An effective borate-mediated approach to 1-trifluoromethyl-1-hydroxy-3- ketophosphonates, phosphinates, and phosphine oxides

Article abstract of DOI:10.1055/s-0030-1260935

Ethyl 1-trifluoromethyl-1-hydroxy-3-oxo-phosphonates, the related (methyl)phosphinates and (phenyl)phosphinates, and phosphine oxides were obtained in good yield via direct phosphonylation of acyltrifluoroacetones with diethyl phosphite, ethyl (methyl)pho

Full text of DOI:10.1055/s-0030-1260935

LETTER
1735
An Effective Borate-Mediated Approach to 1-Trifluoromethyl-1-hydroxy-3-
ketophosphonates, Phosphinates, and Phosphine Oxides
T
riethyl Borate-M
m
ediate
d
Phosphonyl
i
ationo
t
A
cyltrifluoroa
i
cetonesi L. Chizhov,*a Vera Vogel,b Sergey N. Tverdomed,b Valery N. Charushin,a Gerd-Volker Röschenthalerb
a
I. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 620990 Ekaterinburg, GSP-147, Russia
Fax +7(343)3693058; E-mail: dlchizhov@ios.uran.ru
b
School of Engineering and Science, Jacobs University Bremen, P.O. Box 750561, 28725 Bremen, Germany
Received 27 January 2011
can be correspondingly used. However, reports on the
synthesis of 1-hydroxy-3-ketophosphonates and their
properties are scarce. Though, an effective approach to
these compounds via a novel cross aldol reaction of
Abstract: Ethyl 1-trifluoromethyl-1-hydroxy-3-oxo-phosphonates,
the related (methyl)phosphinates and (phenyl)phosphinates, and
phosphine oxides were obtained in good yield via direct phospho-
nylation of acyltrifluoroacetones with diethyl phosphite, ethyl (me-
thyl)phosphonite, ethyl (phenyl)phosphonite, and diphenyl- acylphosphonates (a-ketophosphonates) and ketones has
been recently reported.9
phosphine oxide in the presence of triethyl borate. The subsequent
dehydration of the selected phosphonates and phosphinates pro-
ceeds smoothly affording previously unknown diethyl 1,2-unsatur-
ated 1-trifluoromethyl-3-oxophosphonates, ethyl 1-trifluoro-
As far as fluorinated 1-hydroxy-3-ketophosphonates 2
(Figure 1, R3 = R4 = OAlk) are concerned, it has been
shown that these compounds can be the product of phos-
phonylating fluorinated 1,3-diketones with O-trimethyl-
silyl-substituted phosphites.10 Nevertheless, the given
moisture sensitivity of these phosphorus reagents, the ap-
plication of dialkyl phosphites in this reaction, seems to be
more attractive. However, there is only one report on the
reaction of dialkylphosphites with the highly reactive
hexafluoroacetylacetone.11
methyl-3-oxo(methyl)-, and ethyl 1-trifluoromethyl-3-oxo(phenyl)
phosphinates in good yields.
Key words: acyltrifluoroacetones, phosphonylation, triethyl bo-
rate, fluorinated phosphonate, fluorinated phosphinate, fluorinated
phosphine oxides
Dialkyl 1-hydroxyphosphonates and related alkyl 1-hy-
droxyphosphinates are esters of 1-hydroxyphosphonic
(phosphinic) acids which constitute a prominent group of
organophosphorus compounds that could be found in na-
ture and exhibit attractive biological properties. They are
very potent inhibitors of enzymes such as renin,1 human
immunodeficiency virus (HIV) protease, and poly-
merase.2 They have also been reported to possess
antiviral3 and antitumor4 activity. Therefore the design of
a-hydroxyphosphonates and their derivatives are of prac-
tical importance.
In the view of the possible biological activity of fluorine-
containing phosphonates and as an extension of our con-
tinuing synthetic studies on the reactivity of RF-containing
di- and polycarbonyl compounds, and their derivatives,10–
12
we have focused our attention on 1-RF-1-hydroxy-3-
ketophosphonates 2 (R1 π RF). Despite their potential in-
terest as a promising building block for the construction of
more complex fluorine phosphorus containing com-
pounds, they have not received much attention, probably
owing to the lack of general methods for the synthesis of
these compounds.
From this point of view, 1-hydroxy-3-ketophosphonates 1
(Figure 1) seem to be precursor for tailor-made com-
pounds due to the presence of the versatile carbonyl
group. Moreover, the aldol (1-hydroxy-3-keto) fragment
is rather common in the structure of nonaromatic
polyketide metabolites.5
R2
RF
R1
R1
P(O)(OAlk)R3
P(O)R3R4
O
O
OH
OH
1
2
On the other hand, fluoro-containing phosphonates are
important, taking into account the well-known influence
of fluorine or fluorinated groups in organic molecules on
their physical, chemical, and biological properties.6 Thus,
the development of useful methods for the synthesis of
fluorine-containing phosphonates is of interest for the
synthesis of potentially bioactive substances.7
Figure 1 1-Hydroxy-3-ketophosphonates 1 and target 1-RF-1-
hydroxy-3-ketophosphonates 2
This prompted us to develop a new general and efficient
method for the preparation of 1-RF-1-hydroxy-3-keto-
phosphonates 2 as useful precursors of a wide variety of
tailor-made phosphonates with fluoroalkyl groups. We
reasoned that 1,3-diketones bearing both fluorinated and
nonfluorinated terminal substituents would directly react
with dialkylphosphites and related phosphorus reagents as
it has been shown for hexafluoroacetylacetone.11 Howev-
er, to the best of our knowledge, no data of such a reaction
has been reported.
Methods for nonfluorinated phosphonates with separated
1-hydroxyphosphonate and 3-ketophosphonate units are
well developed.8 Pudovik and phospha-Michael reactions
SYNLETT 2011, No. 12, pp 1735–1739
x
x
.x
x
.2
0
1
1
Advanced online publication: 05.07.2011
DOI: 10.1055/s-0030-1260935; Art ID: B02811ST
© Georg Thieme Verlag Stuttgart · New York

1736
D. L. Chizhov et al.
LETTER
In this communication, we wish to report the successful 1-hydroxy-3-oxo-(methyl)phosphinates 5a–c,e–g were
approach to ethyl esters of 1-trifluoromethyl-1-hydroxy- isolated in good yields (Table 1, entries 12–17). Phospho-
3-oxo-phosphonates 4a–g, (methyl)phosphinates 5a–c,e– nylation of diketones 3a–c,f,g with ethyl (phenyl)phos-
g, (phenyl)phosphinates 6a–c,f,g, and tertiary diphe- phonite gave rise to the corresponding ethyl 1-
nylphosphine oxides 7a,c,d,g involving the direct phos- trifluoromethyl-1-hydroxy-3-oxo-(phenyl)phosphinates
phonylation of acyltrifluoroacetones 3 with diethyl 6a–c,f,g (Table 1, entries 18–22). However, a greater
phosphite, ethyl (methyl)phosphonite, ethyl (phe- amount of the phosphorus reagent (1.5 equiv) was re-
nyl)phosphonite, and diphenylphosphine oxide, and the quired for completeness of the reaction that is likely to be
subsequent dehydration of the selected phosphonates and due to its reduced nucleophilicity. Thus, reaction of dike-
phosphinates to the corresponding unsaturated ketophos- tones 3a,c,d,g with less nucleophilic diphenylphosphine
phonates 8a–c and phosphinates 9a–c and 10a–c.
oxide was completed in the presence of two equivalents of
this reagent to afford the corresponding phosphine oxides
7a,c,d,g in 60 hours (Table 1, entries 23–26).
We have found that phosphonylation of benzoyltrifluoro-
acetone (3a) with diethyl phosphite occurred in acetoni-
trile solution in the presence of 3–5 mol% of triethyl In accord to the 19F NMR and 31P NMR spectra of reaction
borate at ambient temperature affording diethyl 1-trifluo- mixtures, compounds 5a–c,e–g and 6a–c,f,g were formed
romethyl-1-hydroxy-3-oxo-phosphonate (4a) as the sole as nearly 1:1 mixture of diastereomers due to the presence
product (Scheme 1, R2 = R3 = OEt). The conversion of the of carbon and phosphorus stereogenic centers and low di-
diketone was ca. 100% (based on the 19F NMR spectrum) astereoselectivity of the phosphinylation. However, we
in 3 days, when at least a three-fold excess of diethyl failed to separate these diastereomeric mixtures by col-
phosphite was used (Table 1, entry 1). Increasing the tri- umn chromatography in the course of product isolation.
ethyl borate content up to one equivalent accelerated the
Noticeably, the nature of the terminal substituent R1 in
reaction but had no influence on the essential amount of
diketones has no major effect on the reaction outcome.
the phosphorus reagent (Table 1, entry 2). However, when
However the replacement of the trifluoromethyl group by
an acetonitrile solution of 3a, diethyl phosphite, and tri-
difluoromethyl (diketone 3h) or 1,1,2,2-tetrafluoroethyl
(diketone 3i) substituents changes the reaction course dra-
matically. In both cases phosphonylation was not com-
plete even with large excess of the phosphorus reagent (10
ethyl borate in the ratio 1:1.1:1.1 was refluxed for 2 days,
phosphonate 4a was obtained in ca. 100% NMR and 78%
isolated yield (Table 1, entry 3). It should be noted, that in
the absence of borate the phosphonylation did not occur at
equiv) or triethyl borate (3 equiv); the NMR yields were
all.
less than 30% after 100 hours (Table 1, entries 10–11).
The positive effect of triethyl borate on the course of
phosphonylation could be explained by a reversible for-
R2
R3
O
P
mation of the more reactive borate derivative A followed
by a nucleophilic attack of phosphorus under formation of
borate B, and subsequent regeneration of A, as it is out-
lined in Scheme 1. Surprisingly, there were no reports on
reaction of fluorinated diketones with trialkyl borates.
Moreover, it had been shown, that diketones bearing an
electron-withdrawing ester group did not react with tri-
R1
O
R3 PH
R2
F3C
R1
+
B(OEt)3
MeCN
F3C
O
O
O
OH
3
4–7
EtOH B(OEt)3
3, – A
1
alkyl borates.14 Therefore, the H NMR and 19F NMR
R3
O
R3 PH
R2
R2
R3
O
P
R1
••
F3C
P
OH
spectra of mixtures of diketones 3a and triethyl borate in
the ratio 2:1, 1:1, and 1:2 were recorded in CD3CN solu-
tion to confirm the intermediate A formation. The yellow
color of samples and the appearance of additional low in-
tensity signals in the NMR spectra proved that the reac-
tion had taken place. A singlet at d = 5.45 ppm and a four-
R2
R1
O
O
F3C
B
O
O
B
EtO
OEt
A
OEt
EtO
B
1
R1 = Ph (a), 4-O2NC6H4 (b), 2-thienyl (c), 4-EtOC6H4 (d),
Me (e), Et (f), t-Bu (g)
proton quartet at d = 3.53 ppm in the H NMR spectra
were assigned to the olefinic and methylene protons of
two ethoxy groups of the enol borate A. The upfield shift
for olefinic protons of enol ethers of fluorinated 1,3-dike-
tones are well-known.15
R2, R3 = EtO, EtO (4); Me, EtO (5); Ph, EtO (6); Ph, Ph (7)
Scheme 1 Triethyl borate mediated reaction of acyltrifluoroaceto-
nes 3 with derivatives of phosphorous, phosphonous, and phosphi-
nous acids
Additionally, it was observed a singlet at d = 7.07 ppm
that was attributed to the olefinic proton signal for the che-
late ring of benzoyltrifluoroacetonato boron diethoxide.
This signal was deshielded (0.32 ppm) compared to the
olefinic proton of the keto-enol tautomer of 3a, similarly
to that of other boron diketonates.14,16 The trifluoromethyl
groups of A and the boron chelate were shifted downfield
The most suitable conditions (Table 1, entry 3) were used
to react diketones 3b–g with diethyl phosphite, and phos-
phonates 4b–g were obtained (Table 1, entries 4–9).13
When ethyl (methyl)phosphonite reacted with diketones
3a–c,e–g under the found conditions (Scheme 1,
R2 = OEt, R3 = Me), the expected ethyl 1-trifluoromethyl-
Synlett 2011, No. 12, 1735–1739 © Thieme Stuttgart · New York

LETTER
Triethyl Borate-Mediated Phosphonylation of Acyltrifluoroacetones
1737
in comparison to 3a and appeared as singlets at d = 87.5
and 87.2 ppm (C6F6) in the 19F NMR spectra. The total in-
tegration for signals of the enol borate A and the boron
diketonate increased from ca. 2.5% to 5.0% with increas-
ing of the triethyl borate content.
Table 1 Triethyl Borate Mediated Reaction of Diketones 3a–i with
Diethyl Phosphite, Ethyl (Methyl)phosphonite, Ethyl (Phenyl)phos-
phonite, and Diphenylphosphine Oxide
Entry Diketone R1
R2, R3
Catalyst
Time Yield
(h)d (%)e
amounta–c
Noteworthy that, in addition to the doublet signals of
products at d = 86–88 (JFP = ca. 3–4 Hz) in the 19F NMR
spectra of reaction mixtures (Table 1, entries 2–5), addi-
tional low intensive doublets (JFP = ca. 3–5 Hz) with sim-
ilar shifts were observed. Their disappearance after
hydrolysis could stand for the presence of borates B in the
reaction mixtures.
1
2
3a
3a
3a
3b
3c
3d
3e
3f
Ph
Ph
Ph
OEt, OEt 5 mol%, r.t.f 72 100g
OEt, OEt 3 equiv, r.t.f 48 100g
3
OEt, OEt 1.1 equiv
48 78
48 83
48 90
48 86
48 56
48 75
48 91
100 29g
100 17g
24 68
24 87
24 85
24 59
24 70
24 62
48 61
48 78
48 70
48 49
48 70
60 53
60 47
60 52
60 63
4
4-O2NC6H4 OEt, OEt 1.1 equiv
2-thienyl OEt, OEt 1.1 equiv
4-EtOC6H4 OEt, OEt 1.1 equiv
5
This approach is the first example of successful syntheses
of diethyl 1-trifluoromethyl-1-hydroxy-3-oxo-phospho-
nates 4, related phosphinates 5, 6, and tertiary phosphi-
noxides 7 and has advantages with regard to the ease of
operation and the ready availability of starting materials.
In addition, compounds 4–7 could be considered as ana-
logues of b-trifluoromethyl-b-hydroxy ketones, which
proved to be useful building blocks.17
6
7
Me
Et
OEt, OEt 1.1 equiv
OEt, OEt 1.1 equiv
OEt, OEt 1.1 equiv
OEt, OEt 3.0 equivj
OEt, OEt 3.0 equivj
8
9
3g
3hh
3ii
3a
3b
3c
3e
3f
t-Bu
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Thus, dehydration of selected compounds 4–6(a–c) by
means of (CF3CO)2O in the presence of pyridine at 0 °C
affords the respective trifluoromethyl-containing unsatur-
ated 3-oxo-phosphonates 8a–c, (methyl)phosphinates 9a–
c, and (phenyl)phosphinates 10a–c (Scheme 2, Table 2).
Ph
Ph
Me, OEt
1.1 equiv
1.1 equiv
1.1 equiv
1.1 equiv
1.1 equiv
1.1 equiv
1.1 equivk
1.1 equivk
1.1 equivk
1.1 equivk
1.1 equivk
1.5 equivl
1.5 equivl
1.5 equivl
1.5 equivl
4-O2NC6H4 Me, OEt
2-thienyl
Me
Me, OEt
Me, OEt
Me, OEt
Me, OEt
Ph, OEt
O
O
R2
R1
P
EtO
Et
R2
F3C
O
3g
3a
3b
3c
3f
t-Bu
Ph
(Z)-8–10
EtO
P
(CF3CO)2O, 2py
R1
+
F3C
CH2Cl2, 0 °C to r.t.
R2
O
O
OH
4–6
4-O2NC6H4 Ph, OEt
P
R1
EtO
R1 = Ph (a), 4-O2NC6H4 (b), 2-thienyl (c)
R
2-thienyl
Et
Ph, OEt
Ph, OEt
Ph, OEt
Ph, Ph
F3C
(E)-8–10
O
2 = EtO (8), Me (9), Ph (10)
Scheme
2
Dehydration of 1-trifluoromethyl-1-hydroxy-3-oxo-
3g
3a
3c
3d
3g
t-Bu
phosphonates 4a–c, (methyl)phosphinates 5a–c, and (phenyl)phos-
phinates 6a–c
Ph
2-thienyl
Ph, Ph
Compounds 8–10 were isolated in 63–88% yields as a
mixture of E- and Z-isomers with a predominant amount
of Z-isomer (≥ 90%).18 Noteworthy, when the dehydration
occurred at room temperature, the content of the E-isomer
increased up to ca. 20%.
4-EtOC6H4 Ph, Ph
t-Bu Ph, Ph
a Refluxing, if not indicated otherwise.
b MeCN as solvent.
Since phosphonates 8 and phosphinates 9, 10 could be re-
garded as a,b-unsaturated trifluoromethylketones19 and
vinylphosphonates,8b,c,20 this experimentally simple meth-
od may be of great value in RF-phosphorus-containing
building-block chemistry.
c 1.1 Equiv of phosphorus reagent, if not indicated otherwise.
d Monitoring by 19F NMR.
e Isolated yield.
f 3 Equiv of diethyl phosphite.
g NMR yield.
h RF = HCF2.
i RF = HCF2CF2.
The structures of compounds 4–10 were confirmed by el-
emental analysis, 1H NMR, 19F NMR, 31P NMR, and 13
C
j 10 Equiv of diethyl phosphite.
k 1.5 Equiv of ethyl (phenyl)phosphonite.
l 2.0 Equiv of diphenylphosphine oxide.
NMR spectroscopy.13,18 A characteristic feature of the 1H
NMR spectra for phosphonates 4 and tertiary phosphine
oxides 7 in CDCl3 is the presence of an AB system of dou-
blets at d = 2.7–3.6 ppm (2JHa–Hb = 15–19 Hz, 3JHa–P = 11–
Synlett 2011, No. 12, 1735–1739 © Thieme Stuttgart · New York

1738
D. L. Chizhov et al.
LETTER
substrate for the synthesis of a wide variety of phospho-
nates, phosphinates, and phosphine oxides with potential
biological activity. Further studies on the scope of this ap-
proach and synthetic application of the obtained com-
pounds are now in progress.
Table 2 Dehydration of Compounds 4a–c, 5a–c, and 6a–c
Entry
Compd
8a
R1
R2
Yield (%)
1
2
3
4
5
6
4
5
6
Ph
OEt
OEt
OEt
Me
Me
Me
Ph
69
70
74
77
63
81
88
72
65
8b
4-O2NC6H4
2-thienyl
Ph
8c
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
9a
9b
4-O2NC6H4
2-thienyl
Ph
Acknowledgment
9c
D.L.C. is grateful to the Deutsche Forschungsgemeinschaft for ge-
nerous financial support (Grant DFG 436 RUS 113/911/0-1).
10a
10b
10c
4-O2NC6H4
2-thienyl
Ph
References and Notes
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17 Hz, JHb–P = 2–9 Hz) for the methylene protons and
doublet at d = 6.5–6.8 ppm (3JH–P = 8–15 Hz) for the OH
group, which disappeared in the presence of CD3CO2D. In
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ppm (C6F6). In the case of phosphinates 5 and 6, two sets
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1
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fluoroacetones 3 with several derivatives of phosphorous,
phosphonous, and phosphinous acids such as diethyl
phosphite, ethyl (methyl)phosphonite, ethyl (phe-
nyl)phosphonite, and diphenilphosphine oxide in the pres-
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approach from readily available starting material to 1-tri-
fluoromethyl-1-hydroxy-3-oxo-phosphonates, 1,2-unsat-
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(methyl)phosphinate and (phenyl)phosphinate analogues,
and 3-(diphenylphosphoryl)-3-trifluoromethyl-3-hydroxy-
ketones, which may be considered as a CF3-containing
Synlett 2011, No. 12, 1735–1739 © Thieme Stuttgart · New York

LETTER
Triethyl Borate-Mediated Phosphonylation of Acyltrifluoroacetones
1739
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(d) Chaturvedi, A.; Nagar, P. N.; Srivastava, G. Synth. React.
Inorg. Met.-Org. Chem. 1993, 23, 1599.
(17) Pashkevich, K. I.; Filyakova, V. I.; Ratner, V. G.;
Khomutov, O. G. Russ. Chem. Bull. 1998, 47, 1239; and
references cited therein.
(18) General Procedure for the Preparation of Compounds
8–10
(13) Typical Procedure for the Preparation of Compounds 4–
7
A mixture of diketone 3 (10.0 mmol), phosphorus reagent
[11.0 mmol in the case of diethyl phosphite or
To a vigorously stirred solution of phosphonate 4 or
phosphinate 5 or 6 (5.0 mmol) and dry pyridine (0.79 g, 10
mmol) in dry CH2Cl2 (20 mL) a solution of TFAA (2.10 g,
10 mmol) in dry CH2Cl2 (20 mL) was added dropwise at 0
°C. The reaction mixture was stirred for 4 h at the same
temperature, warmed to r.t., washed with cold H2O (ca. 5 °C,
3 × 10 mL), and filtered through layer of silica (4 sm). The
solvent was evaporated and residue was dried in vacuo for
12 h.
ethyl(methyl)phosphonite, 15 mmol in the case of
ethyl(phenyl)phosphonite, or 20 mmol in the case of
diphenylphosphine oxide], and triethylborate (1.60 g, 11.0
mmol in the case of phosphite and phosphonites or 2.92 g,
20.0 mmol in the case of diphenylphosphine oxide) was
refluxed in MeCN (20 mL) for the respective time (Table 1).
All volatile materials were removed in vacuo, and the
residue was dissolved in Et2O (30 mL). The ether solution
was washed with H2O (10 mL) and 10% solution of Na2CO3
(3 × 10 mL). For compounds 6 and 7 a sat. solution of
NaHCO3 was used. Et2O was removed, the crude product
was dissolved in CHCl3 (10 mL) and filtered through a layer
of silica (3 sm). The solvent was evaporated, and the residue
was dried in vacuo for 12 h. For compounds 6 and 7, the
products were purified by column chromatography (EtOAc–
hexane = 1:2).
Data for Diethyl 3-(4-Nitrophenyl)-3-oxo-1-
(trifluoromethyl)prop-1-enylphosphonate (8b)
Yellow viscous oil; E/Z = 10:1.
Compound (Z)-8b: 1H NMR (200 MHz, CDCl3): d = 1.27 (t,
6 H, 2 Me, J = 7.1 Hz), 4.01–4.17 (m, 4 H, 2 OCH2), 7.57
(dq, 1 H, JH–P = 39.0 Hz, JH–F = 1.5 Hz, =CH), 8.02–8.06 (m,
2 H, Ar), 8.31–8.36 (m, 2 H, Ar). 19F NMR (188 MHz,
CDCl3, C6F6): d = 99.27 (s). 31P–1H coupled (81 MHz,
CDCl3, 85% H3PO4): d = 6.67 (dm, JP–H = 39.0 Hz). 31P–1H
decoupled (81 MHz, CDCl3, 85% H3PO4): d = 6.67 (q,
JP–F = 2.5 Hz). 13C NMR (50 MHz, CDCl3): d = 16.00 (d,
3JC–P = 7.1 Hz, Me), 63.80 (d, 2JC–P = 5.7 Hz, OCH2), 121.65
(qd, CF3, 1JC–F = 275.5 Hz, 2JC–P = 15.5 Hz), 124.06 (CH,
Ar), 129.00 (dq, 1JC–P = 182.3 Hz, 2JC–F = 32.5 Hz), 129.82,
(CH, Ar), 139.48 (Ar), 147.39 (m, =CH), 150.82 (Ar),
190.20 (d, 3JC–P = 7.1 Hz, C=O).
Data for Diethyl 1-Hydroxy-3-(4-nitrophenyl)-3-oxo-1-
(trifluoromethyl)propylphosphonate (4b)
Yellowish viscous oil. 1H NMR (200 MHz, CDCl3): d = 1.23
(t, 3 H, Me, J = 7.1 Hz), 1.27 (t, 3 H, Me, J = 7.1 Hz), 3.21
(dd, 1 H, JHa–Hb = 16.1 Hz, JHa–P = 18.6 Hz, CHH), 3.82 (dd,
1 H, JHa–Hb = 16.1 Hz, JHb–P = 7.3 Hz, CHH), 4.10–4.36 (m,
4 H, 2 OCH2), 6.74 (d, 1 H, JH–P = 8.3 Hz, OH) 7.61–7.66
(m, 2 H, Ar), 7.88–7.93 (m, 2 H, Ar). 19F NMR (188 MHz,
CDCl3, C6F6): d = 88.96 (d, JF–P = 5.2 Hz, CF3). 31P–1H
decoupled (81 MHz, CDCl3, 85% H3PO4): d = 16.68 (q,
JP–F = 5.2 Hz). 13C NMR (50 MHz, CDCl3) d = 16.13 (d,
3JC–P = 5.2 Hz, Me), 38.64 (s, CH2), 63.58 (d, 2JC–P = 7.4 Hz,
OCH2), 63.63 (d, 2JC–P = 7.4 Hz, OCH2), 75.58 (dq,
1JC–P = 164.6 Hz, 2JC–F = 29.0 Hz), 124.41 (qd, CF3, 1JC–
F = 285.4 Hz, 2JC–P = 12.6 Hz), 124.42, (CH, Ar), 130.87
(CH, Ar), 143.03 (Ar), 150.70 (Ar), 195.94 (d, 3JC–P = 8.5
Hz, C=O). Anal. Calcd for C14H17NPF3O7: C, 42.12; H, 4.29;
F, 14.28. Found: C, 42.31; H, 4.17; F, 14.42.
Compound (E)-8b: 1H NMR (200 MHz, CDCl3): d = 1.41 (t,
6 H, 2 Me, J = 7.1 Hz), 4.19–4.35 (m, 4 H, 2 OCH2), 7.77 (d,
1 H, JH–P = 24.0 Hz, =CH), 8.02–8.06 (m, 2 H, Ar), 8.31–
8.36 (m, 2 H, Ar). 19F NMR (188 MHz, CDCl3, C6F6):
d = 104.36 (d, JF–P = 5.5 Hz). 31P–1H decoupled (81 MHz,
CDCl3, 85% H3PO4): d = 9.06 (q, JP–F = 5.2 Hz). 13C NMR
(50 MHz, CDCl3): d = 16.20 (d, 3JC–P = 7.0 Hz, Me), 64.09
(d, 2JC–P = 5.7 Hz, OCH2), 124.26 (CH, Ar), 130.04, (CH,
Ar), 148.66 (m, =CH). Signals of carbon without hydrogen
were not found. Anal. Calcd for C14H15NPF3O6: C, 44.11; H,
3.97; F, 14.95. Found: C, 44.03; H, 3.75; F, 15.10.
(19) Nenajdenko, V. G.; Druzhinin, S. V.; Balenkova, E. S.
Chemistry of a,b-Unsaturated Trifluoromethyl Ketones;
Nova Sci. Publ.: New York, 2007.
(14) Singh, Y. P.; Saxena, S.; Rai, A. K. Synth. React. Inorg.
Met.-Org. Chem. 1982, 12, 867.
(15) (a) Jullien, J.; Pechine, J. M.; Perez, F.; Piade, J. J.
Tetrahedron 1982, 38, 1413. (b) Pavlov, A. M.; Chizhov, D.
L.; Charushin, V. N. Russ. J. Org. Chem. 2005, 41, 1449.
(c) Bonacorso, H. G.; Martins, M. A. P.; Bittencourt, S. R.
T.; Lourega, R. V.; Zanatta, N.; Flores, A. F. C. J. Fluorine
Chem. 1999, 99, 177. (d) Mkrtchyan, E. G.; Yachevskii, D.
S.; Chizhov, D. L.; Charushin, V. N. Russ. Chem. Bull. 2005,
54, 2150.
(20) Dembitsky, V. M.; Al Quntar, A. A. A.; Haj-Yehiaa, A.;
Srebnik, M. Mini-Rev. Org. Chem. 2005, 2, 91.
(21) (a) Kenyon, G. L.; Westheimer, F. N. J. Am. Chem. Soc.
1966, 88, 3557. (b) Costisella, B.; Keitel, I.; Gross, H.
Tetrahedron 1981, 37, 1227.
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