Reactions of ethyl triphenylphosphoranylideneacetate with fluorinated β-ketoaldehyde derivatives

Article abstract of DOI:10.1016/j.tet.2007.04.102

The reactions of fluorinated β-ketoaldehyde derivatives: β-alkoxyvinyl polyfluoroalkyl ketones 1 and fluorinated β-ketoacetals 2 with ethyl triphenylphosphoranylideneacetate 3 are described. In the case of ketones 1 the result of the reaction is a mixture

Full text of DOI:10.1016/j.tet.2007.04.102

Tetrahedron 63 (2007) 7246–7255
Reactions of ethyl triphenylphosphoranylideneacetate with
fluorinated b-ketoaldehyde derivatives
*
Ivan S. Kondratov, Igor I. Gerus, Marina V. Furmanova, Sergey I. Vdovenko and
Valery P. Kukhar
Institute of Bioorganic Chemistry and Petrochemistry, National Ukrainian Academy of Science, Murmanska 1,
Kiev-94, 02660, Ukraine
Received 29 November 2006; revised 6 April 2007; accepted 26 April 2007
Available online 10 May 2007
Abstract—The reactions of fluorinated b-ketoaldehyde derivatives: b-alkoxyvinyl polyfluoroalkyl ketones 1 and fluorinated b-ketoacetals 2
with ethyl triphenylphosphoranylideneacetate 3 are described. In the case of ketones 1 the result of the reaction is a mixture of products: fluo-
rinated alkoxydienes 5 (Wittig reaction product) and polyfluoroacyl vinyl ylides 7 (Michael addition product). The reaction with fluorinated
b-ketoacetals 2 leads to a mixture of E- and Z-isomers of polyfluoroalkyl acrylates 8 and 9, respectively. The influence of the nature of fluo-
rinated substituent and solvent or other factors on the outcome of the reactions are discussed.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
the high synthetic potential of these fluorinated building
blocks.
The growing interest in fluorine-containing compounds as
pharmaceuticals, agrochemicals, and tools for modern bio-
chemistry stimulates the development of synthetic methods,
which lead to fluoroorganic molecules.1 While direct intro-
duction of fluorine atoms or polyfluoroalkyl groups is
a very popular route to fluorinated molecules, the methods
based on available fluorine-containing building blocks
are useful too. In the last case, the reactions leading to
C–C bond formation play an important role for further
transformations.
The easily available and well-known fluorinated b-ketoalde-
hyde derivatives are b-alkoxyvinyl polyfluoroalkyl ketones
1 (Fig. 1).5 These compounds can be considered both as
b-ketoaldehyde derivatives with a protected aldehyde group
and a,b-unsaturated ketones. The reactions of nucleophiles
with compounds 1 lead to products of 1,2 or/and 1,4-addition
depending on the nature of the nucleophile and reaction con-
ditions used for the synthesis of various fluorine-containing
products such as fluorinated enaminoketones, protected ami-
no acids, heterocycles, cyanine dyes, and others.6 Neverthe-
less the reaction of enones 1 with phosphorus ylides has not
been previously studied yet, in general, there are just a few
publications concerning the reaction of enones 1 with phos-
phorus-containing reagents.7
Among various C–C bond formation reactions Wittig reac-
tions belong to the most popular organic synthesis.2 It is
also widely used for obtaining fluorinated compounds.3,4
For example, Wittig reaction was one of the keystages in syn-
thesis of fluorine-containing isopentenyl pyrophosphate,3a
cephalosporine,3b retinal,3c juvenile hormones,3d pyreth-
roids,3e aconiates,3f and 3-isopropyl malate,3g hexafluoro-
valine,3h and trifluoroisoleucine,3i chiral ferroelectric liquid
crystals.3j Various types of fluorine-containing molecules
such as polyfluoroalkyl aliphatic and aromatic ketones,
a,b-unsaturated ketones, b-diketones, and b-ketoesters
were introduced in Wittig reactions.3,4 However there are
no reports on the interaction between Wittig reagents and
fluorinated b-ketoaldehydes or their derivatives in spite of
Recently we have reported an approach to other fluorinated
b-ketoaldehyde derivatives—fluorinated b-ketoacetals 2
(Fig. 1, X¼F).8 In contrast to enones 1 these compounds
have just one electrophilic center (the carbonyl carbon
O
O
O
XF2C
XF2C
OR
O
(CH2)n
1
2
Keywords: Wittig reaction; Stabilized ylides; Fluorinated building blocks;
Polyfluoroalkyl ketones; b-Ketoacetals; b-Alkoxy enones.
* Corresponding author. Tel.: +380 44 573 2598; fax: +380 44 573 2552;
e-mail: vanya_ko@mail.ru
X = H, F, Cl, CF3, C2F5
R = alkyl, n = 2, 3
Figure 1. Fluorinated b-ketoaldehyde derivatives.
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.04.102

I. S. Kondratov et al. / Tetrahedron 63 (2007) 7246–7255
7247
H
CO2Et
OEt
atom). Therefore ketoacetals 2 can be used in reactions in-
stead of enones 1 if it is necessary to avoid an undesirable
1,4-addition.8
HF2C
5a
In the course of our research on the use of enones 1 for the
synthesis of bioactive compounds, in the present paper, we
report our investigations on the Wittig reaction between
ethyl triphenylphosphoranylideneacetate 3 and fluorinated
b-ketoaldehyde derivatives 1 and 2.
Figure 2. NOE observation in product 5a.
shown that the C]C double bond (CH]CHOEt fragment)
in products 5a–d retains the 4E-configuration (JHH 13.5–
13.7 Hz) of the starting enones 1. The 2E-configuration
of the formed C]C double bond of products 5a–d
(C]CHCO2Et fragment) was confirmed by NOE experi-
ments for product 5a (Fig. 2). According to the literature3,4
for the Wittig reaction of polyfluoroalkyl ketones the forma-
tion of the E-stereoisomer is favorable because an inter-
action between the largest vicinal polyfluoroalkyl and
ethoxycarbonyl groups is minimal in the intermediate beta-
ine 4. Since compound 5a is formed from enone 1a, bearing
the least hindered polyfluoroalkyl group (CHF2) in compar-
ison with other b-alkoxyvinyl polyfluoroalkyl ketones 1b–e
(CF3, CF2Cl, and C2F5), there is no doubt that products 5b–d
also have 2E-configuration, especially as the spectral data of
compounds 5a–d are very similar.
2. Results and discussion
We have found that enones 1a–e react with ylide 3 and a mix-
ture of two products 5a–d and 7a–e is formed (Scheme 1) in
complete conversion and high yields, moreover, the products
can be easily and effectively separated.
Compounds 5 are ‘normal’ products of the Wittig reaction,
which are formed due to initial ylide addition to carbonyl
group (intermediate 4) with the following triphenylphos-
phine oxide elimination. At the same time products 7 are
formed due to initial ylide attack at the b-position of enone
1 (intermediate 6) with subsequent ethanol elimination. The
latter direction of the reaction is unusual for a,b-unsaturated
carbonyl compounds. It should be mentioned that there are
just a few examples when the addition of a phosphorus ylide
to the b-position of a,b-unsaturated ketones or esters has
been observed.9 The formation of stable ylides with struc-
tures similar to compounds 7 was observed only for cases
when two electron withdrawing groups (EWG) were at-
tached to the double bond (C]C(EWG)2).9b,c Additionally
some highly stabilized ylides (including fluorinated) have
been obtained by synthetic methods,10 which are different
from those mentioned above.9b,c Nevertheless there are no
literature reports on the concurrent formation of 1,2- and
1,4-addition products from a,b-unsaturated carbonyl com-
pounds under Wittig reaction conditions. At the same time
such dual reactivity was observed for b-alkoxyvinyl poly-
fluoroalkyl ketones 1 in addition reactions with nucleophilic
reagents such as sodium borohydride,8 trimethylsilyl
cyanide,11 and tris(trimethylsilyl) phosphite.7c
We have also found that the C]C double bond of com-
pounds 7a–e has the E-configuration (JHH 13.4–13.8 Hz).
Additionally the structure of product 7b was proven by
X-ray analysis (Fig. 3).12 It should be noted that the C]P
˚
(1.765(1) A) is longer than the same bond in similar ylides
13
˚
(1.727 A/1.747 A).
˚
The ratio of the products 5 and 7 depends on the nature of
substituent X (Table 1). Its influence could result from either
steric changes (the increase of polyfluoroalkyl group volume
in series CHF2<<CF3<CF2Cl<C2F5<C3F7) or electronic
changes (the increase of electron withdrawing effect in
series CHF2<<CF3zCF2Cl<C2F5<C3F7). Whereas the in-
fluence of sterical factors is obvious (the increase of substit-
uent X size leads to increasing hindrance to ylide attack on
carbonyl group) and electronic effects caused by substituent
X influence are not so clear. Thus we used 13C NMR spectro-
scopic data from enones 1a–e in order to find possible differ-
ences of electronic density distribution of the conjugated
systems and to elucidate their reactivity. The 13C NMR
data of starting enones 1 do not point to considerable
It is noteworthy that only one stereoisomer of the products
5a–d and 7a–e was formed (demonstrated by NMR, IR spec-
troscopy, and X-ray analysis for compound 7b). It was
O
O-
Ph3P+
EtO2C
O- OEt
OEt
XF2C
CO2Et
+
Ph3PCHCO2Et
XF2C
CF2X
+PPh3
H
OEt
1a-e
3
4a-d
6a-e
-EtOH
-Ph3PO
O
CO2Et
CO2Et
PPh3
XF2C
XF2C
X = H (a), F(b), Cl (c), CF3 (d), C2F5 (e)
OEt
5a-d
7a-e
Scheme 1. Reaction between b-alkoxyvinyl polyfluoroalkyl ketones 1 and ethyl triphenylphosphoranylideneacetate 3 (CH2Cl2, rt, overnight, 100% conversion).

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I. S. Kondratov et al. / Tetrahedron 63 (2007) 7246–7255
Table 2. Product ratios of the reaction between enone 1b and ylide 3 in
various solvents
Solvent
Product ratiosa (%)
5b
7b
CCl4
27
23
23
18
16
14
16
12
73
77
77
82
84
86
84
88
Benzene
Toluene
CHCl3
CH2Cl2
THF
CH3CN
DMF
Ratios were obtained from 19F NMR spectra of reaction mixtures of 1b
(20 mg) and 3 (45 mg) after overnight stirring in 1 mL of the correspond-
ing solvent at rt.
a
The outcome of the Wittig reaction often depends on the
nature of solvent.14 Thus, we investigated the influence of
solvents on the reaction between ylide 3 and enone 1b by
19F NMR spectroscopy method (Table 2). The percentage
of the product 5b decreases mostly with increasing solvent
polarity that can be explained by the changes of electronic
structure of enone 1b as a result of specific solvatation.
This assumption is confirmed by the IR15 and 13C NMR
spectral data16 of enone 1b in various solvents: the increas-
ing solvent polarity results in a decrease of electrophilicity
at carbonyl carbon atom, whereas the reactivity of the
b-position of enone 1b increases.
Figure 3. X-ray structure of compound 7b (as a solvate with CCl4).
Table 1. Product ratios in the reaction mixture and isolated yields in the
reaction between enones 1a–e and ylide 3
Starting enone 1 Substituent X
Product ratiosa in reaction
mixture (isolated yields) (%)
5
7
1a
1b
1c
1d
1e
H
F
Cl
CF3
C2F5
48 (32)
52 (41)
84 (78)
86 (81)
95 (78)
100 (89)
16 (11)
14 (9)
5b (0)
0
It should be mentioned that the data here represents the first
example of a strong dependence between the ratio of prod-
ucts of 1,2- and 1,4-additions of nucleophiles to enones 1
and the nature of a solvent. Moreover, using the data of Table
2 (exact percentage of the products were used, see Supple-
mentary data) we determined that the product ratio depends
linearly on solvent parameters (Kamlet–Taft multiparameter
linear solvatation energy correlation)17 and the high correla-
tion coefficient (R¼0.981) demonstrates the strong sensi-
tivity of the reaction to the nature of the solvents. The
dependence of percentage of 5b and 7b is evaluated by
Eqs. 1 and 2, respectively:
Ratios were obtained from the 19F NMR spectra of reaction mixtures of 1
(2 mmol) and 3 (2.2 mmol) after overnight stirring at rt in 1 mL of
CH2Cl2.
a
Product 6d was observed by 19F NMR spectroscopy in reaction mixture
but not isolated.
b
difference in the electronic structure of enones 1b–e: the sig-
nals of the carbonyl carbon appear at 180–182 ppm and the
signals of the b-carbon atom at about 168 ppm (in CDCl3).
At the same time the corresponding signals in the 13C
NMR spectrum of enone 1a have different values of chemi-
cal shifts in comparison with enones 1b–e: the signal of car-
bonyl carbon atom appears at 187.8 ppm and the signal of
b-carbon atom at 166.4 ppm (in CDCl3). The facts demon-
strate a significant electronic structure difference between
enone 1a and enones 1b–e. Therefore it can be concluded
that the main factor, which exerts influence on the ratio of
the products 5 and 7 is steric hindrance in enones 1a–e pro-
duced by polyfluoroalkyl groups, and that electronic changes
are minor factors, which can only explain the difference of
reactivity between enone 1a and enones 1b–e. Furthermore,
even greater changes in the electronic structure can be ob-
served for the nonfluorinated enone 1f (13C NMR spectros-
copy data: the signals of C]O and b-carbon atoms appear
at 196.9 and 163.0 ppm, correspondingly (in CDCl3)) that
results in no reaction between enone 1f and ylide 3 even after
6 days under reflux in CH2Cl2 (Scheme 2).
u ð%Þ ¼ 29:150 ꢀ 16:062pꢁ ꢀ 14:219a ꢀ 14:817b
þ 4:511d2H=100
ð1Þ
ð2Þ
u ð%Þ ¼ 70:850 þ 16:062pꢁ þ 14:219a þ 14:817b
ꢀ 4:511d2H=100
where p*—index of solvent dipolarity/polarizability,
a—measure of the solvent hydrogen bond donor acidity,
b—measure of the solvent hydrogen bond acceptor basic-
ity, dH—discontinuous polarizability correction term for
polychlorine substituted aliphatic solvents. Equations
show that in addition to polarity (polarizability) of solvent
(regression coefficient of p*), the role of solvent acidity/
basicity is also important (regression coefficients of
a and b) and the growth of solvent acidity (basicity) leads
to increase of ylide product 7b (from signs of coefficients
of a and b).
O
Ph3PCHCO2Et
no reaction
H3C
OMe
1f
Scheme 2. Attempted reaction between enone 1f and ylide 3 (CH2Cl2,
reflux, 6 days, 0% conversion).

I. S. Kondratov et al. / Tetrahedron 63 (2007) 7246–7255
7249
Table 3. Product ratios of stereoisomeric products 8a–f and 9a–f in Wittig
reaction of ketoacetals 2a–f
Products 5 can be considered as polyfluoroalkyl-containing
dienoates and are of interest both as powerful synthons for
further conversions, due to the considerable quantity of func-
tional groups in such a compact molecule, and as potential
biologically active agents.18 But a serious disadvantage to
the wide usage of dienes 5 is their low yields. In order to ob-
tain compounds with a similar carbon skeleton and function-
ality we studied the Wittig reaction of other fluorinated
ketoaldehyde derivatives—ketoacetals 2a–f, which afford
only ‘normal’ Wittig products with ylide 3. Recently we
have reported practical synthetic methods for the preparation
of ketoacetals 2b,f from enone 1b8. Thus, the new com-
pounds 2a,c–e were obtained by the same way in 56–75%
yields (Scheme 3).
Compound
Substituent X
Product ratiosa in reaction
mixture (isolated yields) (%)
E-Isomer (8)
Z-Isomer (9)
2a
2b
2c
2d
2e
2f
H
F
Cl
CF3
C2F5
F
48 (39)
73 (69)
66 (64)
45 (34)
38 (29)
41 (34)
52 (45)
27 (23)
34 (24)
55 (39)
62 (58)
59 (46)
Ratio were obtained from 19F NMR spectra of reaction mixtures of 2
(2 mmol) and 3 (2.2 mmol) after overnight stirring at rt in 1 mL of
CH2Cl2.
a
O
O
proton signals under the irradiation of the CH2 proton signals
but the NOE-effect in compounds 9a–f was much higher in
comparison with 8a–f.
XF2C
HO(CH2)nOH
XF2C
O
O
OEt
(CH2)n
2a-f
The ratio of the products 8a–f and 9a–f was obtained from
1H and 19F NMR spectra of the crude reaction mixture
(Table 3) and two interesting observations can be seen. On
the one hand, the reaction results in a low stereoselectivity
in the C]C double bond formation (38–73% of F-isomer)
that is quite unusual for Wittig reaction between other fluo-
rinated ketones and stabilized ylides: generally F-olefins are
obtained in high percentage (>90%).3,4 On the other hand,
the increase of the stereoselectivity (a growing percentage
of E-isomer) can be expected with the enlargement of poly-
fluoroalkyl substituent volume. However, one can see that
the increase of the E-isomer percentage occurs only under
conversion from 2a to 2b (from X¼H to X¼F, correspond-
ingly), whereas further increase in the polyfluoroalkyl sub-
stituent volume in the starting ketoacetals 2b–e (from
X¼F to X¼C2F5) leads to an increase in the percentage of
‘less favorable’ Z-isomer. These data can be explained by
the additional participation of acetal oxygen atoms in stabi-
lization of the ‘less stable’ conformer of the intermediate
betaines. The fact, that the stereoselectivity depends signif-
icantly on acetal cycle size (compare the reactions with
ketoacetals 2b and 2f) and is not sensitive to the nature of
solvents, confirms this assumption indirectly. It should be
mentioned that the participation of oxygen-containing sub-
stituents (at b-position to carbonyl group) in the stabilization
of Wittig reaction intermediates was earlier proposed to
explain abnormal stereoselectivity in the Wittig reaction of
some carbohydrate derivatives.14c Nevertheless, the same
effect with the participation of fluorinated carbonyl com-
pounds was not described earlier.
1a-e
n=2; X = H (a), F(b), Cl (c), CF3 (d), C2F5 (e)
n=3; X = F (f)
Scheme 3. Synthesis of ketoacetals 2a–f (benzene, PTSA, reflux, 2–5 h,
56–75% yield).
The reaction of ketoacetals 2a–f with ylide 3 leads to a
mixture of isomeric E- and Z-acrylates 8a–f and 9a–f, re-
spectively (Scheme 4). The reaction proceeds in high con-
version and yields and the isomeric acrylates were
separated by column chromatography.
CO2Et
EtO2C
XF2C
O
O
3
XF2C
XF2C
+
O
O
O
O
O
(CH2)n
(CH2)n
(CH2)n
2a-f
8a-f
9a-f
n=2; X = H (a), F(b), Cl (c), CF3 (d), C2F5 (e)
n=3; X = F (f)
Scheme 4. Wittig reaction between ketoacetals 2a–f and ylide 3 (CH2Cl2, rt,
overnight, 100% conversion).
The structure of compounds 8a–f and 9a–f was inferred by
NMR and IR spectroscopy. The configuration of the C]C
double bond of the products 8a–f and 9a–f was confirmed
by NOE-experiments (Fig. 4): both isomers 8a–f and 9a–f
demonstrate changes of integral intensity of the ]CH
In order to explain the ratios of the products 8a–f and 9a–f
we propose the following scheme: the addition of ylide 3
to the carbonyl group of ketoacetals 2a–f leads to intermedi-
ate rotamers A-1 and A-2 (responsible for E-products) and
rotamers C-1 and C-2 (responsible for Z-products) (Scheme
5). In the absence of additional stabilizing factors the stereo-
chemical outcome of Wittig reaction is usually determined
by favorable formation of the intermediate A-2, where inter-
action between the largest vicinal polyfluoroalkyl and eth-
oxycarbonyl groups is minimal. In our case, the stability
of intermediates A-1 and C-1 is enhanced by additional
stabilizing interactions between the phosphorus and acetal
oxygen atoms, but conformer A-1 is less stable than B-1
EtO2C
XF2C
H
H
CO2Et
CH2
O
XF2C
CH2
O
O
O
(CH2)n
9a-f
(CH2)n
8a-f
n=2; X = H (a), F(b), Cl (c), CF3 (d), C2F5 (e)
n=3; X = F (f)
Figure 4. NOE-observation in products 8a–f and 9a–f.

7250
I. S. Kondratov et al. / Tetrahedron 63 (2007) 7246–7255
O-
O-
EtO2C
H
H
EtO2C
Ph3P+
CF2X
O
CF2X
O
Ph3P+
O
O
A-1
O
(CH2)n
(CH2)n
B-1
XF2C
+
Ph3PCHCO2Et
O
O
(CH2)n
2a-f
O-
O-
Ph3P+
Ph3P+
EtO2C
3
H
CF2X
O
CF2X
EtO2C
H
O
O
O
(CH2)n
(CH2)n
A-2
B-2
EtO2C
XF2C
CO2Et
XF2C
n=2; X = H (a), F(b), Cl (c), CF3 (d), C2F5 (e)
n=3; X = F (f)
O
O
(CH2)n
O
O
(CH2)n
8a-f
9a-f
Scheme 5. The stabilizing effect of the acetal oxygen atoms in the Wittig reaction of ketoacetals 2a–f.
(owing to steric interactions between vicinal polyfluoroalkyl
and esters groups). So, the stabilizing participation of the
3. Conclusion
acetal oxygen atom can explain both the high percentage
of Z-products and the observed change of the stereoselectiv-
ity with the increase of polyfluoroalkyl substituent volume.
At the same time the Wittig reaction of ketoacetal 2a (bear-
ing the smallest difluoromethyl group among other poly-
fluoroalkyl ones) results in a mixture of the products with
an unexpectedly high percentage of Z-isomer 9a (see Table
3). This probably results from a decrease of the electron
withdrawing power of the difluoromethyl group that sup-
presses the influence of steric factors only.
The Wittig reaction of fluorinated ketoacetaldehyde deriva-
tives 1a–e and 2a–f with ethyl triphenylphosphoranylide-
neacetates 3 is useful for the synthesis of novel stabilized
fluorinated ylides 5a–e (as a result of ylide attack at the
b-position of enones 1a–e) and acrylates 7a–d, 8a–f, and
9a–f (as a result of ylide attack at the carbonyl group of
compounds 1a–d and 2a–f). The direction of the reaction
depends on many factors such as the nature of solvent and
fluoroalkyl group. Moreover in the case of ketoacetals
2a–f the additional participation of the acetal oxygen atoms
in intermediate betaine stabilization and its influences on the
ratio of isomeric products 8a–f and 9a–f is observed. The
compounds obtained are of interest as fluorinated polyfunc-
tional building blocks for synthesis of products with poten-
tial biological activity, particularly fluorinated mevalonates.
Earlier the similar participation of the acetal oxygen atom
was also observed in an intramolecular hydrogen bond
formation in gem-diols 10 (which are easily formed from
ketoacetals 2 and water).8 However gem-diols 10 and
ketoacetals 2 exist in equilibrium in solution and the equilib-
rium position depends on the nature of the solvent. We
questioned whether the stereochemical outcome of the
Wittig reaction changes if gem-diols 10 are used instead
of ketoacetals 2. We found that the yields and Z- and
E-isomers ratio of the Wittig reaction between hydrates
10a,b and ylide 3 are the same as in the case of ketoacetals
2b,f (Scheme 6).
4. Experimental
4.1. General
IR spectra were recorded on Specord M-80. 1H, 13C, 19F, and
31P NMR spectra were recorded on Varian VXR instrument
at 300 MHz, Varian Unian Plus at 400 MHz, and Bruker
Avance DRX at 500 MHz in CDCl3 solutions. Chemical
shifts were reported in parts per million (ppm). TMS
O
HO OH
1
and CCl3F were used as internal standards for H (13C)
F3C
F3C
-H2O
and 19F, respectively. 31P spectra are referenced to 85%
H3PO4. The conversion of reactions was monitored by
TLC-plates (silica gel 60 F254, Merck). Column chromato-
graphy was carried out on silica gel 60 (Merck no.
109385, particle size 0.040–0.063). Starting materials were
commercially available (Aldrich, Fluka, and Merck). All
solvents and liquid reagents were distilled before using.
Starting enones 1a,d,e,6a 1b,5a and 1c;19 ketoacetals 2b,f;8
and hydrates 10a,b8 were prepared according to the litera-
ture procedures.
O
O
(CH2)n
O
O
(CH2)n
+H2O
10a,b
2b,f
3
n=2 (a), 3 (b)
n=2 (b), 3 (f)
8b,f + 9b,f
n=2 (b), 3 (f)
Scheme 6. gem-Diols 10 in Wittig reaction (CH2Cl2, rt, overnight, 100%
conversion).

I. S. Kondratov et al. / Tetrahedron 63 (2007) 7246–7255
7251
4.1.1. General procedure for the Wittig reaction with
enones 1a–e. To a solution of ylide 3 (2.2 mmol) in 5 mL
of CH2Cl2 the corresponding enones 1a–f (2.0 mmol)
were added under stirring. After 8–12 h monitored by TLC
and NMR the solvent was evaporated and the residue was
crystallized from an appropriate solvent to give the corre-
sponding ylide 7a–e. The filtrate after crystallization was
evaporated and the residue was purified by column chroma-
tography using an appropriate eluent to give the correspond-
ing alkoxydiene 5a–c (alkoxydiene 5d was not isolated) in
w95% purity. The yields of compounds 5a–c and 7a–f as
well as their percentage in the reaction mixture are presented
in Table 1.
4.1.1.4. Ethyl (E)-6,6,6-trifluoro-5-oxo-2-(triphenyl-
phosphoranylidene)-3-hexenoate (7b). Crystallized from
toluene/hexane (1:1) or CCl4; light yellow needles, mp
162–164 ꢂC [Found: C, 66.2; H, 4.6. C26H22F3O3P requires
C, 66.38; H, 4.71%]; nmax (CH2Cl2) 3052, 2984, 1680, 1632,
1522, 1440, 1400, 1368, 1320, 1260, 1190, 1163, 1136,
1102, 1000 cmꢀ1; dH (500 MHz, CDCl3) 0.87 (3H, t, JHH
7.1 Hz, Me), 3.98 (2H, q, JHH 7.1 Hz, CH2), 7.07 (1H, d,
JHH 13.8 Hz, COCH]), 7.35–7.72 (16H, m, Ph and CH–
C]PPh3); dC (126 MHz, CDCl3) 13.8, 59.5, 70.1 (d, JCP
112.6 Hz), 101.5, 118.2 (q, JCF 291.3 Hz), 123.5 (d, JCP
92.1 Hz), 129.2 (d, JCP 12.6 Hz), 133.2 (d, JCP 3.1 Hz),
133.6 (d, JCP 9.7 Hz), 152.3 (d, JCP 14.5 Hz), 167.0 (d, JCP
14.5 Hz), 177.4 (q, JCF 30.9 Hz); dF (470.5 MHz, CDCl3)
ꢀ78.31 (br s, CF3); dP (202 MHz, CDCl3) 30.11 (br s, PPh3).
4.1.1.1. Ethyl (2E,4E)-3-(difluoromethyl)-5-ethoxy-
2,4-pentadienoate (5a). Purified by column chromato-
graphy. CH2Cl2 (with few drops of Et3N) was used as an
eluent; colorless oil [Found: C, 54.7; H, 6.5. C10H14F2O3 re-
quires C, 54.54; H, 6.41%]; Rf (CH2Cl2) 0.74; nmax (CH2Cl2)
3060, 2960, 2928, 2872, 1712, 1632, 1519, 1455, 1381,
1307, 1240, 1189, 1133, 1096, 1033 cmꢀ1; dH (500 MHz,
CDCl3) 1.30 (3H, t, JHH 7.1 Hz, Me), 1.36 (3H, t, JHH
7.1 Hz, Me), 3.96 (2H, q, JHH 7.1 Hz, CH2), 4.20 (2H, q,
JHH 7.1 Hz, CH2), 5.75 (1H, s, ]CH–CO2Et), 6.17 (1H, t,
JHF 54.8 Hz, CHF2), 6.92 (1H, d, JHH 13.5 Hz, C–CH]),
7.22 (1H, d, JHH 13.5 Hz, O–CH]); dC (126 MHz,
CDCl3) 14.2, 14.5, 60.2, 65.7, 98.7, 113.7 (t, JCF 10.1 Hz),
115.2 (t, JCF 242.6 Hz), 144.3 (t, JCF 20.2 Hz), 155.8 (t,
JCF 2.8 Hz), 165.9; dF (470.5 MHz, CDCl3) ꢀ113.86 (d,
JHF 54.8, CHF2).
4.1.1.5. Ethyl (2E,4E)-3-[chloro(difluoro)methyl]-5-
ethoxy-2,4-pentadienoate (5c). Purified bycolumn chroma-
tography. CH2Cl2 (with few drops of Et3N) was used as an
eluent; colorless oil [Found: C, 47.3; H, 5.2. C10H13ClF2O3
requires C, 47.16; H, 5.15%]; Rf (CH2Cl2) 0.81; nmax
(CH2Cl2) 3060, 2985, 2935, 1732, 1560, 1448, 1376,
1132 cmꢀ1; dH (500 MHz, CDCl3) 1.31 (3H, t, JHH 7.1 Hz,
Me), 1.36 (3H, t, JHH 7.1 Hz, Me), 3.98 (2H, q, JHH 7.1 Hz,
CH2), 4.21 (2H, q, JHH 7.1 Hz, CH2), 5.95 (1H, s, ]CH–
CO2Et), 6.92 (1H, d, JHH 13.6 Hz, C–CH]), 7.28 (1H, d,
JHH 13.6 Hz, O–CH]); dC (126 MHz, CDCl3) 14.2, 14.6,
60.6, 65.9, 97.2, 112.3 (t, JCF 8.1 Hz), 124.6 (t, JCF
293.5 Hz), 145.3 (t, JCF 23.6 Hz), 156.8 (t, JCF 3.8 Hz),
165.7; dF (470.5 MHz, CDCl3) ꢀ51.69 (s, CF2Cl).
4.1.1.2. Ethyl (E)-6,6-difluoro-5-oxo-2-(triphenylphos-
phoranylidene)-3-hexenoate (7a). Crystallized from tolu-
ene/hexane (1:2); light yellow needles, mp 163–164 ꢂC
[Found: C, 69.2; H, 5.0. C26H23F2O3P requires C, 69.02;
H, 5.12%]; nmax (CH2Cl2) 3060, 2984, 1677, 1632, 1516,
1440, 1400, 1368, 1303, 1186, 1153, 1104, 1043,
1000 cmꢀ1; dH (500 MHz, CDCl3) 0.85 (3H, t, JHH
6.9 Hz, Me), 3.97 (2H, q, JHH 6.9 Hz, CH2), 5.70 (1H, t,
JHF 55.4 Hz, CHF2), 6.96–7.85 (17H, m, Ph and
CH]CH); dC (126 MHz, CDCl3) 14.0, 59.4, 67.8 (d, JCP
115.5 Hz), 103.1, 111.7 (t, JCF 252.6 Hz), 124.0 (d, JCP
92.4 Hz), 129.2 (d, JCP 12.6 Hz), 133.1 (d, JCP 2.7 Hz),
133.7 (JCP 9.2 Hz), 150.6 (d, JCP 13.5 Hz), 167.3 (d, JCP
15.3 Hz), 184.9 (t, JCF 22.4 Hz); dF (470.5 MHz, CDCl3)
ꢀ125.98 (br s, CHF2); dP (202 MHz, CDCl3) 30.04 (br s,
PPh3).
4.1.1.6. Ethyl (E)-6-chloro-6,6-difluoro-5-oxo-2-(tri-
phenylphosphoranylidene)-3-hexenoate (7c). Crystallized
from diethyl ether/CCl4 (1:2); light yellow needles, mp 151–
152 ꢂC [Found: C, 63.9; H, 4.5. C26H22ClF2O3P requires C,
64.14; H, 4.55%]; nmax (CH2Cl2) 3048, 2990, 1680, 1634,
1513, 1440, 1424, 1392, 1312, 1216, 1163, 1104, 1040,
1000, 947 cmꢀ1; dH (500 MHz, CDCl3) 0.86 (3H, t, JHH
6.9 Hz, Me), 3.97 (2H, q, JHH 6.9 Hz, CH2), 7.08 (1H, d,
JHH 13.4 Hz, COCH]), 7.34–7.75 (16H, m, Ph and CH–
C]PPh3); dC (126 MHz, CDCl3) 13.9, 59.6, 70.3 (d, JCP
115.7 Hz), 100.2, 122.5 (t, JCF 295.0 Hz), 123.6 (d, JCP
92.3 Hz), 129.3 (d, JCP 12.5 Hz), 133.2 (d, JCP 2.5 Hz),
133.8 (d, JCP 9.8 Hz), 152.7 (d, JCP 13.9 Hz), 167.1 (d, JCP
14.8 Hz), 179.2 (t, JCF 24.7 Hz); dF (470.5 MHz, CDCl3)
ꢀ64.70 (br s, CF2Cl); dP (202 MHz, CDCl3) 30.05 (br s,
PPh3).
4.1.1.3. Ethyl (2E,4E)-5-ethoxy-3-(trifluoromethyl)-
2,4-pentadienoate (5b). Purified by column chromato-
graphy. CH2Cl2 (with few drops of Et3N) was used as an
eluent; colorless oil [Found: C, 50.2; H, 5.6. C10H13F3O3
requires C, 50.42; H, 5.50%]; Rf (CH2Cl2) 0.81; nmax
(CH2Cl2) 3060, 2984, 2927, 2872, 1728, 1628, 1448,
1372, 1308, 1260, 1190, 1135, 1031 cmꢀ1; dH (500 MHz,
CDCl3) 1.31 (3H, t, JHH 7.1 Hz, Me), 1.35 (3H, t, JHH
7.1 Hz, Me), 3.97 (2H, q, JHH 7.1 Hz, CH2), 4.21 (2H, q,
JHH 7.1 Hz, CH2), 5.97 (1H, s, ]CH–CO2Et), 6.96 (1H, d,
JHH 13.7 Hz, C–CH]), 7.16 (1H, d, JHH 13.7 Hz, O–
CH]); dC (126 MHz, CDCl3) 14.2, 14.5, 60.5, 66.0, 97.8,
113.9 (q, JCF 6.5 Hz), 122.7 (q, JCF 276.5 Hz), 140.3 (q,
JCF 29.7 Hz), 156.4 (q, JCF 3.4 Hz), 165.5; dF (470.5 MHz,
CDCl3) ꢀ64.21 (s, CF3).
4.1.1.7. Ethyl (E)-6,6,7,7,7-pentafluoro-5-oxo-2-(tri-
phenylphosphoranylidene)-3-heptenoate (7d). Crystal-
lized from diethyl ether/CCl4 (1:2); light yellow needles,
mp 160–162 ꢂC [Found: C, 62.4; H, 4.3. C27H22F5O3P re-
quires C, 62.31; H, 4.26%]; nmax (CH2Cl2) 3052, 2985,
1682, 1633, 1515, 1440, 1394, 1368, 1311, 1192, 1164,
1104, 1058, 992 cmꢀ1; dH (500 MHz, CDCl3) 0.85 (3H, t,
JHH 6.8 Hz, Me), 3.97 (2H, q, JHH 6.8 Hz, CH2), 7.16 (1H,
d, JHH 13.4 Hz, COCH]), 7.41–7.86 (16H, m, Ph and
CH–C]PPh3); dC (126 MHz, CDCl3) 13.9, 59.7, 71.0 (d,
JCP 115.0 Hz), 102.3, 123.5 (d, JCP 92.7 Hz), 129.3 (d, JCP
12.4 Hz), 133.3 (d, JCP 2.3 Hz), 133.7 (d, JCP 9.9 Hz),
152.2 (d, JCP 13.8 Hz), 167.0 (d, JCP 13.8 Hz), 178.1 (t,
JCF 23.2 Hz), low intensity and high multiplicity signals of
carbon atoms of C2F5-fragment overlapped in the area of

7252
I. S. Kondratov et al. / Tetrahedron 63 (2007) 7246–7255
110–130 ppm; dF (470.5 MHz, CDCl3) ꢀ123.32 (2F, br s,
CF2), ꢀ82.78 (3F, s, CF3); dP (202 MHz, CDCl3) 30.20
(br s, PPh3).
35.91; H, 3.01%]; nmax (CH2Cl2) 3060, 2962, 2896, 1760,
1592, 1416, 1392, 1335, 1200, 1140, 1032, 944 cmꢀ1; dH
(500 MHz, CDCl3) 3.10 (2H, d, JHH 4.8 Hz, COCH2),
3.84–4.03 (4H, m, OCH2CH2O), 5.36 (1H, t, JHH 4.8 Hz,
CH2CH); dC (126 MHz, CDCl3) 42.4, 65.1, 99.5, 119.3 (t,
JCF 306.0 Hz), 190.5 (t, JCF 27.4 Hz), low intensity and
high multiplicity signals, which belong to carbon atoms of
C2F5-fragment overlapped in the area of 110–130 ppm; dF
(470.5 MHz, CDCl3) ꢀ124.25 (2F, s, CF2), ꢀ82.40 (3F, s,
CF3).
4.1.1.8. Ethyl (E)-6,6,7,7,8,8,8-heptafluoro-5-oxo-2-
(triphenylphosphoranylidene)-3-octenoate (7e). Crystal-
lized from diethyl ether/CCl4 (1:2); light yellow needles,
mp 136–138 ꢂC [Found: C, 59.3; H, 3.8. C28H22F7O3P re-
quires C, 58.96; H, 3.89%]; nmax (CH2Cl2) 3060, 2984,
1681, 1632, 1513, 1440, 1394, 1312, 1228, 1168, 1104,
1046, 1000, 952 cmꢀ1; dH (400 MHz, CDCl3) 0.86 (3H, t,
JHH 6.8 Hz, Me), 3.98 (2H, q, JHH 6.8 Hz, CH2), 7.15 (1H,
d, JHH 13.4 Hz, COCH]), 7.42–8.04 (16H, m, Ph and
CH–C]PPh3); dC (126 MHz, CDCl3) 13.7, 59.5, 70.8 (d,
JCP 115.5 Hz), 102.6, 123.4 (d, JCP 91.8 Hz), 129.2 (d, JCP
12.7 Hz), 133.2 (d, JCP 2.6 Hz), 133.6 (d, JCP 9.4 Hz),
152.1 (d, JCP 13.7 Hz), 167.1 (d, JCP 14.1 Hz), 178.1 (t,
JCF 23.2 Hz), low intensity and high multiplicity signals of
carbon atoms of C3F7-fragment overlapped in the area of
110–130 ppm; dF (470.5 MHz, CDCl3) ꢀ127.12 (2F, s,
CF3CF2), ꢀ121.03 (2F, br s, CF2CO), ꢀ81.14 (3F, t, JFF
8.8 Hz, CF3CF2); dP (202 MHz, CDCl3) 30.17 (br s, PPh3).
4.1.2.4.
1-(1,3-Dioxolan-2-yl)-3,3,4,4,5,5,5-hepta-
fluoro-2-pentanone (2e). From 3 g of enone 1e and 0.76 g
of ethylene glycol; yield: 1.82 g (57%); light yellow liquid,
bp 59–60 ꢂC (10 Torr) [Found: C, 33.6; H, 2.4. C8H7F7O3 re-
quires C, 33.82; H, 2.48%]; nmax (CH2Cl2) 3060, 2960, 2894,
1760, 1608, 1592, 1421, 1392, 1352, 1327, 1236, 1123,
1016, 944 cmꢀ1; dH (500 MHz, CDCl3) 3.10 (2H, d, JHH
4.9 Hz, COCH2), 3.85–4.06 (4H, m, OCH2CH2O), 5.36
(1H, t, JHH 4.9 Hz, CH2CH); dC (126 MHz, CDCl3) 42.9,
65.1, 99.5, 119.3 (t, JCF 306.0 Hz), 190.3 (t, JCF 26.6 Hz),
low intensity and high multiplicity signals, which belong
to carbon atoms of C3F7-fragment overlapped in the area
of 110–130 ppm; dF (470.5 MHz, CDCl3) ꢀ127.06 (2F, s,
CF3CF2), ꢀ121.96 (2F, q, JFF 8.7 Hz, CF2CO), ꢀ81.10
(3F, t, JFF 8.7 Hz, CF3).
4.1.2. General procedure for synthesis of ketoacetals
2a,c–e. A mixture of the corresponding enone (1 equiv)
1a,c–e, ethylene glycol (1.2 equiv), 20 mL of benzene, and
catalytic amount of p-toluenesulfonic acid (10 mg) was re-
fluxed with the simultaneous distillation of an ethanol/ben-
zene azeotrope. The conversion was monitored by NMR
and, if necessary, additional portion of benzene (10 mL)
was added until enones 1a,c–e disappeared by NMR. Then
benzene was removed and the residue was distilled in vac-
uum giving corresponding products 2a,c–e.
4.1.3. Generalprocedure for the Wittigreactionwith keto-
acetals 2a–f or hydrates 10a,b. To a solution of ylide 3
(2.2 mmol) in 5 mL of CH2Cl2 the corresponding ketoace-
tals 2a–f or gem-diols 10a,b (2 mmol) was added under stir-
ring. After 8–12 h (the reaction monitored by TLC or 19F
NMR) the solvent was evaporated and isomers 8a–f and
9a–f were separated by column chromatography using an
appropriate eluent. The yields of compounds 8a–f and 9a–
f as well as their percentage in the reaction mixture are
presented in Table 3.
4.1.2.1. 3-(1,3-Dioxolan-2-yl)-1,1-difluoroacetone (2a).
From 2.5 g of enone 1a and 1.14 g of ethylene glycol; yield:
1.88 g (68%); light yellow liquid, bp 58–59 ꢂC (20 Torr)
[Found: C, 43.4; H, 4.9. C6H8F2O3 requires C, 43.38; H,
4.85%]; nmax (CH2Cl2) 3060, 2984, 2895, 1752, 1592,
1424, 1392, 1248, 1216, 1135, 1083, 944 cmꢀ1; dH
(500 MHz, CDCl3) 3.04 (2H, d, JHH 5.0 Hz, COCH2),
3.80–4.12 (4H, m, OCH2CH2O), 5.31 (1H, t, JHH 5.0 Hz,
CH2CH), 5.76 (1H, t, JHF 54.0 Hz, CHF2); dC (126 MHz,
CDCl3) 41.5, 65.0, 99.8, 109.5 (t, JCF 252.2 Hz), 195.8 (t,
JCF 26.7 Hz); dF (470.5 MHz, CDCl3) ꢀ128.89 (d, JHF
54.0 Hz, CHF2).
4.1.3.1. Ethyl (E)-3-(1,3-dioxolan-2-ylmethyl)-4,4-di-
fluoro-2-butenoate (8a). CH2Cl2 was used as an eluent; col-
orless oil [Found: C, 50.7; H, 6.0. C10H14F2O4 requires C,
50.85; H, 5.97%]; Rf (CH2Cl2) 0.40; nmax (CH2Cl2) 3060,
2987, 2893, 1722, 1671, 1442, 1391, 1368, 1336, 1248,
1195, 1162, 1130, 1093, 1034, 968, 944 cmꢀ1; dH
(500 MHz, CDCl3) 1.30 (3H, t, JHH 7.1 Hz, Me), 3.07 (2H,
d, JHH 4.8 Hz, CH2CH), 3.82–4.01 (4H, m, OCH2CH2O),
4.22 (2H, q, JHH 7.1 Hz, OCH2Me), 5.11 (1H, t, JHH
4.8 Hz, CH2CH), 6.23 (1H, t, JHF 55.7 Hz, CHF2), 6.25
(1H, s, CH]); dC (126 MHz, CDCl3) 14.1, 31.6, 60.7,
64.9, 102.9, 114.1 (t, JCF 242.2 Hz), 122.4 (t, JCF 9.7 Hz),
144.6 (t, JCF 19.2 Hz), 165.2; dF (470.5 MHz, CDCl3)
ꢀ121.51 (d, JHF 55.7 Hz, CHF2).
4.1.2.2. 1-Chloro-3-(1,3-dioxolan-2-yl)-1,1-difluoro-
acetone (2c). From 5 g of enone 1c and 1.68 g of ethylene
glycol; yield: 4.09 g (75%); light yellow liquid, bp 65–
66 ꢂC (12 Torr) [Found: C, 36.1; H, 3.4. C6H7F2ClO3 re-
quires C, 35.93; H, 3.52%]; nmax (CH2Cl2) 3052, 2986,
2895, 1760, 1597, 1416, 1221, 1136, 1072, 1016,
920 cmꢀ1; dH (500 MHz, CDCl3) 3.09 (2H, d, JHH 4.9 Hz,
COCH2), 3.82–4.05 (4H, m, OCH2CH2O), 5.34 (1H, t, JHH
4.9 Hz, CH2CH); dC (126 MHz, CDCl3) 40.3, 65.1, 99.7,
119.3 (t, JCF 306.0 Hz), 187.8 (t, JCF 30.5 Hz); dF
(470.5 MHz, CDCl3) ꢀ69.60 (s, CF2Cl).
4.1.3.2. Ethyl (Z)-3-(1,3-dioxolan-2-ylmethyl)-4,4-di-
fluoro-2-butenoate (9a). CH2Cl2 was used as an eluent; col-
orless oil [Found: C, 50.7; H, 6.0. C10H14F2O4 requires C,
50.85; H, 5.97%]; Rf (CH2Cl2) 0.46; nmax (CH2Cl2) 3060,
2985, 2893, 1718, 1664, 1472, 1396, 1338, 1246, 1155,
1096, 1028, 944 cmꢀ1; dH (500 MHz, CDCl3) 1.30 (3H, t,
JHH 7.1 Hz, Me), 2.65 (2H, d, JHH 4.8 Hz, CH2CH), 3.85–
4.05 (4H, m, OCH2CH2O), 4.21 (2H, q, JHH 7.1 Hz,
OCH2Me), 5.09 (1H, t, JHH 4.8 Hz, CH2CH), 6.17 (1H, s,
CH]), 7.40 (1H, t, JHF 55.7 Hz, CHF2); dC (126 MHz,
4.1.2.3. 1-(1,3-Dioxolan-2-yl)-3,3,4,4,4-pentafluoro-2-
butanone (2d). From 3 g of enone 1d and 0.90 g of ethylene
glycol; yield: 1.80 g (56%); light yellow liquid, bp 49–51 ꢂC
(10 Torr) [Found: C, 36.1; H, 2.9. C7H7F5O3 requires C,

I. S. Kondratov et al. / Tetrahedron 63 (2007) 7246–7255
7253
CDCl3) 14.1, 31.5, 61.0, 65.0, 102.1, 110.2 (t, JCF 235.9 Hz),
125.8 (t, JCF 8.2 Hz), 145.2 (t, JCF 23.6 Hz), 164.3; dF
(470.5 MHz, CDCl3) ꢀ120.44 (d, JHF 55.7 Hz, CHF2).
(1:4) was used as an eluent; colorless oil [Found: C, 43.5;
H, 4.4. C11H13F5O4 requires C, 43.43; H, 4.31%]; Rf
(EtOAc/hexane, 1:4) 0.52; nmax (CH2Cl2) 3060, 2992,
2895, 1726, 1662, 1448, 1376, 1328, 1220, 1092, 1034,
900 cmꢀ1; dH (500 MHz, CDCl3) 1.31 (3H, t, JHH 7.1 Hz,
Me), 3.06 (2H, d, JHH 4.9 Hz, CH2CH), 3.80–4.00 (4H, m,
OCH2CH2O), 4.23 (2H, q, JHH 7.1 Hz, OCH2Me), 5.16
(1H, t, CH2CH, JHH 4.8 Hz), 6.41 (1H, s, CH]); dC
(126 MHz, CDCl3) 14.0, 31.7, 61.1, 64.9, 102.5, 128.1 (t,
JCF 8.3 Hz), 139.0 (t, JCF 21.6 Hz), 164.3, low intensity
and high multiplicity signals, which belong to carbon atoms
of C2F5-fragment are in the area of 110–130 ppm; dF
(470.5 MHz, CDCl3) ꢀ117.00 (2F, s, CF2), ꢀ83.92 (3F, s,
CF3).
4.1.3.3. Ethyl (E)-3-(1,3-dioxolan-2-ylmethyl)-4,4,4-
trifluoro-2-butenoate (8b). EtOAc/hexane (1:5) was used
as an eluent; colorless oil [Found: C, 47.4; H, 5.2.
C10H13F3O4 requires C, 47.25; H, 5.15%]; Rf (EtOAc/hex-
ane, 1:5) 0.56; nmax (CH2Cl2) 3060, 2984, 2894, 1726,
1672, 1472, 1444, 1376, 1360, 1311, 1183, 1133, 1080,
1035, 900 cmꢀ1; dH (500 MHz, CDCl3) 1.32 (3H, t, JHH
7.1 Hz, Me), 3.08 (2H, d, JHH 4.9 Hz, CH2CH), 3.82–4.01
(4H, m, OCH2CH2O), 4.24 (2H, q, JHH 7.1 Hz, OCH2Me),
5.18 (1H, t, JHH 4.9 Hz, CH2CH), 6.45 (1H, s, CH]); dC
(126 MHz, CDCl3) 14.0, 31.3, 61.0, 64.9, 102.3, 123.1 (q,
JCF 275.4 Hz), 125.3 (q, JCF 6.0 Hz), 139.4 (q, JCF
30.5 Hz), 164.5; dF (470.5 MHz, CDCl3) ꢀ69.81 (s, CF3).
4.1.3.8. Ethyl (Z)-3-(1,3-dioxolan-2-ylmethyl)-4,4,
5,5,5-pentafluoro-2-pentenoate (9d). EtOAc/hexane (1:4)
was used as an eluent; colorless oil [Found: C, 43.5; H,
4.4. C11H13F5O4 requires C, 43.43; H, 4.31%]; Rf (EtOAc/
hexane, 1:4) 0.39; nmax (CH2Cl2) 3060, 2986, 2894, 1737,
1664, 1446, 1376, 1328, 1248, 1194, 1136, 1104, 1032,
944 cmꢀ1; dH (500 MHz, CDCl3) 1.27 (3H, t, JHH 7.1 Hz,
Me), 2.55 (2H, d, JHH 4.7 Hz, CH2CH), 3.83–4.02 (4H, m,
OCH2CH2O), 4.21 (2H, q, JHH 7.1 Hz, OCH2Me), 5.02
(1H, t, JHH 4.7 Hz, CH2CH), 6.55 (1H, s, CH]); dC
(126 MHz, CDCl3) 13.8, 34.8, 61.4, 65.0, 102.0, 129.5 (t,
JCF 22.0 Hz), 131.2 (t, JCF 5.3 Hz), 164.7, low intensity
and high multiplicity signals, which belong to carbon atoms
of C2F5-fragment are in the area of 110–130 ppm; dF
(470.5 MHz, CDCl3) ꢀ114.02 (2F, s, CF2), ꢀ82.93 (3F, s,
CF3).
4.1.3.4. Ethyl (Z)-3-(1,3-dioxolan-2-ylmethyl)-4,4,4-
trifluoro-2-butenoate (9b). EtOAc/hexane (1:5) was used
as an eluent; colorless oil [Found: C, 47.3; H, 5.2.
C10H13F3O4 requires C, 47.25; H, 5.15]; Rf (EtOAc/hexane,
1:5) 0.37; nmax (CH2Cl2) 3060, 2985, 2892, 1735, 1669,
1384, 1260, 1176, 1136, 1098, 1032, 944 cmꢀ1; dH
(500 MHz, CDCl3) 1.30 (3H, t, JHH 7.1 Hz, Me), 2.60 (2H,
d, JHH 4.6 Hz, CH2CH), 3.85–4.04 (4H, m, OCH2CH2O),
4.24 (2H, q, JHH 7.1 Hz, OCH2CH3), 5.06 (1H, t, JHH
4.6 Hz, CH2CH), 6.30 (1H, s, CH]); dC (126 MHz,
CDCl3) 13.9, 35.7 (q, JCF 1.8 Hz), 61.4, 65.1, 101.7, 122.3
(q, JCF 275.5 Hz), 128.5 (q, JCF 3.7 Hz), 132.8 (q, JCF
32.1 Hz), 164.3; dF (470.5 MHz, CDCl3) ꢀ64.63 (s, CF3).
4.1.3.5.
Ethyl
(E)-4-chloro-3-(1,3-dioxolan-2-yl-
4.1.3.9. (E)-4-(1,3-Dioxolan-2-ylmethyl)-5,5,6,6,7,7,7-
heptafluoro-1-methoxy-3-hepten-2-one (8e). EtOAc/hex-
ane (1:4) was used as an eluent; colorless oil [Found: C,
40.8; H, 3.8. C12H13F7O4 requires C, 40.69; H, 3.70%]; Rf
(EtOAc/hexane, 1:4) 0.54; nmax (CH2Cl2) 3060, 2984,
methyl)-4,4-difluoro-2-butenoate (8c). EtOAc/hexane
(1:4) was used as an eluent; colorless oil [Found: C, 44.3;
H, 4.9. C10H13ClF2O4 requires C, 44.38; H, 4.84%]; Rf
(EtOAc/hexane, 1:4) 0.59; nmax (CH2Cl2) 3060, 2985,
2894, 1726, 1664, 1472, 1437, 1376, 1352, 1260, 1200,
1125, 1072, 1037, 968 cmꢀ1; dH (500 MHz, CDCl3) 1.32
(3H, t, JHH 7.1 Hz, Me), 3.13 (2H, d, JHH 4.9 Hz, CH2CH),
3.82–4.02 (4H, m, OCH2CH2O), 4.24 (2H, q, JHH 7.1 Hz,
OCH2Me), 5.23 (1H, t, JHH 4.9 Hz, CH2CH), 6.41 (1H, s,
CH]); dC (126 MHz, CDCl3) 14.1, 31.9, 61.0, 64.9,
102.4, 123.1 (t, JCF 7.5 Hz), 125.9 (t, JCF 292.7 Hz), 144.1
(t, JCF 24.4 Hz), 164.8; dF (470.5 MHz, CDCl3) ꢀ56.47 (s,
CF2Cl).
1729, 1660, 1376, 1344, 1232, 1120, 1037, 992, 962 cmꢀ1
;
dH (500 MHz, CDCl3) 1.31 (3H, t, JHH 7.1 Hz, Me), 3.06
(2H, d, JHH 4.8 Hz, CH2CH), 3.80–3.99 (4H, m, OCH2-
CH2O), 4.24 (2H, q, JHH 7.1 Hz, OCH2Me), 5.16 (1H, t,
JHH 4.8 Hz, CH2CH), 6.40 (1H, s, CH]); dC (126 MHz,
CDCl3) 14.0, 31.9, 61.1, 64.9, 102.6, 128.5 (t, JCF 8.6 Hz),
139.2 (t, JCF 21.7 Hz), 164.3, low intensity and high multi-
plicity signals of C3F7-fragment C atoms are in the area of
110–130 ppm; dF (470.5 MHz, CDCl3) ꢀ126.41 (2F, s,
CF3CF2), ꢀ114.13 (2F, q, JFF 9.7 Hz, CF2CO), ꢀ80.73
(3F, t, JFF 9.7 Hz, CF3CF2).
4.1.3.6.
Ethyl
(Z)-4-chloro-3-(1,3-dioxolan-2-yl-
methyl)-4,4-difluoro-2-butenoate (9c). EtOAc/hexane
(1:4) was used as an eluent; colorless oil [Found: C, 44.3;
H, 4.9. C10H13ClF2O4 requires C, 44.38; H, 4.84%]; Rf
(EtOAc/hexane, 1:4) 0.40; nmax (CH2Cl2) 3060, 2984,
2894, 1733, 1664, 1472, 1424, 1375, 1248, 1123, 1088,
1032, 936 cmꢀ1; dH (500 MHz, CDCl3) 1.30 (3H, t, JHH
7.1 Hz, Me), 2.61 (2H, d, JHH 4.8 Hz, CH2CH), 3.84–4.06
(4H, m, OCH2CH2O), 4.23 (2H, q, JHH 7.1 Hz, OCH2Me),
5.07 (1H, t, JHH 4.8 Hz, CH2CH), 6.20 (1H, s, CH]); dC
(126 MHz, CDCl3) 13.9, 35.4, 61.4, 65.4, 101.8, 124.5 (t,
JCF 292.5 Hz), 125.1 (t, JCF 3.9 Hz), 136.8 (t, JCF
25.7 Hz), 164.8; dF (470.5 MHz, CDCl3) ꢀ52.76 (s, CF2Cl).
4.1.3.10.
(Z)-4-(1,3-Dioxolan-2-ylmethyl)-5,5,6,6,7,
7,7-heptafluoro-1-methoxy-3-hepten-2-one (9e). EtOAc/
hexane (1:4) was used as an eluent; colorless oil [Found:
C, 40.8; H, 3.8. C12H13F7O4 requires C, 40.69; H, 3.70%];
Rf (EtOAc/hexane, 1:4) 0.41; nmax (CH2Cl2) 3060, 2992,
2896, 1738, 1663, 1447, 1374, 1343, 1247, 1119, 1032,
946, 912 cmꢀ1; dH (500 MHz, CDCl3) 1.26 (3H, t, JHH
7.1 Hz, Me), 2.55 (2H, d, JHH 4.5 Hz, CH2CH), 3.82–4.01
(4H, m, OCH2CH2O), 4.20 (2H, q, OCH2Me, JHH 7.1 Hz),
5.02 (1H, t, JHH 4.5 Hz, CH2CH), 6.57 (1H, s, CH]); dC
(126 MHz, CDCl3) 13.7, 34.9 (t, JCF 2.1 Hz), 61.4,
65.0, 102.1, 129.6 (t, JCF 22.7 Hz), 131.4 (t, JCF 5.3 Hz),
164.6, low intensity and high multiplicity signals, which
belong to carbon atoms of C3F7-fragment are in the area of
4.1.3.7.
4,4,5,5,5-pentafluoro-2-pentenoate (8d). EtOAc/hexane
Ethyl
(E)-3-(1,3-dioxolan-2-ylmethyl)-

7254
I. S. Kondratov et al. / Tetrahedron 63 (2007) 7246–7255
Biochemical Applications; Filler, R., Kobayashi, Y.,
Yagupolskii, L. M., Eds.; Elsevier: Amsterdam, 2000; (c)
Hiyama, T. Organofluorine compounds; Springer: Berlin,
2000; (d) Pondee, R.; Liu, H. Bioorg. Chem. 2004, 32, 393–
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J. Fluorine Chem. 2006, 127, 992–1012; (g) Kirk, K. L.
J. Fluorine Chem. 2006, 127, 1013–1029.
110–130 ppm; dF (470.5 MHz, CDCl3) ꢀ124.74 (2F, s,
CF3CF2), ꢀ110.98 (2F, q, JFF 9.7 Hz, CF2CO), ꢀ81.01
(3F, t, JFF 9.7 Hz, CF3CF2).
4.1.3.11. Ethyl (E)-3-(1,3-dioxan-2-ylmethyl)-4,4,4-
trifluoro-2-butenoate (8f). EtOAc/hexane (1:5) was used
as an eluent (Rf 0.42); colorless oil [Found: C, 49.1; H,
5.7. C11H15F3O4 requires C, 49.26; H, 5.64%]; nmax
(CH2Cl2) 3060, 2984, 2932, 1726, 1673, 1470, 1428,
1376, 1360, 1312, 1240, 1203, 1136, 1080, 1033,
900 cmꢀ1; dH (500 MHz, CDCl3) 1.31 (1H, dtt, JHH 13.6,
2.5, 1.1 Hz, OCH2CHaHbCH2O), 1.32 (3H, t, JHH 7.1 Hz,
Me), 2.08 (1H, dtt, JHH 13.6, 12.6, 5.0 Hz, OCH2CHaHb-
CH2O), 3.03 (2H, d, JHH 5.5 Hz, CH2CH), 3.73 (2H, ddd,
JHH 12.6, 11.8, 2.5 Hz, OCHaHbCH2CHaHbO), 4.08 (2H,
ddd, JHH 11.8, 5.0, 1.1 Hz, OCHaHbCH2CHaHbO), 4.25
(2H, q, JHH 7.1 Hz, OCH2Me), 4.73 (1H, t, JHH 5.5 Hz,
CH2CH), 6.42 (1H, s, CH]); dC (126 MHz, CDCl3) 14.0,
25.5, 32.1, 61.0, 66.9, 99.9, 123.1 (q, JCF 275.4 Hz), 125.3
(q, JCF 6.0 Hz), 139.1 (q, JCF 30.2 Hz), 164.5; dF
(470.5 MHz, CDCl3) ꢀ69.49 (s, CF3).
2. (a) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863–
927; (b) Rein, T.; Pedersen, T. M. Synthesis 2002, 579–594.
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823–826; (e) Nagele, U. M.; Hanack, M. Liebigs Ann. Chem.
1989, 847–852; (f) Cantacuzene, D.; Wakselman, C.;
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4.1.3.12. Ethyl (Z)-3-(1,3-dioxan-2-ylmethyl)-4,4,4-tri-
fluoro-2-butenoate (9f). EtOAc/hexane (1:5) was used as an
eluent (Rf 0.27); colorless oil [Found: C, 49.1; H, 5.7.
C11H15F3O4 requires C, 49.26; H, 5.64%]; nmax (CH2Cl2)
3060, 2983, 2930, 1734, 1672, 1469, 1432, 1381, 1284,
1179, 1132, 1100, 1034, 928, 912 cmꢀ1; dH (500 MHz,
CDCl3) 1.30 (3H, t, JHH 7.1 Hz, Me), 1.36 (1H, dtt, JHH
13.6, 2.5, 1.3 Hz, OCH2CHaHbCH2O), 2.08 (1H, dtt,
JHH 13.6, 12.6, 4.6 Hz, OCH2CHaHbCH2O), 2.54 (2H, dd,
JHH 5.2, 1.1 Hz, CH2CH), 3.78 (2H, ddd, JHH 12.6, 10.8,
2.5 Hz, OCHaHbCH2CHaHbO), 4.11 (2H, ddd, JHH 10.8,
4.6, 1.3 Hz, OCHaHbCH2CHaHbO), 4.24 (2H, q, JHH
7.1 Hz, OCH2Me), 4.69 (1H, t, JHH 5.2 Hz, CH2CH), 6.25
(1H, d, JHH 1.1 Hz, CH]); dC (126 MHz, CDCl3) 13.8,
25.5, 36.9 (q, JCF 1.8 Hz), 61.3, 66.9, 99.2, 122.4 (q, JCF
275.5 Hz), 128.3 (q, JCF 3.7 Hz), 132.6 (q, JCF 31.9 Hz),
164.4; dF (470.5 MHz, CDCl3) ꢀ64.52 (s, CF3).
€
4. (a) Machleidt, H.; Hartmann, V.; Bunger, H. Liebigs Ann.
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Acknowledgements
5. (a) Hojo, M.; Masuda, R.; Kokuryo, Y.; Shioda, H.; Matsuo, S.
Chem. Lett. 1976, 499–502; (b) Hojo, M.; Masuda, R.;
Sakaguchi, S.; Takagawa, H. Synthesis 1986, 1016–1017.
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Chem. 1994, 69, 195–198; (b) Nenaidenko, V. G.; Sanin,
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The work was supported by a fellowship from National
Scholarship Program of World Federation of Scientists
ICSC ‘World Laboratory’ (I.S.K.). We thank Enamine Ltd
(Kiev) for technical and financial supports. We also appreci-
ate Mr. Vitaliy V. Polovinko (Enamine Ltd, Kiev) for NMR
experiments and Mrs. S. V. Shishkina and Dr. O. V. Shishkin
(STC ‘Institute for Single Crystals’, Kharkov) for perform-
ing the X-ray diffraction study.
€
Roschenthaler, G.-V. J. Fluorine Chem. 2006, 127, 235–239.
8. Kondratov, I. S.; Gerus, I. I.; Kacharov, A. D.; Gorbunova,
€
M. G.; Kukhar, V. P.; Frohlich, R. J. Fluorine Chem. 2005,
126, 543–550.
Supplementary data
9. (a) Bohlmann, F. Chem. Ber. 1956, 89, 2191–2197; (b)
Bestmann, H. J.; Seng, F. Angew. Chem. 1962, 74, 154–155;
(c) Trippett, S. J. Chem. Soc. 1962, 4733–4734; (d) Freeman,
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1131; (f) An, M.; Toochinda, T.; Bartlett, P. A. J. Org. Chem.
2001, 66, 1326–1333.
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.04.102.
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