Synthesis and pKa values of 2-(3- and 4- pentafluorosulfanylphenyl)-2-fluorocyclopropylamines

Article abstract of DOI:10.1016/j.jfluchem.2013.07.003

Starting from 3- and 4-pentafluorosulfanylbenzaldehydes, a series of cis- and trans-2-aryl-2-fluorocyclopropylamines bearing an SF₅ group in 3- or 4-position of the aryl ring were synthesized in 7 steps via the corresponding cyclopropanecarboxylic acids. While the pK_a values of the carboxylic acids are very little depending on the stereochemistry at the cyclopropane ring and the regiochemistry of the SF₅-substituents in the aryl ring, the pK_a of the corresponding 2-fluorocyclopropylamines is strongly dependent on the stereochemistry at the three-membered ring due to hyperconjugative effects of the CF and the CN bonds. Again, the regiochemistry of SF₅ substitution in the phenyl ring has almost no influence.

Full text of DOI:10.1016/j.jfluchem.2013.07.003

Accepted Manuscript
Title: Synthesis and pKa Values of 2-(3- and
4-Pentafluorosulfanylphenyl)-2-fluorocyclopropylamines
¨
Authors: Benjamin Schinor, Birgit Wibbeling, Gunter Haufe
PII:
S0022-1139(13)00258-3
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2013.07.003
FLUOR 8152
To appear in:
FLUOR
Received date:
Revised date:
Accepted date:
23-5-2013
4-7-2013
5-7-2013
Please cite this article as: B. Schinor, B. Wibbeling, G. Haufe, Synthesis and pKa
Values of 2-(3- and 4-Pentafluorosulfanylphenyl)-2-fluorocyclopropylamines, Journal
of Fluorine Chemistry (2013), http://dx.doi.org/10.1016/j.jfluchem.2013.07.003
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*Graphical Abstract - Pictogram
Graphical Abstract
Page 1 of 24

Synopsis:
3- and 4-SF5-substituted 2-fluoro-2-phenylcyclopropylamines were synthesized from the
corresponding benzaldehydes in 7 steps and their pKa values were determined.
Page 2 of 24

1
Synthesis and pKa Values of 2-(3- and 4-Pentafluorosulfanylphenyl)-2-
fluorocyclopropylamines
Benjamin Schinor, Birgit Wibbeling, Günter Haufe*
Organisch Chemisches Institut, Universität Münster, Corrensstraße 40, D-48149 Münster,
Germany
Tel. +49-251-83-33281. Fax: +49-251-83-39772, E-mail: haufe@uni-muenster.de
Abstract:
Starting from 3- and 4-pentafluorosulfanylbenzaldehydes, a series of cis- and trans-2-aryl-2-
fluorocyclopropylamines bearing an SF5 group in 3- or 4-position of the aryl ring were
synthesized in 7 steps via the corresponding cyclopropanecarboxylic acids. While the pKa
values of the carboxylic acids are very little depending on the stereochemistry at the
cyclopropane ring and the regiochemistry of the SF5-substituents in the aryl ring, the pKa of
the corresponding 2-fluorocyclopropylamines is strongly dependent on the stereochemistry at
the three-membered ring due to hyperconjugative effects of the CF and the CN bonds.
Again, the regiochemistry of SF5 substitution in the phenyl ring has almost no influence.
Keywords:
α-Fluorostyrenes,
2-fluorocyclopropanecarboxylic
acids,
2-
fluorocyclopropylamines, pentafluorosulfanyl(SF5) substituent, pKa values, stereochemistry,
regiochemistry.
1. Introduction
The implementation of a pentafluorosulfanyl(SF5) group into a molecule puts - just like the
trifluoromethyl(CF3) group - particular electronic effects on the compound [1]. Therefore, the
SF5 group is often dubbed as the “super-trifluoromethyl group” [2]. Comparing the
electronegativity, the thermal and chemical stability, the lipophilicity or the steric demand, the
SF5 group is prevailing the CF3 group in all these terms providing interesting possibilities for
changing physicochemical properties and modifying biological effects of a molecule [3].
Looking at the electronic influence of the SF5 substituent the electron withdrawing effect is
similar to that of the CF3 group regarding the 1s photoelectron spectra [4]. But the group
electronegativity of the SF5 substituent is higher with 3.65 compared to 3.36 of the CF3 group
[5]. Another important effect of the SF5 group is its steric demand, which is close to that of
the tert-butyl group and so being considerably bigger than that of a CF3 group. However, CF3
Page 3 of 24

2
and the SF5 substituted compounds often show very similar behavior in enzyme inhibition
because they both represent a highly fluorinated surface having similar electrostatic
properties, although the shapes appear different. While the CF3 group appears as an inverted
cone of electron density, the SF5 group has a pyramidal electron density. Due to these facts,
replacement of a CF3 group with an SF5 group is used to modify agrochemicals such as
Trifluralin or pharmaceuticals like Fluoxetine, Fenfluramine and several others [6].
It is well known that the introduction of a fluorine atom or a fluorinated substituent close to
another functional group has a great influence on the physicochemical properties such as pKa
and log D values or the dipole moment of the particular compound, which has unique
relevance for medicinal chemistry and chemical biology [7-11]. In a previous work we
reported about the effects of a monofluoro substituent and its relative configuration on the pKa
values of cyclopropylamines with fluorine taking a fixed position cis or trans to the amino
function (Figure 1). Placing the fluorine atom in trans-position to the amino group results in a
significantly more acidic compound compared to the cis-isomer 1 and to the corresponding
fluorine free parent compounds. Based on computational studies, this was assigned to
hyperconjugative overlapping of corresponding molecule orbitals and an electron-transfer
from the (CN)  *(CF) in trans-1 (Figure 1) is possible. Such an overlapping is not
possible in cis-1 resulting in a higher electron density of the amino group and hence in a
higher pKa value [12].
Figure 1. Hypothetic orbital interactions in fluorinated phenylcyclopropylamine (cis/trans
correlates to fluorine and the amino group) [9].
Furthermore, we found a decrease in the pKa-values by substitution of the phenyl’s para-
position in fluorinated tranylcypromine analogues with electron withdrawing groups like
fluorine, chlorine and the CF3 group, which correlated with the in vitro activity of these
compounds as monoamine oxidase inhibitors [13].
Within this paper, we report on synthesis and pKa values of diastereomeric meta- and para-
SF5-substituted
2-aryl-2-fluorocyclopropanecarboxylic
acids
and
corresponding
Page 4 of 24

3
cyclopropylamines. The effects of combination of a fluorinated cyclopropane ring and the
electron withdrawing SF5 group in the phenyl ring will be discussed.
2. Results and discussion
2.1.
Synthesis
Similarly to our earlier report [14], we synthesized 2-aryl-2-fluorocyclopropylamines bearing
an SF5 substituent in the 3- or 4-position. The synthetic sequence followed the route starting
with a Wittig olefination of the commercially available 3- and 4-SF5 substituted
benzaldehydes 2a and 2b. Bromofluorination of the obtained styrenes 3a and 3b led to the
bromofluorides 4a and 4b, which gave the α-fluorostyrenes 5a and 5b in good yields by HBr
elimination (Scheme 1). The results of these reactions are depicted in Table 1.
Scheme 1. Synthesis of α-fluoro-(3- and 4-pentafluorosulfanylphenyl)styrenes 5a and 5b.
Table 1. Results of the synthetic sequence towards α-fluoro-(3- and 4-
pentafluorosulfanylphenyl)styrenes 5
Entry Compound
X
Y
Yield [%] 3
Yield [%] 4
Yield [%] 5
1
2
H
SF5
H
84
70
77
62
75
a
SF5
~70*
b
* some amount of the HBr-elimination product 5b detected
According to our earlier procedure [14] the copper(I)-catalyzed cyclopropanation with
ethyldiazoacetate (EDA) in dichloromethane (DCM) gave the diastereomeric ethyl
cyclopropylcarboxylates 6a/b (trans regarding F and CO2Et) and 7a/b (cis regarding F and
CO2Et) in diastereomeric ratios of about 1.2:1 for compounds a and 1:1 for compounds b
(GC). These mixtures were separated by column chromatography. Saponification of the single
diastereomers gave the carboxylic acids 8a/b and 9a/b. The structure of 8b and 9b was
determined by spectroscopic data and proved by X-ray analysis [15]. Succeeding Curtius-
degradation with diphenylphosphoryl azide (DPPA) gave the Boc-protected
cyclopropylamines 10a/b and 11a/b, which were finally deprotected with 6M hydrochloric
acid in THF to yield the amine hydrochlorides 12a/b and 13a/b (Scheme 2). The yields of all
reactions are given in Table 2.
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4
Scheme 2. Synthesis of the 2-fluoro-(3/4-pentafluorosulfanylphenyl)cyclopropylamine
hydrochlorides.
Table 2. Yields of compounds 6 to 13
Yield [%]
Yield [%]
Yield [%]
Yield [%]
Entry Comp.
X
Y
6
7
8
9
10
11
87
45
12
100
95
13
96
94
1
2
H
SF5
H
32
23
59
46
72
30
89
46
a
SF5
63% (1:1 GC)
b
Figure 2. X-Ray structures of compounds 8b and 9b. Thermals ellipsoids are shown with
30% probability [15].
2.2. pKa Values
The pKa values of the carboxylic acids were measured in aqueous solution starting from basic
pH (10 mL 0.1 M NaOH solution) against 0.1 M hydrochloric acid due to the insolubility of
the carboxylic acids at pH 1. When precipitation of the acids starts, the automated titration
was slowed down manually to give more exact titration curves. The amines were dissolved in
0.1 M KNO3-solution and acidified with 0.5 mL of 2 M hydrochloric acid. The pKa values
were determined by titration with 0.1 M NaOH. The results of these measurements are
depicted in Table 3.
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5
Table 3. Results of pKa measurements.
Z = COOH
compound
Z = NH2
a
pKa
compound
pKa
trans-14
3.98
4.14
3.87
3.88
3.71
3.86
trans-1
cis-1
12a
7.02 (6.98b)
7.23 (7.35b)
6.31
X = Y = H
cis-15
8a
X = H, Y = SF5
6.83
9a
13a
6.30
8b
12b
X = SF5, Y = H
6.77
9b
13b
a of the conjugated acid, b reference [16].
Comparison of the pKa values of the diastereomeric 2-fluoro-2-phenylcyclopropanecarboxylic
acids trans-14 and cis-15 and the corresponding amines trans-1 and cis-1 proved the trans-
isomers to be about 0.2 pKa units more acidic. Based on quantum chemical calculations, the
higher acidity of trans- compared to cis-2-fluorocyclopropylamine was ascribed to a
hyperconjugative interaction (Figure 1) leading to different local charge distribution and
different hybridization of the nitrogen atom and hence to stronger proton affinity of the cis-
over the trans-isomer [12]. This effect was found experimentally for the diastereomeric 2-
fluoro-2-phenylcyclopropylamines [16].
The electron withdrawing effect of the SF5 group leads to further acidification by about 0.8
pKa units in case of the trans-2-fluoroamines 12a and 12b independently of the position of the
SF5 substituent in the aromatic ring. In case of the cis-compounds 13a and 13b the difference
is about 0.5 pKa units, regardless the regiochemistry (Table 3). Thus, this effect is mainly an
inductive electron withdrawing effect of the SF5-substituted aromatic ring. In literature, the
pKa values of 3- and 4-SF5 substituted anilines were compared. The pKa value of the
anilinium ion (4.56) was lowered to 2.82 (3-SF5) and 2.17 (4-SF5), respectively. The much
stronger electron withdrawing effect of the SF5 group in para-position was assigned to d-
orbital participation by the sulfur atom and/or hyperconjugation leading to higher acidity in
case of the p-SF5 aniline [17]. Such a hyperconjugation effect of the SF5 group, if at all, is
much weaker in the corresponding 2-aryl-2-fluorocyclopropylamines.
Compared to the fluorinated cyclopropanecarboxylic acids 14 and 15, the difference is 0.1 and
0.2 pKa units, respectively, for the trans-compounds 8a and 8b and about 0.3 pKa units for the
cis-isomers 9a and 9b. Again the position of the SF5 group has almost no influence on the
pKa. Very little effect of regiochemistry was also found in 3- and 4-SF5-benzoic acids [17].
Page 7 of 24

6
3. Conclusion
A 7-steps synthetic sequence provided cis- and trans-2-aryl-2-fluorocyclopropylamines
bearing an SF5 substituent in meta- or para-position of the aryl ring in 6.7% (12a), 2.4%
(12b), 5.5% (13a) or 1.5% (13b) overall yields starting from 3- and 4-pentafluorosulfanyl
benzaldehydes via the diastereomeric 2-aryl-2-fluorocyclopropanecarboxylic acids,
respectively.
Compared
to
those
of
the
cis/trans
isomeric
2-fluoro-2-
phenylcyclopropanecarboxylic acids 14 and 15, the pKa values of the SF5-substituted 2-aryl-2-
fluorocarboxylic acids 8 and 9 are slightly lowered. This effect is very little depending on the
stereochemistry at the cyclopropane ring and the regiochemistry of the SF5-substituents in the
aryl ring. A much stronger effect on the pKa is seen for the corresponding 2-
fluorocyclopropylamines 12 and 13. In contrast this effect is strongly dependent on the
stereochemistry at the three-membered ring due to hyperconjugation of the CF and the CN
bonds. Again, the position of SF5 substitution in the phenyl ring has almost no influence
showing that this effect is largely inductive in nature.
4. Experimental
4.1. General remarks
Melting points are uncorrected. NMR spectra were recorded on Bruker Avance II at 300 and
400 MHz, Bruker DRX at 300 MHz and Agilent DD2 at 500 and 600 MHz (1H), at 25 °C.
TMS (1H and 13C NMR) and CCl3F (19F NMR) were used as internal standards. Mass spectra
(ESI-MS) were measured on a MicroTof Bruker Daltonics. The progress of reactions was
monitored by TLC-plates (silica gel 60 F254, Merck). Column chromatography was carried out
on silica gel 60 (Merck, particle size 0.040–0.063 mm). The 3- and 4-
pentafluorosulfanylbenzaldehydes 2a and 2b are commercially available at Fluorochem, UK.
The known styrenes 3a and 3b were synthesized according to the protocol published in
references [18,19]. The fluorinated phenylcyclopropanecarboxylic acids trans-14 and cis-15
were synthesized analogously to the sequence published in reference [14]. X-Ray diffraction:
Data sets were collected with a Nonius KappaCCD diffractometer. Programs used: data
collection, COLLECT (B.V. Nonius, 1998); data reduction Denzo-SMN [20]; absorption
correction, Denzo [21]; structure solution SHELXS-97 [22]; structure refinement SHELXL-
97 [23] and graphics, XP (Bruker AXS, 2000). Thermals ellipsoids are shown with 30%
probability, R-values are given for observed reflections, and wR2 values are given for all
reflections.
Page 8 of 24

7
4.2. Wittig Olefination
4.2.1. 3-Pentafluorosulfanylstyrene (3a)
Similarly to the procedure given in ref. [18], 3-pentafluorosulfanylbenzaldehyde (3.48 g,
15.0 mmol) was stirred with methyltriphenylphosphonium bromide (6.0 g, 16.8 mmol, 1.1
eq.) and K2CO3 (4.00 g, 32.5 mmol) in 1,4-dioxane (10 mL) at 115 °C for 24 h. Then the
solvent was removed under reduced pressure and the residue was purified by column
chromatography (silica gel, pentane) to give a colorless liquid. Yield: 2.90 g (12.6 mmol, 84
1
3
%). H NMR (300 MHz, CDCl3): δ 5.39 (d, JH,H(cis) = 10.9 Hz, 1 H, HA), 5.82 (d,
3JH,H(trans) = 17.6 Hz, 1 H, HB), 6.73 (dd, 3JH,H(cis) = 10.9, 3JH,H(trans) = 17.6 Hz, 1 H, 2-CH), 7.43
3
4
4
(m, 1 H, 5-CH), 7.54 (d, JH,H = 7.7 Hz, 1 H, 4-CH), 7.63 (ddd, JH,H = 1.1, JH,H = 2.3 Hz,
4JH,H = 8.2 Hz, 1 H, 6-CH), 7.54 (t, 4JH,H = 1.9 Hz, 1 H, 8-CH). 13C NMR (75 MHz, CDCl3): δ
3
3
116.4 (s, 1-C), 123.8 (p, JC,F = 4.7 Hz, 6-C), 125.0 (p, JC,F = 4.7 Hz, 8-C), 128.8 (s, 5-C),
129.0 (s, 4-C), 135.2 (s, 2-C), 138.6 (s, 3-C), 154.4 (m, 7-C). 19F NMR (282 MHz, CDCl3): δ
62.06 (d, 2JF,F = 150.2 Hz, 4 F, SFeq), 83.70 (p, 2JF,F = 150.2 Hz, 1F, SFax).
4.2.2. 4-Pentafluorosulfanylstyrene (3b)
Similarly to the procedure given in ref. [19], 4-pentafluorosulfanylbenzaldehyde (0.65 g,
2.79 mmol) was stirred with methyltriphenylphosphonium bromide (1.09 g, 3.1 mmol,
1.1 eq.) and K2CO3 (804 mg, 5.83 mmol, 2 eq.) in 1,4-dioxane (10 mL) at 90 °C for 12 h.
Then the solvent was removed under reduced pressure and the residue was purified by column
chromatography (silica gel, pentane) to give a yellowish liquid. Yield: 0.47 g (1.95 mmol, 70
1
3
%). H NMR (300 MHz, CDCl3): δ 5.41 (d, JH,H(cis) = 10.9 Hz, 1 H, HA), 5.85 (d,
3JH,H(trans) = 17.6 Hz, 1 H, HB), 6.72 (dd, 3JH,H(cis) = 10.9, 3JH,H(trans) = 17.6 Hz, 1 H, 2-CH), 7.46
3
3
19
(d, JH,H = 8.6 Hz, 2 H, 4/8-CH), 7.70 (d, JH,H = 8.8 Hz, 2 H, 5/7-CH). F NMR (282 MHz,
CDCl3): δ 62.20 (d, 2JF,F = 150.6 Hz, 4 F, SFeq), 83.19 (p, 2JF,F = 150.6 Hz, 1F, SFax).
4.3. Bromofluorination
4.3.1. 2-Bromo-1-fluoro-1-(3-pentafluorosulfanylphenyl)ethane (4a)
Similarly to the general procedure [24] 3a (0.96 g, 4.14 mmol) was treated with triethylamine-
trishydrofluoride (Et3N·3HF, 2.7 mL, 28.1 mmol, 7 eq.) and subsequently N-
bromosuccinimide (NBS, 1.2 g, 7 mmol, 1.5 eq). Due to incomplete reaction pyridinium
polyhydrogenfluoride (OHLA’s reagent, Py·9HF, 1 mL, 4 mmol, 1 eq.) was added and the
solution was stirred for 2 h. After neutralization with ammonia and extraction with pentane 4a
was isolated and purified by column chromatography (silica gel, pentane) to give a colorless
3
liquid. Yield: 1.1 g (77%). 1H NMR (300 MHz, CDCl3): δ 3.66 (dd, JH,H = 4.9,
3
3
3JH,F = 22.0 Hz, 1 H, 1-CH2Br), 3.67 (dd, JH,H = 6.6, JH,F = 17.7 Hz, 1 H, 1-CH2Br), 5.70
Page 9 of 24

8
3
3
2
3
(ddd, JH,H = 4.9, JH,H = 6.7, JH,F = 46.2 Hz, 1 H, 2-CHF), 7.50 (t, JH,H = 7.9 Hz, 1 H,
3
4
3
5-CH), 7.58 (d, JH,H = 7.9 Hz, 1 H, 6-CH), 7.74 (dd, JH,H = 1.9, JH,H = 8.9 Hz, 1 H, 4-CH),
4
7.77 (d, JH,H = 1.9 Hz, 1 H, 8-CH). 19F NMR (282 MHz, CDCl3): δ -175.83 (ddd,
3
2
2
3JH,F = 17.7, JH,F = 22.0, JH,F = 46.3 Hz, 1 F, 2-CHF), 62.91 (d, JF,F = 151.9 Hz, 4 F, SFeq),
84.53 (p, 2JF,F = 151.9 Hz, 1F, SFax). MS (GC/EI), m/z (%): 330/328 (37/38) [M+], 309/311
(3/3) [M+-HF], 249 (3) [M+-Br], 235 (100) [M+-CH2Br], 201 (4) [M+-SF5], 140 (1), 127 (20)
+
+
[SF5 ], 122 (8), 101 (4), 77 (5) [C6H5 ], 63 (1), 50 (2).
4.3.2. 2-Bromo-1-fluoro-1-(4-pentafluorosulfanylbenzyl)ethane (4b)
Similarly to the general procedure [24] 3b (0.64 g, 2.80 mmol) was treated with
triethylamine-trishydrofluoride (Et3N·3HF, 2.7 mL, 28.1 mmol, 10 eq.) and subsequently N-
bromosuccinimide (NBS, 1.2 g, 7 mmol, 2.5 eq) to give 4b as a colorless liquid. Yield: 0.55 g
(~70%, HBr elimination product 5b was also found). 1H NMR (400 MHz, CDCl3): δ 3.65 (m,
2 H, 1-CH2Br), 5.70 (ddd, 3JH,H = 4.6, 3JH,H = 6.2, 2JH,F = 46.4 Hz, 1 H, 2-CHF), 7.48 (m, 2 H,
2
4/8-CH), 7.81 (m, 2 H, 5/7-CH). 13C NMR (101 MHz, CDCl3): δ 33.5 (d, JC,F = 27.6 Hz,
1-C), 91.4 (d, 1JC,F = 180.1 Hz, 2-C), 126.1 (d, 3JC,F = 7.2 Hz, 4/8-C), 126.5 (p, 3JC,F = 4.7 Hz,
3
5/7-C), 140.8 (d, JC,F = 20.8 Hz, 3-C), 154.2 (m, 6-C). 19F NMR (282 MHz, CDCl3): δ -
3
2
3
176.96 (dt, JH,F = 19.5, JH,F = 46.3 Hz, 1 F, 2-CHF), -108.90 (dd, JH,F = 17.4,
3JH,F = 48.7 Hz, 1 F, HBr elimination product 5b), 62.24 (d, 2JF,F = 150.1 Hz, 4 F, SFeq), 83.23
(q, 2JF,F = 150.1 Hz, 1 F, SFax). MS (GC/EI), m/z (%): 309/311 (100/100) [M+-HF], 263/265
+
(2/2), 230 (78) [309-Br], 182/184 (29/28) [309-SF5], 127 (2) [SF5 ], 122 (40) [C8H7F+], 103
+
(47) [122-F], 77 (48) [C6H4 ], 51 (19).
4.4. HBr Elimination
4.4.1. 1-Fluoro-3-pentafluorosulfanylstyrene (5a)
Similarly to the procedure [25], 4a (3.87 g, 11.8 mmol) was treated with potassium-tert-
butanol (KOtBu, 2.81 g, 25.0 mmol, 2.1 eq.) in refluxing pentane for 1 h. Bulb-to-bulb
1
distillation gave 5a as a colorless liquid. Yield: 2.41 g (62%). Bp 60 °C/0.07mbar. H NMR
(300 MHz, CDCl3): δ 5.00 (dd, 2JH,H = 3.9, 3JH,F(cis) = 17.6 Hz, 1 H, HA), 5.14 (dd, 2JH,H = 3.9,
5
3
3JH,F(trans) = 48.9 Hz, 1 H, HB), 7.48 (tq, JH,H = 1.0, JH,H = 7.9 Hz, 1 H, 5-CH), 7.68 (m, 1 H,
5
4
3
4
6-CH), 7.74 (ddd, JH,H = 1.0, JH,H = 2.3, JH,H = 8.3 Hz, 1 H, 4-CH), 7.92 (t, JH,H = 2.0 Hz,
2
1 H, 8-CH). 13C NMR (75 MHz, CDCl3): δ 91.7 (d, JC,F = 22.0 Hz, 1-C), 122.2 (dp,
3
3
3JC,F = 4.7, 7.4 Hz, 8-C), 126.7 (p, JC,F = 4.7 Hz, 6-C), 127.5 (d, JC,F = 6.6 Hz, 4-C), 129.0
4
2
(d, JC,F = 1.3 Hz, 5-C), 133.0 (d, JC,F = 29.8 Hz, 3-C), 154.5 (m, 7-C), 161.0 (d,
3
1JC,F = 250.7 Hz, 2-C). 19F NMR (282 MHz, CDCl3): δ -108.58 (dd, JH,F(cis) = 17.5,
Page 10 of 24

9
2
3JH,F(trans) = 49.0 Hz, 1 F, 2-CF), 62.02 (d, JF,F = 150.8 Hz, 4 F, SFeq), 83.02 (p,
2JF,F = 152.1 Hz, 1 F, SFax). MS (GC/EI), m/z (%): 248 (100) [M+], 229 (1) [M+-HF], 140
+
+
+
(20), 138 (2), 101 (C8H5 ) 89 (4), 75 (12) [C6H4 ], 70 (1), 51 (1) [C4H3 ].
4.4.2. 1-Fluoro-4-pentafluorosulfanylstyrene (5b)
Similarly to the procedure [25] 4b (0.50 g, 1.5 mmol) was treated with KOtBu (0.35 g,
3.1 mmol, 2 eq.) in refluxing pentane for 1 h. Bulb-to-bulb distillation gave 5b as a colorless
1
liquid. Yield: 0.28 g (75%). Bp 56 °C/0.07mbar. H NMR (300 MHz, CDCl3); δ 5.02 (dd,
3
2
3
2JH,H = 3.9, JH,F(cis) = 17.5 Hz, 1 H, HA), 5.17 (dd, JH,H = 3.8, JH,F(trans) = 48.8 Hz, 1 H, HB),
13
7.64 (d, 3JH,H = 8.8 Hz, 2 H, 5/7-CH), 7.78 (m, 2 H, 4/8-CH). C NMR (75 MHz, CDCl3): δ
2
3
92.5 (d, JC,F = 21.8 Hz, 1-C), 124.8 (d, JC,F = 7.0 Hz, 4/8-C), 126.3 (m, 5/7-C), 131.9 (m,
2
1
19
6-C), 135.0 (d, JC,F = 31.1 Hz, 3-C), 161.0 (d, JC,F = 251.3 Hz, 2-C). F NMR (282 MHz,
3
3
CDCl3): δ -108.96 (dd, JH,F(cis) = 17.4, JH,F(trans) = 48.8 Hz, 1 F, 2-CF), 62.20 (d,
2
2JF,F = 150.6 Hz, 4 F, SFeq), 83.02 (p, JF,F = 152.2 Hz, 1 F, SFax). MS (GC/EI), m/z (%): 248
(100) [M+], 231 (49), 229 (4) [M+-F], 203 (5) [M+-C2H2F], 140 (16), 123 (62) [M+-SF5], 103
+
+
+
(7) [123-HF], 89 (31), 75 (42) [C6H3 ], 65 (59), 51 (1) [C4H3 ], 39 (16) [C3H4 ].
4.5. Cyclopropanation
4.5.1. Ethyl 2-fluoro-2-(3-pentafluorosulfanylphenyl)cyclopropylcarboxylates
Similarly to the protocol [14], to a solution of 5a (2.34 g, 9.4 mmol) and Cu(acac)2 (75 mg,
0.2 mmol) (reduced with 3 drops phenylhydrazine) in anhydrous CH2Cl2 (5 mL), a solution of
EDA (2.77 g, 24.0 mmol, 2.6 eq.) in anhydrous CH2Cl2 (10 mL) was added at 40 °C via a
syringe pump over a period of 5 h. After dilution with 100 mL CH2Cl2 the mixture was
washed with sat. NaHCO3 (2×50 mL) and H2O (2×50 mL). After drying (MgSO4) the solvent
was removed by rotary evaporator. Separation of the crude product by column
chromatography (silica gel, pentane/Et2O, 20:1) afforded the pure isomers 6a and 7a as
colorless oils.
1
6a: Yield: 1.0 g (32%). H NMR (400 MHz, CDCl3): δ 1.03 (t, 3JH,H = 7.1 Hz, 3 H, 12-CH3),
2
3
3
2
1.90 (ddd, JH,H = 7.3, JH,H(cis) = 10.4, JH,F(cis) = 19.3 Hz, 1 H, HA), 2.03 (ddd, JH,H = 7.3,
3
3
3
3JH,H(trans) = 7.8, JH,F(trans) = 12.5 Hz, 1 H, HB), 2.62 (ddd, JH,H(trans) = 7.8, JH,H(cis) = 10.5,
3
3
3JH,F(cis) = 18.1 Hz, 1 H, HX), 3.94 (q, JH,H = 7.1 Hz, 2 H, 11-CH2), 7.49 (t, JH,H = 8.1 Hz,
1 H, 7-CH), 7.63 (m, 1 H, 6-CH), 7.76 (m, 1 H, 8-CH), 7.88 (q, 4JH,H = 1.7 Hz, 1 H, 10-CH).
2
13C NMR (101 MHz, CDCl3): δ 13.9 (s, 12-C), 16.8 (d, JC,F = 10.1 Hz, 3-C), 28.2 (d,
1
3
2JC,F = 16.0 Hz, 2-C), 61.1 (s, 11-C), 82.3 (d, JC,F = 222.1 Hz, 4-C), 126.1 (q, JC,F = 4.8 Hz,
3
2
10-C), 126.7 (s, 8-C), 128.8 (s, 7-C), 131.4 (d, JC,F = 4.1 Hz, 6-C), 134.6 (d, JC,F = 20.9 Hz,
Page 11 of 24

10
3
19
5-C), 153.8 (m, 9-C), 168.4 (d, JC,F = 1.8 Hz, 1-C). F NMR (282 MHz, CDCl3): δ -157.22
3
3
3
4
(ddd, JH,F(trans) = 12.5, JH,F(cis) = 18.0, JH,F(cis) = 19.3 Hz, 1 F, 4-CF), 62.15 (dq, JH,F = 1.8,
2JF,F = 150.5 Hz, 4 F, SFeq), 83.41 (p, 2JF,F = 150.5 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd. for
C12H12F6O2SNa+: 357.0354; found 357.0354. MS (GC/EI) m/z (%): 334 (46) [M+], 315 (9)
[M+-F], 306 (8) [M+-C2H4], 289 (15) [M+-C2H5O], 279 (46), 261 (10) [M+-CO2C2H5], 251
+
(100) [C10H7F4OS+], 241 (9) [261-HF], 231 (20) [315-C4H6O2], 206 (5), 203 (1) [C6H4SF5 ],
178 (11), 162 (10), 158 (29), 151 (4), 133 (45), 132 (10) [M+-C6H4SF5], 127 (2), 115 (2), 89
(3), 83 (2), 75 (1), 55 (1).
7a: Yield: 0.71 g (23%). 1H NMR (400 MHz, CDCl3): δ 1.31 (t, 3JH,H = 7.2 Hz, 3 H, 12-CH3),
2
3
3
1.69 (ddd, JH,H = 7.3, JH,H(trans) = 9.5, JH,F(trans) = 10.6 Hz, 1 H, HB), 2.25 (ddd,
3
3
2
3JH,F(trans) = 3.1, JH,H(trans) = 7.9, JH,H(cis) = 9.3 Hz, 1 H, HX), 2.38 (ddd, JH,H = 7.3,
3JH,H(cis) = 8.0, 3JH,F(cis) = 20.3 Hz, 1 H, HA), 4.18 (m, 2 H, 11-CH2), 7.36 (m, 1 H, 6-CH), 7.47
(m, 1 H, 7-CH), 7.67 (m, 2 H, 8/10-CH). 13C NMR (101 MHz, CDCl3): δ 14.2 (s, 12-C), 19.3
2
2
(d, JC,F = 12.1 Hz, 3-C), 29.5 (d, JC,F = 11.4 Hz, 2-C), 61.5 (s, 11-C), 80.2 (d,
1JC,F = 229.0 Hz, 4-C), 122.2 (tq, 3JC,F = 4.5, 9.0 Hz, 10-C), 125.8 (p, 3JC,F = 4.0, 4.5 Hz, 8-C),
3
2
127.3 (d, JC,F = 6.4 Hz, 6-C), 129.3 (s, 7-C), 139.1 (d, JC,F = 21.9 Hz, 5-C), 154.3 (m, 9-C),
3
19
3
167.2 (d, JC,F = 2.3 Hz, 1-C). F NMR (282 MHz, CDCl3): δ -190.28 (ddd, JH,F(trans) = 3.1,
3
2
3JH,F(trans) = 10.7, JH,F(cis) = 20.3 Hz, 1 F, 4-CF), 62.22 (d, JF,F = 150.4 Hz, 4 F, SFeq), 83.54
(p,2JF,F = 150.4 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd. for C12H12F6O2SNa+: 357.0354;
found 357.0353. MS (GC/EI) m/z (%): 334 (38) [M+], 315 (10) [M+-F], 306 (10) [M+-C2H4],
289 (21) [M+-C2H5O], 279 (50), 261 (12) [M+-CO2C2H5], 251 (100) [C10H7F4OS+], 241 (9)
+
[261-HF], 231 (18) [315-C4H6O2], 206 (5), 203 (1) [C6H4SF5 ], 184 (1), 178 (11), 162 (10),
158 (20), 151 (4), 133 (40), 132 (10) [M+-C6H4SF5], 115 (2), 89 (3), 83 (2), 75 (1), 55 (1).
4.5.2. Ethyl 2-fluoro-2-(4-pentafluorosulfanylphenyl)cyclopropylcarboxylates
Similarly to the protocol [14], to a solution of 5b (0.95 g, 3.8 mmol) and Cu(acac)2 (75 mg,
0.2 mmol) (reduced with 3 drops of phenylhydrazine) in anhydrous CH2Cl2 (3 mL), a solution
of EDA (1.61 g, 11.4 mmol, 3.0 eq.) in anhydrous CH2Cl2 (10 mL) was added at 40 °C via a
syringe pump over a period of 5 h. After dilution with 50 mL CH2Cl2 the mixture was washed
with sat. NaHCO3 (2×50 mL) and H2O (2×50 mL). After drying (MgSO4) the solvent was
removed by rotary evaporator. Separation of the crude product (1:1 mixture of diastereomers
6b and 7b) by column chromatography (silica gel, cyclohexane/EtOAc, 40:1) was incomplete
and provided a fraction with both diastereomers and pure fractions of 6b and 7b as colorless
oils. Yield (all fractions): 0.74 g (63%).
Page 12 of 24

11
1
3
6b: H NMR (300 MHz, CDCl3): δ 1.04 (t, JH,H = 7.1 Hz, 3 H, 12-CH3), 1.91 (ddd,
3
3
2
2JH,H = 7.4, JH,H(cis) = 10.5, JH,F(cis) = 19.5 Hz, 1 H, HA), 2.03 (dt, JH,H = 7.4, 3JH,H(trans) = 7.9
Hz 3JH,F(trans) = 12.9 Hz, 1 H, HB), 2.61 (ddd, 3JH,H(trans) = 7.9 Hz, 3JH,H(cis) = 10.5 Hz, 3JH,F(cis)
=
3
3
18.4 Hz, 1H, HX), 3.95 (q, JH,H = 7.0 Hz, 2 H, 11-CH2), 7.56 (d, JH,H = 8.2 Hz, 2 H, 6/10-
3
13
CH), 7.75 (d, JH,H = 8.4 Hz, 2 H, 7/9-CH). C NMR (75 MHz, CDCl3): δ 13.9 (s, 12-C),
2
2
17.0 (d, JC,F = 9.9 Hz, 3-C), 28.6 (d, JC,F = 16.0 Hz, 2-C), 61.1 (s, 11-C), 81.8 (d,
1JC,F = 221.6 Hz, 4-C), 125.8 (t, 4JC,F = 4.7 Hz, 7/9-C), 128.2 (d, 3JC,F = 5.0 Hz, 6/10-C), 136.9
3
19
(d, 2JC,F = 21.2 Hz, 5-C), 142.2 (m, 8-C), 168.4 (d, JC,F = 1.9 Hz, 1-C). F NMR (282 MHz,
CDCl3): δ -159.45 (ddd, 3JH,F(trans) = 12.6, 3JH,F(cis) = 18.4, 3JH,F(cis) = 19.5 Hz, 1 F, 4-CF), 62.23
(d, 2JF,F = 150.7 Hz, 4 F, SFeq), 83.08 (p, 2JF,F = 150.7 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd.
for C12H12F6O2SNa+: 357.0354; found 357.0354. MS (GC/EI) m/z (%): 334 (21) [M+], 315 (5)
[M+-F], 306 (21) [M+-C2H5], 286 (8) [315-C2H5O], 279 (32), 261 (9) [M+-C3H5O2], 251 (73)
[C10H7F4OS+], 231 (16) [251-HF], 207 (4) [M+-SF5], 179 (4) [306–SF5], 162 (19)
+
[C10H7FO+], 151 (5), 134 (100) [C9H7F+], 132 (60) [C6H8FO2 ], 115 (11) [134-F], 89 (6), 83
(5), 55 (19).
1
3
7b: H NMR (300 MHz, CDCl3): δ 1.30 (t, JH,H = 7.1 Hz, 3 H, 12-CH3), 1.67 (ddd,
3
3
3
2JH,H = 7.2, JH,H(cis) = 9.5, JH,F(trans) = 10.6 Hz, 1 H, HB), 2.23 (ddd, JH,F(trans) = 3.0,
3
2
3
3JH,H(trans) = 8.0, JH,H(cis) = 9.4 Hz, 1 H, HX), 2.39 (ddd, JH,H = 7.2, JH,H(trans) = 8.0,
3JH,F(cis) = 20.3 Hz, 1 H, HA), 4.24 (qm, 3JH,H = 7.1 Hz, 2 H, 11-CH2), 7.36 (m, 2 H, 6/10-CH),
7.78 (m, 2 H, 7/9-CH). 13C NMR (75 MHz, CDCl3): δ 14.2 (s, 12-C), 19.6 (d, 2JC,F = 12.1 Hz,
2
1
3-C), 29.9 (d, JC,F = 11.3 Hz, 2-C), 61.5 (s, 11-C), 79.8 (d, JC,F = 229.2 Hz, 4-C), 124.1 (d,
3
3JC,F = 7.4 Hz, 6/10-C), 126.3 (m, 7/9-C), 141.6 (d, JC,F = 22.3 Hz, 5-C), 153.3 (m, 8-C),
3
19
3
167.0 (d, JC,F = 2.4 Hz, 1-C). F NMR (282 MHz, CDCl3): δ -192.72 (ddd, JH,F(trans) = 3.0,
3
2
3JH,F(trans) = 10.6, JH,F(cis) = 20.5 Hz, 1 F, 4-CF), 62.38 (d, JF,F = 149.8 Hz, 4 F, SFeq), 83.61
2
(p, JF,F = 149.8 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd. for C12H12F6O2SNa+: 357.0354;
found 357.0345. MS (GC/EI), m/z (%): 334 (14) [M+], 315 (4) [M+-F], 306 (18) [M+-C2H5],
289 (8), 279 (29), 261 (9) [M+-C3H5O2], 251 (60) [C10H7F4OS+], 231 (13) [251-HF], 207 (4)
[M+-SF5], 179 (3) [306–SF5], 162 (22) [C10H7FO+], 151 (5), 134 (100) [C9H7F+], 132 (63)
+
[C6H8FO2 ], 115 (12) [134-F], 107 (7), 89 (6), 83 (5), 55 (19).
4.6. Saponification
4.6.1. cis-2-Fluoro-2-(3-pentafluorosulfanylphenyl)-cyclopropylcarboxylic acid (8a)
Similarly to the procedure [14] 6a (1.1 g, 3.3 mmol) was treated with KOH (1.85 g, 33 mmol,
10 eq.) in methanol (15 mL) and stirred at room temperature for 12 h. Subsequently the
mixture was diluted with ice/water (50 mL) and extracted with CH2Cl2 (2×20 mL). This
Page 13 of 24

12
solution was discarded. The aqueous layer was acidified to pH 1 and extracted with CH2Cl2
(3×20 mL). The combined organic layers were washed with H2O (2×50 mL). After drying
(MgSO4) the solvent was removed by rotary evaporator to give the corresponding carboxylic
acid 8a. The acid was purified by recrystallization from CH2Cl2/pentane to give white
1
needles. Yield: 0.6 g (59%). Mp 179 °C (CH2Cl2/pentane). H NMR (300 MHz, MeOD): δ
2
3
3
2
1.92 (ddd, JH,H = 7.4, JH,H(cis) = 10.4, JH,F(cis) = 19.6 Hz, 1 H, HA), 2.01 (ddd, JH,H = 7.4,
3
3
3
3JH,H(trans) = 7.8, JH,F(trans) = 12.7 Hz, 1 H, HB), 2.62 (ddd, JH,H(trans) = 7.8, JH,H(cis) = 10.4,
4
3
3JH,F(cis) = 18.4 Hz, 1 H, HX), 7.58 (m, 1 H, 7-CH), 7.73 (dd, JH,F = 1.4, JH,H = 7.8 Hz, 1 H,
4
6-CH), 7.83 (m, 1 H, 8-CH), 7.91 (q, JH,F = 1.8 Hz, 1 H, 10-CH). 13C NMR (75 MHz,
2
2
MeOD): δ 17.5 (d, JC,F = 10.2 Hz, 3-C), 29.2 (d, JC,F = 15.8 Hz, 2-C), 83.6 (d,
3
1JC,F = 220.7 Hz, 4-C), 127.0 (q, JC,F = 4.7 Hz, 8-C), 127.7 (m, 10-C), 130.2 (s, 7-C), 133.0
3
2
2
(d, JC,F = 4.3 Hz, 6-C), 136.4 (d, JC,F = 20.9 Hz, 5-C), 155.0 (t, JC,F = 17.3 Hz, 9-C), 171.9
4
3
(d, JC,F = 1.4 Hz, 1-C). 19F NMR (282 MHz, CDCl3): δ -156.63 (ddd, JH,F = 12.7,
3
3
2
3JH,F = 18.6, JH,F = 19.6 Hz, 1 F, 4-CF), 62.12 (dq, JH,F = 1.9, JF,F = 150.4 Hz, 4 F, SFeq),
2
83.45 (p, JF,F = 150.4 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd. for C10H8F6O2S·Na+:
329.0041; found 329.0036. HRMS (ESI neg.), m/z: calcd. for C10H7F6O2S-: 305.0076; found
305.0082; calcd. for [C10H7F6O2S-]2+H+: 611.0215; found 611.0245.
4.6.2. trans-2-Fluoro-2-(3-pentafluorosulfanylphenyl)-cyclopropylcarboxylic acid (9a)
Similarly to the procedure [14] 7a (0.71 g, 2.1 mmol) was treated with KOH (1.18 g,
21 mmol, 10 eq.) in methanol (15 mL) and stirred for 12 h at roomtemperature. Subsequently
the mixture was diluted with ice/water (50 mL) and extracted with CH2Cl2 (2×20 mL). This
solution was discarded. The aqueous layer was acidified to pH 1 and again extracted with
CH2Cl2 (3×20 mL). The combined organic layers were washed with H2O (2×50 mL). After
drying (MgSO4) the solvent was removed by rotary evaporator to give the corresponding
carboxylic acid 9a. For purification the acid was recrystallized from CH2Cl2/pentane to give
1
white needles. Yield: 0.47 g (72%). Mp 147 °C (CH2Cl2/pentane). H NMR (300 MHz,
2
3
3
CDCl3): δ 1.78 (ddd, JH,H = 7.3, JH,H(cis) = 9.4, JH,F(trans) = 10.7 Hz, 1 H, HB), 2.26 (ddd,
3
3
2
3JH,F(trans) = 2.6, JH,H(trans) = 7.8, JH,H(cis) = 9.4 Hz, 1 H, HX), 2.41 (ddd, JH,H = 7.3,
3
3
3JH,H(trans) = 7.8, JH,F(cis) = 20.2 Hz, 1 H, HA), 7.41 (d, JH,H = 7.9 Hz, 1 H, 8-CH), 7.51 (t,
3JH,H = 7.9 Hz, 1 H, 7-CH), 7.74 (m, 2 H, 6/10-CH), 11.64 (br s, 1 H, 1-COOH). 13C NMR
2
2
(75 MHz, CDCl3): δ 19.6 (d, JC,F = 12.0 Hz, 3-C), 29.0 (d, JC,F = 11.4 Hz, 2-C), 80.7 (d,
3
3
1JC,F = 230.9 Hz, 4-C), 122.4 (dt, JC,F = 4.6, 7.9 Hz, 10-C), 126.0 (p, JC,F = 4.9 Hz, 8-C),
3
2
127.5 (d, JC,F = 6.2 Hz, 6-C), 129.3 (s, 7-C), 138.3 (d, JC,F = 21.9 Hz, 5-C), 154.2 (p,
2JC,F = 17.2 Hz, 9-C), 173.9 (s, 1-C). 19F NMR (282 MHz, CDCl3): δ -188.38 (ddd,
Page 14 of 24

13
3
3
2
3JH,F(trans) = 2.6, JH,F(trans) = 10.8, JH,F(cis) = 20.4 Hz, 1 F, 4-CF), 62.19 (d, JF,F = 150.0 Hz,
2
4 F, SFeq), 83.13 (p, JF,F = 150.0 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd. for
C10H8F6O2S·Na+: 329.0041; found 329.0040. HRMS (ESI neg.), m/z: calcd. for C10H7F6O2S-:
305.0076; found 305.0077; calcd. for [C10H7F6O2S-]2+H+: 611.0215; found 611.0245.
4.6.3. cis-2-Fluoro-2-(4-pentafluorosulfanylphenyl)-cyclopropylcarboxylic acid (8b)
Similarly to the procedure [14] 6b (1.38 g, 4.5 mmol) was treated with KOH (2.52 g,
45 mmol, 10 eq.) in methanol (15 mL) and stirred at room temperature for 12 h. Subsequently
the mixture was diluted with ice/water and extracted with CH2Cl2 (2×20 mL). This solution
was discarded. The aqueous layer was acidified to pH 1 and again extracted with CH2Cl2
(3×20 mL). The combined organic layers were washed with H2O (2×50 mL). After drying
(MgSO4) the solvent was removed by rotary evaporator to give the corresponding carboxylic
acid 8b. The acid was purified by recrystallization from EtOAc/pentane to give white needles.
1
Yield: 0.64 g (46%). Mp 128 °C (EtOAc/pentane). H NMR (300 MHz, CDCl3): δ 1.89-2.05
3
3
3
(m, 2 H, HA/HB), 2.57 (ddd, JH,H(trans) = 7.9, JH,H(cis) = 10.2, JH,F(cis) = 18.0 Hz, 1 H, HX),
3
4
3
7.53 (d, JH,H = 8.0 Hz, 2 H, 6/10-CH), 7.74 (dp, JH,F = 1.1, JH,H = 8.1 Hz, 2 H, 7/9-CH),
13
2
9.91 (br s, 1 H, 1-COOH). C NMR (75 MHz, CDCl3): δ 17.6 (d, JC,F = 9.9 Hz, 3-C), 28.2
(d, 2JC,F = 16.9 Hz, 2-C), 82.3 (d, 1JC,F = 223.0 Hz, 1-C), 125.9 (t, 3JC,F = 4.7 Hz, 7/9-C), 128.3
3
2
(d, JC,F = 4.9 Hz, 6/10-C), 136.2 (d, JC,F = 20.8 Hz, 5-C), 152.8 (m, 8-C), 174.3 (d,
3JC,F = 1.7 Hz, 1-C). 19F NMR (282 MHz, CDCl3): δ -157.6 (m, 1 F, 4-CF), 62.15 (d,
2
2JF,F = 150.0 Hz, 4 F, SFeq), 83.32 (p, JF,F = 150.0 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd.
for C10H8F6O2S·Na+: 329.0041; found 329.0036. HRMS (ESI neg.), m/z: calcd. for
C10H7F6O2S-: 305.0076; found 305.0067.
X-ray crystal structure analysis of 8b (haf5673) [15]: formula C10H8F6O2S, M = 306.22,
colorless crystal, 0.30 × 0.15 × 0.15 mm, a = 5.7172(3), b = 19.3208(8), c = 10.7850(4) Å, β
= 104.516(3)°, V = 1153.29(9) Å3, ρcalc = 1.764 gcm-3, μ = 3.285 mm-1, empirical absorption
correction (0.439 ≤ T ≤ 0.638), Z = 4, monoclinic, space group P21/c (No. 14), λ = 1.54178 Å,
T = 223(2) K, ω and φ scans, 7791 reflections collected (±h, ±k, ±l), [(sin)/λ] = 0.60 Å-1,
1989 independent (Rint = 0.034) and 1895 observed reflections [I>2σ(I)], 173 refined
parameters, R = 0.033, wR2 = 0.092, max. (min.) residual electron density 0.23 (-0.35) e.Å-3,
the hydrogen atoms were calculated and refined as riding atoms.
4.6.4. trans-2-Fluoro-2-(4-pentafluorosulfanylphenyl)-cyclopropylcarboxylic acid (9b)
Similarly to the procedure [14] 7b (0.8 g, 2.6 mmol) was treated with KOH (1.45 g, 26 mmol,
10 eq.) in methanol (15 mL) and stirred at room temperature for 12 h. Subsequently the
Page 15 of 24

14
mixture was diluted with ice/water (50 mL) and extracted with CH2Cl2 (2×20 mL). This
solution was discarded. The aqueous layer was acidified to pH 1 and again extracted with
CH2Cl2 (3×20 mL). The combined organic layers were washed with H2O (2×50 mL). After
drying (MgSO4) the solvent was removed by rotary evaporator to give the corresponding
carboxylic acid 9b, which was purified by recrystallization from EtOAc/pentane to give white
1
needles. Yield: 0.24 g (30%). Mp 146 °C (EtOAc/pentane). H NMR (300 MHz, CDCl3): δ
1.77 (ddd, 2JH,H = 7.3, 3JH,H(cis) = 9.4, 3JH,F(trans) = 10.7 Hz, 1 H, HB), 2.26 (ddd, 3JH,F(trans) = 2.6,
3
2
3
3JH,H(trans) = 7.9, JH,H(cis) = 9.3 Hz, 1 H, HX), 2.42 (ddd, JH,H = 7.3 JH,H(trans) = 7.9,
3
3
3JH,F(cis) = 20.2 Hz, 1 H, HA), 7.38 (d, JH,H = 8.5 Hz, 2 H, 6/10-CH), 7.79 (d, JH,H = 8.4 Hz,
2 H, 7/9-CH), 11.24 (br s, 1 H, 1-COOH). 13C NMR (75 MHz, CDCl3): δ 20.0 (d,
2
1
2JC,F = 12.0 Hz, 3-C), 29.4 (d, JC,F = 11.2 Hz, 2-C), 80.4 (d, JC,F = 230.8 Hz, 4-C), 124.4 (d,
2
3JC,F = 7.3 Hz, 6/10-C), 126.5 (m, 7/9-C), 140.9 (d, JC,F = 22.1 Hz, 5-C), 153.5 (m, 8-C),
173.5 (s, 1-C). 19F NMR (282 MHz, CDCl3): δ -191.07 (ddd, 3JH,F(trans) = 2.6, 3JH,F(trans) = 10.8,
2
3JH,F(cis) = 20.4 Hz, 1 F, 4-CF), 62.34 (d, JF,F = 150.0 Hz, 4 F, SFeq), 83.29 (p,
2JF,F = 150.0 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd. for C10H8F6O2S·Na+: 329.0041; found
329.0036. HRMS (ESI neg.), m/z: calcd. for C10H7F6O2S-: 305.0076; found 305.0067.
X-ray crystal structure analysis of 9b (haf5672) [15]: formula C10H8F6O2S, M = 306.22,
colorless crystal, 0.50 × 0.17 × 0.03 mm, a = 17.1116(10), b = 5.1647(3), c = 13.5304(17) Å,
β = 104.206(7)°, V = 1159.20(17) Å3, ρcalc = 1.755 gcm-3, μ = 3.268 mm-1, empirical
absorption correction (0.291 ≤ T ≤ 0.908), Z = 4, monoclinic, space group P21/c (No. 14), λ =
1.54178 Å, T = 223(2) K, ω and φ scans, 7806 reflections collected (±h, ±k, ±l), [(sin)/λ] =
0.60 Å-1, 1951 independent (Rint = 0.049) and 1663 observed reflections [I>2σ(I)], 173 refined
parameters, R = 0.049, wR2 = 0.158, max. (min.) residual electron density 0.29 (-0.23) e.Å-3,
the hydrogen atoms were calculated and refined as riding atoms.
4.7. Curtius degradation
4.7.1. tert-Butyl cis-[2-fluoro-2-(3-pentafluorosulfanylphenyl)cyclopropyl]carbamate (10a)
Similarly to the procedure [14] 8a (0.31 g, 1.0 mmol) was treated with triethylamine (152 mg,
1.5 mmol, 1.5 eq.), tert-butanol (0.74 g, 10 mmol, 10 eq.) and diphenylphosphorylazide
(DPPA, 824 mg, 3 mmol, 3 eq.) in dry cyclohexane (15 mL). After reflux for 12 h Boc2O
(328 mg, 1.5 mmol, 1.5 eq.) was added. Subsequently the mixture was diluted with EtOAc
(50 mL) and washed with 5% citric acid (20 mL), sat. NaHCO3 (20 mL), water (20 mL) and
sat. NaCl solution (20 mL). After drying (MgSO4) the solvent was removed by rotary
evaporator to give the Boc-protected amine 10a. Column chromatography (silica gel,
cyclohexane/EtOAc, 10:1) and subsequent recrystallization from pentane/CH2Cl2 furnished
Page 16 of 24

15
1
10a as a white solid. Yield: 334 mg (89%). Mp 118 °C (pentane/CH2Cl2). H NMR (400
3
2
MHz, DMSO): δ 1.08 (s, 9 H, 12/13/14-CH3), 1.65 (ddd, JH,H(trans) = 6.1, JH,H = 9.4,
2
3
3
3JH,F(trans) = 13.8 Hz, 1 H, HB), 1.81 (ddd, JH,H = 9.4, JH,H(cis) = 9.8, JH,F(cis) = 22.2 Hz, 1 H,
3
3
3
HA), 3.18 (ddd, JH,H(trans) = 6.1, JH,H(cis) = 9.8, JH,F(cis) = 13.4 Hz, 1 H, HX), 7.15 (dt,
3
3
4JH,H = 1.1, JH,H = 8.5 Hz, 1 H, 6-CH), 7.65 (t, JH,H = 8.5 Hz, 1 H, 7-CH), 7.72 (s, 1 H,
4
3
10-CH), 7.86 (dt, JH,H = 2.0, JH,H = 7.6 Hz, 1 H, 8-CH). 13C NMR (101 MHz, DMSO): δ
2
2
16.7 (d, JC,F = 10.8 Hz, 3-C), 27.6 (s, 12/13/14-C), 34.5 (d, JC,F = 18.3 Hz, 3-C), 78.0 (s,
1
3
3
11-C), 81.4 (d, JC,F = 216.7 Hz, 4-C), 119.8 (d, JC,F = 5.0 Hz, 6-C), 123.0 (dt, JC,F = 4.5,
2
3JC,F = 7.2 Hz, 10-C), 125.1 (m, 8-C), 129.2 (s, 7-C), 136.1 (d, JC,F = 20.8 Hz, 5-C), 152.5
3
(m, 9-C), 155.6 (s, 1-C). 19F NMR (282 MHz, DMSO): δ -172.87 (ddd, JH,F(cis) = 13.4,
3
2
3JH,F(trans) = 13.8, JH,F(cis) = 22.3 Hz, 1 F, 4-CF), 62.37 (d, JF,F = 149.9 Hz, 4 F, SFeq), 83.83
2
(p, JF,F = 150.0 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd. for C14H17F6NO2SNa+: 400.0776;
found 400.0778; calcd. for (C14H17F6NO2S)2Na+: 777.1661; found 777.1645. HRMS (ESI
neg.), m/z: calcd. for C14H16F6NO2S-: 376.0811; found 305.0811. MS (GC/EI), m/z (%): 377
(0) [M+], 342 (1), 321 (2) [M+-C4H8], 303 (1) [M+-HOC4H9], 277 (11) [M+-CO2C4H9], 256
(16), 248 (1) [C10H9F3NOS+], 236 (2), 218 (1), 193 (3) [321-SF5], 176 (1) [302-SF5], 149 (3)
+
+
+
[277-SF5], 133 (5), 121 (2), 101 (5) [CO2C4H9 ], 89 (2) [SF3 ], 74 (2), 57 (100) [C4H9 ], 41
+
(16) [C3H5 ].
4.7.2. tert-Butyl trans-[2-fluoro-2-(3-pentafluorosulfanylphenyl)cyclopropyl]carbamate (11a)
Similarly to the procedure [14] 9a (0.31 g, 1.0 mmol) was treated with triethylamine (152 mg,
1.5 mmol, 1.5 eq.), tert-butanol (0.74 g, 10 mmol, 10 eq.) and DPPA (824 mg, 3 mmol, 3 eq.)
in dry cyclohexane (15 mL). After refluxing for 12 h Boc2O (328 mg, 1.5 mmol, 1.5 eq.) was
added. Subsequently the mixture was diluted with EtOAc (50 mL) and washed with 5% citric
acid (20 mL), sat. NaHCO3 (20 mL), water (20 mL) and sat. NaCl solution (20 mL). After
drying (MgSO4) the solvent was removed by rotary evaporator to give the Boc-protected
amine 11a. Column chromatography (silica gel, cyclohexane/EtOAc, 6:1) and subsequent
recrystallization from pentane/EtOAc furnished 11a as white solid. Yield: 329 mg (87%). Mp
1
128 °C (pentane/CH2Cl2). H NMR (400 MHz, DMSO): δ 1.39 (s, 9 H, 12/13/14-CH3), 1.59
3
2
3
2
(ddd, JH,H(trans) = 6.5, JH,H = 8.4, JH,F(cis) = 22.7 Hz, 1 H, HA), 1.74 (ddd, JH,H = 8.4,
3
3
3
3JH,H(cis) = 9.8, JH,F(trans) = 13.6 Hz, 1 H, HB), 2.85 (ddd, JH,F(trans) = 3.6, JH,H(trans) = 6.5,
3
3
3JH,H(cis) = 9.8 Hz, 1 H, HX), 7.57 (d, JH,H = 7.8 Hz, 1 H, 6-CH), 7.65 (t, JH,H = 8.1 Hz, 1 H,
7-CH), 7.77 (s, 1 H, 10-CH), 7.86 (dd, 4JH,H = 2.5, 3JH,H = 8.2 Hz, 1 H, 8-CH). 13C NMR (101
2
2
MHz, DMSO): δ 18.0 (d, JC,F = 11.0 Hz, 3-C), 28.0 (s, 12/13/14-C), 35.0 (d, JC,F = 9.9 Hz,
2-C), 78.3 (s, 11-C), 78.4 (d, 1JC,F = 218.6 Hz, 4-C), 119.8 (d, 3JC,F = 5.0 Hz, 6-C), 121.4 (dq,
Page 17 of 24

16
3
3
3
3
3JC,F = 4.2, JC,F = 5.3, JC,F = 10.7 Hz, 10-C), 124.9 (dq, JC,F = 7.9, JC,F = 9.3 Hz, 8-C),
2
129.8 (s, 7-C), 140.1 (d, JC,F = 21.0 Hz, 5-C), 153.2 (m, 9-C), 156.3 (s, 1-C). 19F NMR (282
3
3
3
MHz, CDCl3): δ -193.28 (ddd, JH,F(trans) = 3.6 , JH,F(trans) = 13.2, JH,F(cis) = 22.1 Hz, 1 F,
2
2
4-CF), 62.17 (d, JF,F = 150.2 Hz, 4 F, SFeq), 83.12 (p, JF,F = 150.2 Hz, 1 F, SFax). HRMS
(ESI), m/z: calcd. for C14H17F6NO2SNa+: 400.0777; found 400.0778; calcd. for
(C14H17F6NO2S)2Na+: 777.1661; found 777.1662. MS (GC/EI), m/z (%): 377 (0) [M+], 342
(1), 321 (2) [M+-C4H9], 303 (1) [M+-HOC4H9], 277 (13) [M+-CO2C4H9], 256 (16), 248 (1)
[C10H9F3NOS+], 236 (2), 218 (1), 209 (1), 193 (3) [321-SF5], 176 (1) [302-SF5], 149 (3) [277-
+
+
+
SF5], 133 (5), 121 (1), 101 (4) [CO2C4H9 ], 89 (2) [SF3 ], 74 (2), 57 (100) [C4H9 ], 41 (16)
+
[C3H5 ].
4.7.3. tert-Butyl cis-[2-fluoro-2-(4-pentafluorosulfanylphenyl)cyclopropyl]carbamate (10b)
Similarly to the procedure [14] 8b (0.64 g, 2.1 mmol) was treated with triethylamine (319 mg,
3.2 mmol, 1.5 eq.), tert-butanol (1.56 g, 21 mmol, 10 eq.) and DPPA (1.73 g, 6.3 mmol, 3 eq.)
in dry cyclohexane (20 mL). After refluxing for 12 h Boc2O (688 mg, 3.2 mmol, 1.5 eq.) was
added. Subsequently the mixture was diluted with EtOAc (50 mL) and washed with 5% citric
acid (20 mL), sat. NaHCO3 (20 mL), water (20 mL) and sat. NaCl solution (20 mL). After
drying (MgSO4) the solvent was removed by rotary evaporator to give the Boc-protected
amine 10b. Column chromatography (silica gel, cyclohexane/EtOAc, 6:1) and subsequent
recrystallization from pentane/EtOAc furnished 10b as white solid. Yield: 362 mg (46%). Mp
1
185 °C (pentane/EtOAc). H NMR (400 MHz, DMSO): δ 1.09 (s, 9 H, 12/13/14-CH3), 1.71
3
2
3
2
(ddd, JH,H(trans) = 6.1, JH,H = 9.2, JH,F(trans) = 13.8 Hz, 1 H, HB), 1.83 (ddd, JH,H = 9.2,
3
3
3
3JH,H(cis) = 10.1, JH,F(cis) = 22.3 Hz, 1 H, HA), 3.19 (ddd, JH,H(trans) = 6.1, JH,H(cis) = 10.1,
3
3
3JH,F(cis) = 14.2 Hz, 1 H, HX), 7.52 (d, JH,H = 8.5 Hz, 2 H, 6/10-CH), 7.88 (d, JH,H = 8.3 Hz,
2
2 H, 7/9-CH). 13C NMR (101 MHz, DMSO): δ 17.1 (d, JC,F = 11.2 Hz, 3-C), 27.4 (s,
2
1
12/13/14-C), 34.8 (d, JC,F = 18.3 Hz, 2-C), 78.1 (s, 11-C), 81.0 (d, JC,F = 216.9 Hz, 4-C),
3
125.0 (m, 7/9-C), 126.0 (d, JC,F = 7.1 Hz, 6/10-C), 139.2 (d, 2JC,F = 18.7 Hz, 5-C), 151.8 (m,
3
8-C), 155.4 (s, 1-C). 19F NMR (282 MHz, DMSO): δ -176.13 (ddd, JH,F(trans) = 13.8 Hz,
3JH,F(cis) = 14.2, 3JH,F(cis) = 22.3 Hz, 1 F, 4-CF), 64.53 (d, 2JF,F = 150.6 Hz, 4 F, SFeq), 87.81 (p,
2JF,F = 150.6 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd. for C14H17F6NO2SNa+: 400.0776; found
400.0775. MS (GC/EI), m/z (%): 377 (0) [M+], 342 (0) [362-HF], 321 (2) [M+-C4H8], 303 (1)
+
[M+-HOC4H9], 284 (1) [303-F], 277 (8) [M+-CO2C4H9], 256 (9), 240 (1) [C9H5SF5 ], 229 (1),
206 (1), 193 (2) [321-SF5], 176 (3) [302-SF5], 149 (3) [277-SF5], 133 (4), 121 (2), 101 (3)
+
+
+
+
[CO2C4H9 ], 89 (2) [SF3 ], 75 (1), 57 (100) [C4H9 ], 41 (15) [C3H5 ].
Page 18 of 24

17
4.7.4. tert-Butyl trans-[2-fluoro-2-(4-pentafluorosulfanylphenyl)cyclopropyl]carbamate (11b)
Similarly to the procedure [14] 9b (0.24 g, 0.8 mmol) was ) was treated with triethylamine
(121 mg, 1.2 mmol, 1.5 eq.), tert-butanol (0.60 g, 8 mmol, 10 eq.) and DPPA (659 mg,
2.4 mmol, 3 eq.) in dry cyclohexane (15 mL). After refluxing for 12 h Boc2O (262 mg,
1.2 mmol, 1.5 eq.) was added. Subsequently the mixture was diluted with EtOAc (50 mL) and
washed with 5% citric acid (20 mL), sat. NaHCO3 (20 mL), water (20 mL) and sat. NaCl
solution (20 mL). After drying (MgSO4) the solvent was removed by rotary evaporator to give
the corresponding Boc-protected amine 11b. Column chromatography (silica gel,
cyclohexane/EtOAc, 6:1) and subsequent recrystallization from pentane/EtOAc furnished 11b
1
as white solid. Yield: 131 mg (45%). Mp 190 °C (pentane/EtOAc). H NMR (600 MHz,
3
2
DMSO): δ 1.37 (s, 9 H, 12/13/14-CH3), 1.65 (ddd, JH,H(trans) = 6.6, JH,H = 8.5,
3
3
3JH,F(cis) = 22.2 Hz, 1 H, HA), 1.72 (ddd, 2JH,H = 8.5, JH,H(trans) = 9.9, JH,F(trans) = 13.7 Hz, 1 H,
3
3
3
HB), 2.86 (ddd, JH,F(trans) = 3.7, JH,H(trans) = 6.6, JH,H(cis) = 9.9 Hz, 1 H, HX), 7.50 (d,
3
3JH,H = 8.6 Hz, 2 H, 6/10-CH), 7.86 (d, JH,H = 8.6 Hz, 2 H, 7/9-CH). 13C NMR (151 MHz,
2
2
DMSO): δ 19.0 (d, JC,F = 10.8 Hz, 3-C), 28.5 (s, 12/13/14-C), 36.4 (d, JC,F = 9.6 Hz, 2-C),
1
3
78.6 (d, JC,F = 218.1 Hz, 4-C), 78.7 (s, 11-C), 124.7 (m, 7/9-C), 126.3 (d, JC,F = 8.9 Hz,
6/10-C), 143.9 (d, 3JC,F = 20.9 Hz, 5-C), 152.0 (m, 8-C), 157.4 (s, 1-C). 19F NMR (282 MHz,
3
3
DMSO): δ -196.81 (dd, JH,F(trans) = 13.7, JH,F(cis) = 22.2 Hz, 1 F, 4-CF), 64.40 (d,
3
3JH,F = 150.6 Hz, 4 F, SFeq), 87.42 (p, JH,F = 150.1, 1 F, SFax). HRMS (ESI), m/z: calcd. for
C14H17F6NO2SNa+: 400.0776; found 400.0770. HRMS (ESI neg.), m/z: calcd. for
C14H16F6NO2S-: 376.0811; found 305.0809. MS (GC/EI), m/z (%): 377 (0) [M+], 321 (2) [M+-
C4H8], 304 (1) [M+-OC4H9], 284 (1) [304-HF], 277 (7) [M+-CO2C4H8], 256 (9) [277-H-HF],
248 (2) [C8H6F6S+], 229 (1), 206 (1), 193 (1) [321-SF5], 176 (2) [302-SF5], 149 (1) [277-SF5],
+
+
+
133 (4), 121 (2), 101 (3) [CO2C4H9 ], 89 (2) [SF3 ], 74 (2), 59 (16), 57 (100) [C4H9 ], 41 (15)
+
[C3H5 ].
4.8. Deprotection
4.8.1. cis-2-Fluoro-2-(3-pentafluorosulfanylphenyl)cyclopropylamine hydrochloride (12a)
Similarly to procedure [14] 10a (189 mg, 0.5 mmol) was treated with 6M HCl (3 mL) in THF
(3 mL). After stirring for 12 h the solvents were removed under reduced pressure to yield the
corresponding amine hydrochloride. Recrystallization from MeOH/Et2O furnished 12a as a
white solid: Yield: 157 mg (100%). Mp 170 °C (MeOH/Et2O, decomposition). 1H NMR (300
3
2
3
MHz, MeOD): δ 1.90 (ddd, JH,H(trans) = 6.3, JH,H = 9.4, JH,F(trans) = 10.5 Hz, 1 H, HB), 2.06
2
3
3
3
(ddd, JH,H = 9.3, JH,H(cis) = 10.2, JH,F(cis) = 20.3 Hz, 1 H, HA), 3.49 (ddd, JH,H(trans) = 6.3,
3
3
3JH,H(cis) = 10.2, JH,F(cis) = 14.3 Hz, 1 H, Hx), 7.77 (t, JH,H = 8.0 Hz, 1 H, 6-CH), 7.90 (d,
Page 19 of 24

18
3JH,H = 7.2 Hz, 1 H, 7-CH), 8.01 (ddd, JH,H = 1.2, JH,H = 2.2, JH,H = 8.3 Hz, 1 H, 5-CH),
4
4
3
13
2
8.14 (dd, 4JH,H = 1.8 Hz, 1 H, 9-CH). C NMR (75 MHz, MeOD): δ 16.2 (d, JC,F = 13.0 Hz,
2
1
3
2-C), 32.9 (d, JC,F = 21.5 Hz, 1-C), 79.8 (d, JC,F = 221.0 Hz, 3-C), 128.3 (p, JC,F = 4.4 Hz,
7-C), 129.3 (dp, 3JC,F = 4.7, 6.9 Hz, 9-C), 131.4 (s, 6-C), 133.5 (d, 2JC,F = 20.1 Hz, 4-C), 134.1
3
2
(d, JC,F = 2.4 Hz, 5-C), 155.5 (p, JC,F = 17.9 Hz, 8-C). 19F NMR (282 MHz, MeOD): δ
4
3
3
3
-160.63 (dddd, JH,F = 1.4, JH,F(trans) = 10.6, JH,F(cis) = 14.4, JH,F(cis) = 20.4 Hz, 1 F, 3-CF),
63.04 (d, 2JF,F = 147.3 Hz, 4 F, SFeq), 83.53 (p, 2JF,F = 147.3 Hz, 1 F, SFax). HRMS (ESI), m/z:
calcd. for C9H9F6NSH+: 278.0433; found 278.0440; m/z: calcd. for C9H8F5NSH+ [MH-HF]:
258.0370; found 258.0378. Elemental analysis: calcd for C9H10ClF6NS: C, 34.46; H, 3.21; N,
4.47; found: C, 34.37; H, 3.11; N, 4.35.
4.8.2. trans-2-Fluoro-2-(3-pentafluorosulfanylphenyl)cyclopropylamine hydrochloride (13a)
Similarly to the procedure [14] 11a (151 mg, 0.4 mmol) was treated with 6M HCl (3 mL) in
THF (3 mL). After stirring for 12 h the solvents were removed under reduced pressure to
yield the corresponding amine hydrochloride. Recrystallization from MeOH/Et2O furnished
1
13a as a white solid. Yield: 121 mg (96%). Mp 180 °C (MeOH/Et2O, decomposition). H
3
2
3
NMR (600 MHz, MeOD): δ 1.91 (ddd, JH,H(trans) = 6.2, JH,H = 9.4, JH,F(cis) = 22.9 Hz, 1 H,
3
2
3
HA), 1.95 (ddd, JH,H(cis) = 9.3, JH,H = 9.4, JH,F(trans) = 14.2 Hz, 1 H, HB), 3.17 (ddd,
3
3
4
3JH,F(trans) = 0.9, JH,H(trans) = 6.2, JH,H(cis) = 9.3 Hz, 1 H, HX), 7.61 (dd, JH,H = 1.5,
3
4
3JH,H = 8.1 Hz, 1 H, 5-CH), 7.66 (t, JH,H = 8.1 Hz, 1 H, 6-CH), 7.90 (ddt, JH,H = 0.8,
3
4
4
4JH,H = 1.5, JH,H = 7.6 Hz, 1 H, 7-CH), 7.93 (q, JH,H = 1.0, JH,H = 1.5 Hz, 1 H, 9-CH). 13C
2
2
NMR (75 MHz, MeOD): δ 18.1 (d, JC,F = 12.0 Hz, 2-C), 32.8 (d, JC,F = 9.9 Hz, 1-C), 78.7
1
3
3
(d, JC,F = 219.8 Hz, 3-C), 124.4 (dp, JC,F = 5.0, 9.9 Hz, 9-C), 127.7 (p, JC,F = 5.0 Hz, 7-C),
3
2
130.0 (d, JC,F = 5.7 Hz, 5-C), 131.1 (s, 6-C), 138.2 (d, JC,F = 20.9 Hz, 4-C), 155.3 (m, 8-C).
3
19F NMR (564 MHz, MeOD): δ -189.61 (dd, 3JH,F(trans) = 14.1, JH,F(cis) = 22.9 Hz, 1 F, 3-CF),
62.91 (d, 2JF,F = 148.5 Hz, 4 F, SFeq), 83.94 (p, 2JF,F = 148.5 Hz, 1 F, SFax). HRMS (ESI), m/z:
calcd. for C9H9F6NSH+: 278.0433; found 278.0445; m/z: calcd. for C9H8F5NSH+ [MH-HF]:
258.0370; found 258.0379. Elemental analysis: calcd. for C9H10ClF6NS: C, 34.46; H, 3.21; N,
4.47; found: C, 34.18; H, 3.11; N, 4.29.
4.8.3. cis-2-Fluoro-2-(4-pentafluorosulfanylphenyl)cyclopropylamine hydrochloride (12b)
Similarly to procedure [14] 10b (334 mg, 0.9 mmol) was treated with 6M HCl (3 mL) in THF
(3 mL). After stirring for 12 h the solvents were removed under reduced pressure to yield the
corresponding amine hydrochloride. Recrystallization from MeOH/Et2O furnished 12b as a
1
white solid. Yield: 263 mg (95%). Mp 170 °C (MeOH/Et2O, decomposition). H NMR (600
Page 20 of 24

19
3
2
3
MHz, MeOD): δ 1.94 (ddd, JH,H(trans) = 6.3, JH,H = 9.4, JH,F(trans) = 10.7 Hz, 1 H, HB), 2.05
2
3
3
3
(ddd, JH,H = 9.4, JH,H(cis) = 10.3, JH,F(cis) = 20.4 Hz, 1 H, HA), 3.47 (ddd, JH,H(trans) = 6.3,
3
3
3JH,H(cis) = 10.3, JH,F(cis) = 14.5 Hz, 1 H, HX), 7.83 (d, JH,H = 8.0 Hz, 2 H, 5/9-CH), 8.00 (d,
13
2
3JH,H = 8.1 Hz, 2 H, 6/8-CH). C NMR (151 MHz, MeOD): δ 16.2 (d, JC,F = 12.8 Hz, 2-C),
33.1 (d, 2JC,F = 21.2 Hz, 1-C), 79.3 (d, 1JC,F = 220.9 Hz, 3-C), 128.0 (p, 3JC,F = 4.7 Hz, 6/8-C),
3
2
2
130.8 (d, JC,F = 4.1 Hz, 5/9-C), 136.1 (d, JC,F = 20.0 Hz, 4-C), 156.0 (p, JC,F = 18.1 Hz,
19
3
3
7-C). F NMR (564 MHz, MeOD): δ -164.29 (ddd, JH,F(trans) = 10.7 Hz, JH,F(cis) = 14.5 Hz,
2
3JH,F(cis) = 19.8 Hz, 1 F, 3-CF), 62.79 (d, JF,F = 148.2 Hz, 4 F, SFeq), 83.55 (p,
2JF,F = 148.1 Hz, 1 F, SFax). HRMS (ESI), m/z: calcd. for C9H9F6NSH+: 278.0433; found
278.0461; m/z: calcd. for C9H8F5NSH+ [MH-HF]: 258.0370; found 258.0379. Elemental
analysis: calcd. for C9H10ClF6NS: C, 34.46; H, 3.21; N, 4.47; found: C, 34.78; H, 3.20; N,
4.49.
4.8.4. trans-2-Fluoro-2-(4-pentafluorosulfanylphenyl)cyclopropylamine hydrochloride (13b)
Similarly to procedure [14] 11b (60 mg, 0.2 mmol) was treated with 6M HCl (3 mL) in THF
(3 mL). After stirring for 12 h the solvents were removed under reduced pressure to yield the
corresponding amine hydrochloride. Recrystallization from MeOH/Et2O furnished 13b as a
1
white solid. Yield: 50 mg (94%). Mp 190 °C (MeOH/Et2O, decomposition). H NMR (600
3
MHz, MeOD): δ 1.95 (m, 2 H, HA/ HB), 3.19 (m, 1 H, HX), 7.57 (d, JH,H = 8.6 Hz, 2 H,
3
5/9-CH), 7.90 (d, JH,H = 8.2 Hz, 1 H, 6/8-CH). 13C NMR (151 MHz, MeOD): δ 18.8 (d,
2
1
2JC,F = 11.7 Hz, 2-C), 33.2 (d, JC,F = 9.7 Hz, 1-C), 78.4 (d, JC,F = 220.0 Hz, 3-C), 126.3 (d,
3
2
3JC,F = 6.9 Hz, 5/9-C), 127.6 (p, JC,F = 4.7 Hz, 6/8-C), 141.2 (d, JC,F = 21.0 Hz, 4-C), 154.9
2
3
(p, JC,F = 17.5 Hz, 7-C). 19F NMR (564 MHz, MeOD): δ -193.86 (dd, JH,F(trans) = 15.4,
2
2
3JH,F(cis) = 21.7 Hz, 1 F, 3-CF), 62.98 (d, JF,F = 147.7 Hz, 4 F, SFeq), 83.98 (p, JF,F = 147.6,
1 F, SFax). HRMS (ESI), m/z: calcd. for C9H9F6NSH+: 278.0433; found 278.0441. Elemental
analysis: calcd. for C9H10ClF6NS: C, 34.46; H, 3.21; N, 4.47; found: C, 34.64; H, 3.30; N,
4.38.
Supplementary information
Copies of the NMR spectra of all the synthesized compounds are available.
Acknowledgement
Financial support by the Deutsche Forschungsgemeinschaft DFG as a contribution of
Collaborative Research Center (SFB 656, project B1) is gratefully acknowledged.
Page 21 of 24

20
References
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Page 23 of 24

Highlights:
•
•
•
•
•
3- and 4-SF5-substituted benzaldehydes were transformed to the hitherto unknown
styrenes by Wittig reactions.
SF5-substituted α-fluorostyrenes were synthesized by bromofluorination and subsequent
HBr elimination.
Copper(I)-catalyzed reactions with ethyldiazoacetate gave diastereomeric ethyl 2-aryl-2-
fluorocyclopropanecarboxylates.
the diastereomers were saponified and the acids were transformed to corresponding
cyclopropylamines by Curtius degradation.
pKa values of the cyclopropanecarboxylic acids and the cyclopropylamines were
determined.
Page 24 of 24