Synthesis of α-(Pentafluorosulfanyl)- and α-(Trifluoromethyl)-Substituted Carboxylic Acid Derivatives by Ireland-Claisen Rearrangement

Article abstract of DOI:10.1021/acs.joc.6b02805

Earlier studies have shown that [3,3]-sigmatropic rearrangements of allyl esters are useful for the construction of fluorine-containing carboxylic acid derivatives. This paper describes the synthesis of 3-aryl-pent-4-enoic acid derivatives bearing either a pentafluorosulfanyl (SF₅) or a trifluoromethyl (CF₃) substituent in the 2-position by treatment of corresponding SF₅- or CF₃-acetates of p-substituted cinnamyl alcohols with triethylamine followed by trimethylsilyl triflate (TMSOTf). This Ireland-Claisen rearrangement delivered approximate 1:1 mixtures of syn/anti diastereoisomers due to tiny differences (<0.5 kcal/mol) both in the energy of (Z)/(E)-isomeric ester enolates and in the alternative Zimmerman-Traxler transition states of model compounds as shown by DFT calculations. Acidic reaction conditions have to be avoided since addition of the reagents in opposite sequence (first TMSOTf then Et₃N) led to oligomerization of the cinnamyl SF₅- and CF₃-acetates. Treatment of the corresponding regioisomeric 1-phenyl-prop-2-en-1-yl acetates under the latter conditions resulted in [1,3]-sigmatropic rearrangement and subsequent oligomerization of the intermediately formed cinnamyl esters. When Et₃N was added first followed by TMSOTf, no further reaction of the formed ester was detected.

Full text of DOI:10.1021/acs.joc.6b02805

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Article
Synthesis of #-(Pentafluorosulfanyl)- and #-(Trifluoromethyl)-substituted
Carboxylic Acid Derivatives by Ireland-Claisen Rearrangement
Anna-Lena Dreier, Bernd Beutel, Christian Mück-Lichtenfeld,
Andrej V Matsnev, Joseph S. Thrasher, and Günter Haufe
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02805 • Publication Date (Web): 30 Dec 2016
Downloaded from http://pubs.acs.org on December 30, 2016
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Synthesis of α-(Pentafluorosulfanyl)- and α-(Trifluoromethyl)-substituted Carboxylic
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Acid Derivatives by Ireland-Claisen Rearrangement
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Anna-Lena Dreier,† Bernd Beutel,† Christian Mück-Lichtenfeld,† Andrej V. Matsnev,‡ Joseph
S. Thrasher,‡ and Günter Haufe *,†,§
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†
Organisch-Chemisches Institut, Universität Münster, Corrensstraße 40, 48149 Münster,
Germany
‡ Department of Chemistry, Advanced Materials Research Laboratory, Clemson University,
91 Technology Drive, Anderson, South Carolina 29625, United States of America
§
Cells-in-Motion Cluster of Excellence, Universität Münster, Waldeyerstraße 15, 48149
Münster, Germany
E-mail: haufe@uni-muenster.de
Keywords: C-C bond formation • DFT calculation • [3,3]-sigmatropic rearrangement • SF5-
chemistry • synthesis.
Abstract: Earlier studies have shown that [3,3]-sigmatropic rearrangements of allyl esters are
useful for the construction of fluorine-containing carboxylic acid derivatives. This paper
describes the synthesis of 3-aryl-pent-4-enoic acid derivatives bearing either a
pentafluorosulfanyl (SF5) or a trifluoromethyl (CF3) substituent in the 2-position by treatment
of corresponding SF5 or CF3 acetates of p-substituted cinnamyl alcohols with trimethylamine
followed by trimethylsilyl triflate (TMSOTf). This Ireland-Claisen rearrangement delivered
approximate 1:1 mixtures of syn/anti-diastereoisomers due to tiny differences (<0.5 kcal/mol)
both in the energy of (Z)/(E)-isomeric ester enolates and in the alternative Zimmermann-
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Traxler transition states of model compounds as shown by DFT calculations. Acidic reaction
conditions have to be avoided since addition of the reagents in opposite sequence (first
TMSOTf then Et3N) led to oligomerization of the cinnamyl SF5- and CF3-acetates. Treatment
of the corresponding regioisomeric 1-phenyl-prop-2-en-1-yl acetates under the latter
conditions resulted in [1,3]-sigmatropic rearrangement and subsequent oligomerization of the
intermediately formed cinnamyl esters. When Et3N was added first followed by TMSOTf, no
further reaction of the formed ester was detected.
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Introduction
Rearrangement reactions belong to the most widely used methods to achieve an extension of
the carbon scaffold of a given molecule. Here [3,3]-sigmatropic rearrangement reactions of
the Claisen-type are of significant importance.1 In 1912 Claisen described both the thermally
induced rearrangement of an allyl aryl ether as well as the conversion of an allyl vinyl ether to
the corresponding allyl phenol and carbonyl compounds, respectively.2 As of now, several
variations of the original Claisen rearrangements have been developed. The Ireland-Claisen
rearrangement is one of the well-known and most frequently employed variants. In this
reaction, which was discovered in 1972, an allylic ester is initially transformed into the
corresponding ester enolate. This 3-oxa-1,5-diene system then rearranges to form a γ,δ-
unsaturated carboxylic acid.3 Like the aromatic and aliphatic Claisen rearrangements, the
Ireland-Claisen variant can be performed in a stereoselective fashion. Thereby, the
stereochemistry of the product(s) is determined by the geometry of the intermediately formed
ester enolate(s) as well as by the conformation of the six-membered transition state(s).3b
Additional advantages of the Ireland-Claisen rearrangement are mild reaction conditions and
the tolerance of various functional groups.1c,1d,4
Due to the general interest in organofluorine compounds,5 Ireland-Claisen rearrangement
reactions of substrates containing fluorine or the CF3-group have been previously studied by
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us6 and others.7 Likewise, in recent years the pentafluorosulfanyl (SF5)-group became
increasingly interesting8 as a potential substitute for the CF3-group. However, all our attempts
to involve different 3-pentafluorosulfanyl allylic esters with an SF5-group as part of the allylic
system in the rearrangement step failed.9 In contrast, Ireland-Claisen rearrangement of allylic
SF5-acetates 1 derived from aliphatic allylic alcohols with either a fluorine atom or a
hydrogen atom in the 2-position were converted into the corresponding carboxylic acids 2
using trimethylsilyltriflate (TMSOTf) and triethylamine in dichloromethane.10 (Scheme 1).
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Scheme 1. Stereoselective synthesis of trans-configurated α-SF5-substituted γ,-
unsaturated carboxylic acids 2 by Ireland-Claisen rearrangements.10
The trans-configurated products were formed exclusively, although both (Z)- and (E)-
ketene trimethylsilyl acetals were formed intermediately as proved in time-dependent NMR
experiments. While the (Z)-ketene trimethylsilyl acetals rearranged smoothly, the (E)-isomers
were stable under these and even more forcing conditions.10 During aqueous work-up, the
starting allylic esters are regenerated from the latter intermediates. As a consequence,
incomplete conversion of the starting material 1 was observed in all cases. The (Z)-ketene
trimethylsilyl acetals most likely rearrange via an energetically favored six-membered
transition state to give the trans-configurated carboxylic acids 2. For the first time, SF5-
substituted ester enolates were verified and characterized by NMR spectroscopy. Esters 1 with
a phenyl group (R = Ph) could not be converted into the corresponding carboxylic acids under
the conditions shown in Scheme 1. Instead complex mixtures of unidentified products were
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obtained.10 Very recently, aldol-type reactions of SF5-substituted acetic acid esters with
aldehydes proceeding via analogous ester enolates have been described.11
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Herein, we would like to present our recent results on Ireland-Claisen rearrangements of 2-
(pentafluorosulfanyl)acetic acid cinnamyl esters. Moreover, we compare these reactions
concerning reactivity and selectivity with those of the corresponding allylic CF3- and CH3-
substituted acetates and illuminate the importance of the particular reaction conditions.
Furthermore, two earlier attempts to rearrange SF5-substituted acetates of secondary allyl
alcohols10 were repeated under the new optimized conditions.
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Results and Discussion
Synthesis of cinnamyl SF5- and CF3-acetates
For the [3,3]-sigmatropic rearrangements besides cinnamyl alcohol (5a) itself, also the 4-
fluoro and 4-methyl derivatives 5b and 5c12 were synthesized by a two-step procedure starting
from the commercial acids 3b and 3c according to known procedures (Scheme 2).13,14 Direct
reduction of the acids with either lithium aluminum hydride (LAH)15 or the borane
dimethylsulfide complex16 were not successful.
Scheme 2. Preparation of cinnamyl alcohols 5b and 5c.
Esterification of the alcohols 5 with 2-(pentafluorosulfanyl)acetic acid (6a)17 and
commercially available 3,3,3-trifluoromethyl-propionic acid (6b) in the presence of N,N′-di-
cyclohexyl carbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) according to the
protocol independently developed by Neises and Steglich18a and Hassner and Alexanian18b
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gave the desired SF5- and CF3-substituted allylic esters 7a, 7b, and 7d-g. For the purpose of
comparison in the Ireland-Claisen rearrangement, the known propionate 7c19 was prepared
analogously starting from cinnamyl alcohol (5a) and propionic acid (6c) (Table 1).
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Table 1. Synthesis of allylic esters
Entry
Alcohol
5a
Y
R
Ester
7a
Yield [%]
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7
SF5
CF3
CH3
SF5
CF3
SF5
CF3
H
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89
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H
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7b
7c
H
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F
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7e
F
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CH3
CH3
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7f
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7g
The seven esters 7a-7g produced in this way were isolated in high purity after column
chromatography in yields between 59 and 89%. No significant difference in yields of the SF5-
and the CF3-substituted compounds has been observed.
Attempts of Ireland-Claisen rearrangements
Having allylic esters 7a and 7b in hand, Ireland-Claisen rearrangements were attempted under
the conditions (1. TMSOTf, 2. Et3N, DCM, reflux) originally developed for intermediate
formation of (trifluoromethyl)ketene silyl acetals (-CF3-ester enolate equivalents) in aldol-
type reactions and ester enolate Claisen rearrangements20 and optimized for rearrangements of
allylic SF5-acetates of type 1 derived from aliphatic allylic alcohols with either a fluorine
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atom or a hydrogen atom in the 2-position.10 Surprisingly, the expected α,β-disubstituted
carboxylic acids 8a and 8b were not obtained. Instead an oligomerization of the starting
allylic esters occurred (see below). Interestingly, compound 9a and the corresponding CF3
and even the CH3 analogues 9b and 9c also failed to rearrange to the expected products 10a,
10b, and 10c (Scheme 3), respectively. Under the same conditions they oligomerized as well.
Also, the p-fluorophenyl and the 1-naphthyl analogues 9d and 9e (Y = CF3, not shown in
Scheme 3) have been synthesized. Likewise, these allylic esters oligomerized under the
aforementioned conditions.
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Scheme 3. Failure of [3,3]-sigmatropic rearrangement of cinnamyl 7a and 7b and
substituted 1-phenylprop-2-en-1-yl-acetates 9a-9c.
This is surprising since, in the latter cases, extension of the π-system from benzenes 9a-9c
to styrene derivatives 10a-10c and formation of a disubstituted double bond from a
monosubstituted terminal one in the starting materials were expected to be driving forces for
the [3,3]-sigmatropic rearrangement. Instead of the target products, mixtures of oligomers
were formed according to the ESI-mass spectra, which show products with m/z values
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between 500 and 1200. Moreover, in the H NMR spectra of the crude product mixtures,
broad multiplets and absence of signals of vinylic protons provide hints on oligomeric
structures (see SI).
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Comparing the spectra of the mixtures of oligomeric products formed from either the
cinnamyl acetates 7a and 7b or the secondary allyl acetates 9a and 9b, we realized that they
looked almost identical. Consequently, we anticipated that slightly acidic conditions are
created when TMSOTf is added to the allylic esters in methylene chloride before Et3N
addition. In case of esters 9 this gives rise to the possibility of an electrophilic attack of a
proton or a trimethylsilyl cation equivalent E+ on the carbonyl oxygen initiating a [1,3]-
sigmatropic shift of the ester function. This leads to the formation of benzylic cations of the
corresponding cinnamyl esters 7, which oligomerize under the acidic conditions (Scheme 4).
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Scheme 4. Anticipated mechanism of [1,3]-sigmatropic rearrangement of substituted 1-
phenylprop-2-en-1-yl-acetates 9 and subsequent oligomerization of the benzylic cations
of the corresponding cinnamyl acetates 7.
TMSOTf is known to have some ionic character in dry, fairly non-polar solvents like
methylene chloride, but it is more ionic in a polar environment.21 Moreover, the reagent is
useful as a Lewis acid in many carbonyl reactions22 and has been used as a catalyst in cationic
polymerization reactions.23
In order to test whether standard Ireland-Claisen conditions3,6,7 might work, we treated
compound 9b with LDA (1.2 equiv) and TMSCl (1.2 equiv) in THF at -78 °C to room
temperature in an attempt to obtain 10b (Scheme 5). However, only the starting allylic ester
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9b was recovered after workup. No products with a CF3 group were found in the F NMR
spectrum of the crude product. Treatment of 9b with 2.5 equiv of LDA led to decomposition.
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Scheme 5. Failure of Ireland-Claisen rearrangement of 1-phenylprop-2-en-1-yl-(3,3,3-
trifluoropropionate) (9b).
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In contrast, 1-(phenylprop-2-en-1-yl) propionate (9c) and its p-fluorophenyl- and 1-
naphthyl derivatives 9f and 9g formed from the corresponding allylic alcohols underwent
[3,3]-sigmatropic rearrangements under identical conditions, and the corresponding methyl
esters 10c, 10f, and 10g were isolated after methylation of the initially formed carboxylic
acids with methyl iodide (Scheme 6).
Scheme 6. [3,3]-Sigmatropic rearrangement of substituted 1-arylprop-2-en-1-yl-
propionates 9.
Rearrangements under the new reaction conditions
From the results described in the former section, we concluded that an initial acidic
environment is responsible for the failure of rearrangement of compounds 9a, 9b, and the
substituted cinnamyl acetates 7. Therefore, we hypothesized that basic conditions from the
beginning might facilitate the rearrangement. We first chose compound 1a to study the
reaction by 19F NMR spectroscopy. Indeed, when the order of addition of the reagents to
compound 1a in dichloromethane-d2 was reversed, i.e. first addition of triethylamine followed
by TMSOTf, the formation of the intermediate (Z)-ketene trimethylsilyl acetal was faster (19F
NMR spectroscopy, see SI) and after refluxing for 24 hours and work-up, the yield of 2a was
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increased from 65% under the original conditions10 to 93% (19F NMR spectroscopy) (Scheme
7, Figure 1).
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Scheme 7. Results of the treatment of 1a and 9a under the optimized reaction conditions.
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original reaction conditions
(1. TMSOTf, 2. Et3N)
new reaction conditions
(1. Et3N, 2. TMSOTf)
Figure 1. Comparison of the results of [3,3]-sigmatropic rearrangement of 1a under the
original (1. TMSOTF, 2. Et3N, top) and the new (1. Et3N, 2. TMSOTf, bottom) reaction
conditions (SF5-part of 19F NMR spectra after work up).
In contrast, the allylic ester 9a, which yielded oligomeric products under the original
conditions,10 did not react under these new conditions (Scheme 7).
It is surprising that 9a and also 9b did not rearrange with Et3N/TMSOTf since DFT
calculations (TPSS-D3/def2-TZVP + COSMO) show that the methylene protons of 9a and 9b
should be significantly more acidic than those of 9c. This was estimated by the free energies
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of proton transfer from the model esters C, D, and E to the cyclopentadienyl anion
(cyclopentadiene: pKa = 18, in CH2Cl2) forming ester enolates (Table 2, for details see SI).
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Table 2. Calculated free energies of proton transfer [kcal/mol, 298 K] to model (E)- and
(Z)-ester enolates and pKa values of substituted acetic acid esters in CH2Cl2.
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Anion
Ester enolates C
Ester enolates D
Ester enolates E
(E)
(Z)
(E)
(Z)
(E)
(Z)
16.5
-2.01
pKa
33.4
20.97
32.6
19.9
2.54
19.6
2.18
16.1
19.86
-2.58
G298
Moreover, when comparing the activation energies for the [3,3]-sigmatropic
rearrangements of the ketene silylacetal of 9a with that of model compounds A and B
(derived from the SF5-acetic esters of 2-fluoro-but-1-en-3-ol and but-1-en-3-ol, see SI), it
becomes clear that all rearrangements should proceed. In all cases the (E)-ketene
trimethylsilyl acetals are thermodynamically favored by 1-2 kcal/mol over the (Z)-ketene
trimethylsilyl acetals (Table 3).
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Table 3. Relative energies of (Z/E)-isomeric ketene trimethylsilyl acetals and chair and
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boat transition states of [3,3]-sigmatropic rearrangements
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Ketene
TSchair
TSboat
TSchair
TSboat
G298
[kcal/mol]
(E)
G298
[kcal/mol]
(Z)
trimethylsilyl
acetals
[kcal/mol] [kcal/mol]
[kcal/mol] [kcal/mol]
(E)
(E)
(Z)
(Z)
0.0
22.9
26.9
24.8
18.1
23.3
21.3
2.0
14.9
18.2
16.8
20.3
22.0
20.4
9a
A
0.0
0.9
0.0
1.2
B
In all cases the activation energies for the transformation of the (Z)-ketene trimethylsilyl
acetals to the favored chair transition states of [3,3]-sigmatropic rearrangements are 4-5
kcal/mol lower in energy than those of the boat transition states. Moreover, the activation
energy for the transformation of the (E)-ketene trimethylsilyl acetals to the favored boat
transition states is 3-5 kcal/mol higher in energy when compared to the activation energy for
the transformation of the (Z)-ketene trimethylsilyl acetals to their chair transition states. As
previously stated from NMR experiments with 1a,10 and proved by the present calculations,
the rearrangement is proceeding exclusively via the corresponding (Z)-ketene trimethylsilyl
acetal, while the (E)-ketene trimethylsilyl acetal did not rearrange. The latter was hydrolyzed
to the starting ester 1a during aqueous work up. Thus, from an energetic point of view, the
phenyl-substituted ester 9a should rearrange more easily, provided that the ester enolates were
formed at all under the respective reaction conditions.
Fortunately, the undesired oligomerization reactions of cinnamyl acetates 7 occurring
under the original reaction conditions10 could be suppressed by using the new conditions and
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thereby avoiding an acidic environment. In this case [3,3]-sigmatropic rearrangements
resulted in the formation of almost 1:1 mixtures of the target diastereoisomeric products 8
(Table 4). In analogy to our earlier studies,10 the amount of the carboxylic acids 8 in the crude
reaction mixture was determined by 19F NMR spectroscopy. Subsequent conversion of the
acids 8 into the methyl esters 15 allowed for a simpler isolation and purification of the γ,δ-
unsaturated α-substituted carboxylic esters by column chromatography. Surprisingly, the
initially used alkylation method (K2CO3, MeI, DMF, 0 °C, 3 h) did not exclusively give the
target methyl esters 15, since the SF5-group served as a leaving group24 and was partially
substituted by a formate group, probably via an intermediate -lactone (see SI). Therefore, the
carboxylic acids 8 were treated with methanol in the presence of DCC and a catalytic amount
of DMAP18 (Table 4).
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Table 4. Synthesis of α-substituted carboxylic acids 8 and by Ireland-Claisen
rearrangements and esterification to 15.
Entry Esters
Y
R
Acids Yield
dr[a]
Esters Yield
dr[a]
[%][a]
[%][b]
7
8
15
1
2
3
4
5
6
7
SF5
CF3
CH3
SF5
CF3
SF5
CF3
H
92
94
62:38
54:46
40
35
33
45
30
22
22
47:53
54:46
30:70[d]
39:61
56:44
49:51
52:48
7a
7b
7c
7d
7e
7f
8a
8b
8c
8d
8e
8f
15a
15b
15c
15d
15e
15f
H
[c]
[c]
H
-
-
F
92
75
68
78
52:48
55:45
63:37
49:51
F
CH3
CH3
7g
8g
15g
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[a] Determined by 19F NMR spectroscopy; [b] isolated yield over two steps; [c] not
determined; [d] determined by GC.
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The esters 7 were rearranged to the corresponding carboxylic acids 8 in 68-94% yields (19F
NMR spectroscopy), whereby no significant influence of the SF5- and CF3-substituents on the
conversion of the starting materials has been observed. All carboxylic acids 8 were obtained
as approximate 1:1-mixtures of both diastereomers. Unfortunately, we were not able to
separate the acids or the esters in order to assign the syn/anti-configurations to specific
compounds.
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In order to find an explanation for the observed low diastereoselectivity, DFT calculations
(PW6B95-D3//TPSS-D3/def2-TZVP + COSMO solvation model), were carried out (for
details see SI). As a model system, the Ireland-Claisen rearrangement of the SF5-substituted
allylic ester 7a to the corresponding carboxylic acids 8a was chosen, and all four possible
transition states – depending on the original geometry of the ketene trimethylsilyl acetal [(Z)-
/(E)-configuration] as well as on the feasible geometry of the transition states itself (chair-
/boat-conformation) – were determined (see SI). The four different transition states are shown
in Figure 2 along with the relative energies and the corresponding free energy barriers (ΔG‡)
for the [3,3]-sigmatropic rearrangement reaction.
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TS I (Z)/chair
TS II (Z)/boat
0.0 kcal/mol
0.4 kcal/mol
ΔG‡ = +19.1 kcal/mol
ΔG‡ = +19.5 kcal/mol
TS III (E)/chair
1.6 kcal/mol
TS IV (E)/boat
0.5 kcal/mol
ΔG‡ = +20.6 kcal/mol
ΔG‡ = +19.5 kcal/mol
Figure 2. Optimized transition states (DFT) of the Ireland-Claisen rearrangement of the
model compound 7a with Et3N/TMSOTf to form diastereomeric acids 8a.
The calculated relative energies indicate that the formation of acids 8 is generally possible
via all four transition states, although the transition states I, II, and IV are energetically
slightly favored. Furthermore, the free energy barriers suggest that the rearrangement reaction
is more likely to proceed via the two (Z)-configurated transition states I and II with the lowest
energy barriers resulting in either the syn- or the anti-diastereoisomer. However, transition
states III and IV would lead to a similar product ratio of syn- and anti-isomers. Scheme 8
shows the anticipated mechanistic pathway – based on the DFT calculations – for the
rearrangement of compound 7a with the (Z)-ketene trimethylsilyl acetal as favored
intermediate.
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Scheme 8. Anticipated mechanistic pathway of the Ireland-Claisen rearrangement of
compound 7a with Et3N/TMSOTf.
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Conclusions
Ireland-Claisen rearrangements of SF5- and CF3-substituted acetic acid cinnamyl esters 7 have
been investigated. While treatment with trimethylsilyl triflate (TMSOTf) followed by Et3N
and subsequent refluxing in dichloromethane resulted in oligomerization, avoiding initial
acidic conditions by reversing the addition sequence of reagents enabled the formation of the
target diastereomeric 3-aryl-2-pentafluorosulfanylpent-4-enoic and 3-aryl-2-trifluoromethyl-
pent-4-enoic acids 8 in good yields. The reaction products were obtained as approximate 1:1-
mixtures of syn- and anti-isomers. The unexpected low diastereoselectivity is explained by
similar energies of the intermediate (E)- and (Z)-ketene trimethylsilyl acetals and very tiny
differences of energy barriers (DFT calculations) for the different transition states of the [3,3]-
sigmatropic rearrangement reactions. Applying the new reaction conditions to the
rearrangement of the SF5-substituted acetic acid ester 1a of 2-fluorododec-1-en-3-ol resulted
in a higher yield of product 2a due to faster formation of the rearranging (Z)-ketene
trimethylsilyl acetal. The corresponding esters of 1-phenyl-prop-2-en-1-ol 9a and 9b failed to
rearrange even under the new conditions.
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Experimental Section
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8
General remarks: All reactions involving air and/or moisture sensitive compounds were
performed under argon atmosphere applying the Schlenk technique. DCM was dried over
CaH2 and distilled. THF was freshly distilled over sodium and benzophenone. TLC was
performed on coated silica gel plates Merck 60 F254. The spots were detected with alkaline
KMnO4 solution. For the purification of the compounds by column chromatography, silica gel
Merck 60 (0.063-0.2 mm) was used. Solvents for chromatography were purified prior to use.
The NMR spectra were recorded either at 300 MHz, 400 MHz, or 500 MHz spectrometers. 1H
NMR spectra were referenced to TMS, 13C NMR spectra to the used deuterated solvent
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CDCl3 or CD2Cl2, and F NMR spectra to CFCl3 as the internal standards. Actually, the SF5
group is an AB4 spin pattern, although with high-field NMR spectrometers this pattern moves
toward AX4 so that the A part, which is given by the single axial fluorine atom, is marked as a
quintet (qn). In all cases the signal of the four equatorial fluorine atoms appeared as a doublet
of multiplets (dm). The coupling between the axial and the equatorial fluorine atoms
correlates with the doublet coupling constant. Electrospray ionization (ESI) mass
spectrometry was performed on a MicroToF spectrometer. 1-Phenylprop-2-en-1-ol,25 1-(4-
fluorophenyl)prop-2-en-1-ol,26 1-(naphthalen-1-yl)prop-2-en-1-ol,27 and 1-phenylprop-2-en-1-
yl-(2-pentafluorosulfanyl)acetate (9a)10 were synthesized according to known procedures. The
spectroscopic data are in agreement with published ones. The allylic alcohols 5b and 5c12
were prepared in two-steps from the corresponding cinnamic acids 3b and 3c via the
corresponding methyl esters 4b28and 4c.29
DFT Calculations: All calculations were performed with the TURBOMOLE program (6.6).30
The structures were optimized without any geometry constraints using the TPSS functional31
and an atom-pairwise dispersion correction (D3).32,33 A flexible triple zeta basis set (def2-
TZVP)34 was used in all calculations. For the calculation of zero point vibrational energies
and free enthalpy contributions, a rotor approximation was applied for vibrational modes with
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wavenumbers below 100 cm-1.35 In addition, in the Ireland-Claisen reactions, single point
calculations were performed with the hybrid functional PW6B95(-D3).36 Implicit solvation
was taken into account in these single point calculations with the COSMO model37 as
implemented in Turbomole (ε = 9.08, CH2Cl2).
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General procedure for the synthesis of allylic esters 7: DCC (1.2 equiv) was dissolved in
dry DCM (8 mL) before the allylic alcohol 5 (1.2 mmol, 1.0 equiv) followed by the
corresponding carboxylic acid (1.2 equiv) were added under argon atmosphere. A white
precipitate was formed and a catalytic amount of DMAP was added. The mixture was stirred
at rt overnight. The suspension was diluted with Et2O (25 mL) before the formed urea
derivative was filtered off. The remaining solution was washed with H2O (3  10 mL), 5%
acetic acid (3  10 mL), and brine (3  10 mL) and dried over MgSO4 before the solvent was
removed under reduced pressure. The crude products were purified by column
chromatography as indicated below.
Cinnamyl 2-(pentafluorosulfanyl)acetate (7a). The allylic ester 7a was prepared according to
the aforementioned general procedure starting from cinnamyl alcohol (5a) (150 mg, 1.12
mmol) and 2-(pentafluorosulfanyl)acetic acid (6a)17 (259 mg, 1.39 mmol). After column
chromatography (cyclohexane/EtOAc, 5:1) the target product was obtained as a colorless oil.
1
Yield: 297 mg (88%). H NMR (400 MHz, CDCl3): δ 7.48 – 7.17 (m, 5H), 6.70 (dt,
J = 15.9 Hz, J = 1.4 Hz, 1H), 6.27 (dt, J = 15.7 Hz, J = 6.7 Hz, 1H), 4.85 (dd, J = 6.6 Hz,
J = 1.3 Hz, 2H), 4.33 (qn, J = 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 162.1 (qn,
19
J = 4.5 Hz,), 135.9, 135.9, 128.8, 128.6, 126.9, 121.5, 70.7 (qn, J = 16.9 Hz), 67.3. F NMR
(282 MHz, CDCl3): δ 79.0 (qn, 1F), 71.0 (dm, J = 147.8 Hz, 4F). MS-ESI: m/z 325.0292
[M+Na]+ calcd. for C11H11F5O2SNa+ 325.0292.
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Cinnamyl 3,3,3-trifluoropropanoate (7b). The allylic ester 7b was prepared according to the
aforementioned general procedure starting from cinnamyl alcohol (5a) (150 mg, 1.12 mmol)
and 3,3,3-trifluoropropanoic acid (6b) (178 mg, 1.39 mmol). After column chromatography
(cyclohexane/EtOAc, 5:1) the target product was obtained as a colorless liquid. Yield: 236 mg
(87%). 1H NMR (300 MHz, CDCl3): δ 7.45 – 7.22 (m, 5H), 6.68 (dt, J = 15.9 Hz, J = 1.3 Hz,
1H), 6.26 (dt, J = 15.9 Hz, J = 6.5 Hz, 1H), 4.82 (dd, J = 6.5 Hz, J = 1.3 Hz, 2H), 3.21 (q,
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J = 10.1 Hz, 2H). C NMR (75 MHz, CDCl3): δ 164.1 (q, J = 4.2 Hz), 136.0, 135.4, 128.8,
128.5, 126.8, 123.4 (q, J = 276.2 Hz,), 122.0, 66.5, 39.7 (q, J = 31.1 Hz). 19F NMR
(282 MHz, CDCl3): δ -63.4 (t, J = 10.1 Hz, 3F). MS-ESI: m/z 267.0602 [M+Na]+ calcd. for
C12H11F3O2Na+ 267.0603.
Cinnamyl propionate (7c). The allylic ester 7c was prepared according to the aforementioned
general procedure starting from cinnamyl alcohol (5a) (219 mg, 1.63 mmol) and propionic
acid (6c) (144 mg, 1.95 mmol). After column chromatography (cyclohexane/EtOAc, 10:1) the
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target product was obtained as a colorless liquid. Yield: 275 mg (89%). H NMR (300 MHz,
CDCl3): δ 7.43 – 7.20 (m, 5H), 6.64 (dt, J = 15.9 Hz, J = 1.4 Hz, 1H), 6.28 (dt, J = 15.9 Hz,
J = 6.4 Hz, 1H), 4.73 (dd, J = 6.4 Hz, J = 1.4 Hz, 2H), 2.37 (q, J = 7.6 Hz, 2H), 1.16 (t,
J = 7.6 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 174.3, 136.3, 134.1, 128.7, 128.1, 126.7,
123.4, 65.0, 27.7, 9.2. The spectroscopic data agree with those given in the literature.16 MS-
ESI: m/z 213.0882 [M+Na]+ calcd. for C12H14O2Na+ 213.0886.
(E)-4-Fluorocinnamyl 2-(pentafluorosulfanyl)acetate (7d). The allylic ester 7d was prepared
according to the aforementioned general procedure starting from (E)-3-(4-fluorophenyl)prop-
2-en-1-ol (5b) (150 mg, 0.99 mmol) and 2-(pentafluorosulfanyl)acetic acid (6a) (221 mg, 1.19
mmol). After column chromatography (cyclohexane/EtOAc, 5:1) the target product was
1
obtained as a clear liquid. Yield: 189 mg (60%). H NMR (400 MHz, CDCl3): δ 7.43 – 7.29
(m, 2H), 7.10 – 6.93 (m, 2H), 6.67 (dt, J = 15.8 Hz, J = 1.3 Hz, 1H), 6.19 (dt, J = 15.9 Hz,
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J = 6.7 Hz, 1H), 4.84 (dd, J = 6.7 Hz, J = 1.3 Hz, 2H), 4.34 (qn, J = 7.7 Hz, 2H). C NMR
(100 MHz, CDCl3): δ 162.9 (d, J = 248.0 Hz), 162.1 (qn, J = 4.6 Hz), 134.7, 132.1, 128.5 (d,
J = 8.2 Hz), 121.2 (d, J = 2.3 Hz), 115.8 (d, J = 21.8 Hz), 70.7 (qn, J = 16.9 Hz), 67.2. 19F
NMR (282 MHz, CDCl3): δ 79.0 (qn, 1F), 71.0 (dm, J = 147.7 Hz, 4F), -113.6 (tt, J = 8.6 Hz,
J = 4.3 Hz, 1F). MS-ESI: m/z 343.0203 [M+Na]+ calcd. for C11H10F6O2SNa+ 343.0198.
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(E)-4-Fluorocinnamyl 3,3,3-trifluoropropanoate (7e). The allylic ester 7e was prepared
according to the aforementioned general procedure starting from (E)-3-(4-fluorophenyl)prop-
2-en-1-ol (5b) (150 mg, 0.99 mmol) and 3,3,3-trifluoropropanoic acid (6b) (152 mg, 1.19
mmol). After column chromatography (cyclohexane/EtOAc, 5:1) the target product was
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obtained as a clear oil. Yield: 152 mg (59%). H NMR (400 MHz, CDCl3): δ 7.40 – 7.31 (m,
2H), 7.09 – 6.95 (m, 2H), 6.64 (dt, J = 15.8 Hz, J = 1.3 Hz, 1H), 6.19 (dt, J = 15.9 Hz,
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J = 6.5 Hz, 1H), 4.81 (dd, J = 6.6 Hz, J = 1.3 Hz, 2H), 3.22 (q, J = 10.1 Hz, 2H). C NMR
(100 MHz, CDCl3): δ 164.1 (q, J = 4.3 Hz), 162.9 (d, J = 247.8 Hz), 134.2, 132.2 (d,
J = 3.3 Hz), 128.4 (d, J = 8.2 Hz), 123.5 (q, J = 276.2 Hz), 121.8 (d, J = 2.3 Hz), 115.8 (d,
J = 21.7 Hz), 66.3, 39.8 (q, J = 31.1 Hz). 19F NMR (282 MHz, CDCl3): δ -63.9 (t,
J = 10.1 Hz, 3F), -113.6 – -113.8 (m, 1F). MS-ESI: m/z 285.0518 [M+Na]+ calcd. for
C12H10F4O2Na+ 285.0509.
(E)-4-Methylcinnamyl 2-(pentafluorosulfanyl)acetate (7f). The allylic ester 7f was prepared
according to the aforementioned general procedure starting from (E)-3-(p-tolyl)prop-2-en-1-ol
(5c) (150 mg, 1.01 mmol) and 2-(pentafluorosulfanyl)-acetic acid (6a) (150 mg, 1.01 mmol).
After column chromatography (cyclohexane/EtOAc, 5:1) the target product was obtained as a
clear liquid. Yield: 225 mg (83%).1H NMR (400 MHz, CDCl3): δ 7.32 – 7.27 (m, 2H), 7.17 –
7.12 (m, 2H), 6.67 (dt, J = 15.7 Hz, J = 1.3 Hz, 1H), 6.22 (dt, J = 15.8 Hz, J = 6.7 Hz, 1H),
4.84 (dd, J = 6.8 Hz, J = 1.3 Hz, 2H), 4.32 (qn, J = 7.7 Hz, 2H), 2.34 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 162.1 (qn, J = 4.5 Hz), 138.6, 135.9, 133.1, 129.5, 126.8, 120.4, 70.7
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(qn, J = 17.0 Hz), 67.5, 21.3. 19F NMR (282 MHz, CDCl3): δ 79.0 (qn, 1F), 70.9 (dm,
J = 147.7 Hz, 4F). MS-ESI: m/z 339.0449 [M+Na]+ calcd. for C12H13F5O2SNa+ 339.0449.
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(E)-4-Methylcinnamyl 3,3,3-trifluoropropanoate (7g). The allylic ester 7g was prepared
according to the aforementioned general procedure starting from (E)-3-(p-tolyl)prop-2-en-1-ol
(5c) (150 mg, 1.01 mmol) and 3,3,3-trifluoropropanoic acid (6b) (155 mg, 1.21 mmol). After
column chromatography (cyclohexane/EtOAc, 5:1) the target product was obtained as a clear
liquid. Yield: 221 mg (85%).1H NMR (400 MHz, CDCl3): δ 7.31 – 7.26 (m, 2H), 7.18 – 7.07
(m, 2H), 6.65 (dt, J = 15.7 Hz, J = 1.3 Hz, 1H), 6.21 (dt, J = 15.8 Hz, J = 6.6 Hz, 1H), 4.81
(dd, J = 6.7 Hz, J = 1.3 Hz, 2H), 3.20 (q, J = 10.1 Hz, 2H), 2.34 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 164.1 (q, J = 4.2 Hz), 138.4, 135.4, 133.2, 129.5, 126.7, 123.5 (q, J = 275.8 Hz),
120.9, 66.6, 39.7 (q, J = 30.9 Hz), 21.4. 19F NMR (282 MHz, CDCl3): δ -63.5 (t, J = 10.1 Hz,
3F). MS-ESI: m/z 281.0765 [M+Na]+ calcd. for C13H13F3O2Na+ 281.0760.
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General procedure for the Ireland-Claisen rearrangements: The corresponding allylic
ester (1.00 mmol, 1.00 equiv) was dissolved in dry DCM (3 mL) and Et3N (3.0 equiv)
followed by TMSOTf (1.2 equiv) were added to a sealable tube. The tube was sealed, and the
reaction mixture was heated at 40 °C for 24 h. The sealed tube was then opened and Et2O
(20 mL) and 2 M HCl (10 mL) were added to the solution, and the mixture was stirred at rt for
3 h (elimination of the TMS group). The phases were separated, and the aqueous layer was
extracted with Et2O (3 × 20 mL). The combined organic layers were washed with 2 M HCl
(20 mL) and brine (20 mL) and dried over MgSO4 before the solvent was removed under
vacuum. The produced crude diastereomeric carboxylic acids 8 were investigated by 19F
NMR spectroscopy and by ESI mass spectrometry and used without purification for the
esterification reaction to obtain the diastereomeric methyl esters 15.
2-(Pentafluorosulfanyl)-3-phenylpent-4-enoic acids (8a). According to the general procedure
cinnamyl 2-(pentafluorosulfanyl)acetate (7a) (0.151 g, 0.50 mmol, 1.0 equiv) was rearranged.
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The formed product was analyzed and subsequently alkylated without purification. Yield:
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0.172 g (crude, 93% of 8a, F NMR). F NMR (282 MHz, CDCl3): δ 67.7 and 67.9 (dm,
2JF,F = 147.2 Hz and 2JF,F = 146.9 Hz, 4F), 80.8 and 81.2 (qn, 2JF,F = 147.7 Hz or 2JF,F = 147.0
Hz, 1F). MS-ES(+)-EM: calcd for C11H11F5O2SNa+: m/z = 325.0308 [M+Na]+, found
325.0292. MS-ES()-EM calcd for C11H10F5O2S: m/z = 301.0316 [M-H] found 301.0327.
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2-(Trifluoromethyl)-3-phenylpent-4-enoic acids (8b). According to the general procedure (E)-
cinnamyl 3,3,3-trifluoropropanoate (7b) (0.122 g, 0.50 mmol, 1.0 equiv) was rearranged. The
formed product was analyzed and subsequently alkylated without purification. Yield: 0.118 g
(crude, 52% of 8b, 19F NMR). 19F NMR (282 MHz, CDCl3): δ -64.2 and -63.8 (d or dd,
3JH,F = 7.5 Hz or 3JH,F = 7.7 Hz, 4JH,F = 1.3 Hz, 3F). MS-ES(+)-EM: calcd for C12H11F3O2Na+:
m/z = 267.0604 [M+Na]+, found 267.0603. MS-ES(-)-EM calcd for C12H10F3O2 : m/z =

243.0644 [M-H], found 243.0638.
3-(4-Fluorophenyl)-2-(pentafluorosulfanyl)pent-4-enoic acids (8d). According to the general
procedure (E)-4-fluorocinnamyl 2-(pentafluorosulfanyl)acetate (7d) (0.128 g, 0.40 mmol,
1.0 equiv) was rearranged. The formed product was analyzed and subsequently alkylated
without purification. Yield: 0.153 g (crude, 90% of 8d, 19F NMR). 19F NMR (282 MHz,
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CDCl3): δ -115.3 and -114.6 (tt, JH,F = 8.5 Hz, JH,F = 5.2 Hz, 1F), 67.7 and 67.8 (dm,
2JF,F = 147.1 Hz or JF,F = 147.0 Hz, 4F), 80.8 and 81.3 (qn, JF,F = 148.2 Hz or
2JF,F = 146.9 Hz, 1F). MS-ES(+)-EM: calcd for C11H10F6O2SNa+: m/z = 343.0210 [M+Na]+,
found 343.0198. MS-ES(-)-EM: calcd for C11H9F6O2S: m/z = 319.0239 [M-H], found
319.0233.
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2-(Trifluoromethyl)-3-(4-fluorophenyl)pent-4-enoic acids (8e). According to the general
procedure (E)-4-fluorocinnamyl 3,3,3-trifluoropropanoate (7e) (0.262 g, 1.00 mmol,
1.0 equiv) was rearranged. The formed product was analyzed and subsequently alkylated
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without purification. Yield: 0.225 g (crude, 16% of 8e, 19F NMR). 19F NMR (282 MHz,
CDCl3): δ -114.8 and -114.6 (tt, 3JH,F = 8.8 Hz, 4JH,F = 5.4 Hz or 3JH,F = 8.6 Hz, 4JH,F = 5.3 Hz,
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1F, 9-CF), -64.7 and -64.4 (d or dd, JH,F = 7.6 Hz or JH,F = 7.8 Hz, JH,F = 1.3 Hz, 3F, 12-
CF3). MS-ES(+)-EM: calcd. for C12H10F4O2Na+: m/z = 285.0514 [M+Na]+, found 285.0509.
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MS-ES(-)-EM: calcd. for C12H9F4O2 , m/z = 261.0543 [M-H] found 261.0544.
2-(Pentafluorosulfanyl)-3-(p-tolyl)pent-4-enoic acids (8f). According to the general procedure
(E)-4-methylcinnamyl 2-(pentafluorosulfanyl)acetate (7f) (0.158 g. 0.50 mmol, 1.0 equiv)
was rearranged. The formed product was analyzed and subsequently alkylated without
purification. Yield: 0.135 g (crude, 84% of 8f, 19F NMR). 19F NMR (282 MHz, CDCl3): δ
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67.7 and 67.8 (dm, JF,F = 147.3 Hz or JF,F = 146.9 Hz, 4F), 80.8 and 81.2 (qn,
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2JF,F = 147.1 Hz or JF,F = 147.1 Hz, 1F). MS-ES(+)-EM: calcd. for C12H13F5O2SNa+: m/z =
339.0447 [M+Na]+, found 339.0449. MS-ES(-)-EM: calcd. for C12H12F5O2S: m/z = 315.0483
[M-H], found 315.0484.
2-(Trifluoromethyl)-3-(p-tolyl)pent-4-enoic acids (8g). According to the general procedure
(E)-4-methylcinnamyl 3,3,3-trifluoropropanoate (7g) (0.258 g, 1.00 mmol, 1.0 equiv) was
rearranged. The formed product was analyzed and subsequently alkylated without
purification. Yield: 0.220 g (crude, 57% of 8g, 19F NMR). 19F NMR (282 MHz, CDCl3): δ
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-64.7 and -64.3 (d or dd, JH,F = 7.5 Hz or JH,F = 7.7 Hz, JH,F = 1.3 Hz, 3F). MS-ES(+)-EM:
calcd for C13H13F3O2Na+: m/z = 281.0758 [M+Na]+, found 281.0760. MS-ES(-)-EM: calcd.

for C13H12F3O2 , m/z = 257.0805 [M-H], found 257.0795.
Methylation of carboxylic acids 8 with K2CO3/MeI in DMF
The rearrangement products 8 have been difficult to isolate. Therefore, we preferred to
methylate them with methyl iodide. First, we attempted methylation with potassium carbonate
in DMF. However, under these conditions, the yields of the desired SF5-substituted methyl
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esters 15 were rather low, and side products were formed in yields up to 50% (determined by
GC). By way of example, the crude product mixture 8f was treated with K2CO3/DMF/MeI,
and the product mixture was separated by repeated column chromatography. Besides the
fraction of the target diastereomeric SF5-substituted esters 15f, we also isolated a fraction of
an 1:1 mixture of the diastereomeric methyl α-formyl carboxylates, which could not be
separated. Thus, the SF5 group is a leaving group under these conditions. In the literature,
several examples have been reported where the SF5 group served as a leaving group,38 and we
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found other examples more recently.24 The decomposition of the SF5 anion to generate
fluoride and SF4 and subsequent decomposition of SF4 might be a driving force for the
reaction.39
Procedure for methylation of carboxylic acids 8f with MeI/K2CO3 in DMF. A stirred
suspension of the diastereomeric acids 8f (135 mg, 0.427 mmol) and K2CO3 (88 mg,
0.640 mmol) in DMF (2.0 mL) was cooled to 0 °C, and methyl iodide (0.05 mL, 0.854 mmol)
was added slowly. Stirring was continued at 0 °C for 3 h. Then the reaction was stopped by
the addition of water (10 mL). The mixture was extracted with diethyl ether (3  10 mL). The
organic layers were combined, washed once with water (10 mL) and with brine (4  5 mL),
and dried over MgSO4. The solvent was removed under reduced pressure, and the resulting
crude clear oil (104 mg) was purified by column chromatography on silica gel
(pentane/diethyl ether, 20:1). After three runs, a mixture of the SF5-substituted esters 15f
(12 mg, 8%, see below) and a mixture of the formates A and B were isolated. Yield: 39 mg
(37%). The relative configuration could not be assigned to the respective isomers A and B.
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Isomer A: H NMR (400 MHz, CDCl3): δ = 8.08 (t, JH,H = 0.9 Hz, 1H), 7.18-7.10 (m, 4H),
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6.17 (ddd, JH,Htrans = 17.0, JH,Hcis = 10.3, JH,H = 8.7 Hz, 1H), 5.43 (dd, JH,H = 6.8 Hz,
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4JH,H = 1.0 Hz, 1H), 5.23 (ddd, JH,Hcis = 10.3, JH,Hgem = 1.5 Hz, JH,H = 0.8 Hz, 1H), 5.19
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(ddd, JH,Htrans = 16.9, JH,Hgem = 1.3 Hz, JH,H = 1.3 Hz, 1H,), 3.92-3.88 (m, 1H, 3-CH), 3.67
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(s, 3H, 6-CH3), 2.30 (s, 3H) ppm. 13C NMR (121 MHz, CDCl3): δ = 168.9 (s), 160.1 (s),
137.2 (s), 135.7 or 132.2 (s),134.9 (d), 129.5 (d), 128.4 or 128.0 (d,), 118.7 (t), 74.8 (d), 52.5
or 52.3 (q), 50.9 (d), 21.2 (q).
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Isomer B: H NMR (400 MHz, CDCl3): δ = 8.05 (t, JH,H = 0.9 Hz, 1H), 7.18-7.10 (m, 4H),
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6.03 (ddd, JH,Htrans = 17.0, JH,Hcis = 10.3, JH,H = 8.0 Hz), 5.41 (dd, JH,H = 4.8 Hz,
4JH,H = 1.0 Hz, 1H), 5.16 (ddd, JH,Hcis = 10.3, JH,Hgem = 1.1 Hz, JH,H = 1.1 Hz, 1H), 5.14
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2.30 (s, 3H) ppm. 13C NMR (121 MHz, CDCl3): δ = 168.8 (s), 160.1 (s), 137.2 (s), 136.1 (d),
135.7 (s) or 132.2 (s), 129.5 (d), 128.4 (d) or 128.0 (d), 117.8 (t), 75.2 (d), 52.5 (q) or 52.3 (q),
50.6 (d), 21.2 (q).
ESI-MS+ (for isomers A and B): calcd. for [C14H16O4+Na]+ m/z = 271.0941, found: 271.0951
[M+Na]+.
Therefore, the methyl esters 15 were prepared analogously to the allylic esters. DCC
(1.2 equiv) was dissolved in dry DCM (5 mL) before MeOH (1.0 equiv) followed by the
corresponding carboxylic acids 8 (0.5 mmol, 1.0 equiv) were added under argon atmosphere.
A white precipitate was formed and a catalytic amount of DMAP was added. The mixture was
stirred at rt overnight. The suspension was diluted with Et2O (20 mL) before the formed urea
derivative was filtered off. The remaining solution was washed with H2O (3  10 mL), 5%
acetic acid (3  10 mL), and brine (3  10 mL) and dried over MgSO4 before the solvent was
removed under reduced pressure, and the mixture of diastereomeric methyl esters 15 was
purified as described for the particular compounds.
Methyl 2-(pentafluorosulfanyl)-3-phenylpent-4-enoates (15a). The title compounds were
prepared according to the aforementioned general procedure starting from cinnamyl 2-
(pentafluorosulfanyl)acetate (7a) (120 mg, 0.40 mmol) over two steps. After column
chromatography (cyclohexane/EtOAc, 10:1) the target product was obtained as a clear oil.
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Yield: 51 mg (40%). H NMR (300 MHz, CDCl3): δ 7.37 – 7.13 (m, 5H), 6.16 – 5.98 (m,
1H), 5.20 – 5.07 (m, 2H), 4.89/4.88 (qn/dqn, J = 5.9 Hz/J = 11.2 Hz, J = 5.9 Hz, 1H), 4.29 –
4.19 (m, 1H), 3.74/3.43 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 165.2/164.8 (qn,
J = 3.1 Hz/J = 3.5 Hz), 139.7 (qn, J = 1.5 Hz)/139.2, 137.9 (qn, J = 1.4 Hz)/135.9,
129.2/129.0, 128.0/127.7, 127.8/127.5, 118.6/116.6, 89.3/88.8 (qn, J = 9.2 Hz), 53.2/53.0,
51.8/51.4 (qn, J = 2.2 Hz). 19F NMR (282 MHz, CDCl3): δ 81.8/81.3 (qn, 1F), 67.3/67.1 (dm,
J = 146.8 Hz/J = 147.1 Hz). MS-ESI: m/z 339.0456 [M+Na]+ calcd. for C12H13F5O2SNa+
339.0449.
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Methyl 3-phenyl-2-(trifluoromethyl)pent-4-enoates (15b). The diastereomeric target
compounds were prepared according to the aforementioned general procedure starting from
cinnamyl 3,3,3-trifluoropropanoate (7b) (157 mg, 0.64 mmol) over two steps. After column
chromatography (cyclohexane/EtOAc, 10:1) the target product was obtained as a clear oil.
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Yield: 44 mg (35%). H NMR (300 MHz, CDCl3): δ 7.37 – 7.15 (m, 5H), 6.10 – 5.91 (m,
1H), 5.26 – 5.06 (m, 2H), 4.02 – 3.88 (m, 1H), 3.74/3.43 (s, 3H), 3.61/3.59 (dq, J = 10.7 Hz,
J = 7.7 Hz/ J = 11.2 Hz, J = 7.8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 167.2/166.9 (q,
J = 3.5 Hz/J = 3.4 Hz), 139.3/139.2, 136.9, 129.0/129.0, 127.9/127.8, 127.6/127.6,
124.2/124.1 (q, J = 281.5 Hz), 117.6/117.5, 56.0/56.0 (q, J = 25.9 Hz/J = 25.8 Hz), 52.7/52.6,
48.9/48.4 (q J = 1.9 Hz/J = 1.5 Hz). 19F NMR (282 MHz, CDCl3): δ -64.8/-64.4 (d/dd,
J = 7.6 Hz/J = 7.8 Hz, J = 1.3 Hz, 3F). MS-ESI: m/z 281.0767 [M+Na]+ calcd. for
C13H13F3O2Na+ 281.0760.
Methyl 2-methyl-3-phenylpent-4-enoates (15c). The diastereomeric target compounds were
prepared according to the aforementioned general procedure starting from cinnamyl
propionate (7c) (125 mg, 0.66 mmol) over two steps. After column chromatography
(cyclohexane/EtOAc, 10:1) the target product was obtained as a clear oil. Yield: 45 mg
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(33%). H NMR (400 MHz, CDCl3): δ 7.34 – 7.15 (m, 5H), 6.00/5.93 (ddd, J = 17.1,
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J = 10.3 Hz, J = 8.4 Hz/ J = 17.3, J = 10.4 Hz, J = 9.7 Hz 1H), 5.13/5.05 (ddd/dt, J = 16.9 Hz,
J = 1.6 Hz, J = 0.9 Hz/J = 10.0 Hz, J = 1.3 Hz, 1H), 5.11/5.01 (dd/ddd, J = 10.0 Hz,
J = 1.5 Hz/J = 10.1 Hz, J = 1.6 Hz, J = 0.8 Hz), 3.53 – 3.40 (m, 1H), 3.68/3.43 (s, 3H),
1.22/0.97 (d, J = 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 176.2/175.9, 142.4/141.4,
139.9/138.7, 128.9/128.6, 128.2/127.7, 126.9/126.7, 116.9/115.6, 53.9/53.8, 51.6/51.5,
45.4/45.1, 16.0/15.7. MS-ESI: m/z 227.1057 [M+Na]+ calcd. for C13H16O2Na+ 227.1043.
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Methyl 3-(4-fluorophenyl)-2-(pentafluorosulfanyl)pent-4-enoates (15d). The diastereomeric
target compounds were prepared according to the aforementioned general procedure starting
from (E)-3-(4-fluorophenyl)allyl 2-(pentafluorosulfanyl)acetate (7d) (150 mg, 0.47 mmol)
over two steps. After column chromatography (cyclohexane/EtOAc, 10:1) the target product
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was obtained as a clear oil. Yield: 70 mg (45%). H NMR (300 MHz, CDCl3): δ 7.23 – 6.94
(m, 4H), 6.13 – 5.95 (m, 1H), 5.19 – 5.08 (m, 2H), 4.83/4.82 (qn/dqn, J = 5.8 Hz/J = 11.7 Hz,
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J = 5.9 Hz, 1H), 4.30 – 4.19 (m, 1H), 3.75/3.47 (s, 3H). C NMR (100 MHz, CDCl3): δ
165.0/164.7 (qn, J = 3.0 Hz/J = 3.2 Hz), 162.1/162.1 (d, J = 247.3 Hz/J = 246.4 Hz),
137.6/135.8, 135.4/135.1, 129.7/129.4 (d, J = 8.2 Hz/J = 8.1 Hz), 118.7/116.8, 116.1/115.9 (d,
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J = 21.6 Hz), 89.2/88.8 (qn, J = 8.9 Hz), 53.2/53.0, 51.0/50.6 (qn, J = 2.6 Hz/J = 2.2 Hz). F
NMR (282 MHz, CDCl3): δ 81.6/81.3 (qn, 1F), 67.4/67.2 (dm, J = 146.8 Hz/J = 147.0 Hz,
4F), -114.6/-115.3 (tt, J = 8.4 Hz, J = 5.2 Hz/J = 8.5 Hz, J = 5.2 Hz, 1F). MS-ESI: m/z
357.0367 [M+Na]+ calcd. for C12H12F6O2SNa+ 357.0354.
Methyl 3-(4-fluorophenyl)-2-(trifluoromethyl)pent-4-enoates (15e). The diastereomeric target
compounds were prepared according to the aforementioned general procedure starting from
(E)-3-(4-fluorophenyl)allyl 3,3,3-trifluoropropanoate (7e) (150 mg, 0.57 mmol) over two
steps. After column chromatography (cyclohexane/EtOAc, 10:1) the target product was
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obtained as a clear oil. Yield: 47 mg (30%). H NMR (300 MHz, CDCl3): δ 7.24 – 7.12 (m,
2H), 7.07 – 6.96 (m, 2H), 6.06 – 5.89 (m, 1H), 5.22 – 5.08 (m, 2H), 4.02 – 3.88 (m, 1H),
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3.55/3.55 (dq, J = 11.2 Hz, J = 7.0 Hz/J = 10.6 Hz, J = 7.6 Hz, 1H), 3.76/3.47 (s, 3H). 13C
NMR (75 MHz, CDCl3): δ 167.0/166.8 (q, J = 3.3 Hz/ J = 3.5 Hz), 162.1/162.1 (d,
J = 245.9 Hz/ J = 246.4 Hz), 136.6, 135.1/134.9, 129.5 (d, J = 7.8 Hz), 124.1/124.0 (q,
J = 281.4 Hz/ J = 281.6 Hz), 117.7, 115.9/115.9 (d, J = 21.4 Hz/ J = 21.5 Hz), 56.1 (q,
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J = 26.0 Hz), 52.8/52.6, 48.1/47.6 (q, J = 1.9 Hz/J = 1.7 Hz). F NMR (282 MHz, CDCl3): δ
-64.4/-64.9 (dd/d, J = 7.8 Hz, J = 1.2 Hz/J = 7.6 Hz, 3F), -115.2/-115.5 (tt, J = 8.5 Hz,
J = 5.2 Hz/J = 8.6 Hz, J = 5.2 Hz, 1F). MS-ESI: m/z 299.0677 [M+Na]+ calcd. for
C13H12F4O2Na+ 299.0666.
Methyl 2-(pentafluorosulfanyl)-3-(p-tolyl)pent-3-enoates (15f). The diastereomeric target
compounds were prepared according to the aforementioned general procedure starting from
(E)-3-(p-tolyl)allyl 2-(pentafluorosulfanyl)acetate (7f) (130 mg, 0.41 mmol) over two steps.
After column chromatography (cyclohexane/EtOAc, 10:1) the target product was obtained as
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a clear oil. Yield: 31 mg (22%). H NMR (500 MHz, CDCl3): δ 7.17 – 7.02 (m, 4H), 6.12 –
6.02 (m, 1H), 5.17 – 5.05 (m, 2H), 4.88 – 4.81 (m, 1H), 4.23 – 4.18 (m, 1H), 3.74/3.46 (s,
3H), 2.33/2.30 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 165.2/164.8 (qn, J = 2.7 Hz/
J = 3.6 Hz), 138.1/136.7, 137.5/137.3, 136.2/136.2, 129.9/129.7, 127.8/127.6, 118.3/116.3,
89.4/88.9 (qn, J = 8.4 Hz/J = 8.9 Hz), 53.1/53.0, 51.5/51.0 (qn, J = 2.4 Hz), 21.2/21.2. 19F
NMR (471 MHz, CDCl3): δ 82.4/82.0 (qn, 1F), 67.7/67.5 (dm, J = 147.2 Hz/J = 146.1 Hz,
4F). MS-ESI: m/z 353.0607 [M+Na]+ calcd. for C13H15F5O2SNa+ 353.0605.
Methyl 3-(p-tolyl)-2-(trifluoromethyl)pent-4-enoates (15g). The diastereomeric target
compounds were prepared according to the aforementioned general procedure starting from
(E)-3-(p-tolyl)allyl 3,3,3-trifluoropropanoate (7g) (130 mg, 0.50 mmol) over two steps. After
column chromatography (cyclohexane/EtOAc, 10:1) the target product was obtained as a
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clear oil. Yield: 30 mg (22%). H NMR (500 MHz, CDCl3): δ 7.16 – 7.03 (m, 4H), 6.04 –
5.93 (m, 1H), 5.20 – 5.06 (m, 2H), 3.96 – 3.87 (m, 1H), 3.76/3.47 (s, 3H), 3.63 – 3.54 (m,
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1H), 2.33/2.31 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 167.2/166.9 (q, J = 3.3 Hz/
J = 3.6 Hz), 137.3/137.2, 137.2/137.1, 136.4/136.2, 129.7/129.7, 127.7/127.6, 124.3/124.1 (q,
J = 281.5 Hz), 117.3/117.2, 56.1/56.1 (q, J = 25.8 Hz/J = 25.7 Hz), 52.7/52.5, 48.5/48.1 (q,
J = 1.8 Hz/J = 1.9 Hz), 21.2/21.2. 19F NMR (471 MHz, CDCl3): δ -64.4/-64.8 (dd/d,
J = 7.9 Hz, J = 1.3 Hz/J = 7.6 Hz, 3F). MS-ESI: m/z 295.0924 [M+Na]+ calcd. for
C14H15F3O2Na+ 295.0916.
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General procedure for synthesis of propionic and trifluoropropionic acid allylic esters
DCC (1.2 equiv) is dissolved in dry DCM (8 mL) before the allylic alcohol (1.2 mmol,
1.0 equiv) and the corresponding carboxylic acid (1.2 equiv) are added under an argon
atmosphere. A white precipitate is formed, and a catalytic amount of DMAP is added. The
mixture is stirred at rt overnight. The suspension is diluted with Et2O (25 mL) before the
formed urea derivative is filtered off. The remaining solution is washed with H2O (3 
10 mL), 5% acetic acid (3  10 mL), and brine (3  10 mL) and dried over MgSO4 before the
solvent is removed under reduced pressure. The crude products are purified by column
chromatography (silica gel) as indicated below.
1-Phenylprop-2-en-1-yl 3,3,3-trifluoropropionate (9b). According to the above general
procedure 1-phenylprop-2-en-1-ol (170 mg, 1.27 mmol) was reacted with 3,3,3-
trifluoropropionic acid. The crude product was purified by column chromatography
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(cyclohexane/EtOAc, 5:1) to give the product as a colorless liquid. Yield: 248 mg (80%). H
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NMR (300 MHz, CDCl3): δ 3.21 (q, JH,F = 10.0 Hz, 2H), 5.21 – 5.39 (m, 2H), 6.00 (ddd,
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3JH,H = 16.5 Hz, JH,H = 10.4 Hz, JH,H = 6.0 Hz, 1H), 6.32 (dt, JH,H = 6.0 Hz, JH,H = 1.3 Hz,
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1H), 7.24 – 7.44 (m, 5H). C NMR (75 MHz, CDCl3): δ 40.0 (qt, JC,F = 31.0 Hz), 77.9 (d),
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117.8 (t), 123.4 (q, JC,F = 276.9 Hz), 127.3 (d), 128.7 (d), 128.8 (d), 135.4 (d), 138.0 (s),
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163.2 (q, JC,F = 4.2 Hz). F NMR (282 MHz, CDCl3): δ -63.3 (t, JH,F = 10.1 Hz, 3F). MS-
ES(+)-EM: m/z calcd for C12H11F3O2Na+ 267.0603; found 267.0610 [M+Na]+.
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Page 29 of 36
The Journal of Organic Chemistry
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1-Phenylprop-2-en-1-yl propionate (9c). According to the above general procedure 1-
phenylprop-2-en-1-ol (500 mg, 3.73 mmol) was reacted with propionic acid. The crude
product was purified by column chromatography (cyclohexane/EtOAc, 5:1) to give the
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product as a colorless liquid. Yield: 556 mg (78%). H NMR (400 MHz, CDCl3): δ 1.15 (t,
3JH,H = 7.6 Hz, 3H), 2.39 (2q, JH,H = 7.5 Hz u. JH,H = 7.6 Hz, 2H), 5.23 (dt, JH,H = 10.4 Hz,
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2JH,H = 4JH,H = 1.3 Hz, 1H), 5.29 (dt, JH,H = 17.1 Hz, JH,H = 4JH,H = 1.4 Hz, 1H), 6.00 (ddd,
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3JH,H = 17.2 Hz, JH,H = 10.4 Hz, JH,H = 5.9 Hz, 1H), 6.28 (dt, JH,H = 5.9 Hz, JH,H = 1.4 Hz,
1H), 7.25 – 7.39 (m, 5H). 13C NMR (100 MHz, CDCl3): δ 9.2 (q), 27.9 (t), 76.1 (d), 116.9 (t),
127.2 (d), 128.2 (d), 128.6 (d), 136.5 (d), 139.1 (s), 173.4 (s).
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The compound was mentioned in the literature, but no spectroscopic data were given.40
1-(4-Fluorophenylprop-2-en-1-yl) 3,3,3-trifluoropropionate (9d). According to the above
general procedure 1-(4-fluorophenyl)prop-2-en-1-ol (200 mg, 1.31 mmol) was reacted with
3,3,3-trifluoropropionic acid. The crude product was purified by column chromatography
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(cyclohexane/EtOAc, 10:1) to give a colorless liquid. Yield: 240 mg (70%). H NMR
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(300 MHz, CDCl3): δ 3.22 (q, JH,F = 10.1 Hz, 2H), 5.30 (dt, JH,H = 10.5 Hz,
2JH,H = 4JH,H = 1.2 Hz, 1H), 5.32 (dt, JH,H = 17.2 Hz, JH,H = 4JH,H = 1.3 Hz, 1H), 5.98 (ddd,
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3JH,H = 17.1 Hz, JH,H = 10.5 Hz, JH,H = 5.8 Hz, 1H), 6.31 (dt, JH,H = 5.8 Hz, JH,H = 1.4 Hz,
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1H), 7.00 – 7.13 (m, 2H), 7.28 – 7.39 (m, 2H). 13C NMR (75 MHz, CDCl3): δ 40.0 (qt,
2JC,F = 31.1 Hz), 77.2 (d), 115.8 (dd, JC,F = 21.7 Hz), 118.0 (t), 123.4 (q, JC,F = 275.3 Hz),
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129.2 (dd, JC,F = 8.3 Hz), 133.8 (d, JC,F = 3.2 Hz), 135.2 (d), 162.8 (d, JC,F = 247.5 Hz),
163.2 (q, JC,F = 4.3 Hz). 19F NMR (282 MHz, CDCl3): δ -113.1 (tt, JH,F = 8.6 Hz,
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4JH,F = 5.3 Hz, 1F), -63.3 (t, JH,F = 10.1 Hz, 3F). MS-ES(+)-EM: m/z calcd for
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C12H10F4O2Na+ 285.0509; found 285.0511 [M+Na]+.
1-(Naphthalenylprop-2-en-1-yl) 3,3,3-trifluoropropionate (9e). According to the above
general procedure 1-(naphthalenyl)prop-2-en-1-ol (200 mg, 1.09 mmol) was reacted with
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