Synthesis of γ-butyrolactones containing α,α-difluoromethylenyl bisphosphonate initiated by Na2S2O4

Article abstract of DOI:10.1016/j.jfluchem.2006.11.009

Diethyl iododifluoromethylphosphonate (1) reacted with 4-pentenoic acids in the presence of Na₂S₂O₄ in aqueous acetonitrile solution at ambient temperature to afford various γ-butyrolactones containing α,α-difluoromethylenyl bisphosphonate moiety in moderate to good yields.

Full text of DOI:10.1016/j.jfluchem.2006.11.009

Journal of Fluorine Chemistry 128 (2007) 174–178
www.elsevier.com/locate/fluor
Synthesis of g-butyrolactones containing a,a-difluoromethylenyl
bisphosphonate initiated by Na2S2O4
a
Xueyan Yang a, Yaoping Zhu a, Xiang Fang a, Xianjin Yang a, Fanhong Wu a,b, , Yongjia Shen
*
a Laboratory for Advanced Material, Institute of Fine Chemicals, ECUST, Shanghai 200237, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
Received 20 October 2006; received in revised form 13 November 2006; accepted 22 November 2006
Available online 25 November 2006
Abstract
Diethyl iododifluoromethylphosphonate (1) reacted with 4-pentenoic acids in the presence of Na2S2O4 in aqueous acetonitrile solution at
ambient temperature to afford various g-butyrolactones containing a,a-difluoromethylenyl bisphosphonate moiety in moderate to good yields.
# 2006 Elsevier B.V. All rights reserved.
Keywords: Fluorinated phosphonate; 4-Pentenoic acids; Difluoromethylene; g-Butyrolactones
1. Introduction
of diethyl (iododifluoromethyl)phosphonate (1) with 4-pente-
noic acids.
Phosphorous compounds play an important role in all living
organisms and there are a great number of reports on the
preparation and biochemical studies on such compounds [1].
The introduction of the gem-difluoromethylene (CF2) moiety
into organic compounds has attracted much attention in recent
years because this group is usually regarded as an isopolar and
isosteric replacement for oxygen [2]. It was suggested that
(a,a-difluoroalky)phosphonates could mimic phosphate pro-
viding better bioactivities than corresponding phosphonates
[3]. Therefore, (a,a-difluoroalky)phosphonates have been
investigated as phosphonate analogues [4], enzyme inhibitors
[5], and chelating agents [6]. Since g-lactone represents a
significant kind of compounds with biological activity [7], we
focus on the synthesis of difluoromethylenated g-lactones
functionalized by bisphosphonate. There are limited reports on
the synthesis of g-lactones containing bisphosphonate [8,9],
especially in those containing difluoromethylenyl group [10].
The new synthetic route of such compounds is still interesting
and desirable. Here, we report the synthesis of g-butyrolactones
containing difluoromethylenyl bisphosphonate by the reaction
2. Results and discussion
Diethyl (iododifluoromethyl) phosphonate (1) was synthe-
sized in high yield via iodination of the zinc reagent,
(EtO)2P(O)CF2ZnBr, which was prepared by treating (bromo-
difluoromethyl)phosphonate (3) with activated Zn powder in
monoglyme, as known methods [11]. 3 was obtained in
excellent yield from triethyl phosphite (2) according to
literature [12] (Scheme 1).
The addition reaction of 1 to olefins has been completed in
the presence of Pd(PPh3)4 [13–15], Cu [14] or Na2S2O4 [16].
We investigated into the reaction of 1 with various 4-pentenoic
acids. Different initiators were applied to the reaction (Scheme
2). The details were summarized in Table 1. The results showed
that in the presence of Na2SO3, the reaction was completed with
85% conversion of 1 and 68% yield of g-lactone 5c (Table 1,
entry 1). The results were much unsatisfactory when thiourea
dioxide or rongalite were used as the initiator (Table 1, entries 4
and 5). When the reaction was carried out in the presence of
NaHSO3 or Na2S2O5, both the conversions and the yields were
very low (Table 1, entries 2 and 3). While treatment of 1 with
2-ethyl-4-pentenoic acid (4c) in the presence of Na2S2O4 in
CH3CN–H2O (v/v = 3:1) at 25 8C gave lactone (5c) in good
yield (81%) (Table 1, entry 6).
* Corresponding author at: Key Laboratory of Organofluorine Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China. Tel.: +86 21 64253530; fax: +86 21 64253074.
E-mail address: wfh@ecust.edu.cn (F. Wu).
0022-1139/$ – see front matter # 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2006.11.009

X. Yang et al. / Journal of Fluorine Chemistry 128 (2007) 174–178
175
Scheme 1.
Scheme 2.
Table 1
The reaction of 1 with 4c in the presence of different initiatora
Entry
Initiator
1:initiator:NaHCO3
Solvent (CH3CN/H2O)
Reaction temperature (8C)
Conversion of 1 (%)
Yieldb (%)
1
2
3
4
5
6
Na2SO3
1:2:2
3:1
3:1
3:1
3:1
3:1
3:1
25
25
25
25
25
25
85
10
68
9
NaHSO3
1:2:2
Na2S2O5
1:2:2
14
3
Rongalite
Thiourea dioxide
Na2S2O4
1:1.4:2
1:2.4:2.4
1:1.4:1.4
47
11
20
81
70
100
a
1:4c:NaOH = 1:1:1 for 8 h.
The yields were based on GC.
b
It was found that CH3CN–H2O (v/v = 3:1) could be used
dominated in the reaction. We supposed that the major cis-
or trans-isomer resulted from the major configuration of
the products: 6 (exo-RCH2 and exo-CH2CF2P), 7 (exo-Ph,
endo-CH2CF2P for the repulsion of large Ph) or 8 (exo-
CH2CF2P, endo-NHCOR0 for the hydrogen bond between NH
and C O) (Scheme 3). The purification of the mixture of two
isomers was easily achieved by the column chromatograph
eluting with the mixture of petroleum and ethyl acetate
(Scheme 4).
as the solvent in this reaction (Table 2, entry 1). When
CH3CN–H2O (v/v = 1:1) or CH3CN–H2O (v/v = 1:3) were
utilized, the yields decreased (Table 2, entries 2 and 3). The
temperature variation also affected the reaction. For example,
when the reaction of 1 with 4c took place at 0 8C for 8 h, only
65% yield were given (Table 2, entry 4). The yield was also
reduced if the temperature was higher than 25 8C (Table 2,
entry 5).
The results of the reaction of 1 with different 4-pentenoic
acids 4 were listed in Table 3. It showed that for 2-
substituted-4-pentinoic acids (Table 3, entries 2–9), a mixture
of cis-/trans- isomers in ratios of between 1.05:1 and 1:1.83
was obtained. For substituents RCH2 (R H, CH3, C2H5,
C3H7, Ph) on 2-position of 4-pentenoic acids (4b–4f), cis-
isomer was formed as the main products. While for group
Ph, NHCOPh, NHCOPhOCH3-p (4g–4i), trans-lactones
The mechanism of fluoroalkylation-lactonization has been
suggested in our previous publications [15]. Similarly, the
reaction of 1 with 4-pentenoic acids 4 to give corresponding g-
butyrolactones 5 may also involve the addition of RFI to double
bond through a mechanism of singe electron transfer (SET)
Table 3
The reaction of 1 with different unsaturated acids 5a–ia
Entry R1
R2
R3
Product Yield (%)b cis-/trans-
Table 2
Effect of solvent and temperature on the reaction of 1 with 4ca
1
2
3
4
5
6
7
8
9
H (4a)
CH3 (4b)
C2H5 (4c)
n-C3H7 (4d)
n-C4H9 (4e)
CH2Ph (4f)
Ph (4g)
NHCOPh (4h)
NHCOPhOCH3-p (4i)
CH3 CH3 5a
64.0
60.0
56.0
65.2
55.0
48.6
59.7
40.0
39.0
–
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
5b
5c
5d
5e
5f
5g
5h
5i
1.05:1
1.26:1
1.27:1
1.25:1
1.18:1
1:1.83
1:1.67
1:1.40
Entry
Solvent
Reaction
Conversion
Yieldb
(%)
(CH3CN/H2O)
temperature (8C)
of 1 (%)
1
2
3
4
5
3:1
1:3
1:1
3:1
3:1
25
25
25
0
100
100
100
100
100
81
58
60
65
63
45
a
a
1:4c:Na2S2O4:NaHCO3:NaOH = 1:1:1.4:1.4:1 for 8 h.
The yields were based on GC.
1:4:NaOH = 1:1:1 in CH3CN/H2O = 3:1 (v/v) at 25 8C for 8 h.
Isolated yield.
b
b

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X. Yang et al. / Journal of Fluorine Chemistry 128 (2007) 174–178
3.1. General procedure for the reaction of 1 with 4-
pentenoic acids 4
To the mixture of NaOH (3 mmol, 120 mg), acids 4 (3 mmol),
phosphonate 1 (3 mmol, 940 mg), water (3 ml), acetonitrile
(9 ml) was added the mixture of Na2S2O4 (4.2 mmol, 730 mg)
and NaHCO3 (4.2 mmol, 350 mg) in 30 min. After stirring for
8 h, water (ca. 20 ml) was added and then extracted with ethyl
etherof3 ꢀ 20 ml. Thecombinedorganiclayerwaswashedwith
saturated brine and dried over anhydrous sodium sulfate. After
the evaporation of ethyl ether, the residuewas purified by column
chromatographyelutingwithpetroleumetherandethylacetateto
give the corresponding lactones.
Scheme 3.
process and then followed by intramolecular SN2 reaction. The
mechnism is illustrated in Fig. 1.
3.2. [2-(3,3-Dimethyl-5-oxo-tetrahydro-furan-2-yl)-1,1-
difluoro-ethyl]-phosphonic acid diethyl ester (5a)
3. Experimental
IR spectra were measured on a Nicolet Magna IR-550
spectrometer. High-resolution mass spectra were obtained on a
Finnigan GC-MS-4021 spectrometer. NMR spectra were
recorded in CDCl3 solution on a Bruker AC-500 spectrometer
operating at 500 MHz (1H NMR), 125.8 MHz (13C NMR) and
470.5 MHz (19F NMR). Chemical shifts (d) are given in ppm
Colorless oil; IR (film, ymax, cmꢁ1): 1784, 1273, 1158, 1022;
1H NMR d (ppm): 4.53–4.50 (1H, m), 4.35–4.25 (4H, m), 2.32
(1H, AB, J = 16.5 Hz), 2.39 (1H, AB, J = 16.5 Hz), 2.38–2.28
(2H, m), 1.42–1.38 (6H, m), 1.19 (3H, s), 1.04 (3H, s); 19F
NMR d (ppm): ꢁ111.17 to ꢁ113.66 (2F, m); 13C NMR d (ppm):
16.9, 17.0, 21.8, 24.7, 34.1–34.6 (m), 40.4, 44.8, 65.4 (d, JP–
C = 7.0 Hz), 65.6 (d, JP–C = 6.8 Hz), 81.4–81.5 (m), 117–123
(m, CF2), 176; HRMS for M+: C12H21O5F2P. Calc.: 314.1095;
Found: 314.1083.
1
relative to TMS for H and 13C, and relative to CFCl3 for 19F
NMR. Column chromatography was performed using silica gel
H, particle size 20–30 mm. Melting points are uncorrected.
Scheme 4.
Fig. 1. Mechanism of the reaction of 4 with unsaturated acids.

X. Yang et al. / Journal of Fluorine Chemistry 128 (2007) 174–178
177
3.3. [1,1-Difluoro-2-(4-methyl-5-oxo-tetrahydro-furan-2-
yl)-ethyl]-phosphonic acid diethyl ester (5b)
2.66–2.55 (3H, stack), 2.41–2.31 (1H, m), 1.85–1.81 (1H, m),
1.68–1.60 (1H, m), 1.52–1.46 (1H, m), 1.40 (6H, t, J = 7.1 Hz),
1.38–1.30 (4H, m), 0.92 (3H, t, J = 7.0 Hz); trans-: 4.94–4.91
(1H, m), 4.32–4.26 (4H, m), 2.66–2.55 (2H, stack), 2.41–2.31
(1H, m), 2.21 (2H, t, J = 7.0 Hz), 1.95–1.91 (1H, m), 1.40 (6H,
t, J = 7.1 Hz), 1.38–1.30 (5H, m), 0.92 (3H, t, J = 7.0 Hz); 19F
NMR d (ppm): ꢁ110.6 to ꢁ113.1 (2F, m); 13C NMR d (ppm):
cis-: 14.5, 17.0, 17.1, 23.1, 30.0, 30.9, 36.8, 41.3, 40.0–40.5
(m), 65.5, 65.6, 72.7–72.8 (m), 116–122 (m, CF2), 178.7; trans-
: 14.5, 17.0, 17.1, 23.0, 30.0, 30.5, 34.9, 39.6, 40.0–40.5 (m),
65.4, 65.5, 72.7–72.8 (m, CF2), 116–122 (m), 179.2; HRMS for
M+: C14H25O5F2P. Calc: 342.1408; Found: 342.1411.
Colorless oil; IR (film, ymax, cmꢁ1): 1777, 1271, 1167, 1025;
1H NMR d (ppm): cis-: 4.73–4.75 (1H, m), 4.33–4.27 (4H, m),
2.74–2.60 (2H, stack), 2.60–2.55 (1H, m), 2.40–2.34 (1H, m),
1.69–1.64 (1H, m), 1.40 (6H, t, J = 6.8 Hz), 1.28 (3H, d,
J = 6.5 Hz); trans-: 4.97–4.94 (1H, m), 4.33–4.27 (4H, m),
2.74–2.60 (1H, m), 2.60–2.55 (1H, m), 2.40–2.34 (1H, m),
2.31–2.25 (1H, m), 2.22–2.13 (1H, m), 1.40 (6H, t, J = 6.8 Hz),
1.31 (3H, d, J = 7.3 Hz); 19F NMR d (ppm): ꢁ110.6 to ꢁ112.8
(2F, m); 13C NMR d (ppm): cis-: 15.5, 16.9, 17.0, 36.1, 38.8,
39.9–40.4 (m), 65.5, 65.6, 72.2–72.4 (m), 118–122 (m, CF2),
179.2; trans-: 16.3, 16.9, 17.0, 34.2, 36.7, 38.7–39.9 (m), 65.4,
65.5, 72.2–72.4 (m), 118–122 (m, CF2), 179.7; HRMS for M+:
C11H19O5F2P. Calc: 300.0938 Found: 300.0931.
3.7. [2-(4-Benzyl-5-oxo-tetrahydro-furan-2-yl)-1,1-
difluoro-ethyl]-phosphonic acid diethyl ester (5f)
Colorless oil; IR (film, ymax, cmꢁ1): 1777, 1272, 1165, 1023;
1H NMR d (ppm): cis-: 7.32–7.18 (5H, m), 4.75–4.72 (1H, m),
4.29–4.24 (4H, m), 3.18 (1H, ABX, J1 = 13.8 Hz, J2 = 4.5 Hz),
2.96–2.92 (2H, stack), 2.74 (1H, ABX, J1 = 14.0 Hz,
J2 = 9.2 Hz), 2.68–2.50 (1H, m), 2.45–2.20 (1H, m), 1.73–
1.67 (1H,m), 1.37 (6H, t, J = 7.0 Hz); trans-: 7.32–7.18 (5H,
m), 4.75–4.72 (1H, m), 4.29–4.24 (4H, m), 3.29 (1H, ABX,
J1 = 14.0 Hz, J2 = 4.2 Hz), 2.74 (1H, ABX, J1 = 14.0 Hz,
J2 = 9.2 Hz), 2.68–2.50 (1H, m), 2.50–2.42 (1H, m), 2.45–
2.20 (2H, stack), 2.11–2.05 (1H, m), 1.38 (6H, t, J = 7.0 Hz);
19F NMR d (ppm): ꢁ110.7 to ꢁ112.9 (2F, m); 13C NMR d
(ppm): cis-: 15.3, 15.4, 32.3, 34.9, 38.2–38.7 (m), 41.4, 63.8,
63.9, 71.0–71.1 (m), 117–122 (m, CF2), 125.7, 127.7, 127.9,
137.2, 176.2; trans-: 15.3, 15.4, 28.6, 34.5, 38.2–38.7 (m), 39.6,
63.7, 63.8, 71.0–71.1 (m), 117–122 (m, CF2), 125.9, 127.8,
128.0, 136.8, 176.8; HRMS for M+: C17H23O5F2P. Calc:
376.1252; Found: 376.1219.
3.4. [2-(4-Ethyl-5-oxo-tetrahydro-furan-2-yl)-1,1-difluoro-
ethyl]-phosphonic acid diethyl ester (5c)
Colorless oil; IR (film, ymax, cmꢁ1): 1778, 1272, 1167, 1024;
1H NMR d (ppm): cis-: 4.78–4.74 (1H, m), 4.33–4.26 (4H, m),
2.66–2.55 (3H, stack), 2.41–2.29 (1H, m), 1.88–1.80 (1H, m),
1.68–1.62 (1H, m), 1.60–1.52 (1H, m), 1.40 (6H, t, J = 7.0 Hz),
1.00 (t, 3H, J = 7.5 Hz); trans-: 4.93–4.91 (1H, m), 4.33–4.26
(4H, m), 2.66–2.55 (2H, stack), 2.41–2.29 (1H, m), 2.21 (2H, t,
J = 7.0 Hz), 1.99–1.90 (1H, m), 1.51–1.42 (1H, m), 1.40 (6H, t,
J = 7.0 Hz), 1.03 (3H, t, J = 7.4 Hz); 19F NMR d (ppm): ꢁ110.5
to ꢁ112.8; 13C NMR d (ppm): cis-: 11.8, 16.7, 16.8, 23.4, 35.8,
40.6–40.7 (m), 42.3, 65.4, 65.3, 72.3–73.5 (m), 116–124 (m,
CF2), 178.3; trans-: 11.9, 16.7, 16.8, 24.2, 34.1, 39.7–40.0 (m),
40.7, 65.2,65.3, 72.3–72.5(m), 116–124(m, CF2), 178.8;HRMS
for M+: C12H21O5F2P. Calc: 314.1095; Found: 314.1095.
3.5. [1,1-Difluoro-2-(5-oxo-4-propyl-tetrahydro-furan-2-
yl)-ethyl]-phosphonic acid diethyl ester (5d)
3.8. [1,1-Difluoro-2-(5-oxo-4-phenyl-tetrahydro-furan-2-
yl)-ethyl]-phosphonic acid diethyl ester (5g)
Colorless oil; IR (film, ymax, cmꢁ1): 1774, 1269, 1165, 1029;
1H NMR d (ppm): cis-: 4.78–4.75 (1H, m), 4.33–4.26 (4H, m),
2.75–2.50 (3H, stack), 2.45–2.27 (1H, m), 1.82–1.75 (1H, m),
1.70–1.60 (1H, m), 1.50–1.29 (3H, m), 1.38 (6H, t, J = 7.3 Hz),
0.96 (3H, t, J = 7.2 Hz); trans-: 4.94–4.92 (1H, m), 4.33–4.26
(4H, m), 2.75–2.50 (2H, stack), 2.45–2.27 (1H, m), 2.21 (t, 2H,
J = 7.2 Hz), 1.95–1.85 (1H, m), 1.50–1.29 (3H, m), 1.38 (6H, t,
J = 7.3 Hz), 0.95 (t, 3H, J = 7.2 Hz); 19F NMR d (ppm): ꢁ110.6
to ꢁ112.9 (2F, m);.13C NMR d (ppm): cis-: 14.3, 17.0, 17.1,
21.1, 32.8, 36.8, 39.8–40.5 (m), 41.0, 65.6, 65.7, 72.6–72.8 (m),
116–122 (m, CF2), 178.7; trans-: 14.4, 17.0, 17.1, 21.1, 33.3,
34.9, 39.4, 39.8–40.5 (m), 65.5, 65.6, 72.6–72.8 (m), 116–122
(m, CF2), 179.2; HRMS for M+: C13H23O5F2P. Calc: 328.1251;
Found: 328.1266.
Colorless oil; IR (film, ymax, cmꢁ1): 1776, 1269, 1161, 1021;
1H NMR d (ppm): cis-: 7.39–7.26 (5H, m), 4.94–4.91 (1H, m),
4.34–4.27 (4H, m), 3.94–3.89 (1H, m), 2.97–2.92 (1H, m),
2.88–2.55 (1H, m), 2.50–2.39 (1H, m), 2.21–2.15 (1H, m),
1.42–1.29 (6H, m); trans-: 7.39–7.26 (5H, m), 5.09–5.04 (1H,
m), 4.34–4.27 (4H, m), 3.94–3.89 (1H, m), 2.88–2.55 (2H,
stack), 2.58–2.50 (1H, m), 2.50–2.39 (1H, m), 1.42–1.29 (6H,
m). 19F NMR d (ppm): ꢁ110.5 to ꢁ112.8 (2F, m); 13C NMR d
(ppm): cis-: 16.3, 16.4, 37.3, 38.8–39.7 (m), 46.7, 64.9, 65.0,
71.7–71.9 (m), 116–122 (m, CF2), 127.7, 128.6, 128.9, 135.9,
175.9; trans-: 16.3, 16.4, 36.9, 38.8–39.7 (m), 45.2, 65.0, 65.1,
72.2–72.4 (m), 116–122 (m, CF2), 127.5, 128.0, 129.1, 136.3,
176.3; HRMS for M+: C16H21O5F2P. Calc: 362.1095; Found:
362.1096.
3.6. [2-(4-Butyl-5-oxo-tetrahydro-furan-2-yl)-1,1-difluoro-
ethyl]-phosphonic acid diethyl ester (5e)
3.9. [2-(4-Benzoylamino-5-oxo-tetrahydro-furan-2-yl)-1,1-
difluoro-ethyl]-phosphonic acid diethyl ester (5h)
Colorless oil; IR (film, ymax, cmꢁ1): 1777, 1273, 1165, 1022;
1H NMR d (ppm): cis-: 4.78–4.75 (1H, m), 4.32–4.26 (4H, m),
White solid; mp. 78–80 8C; IR (KBr, ymax, cmꢁ1): 3332,
1777, 1655, 1292, 1189, 1041; 1H NMR d (ppm): cis-: 7.81–7.27

178
X. Yang et al. / Journal of Fluorine Chemistry 128 (2007) 174–178
(5H, m), 6.86 (1H, d, J = 5.4 Hz), 5.01–4.92 (1H, m), 4.78–4.67
(1H, m), 4.33–4.28 (4H, m), 3.19–3.12 (1H, m), 2.70–2.57 (2H,
m), 2.11–2.05 (1H, m), 1.4 (6H, t, J = 7.0 Hz); trans-: 7.81–7.27
(5H, m), 6.90 (1H, d, J = 6.0 Hz), 5.25–5.19 (1H, m), 4.66–4.55
(1H, m), 4.33–4.28 (4H, m), 2.79–2.72 (1H, m), 2.70–2.40 (3H,
stack), 1.4 (6H, t, J = 7.0 Hz); 19F NMR d (ppm): ꢁ111.3 to
ꢁ112.3 (2F, m); 13C NMR d (ppm): cis-: 16.9, 17.0, 36.8, 39.8–
40.1 (m), 50.9, 65.6, 65.7, 72.3–72.4 (m), 116–123 (m,
CF2), 127.8, 129.2, 132.6, 133.6, 168.21, 175.2; trans-:
16.9, 17.0, 35.1, 39.8–40.1 (m), 49.2, 65.5, 65.6, 72.1–72.2
(m), 116–123 (m, CF2), 127.9, 129.1, 132.6, 133.5, 168.24,
175.6; HRMS for M+: C17H22NO6F2P. Calc: 405.1153; Found:
405.1154.
Acknowledgements
We thank the National Natural Science Foundation of China
(20672034) and the Shanghai Scientific and Technology
Committee (Grant No. 03QB14012) for financial support.
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(5i)
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(b) M.A. Jasenka, H. Peter, U. Nassim, J. Org. Chem. 60 (1995) 2563–
2569.
[5] (a) S. Halazy, A. Ehrhard, A. Eggenspoller, B. Berges-Gross, C. Danzin,
Tetrahedron 52 (1996) 177–184;
Colorless oil; IR (film, ymax, cmꢁ1): 3331, 1786, 1655,
1290, 1180, 1024; 1H NMR d (ppm): cis-: 7.78–6.91 (4H, m),
6.72 (1H, d, J = 5.4 Hz), 4.98–4.91 (1H, m), 4.82–4.76 (1H,
m), 4.33–4.28 (4H, m), 3.85 (3H, s), 3.15–3.11 (1H, m),
2.70–2.40 (2H, m), 2.10–2.04 (1H, m), 1.40 (6H, t,
J = 7.0 Hz); trans-: 7.78–6.91 (4H, m), 6.76 (1H, d,
J = 5.9 Hz), 5.22–5.19 (1H, m), 4.71–4.64 (1H, m), 4.33–
4.28 (4H, m), 3.85 (3H, s), 2.69–2.61 (1H, m), 2.70–2.40 (3H,
stack), 1.40 (6H, t, J = 7.0 Hz). 19F NMR d (ppm): ꢁ111.3 to
ꢁ112.4 (2F, m); 13C NMR d (ppm): cis-: 16.9, 17.0, 37.0,
39.7–40.1 (m), 50.9, 56.0, 65.6, 65.7, 72.3–72.4 (m), 114.4,
116–122 (m, CF2), 125.9, 129.7, 129.8, 167.8, 175.4; trans-:
16.9, 17.0, 35.2, 39.7–40.1 (m), 49.2, 56.0, 65.5, 65.6, 72.9–
73.0 (m), 114.4, 116–122 (m, CF2), 125.7, 129.8, 163.3,
167.7, 175.8. HRMS for M+: C18H24F2NO7P. Calc: 435.1258;
Found: 435.1255.
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317;
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4831;
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