(E)-Trimethyl(perfluoroprop-1-enyl)silane as a reagent to transfer perfluoroprop-1-enyl group to ketones and aldehydes catalyzed by fluoride

Article abstract of DOI:10.1021/op5001385

Analogous to trifluoromethyltrimethylsilane (Ruppert's reagent) (E)-trimethyl(perfluoroprop-1-enyl)silane (1), prepared by deprotonation of (Z)-1,2,3,3,3-pentafluoroprop-1-ene (2a) at -78 °C in the presence of chlorotrimethylsilane, was shown to transfer the perfluoroprop-1-enyl group to a number of electrophiles containing carbonyl group in the presence of catalytic amount of fluoride anion. The perfluoroprop-1-enyl group was transferred to formaldehyde, acetaldehyde, benzaldehyde, acetone, trifluoroacetophenone resulting in formation of corresponding TMS-ethers of secondary and tertiary alcohols containing Z-CF₃CF=CF- fragment. With some substrates such as hexafluoroacetone, formaldehyde, and trifluoroacetophenone, substituted 5-membered dioxolane products of the reaction can be obtained, depending on the reaction conditions and the source of fluoride catalyst.

Full text of DOI:10.1021/op5001385

Article
pubs.acs.org/OPRD
(E)‑Trimethyl(perfluoroprop-1-enyl)silane As a Reagent to Transfer
Perfluoroprop-1-enyl Group to Ketones and Aldehydes Catalyzed by
Fluoride
Roman B. Larichev,*,† Viacheslav A. Petrov,*,‡ Gerard J. Grier,‡ Mario J. Nappa,† William J. Marshall,‡
Alexander A. Marchione,‡ and Rebecca J. Dooley‡
‡
†DuPont Chemicals and Fluoroproducts, DuPont Central Research and Development, DuPont, PO Box 8352, Wilmington,
Delaware 19803, United States
ABSTRACT: Analogous to trifluoromethyltrimethylsilane (Ruppert’s reagent) (E)-trimethyl(perfluoroprop-1-enyl)silane (1),
prepared by deprotonation of (Z)-1,2,3,3,3-pentafluoroprop-1-ene (2a) at −78 °C in the presence of chlorotrimethylsilane, was
shown to transfer the perfluoroprop-1-enyl group to a number of electrophiles containing carbonyl group in the presence of
catalytic amount of fluoride anion. The perfluoroprop-1-enyl group was transferred to formaldehyde, acetaldehyde,
benzaldehyde, acetone, trifluoroacetophenone resulting in formation of corresponding TMS-ethers of secondary and tertiary
alcohols containing Z-CF3CFCF− fragment. With some substrates such as hexafluoroacetone, formaldehyde, and
trifluoroacetophenone, substituted 5-membered dioxolane products of the reaction can be obtained, depending on the reaction
conditions and the source of fluoride catalyst.
unexpected double addition of some substrates to the
pentafluoropropenyl anion were observed which resulted in
formation of novel fluorinated derivatives containing 1,3-
dioxolane ring.
INTRODUCTION
■
When a perfluoroalkyl group is introduced into an organic
compound, physical, chemical, and biological properties of the
new compound are remarkably changed due to high electro-
negativity of fluorine (4.0 on Pauling’s electronegativity scale)
combined with the strength of C−F bond. Straightforward and
reliable procedures for the introduction of the perfluoroalkyl
groups are of a great value. Perfluoroalkyl silicon compounds of
the general formula RFSiR3 (R = alkyl) have become
particularly popular in both organic and organometallic
synthesis. The most used reagent for a broad variety of
trifluoromethylation reactions is CF3SiMe3, which is often
referred to as the Ruppert-Prakash reagent. The original report
by Ruppert et al.1 on the synthesis of CF3SiMe3 in 1984 was
followed by demonstration of clean transfer of trifluoromethyl
group to carbonyl compounds.2 Many literature examples
report using the Ruppert-Prakash reagent in synthesis as a
method for trifluoromethylation.3−6
In contrast, the use of fluorinated vinylsilanes has been
limited to very few examples. Thus, the transfer of a
trifluorovinyl group from trifluorovinyltrimethylsilane to
benzaldehyde promoted by fluoride ion was reported by the
Yagupolskii group7 (Scheme 1). Later this group reported
analogous transfer of trifluorovinyl group to aromatic ketones.8
Recently Burton reported fluoride ion catalyzed highly
stereoselective nucleophilic addition of the difluoroiodovinyl
group to aromatic aldehydes using E-(1,2-difluoro-2-iodovinyl)-
trialkylsilane reagent9 (Scheme 2).
RESULTS AND DISCUSSION
■
The synthesis of Z-CF3CFCFSi(CH3)3 as a pure isomer was
claimed by Tarrant.10 In this paper it was reported that 1:1
mixture of E- and Z-isomers of CF3CFCFH can be
deprotonated at low temperature and converted into Z-
CF3CFCFSi(CH3)3 in 90% yield after treatment with
chlorotrimethylsilane. This claim was later addressed by the
Burton group demonstrating that the mixture of E- and Z-
isomers of CF3CFCFH lithiated with n-BuLi at −78 °C and
subsequently quenched with Me3SiCl affords a corresponding
mixture of E- and Z-CF3CFCFSi(CH3)3 rather than pure Z-
isomer.11 It should also be pointed out that the synthesis of a
mixture of E- and Z-isomers of CF3CFCFSi(CH3)3 by using
bis(trimethylsilyl)mercury reagent was reported by Haszel-
dine.12 However, synthesis of the pure E-CF3CFCFSi(CH3)3
(1) as well as transfer of pentafluoropropenyl group to
electrophiles using these silanes have not been reported.
In all three mentioned reports a mixture of Z-CF3CFCFH
(2a) and E-CF3CFCFH (2b) was used as a starting material.
In order to prepare pure E-CF3CFCFSi(CH3)3 (1) we
decided to use pure 2a which can be obtained using thermal
isomerization of 1:1 mixture of 2a and 2b prepared by
sequential addition of hydrogen to double bond of hexa-
fluoropropylene followed by dehydrofluorination.13 The
mixture of 2a and 2b was isomerized at elevated temperature
However, transfer of a pentafluoropropenyl group to
electrophiles using a corresponding silane has not been
described. Here we report the use of E-CF3CFCFSi(CH3)3
(1) as a reagent to transfer a pentafluoropropenyl group to
electrophiles such as aldehydes and ketones. In majority of
cases the product of the transfer is a siloxane that can be
converted to the corresponding alcohol by hydrolysis. Also
Special Issue: Fluorine Chemistry 14
Received: April 23, 2014
Published: July 9, 2014
© 2014 American Chemical Society
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Scheme 1. Fluoride promoted trifluorovinyl addition to benzaldehyde
Scheme 2. Fluoride-promoted difluoroiodovinyl addition to substituted benzaldehyde
over a catalyst to obtain the thermodynamically stable isomer
2a with 95+% purity.14 After that 2a was further purified to 99+
% level by distillation.
transferred to benzaldehyde than trifluorovinyl group of CF2
CFSiMe3 under the same conditions.
In order to study the scope of the reaction, other carbonyl-
containing substrates were tested as electrophiles in the
reaction with 1. The substrates along with yields of
corresponding products (siloxanes or alcohols) are shown in
Table 1, and the details of synthesis are described in the
Experimental Section section. Compound 5 was isolated by
distillation as colorless liquid with a boiling point 30 °C at 0.12
mmHg. Compound 9 was isolated by sublimation under
vacuum as white crystalline solid. It should be pointed out that
When attempting the synthesis of 1 by first generating anion
CF3CFCF¯ by deprotonation of 2a using either n-BuLi or
LDA at −78 °C in THF or ether solvent, only decomposition
products were observed by NMR analysis, after quick darkening
of the reaction mixture within minutes even at −78 °C. We
found that changing addition order of the reagents has a
significant effect on the process and the best approach was to
add chlorotrimethylsilane (TMS-Cl) to LDA solution at −78
°C in ether followed by addition of 2a. With this order of
addition 1 was formed in satisfactory yield (77%), presumably
due to the fact that anion CF3CFCF¯ was trapped by TMS-
Cl as soon as it was forming. After addition of 2a to the
reaction mixture, the light yellow reaction solution was allowed
to warm up to room temperature, filtered to remove LiCl, and
compound 1 was isolated by distillation. Ether is preferred as a
solvent over THF due to a lower boiling point which makes the
isolation of 1 (boiling point is 94 °C) easier.
1
only one isomer was identified by H and 19F NMR analyses
which indicated that the nucleophilic attack of the fluorinated
anion occurs selectively from one side of the carbonyl double
bond. The crystal structure of 9 shown in Figure 1 reveals the
exo-isomer which suggests that the nucleophilic attack at the
carbonyl group occurs from the less sterically hindered
position. Also, contrary to all other products, compound 9 is
isolated as alcohol, rather than a trimethylsilyl ether.
Presumably due to the steric hindrance, the TMS-ether
hydrolyzes to the alcohol rapidly upon an aqueous workup.
Compounds 6−8 were not isolated due to the small scale for
these reactions, but instead the reaction mixtures were
characterized by NMR analysis. Reaction of acetone with 1 at
room temperature afforded a mixture of 2a and 8 in a ratio 4:1,
however, when reaction was carried out at −30 °C the ratio
changed to 1:1. Presumably enolizable substrates may afford
low yields of the desired addition product due to their facile
deprotonation by the fluorinated anion to give 2a and enolate
tautomer. The GC/MS analysis of the reaction mixture
detected small amounts of two side products that originated
from the corresponding enolate, CH3C(O)CH2C(CH3)2OSi-
(CH3)3 and CH3C(O)CHC(CH3)2. Also a reaction of 1
with 1,1,1-trifluoroacetone produced mostly 2a along with a
complex mixture of species containing CF3 group according to
19F NMR analysis, while no addition product was observed in
this case.
With silane 1 in hand we set out to study its reactions with
electrophiles containing a carbonyl group. After equimolar
amounts of benzaldehyde and 1 were combined in anhydrous
THF at room temperature in the presence of 5 mol % of CsF
and the reaction mixture was agitated at ambient temperature
for 3 h (Scheme 3), we were pleased to find that all the starting
Scheme 3. Fluoride-catalyzed pentafluoropropenyl addition
to benzaldehyde
material 1 was gone and an expected product 4 was observed
by 19F NMR analysis along with a small amount of 2a which
presumably formed due to a reaction of 1 with adventitious
moisture in reaction mixture and with small amount of
fluorotrimethylsilane (TMS-F). Both 2a and TMS-F along
with THF are easily distilled off to afford crude product 4. Pure
4 (>99%) was obtained as a colorless liquid by vacuum
distillation in 66% isolated yield. As compared to the synthesis
of 3 (Scheme 1), our improvements include using catalytic CsF
(5 mol %) as well as shortening reaction time to just 3 h even in
the less polar THF instead of DME. These differences indicate
that the pentafluoropropenyl group of 1 is more readily
In order to prepare compound 7, potassium fluoride had to
be used as a catalyst, while catalysis with cesium fluoride affords
a different type of product which is described later in the paper.
This reaction was much slower than previously described CsF
catalyzed reactions, so it took 15 days at room temperature to
complete conversion of 1 into 7. A very significant portion of 1
is lost to the common side product, 2a (about 40%), due to
inevitable presence of moisture in paraformaldehyde.
In order to demonstrate that the TMS-ethers can be easily
hydrolyzed to the corresponding alcohols, compound 4 was
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Table 1. Substrates and products of fluoride promoted reactions of 1 with aldehydes and ketones
a
b
Yield determined by 19F NMR integration, Yield of the reaction carried out at −30 °C
Scheme 4. Hydrolysis of TMS-ether 4 to secondary alcohol
13
Scheme 5. (a) Fluoride-promoted reaction of 1 with 2 equiv
of HFA to afford 10; (b) 19F−19F through-space NOE
interactions and coupling in 10
Figure 1. Crystal structure of 9 with thermal ellipsoids drawn to the
30% probability level.
treated by 1 M aqueous solution of HCl at elevated
temperature. At 50 °C no reaction was detected, while at 100
°C an essentially complete conversion to alcohol 13 was
observed (Scheme 4). Most likely analogous hydrolysis can be
done for TMS-ethers 5−8 to obtain corresponding alcohols,
however, these reactions were not attempted in this study.
An unexpected result was observed when 1 was reacted with
hexafluoroacetone (HFA) in the presence of CsF in THF.
Along with unreacted 1 was observed a new fluorinated
compound that had only one vinylic fluorine according to 19F
NMR. The analysis by GC/MS showed that the molecular
weight of the new material is 444 g/mol which is consistent
with the structure 10 (Scheme 5). Formation of 10 probably is
a result of adding a second HFA equivalent to the initial 1:1
adduct followed by nucleophilic intramolecular cyclization
giving a 5-membered ring after the loss of fluoride ion and
reestablishing the double bond. In fact the product of a single
addition is not observed even in a small amount. When 2 equiv
of HFA are added, a full conversion of 1 to 10 was observed
while reaction mixture remained almost colorless throughout
the reaction. The pure product was obtained by distillation in
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Scheme 6. Proposed rationale for the stereochemistry of 10
69% isolated yield. An interesting detail about this reaction is
that due to limited solubility, 10 forms a separate liquid phase.
Another interesting feature of this process is the orientation
of the substituents around the double bond in the product. The
Scheme 7. Synthesis of 11 by the reaction of 1 with 2 equiv
of 2,2,2-trifluoroacetophenone catalyzed by
tetrabutylammonium fluoride; compound 11 is a mixture of
two stereoisomers
a
six fluorine atoms of two CF3 groups on the carbon atom
adjacent to the double bond are coupled to the only fluorine
substituent on the double bond with a very significant coupling
constant of 16 Hz and are not coupled at all to the cCF3 group
on the double bond (Scheme 5b). That suggests a through-
space coupling and orientation on the same side of the double
bond for the single fluorine and C(aCF3)2 group. This
orientation was confirmed by the 19F NOESY NMR experi-
ment. As expected, the strongest interaction was observed
c
between vinylic fluorine and CF3. There was also interaction
between vinylic fluorine and group C(aCF3)2, while there was
no interaction between cCF3 and C(aCF3)2 or C(bCF3)2 groups.
These observations are consistent with the structure 10. Such
orientation is opposite to the expected orientation derived from
the fluorinated anion intermediate. However, the explanation
can be found in the proposed transition state shown in Scheme
6. The intermediate alkoxy anion can attack the double bond
either from the top or from the bottom. The intermediate
formed by attack from the top shown in Scheme 6 has a
freedom to rotate around the bond that used to be the double
bond and to relieve the strain of having two bulky substituents
on the same side. The C(CF3)2 substituent moves away from
the CF3 group on the opposite side of the former double bond,
but also in such a staggered orientation so that the electron pair
of the anion is in a periplanar position to the fluorine that is
about to leave (intermediate B). Thus, when the double bound
is reestablished, the orientation of compound 10 is obtained.
When the attack by alkoxy anion occurs from the bottom, the
rotation takes the C(CF3)2 substituent into an antiperiplanar
position to CF3 group, and the departure of fluoride occurs also
from an antiperiplanar position to the anion electron pair,
resulting again in compound 10.
When tetrabutylammonium fluoride was substituted for
cesium fluoride in the reaction of 1 with 2 equiv of 2,2,2-
trifluoro-1-phenylethanone in THF, a new 60:40 product
mixture was observed instead of the expected product 5. The
two products have analogous sets of peaks in 19F NMR
spectrum with three CF3 groups and with only one vinylic
fluorine just like compound 10. In addition, the GC/MS
analysis suggested that both new products have molecular
weight 460 g/mol, which is consistent with the dioxolane
structure 11 (Scheme 7). These two species were not observed
when the same reaction was done with catalytic CsF (entry 2,
Table 1).
Figure 2. Through-space NOE interactions in 11a−b.
a
5
interaction with the CF3 group and a coupling constant JFF
=
16.7 Hz; also it has a heteronuclear NOE with two protons in
the ortho-position of the phenyl ring. On the other hand the
bCF3 group has no interactions with any other fluorine atoms in
the molecule which indicates that it can be on the −CPhCF3−
group between two oxygen atoms, pointed away from the
double bond, and on the opposite side of the plane of dioxolane
a
ring from the CF3 group. Thus, just as in compound 10 the
bulky group, which in this case is the −CPhCF3− group, rotates
away from the CF3 group on the double bond into a trans-
position, and cis to the smaller vinylic fluorine atom. In the
minor isomer 11b (40%) the vinylic fluorine has the same
interactions with the cCF3 group and protons in ortho-position
indicating the same orientation around the double bond as in
isomer 11a, but there is also significant interaction between
cCF3 and dCF3 groups (6JFF = 3.9 Hz), suggesting that they are
located on the same side of the plane of the dioxolane ring.
From the thermodynamic point of view it also makes sense that
the major isomer would have the two bulkier phenyl groups on
the opposite sides of the ring to alleviate the steric hindrance.
As we can see, the reaction of 1 with various electrophiles can
give either TMS−ether as a product, or it can go further and
give a product of double addition with a substituted dioxolane
ring. An important conclusion can be made from the synthesis
of 11 using tetrabutylammonium fluoride as a catalyst.
Apparently, whether the TMS−ether or dioxolane derivative
is formed depends not only on the nature of the substrate, but
also on the catalyst. Thus, for the same substrate, 2,2,2-
trifluoro-1-phenylethanone, both TMS−ether and dioxolane
derivative can be prepared, depending on the catalyst. In fact,
In order to elucidate the exact orientation of substituents in
the two new species, the 19F NOESY NMR and the 1H HOESY
NMR experiments were performed on the product mixture.
Observed interactions and couplings can only be consistent
with the structures shown in Figure 2. In the major isomer 11a
(60%) the vinylic fluorine has a strong through-space NOE
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while the reaction of 1 with paraformaldehyde in the presence
of KF as a catalyst gave the TMS−ether 7, the analogous
reaction catalyzed by cesium fluoride afforded clean, cyclic
product 12 (Scheme 8). It was identified by the single vinylic
fluorine in the 19F NMR spectrum with the chemical shift at
−167.2 ppm.
CONCLUSION
■
The results reported here show that compound 1 serves as a
convenient reagent to transfer the Z-CF3CFCF− group to
aldehydes and ketones under ambient conditions. Two
outcomes of the reaction are possible, depending on the
nature of a substrate and a catalyst. In the first one the reaction
stops at a single addition of a substrate to the fluorinated anion
to afford a TMS−ether with retention of the stereochemistry
around the double bond. In the second outcome, a double
addition of a substrate occurs to afford 5-membered dioxolane
products with the orientation around the double bond that is
opposite to the expected orientation derived from 1, due to the
steric factors.
Scheme 8. Fluoride-promoted reaction of 1 with
paraformaldehyde to afford 12
EXPERIMENTAL SECTION
■
All reactions were performed in dried glassware, under an
atmosphere of nitrogen. 1H and 19F NMR spectra were
recorded on a Bruker DRX-500 spectrometer. 1H NMR spectra
were referenced to the protio impurity in the solvent. 19F NMR
spectra were referenced to external CFCl3 (0.00 ppm). GC and
GC/MS analyses were carried out on an HP-6890 instrument,
using an HP-1 capillary column and either TCD (GC) or mass-
selective (GS/MS) detectors, respectively. Anhydrous THF and
ether were purchased from Aldrich and used without further
purification. KF and CsF (Aldrich) were dried at 150−180 °C
under dynamic vacuum for 4−6 h and then were stored and
handled inside a drybox. Pure 2a was obtained using thermal
isomerization of a 1:1 mixture of 2a and 2b prepared by
sequential addition of hydrogen to the double bond of
hexafluoropropylene followed by dehydrofluorination.13 The
mixture of 2a and 2b was isomerized at elevated temperature
over a catalyst to obtain the thermodynamically stable isomer
An attempt was made to prepare a dioxolane derivative with
benzaldehyde as a substrate using tetrabutylammonium
fluoride. The starting material 1 had reacted, and a complex
mixture was obtained. Although no product could be isolated
from that mixture, after partial purification by column
chromatography on silica gel with ethyl acetate, a small amount
of the two isomers of dioxolane derivative were observed in the
19F NMR spectrum along with unidentified materials. The two
isomers had signals for vinylic fluorine atoms with a signature
chemical shift of −161.9 and −164.8 ppm. It was difficult to
fully characterize these two isomers due to very low yield
(about 5%), but clearly the reaction took a different path
compared to the reaction catalyzed by cesium fluoride. It can be
noticed that a catalyst with tighter pairing of fluoride with
countercation favors formation of TMS−ether, while a catalyst
with less coordinated fluoride is more likely to produce a
dioxolane derivative for the same substrate (Table 2).
Table 2
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2a with 95+% purity.14 After that 2a was further purified to 99+
% level by distillation.
mL Schlenk flask were added cesium fluoride (350 mg, 2.3
mmol), anhydrous THF (40 mL), trifluoroacetophenone (5.7
g, 33 mmol), and last was added E-CF3CFCFSi(CH3)3 (7.4
g, 36 mmol). The mixture was stirred for 3 h at room
temperature and the resultant solution was filtered. The
product was isolated by vacuum distillation as colorless liquid
(5.9 g, 48% yield, bp 30 °C/0.12 mmHg).
Crystallography. X-ray data for 9 were collected at −100
°C using a Bruker 1K CCD system equipped with a sealed-tube
molybdenum source and a graphite monochromator. The
structures were solved and refined using the Shelxtl15 software
package, refinement by full-matrix least-squares on F2,
scattering factors from International Tables, Vol. C, Tables
4.2.6.8 and 6.1.1.4. Crystallographic data (including structure
factors) for this structure have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC #990931. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK, (fax: +44 1223 336033 or e-
mail: deposit@ccdc.cam.ac.uk).
1H NMR (CDCl3, 500 MHz, 25 °C) δ 0.06 (s, 9H,
Si(CH3)3), 7.44−7.64 (m, 5H, C6H5).
19F NMR (C6D6, 470.2 MHz, 25 °C) δ −61.95 (m, 3F,
CCF3), −72.69 (dm, J = 12. Hz, 3F, CFCF3), −121.96 (m, 1F),
−146.26 (m, 1F).
Hydrolysis of (Z)-Trimethyl(2,3,4,4,4-pentafluoro-1-
phenylbut-2-enyloxy)silane (3) to the Corresponding
Alcohol (Z)-2,3,4,4,4-Pentafluoro-1-phenylbut-2-en-1-ol
(13). To the 50 mL flask were added (3.0 g, 9.7 mmol) and 1.0
M HCl solution (20 mL). The resultant biphasic mixture was
heated at 50 °C for 30 min. No change was detected by 19F
NMR analysis. The temperature was raised to 100 °C, and
stirring continued for 1 h. A full conversion into the product
was observed. The organic phase was separated, solvent
removed, and the product obtained as colorless liquid (2.1 g,
90% yield).
Preparation of (E)-Trimethyl(perfluoroprop-1-enyl)-
silane (1). To the 500 mL flask was added anhydrous ether
(120 mL) and cooled to −78 °C on dry ice/acetone bath. Then
2.0 M n-BuLi in pentane (100 mL, 0.20 mol) was added
followed by slow addition of diisopropylamine (28.3 mL, 20.3
g, 0.20 mol). The resultant mixture was allowed to warm up to
0 °C while stirring for 30 min. Then the mixture was cooled
down to −78 °C again, chlorotrimethylsilane (21.7 g, 25.3 mL,
0.20 mol) was slowly added, and (Z)-1,2,3,3,3-pentafluoroprop-
1-ene (26.5 g, 0.20 mol) was slowly bubbled through the
agitated reaction mixture. After that the reaction mixture was
allowed to warm up to room temperature and stirred for 1 h,
and the resultant mixture was filtered and washed with 0.5 M
aqueous solution of HCl (2 × 250 mL). Then the organic
phase was dried over MgSO4, and the product was isolated by
distillation as colorless liquid (31.5 g, 77% yield, bp 94 °C).
MS: m/z, 204 (M+), 189 (−CH3), 93, 89, 81, 77, 73, 69
(CF3).
1H NMR (CDCl3, 500 MHz, 25 °C) δ 5.71 (br d, 3JFH = 26.9
Hz, 1H, CH), 7.38−7.45 (5H, C6H5).
19F NMR (CDCl3, 470.23 MHz, 25 °C) δ −65.39 (dd, 3JFF
=
11.7 Hz, 4JFF = 8.7 Hz, 3F, CFCF3), −139.09 (dqd, 3JFH = 26.9
4
3
Hz, JFF = 8.7 Hz, JFF = 4.1 Hz, 1F, CFCCH), −155.15 (qdd,
3JFF = 11.7 Hz, JFF = 4.1 Hz, JFH = 1.6 Hz, 1F, CF3CF).
Preparation of (Z)-Trimethyl(3,4,5,5,5-pentafluoro-
pent-3-en-2-yloxy)silane (6). To the 50 mL Schlenk flask
were added cesium fluoride (200 mg, 1.3 mmol), anhydrous
THF (15 mL), acetaldehyde (0.43 g, 9.8 mmol), and E-
CF3CFCFSi(CH3)3 (2.0 g, 9.8 mmol). The resultant mixture
was stirred for 6 h at room temperature. The product was
observed by NMR analysis in the reaction mixture (50% yield
based on integration in 19F NMR spectrum).
3
4
1H NMR (CDCl3, 500 MHz, 25 °C) δ 0.30 (s, 9H,
Si(CH3)3).
19F NMR (CDCl3, 470.23 MHz, 25 °C) δ −67.58 (dddectet,
3JFF = 13.5 Hz, 4JFF = 6.5 Hz, 6JFH = 0.8 Hz, 3F, CF3), −137.66
(dqdectet, 3JFF = 11.1 Hz, 4JFF = 6.5 Hz, 4JFH = 1.1 Hz, 1F, CF),
19F NMR (377.44 MHz, 25 °C) δ −66.34 (dd, JFF = 12.0
3
3
3
−142.13 (qd, JFF = 13.5 Hz, JFF = 11.1 Hz, 1F, CFCF3).
Hz, 4JFF = 8.6 Hz, 3F, CF3), −139.32 (dqd, 3JFH = 26.3 Hz, 4JFF
13C NMR (CDCl3, 125.68 MHz, 25 °C) δ −2.31 (s, 3C,
= 8.6 Hz, JFF = 4.0 Hz, 1F, CFCH), −160.37 (qd, JFF = 12.0
3
3
1
2
3
3
Si(CH3)3), 119.44 (qdd, JCF = 270 Hz, JCF = 37.5 Hz, JCF
=
Hz, JFF = 4.0 Hz, 1F, CF).
11 Hz, 1C, CF3), 145.21 (dqd, 1JCF = 271 Hz, 2JCF = 40 Hz, 2JCF
Preparation of (Z)-Trimethyl(2,3,4,4,4-pentafluoro-
but-2-enyloxy)silane (7). To the 100 mL Schlenk flask
were added paraformaldehyde (1.3 g, 43 mmol), potassium
fluoride (200 mg, 3.4 mmol) anhydrous THF (20 mL), and E-
CF3CFCFSi(CH3)3 (3.8 g, 18 mmol). The resultant mixture
was stirred for 15 days at room temperature. The product was
observed by NMR analysis in the reaction mixture (45% yield
based on integration in 19F NMR spectrum).
1
2
= 21 Hz, 1C CFCF3), 158.56 (ddq, JCF = 287 Hz, JCF = 6.5
Hz, JCF = 3 Hz, 1C, CFSi).
3
Preparation of (Z)-Trimethyl(2,3,4,4,4-pentafluoro-1-
phenylbut-2-enyloxy)silane (4). To the 100 mL Schlenk
flask were added cesium fluoride (350 mg, 2.3 mmol)
anhydrous THF (40 mL), benzaldehyde (4.5 g, 42 mmol),
and E-CF3CFCFSi(CH3)3 (9.2 g, 45 mmol). The resultant
mixture was stirred for 3 h at room temperature. The product
was isolated by vacuum distillation as colorless liquid (8.6 g,
66% yield, bp 43 °C/0.25 mmHg).
1H NMR (CDCl3, 500 MHz, 25 °C) δ 0.16 (s, 9H,
Si(CH3)3), 4.37 (ddq, 3JFH = 23.9 Hz, 4JFH = 3.4 Hz, 5JFH = 1.4
Hz, 2H, CH2).
MS: m/z, 310 (M+), 295 (−CH3), 241 (−CF3), 217, 201,
171, 151, 77 (Ph), 73 (TMS).
19F NMR (CDCl3, 470.24 MHz, 25 °C) δ −66.48 (ddt, JFF
3
= 12.0 Hz, 4JFF = 8.6 Hz, 5JFH = 1.4 Hz, 3F, CF3), −127.24 (tqd,
1H NMR (CDCl3, 401.13 MHz, 25 °C) δ 0.19 (s, 9H,
4
3
3JFH = 23.9 Hz, JFF = 8.6 Hz, JFF = 3.5 Hz, 1F, CFCH2),
−155.53 (qdt, 3JFF = 12.0 Hz, 3JFF = 3.5 Hz, 4JFH = 3.4, 1F, CF).
Preparation of (Z)-Trimethyl(3,4,5,5,5-pentafluoro-2-
methylpent-3-en-2-yloxy)silane (8). To the 100-mL
Schlenk flask were added CsF (200 mg, 1.3 mmol), anhydrous
THF (10 mL) and the mixture was cooled to −30 °C. Then
dry acetone (0.44 g, 7.6 mmol) was added followed by addition
of E-CF3CFCFSi(CH3)3 (1.5 g, 7.4 mmol) and the mixture
was stirred for 3 hours at −30 °C. The product was observed by
3
Si(CH3)3), 5.70 (d, JFH = 26.7 Hz, 1H, CH), 7.34−7.46 (m,
5H, C6H5).
19F NMR (CDCl3, 377.44 MHz, 25 °C) δ −65.02 (dd, 3JFF
=
12.0 Hz, 4JFF = 8.8 Hz, 3F, CF3), −137.56 (dqd, 3JFH = 26.7 Hz,
4JFF = 8.8 Hz, 3JFF = 4.5 Hz, 1F, CFCH), −157.06 (qdd, 3JFF
=
3
4
12.0 Hz, JFF = 4.5 Hz, JFH = 1.8 Hz, 1F, CF).
Preparation of (Z)-Trimethyl(1,1,1,3,4,5,5,5-octa-
fluoro-2-phenylpent-3-en-2-yloxy)silane (5). To the 100
1065
dx.doi.org/10.1021/op5001385 | Org. Process Res. Dev. 2014, 18, 1060−1066

Organic Process Research & Development
Article
NMR and GC analyses in the reaction mixture (28% yield
based on 19F NMR and GC integration).
Hz, 6JFF = 3.8 Hz, 3F, CF3), −82.66 (q, 6JFF = 3.8 Hz, 3F, CF3),
5
3
−164.72 (qq, JFF = 21 Hz, JFF = 10.9 Hz, 1F, CF).
Preparation of (E)-4-(perfluoroethylidene)-1,3-dioxo-
lane (12). To the 100 mL Schlenk flask were added
paraformaldehyde (2.0 g, 67 mmol), cesium fluoride (200
mg, 1.3 mmol) anhydrous THF (15 mL), and E-CF3CF
CFSi(CH3)3 (5.3 g, 26 mmol) and the resultant mixture was
stirred for 20 h at room temperature. After that the mixture was
washed with a 1.0 M aqueous solution of HCl (20 mL). The
product was isolated by distillation as colorless liquid (1.1 g,
25% yield).
1H NMR (CDCl3, 400 MHz, 21 °C) δ 0.16 (s, 9H,
Si(CH3)3), 1.51 (dd, JFH = 2.4 Hz, JFH = 0.9 Hz, 6H, 2CH3).
19F NMR (377.44 MHz, 25 °C) δ −61.65 (dd, 3JFF = 9.8 Hz,
4
4JFF = 7.8 Hz, 3F, CFCF3), −126.9 (qm, JFF = 9.8 Hz, 1F,
3
CFCCH), −157.4 (qm, JFF = 7.8 Hz, 1F, CF3CF).
Preparation of (Z)-2-(Perfluoroprop-1-enyl)bicyclo-
[2.2.1]heptan-2-ol (9). To the 100 mL Schlenk were added
cesium fluoride (400 mg, 2.6 mmol), norcamphor (3.5 g, 32
mmol), anhydrous THF (30 mL), and E-CF3CFCFSi(CH3)3
(8 g, 39 mmol). The resultant mixture was stirred for 16 h at
room temperature. After that the mixture was washed with a 0.5
M aqueous solution of HCl (50 mL), and THF solvent was
removed to vacuum. The product was isolated by sublimation
as off-white crystalline material (3.4 g, 44% yield).
4
1H NMR (CDCl3, 500 MHz, 25 °C) δ 4.68 (dq, JFH = 3.4,
5JFH = 2.8, 2H, CH2), 5.34 (s, 2H, OCH2O).
3
19F NMR (CDCl3, 470.2 MHz, 25 °C) δ −68.14 (dt, JFF
=
5
3
14.8 Hz, JFH = 2.8 Hz, 3F, CF3), −167.21 (qt, JFF = 14.8 Hz,
4JFH = 3.4, 1F, CF).
MS: m/z, 224 (MH+, −F), 222 (−HF), 196, 178, 160,159,
131, 109, 68, 67.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: Roman.Larichev@dupont.com
*E-mail: Viacheslav.A.Petrov@dupont.com
■
1H NMR (CDCl3, 499.75 MHz, 21 °C) δ 1.33−1.50 (4H),
1.60−1.68 (2H), 1.97 (m, 1H), 2.01 (br s, 1H, OH), 2.25 (m,
1H), 2.32 (m, 1H), 2.60 (m, 1H).
19F NMR (CDCl3, 470.24 MHz, 21 °C) δ −64.00 (dd, 3JFF
=
Notes
4
4
10.3 Hz, JFF = 8.7 Hz, 3F, CF3), −121.22 (qm, JFF = 8.7 Hz,
The authors declare no competing financial interest.
3
1F, CF), −155.86 (q, JFF = 10.3 Hz, 1F, CFCF3).
Preparation of (E)-5-(Perfluoroethylidene)-2,2,4,4-
tetrakis(trifluoromethyl)-1,3-dioxolane (10). To the 250
mL flask equipped with dry ice condenser were added cesium
fluoride (1 g, 6.6 mmol), anhydrous THF (20 mL) and the
mixture was cooled to 0 °C. Then hexafluoroacetone (20 g,
0.12 mol) was bubbled through the solution followed by
addition of E-CF3CFCFSi(CH3)3 (10 g, 0.049 mol). The
resultant reaction mixture was stirred for 4 h at room
temperature. The mixture was transferred to a separatory
funnel, and the bottom phase was separated. It was washed with
1 M aqueous solution of HCl (2 × 30 mL) and dried over
MgSO4 (anh), and the product was obtained as colorless liquid
(15 g, 69% yield, bp 100 °C).
REFERENCES
■
(1) Ruppert, I.; Schlich, K.; Volbach, W. Tetrahedron Lett. 1984, 25,
2195−8.
(2) Prakash, G. K. S.; Krishnamurti, R.; Olah, G. A. J. Am. Chem. Soc.
1989, 111, 393−5.
(3) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. (Washington, D.C.)
1997, 97, 757−786.
(4) Prakash, G. K. S.; Mandal, M. J. Fluorine Chem. 2001, 112, 123−
131.
(5) Singh, R. P.; Shreeve, J. M. Tetrahedron 2000, 56, 7613−7632.
(6) In March of 2014 a search in SciFinder gaves over 400
publications mentioning trifluoromethylation with Ruppert−Prakash
reagent.
(7) Kirij, N. V.; Dontsova, D. A.; Pavlenko, N. V.; Yagupolskii, Y. L.;
Scherer, H.; Tyrra, W.; Naumann, D. Eur. J. Org. Chem. 2008, 2267−
2272.
(8) Kirij, N. V.; Dontsova, D. A.; Pavlenko, N. V.; Yagupolskii, Y. L.;
Tyrra, W.; Naumann, D. J. Fluorine Chem. 2010, 131, 184−189.
(9) He, Y.-B.; Nguyen, B. V.; Burton, D. J. J. Fluorine Chem. 2011,
132, 940−944.
(10) Tarrant, P.; Whitfield, R. W., Jr.; Summerville, R. H. J. Fluorine
Chem. 1971, 1, 31−40.
(11) Hahnfeld, J. L.; Burton, D. J. Tetrahedron Lett. 1975, 773−6.
(12) Fields, R.; Haszeldine, R. N.; Hubbard, A. F. J. Chem. Soc. C
1971, 3838−3843.
(13) Nappa, M. J.; Rao, V. N. M. WO/1998/33755A1, 1998; p 18
pp.
(14) Nappa, M. J. Pat. WO/2009/026080A1, 2009.
(15) Sheldrick, G. SHELXTL Software Suite, v. 6.0; Bruker Axes
Corp.: Madison WI, 1996.
MS: m/z, 444 (M+), 425 (−F), 375 (−CF3), 325
(−CF2CF3), 259, 159, 97, 69 (CF3).
3
19F NMR (CDCl3, 470.23 MHz, 25 °C) δ −68.69 (d, JFF
=
5
6
10.1 Hz, 3F, CF3), −72.23 (dseptet, JFH = 16.0 Hz, JFF = 5.1
6
Hz, 6F, 2CF3), −78.59 (septet, JFF = 5.1 Hz, 6F, 2CF3),
5
3
−156.69 (septetq, JFF = 16.0 Hz, JFF = 10.1 Hz, 1F, CF).
Preparation of (E)-5-(Perfluoroethylidene)-2,4-di-
phenyl-2,4-bis(trifluoromethyl)-1,3-dioxolane (11). To
the 100 mL Schlenk flask were added tetrabutylammonium
fluoride monohydrate (500 mg, 1.8 mmol), anhydrous THF
(20 mL), trifluoroacetophenone (14 g, 80 mmol), and last was
added E-CF3CFCFSi(CH3)3 (6.9 g, 34 mmol). The mixture
was stirred at room temperature for 16 h, and the resultant
solution was filtered. The product was isolated by vacuum
distillation as pale-yellow liquid (11.4 g, 73% yield, bp 73 °C/
0.075 mmHg).
MS: m/z, 441 (−F), 391 (−CF3), 286, 258, 217, 189, 169,
105, 77.
1H NMR (CDCl3, 400.55 MHz, 21 °C) δ 7.10−7.62
(overlapping peaks for aromatic protons of both isomers).
Major isomer. 19F NMR (CDCl3, 376.89 MHz, 21 °C) δ
3
5
−67.72 (d, JFF = 10.9 Hz, 3F, CFCF3), −74.18 (d, JFF = 16.7
3
Hz, 3F, CF3), −81.91 (s, 3F, CF3), −164.31 (qq, JFF = 16.7
3
Hz, JFF = 10.9 Hz, 1F, CF).
Minor isomer. 19F NMR (CDCl3, 376.89 MHz, 21 °C) δ
3
5
−67.68 (d, JFF = 10.9 Hz, 3F, CFCF3), −73.86 (dq, JFF = 21
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dx.doi.org/10.1021/op5001385 | Org. Process Res. Dev. 2014, 18, 1060−1066