Strong influence of the trifluoromethyl group on the chemoselectivity of [3+2]-cycloadditions of thiocarbonyl S-methanides with α,β-unsaturated ketones

Article abstract of DOI:10.1016/j.jfluchem.2016.08.009

The in situ-generated reactive thiocarbonyl S-methanides were reacted with fluorinated enones. The type of the obtained [3+2]-cycloadduct depends strongly on the location of the activating CF₃group. In the case of enones containing the CF₃

Full text of DOI:10.1016/j.jfluchem.2016.08.009

Accepted Manuscript
Title: Strong influence of the trifluoromethyl group on the
chemoselectivity of [3+2]-cycloadditions of thiocarbonyl
S-methanides with ␣,␤-unsaturated ketones
Author: Grzegorz Mlosto n´ Paulina Grzelak Heinz
Heimgartner
PII:
S0022-1139(16)30171-3
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2016.08.009
FLUOR 8840
To appear in:
FLUOR
Received date:
Revised date:
Accepted date:
2-7-2016
20-8-2016
20-8-2016
Please cite this article as: Grzegorz Mlosto n´ , Paulina Grzelak, Heinz Heimgartner,
Strong influence of the trifluoromethyl group on the chemoselectivity of [3+2]-
cycloadditions of thiocarbonyl S-methanides with ␣,␤-unsaturated ketones, Journal
of Fluorine Chemistry http://dx.doi.org/10.1016/j.jfluchem.2016.08.009
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Strong influence of the trifluoromethyl group on the chemoselectivity of
3+2]-cycloadditions of thiocarbonylS-methanides with α,β-unsaturated
ketones
[
a,*
a,†
b
Grzegorz Mlostoń , Paulina Grzelak , Heinz Heimgartner
aDepartment of Organic and Applied Chemistry, University of Łódź, Tamka 12, PL-91-403,
Łódź, Poland
bDepartment of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich,
Switzerland
*
Corresponding author: Tel.: +48 42 635 57 61; fax: +48 42 665 51 62.
E-mail address: gmloston@uni.lodz.pl (G. Mlostoń).
†
Part of the planned Ph.D. Thesis of P. G., University of Łódź.

Graphical abstract:
HIGHLIGHTS




Selected fluorinated enones were reacted with thiocarbonyl S-methanides
Type of the obtained [3+2]-cycloadduct depends on the location of the CF
3
unit
Tetrahydrothiophene derivatives were obtained from the CF
3
CH=CH enones
1,3-Oxathiole derivatives were obtained from the CF C=O enones
3
ABSTRACT
The in situ-generated reactive thiocarbonylS-methanides were reacted with fluorinated
enones. The type of the obtained [3+2]-cycloadduct depends strongly on the location of the
activating CF
3
group. In the case of enones containing the CF CH=CH moiety, the [3+2]-
3
cycloaddition occurs chemo- and regioselectively onto the C=C bond to
givetrifluoromethylatedtetrahydrothiophene derivatives. On the other hand, enones containing
the CF –C=O unit react as carbonyl dipolarophiles leading to trifluoromethylated 1,3-
3
oxathiolanes also in a chemo- and regioselective manner. These are the first reported reactions
of thiocarbonylS-methanides with α,β-unsaturated ketones.
Keywords:Fluorinated enones, Thiocarbonyl ylides, [3+2]-Cycloaddition, Sulfur heterocycles,
Chemoselectivity, Regioselectivity

1
. Introduction
ThiocarbonylS-methanides 1 belong to the class of electron-rich S-centered 1,3-
dipoles, with have been studied extensively in the last two decades [1]. They cannot be
isolated but are generated in situ, preferably by thermal decomposition of corresponding 2,2-
disubstituted 1,3,4-thiadiazolines. In the presence of a suitable dipolarophile, they undergo
[
3+2]-cycloaddition leading to diverse five-membered sulphur hererocycles. In addition, some
ethylenic dipolarophiles, activated by strongly electron-withdrawing substituents (e.g.
CF ,C≡N, CO R), react with thiocarbonylS-methanides via a stepwise mechanism with a
3
2
zwitterionicintermediate to give also seven-membered sulfur heterocycles [2].
In general, electron-deficient dipolarophiles are the preferred reaction partners for
[
3+2]-cycloadditions of 1, and α,β-unsaturated ketones are well known as active dieno- and
dipolarophiles. However, their reactions with thiocarbonylS-methanides have not been
reported to date.
Due to our ongoing interest in the development of methods for the preparation of fluorinated
heterocyclic compounds, α,β-unsaturated ketones of types 2 and 3, bearing a CF group, were
3
prepared and tested as dipolarophiles in reactions with in situ-generated aromatic and
cycloaliphatic thiocarbonylS-methanides.Up to know, fluorinated α,β-unsaturated ketones
have widely been applied for the synthesis of fluorinated heterocycles with diverse ring size,
but their reactions with 1,3-dipoles, leading to 5-membered heterocyclic products, are very
little known [3a].
2
. Results and discussion
The fluorinated α,β-unsaturatedketones 2 and 3 are attractive building blocks for the
preparation of more complex fluorinated organic compounds, mainly via heterocyclization
reactions, e.g. regioselective syntheses of pyrazoles with hydrazine and its derivatives [3b–c].
The synthesis of 1-aryl-4,4,4-trifluorobut-2-en-1-ones 2 was described recently [4a–c],
starting with 2-bromo-3,3,3-trifluoropropene, which in the first step is treated with LDA, and
the formed acetylide reacts with an aromatic aldehyde. Subsequent reduction of the C≡C
group and oxidation of theintermediate allylalcohol lead to chalcones2. In general, derivatives
2
are little known compounds and only few examples of their applications have been reported.
On the other hand, the 4-aryl-1,1,1-trifluorobut-3-en-2-ones 3 are easily available via aldol
condensation of trifluoroacetone and aryl or hetaryl aldehydes, and they have been widely

applied in organic synthesis, including chemoselective [3+2]-cycloaddition onto the C=C
bond with selected diazo compounds [5].
The precursor of thiobenzophenone S-methanide (1a), i.e. 2,2-diphenyl-1,3,4-
°
thiadiazoline 4a, was prepared from thiobenzophenone and diazomethane in THF at 70 C,
and after addition of an equivalent amount of the α,β-unsaturated ketone 2a, the mixture was
°
warmed to 40 C. At this temperature, elimination of N
2
starts and the reactive 1a was
1
generated and trapped by the dipolarophile2a. The H NMR analysis of the crude mixture
indicated the formation of a single product, which was identified as tetrahydrothiophene
1
derivative 5a (Scheme 1, Table 1). Characteristic signals in the H NMR spectrum attributed
2
to the H
2
C(5) group are two doublet doublet at 2.87 and 3.16 ppm with JH,H = 12.0 Hz and
3JH,H = 10.2 and 7.8 Hz, respectively. Two others signals at 4.15–4.24 ppm (m) and 5.15 (d,
3JH,H = 7.2 Hz) were assigned to HC(4) and HC(3), respectively. The coupling constant3JH,H
.2 Hz for HC(3) (4.2 Hz in 5b and 5c, 6.0 in 5d) can be attributed to the trans-configuration
=
7
in this series of tetrahydrothiophenes 5. This conclusion is based on the assumption that 1,3-
dipolar cycloadditions of thiocarbonylylides of type 1 with C=C dipolarophiles containing
two vicinal electron-withdrawing groups occur under retention of the configuration [2b, 6]. In
general, coupling constants 3JH(3),H(4) in tetrahydrothiophenes of type 5 are with limited
diagnostic value for determination of configuration along the C(3)–C(4) bond. A strong IR
absorption localized at 1690 cm–1 confirmed the presence of the benzoyl group. The
regioselective formation of 5a results from the preferred orientation of the nucleophilic
terminus of 1a, i.e. CH , toward the β-position of the Michael-type dipolarophile 2a.
2
The cycloaliphatic thiocarbonylS-methanides 1b and 1c were generated in situ by
heating of the precursors 4b and 4c, respectively, in THF at 45 °C in the presence of an enone
2
. In each experiment, only one product was formed and identified as an analogue of 5a
Table 1).
Firstly, the reactivity of enones of type 3 was tested in the reaction of 3a with 1b using
equimolar amounts of 3a and 4b. After completion of the N -evolution, the analysis of the
(
2
crude mixture showed that, along with a new product, substantial amounts of 3a were still
present. In addition, the spiro-thiirane formed via electrocyclic ring closure of 1b [6a] was
present in the mixture in ca. 25%. This result points out that the reactivity of enones 3 is
reduced in comparison with those of the isomers 2. Therefore, 3 and 4 were used in a molar
ration of 1:1.1.

The IR spectrum of the product obtained from the ylide1b and the enone 3a evidenced
the absence of a carbonyl group. On the other hand, the elemental analysis and the mass
1
spectrum confirmed that the product is a 1:1 adduct of 1b and 3a. In the H NMR spectrum,
along with four signals for the methyl groups (1.22, 1.30, 1.35 and 1.40 ppm), two doublets at
6
.22 and 6.92 (3JH,H = 16.2 Hz) revealed the presence of a styryl residue. In addition, an AB-
system at 3.19 and 3.45 ppm with 2JH,H = 12.0 Hz is a typical pattern for the CH
unit in five-
2
membered cycloadducts of thiocarbonyl S-methanides [7]. Based on these data, the structure
of the product was formulated as 1,3-oxathiolane 6b. An additional support for this structure
was the 13C NMR absorption at 102.9 ppm, which is characteristic for C(2) in 1,3-
oxathiolanes and related systems [8]. In all experiments with enones of type 3 and
thiocarbonyl S-methanides 1, 1,3-oxathiolanes 6 were obtained as the sole products formed
via the [3+2]-cycloaddition onto the C=O bond. Their structures were provided by the
spectroscopic data, which correlated well with those discussed for 6c.
These results are in line with earlier reports on [3+2]-cycloadditions of diverse 1,3-
dipoles with ketones, which are, in general, poor dipolarophiles, and only activation by one or
two electron-withdrawing groups attached to the C=O function allow a smooth formation of
the five-membered cycloadducts [7,9].
3
. Conclusions
The presented study showed that the activation of α,β-unsaturated ketones by the electron-
withdrawing CF group enables the [3+2]-cycloadditions with electron-rich thiocarbonyl S-
methanides. However, depending on the location of the CF group, the reactive dipolarophilic
3
3
part of the enones is either the C=C or the C=O group. The activated C=C bond in enones 2
reacts as exclusive dipolarophile, whereas in enones 3 the activated C=O group is the more
reactive -system for the [3+2]-cycloaddition reaction with thiocarbonyl S-methanides.
Furthermore, the experiments evidenced that enones 2 are potent dipolarophiles, which
efficiently trap the in situ-generated S-methanides 1 without formation of any side products
such as thiiranes or 1,4-dithianes. The reported results indicate that fluorinated enones both of
type 2 and 3 can be considered as attractive dipolarophiles for further exploration in [3+2]-
cycloadditions with diverse 1,3-dipoles leading to fluoroalkylated, 5-membered heterocycles.

4
. Experimental
4
.1. General information
Melting points were determined on a Mel-Temp II apparatus(Aldrich) in capillaries,
1
13
1
19
and they are uncorrected. The H, C{ H} and F NMR spectra were recorded on Bruker
Avance III 600 or Varian Gemini BB 200 spectrometers using solvent signals as reference.
1
3
Assignments of signals in C NMR spectra were made on the basis of HMQC experiments.
The IR spectra were measured using an NEXUS FT-IR spectrophotometer. HR-ESI-MS were
recorded on a Bruker maxis spectrometer in the laboratory of Mass spectrometry at the
University of Zurich. Elemental analyses were performed in the Microanalytical Laboratory
of the Faculty of Chemistry in Lodz.
4
.2. Materials
Commercial
trifluoroacetonewere purchased from Sigma-Aldrich. 1,1,3,3-Tetramethyl-8-thia-5,6-
diazaspiro[3.4]oct-5-en-2-one (4b) [10] and spiro[1,3,4-thiadiazol-2(5H),2’-
aldehydes,
2-bromo-3,3,3-trifluoropropene,
and
1,1,1-
3
,7
tricyclo[3.3.1.1 ]decane] (4c) [11] were prepared according to known protocols.
Tetrahydrofuran (THF) was dried over sodium with benzophenone and freshly distilled prior
to its use.
Enones 2 were prepared in a multi-step procedure starting with 2-bromo-3,3,3-
trifluoropropene according to a literature protocol [4a].
(E)-4,4,4-Trifluoro-1-phenylbut-2-en-1-one (2a) [4b]. Yield: 80%. Thick yellow oil ([4b]:
1
yellow oil). H NMR (600 MHz, CDCl
3
): δ6.79–6.85 (m, 1H), 7.52–7.55 (m, 3H), 7.63–7.66
): δ–65.0 (dd, J = 6.8, 2.3 Hz,
1
9
(
m, 1H), 7.98 (d, J = 8.4 Hz, 2H). FNMR(565 MHz, CDCl
3
CF ).
3
(E)-4,4,4-Trifluoro-1-(4-methoxyphenyl)but-2-en-1-one (2b) [4b]. Yield: 75%. Yellow solid,
1
m.p. 40.0–41.0 °C ([4b]: 41.0–43.0 °C). H NMR (600 MHz, CDCl
3
): δ 3.90 (s, 3H, OCH ),
3
6
2
.76–6.82 (m, 1H), 6.98–7.01 (m, 2H), 7.53 (dq, JH,H = 15.6 Hz, JH,F = 1.8), 7.97–7.99 (m,
1
9
H), Hz, 1H). F NMR (188 MHz, CDCl
Enones 3 were prepared from trifluoroacetone and the corresponding aldehyde
according to the known procedure [12].
3
): δ–65.6 (dd, J = 6.4, 2.1 Hz, CF
3
).

(E)-1,1,1-Trifluoro-4-phenylbut-3-en-2-one(3a). Yield: 40%. Yellow oil ([13]; light yellow
1
oil). H-NMR (600 MHz, CDCl
3
): δ 7.02 (d, J = 16.2 Hz, 1H), 7.44–7.47 (m, 2H), 7.49–7.51
19
(
m, 1H), 7.64 (d, J = 7.8 Hz, 2H), 7.97 (d, J = 15.6 Hz, 1H). F NMR (188 MHz, CDCl
3
): δ –
7
8.2 (s, CF ).
3
(E)-1,1,1-Trifluoro-4-(4-methoxyphenyl)but-3-en-2-one(3b).Yield: 34%. Yellow solid, m.p.
1
3
9.0–40.0°C ([14]: yellow solid, 38.0 °C). H NMR (600 MHz, CDCl
3
): δ 3.88 (s, 3H,
OCH
3
), 6.89 (d, J = 15.6 Hz, 1H), 6.96 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.94 (d,
1
9
J = 15.6 Hz, 1H). F NMR (188 MHz, CDCl
3
): δ –78.0 (s, CF ).
3
(E)-1,1,1-Trifluoro-4-(furan-2-yl)but-3-en-2-one(3c).Yield: 58%. Yellow oil ([12]: light
1
yellow oil). H NMR (600 MHz, CDCl
3
): δ 6.56–6.57 (m, 1H), 6.87–6.89 (m, 2H), 7.58–7.61
): δ –78.2 (s, CF ).
(
m, 1H), 7.68 (d, J = 15.6 Hz, 1H). 19F NMR (188 MHz, CDCl
3
3
(E)-1,1,1-Trifluoro-4-(thiophen-2-yl)but-3-en-2-one (3d). Yield: 32%. Yellow solid, m.p.
1
3
7
1
5.0–36.0 °C ([12]: 37.0–38.0 °C). H NMR (600 MHz, CDCl
3
): δ 6.78 (d, J = 15.6 Hz, 1H),
.15 (dd, J = 4.8, 3.6 Hz, 1H), 7.48 (d, J = 3.6 Hz, 1H), 7.58 (d, J = 4.8 Hz, 1H), 8.07 (d, J =
1
9
5.6 Hz, 1H). F NMR (188 MHz, CDCl
3
): δ –78.1 (s, CF ).
3
4
.3. Reactions of fluorinated enones 2 and 3 with thiocarbonyl S-methanides – General
procedures
4
.3.1.With thiobenzophenone S-methanide
A solution of thiobenzophenone (198 mg, 1 mmol) in dry THF (0.5 ml) was cooled to
°

78 C and treated with small portions of an ethereal CH
2
2
N solution until the dark blue color
disappeared. A solution of the corresponding enone2a or 3c (1mmol) in dry THF (0.5 ml) was
°
added at 78 C. Then, the mixture was allowed to warm slowly to r.t. After 30 min, the
solvent was evaporated, and the crude product was purified chromatographically, using as an
eluent a mixture of petroleum ether and ethyl acetate (8:2).
4
.3.1.1. trans-[2,2-Diphenyl-4-(trifluoromethyl)tetrahydrothiophen-3-yl](phenyl)methanone
1
(
5a). Yield: 210.0 mg (51%). Colorless crystals, m.p. 128.1–128.6 °C, (P.E.). H NMR (600
MHz, CDCl
3
): δ 2.87 (dd, J = 12.0, 10.2 Hz, 1H), 3.16 (dd, J = 12.0, 7.8 Hz, 1H), 4.15–4.24
(m, 1H), 5.15 (d, J = 7.2 Hz, 1H), 6.87–6.93 (m, 3H), 7.02–7.04 (m, 2H), 7.10–7.13 (m, 2H),
7
.15–7.17 (m, 1H), 7.19–7.22 (m, 2H), 7.27–7.30 (m, 1H), 7.32–7.34 (m, 2H), 7.46 (d, J =
13
): δ30.1 (q, 3JC,F = 2.0 Hz, CH
), 51.6 (q, 2JC,F = 26.7
7
.4Hz, 2H). C NMR (150 MHz, CDCl
3
2
Hz, C(4)), 55.0 (C(2)), 72.2 (C(3)), 127.1 (q, 1JC,F = 137.1 Hz, CF
), 127.4, 127.5, 127.6,
3

1
1
1
6
28.0, 128.2, 128.3, 128.3, 130.2, 132.7 (15 arom. CH), 138.4, 140.8, 145.2 (3 arom. C),
1
9
98.3 (C=O). F NMR (188 MHz, CDCl
3
): δ –68.9 (d, J = 9.0 Hz, CF
3
). IR (KBr):  2920,
(412.49): C,
–1
690, 1597, 1448, 1268, 1163, 1108, 1005, 698 cm . Anal. calcd for C24
9.87; H, 4.65; S, 7.77; found: C, 69.95; H, 4.88; S, 7.54.
H19OSF
3
4
.3.1.2. (E)-5-[2-(Furan-2-yl)vinyl]-2,2-diphenyl-5-(trifluoromethyl)-1,3-oxathiolane (6a).
1
Yield: 237.2 mg (59%). White solid, m.p. 102.5–103.0 °C (purified chromatographically). H
NMR (600 MHz, CDCl
3
): δ 3.16 (d, J = 12.0 Hz, 1H), 3.47 (d, J = 12.0 Hz, 1H), 6.06 (d, J =
6.2 Hz, 1H), 6.10 (d, J = 3.6 Hz, 1H), 6.25 (dd, J = 3.6, 1.8 Hz, 1H), 6.48 (d, J = 15.6 Hz,
H), 6.96–7.05 (m, 2H), 7.15–7.25 (m, 5H), 7.47–7.50 (m, 4 H). 13C NMR (150
): δ 39.7 (CH
), 89.5 (q, 2JC,F = 29.1 Hz, C(5)), 102.8 (C(2)), 110.2, 111.6, 122.3,
23.3 (4 arom. CH), 124.4 (q, 1JC,F = 283.8 Hz, CF
), 126.7, 127.9, 128.0, 128.2, 128.2, 128.3,
42.8 (9 arom. CH + 2 CH olefin), 143.3, 143.8, 151.5 (3 arom. C). F NMR (188 MHz,
1
1
MHz,CDCl
3
2
1
1
3
1
9
CDCl
3
): δ –76.9 (s, CF
3
). IR (KBr):  2914, 1665, 1486, 1445, 1318, 1147, 1011, 960, 744
–
1
+
cm . HR-ESI-MS: Calcd for C22
H
18
O
2
F
3
S ([M+1] ): m/z 403.09741; found: m/z 403.09757.
4
.3.2. With S-methanides of cycloaliphatic thioketones
The corresponding 1,3,4-thiadiazoline 4b or 4c (1.1 mmol) and the corresponding
chalcon 2a,2b or 3a–3d (1 mmol) was dissolved in dry THF(2 ml). The magnetically stirred
°
mixture was heated in an oil bath (45–50 C) for ca. 3h until the gas burette combined with the
flask indicated the evolution of stoichiometric amounts of N . After removal of the solvent
2
under vacuum, crude products were purified chromatographically, using as an eluent a
mixture of petroleum ether and ethyl acetate (8:2).
4
.3.2.1.
trans-8-Benzoyl-1,1,3,3-tetramethyl-7-(trifluoromethyl)-5-thiaspiro[3.4]octan-2-
1
one(5b). Yield: 244.2 mg (66%). Colorless crystals, m.p. 114.0–114.5 °C (P.E.). H NMR
(
600 MHz, CDCl
3
): δ 1.13, 1.23, 1.44, 1.57 (4s, 12H, 4 CH
3
), 2.84 (dd, J = 12.0, 9.0 Hz, 1H),
3
2
2
.15 (dd, J = 12.0, 7.8 Hz, 1H), 3.19–3.27 (m, 1H), 4.81 (d, J = 4.2 Hz, 1H), 7.51–7.54 (m,
1
3
H), 7.62–7.64 (m,1H), 8.03 (d, J = 7.2 Hz, 2H). C NMR (150 MHz, CDCl
3.7, 26.0 (4 CH ), 48.7, 62.8, 68.0 (3C
), 31.6 (q, 3JC,F = 2.5 Hz, CH ), 54.4 (q, 2JC,F = 26.8
), 128.6, 129.3, 134.1 (5 arom. CH),
36.5 (1 arom. C), 200.5, 219.4 (2 C=O). F NMR (188 MHZ, CDCl ): δ –68.9 (d, J = 8.8
Hz, CF ). IR (KBr):  2974, 1782, 1679, 1448, 1268, 1157, 1116, 907, 710 cm . HR-ESI-
3
): δ 19.5, 22.2,
3
2
q
Hz, C(4)), 71.5 (C(3)), 126.5 (q, 1JC,F = 277.9 Hz, CF
3
1
9
1
3
–1
3

+
MS: Calcd for C19
H
22
O
2
F S ([M+1] ): m/z 371.12871;found: m/z 371.12872. Anal. calcd for
3
C
19
H
19
O SF
2 3
(370.46): C, 61.60; H, 5.72; S, 8.65; found: C, 61.41; H, 5.74; S, 8.43.
4
.3.2.2.
trans-8-(4-Methoxybenzoyl)-1,1,3,3-tetramethyl-7-(trifluoromethyl)-5-
thiaspiro[3.4]octan-2-one (5c). Yield: 335.3g (83%). White solid, m.p. 82.0–82.7 °C
1
(
purified chromatographically). H NMR (600 MHz, CDCl
3
): δ 1.08, 1.18, 1.38, 1.52 (4s, 12H,
4
3
2
CH
3
), 2.77 (dd, J = 12.0, 9.0 Hz, 1H), 3.10 (dd, J = 12.0, 8.4 Hz, 1H),3.15–3.22 (m, 1H),
), 4.71 (d, J = 4.2 Hz, 1H), 6.95 (d, J = 9.0 Hz, 2H), 7.97 (d, J = 8.4 Hz,
H). C NMR (150 MHz, CDCl ): δ 19.3, 22.0, 23.6, 25.7 (4 CH
), 31.5 (q, 3JC,F = 2.0 Hz,
), 48.2, 62.7, 67.8, (3C),54.4 (q, 2JC,F = 26.5 Hz, C(4)), 55.6 (OCH
), 71.3 (C(3)), 114.4
2 arom CH), 126.6 (q, 1JC,F = 277.9 Hz, CF
), 129.5, 130.8 (3 arom. CH), 164.3 (1arom. C),
98.7, 219.4 (2 C=O). F NMR (188 MHz, CDCl ): δ –68.9 (d, J = 8.8 Hz, CF ). IR (film): 
.84 (s, 3H, OCH
3
1
3
3
3
CH
2
3
(
3
1
9
1
2
3
3
–
1
968, 1780, 1673, 1464, 1258, 1163, 1112, 1027, 736 cm .HR-ESI-MS: Calcd for
+
C
20
H
24
O
3
F
3
S ([M+1] ): m/z 401.13928; found: m/z 401.13920.
4
2
.3.2.3.
trans-(4-Methoxyphenyl){4’-(trifluoromethyl)-3,4-dihydro-2H-spiro[adamantane-
1
,2’-thiophen]-3-yl}methanone(5d). Yield: 246.0 mg (60%). Colorless oil. H NMR (600
MHz, CDCl
3
): δ 1.34–1.36 (m, 2H), 1.59–1.70 (m, 5H), 1.80 (br s, 1H), 1.90–1.94 (m, 2H),
.99–2.05 (m, 2H), 2.17 (br s, 1H),2.68–2.70 (m, 1H), 2.98–3.07 (m, 2H), 3.44–3.50 (m, 1H),
.87 (s, 3H, OCH ), 4.37 (d, J= 6.0Hz, 1H), 6.96 (d, J = 9.0 Hz, 2H), 8.00 (d, J = 9.0 Hz,
H). C NMR (150 MHz, CDCl ): δ26.78, 26.79,29.49, 29.50 (4 CH), 34.2, 35.1, 35.3,35.4,
7.0, 37.7, 38.4 (7 CH ), 52.6 (C(2)), 55.6 (OCH
), 56.2(q, 2JC,F = 26.1 Hz, C(4)), 71.4 (C(3)),
14.3, 130.7 (4 arom. CH), 126.5 (q, 1JC,F = 277.9 Hz, CF
), 131.0,163.9 (2 arom. C),199.1
): δ–69.4 (d, J = 9.0 Hz, CF ). IR (KBr): 2911, 1673,
1
3
2
3
1
3
1
3
3
2
3
3
1
9
(C=O). F NMR(188 MHz, CDCl
3
3
–1
1
600, 1511, 1454, 1375, 1258, 1166, 1112, 1030, 840 cm . HR-ESI-MS: Calcd for
+
C
22
H
26
O
2
F S ([M+1] ): m/z 411.16001; found: m/z 411.15988.
3
4
.3.2.4. (E)-1,1,3,3-Tetramethyl-6-styryl-6-(trifluoromethyl)-5-oxa-8-thiaspiro[3.4]octan-2-
one (6b). Yield: 288.6 mg (78%). White solid, m.p. 51.3–52.0 °C (purified
1
chromatographically). H NMR (600 MHz, CDCl
3
): δ 1.22, 1.30, 1.35, 1.40 (4s, 12H, 4 CH ),
3
3
1
.19 (d, J = 12.0 Hz, 1H), 3.45 (d, J = 12.0 Hz, 1H), 6.22 (d, J = 16.2 Hz, 1H), 6.92 (d, J =
6.2 Hz, 1H), 7.30–7.33 (m, 1H), 7.35–7.39 (m, 2H), 7.41–7.42 (m, 2H). C NMR (150
1
3
MHz, CDCl
3
): δ 19.9, 20.9, 22.5, 22.8 (4 CH
3
), 37.6 (CH
2
), 65.7, 67.1 (C(1), C(3)), 89.0 (q,
2
1
JC,F = 28.8 Hz, C(6)), 102.8 (C(4)), 123.5 (1 arom. CH), 124.5 (q, JC,F = 283.6 Hz, CF
3
),
9
1
1
27.0, 128.8, 128.9, 135.2 (4 arom. CH + 2 CH olefin), 135.5 (1 arom. C), 219.6 ( C=O). F

NMR (188 MHz, CDCl
3
): δ –77.0 (s, CF
3
). IR (KBr):  2977, 1774, 1464, 1299, 1185, 1160,
–
1
+
1
068, 1030, 758 cm . HR-ESI-MS: Calcd for C19
H
22
O
2
3
F S ([M+1] ): m/z 371.12871; found:
m/z 371.12872.
4
.3.2.5.
(E)-6-(4-Methoxystyryl)-1,1,3,3-tetramethyl-6-(trifluoromethyl)-5-oxa-8-
1
thiaspiro[3.4]octan-2-one(6c). Yield: 276.0 mg (69%). Colorless oil. H NMR (600 MHz,
CDCl
Hz, 1H), 3.82 (s, 3H, OCH
.0 Hz, 2H), 7.35 (d, J = 9.0 Hz, 2H). C NMR (150 MHz, CDCl
3
): δ 1.21, 1.29, 1.33, 1.38 (4s, 12H, 4 CH
3
), 3.18 (d, J = 12.0 Hz, 1H), 3.43 (d, J = 12.0
3
), 6.07 (d, J = 16.2 Hz, 1H), 6.85 (d, J = 16.2 Hz, 1H), 6.89 (d, J =
1
3
9
3
): δ 19.8, 20.9, 22.5, 22.8
2
(
1
4 CH
3
), 37.6 (CH
2
), 55.6 (OCH
3
), 65.7, 67.0 (C(1), C(3)), 89.1 (q, JC,F = 28.8 Hz, C(6)),
1
02.7 (C(4)), 114.4 (2 arom. CH), 124.5 (q, JC,F = 283.5 Hz, CF
3
1
), 121.2,128.2, 128.3
9
(2arom. CH + 2 CH olefin), 134.6, 160.3 (2 arom. C), 219.8 (C=O). F NMR (188 MHz,
CDCl
3
): δ –77.1 (s, CF
3
).IR (film):  2965, 1784, 1609, 1511, 1464, 1252, 1176, 1071, 818,
–
1
+
6
4
98 cm . HR-ESI-MS: Calcd for C20
01.13941.
H
24
O
3
3
F S ([M+1] ): m/z 401.133928; found: m/z
4
.3.2.6.
(E)-1,1,3,3-Tetramethyl-6-[(2-(thiophen-2-yl)vinyl]-6-(trifluoromethyl)-5-oxa-8-
thiaspiro[3.4]octan-2-one(6d). Yield: 327.1 mg (87%). White solid, m.p. 58.0–58.5 °C
1
(
purified chromatographically). H NMR (600 MHz, CDCl
3
): δ 1.22, 1.28, 1.33, 1.38 (4s,
1
6
2
2H, 4 CH ), 3.16 (d, J = 12.0 Hz, 1H), 3.42 (d, J = 12.0 Hz, 1H), 6.03 (d, J = 15.6 Hz, 1H),
3
1
3
.99–7.06 (m, 3H), 7.25 (d, J = 5.4 Hz, 1H). C NMR (150 MHz, CDCl
3
): δ 19.8, 20.8, 22.5,
2
2.7 (4 CH
3
), 37.6 (CH
2
), 65.7, 67.1 (C(1), C(3)), 88.8 (q, JC,F = 28.9 Hz, C(6)), 102.9
1
(C(4)), 122.6 (1 arom. C), 124.3 (q, JC,F = 283.5 Hz, CF
3
1
), 125.9, 127.6, 127.7, 128.3 (2
9
arom. CH + 2 CH olefin), 140.4 (1 arom. C), 219.5 (C=O). F NMR (188 MHz, CDCl
3
): δ –
–1
7
7.0 (s, CF
Calcd for C17
forC17
3
). IR (KBr):  2965, 1771, 1464, 1245, 1169, 1068, 1030, 701 cm . HR-ESI-MS:
+
H
20
O
2
F
3
S
2
([M+1] ): m/z 377.08513; found: m/z 377.08523. Anal. calcd
H
19
O
2
S
2
F
3
(376.48): C, 54.23; H, 5.10; S, 17.03; found: C, 54.23; H, 5.27; S, 17.16.
4
.3.2.7.
(E)-5’-(4-Methoxystyryl)-5’-(trifluoromethyl)spiro[adamantane-2,2’-
1
[1,3]oxathiolane(6e). Yield: 270.6 mg (66%). Colorless oil. H NMR (600 MHz, CDCl
3
): δ
1
1
6
.65–1.77 (m, 5H), 1.82–1.90 (m, 4H), 2.04–2.11 (m, 2H), 2.20–2.27 (m, 2H), 2.372.43 (m,
H), 3.11, 3.56 (AB, J = 12.0 Hz, 2H), 3.82 (s, 3H, OCH ), 6.08 (d, J = 15.6 Hz, 1H), 6.87–
.90 (m, 3H), 7.35 (d, J = 9.0 Hz, 2H). 13C NMR (150 MHz, CDCl
3
3
): δ 26.7, 26.9 (2
2
CH),33.8, 34.9, 37.4, 37.4, 37.6, 37.7 (6 CH
=
1
2
), 40.0, 40.9 (2 CH), 55.4 (OCH
3
), 88.6 (q, JC,F
28.8 Hz, C(5’)), 105.2 (C(2’)), 114.2, 122.7 (4 arom. CH), 124.6 (q, 1JC,F = 283.3 Hz, CF
),
3
1
9
28.4 (1 CH olefin), 128.7 (1 arom. C), 133.9 (1 CH olefin), 160.0 (1 arom. C). FNMR (188
MHz, CDCl
3
): δ –78.5 (s, CF
3
). IR (film): 2917, 1603, 1515, 1454, 1249, 1173, 1103, 973,
–
1
+
7
4
39 cm . HR-ESI-MS: Calcd for C22
11.15998.
H
26
O
2
3
F S ([M+1] ): m/z 411.16001; found: m/z
Acknowledgement
The authors thank the National Science Center (Cracow) for financial support (Grant Opus-7
UMO-2014/13/B/ST5/04004) and PD Dr. L. Bigler, University of Zürich, for ESI-HRMS.
#

References
[
1]
a) G. Mlostoń, H. Heimgartner, Pol. J. Chem. 74 (2000) 15031533; b) G. Mlostoń, H.
Heimgartner, in ‘Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry
Toward Heterocycles and Natural Products’, Eds. A. Padwa, W. H. Pearson, J. Wiley
&
Sons, New York, 2002, pp. 315360.
[
2]
a) R. Huisgen, G. Mlostoń, E. Langhals, Helv. Chim. Acta 84 (2001) 18051820;
b) R. Huisgen, G. Mlostoń, H. Giera, E. Langhals, Tetrahedron 58 (2002) 507519;
c) R. Huisgen, G. Mlostoń, E. Langhals, T. Oshima, Helv. Chim. Acta 85 (2002)
2
6682685.
[
[
3]
4]
a) V. G. Nenajdenko, E. S. Balenkova, Arkivoc i (2011) 246328;
b) B. J. Gaede, L. L. McDermott, J. Heterocyclic Chem. 30 (1993) 4954;
c) Y. Wang, J. Han, J. Chen, W. Cao, Tetrahedron 71 (2016) 82568262.
a) N. Ikeda, T. Konno, J. Fluorine Chem. 173 (2015) 69–76;
b) A. T. Davies, J. E. Taylor, J. Douglas, C. J. Collett, L. C. Morrill, C. Fallan, A. M.
Z. Slawin, G. Churchill, A. D. Smith, J. Org. Chem. 78 (2013) 92439257;
c) T. Yamazaki, T. Kawasaki-Takasuka, A. Furuta, S. Sakamoto, Tetrahedron 65
(
2009) 59455948.
V. G. Nenajdenko, A. V. Statsuk, E. S. Balenkova, Chem. Heterocycl. Comp. 39
2003) 598603.
[
[
5]
6]
(
a) R. Huisgen, G. Mlostoń, C. Fulka, Heterocycles 23 (1985) 22072212;
b) G. Mlostoń, R. Huisgen, H. Huber, D. S. Stephenson, J. Heterocyclic Chem. 36
(1999) 959968.
[
[
7]
8]
G. Mlostoń, R. Huisgen, K. Polborn, Tetrahedron 55 (1999) 1147511494.
a) A. V. Nikolaev, A. V. Ivanov, L. L. Rodina, G. Mlostoń, Beilstein J. Org. Chem. 9
(2013) 27512761;
b) R. Huisgen, G. Mlostoń, K. Polborn, R. Sustmann, W. Sicking, Liebigs Ann./
Recueil (1997), 179185.
[
9]
a) G. Mlostoń, T. Gendek, H. Heimgartner, Helv. Chim. Acta 79 (1996) 15371548;
b) V. K. Soloshonok, V. P. Kukhar, J. Org. Chem. USSR 26 (1990) 358363;
c) P. Wipf, R. Prewo, J. H. Bieri, G. Germain, H. Heimgartner, Helv. Chim. Acta 71
(1988) 11771190;

d) W. Stegmann, P. Uebelhart, H. Heimgartner, Helv. Chim. Acta 66 (1983)
2522268.
10] R. Huisgen, J. Panelle, G. Mloston, A. Buyle-Padias, H. K. Hall, J. Am. Chem. Soc.
14 (1992) 266274.
2
[
1
[
[
11] R. Huisgen, G. Mlostoń, Polish J. Chem. 73 (1999) 635644.
12] Ch. Zheng, Y. Li, Y. Yang, H. Wang, H. Cui, J. Zhang, G. Zhao, Adv. Synth. Catal.
3
51 (2009) 16851691.
13] P. P. Yeh, D. S. B. Daniels, D. B. Cordes, A. M. Z. Slawin, A. D. Smith,Org. Lett. 16
2014) 964967.
14] A. Gazit, Z. Rappoport, J. Chem. Soc. Perkin Trans. 1 (1984) 28632870.
[
[
(

Fig. 1.Stuctures of thiocarbonylS-methanides 1 and α,β-unsaturated ketones 2 and 3.

Scheme 1. Reactions of thiocarbonyl S-methanides 1 with fluorinated α,β-unsaturated ketones
and 3.
2

Table 1
Formation of trifluoromethylated tetrahydrothiophenes 5 and 1,3-oxathiolanes 6 in reactions
of thiocarbonylS-methanides with α,β-unsaturated ketones 2 and 3.
2 Ar
a Ph
5 Yield [%]a) 3 Ar
6
a
Yield [%] a)
59
1
a Ph,Ph
a 51
c
Ph
b
c
a Ph
b 66
c 83
a
b
d
b
c
78
69
87
4
-MeOC
6
6
H
4
4
b 4-MeOC
6
6
H
4
4
d
4
-MeOC
H
b 4-MeOC
H
d 60
b
e
66
a) Yield of isolated products, calculated with respect to the enone 2 or 3.