2
24.0 (d, JPC = 10.0 Hz), 45.8 (d, JPC = 12.2 Hz),
64.6 (d, 2 JPC = 7.1 Hz), 65.2 (d, 2 JPC = 7.1 Hz), 110.1
(dd, 1 JPC = 195.9 Hz, 1 JFC = 257.5 Hz) ppm; 31P NMR
2
(121.5 MHz, CDCl3): δ = 4.73 (d, JFP = 90.5 Hz)
ppm; 19F NMR (282 MHz, CDCl3): δ = −126.78 (dq,
Heteroatom Chemistry DOI 10.1002/hc

A Facile and Efficient Synthesis of Diethyl α,α-Chlorofluoroalkanephosphonates 255
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Heteroatom Chemistry DOI 10.1002/hc