Synthesis of α-trifluoromethylated amides by Eschenmoser-Claisen-type rearrangement of allylic alcohols

Article abstract of DOI:10.1016/j.jfluchem.2012.07.011

A new, mild method to prepare α-trifluoromethylated amides bearing an additional trans-configured double bond in γ-position is described. Treatment at room temperature of fluorinated and non-fluorinated allylic alcohols 1 and 2 with the 1,1,3,3,3-pentafluoropropene-diethylamine adduct (PFPDEA) in the presence of triethylamine as base gave the products of [3,3]-sigmatropic Eschenmoser-Claisen-type rearrangements with good yields and excellent diastereoselectivity due to chair-like conformations of transition states. Starting with enantiomerically enriched allylic alcohols chirality transfer from carbon 3 of the allylic system to carbon 2 of the final α-trifluoromethyl carboxamides was observed. This methodology was applied to both simple and more complex, including terpenic, allylic alcohols and might be developed to an alternative strategy to the well-known electrophilic α-trifluoromethylation of carbonyl compounds.

Full text of DOI:10.1016/j.jfluchem.2012.07.011

Journal of Fluorine Chemistry 143 (2012) 189–197
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of
a
-trifluoromethylated amides by Eschenmoser–Claisen-type
rearrangement of allylic alcohols
a
b
a
Justyna Walkowiak a, , Magdalena Tomas-Szwaczyk , Gu¨nter Haufe , Henryk Koroniak
*
a Adam Mickiewicz University, Faculty of Chemistry, Grunwaldzka 6, 60-780 Poznan´, Poland
b Organisch-Chemisches Institut, Westfa¨lische-Wilhelms Universita¨t, Corrensstraße 40, 48149 Mu¨nster, Germany
A R T I C L E I N F O
A B S T R A C T
Article history:
A new, mild method to prepare
a
-trifluoromethylated amides bearing an additional trans-configured
Received 16 April 2012
Received in revised form 19 July 2012
Accepted 24 July 2012
double bond in
g
-position is described. Treatment at room temperature of fluorinated and non-
fluorinated allylic alcohols
1
and with the 1,1,3,3,3-pentafluoropropene–diethylamine adduct
2
(PFPDEA) in the presence of triethylamine as base gave the products of [3,3]-sigmatropic
Eschenmoser–Claisen-type rearrangements with good yields and excellent diastereoselectivity due to
chair-like conformations of transition states. Starting with enantiomerically enriched allylic alcohols
Available online 7 August 2012
Dedicated to Professor David O’Hagan on the
occasion of receiving the ACS Award for
Creative Work in Fluorine Chemistry.
chirality transfer from carbon 3 of the allylic system to carbon 2 of the final
a-trifluoromethyl
carboxamides was observed. This methodology was applied to both simple and more complex, including
terpenic, allylic alcohols and might be developed to an alternative strategy to the well-known
electrophilic
a-trifluoromethylation of carbonyl compounds.
Keywords:
Claisen rearrangement
Trifluoromethyl compounds
Amides
ß 2012 Elsevier B.V. All rights reserved.
Allylic alcohols
Reaction mechanisms
1. Introduction
Ireland–Claisen [8] and the Eschenmoser [9] rearrangements
should be mentioned.
The steadily growing demand of fluoroorganic compounds both
for the design of new biologically active compounds and new
functional materials stimulated considerably interest in the
development of new convenient and selective ways to introduce
fluorine atom(s) into molecules. New methods of transformation of
non-fluorinated into fluorinated groups were studied, e.g. methyl
into trifluoromethyl group [1]. Hence, many reactions to construct
organic fluoro compounds were developed, including Claisen-type
rearrangements, which are powerful carbon–carbon bond-forming
reactions frequently applied for transformations of carbon
skeletons in organic synthesis [2]. These thermal [3,3]-sigmatropic
rearrangements, according to the Woodward–Hoffmann rules
proceed suprafacial. The highly ordered six-membered cyclic
transition states along with the restrictions imposed by the orbital
symmetry rules, allow one to expect excellent stereoselectivity [3].
Plenty of variants of this type of rearrangement have been
developed until very recently. As the most common, regularly used
in synthesis with non-fluorinated compounds, the Carroll [4],
the Johnson [5], the Reformatsky [6], the ester enolate [7], the
This methodology, however, was also useful for the conversion
of selectively fluorinated substrates and for the elaboration of
simple fluorinated building blocks. For instance, Claisen rearran-
gements of polyfluorinated allylvinyl ethers [10], Johnson–Claisen
rearrangements of allylic alcohols with a terminal difluorinated
double bond [11], and Ireland–Claisen rearrangements with
terminal difluorinated allylic esters have been described [12].
On the other hand, there are known less examples for rearrange-
ments of monofluorinated olefins. A classical aromatic Claisen
rearrangement of the bis-2-fluoroallyl ether of p-diphenol was
applied to obtain a fluorinated derivative of the anti-malaria agent
Bialamicol [13]. Several different examples of Johnson–Claisen
rearrangement of 2-fluoro [14] and 3-fluoroallylic alcohols [15] as
well as Ireland–Claisen rearrangement of vinyl fluorides [16] and
the Kazmaier variant [17] of this rearrangement using amino acid
esters of the fluorinated allylic alcohols [18,19] have been also
published. As a result of the above-mentioned rearrangements
formation of corresponding fluorinated
g,d-unsaturated deriva-
tives such as acids, esters or amino acids was observed. Claisen
rearrangement had also been used to introduce a fluoro(trifluor-
omethyl)methylene moiety by treatment of allylic alcohols with
the perfluoropropene-diethylamine adduct (PPDA) [20]. Such
* Corresponding author. Tel.: +48 61 8291225; fax: +48 61 8291505.
E-mail address: Justyna.A.Walkowiak@amu.edu.pl (J. Walkowiak).
reaction led to the formation of g,d-unsaturated amides containing
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.07.011

190
J. Walkowiak et al. / Journal of Fluorine Chemistry 143 (2012) 189–197
[3,3]-sigmatropic rearrangement of an intermediary N,N-diethyl-
3,3,3-trifluoro-1-(2-fluoroalk-1-en-3-yloxy)prop-1-en-1-amine
(cf. discussion below and Scheme 5).
Simultaneously in competitive studies, the influence of a vinylic
fluoride on the reactivity of allylic alcohols towards PFPDEA was
investigated. The reaction of PFPDEA with oct-1-en-3-ol (2)
applied as a model molecule, gave only substitution products, the
allylfluorides 3-fluorooct-1-ene (4) and 1-fluorooct-2-ene (6). In
contrast to its fluorinated analogues 1a–c, there was no formation
of a rearranged amide 8 observed under these conditions (Scheme
1 and Table 1).
Scheme 1. Reagents and conditions: (i) (a) PFPDEA (2 equiv.), CH2Cl2, rt, 48 h; (b)
Et3N (2 equiv.), PFPDEA (2 equiv.), CH2Cl2, rt, 48 h; (ii) H2O, excess.
at the
a
position a fluorine as well as a trifluoromethyl group.
Surprisingly, the reaction of both fluorinated (1) and non-
fluorinated (2) allylic alcohols with PFPDEA in the presence of two
equivalents of triethylamine led to the fluorinated g,d-unsaturated
Although the PPDA [21] is one of the reagents used for the
conversion of alcohols into alkylfluorides [22], the reaction of
allylic alcohols in the presence of N,N-diisopropylethylamine did
not produce the corresponding allylic fluorides but Eschenmoser–
Claisen-type rearranged amides were formed.
Recently, the 1,1,3,3,3-pentafluoropropene diethylamine ad-
duct (PFPDEA), a variation of Ishikawa’s reagent, has been
developed in our laboratory and applied as a new reagent for
the direct transformation of alcohols to corresponding alkylfluor-
ides [23]. Furthermore, we reported PFPDEA to produce 3,3,3-
trifluoropropionic esters in the reaction with vicinal fluorohydrins
[24]. In this paper, applications of this new fluorinating agent in
reactions of both fluorinated and non-fluorinated allylic alcohols
amides 7 or 8 exclusively. It seems that modification of the
conditions by addition of 2 equiv. of the weak base Et3N inhibits
the nucleophilic substitution and favours amidation leading to the
formation of amides 7 and 8 via Eschenmoser–Claisen-type
rearrangement. The reaction has to be carried out by slow addition
of the fluorinating agent (2 equiv.) to the mixture of the alcohol
(1 equiv.) and triethylamine (2 equiv.) in the presence of inert
solvents such as CH2Cl2 at room temperature. In contrast,
according to the literature protocols, for Eschenmoser rearrange-
ments of g-trifluoromethylated allylic alcohols refluxing with N,N-
dimethyl-acetamide dimethylacetal in high boiling solvents was
required [29].
Claisen rearrangements proceed via highly ordered cyclic
transition states (see Scheme 6). Along with the restrictions
imposed by the orbital symmetry rules all the performed reactions
gave the corresponding trans-configurated alk-4-enamides in fair
to excellent yields (Table 2).
are described. We wish to report on stereoselective synthesis of
fluoro- -trifluoromethyl- -unsaturated amides under mild con-
ditions by Eschenmoser–Claisen-type rearrangement. This might
be developed as an alternative option to electrophilic
trifluoromethylation reactions of carbonyl compounds [25].
g-
a
g
,d
a-
Having this method for complete control of the stereochemistry
of double bond formation in position 4 in hand, a chirality transfer
from carbon 3 of the allylic alcohol to carbon 2 of the formed
amides should be possible. Thus, under the same conditions the
enantiomerically enriched (R)-2-fluorooctadec-1-en-3-ol, (R)-1c,
obtained by lipase-catalysed resolution [26] and optically pure (R)-
oct-1-en-3-ol, (R)-2a, were subjected to the reaction with PFPDEA.
Indeed, both allylic alcohols underwent rearrangement with
transmission of chirality forming the corresponding optically
active 2-trifluoromethylated trans-alk-4-enamides (R)-7c and (R)-
8 in good yields (Table 2). The enantiomeric excess of the products
was determined by 19F NMR using the enantiopure shift reagent
2. Results and discussion
In our previous studies, we found that widening the field of
application of PFPDEA to more complex molecules containing a
hydroxyl group in different neighbourhood leads to formation of
3,3,3-trifluoropropionate derivatives as competing products in
addition to the expected alkylfluorides [24]. Therefore, taking the
advantage of esterification properties of this new fluorinating
agent to obtain trifluoropropionic acid esters exclusively would be
a convenient method of allylic alcohols esterification. Such esters
were shown to undergo Ireland–Claisen rearrangements to give
trifluoromethyl- -unsaturated carboxylic acids [26].
a-
g,d
(R)-(ꢀ)-N-(3,5-dinitrobenzoyl)-
a
-methylbenzylamine
(DNBA)
Fluorinated allylic alcohols 1a–c prepared according to a well-
established three-step sequence [27] and 1d [28] were subjected to
the reaction with 2 equiv. of PFPDEA under mild conditions (i.e. in
dichloromethane at room temperature). In contrast to the products
we expected according to our earlier results [24], formation of
trifluoropropionates was not observed. Instead, a complex mixture
of products was formed. Among them the following three
compounds were identified: 2,3-difluoroalk-1-enes 3, 1,2-difluor-
oalk-2-enes 5 and (Z)-N,N-diethyl-4-fluoro-2-(trifluoro-methy-
l)alk-4-enamides 7 (Scheme 1 and Table 1). Compounds 3 and 5
were obtained as products of nucleophilic substitution without or
with allylic rearrangement, while the amides 7 were formed via the
(Scheme 2).
However, in both cases decrease of the optical purity of the
obtained products was observed. Three plausible explanations of
such a partial racemization might be considered: (i) the initial
basic reaction conditions may cause partial racemization of
starting material; (ii) in the formed products the hydrogen at
a-
position to the amide function is quite acidic because of the
electron withdrawing effect of the trifluoromethyl group and the
Table 2
Yield of alk-4-enamides
7 and 8 in the reaction of allylic alcohols with
PFPDEA + Et3N (reaction conditions B).
Alcohols
X
R
Products
Yield [%]a
Table 1
Products distribution in reaction of allylic alcohols with 2 equiv. PFPDEA (reaction
1a
F
C7H15
C13H27
C15H31
H
7a
88
conditions A).
1b
F
7b
91
1c
F
7c
72
Alcohols
X
R
Products (yield [%])a
1d
F
7d
41
1a
1b
1c
2a
F
C7H15
C13H27
C15H31
C5H11
3a (63)
3b (61)
3c (44)
4a (36)
5a (15)
7a (4)
7b (4)
7c (33)
–
2a
H
H
H
H
C5H11
H
8a
88
F
5b (15)
5c (11)
6a (24)
2b
8b
40
F
(R)-1c (65% ee)
(R)-2a (>98.5% ee)
C15H31
H
(R)-7c
(R)-8a
76 (47% ee)
93 (78% ee)
H
a
a
Yields of isolated products.
Yields of isolated products.

J. Walkowiak et al. / Journal of Fluorine Chemistry 143 (2012) 189–197
191
after treatment with triethylamine under ambient conditions did
not show any changes.
At the next stage, we attempted to extend the method’s field of
application to other available nonfluorinated allylic alcohols. The
developed procedure leading to the formation of desired Eschen-
moser–Claisen rearranged products was employed in the reactions
of more complex allylic derivatives containing hydroxyl group in
different neighbourhood. Substrates possessing (i) primary hy-
droxyl group: geraniol (9a), farnesol (9b), peryllil alcohol (10), 2-
methyl-3-phenylprop-2-en-1-ol (11), myrtenol (12), furfuryl
alcohol (13), (ii) secondary hydroxyl group: carveol (14), trans-
pinocarveol (15), (iii) tertiary hydroxyl group: linalool (16a), trans-
nerolidol (16b) were examined (Table 3).
Studies aimed at probing the efficiency of this methodology for
the preparation of wider range of rearranged amides from alcohols
9–16 indicated that allylic alcohol’s structure has a substantial
influence on the desired rearranged product formation (Table 3).
Eschenmoser–Claisen type rearrangement has been also applied
to introduce trifluoromethyl moiety by treatment of 5-(hydro-
xymethyl)uracil 17 with PFPDEA in the presence of triethylamine
(Scheme 3). Such reaction led to exclusive formation of uracil
derivative 37 containing a methyl group at position 5 and a 2-(N,N-
diethyl-3,3,3-trifluoropropanamidyl) function at position 6.
The experimental results obtained in this work provided
interesting insight into the general mechanism of action of the
pentafluoropropene-diethylamine adduct towards different alco-
hols. The fluorination reactions with the use of PFPDEA or other
Scheme 2. Chirality transfer in the reaction of enantioenriched allylic alcohols 1c
and 2a with PFPDEA in the presence of triethylamine.
carboxamide function. Therefore, partial racemization might occur
via the enolate. Eventually, least desirable alternative, (iii) the
involved reaction mechanism, e.g. formation of the intermediate
and rearrangement itself is not as stereoselective as to be expected.
Essentially, Ireland–Claisen rearrangements of analogous 3,3,3-
trifluoropropanoic acid allyl esters with triethylamine and
trimethylsilyltriflate proceeded under complete racemization [26].
In order to prove the first of the preceding reasons for the
observed decrease of enantiomeric excess in products 7c and 8
(Scheme 2), blind experiments of allylic alcohol’s behaviour in the
presence of triethylamine by measuring the optical rotation
revealed surprising results. Unexpectedly, within half an hour
after addition of the base full racemization of the fluoroallylic
alcohol (R)-1c (65% ee) was observed, whereas the same conditions
caused only partial racemization of (R)-3-octenol (R)-2a after 24 h.
Subsequently, the optical rotation measurements of the isolated
enantiomerically enriched fluorinated amides (R)-7c and (R)-8a
Table 3
Products of the reaction of allylic alcohols 9–16 with PFPDEA + Et3N.
Substrate
Amide
(yield)a
Structure
19F NMR chemical Fluorides
Structure
19F NMR chemical
shift [ppm]b
shift [ppm]b
(yield)a
3
2
9a
20a (3%)
ꢀ67.5 (d, JF,H
=
18a (26%)
ꢀ207.4 (t, JF,H = 47.9 Hz, 1 F)
CF3
7.9 Hz, 3 F)
2
NEt2
2
2
2
OH
F
O
19a (32%)
18b (22%)
ꢀ148.2 (m, 1 F)
F
3
2
9b
10
20b (3%)
ꢀ67.5 (d, JF,H
=
ꢀ207.4 (t, JF,H = 47.9 Hz, 1 F)
CF3
7.7 Hz, 1 F)
NEt2
2
2
2
2
2
2
2
F
OH
O
19b (36%)
21 (44%)
ꢀ148.1 (m, 1 F)
F
2
3
2
23 (7%)
ꢀ67.4 (d, JF,H
=
ꢀ211.7 (t, JF,H = 48.8 Hz, 1 F)
OH
F
O
8.0 Hz, 3 F)
NEt2
CF3
22 (4%)
ꢀ180.7 (m, 1 F)
F
3
2
11
12
26 (8%)
ꢀ67.3 (d, JF,H
=
=
24 (28%)
25 (26%)
ꢀ212.3 (t, JF,H = 47.4 Hz, 1 F)
CF3
7.9 Hz, 3 F)
NEt2
OH
F
2
O
ꢀ173.7 (d, JF,H = 47.4 Hz, 1 F)
F
3
2
4
29 (23%)
ꢀ67.9 (d, JF,H
27 (35%)
28 (22%)
ꢀ214.4 (tdd, JF,H = 47.6 Hz,
O
4
7.9 Hz, 3 F)
JF,H = 14.8 Hz, JF,H = 8.6 Hz, 1 F)
NEt2
CF3
OH
F
2
3
ꢀ137.2 (dddd, JF,H = 44.8 Hz,
3
4
F
JF,H = 34.6 Hz, JF,H = 32.4 Hz, JF,H
=
2.9 Hz, 1 F)

192
J. Walkowiak et al. / Journal of Fluorine Chemistry 143 (2012) 189–197
Table 3 (Continued )
Substrate
Amide
(yield)a
Structure
19F NMR chemical Fluorides
Structure
19F NMR chemical
shift [ppm]b
shift [ppm]b
(yield)a
3
2
13
30 (40%)
ꢀ68.4 (d, JF,H
=
31 (11%)
ꢀ201.3 (t, JF,H = 49.7 Hz, 1 F)
CF3
F
OH
7.8 Hz, 3 F)
NEt2
O
O
O
2
O
32 (29%)
34 (55%)
ꢀ109.3 (d, JF,H = 68.2 Hz, 1 F)
F
O
2
14
33 (0%)
–
ꢀ178.1 (ddd, JF,H = 50.1 Hz,
O
3JF,H =15.7 Hz, JF,H
=
3
NEt2
OH
F
4.6 Hz, 1 F); ꢀ166.8 (m, 1 F)
CF3
3
2
15
35 (86%)
ꢀ67.8 (d, JF,H
=
28 (3%)
27 (3%)
ꢀ137.2 (dddd, JF,H = 44.8 Hz,
3JF,H =34.6 Hz, JF,H = 32.4 Hz,
F
3
8.0 Hz, 3 F)
O
4JF,H =2.9 Hz, 1 F)
OH
NEt2
CF3
2
ꢀ214.4 (tdd, JF,H = 47.6 Hz,
4
4JF,H =14.8 Hz, JF,H = 8.6 Hz, 1 F)
F
3
16a
36a (30%)
ꢀ67.7 (d, JF,H
=
=
19a (<1%)
18a (<1%)
ꢀ148.2 (m, 1 F)
CF3
OH
F
7.9 Hz, 3 F)
NEt2
2
2
2
O
2
ꢀ207.4 (t, JF,H = 47.9 Hz, 1 F)
2
F
3
16b
36b (40%)
ꢀ68.2 (d, JF,H
19b (<1%)
18b (<1%)
ꢀ148.1 (m, 1 F)
OH
F
7.9 Hz, 3 F)
2
2
2
2
2
2
2
O
F3C
2
ꢀ207.4 (t, JF,H = 47.9 Hz, 1 F)
NEt2
2
F
a
Yields determined by 19F NMR using m-fluorotoluene as internal standard (19F NMR (282 MHz, CDCl3):
19F NMR (282 MHz, CDCl3).
d
= ꢀ114.1 (m, 1 F)).
b
fluoro amino reagents (FARs) were reported to follow a SNi
Since the formation of thermodynamically stable diethyl 3,3,3-
trifluoropropionamide, CF3CH2C(O)NEt2, is considered to be a
driving force of fluoride substitution, decomposition of intermedi-
ate TFMAE can also generate stable allylic carbocation (Scheme 5,
pathway c). Subsequent nucleophilic attack of fluoride at carbon C-
1 or C-3 gives a mixture of two allylic fluorides as products.
Therefore fluorination in an SN1 reaction cannot be neglected.
Alternatively, the intermediates TFMAE can react as 1,5-diene
systems. Consequently, trans-configurated 2-trifluoroalk-4-enam-
ides are formed by [3,3]-sigmatropic Eschenmoser–Claisen-type
rearrangement via a six-membered transition state (Scheme 6).
Under the original conditions, only the reactions of the fluoroallylic
alcohols 1a–c with PFPDEA under standard conditions gave low
amount of rearranged products (see Table 1). However, modifica-
tion of the reaction conditions by addition of two equivalents of
triethylamine resulted in exclusive formation of the rearranged
products (see Table 2). Thus, in the absence of HF under more basic
conditions, the rearrangement is favoured.
mechanism and go through a two-step process [30]. Formation of
products obtained in the reaction of PFPDEA with allylic alcohols
confirmed the suggested mechanism [24]. In the first step the
fluorinating agent reacts with alcohols forming the intermediate
hydrofluoride of a trifluoromethylated amide enolate (TFMAE) as a
result of nucleophilic substitution of the vinylic fluorine by alcohol
and hydrogen fluoride elimination (Scheme 4).
The second step – decomposition of TFMAE, however can
proceed via different transition states leading to different products
as depicted in Scheme 5. Most probably, allylic fluorides are
generated when the intermediate TFMAE decomposes via either a
six membered transition state TS 2 or transition state TS 1. In this
way the major fluorides are formed without allylic rearrangement
by fluoride attack at carbon C-3 bearing the leaving group (Scheme
5, pathway b). These are examples of an intramolecular
nucleophilic substitution, SNi, and typical nucleophilic substitu-
tion, SN2, respectively.
Decomposition of the intermediate TFMAE through a less
favoured, transition state TS 3 is also possible (Scheme 5, pathway
a). In this case the nucleophilic attack of fluoride occurs at carbon
C-1 resulting in the formation of the minor product via an SN20
reaction with allylic rearrangement.
Subsequent investigations showed that the rearrangements of
optically active fluorinated and non-fluorinated allylic alcohols
with PFPDEA allowed the generation of enantioenriched amides
through an intramolecular chirality transfer from carbon 3 of the
allylic system to carbon 2 of the formed carboxyamides. Again, the
Scheme 3. Reaction of 5-(hydroxymethyl)uracil 17 with PFPDEA in the presence of
Scheme 4. Formation of the intermediate TFMAE from allylic alcohols and PFPDEA.
triethylamine.

J. Walkowiak et al. / Journal of Fluorine Chemistry 143 (2012) 189–197
193
F
and (R)-2a react with PFPDEA to give the corresponding
enantiomerically enriched amides (R)-7c and (R)-8a with a lower
enantiomeric excess than expected due to partial racemization of
the starting fluorinated allylic alcohols 1c and 2a. Applying more
complex allylic alcohols 9–17 the Eschenmoser–Claisen-type
rearrangement competes with substitution of the OH group by
fluoride without or with allylic rearrangement, leading to the
allylic fluorides as major products in several cases. Depending on
X
X
"F
"
R
SN2'
path a
X
O
R
+
O
R
F3C
O
O
F3C
NEt2
NEt2
F3C
NEt2
TFMAE
TS 3
SN2 or SNi
path b
SN1
_
NEt2
path c
"
CF3
the structure of the allylic alcohol, the desired
a-trifluoromethyl
X
"F
"
carboxamides were formed as main products in other cases.
Nevertheless, all obtained results strongly support the postulated
two-step mechanism of reactions of PFPDEA with alcohols.
Presently, we are developing the described rearrangement as a
new tool for the introduction of the trifluoromethyl moiety into
organic molecules and will investigate the downstream chemistry
"F
O
R
F
F3C
NEt2
R
R
TS 1
or
X
X
+
O
CF3
X
R
of
a-trifluoromethyl carboxamides in future.
F3C
O
F
F
NEt2
+
R
R
4. Experimental
Et2N
F
H
X
X
4.1. General methods
TS 2
Scheme 5. Anticipated mechanisms for the formation of allylic fluorides.
NMR spectra were recorded in deuterated solvents at 300 MHz
(1H), at 75 MHz (13C) and at 282 MHz (19F), calibrated using an
internal reference: TMS (1H), CDCl3
shifts (
( (
13C), or CFCl3 19F). Chemical
d
) are quoted in parts per million (ppm) and coupling
constants (J) are measured in Hertz (Hz). The following abbrevia-
tions are used to describe multiplicities s = singlet, d = doublet,
t = triplet, q = quartet, b = broad, m = multiplet. For 13C NMR data,
additionally the multiplicity of the CH coupling determined by
DEPT experiments are given. Optical rotations were measured at
20 8C (cell: diameter 3.5 mm ꢁ length 100 mm). Mass spectra were
recorded by GC/MS coupling (EI, 70 eV). HRMS (EI) were recorded
using a AMD-402 spectrometer. Gas chromatography analyses
were performed using a column HP-5 (30 m, 1 0.32 mm, film
Scheme 6. Eschenmoser–Claisen-type rearrangement of trifluoromethylated amide
enolates TFMAE.
0.25
mm, carrier gas N2). Thin-layer chromatography (TLC) was
performed on coated silica gel plate Merck 60 F254. Visualization of
the reaction components was achieved using UV fluorescence
(254 nm) and cerium(IV) ammonium nitrate or KMnO4 solution
stain. For purification of products column chromatography was
carried out over Merck silica gel 60 (0.063–0.2 mm). All reagents
purchased from suppliers were used without further purification.
CH2Cl2 was dried and distilled over P2O5. Solvents for chromatog-
raphy were distilled prior to use. Fluorinated allylic alcohols were
prepared as described in the literature [27].
Scheme 7. Stereochemistry of the Eschenmoser–Claisen rearrangement of
trifluoromethylated amide enolates TFMAE.
intermediate TFMAE is rearranged via a chair-like transition state
where the long alkyl chain R attached to the stereogenic carbon
adopts an equatorial conformation. Similarly, the trifluoromethyl
group at the double bond also arranges in an equatorial position
(Scheme 7).
4.2. General procedures
Consequently, the (R)-configurations for both (Z)-4-fluoro-2-
trifluoromethylicos-4-enoic acid amide (7c) and (E)-2-trifluoro-
methyldec-4-enoic acid amide (8) are assumed from the mecha-
nism of the reaction. However, the determination of enantiomeric
excess using enantiopure shift reagent in NMR revealed that not
complete chirality transfer occurred (see discussion above).
4.2.1. Fluorination of allylic alcohols: general procedure (GP1)
To a solution of allylic alcohol 1 or 2 (1 equiv.) in dry CH2Cl2
(2.5 mL), a solution of pentafluoropropene-diethylamine adduct
(PFPDEA, 2 equiv.) in dry CH2Cl2 (2.5 mL) was dropwise added. The
resulting mixture was stirred at r.t. for 14 h and then quenched
with water (10 mL). The organic layer was extracted with CH2Cl2
(3ꢁ 10 mL). The combined organic layers were washed with
saturated aqueous NaHCO3 solution (10 mL) and brine (2ꢁ 10 mL).
The organic phase was dried over MgSO4 and the solvent was
evaporated. The crude product was purified by column chroma-
tography.
3. Conclusion
This study on the application of the new fluorinating agent
PFPDEA has shown, that one-pot reactions of fluorinated (1) and
non-fluorinated (2) allylic alcohols with this pentafluoropropene-
diethylamine adduct in the presence of two equivalents of
triethylamine afforded N,N-diethyl-4-fluoro-2-(trifluoromethy-
4.2.1.1. Fluorination of 2-fluorodec-1-en-3-ol (1a). According to the
general procedure GP1, in the reaction of the fluorinating agent
PFPDEA (1.450 g, 7.83 mmol) with 2-fluorodec-1-en-3-ol (1a,
1.001 g, 5.75 mmol) in dry CH2Cl2 (15 mL) a mixture of 3a, 5a and
7a was obtained.
l)alk-4-enamides
7 and N,N-diethyl-2-(trifluoromethyl)alk-4-
enamides 8 with high stereoselectivity. These reactions involve
Eschenmoser–Claisen-type rearrangements of an intermediary
N,N-diethyl-3,3,3-trifluoro-1-(alk-1-en-3-yloxy)prop-1-en-1-
amine (TFMAE). However, the optically active substrates (R)-1c
2,3-Difluorodec-1-ene (3a). Yield: 63% (GC). 1H NMR
2
3
(300 MHz, CDCl3):
d = 4.82 (ddt, JH,F = 45.3 Hz, JH,F = 13.5 Hz,

194
J. Walkowiak et al. / Journal of Fluorine Chemistry 143 (2012) 189–197
3JH,H = 6.7 Hz, 1 H, CHF), 4.77 (m, 3JH,F = 16.9 Hz, 1 H,55CH0H00), 4.63
(m, 3JH,F = 48.5 Hz, 1 H,55CH0H00), 1.79 (m, 1 H, CH0H00), 1.40 (m, 1 H,
(88) [C4H7+], 43 (98) [C3H7+], 41 (100) [C3H5+]. HR MS (EI): m/z [M+]
calcd for C16H30F2: 260.2316; found: 260.2315.
3
CH0H00), 1.29 (m, 10 H, CH2), 0.88 (m, JH,H = 7.1 Hz, 3 H, CH3); 13C
NMR (75 MHz, CDCl3):
d
= 162.7 (dd, 1JC,F = 261.1 Hz,
4.2.1.3. Fluorination of 2-fluorooctadec-1-en-3-ol (1c). According to
the general procedure a mixture of 3c, 5c and 7c was obtained in
the reaction of the fluorinating agent PFPDEA (0.963 g, 5.21 mmol)
with 2-fluorooctadec-1-en-3-ol (1c, 0.738 g, 2.58 mmol).
2
3
2JC,F = 21.9 Hz, 55CF), 92.4 (dd, JC,F = 17.2 Hz, JC,F = 4.8 Hz,
1
2
55CH2), 89.5 (dd, JC,F = 172.5 Hz, JC,F = 30.8 Hz, CHF), 22.7–32.1
(CH2), 14.1 (CH3); 19F NMR (282 MHz, CDCl3):
d
= ꢀ184.3 (ddd,
3
3
2JF,H = 45.3 Hz, JF,F = 25.6 Hz, JF,H = 20.9 Hz, 1 F, CHF), ꢀ113.6
(dddd, 3JF,H = 48.4 Hz, 3JF,F = 25.7 Hz, 3JF,H = 16.8 Hz, 3JF,H = 12.6 Hz,
1 F, 55CF); GC MS (70 eV) m/z (%): 176 (3) [M+], 156 (10) [M+ꢀHF],
136 (6) [156ꢀHF], 127 (7) [156ꢀC2H5], 121 (9) [136ꢀCH3], 113
(16) [127ꢀCH2], 107 (11) [127ꢀHF], 99 (28) [113ꢀCH2], 69 (34)
[C5H9+], 56 (82) [C4H8+], 43 (93) [C3H7+], 41 (100) [C3H5+]. HR MS
(EI): m/z [M+] calcd for C10H18F2: 176.1337; found: 176.1335.
1,2-Difluorodec-2-ene (5a). Yield: 15% (GC). 1H NMR
2,3-Difluorooctadec-1-ene (3c). Yield: 44% (GC). 1H NMR
2
3
(300 MHz, CDCl3):
d = 4.82 (ddt, JH,F = 47.3 Hz, JH,F = 12.8 Hz,
3JH,H = 6.5 Hz, 1 H, CHF), 4.76 (m, 3JH,F = 17.1 Hz, 1 H,55CH0H00), 4.62
(m, 3JH,F = 47.7 Hz, 1 H,55CH0H00), 1.79 (m, 1 H, CH0H00), 1.42 (m, 1 H,
CH0H00), 1.29 (m, 26 H, CH2), 0.88 (m, JH,H = 7.1 Hz, 3 H, CH3); 13C
3
NMR (75 MHz, CDCl3):
2JC,F = 23.2 Hz, 55CF), 92.4 (dd, JC,F = 16.5 Hz, JC,F = 5.3 Hz,
d
= 162.7 (dd, 1JC,F = 262.5 Hz,
2
3
1
2
55CH2), 89.5 (dd, JC,F = 172.5 Hz, JC,F = 33.3 Hz, CHF), 22.7–32.1
(CH2), 14.1 (CH3); 19F NMR (282 MHz, CDCl3):
3
3
4
(300 MHz, CDC):
d
= 5.00 (ddt, JH–F = 35.1 Hz, JH,H = 7.6 Hz, JH–
d
= ꢀ184.3 (ddd,
F = 5.4 Hz, 1 H, 55CH), 4.76 (dd, 2JH–F = 48.1 Hz, 3JH–F = 18.4 Hz, 2 H,
2JF,H = 47.3 Hz, JF,F = 24.9 Hz, JF,H = 20.9 Hz, 1 F, CHF), ꢀ113.6
(dddd, 3JF,H = 47.0 Hz, 3JF,F = 25.4 Hz, 3JF,H = 16.7 Hz, 3JF,H = 12.4 Hz,
1 H, 55CF); GC MS (70 eV) m/z (%): 288 (1) [M+], 268 (2) [M+ꢀHF],
248 (1) [268ꢀHF], 233 (1) [248ꢀCH3], 221 (1) [248ꢀC2H3], 219 (1)
[248ꢀC2H5], 208 (3) [221ꢀCH], 205 (0) [219ꢀCH2], 191 (0)
[205ꢀCH2], 177 (1) [191ꢀCH2], 163 (2) [177ꢀCH2], 149 (3)
[163ꢀCH2], 135 (7) [149ꢀCH2], 121 (10) [135ꢀCH2], 107 (9)
[121ꢀCH2], 97 (42) [C7H13+], 95 (29) [C7H11+], 83 [C6H11+], 82 (21)
[C6H10+], 69 (49) [C5H9+], 57 (82) [C4H9+], 55 (59) [C4H7+], 43 (63)
[C3H7+], 41 (100) [C3H5+]. HR MS (EI): m/z [M+] calcd for C16H30F2:
288.2629; found: 288.2627.
3
3
3
3
CH2F), 2.12 (dt, JH,H = 7.2 Hz, JH,H = 7.0 Hz, 2 H, CH2), 1.23–1.47
(m, 10 H, CH2), 0.89 (m, 3JH,H = 6.5 Hz, 3 H, CH3); 13C NMR (75 MHz,
1
2
CDCl3):
d = 160.2 (dd, JC,F = 261.6 Hz, JC,F = 18.3 Hz, 55CF), 113.6
2
3
1
(dd, JC,F = 13.8 Hz, JC,F = 8.8 Hz, 55CH), 80.4 (dd, JC,F = 168.2 Hz,
2JC,F = 33.2 Hz, CH2F), 22.7–32.1 (CH2), 14.1 (CH3); 19F NMR
2
3
(282 MHz, CDCl3):
d
= ꢀ215.6 (tdd, JF,H = 48.2 Hz, JF,F = 31.4 Hz,
4JF,H = 5.6 Hz, 1 F, CH2F), ꢀ122.0 (ddt, 3JF,H = 35.1 Hz, 3JF,F = 31.5 Hz,
3JF,H = 18.5 Hz, 1 F,55CF); GC MS (70 eV) m/z (%): 176 (2) [M+], 156
(6) [M+ꢀHF], 143 (2) [M+ꢀCH2F], 127 (7) [156ꢀC2H5], 123 (9)
[143ꢀHF], 113 (16) [127ꢀCH2], 107 (11) [127ꢀHF], 99 (28)
[113ꢀCH2], 69 (27) [C5H9+], 55 (53) [C4H7+], 56 (41) [C4H8+], 43
(100) [C3H7+], 41 (77) [C3H5+]. HR MS (EI): m/z [M+] calcd for
1,2-Difluorooctadec-2-ene (5c). Yield: 11% (CG). 1H NMR
3
3
(300 MHz, CDCl3):
d = 5.00 (ddt, JH,F = 35.0 Hz, JH,F = 7.6 Hz,
2
3
C
10H18F2: 176.1337; found: 176.1335.
4JH,F = 5.2 Hz, 1 H, 55CH), 4.75 (dd, JH,F = 48.2 Hz, JH,F = 18.2 Hz,
3
3
2 H, CH2F), 2.14 (dt, JH,H = 7.0 Hz, JH,H = 6.9 Hz, 2 H, CH2), 1.19–
3
4.2.1.2. Fluorination of 2-fluorohexadec-1-en-3-ol (1b). According
to the general procedure, in the reaction of the fluorinating agent
PFPDEA (0.992 g, 5.36 mmol) with 2-fluorohexadec-1-en-3-ol (1b,
1.003 g, 3.88 mmol) a mixture of 3b, 5b and 7b was obtained.
2,3-Difluorohexadec-1-ene (3b). Yield: 61% (GC). 1H NMR
1.51 (m, 26 H, CH2), 0.88 (t, JH,H = 6.5 Hz, 3 H, CH3); 13C NMR
1
2
(75 MHz, CDCl3):
d = 160.2 (dd, JC,F = 258.3 Hz, JC,F = 18.4 Hz,
2
3
=CF), 113.2 (dd, JC,F = 13.9 Hz, JC,F = 9.2 Hz, 55CH), 80.9 (ddt,
1JC,F = 166.8 Hz, JC,F = 31.8 Hz, CH2F), 22.7–32.2 (CH2), 14.1 (q,
2
2
CH3); 19F NMR (282 MHz, CDCl3):
d
= ꢀ215.6 (tdd, JF,H = 48.5 Hz,
2
3
(300 MHz, CDCl3):
d
= 4.82 (ddt, JH,F = 47.3 Hz, JH,F = 12.9 Hz,
3JF,F = 31.1 Hz, 4JF,H = 5.5 Hz, 1 H, CH2F), ꢀ122.0 (ddt, 3JF,H = 34.9 Hz,
3JF,F = 31.1 Hz, 3JF,H = 17.9 Hz, 1 H, =CF); GC MS (70 eV) m/z (%): 288
(1) [M+], 268 (2) [M+ꢀHF], 248 (0) [268ꢀHF], 235 (2) [268ꢀCH2F],
233 (0) [248ꢀCH3], 221 (0) [248ꢀC2H3; 235ꢀCH2], 219 (0)
[248ꢀC2H5], 208 (3) [221ꢀCH], 205 (1) [219ꢀCH2], 191 (1)
[205ꢀCH2], 177 (3) [191ꢀCH2], 163 (2) [177ꢀCH2], 149 (4)
[163ꢀCH2], 135 (7) [149ꢀCH2], 121 (10) [135ꢀCH2], 107 (9)
[121ꢀCH2], 97 (42) [C7H13+], 95 (29) [C7H11+], 83 [C6H11+], 82 (21)
[C6H10+], 69 (49) [C5H9+], 57 (82) [C4H9+], 55 (59) [C4H7+], 43 (63)
[C3H7+], 41 (100) [C3H5+]. HR MS (EI): m/z [M+] calcd for C16H30F2:
288.2629; found: 288.2625.
3JH,H = 6.5 Hz, 1 H, CHF), 4.76 (m, 3JH,F = 16.8 Hz, 1 H,55CH0H00), 4.61
(m, 3JH,F = 47.0 Hz, 1 H,55CH0H00), 1.77 (m, 1 H, CH0H00), 1.41 (m, 1 H,
CH0H00), 1.29 (m, 22 H, CH2), 0.88 (m, JH,H = 7.1 Hz, 3 H, CH3); 13C
3
NMR (75 MHz, CDCl3):
2JC,F = 22.7 Hz, 55CF), 92.4 (dd, JC,F = 16.4 Hz, JC,F = 4.3 Hz,
d
= 162.7 (dd, 1JC,F = 260.3 Hz,
2
3
1
2
55CH2), 89.5 (dd, JC,F = 171.7 Hz, JC,F = 32.7 Hz, CHF), 22.7–32.1
(CH2), 14.1 (CH3); 19F NMR (282 MHz, CDCl3):
d
= ꢀ184.3 (ddd,
2JF,H = 47.3 Hz, JF,F = 24.9 Hz, JF,H = 20.9 Hz, 1 F, CHF), ꢀ113.6
(dddd, 3JF,H = 47.0 Hz, 3JF,F = 25.4 Hz, 3JF,H = 16.7 Hz, 3JF,H = 12.4 Hz,
1 F, 55CF); GC MS (70 eV) m/z (%): 260 (0) [M+], 240 (3) [M+ꢀHF],
220 (4) [240ꢀHF], 191 (1) [220ꢀC2H5], 163 (2) [191ꢀC2H4], 149 (3)
[163ꢀCH2], 135 (7) [149ꢀCH2], 121 (10) [135ꢀCH2], 107 (9)
[121ꢀCH2], 95 (23) [C7H11+], 82 (21) [C6H10+], 69 (26) [C5H9+], 56
(57) [C4H8+], 43 (63) [C3H7+], 41 (100) [C3H5+]. HR MS (EI): m/z [M+]
calcd for C16H30F2: 260.2316; found: 260.2314.
3
3
4.2.1.4. Fluorination of oct-1-en-3-ol (2). According to the general
procedure mixture of 4 and 6 was obtained in the reaction of the
fluorinating agent PFPDEA (1.965 g, 10.61 mmol) with oct-1-en-3-
ol (2) (1.002 g, 7.80 mmol).
1,2-Difluorohexadec-2-ene (5b). Yield: 15% (GC). 1H NMR
3-Fluorooct-1-ene (4a). Yield: 36% (GC). 1H NMR (300 MHz,
3
3
(300 MHz, CDCl3):
d
= 5.00 (ddt, JH,F = 35.2 Hz, JH,H = 7.6 Hz,
CDCl3):
d
= 5.88
(dddd,
3JH,H = 17.2 Hz,
3JH,H = 10.6 Hz,
2
3
4JH,F = 5.3 Hz, 1 H, 55CH), 4.75 (dd, JH,F = 48.1 Hz, JH,F = 18.5 Hz,
3JH,H = 6.2 Hz, 3JH,F = 10.2 Hz, 1 H, 55CH), 5.29 (ddd, 3JH,H = 17.4 Hz,
3
3
2 H, CH2F), 2.13 (dt, JH,H = 6.9 Hz, JH,H = 6.7 Hz, 2 H, CH2), 1.26–
1.49 (m, 22 H, CH2), 0.88 (t, 3J(H,H) = 6.5 Hz, 3 H, CH3); 13C NMR
2JH,H = 1.3 Hz, 4JH,F = 3.6 Hz,
1
H, 55CH0H00), 5.19 (ddd,
3JH,H = 10.7 Hz, JH,H = 1.2 Hz, JH,F = 1.2 Hz, 1 H, 55CH0H00), 4.84
2
4
1
2
2
3
3
4
(75 MHz, CDCl3):
d
= 160.0 (dd, JC,F = 254.1 Hz, JC,F = 17.0 Hz,
(ddtt, JH,F = 48.7 Hz, JH,H = 6.2 Hz, JH,H = 6.2 Hz, JH,H = 1.1 Hz, 1
H, CHF), 1.67 (m, 1 H, CH0H00), 1.56 (m, 1 H, CH0H00), 1.30 (m, 6 H,
2
3
55CF), 113.3 (dd, JC,F = 13.8 Hz, JC,F = 8.8 Hz, 55CH), 80.2 (dd,
1JC,F = 168.2 Hz, 2JC,F = 33.2 Hz, CH2F), 22.7–32.1 (CH2), 14.1 (CH3);
CH2), 0.90 (t, JH,H = 7.4 Hz, 3 H, CH3); 13C NMR (75 MHz, CDCl3):
3
2
2
3
19F NMR (282 MHz, CDCl3):
d
= ꢀ215.6 (tdd, JF,H = 48.5 Hz,
d = 136.9 (d, JC,F = 21.3 Hz, 55CH), 116.5 (d, JC,F = 10.7 Hz, 55CH2),
93.6 (d, JC,F = 166.7 Hz, CHF), 31.5 (dt, JC,F = 17.7 Hz, CH2), 28.5
(CH2), 24.3 (CH2), 22.5 (CH2), 13.9 (CH3); 19F NMR (282 MHz,
3JF,F = 31.4 Hz, 4JF,H = 5.5 Hz, 1 F, CH2F), ꢀ122.0 (ddt, 3JF,H = 35.3 Hz,
3JF,F = 31.5 Hz, 3JF,H = 18.8 Hz, 1 H,55CF); GC MS (70 eV) m/z (%): 260
(0) [M+], 240 (1) [M+ꢀHF], 220 (4) [240ꢀHF], 149 (3) [220ꢀC5H11],
135 (8) [149ꢀCH2], 121 (10) [135ꢀCH2], 107 (14) [121ꢀCH2], 95
(39) [C7H11+], 82 (61) [C6H10+], 69 (57) [C5H9+], 56 (31) [C4H8+], 55
1
2
CDCl3):
d
= ꢀ177.5 (m, 1 F, CHF); GC MS (70 eV) m/z (%): 130 (0)
[M+], 110 (27) [M+ꢀHF], 95 (8) [110ꢀCH3], 81 (33) [95ꢀCH2], 69
(100) [95ꢀC2H2; C5H9+], 67 (49) [81ꢀCH2; C5H7+], 55 (53)

J. Walkowiak et al. / Journal of Fluorine Chemistry 143 (2012) 189–197
195
3
3
[69ꢀCH2], 54 (61) [69ꢀCH3], 41 (60) [C3H5+]. HR MS (EI): m/z [M+]
calcd for C8H15F: 130.1158; found: 130.1156.
(300 MHz, CDCl3): d = 4.68 (dt, JH,F = 38.2 Hz, JH,H = 7.6 Hz, 1 H,
3
3
3
55CH), 3.63 (ddq, JH,F = 7.9 Hz, JH,H = 3.6 Hz, JH,H = 10.6 Hz, 1 H,
CHCF3), 3.40 (q, 3JH,H = 7.2 Hz, 2 H, CH2), 3.33 (q, 3JH,H = 7.0 Hz, 2 H,
CH2), 2.90 (ddd, 2JH,H = 14.3 Hz, 3JH,F = 28.6 Hz, 3JH,H = 10.6 Hz, 1 H,
CH0H00), 2.60 (ddd, 2JH,H = 14.3 Hz, 3JH,F = 13.3 Hz, 3JH,H = 3.4 Hz, 1 H,
CH0H00), 2.01 (dt, 3JH,H = 6.8 Hz, 3JH,H = 6.7 Hz, 2 H, CH2), 1.26 (m, 22
H, CH2), 1.19 (t, 3JH,H = 7.2 Hz, 3 H, CH3), 1.12 (t, 3JH,H = 7.0 Hz, 3 H,
1-Fluorooct-2-ene (6a). Yield: 24% (GC). 1H NMR (300 MHz,
CDCl3):
d
= 5.84 (dd, 3JH,F = 20.6 Hz, 3JH,H = 14.8 Hz, 1 H,55CH), 5.66
3
3
(dt, JH,H = 14.8 Hz, JH,H = 6.6 Hz,
1
H, 55CH), 4.77 (ddd,
2JH,F = 47.5 Hz, JH,H = 6.3 Hz, JH,H = 0.7 Hz, 1 H, CH2F), 2.07 (dt,
3
4
3JH,H = 6.7 Hz, JH,H = 6.5 Hz, 2 H, CH2), 1.32 (m, 6 H, CH2), 0.91 (t,
3
3JH,H = 7.4 Hz, 3 H, CH3); 13C NMR (75 MHz, CDCl3):
d
= 137.6 (d,
CH3), 0.88 (t, JH,H = 6.7 Hz, 3 H, CH3); 13C NMR (75 MHz, CDCl3):
3
2
1
3JC,F = 13.5 Hz, 55CH), 124.5 (d, JC,F = 16.3 Hz, 55CH), 83.6 (d,
d
= 164.8 (s, CO), 154.3 (d, JC,F = 250.7 Hz, 55CF), 124.8 (q,
1JC,F = 159.9 Hz, CH2F), 35.2 (CH2), 32.1 (CH2), 24.4 (CH2), 22.5
1JC,F = 280.7 Hz, CF3), 109.4 (d, JC,F = 15.5 Hz, 55CH), 43.0 (q,
2JC,F = 25.9 Hz, CHCF3), 42.6 (CH2), 41.4 (CH2), 31.9 (CH2), 30.3
(dq, 2JC,F = 28.2 Hz, 3JC,F = 2.4 Hz, CH2), 22.7–29.4 (CH2), 14.3 (CH3),
2
(CH2), 13.9 (CH3); 19F NMR (282 MHz, CDCl3):
d
= ꢀ208.4 (m, 1F,
CH2F). GC MS m/z (%) 130 (0) [M+], 110 (25) [M+ꢀHF], 95 (11)
[110ꢀCH3], 81 (40) [95ꢀCH2], 69 (63) [95ꢀC2H2; C5H9+], 67 (65)
[81ꢀCH2; C5H7+], 55 (53) [69ꢀCH2], 54 (79) [69ꢀCH3], 44 (100), 41
(60) [C3H5+]. HR MS (EI): m/z [M+] calcd for C8H15F: 130.1158;
found: 130.1156.
14.1 (CH3), 12.8 (CH3); 19F NMR (282 MHz, CDCl3):
d
= ꢀ114.3
(ddd, 3JF,H = 38.1 Hz, 3JF,H = 13.3 Hz, 3JF,H = 28.6 Hz, 1 F,55CF), ꢀ68.4
(d, 3JF,H = 8.2 Hz, 3 F, CF3); GC MS (70 eV) m/z (%): 423 (4) [M+], 408
(2) [M+ꢀCH3], 394 (2) [M+ꢀC2H5], 380 (3) [M+ꢀC3H7], 366 (6)
[M+ꢀC4H9], 352 (4) [M+ꢀC5H11], 338 (3) [M+ꢀC6H13], 324 (7)
[M+ꢀC7H15], 310 (27) [M+ꢀC8H17], 296 (7) [310+HꢀCH3], 282 (4)
[310+HꢀC2H5], 268 (12) [310+HꢀC3H7], 254 (100) [310+HꢀC4H9],
226 (4) [254ꢀC2H4], 206 (2) [226ꢀHF], 183 (24) [254+H+ꢀC4H10N],
168 (10) [183ꢀCH3], 154 (7) [183ꢀHꢀCO], 115 (2) [183+HꢀCF3],
113 (0) [C8H17+], 100 (20) [H10C4NCO+], 99 (0) [C7H15+], 85 (2)
[C6H13+], 72 (14) [100ꢀCO], 58 (16) [C3H8N+], 57 (5) [C4H9+], 43
(10) [C3H7+], 41 (8) [C3H5+]. Anal. calcd for: C23H41F4NO: C, 65.22;
H, 9.76; N, 3.31. Found: C, 65.43; H, 9.84; N, 3.14.
4.2.2. Eschenmoser–Claisen-type rearrangement: general procedure
(GP2)
To a solution of allylic alcohol (1 equiv.) and triethylamine
(2 equiv.) in dry dichloromethane (5 mL), a solution of penta-
fluoropropene-diethylamine adduct (2 equiv.) in dry dichloro-
methane (5 mL) was dropwise added. The resulting mixture was
stirred over 48 h at room temperature and then quenched with
water (10 mL). The organic layer was extracted with dichlor-
omethane (3ꢁ 10 mL). The combined organic layers were washed
with saturated aqueous solutions of NaHCO3 (1ꢁ 10 mL) and NaCl
(2ꢁ 10 mL). The organic phase was dried over MgSO4 and the
solvent was evaporated. The crude product was purified by column
chromatography.
(Z)-N,N-Diethyl-4-fluoro-2-(trifluoromethyl)icos-4-enamide
(7c). According to the general procedure 7c was obtained in the
reaction of the fluorinating agent PFPDEA (0.548 g, 2.96 mmol)
with 2-fluorooctadec-1-en-3-ol 1c (0.404 g, 1.41 mmol) and
triethylamine (0.356 g, 2.52 mmol). The product 7c was purified
by column chromatography with cyclohexane/ethyl acetate (40:1).
Yield: 72% (0.459 g, 1.02 mmol). 1H NMR (300 MHz, CDCl3):
(Z)-N,N-Diethyl-4-fluoro-2-(trifluoromethyl)dodec-4-enam-
ide (7a). According to the general procedure GP2 7a was obtained
in the reaction of the fluorinating agent PFPDEA (1.098 g,
5.93 mmol) with 2-fluorodec-1-en-3-ol (1a) (0.504 g, 2.89 mmol)
and triethylamine (0.675 g, 6.67 mmol). The product 7a was
purified by column chromatography with cyclohexane/ethyl
acetate (15:1). Yield: 80% (0.788 g, 2.31 mmol). 1H NMR
3
3
d
= 4.68 (dt, JH,F = 38.4 Hz, JH,H = 7.6 Hz, 1 H, 55CH), 3.63 (ddq,
3JH,H = 10.5 Hz, JH,F = 7.8 Hz, JH,H = 3.6 Hz, 1 H, CHCF3), 3.40 (q,
3
3
3JH,H = 7.3 Hz, 2 H, CH2), 3.33 (q, 3JH,H = 7.1 Hz, 2 H, CH2), 2.90 (ddd,
3
3
2JH,H = 14.3 Hz, JH,F = 28.6 Hz, JH,H = 10.5 Hz, 1 H, CH0H00), 2.60
(ddd, 2JH,H = 14.3 Hz, 3JH,F = 13.3 Hz, 3JH,H = 3.6 Hz, 1 H, CH0H00), 2.01
(dt, 3JH,H = 6.9 Hz, 3JH,H = 6.9 Hz, 2 H, CH2), 1.26 (m, 26 H, CH2), 1.19
(t, 3JH,H = 7.3 Hz, 3 H, CH3), 1.12 (t, 3JH,H = 7.1 Hz, 3 H, CH3), 0.88 (t,
3
3
(300 MHz, CDCl3):
d = 4.68 (dt, JH,F = 38.2 Hz, JH,H = 7.6 Hz, 1 H,
3
3
3
55CH), 3.63 (ddq, JH,H = 11.1 Hz, JH,F = 7.9 Hz, JH,H = 3.6 Hz, 1 H,
CHCF3), 3.40 (q, 3JH,H = 7.2 Hz, 2 H, CH2), 3.33 (q, 3JH,H = 7.1 Hz, 2 H,
CH2), 2.90 (ddd, 2JH,H = 14.3 Hz, 3JH,F = 28.5 Hz, 3JH,H = 10.6 Hz, 1 H,
CH0H00), 2.60 (ddd, 2JH,H = 13.2 Hz, 3JH,F = 13.3 Hz, 3JH,H = 3.4 Hz, 1 H,
CH0H00), 2.01 (dt, 3JH,H = 6.9 Hz, 3JH,H = 6.7 Hz, 2 H, CH2), 1.28 (m, 12
H, CH2), 1.19 (t, 3JH,H = 7.2 Hz, 3 H, CH3), 1.12 (t, 3JH,H = 7.1 Hz, 3 H),
3JH,H = 6.7 Hz, 3 H, CH3); 13C NMR (75 MHz, CDCl3):
d = 164.7 (s,
CO), 154.2 (d, 1JC,F = 252.0 Hz,55CF), 124.9 (q, 1JC,F = 280.4 Hz, CF3),
109.3 (d, 2JC,F = 14.2 Hz, 55CH), 43.0 (q, 2JC,F = 25.5 Hz, CHCF3), 42.5
(CH2), 41.3 (CH2), 31.9 (CH2), 30.3 (dq, 2JC,F = 28.3 Hz, 3JC,F = 2.6 Hz,
CH2), 22.6–29.6 (CH2), 14.3 (CH3), 14. (CH3), 12.8 (CH3); 19F NMR
3
3
3
0.88 (t, JH,H = 6.8 Hz, 3 H, CH3); 13C NMR (75 MHz, CDCl3):
(282 MHz, CDCl3):
d
= ꢀ114.3 (ddd, JF,H = 38.4 Hz, JF,H = 13.3 Hz,
1
3
d
= 164.8 (CO), 154.3 (d, JC,F = 250.1 Hz, 55CF), 124.9 (q,
3JF,H = 28.6 Hz, 1 F, 55CF), ꢀ68.4 (d, JF,H = 9.4 Hz, 3 F, CF3); GC MS
(70 eV) m/z (%): 451 (4) [M+], 436 (1) [M+ꢀCH3], 422 (3)
[M+ꢀC2H5], 408 (2) [M+ꢀC3H7], 394 (3) [M+ꢀC4H9], 380 (5)
[M+ꢀC5H11], 366 (7) [M+ꢀC6H13], 352 (4) [M+ꢀC7H15], 338 (4)
[M+ꢀC8H17], 324 (9) [M+ꢀC9H19], 310 (25) [M+ꢀC10H21], 296 (8)
[310+HꢀCH3], 282 (6) [310+HꢀC2H5], 268 (13) [310+HꢀC3H7], 254
(100) [310+HꢀC4H9], 226 (4) [254ꢀC2H4], 206 (1) [226ꢀHF], 183
(27) [254+HꢀC4H10N], 168 (9) [183ꢀCH3], 154 (7) [183ꢀHꢀCO],
115 (1) [183+HꢀCF3], 113 (0) [C8H17+], 100 (20) [H10C4NCO+], 99
(0) [C7H15+], 85 (1) [C6H13+], 72 (17) [100ꢀCO], 71 (3) [C5H11+], 58
(9) [C3H8N+], 57 (8) [C4H9+], 43 (11) [C3H7+], 41 (9) [C3H5+]. Anal.
calcd for C25H45F4NO: C, 66.49; H, 10.04; N, 3.10. Found: C, 66.62;
H, 10.34; N, 3.26.
1JC,F = 280.7 Hz, CF3), 109.5 (dd, JC,F = 10 Hz, 55CH), 43.1 (dq,
2
2JC,F = 29.6 Hz, CHCF3), 42.6 (CH2), 41.4 (CH2), 31.8 (CH2), 30.4 (dq,
2JC,F = 28.1 Hz, JC,F = 2.4 Hz, CH0H00), 22.7–29.4 (CH2), 14.4 (CH3),
3
14.1 (CH3), 12.8 (CH3); 19F NMR (282 MHz, CDCl3):
d
= ꢀ114.2
(ddd, 3JF,H = 38.4 Hz, 3JF,H = 28.5 Hz, 3JF,H = 13.3 Hz, 1 F,55CF), ꢀ68.4
(d, JF,H = 8.3 Hz, 3 F, CF3); GC MS m/z (%) 339 (6) [M+], 324 (3)
3
[M+ꢀCH3], 310 (32) [M+ꢀC2H5], 296 (8) [M+ꢀC3H7], 282 (4)
[M+ꢀC4H9], 268 (12) [M+ꢀC5H11], 254 (100) [M+ꢀC6H13], 226 (6)
[254ꢀC2H4], 206 (3) [226ꢀHF], 183 (25) [254 +HꢀC4H10N], 168
(15) [183ꢀCH3], 154 (10) [183ꢀHꢀCO], 115 (2) [183+HꢀCF3], 100
(32) [H10C4NCO+], 72 (23) [100ꢀCO], 58 (16) [C3H8N+], 41 (8)
[C3H5+]. Anal. calcd for C17H29F4NO: C, 60.16; H, 8.61; N, 4.13.
Found: C, 60.38; H, 8.67; N, 4.22.
(Z)-N,N-Diethyl-4-fluoro-2-(trifluoromethyl)octadec-4-
enamide (7b). According to the general procedure 7b was obtained
in the reaction of the fluorinating agent PFPDEA (0.735 g,
3.97 mmol) with 2-fluorohexadec-1-en-3-ol 1b (0.485 g,
1.88 mmol) and triethylamine (0.458 g, 4.53 mmol). The product
7b was purified by column chromatography with cyclohexane/
ethyl acetate (35:1). Yield: 91% (0.723 g, 1.69 mmol). 1H NMR
N,N-Diethyl-4-fluoro-2-(trifluoromethyl)pent-4-enamide
(7d). According to the general procedure 7d was obtained in the
reaction of the fluorinating agent PFPDEA (1.10 g, 6.00 mmol) with
2-fluoroprop-1-en-3-ol 1d (0.230 g, 3.00 mmol) and triethylamine
(0.607 g, 6.00 mmol). The product 7d was purified by column
chromatography with cyclohexane/ethyl acetate (10:1). Yield: 40%
(0.290 g, 1.20 mmol). 1H NMR (300 MHz, CDCl3):
3JH,F = 16.9 Hz, 2JH,H = 3.0 Hz, 1 H,55CH0H00), 4.35 (dd, 3JH,F = 49.8 Hz,
d = 4.55 (dd,

196
J. Walkowiak et al. / Journal of Fluorine Chemistry 143 (2012) 189–197
2JH,H = 3.0 Hz, 1 H, 55CH0H00), 3.59 (m, 1 H, CHCF3), 3.30 (m, 4 H,
CH2), 2.93 (ddd, 3JH,F = 27.4 Hz, 2JH,H = 14.4 Hz, 3JH,H = 10.6 Hz, 1 H,
CH0H00), 2.57 (ddd, 2JH,H = 14.4 Hz, 3JH,F = 12.2 Hz, 3JH,H = 3.7 Hz, 1 H,
NMR (282 MHz, CDCl3):
d
= ꢀ68.2 (d, 3JF,H = 9.7 Hz, 3 F, CF3); GC MS
(70 eV) m/z (%): 293 (10) [M+], 278 (6) [M+ꢀCH3], 264 (4)
[M+ꢀC2H4], 250 (10) [M+ꢀC3H7], 236 (100) [M+ꢀC4H9], 224 (63)
[M+ꢀCF3], 183 (45) [236+HꢀC4H6], 168 (28) [183ꢀCH3], 154 (22)
[183ꢀC2H5], 140 (5) [183ꢀC3H8], 126 (9) [183ꢀC3H8N], 100 (52)
[H10C4NCO+], 72 (39) [100ꢀCO], 58 (28) [C3H8N+]. Anal. calcd for
C15H26NOF3: C, 61.41; H, 8.93; N, 4.77. Found: C, 61.52; H, 9.09; N,
4.75.
3
3
CH0H00), 1.13 (t, JH,H = 7.2 Hz, 3 H, CH3), 1.05 (t, JH,H = 7.1 Hz 3 H,
CH3); 13C NMR (75 MHz, CDCl3):
d = 164.3 (CO), 161.4 (d,
1
1JC,F = 255.7 Hz, 55CF), 124.7 (q, JC,F = 280.6 Hz, CF3), 93.5 (d,
2JC,F = 18.8 Hz, 55CH2), 42.7 (qd, JC,F = 26.4 Hz, JC,F = 1.6 Hz,
CHCF3), 42.5 (CH2), 41.3 (CH2), 30.0 (dq, JC,F = 27.3 Hz,
3JC,F = 2.7 Hz, CH2), 14.3 (CH3), 12.7 (CH3); 19F NMR (282 MHz,
2
3
2
N,N-Diethyl-2-(trifluoromethyl)pent-4-enamide (8b).
According to the general procedure 8b was obtained in the reaction
of the fluorinating agent PFPDEA (1.10 g, 6.00 mmol) with 2-
fluoroprop-1-en-3-ol 2b (0.230 g, 3.00 mmol) and triethylamine
(0.607 g, 6.00 mmol). The product 8b was purified by column
chromatography with cyclohexane/ethyl acetate (10:1). Yield: 40%
CDCl3):
d
= ꢀ99.4
(dddd,
3JF,H = 49.8 Hz,
3JF,H = 27.4 Hz,
3
3JF,H = 16.9 Hz, JF,H = 12.2 Hz, 1 F, 55CF), ꢀ68.4 (d, JF,H = 7.8 Hz, 3
F, CF3). Anal. calcd for C10H15F4NO: C, 49.79; H, 6.27; N, 5.81.
Found: C, 49.85; H, 6.34; N, 5.96.
3
(2R)-N,N-Diethyl-4-fluoro-2-(trifluoromethyl)icos-4(Z)-
enamide ((R)-7c). According to the general procedure (R)-7c was
obtained in the reaction of the fluorinating agent PFPDEA (0.391 g,
2.11 mmol) with (R)-2-fluorooctadec-1-en-3-ol (65% ee) (R)-1c
(0.301 g, 1.05 mmol) and triethylamine (0.213 g, 2.10 mmol). The
product (R)-7c was purified by column chromatography with
cyclohexane/ethyl acetate (40:1). Yield: 76% (0.361 g, 0.80 mmol).
(0.290 g, 1.20 mmol). 1H NMR (300 MHz, CDCl3):
d = 5.69 (ddt,
3JH,H = 17.2 Hz, 3JH,H = 10.0 Hz, 3JH,H = 7.1 Hz, 1 H, 55CH), 5.18 (ddd,
3
3
2JH,H = 1.6 Hz, JH,H = 17.2 Hz, JH,H = 3.6 Hz, 1 H, 55CH0H00), 5.09
(ddt, 2JH,H = 1.6 Hz, 3JH,H = 10.0 Hz, 3JH,H = 1.0 Hz, 1 H,55CH0H00), 3.42
2
(m, 4 H, CH2), 3.35 (m, 1 H, CHCF3), 2.81 (ddddd, JH,H = 13.2 Hz,
3
3
3
3JH,H = 10.5 Hz, JH,H = 7.1 Hz, JH,H = 1.4 Hz, JH,H = 1.0 Hz, 1 H,
2
3
3
[
a
]
25 +8.8 (c 0.51, CHCl3). 1H NMR (300 MHz, CDCl3):
d
= 4.68 (dt,
CH0H00), 2.50 (ddd, JH,H = 13.2 Hz, JH,H = 7.5 Hz, JH,H = 3.6 Hz, 1
D
3JH,F = 38.4 Hz, 3JH,H = 7.6 Hz, 1 H, 55CH), 3.63 (ddq, 3JH,H = 10.5 Hz,
3JH,F = 7.8 Hz, 3JH,H = 3.6 Hz, 1 H, CHCF3), 3.40 (q, 3JH,H = 7.3 Hz, 2 H,
H, CH0H00), 1.19 (t, 3JH,H = 7.1 Hz, 3 H, CH3), 1.13 (t, 3JH,H = 7.1 Hz 3 H,
CH3); 13C NMR (75 MHz, CDCl3):
d
= 165.2 (CO), 132.9 (55CH), 125.0
3
2
1
2
CH2), 3.33 (q, JH,H = 7.1 Hz, 2 H, CH2), 2.90 (ddd, JH,H = 14.3 Hz,
3JH,F = 28.6 Hz, 3JH,H = 10.5 Hz,
(q, JC,F = 280.6 Hz, CF3), 118.7 (55CH2), 45.6 (q, JC,F = 25.6 Hz,
1
H, CH0H00), 2.60 (ddd,
CHCF3), 42.4 (CH2), 41.1 (CH2), 31.2 (CH2), 14.6 (CH3), 12.8 (CH3);
19F NMR (282 MHz, CDCl3):
Anal. calcd for C10H16F3NO: C, 53.80; H, 7.22; N, 6.27. Found: C,
53.92; H, 7.41; N, 6.41.
(2R)-N,N-Diethyl-2-(trifluoromethyl)dec-4(E)-enamide ((R)-
8a). According to the general procedure (R)-8a was obtained in the
reaction of the fluorinating agent PFPDEA (0.578 g, 3.12 mmol)
with (R)-oct-1-en-3-ol (R)-2a (0.200 g, 1.56 mmol) and triethyla-
mine (0.316 g, 3.12 mmol). The product (R)-8a was purified by
2JH,H = 14.3 Hz, JH,F = 13.3 Hz, JH,H = 3.6 Hz, 1 H, CH0H00), 2.01
(dt, 3JH,H = 6.9 Hz, 3JH,H = 6.9 Hz, 2 H, CH2), 1.26 (m, 26 H, CH2), 1.19
(t, 3JH,H = 7.3 Hz, 3 H, CH3), 1.12 (t, 3JH,H = 7.1 Hz, 3 H, CH3), 0.88 (t,
d
= ꢀ68.2 (d, JF,H = 7.9 Hz, 3 F, CF3).
3
3
3
3JH,H = 6.7 Hz, 3 H, CH3); 13C NMR (75 MHz, CDCl3):
d
= 164.7 (s,
CO), 154.2 (d, 1JC,F = 252.0 Hz,55CF), 124.9 (q, 1JC,F = 280.4 Hz, CF3),
109.3 (d, 2JC,F = 14.2 Hz, 55CH), 43.0 (q, 2JC,F = 25.5 Hz, CHCF3), 42.5
(CH2), 41.3 (CH2), 31.9 (CH2), 30.3 (dq, 2JC,F = 28.3 Hz, 3JC,F = 2.6 Hz,
CH2), 22.6–29.6 (CH2), 14.3 (CH3), 14. (CH3), 12.8 (CH3); 19F NMR
3
3
(282 MHz, CDCl3):
d
= ꢀ114.3 (ddd, JF,H = 38.4 Hz, JF,H = 13.3 Hz,
column chromatography with cyclohexane/ethyl acetate (10:1).
Yield: 93% (0.423 g, 1.45 mmol). [
3
25
3JF,H = 28.6 Hz, 1 F, 55CF), ꢀ68.4 (d, JF,H = 9.4 Hz, 3 F, CF3); GC MS
(70 eV) m/z (%): 451 (4) [M+], 436 (1) [M+ꢀCH3], 422 (3)
[M+ꢀC2H5], 408 (2) [M+ꢀC3H7], 394 (3) [M+ꢀC4H9], 380 (5)
[M+ꢀC5H11], 366 (7) [M+ꢀC6H13], 352 (4) [M+ꢀC7H15], 338 (4)
[M+ꢀC8H17], 324 (9) [M+ꢀC9H19], 310 (25) [M+ꢀC10H21], 296 (8)
[310+HꢀCH3], 282 (6) [310+HꢀC2H5], 268 (13) [310+HꢀC3H7], 254
(100) [310+HꢀC4H9], 226 (4) [254ꢀC2H4], 206 (1) [226ꢀCF], 183
(27) [254+HꢀC4H10N], 168 (9) [183ꢀCH3], 154 (7) [183ꢀHꢀCO],
115 (1) [183+HꢀCF3], 113 (0) [C8H17+], 100 (20) [H10C4NCO+], 99
(0) [C7H15+], 85 (1) [C6H13+], 72 (17) [100ꢀCO], 71 (3) [C5H11+], 58
(9) [C3H8N+], 57 (8) [C4H9+], 43 (11) [C3H7+], 41 (9) [C3H5+]. Anal.
calcd for C25H45F4NO: C, 66.49; H, 10.04; N, 3.10. Found: C, 66.62;
H, 10.34; N, 3.26.
a
]
+36.8 (c 0.75, CHCl3). 1H
D
NMR (300 MHz, CDCl3):
d
= 5.59 (ddd, 3JH,H = 14.9 Hz,
3
3
3JH,H = 7.3 Hz, JH,H = 6.8 Hz, 1 H, 55CH), 5.28 (dt, JH,H = 14.9 Hz,
3JH,H = 7.2 Hz, 1 H, 55CH), 3.41 (q, 3JH,H = 7.2 Hz, 2 H, CH2), 3.32 (q,
3JH,H = 7.2 Hz, 2 H, CH2), 3.30 (m, 1 H, CHCF3), 2.72 (ddd,
3
3
4
2JH,H = 13.4 Hz, JH,H = 10.5 Hz, JH,H = 7.1 Hz, JH,H = 0.8 Hz, 1 H,
CH0H00), 2.43 (ddd, 2JH,H = 13.3 Hz, 3JH,H = 7.2 Hz, 3JH,H = 4.8 Hz, 1 H,
3
3
CH0H00), 1.96 (dt, JH,H = 6.8 Hz, JH,H = 6.8 Hz, 2 H, CH2), 1.23–1.37
(m, 6 H, CH2), 1.18 (t, 3JH,H = 7.2 Hz, 3 H, CH3), 1.13 (t, 3JH,H = 7.2 Hz,
3
3 H, CH3), 0.87 (t, JH,H = 6.9 Hz, 3 H, CH3); 13C NMR (75 MHz,
1
CDCl3):
d
= 165.9 (s, CO), 135.4 (55CH), 125.5 (q, JC,F = 280.9 Hz,
CF3), 124.5 (55CH), 46.6 (tq, 2JC,F = 25.5 Hz, CHCF3), 42.8 (CH2), 41.5
(CH2), 32.7 (CH2), 31.7 (CH2), 30.5 (q, 3JC,F = 2.6 Hz, CH2), 29.2 (CH2),
22.8 (CH2), 15.0 (CH3), 14.3 (CH3), 13.2 (CH3); 19F NMR (282 MHz,
(E)-N,N-Diethyl-2-(trifluoromethyl)dec-4-enamide (8a).
According to the general procedure 8 was obtained in the reaction
of the fluorinating agent PFPDEA (1.730 g, 9.30 mmol) with oct-1-
CDCl3):
d
= ꢀ68.2 (d, 3JF,H = 9.7 Hz, 3 F, CF3); GC MS (70 eV) m/z (%):
293 (10) [M+], 278 (6) [M+ꢀCH3], 264 (4) [M+ꢀC2H4], 250 (10)
[M+ꢀC3H7], 236 (100) [M+ꢀC4H9], 224 (63) [M+ꢀCF3], 183 (45)
[236+HꢀC4H6], 168 (28) [183ꢀCH3], 154 (22) [183ꢀC2H5], 140 (5)
[183ꢀC3H8], 126 (9) [183ꢀC3H8N], 100 (52) [H10C4NCO+], 72 (39)
[100ꢀCO], 58 (28) [C3H8N+]. Anal. calcd for C15H26NOF3: C, 61.41;
H, 8.93; N, 4.77. Found: C, 61.62; H, 9.17; N, 4.69.
en-3-ol
2 (0.500 g, 3.90 mmol) and triethylamine (0.811 g,
8.01 mmol). The product 8 was purified by column chromatogra-
phy with cyclohexane/ethyl acetate (10:1). Yield: 88% (1.001 g,
3.43 mmol). 1H NMR (300 MHz, CDCl3):
d = 5.59 (ddd,
3
3
3JH,H = 14.9 Hz, JH,H = 7.3 Hz, JH,H = 6.8 Hz, 1 H, 55CH), 5.28 (dt,
3JH,H = 14.9 Hz, 3JH,H = 7.2 Hz, 1 H,55CH), 3.41 (q, 3JH,H = 7.2 Hz, 2 H,
N,N-Diethyl-3,3,3-trifluoro-2-(5-methyl-2,6-dioxo-1,2,3,6-
tetra-hydropyrimidin-4-yl)-propanamide (37). According to the
general procedure 37 was obtained in the reaction of the
fluorinating agent PFPDEA (0.741 g, 4.00 mmol) with 5-(hydro-
xymethyl)uracil 17 (0.284 g, 2.00 mmol) and triethylamine
(0.437 g, 4.00 mmol). The product 37 was purified by column
chromatography with chloroform/methanol (95:5). Yield: 46%
3
CH2), 3.32 (q, JH,H = 7.2 Hz, 2 H, CH2), 3.30 (m, 1 H, CHCF3), 2.72
(ddd, 2JH,H = 13.4 Hz, 3JH,H = 10.5 Hz, 3JH,H = 7.1 Hz, 4JH,H = 0.8 Hz, 1
H, CH0H00), 2.43 (ddd, 2JH,H = 13.3 Hz, 3JH,H = 7.2 Hz, 3JH,H = 4.8 Hz, 1
3
3
H, CH0H00), 1.96 (dt, JH,H = 6.8 Hz, JH,H = 6.8 Hz, 2 H, CH2), 1.23–
3
1.37 (m, 6 H, CH2), 1.18 (t, JH,H = 7.2 Hz, 3 H, CH3), 1.13 (t,
3JH,H = 7.2 Hz, 3 H, CH3), 0.87 (t, 3JH,H = 6.9 Hz, 3 H, CH3); 13C NMR
(75 MHz, CDCl3):
d
= 165.9 (s, CO), 135.4 (55CH), 125.5 (q,
(0.283 g, 0.92 mmol). 1H NMR (300 MHz, DMSO-d6):
d = 11.3 (s, 1
H, NH), 10.9 (s, 1 H, NH), 3.95, (m, 1 H, CHCF3), 3.35 (s, 3 H, CH3),
1JC,F = 280.9 Hz, CF3), 124.5 (55CH), 46.6 (tq, 2JC,F = 25.5 Hz, CHCF3),
42.8 (CH2), 41.5 (CH2), 32.7 (CH2), 31.7 (CH2), 30.5 (q, 3JC,F = 2.6 Hz,
3
3.26 (m, 2 H, CH2), 2.67 (m, 2 H, CH2), 1.01 (t, JH,H = 7.1 Hz, 3 H,
CH2), 29.2 (CH2), 22.8 (CH2), 15.0 (CH3), 14.3 (CH3), 13.2 (CH3); 19
F
CH3), 0.93 (t, JH,H = 7.0 Hz, 3 H, CH3); 13C NMR (75 MHz, CDCl3):
3

J. Walkowiak et al. / Journal of Fluorine Chemistry 143 (2012) 189–197
197
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d
= 164.6 (CO), 164.5 (55C(CO)NH), 151.1 (NH(CO)NH) 140.6
1
(55C(NH)CH), 125.3 (q, JC,F = 280.7 Hz, CF3), 106.3 (=C(CO)CH3),
42.8 (q, JC,F = 24.5 Hz, CHCF3), 41.9 (CH2), 40.3 (CH2), 24.7 (CH3),
14.3 (CH3), 12.8 (CH3); 19F NMR (282 MHz, DMSO-d6):
3JF,H = 8.3 Hz, 3 F, CF3); GC MS (70 eV) m/z (%): 307 (12) [M+], 238
(6) [M+ꢀCF3], 235 (4) [M+ꢀNC4H10], 215 (16) [235ꢀHF], 207 (5)
[235ꢀCO], 187 (10) [207ꢀHF], 182 (2) [C7H11NOF3+], 165 (9), 137
(7) 125 (28) [C5H5N2O2+], 100 (7) [H10C4NCO+], 72 (100) [H10C4N+],
58 (35) [C3H8N+]. Anal. calcd for C12H16N3O3F3: C, 46.91; H, 5.25; N,
13.68. Found: C, 46.97; H, 5.30; N, 13.69.
2
d
= ꢀ65.6 (d,
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Financial support by the Deutsche Forschungsgemeinschaft is
gratefully acknowledged (Sonderforschungsbereich 424 stipends
for J.W.). We are indebted to DSc Marcin Hoffmann for advice and
fruitful discussions on the DFT calculations results. Part of this
work was supported also by Polish Ministry of Science and
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National Education (grant No.
Pentafluoropropene sample (PFP) was kindly provided to us by
SynQuest Laboratories Ltd.
N N204 027738 to M.T.-S.).
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Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.jfluchem.2012.07.011.
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