A mild and efficient procedure for the N-functionalization of S-perfluoroalkylated aryl sulfoximines

Article abstract of DOI:10.1055/s-0033-1338440

N-Acylated perfluoroalkylated sulfoximines are synthesized easily from the corresponding free NH-sulfoximines on reaction with acid chlorides. This mild procedure is extended to diacid chlorides for the preparation of dimeric N-bridged sulfoximines and to reactions with chloroformates, carbamoyl chlorides, chlorothio-noformates and thiocarbamoyl chlorides as electrophiles. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1338440

PAPER
▌1505
paper
A Mild and Efficient Procedure for the N-Functionalization of
S-Perfluoroalkylated Aryl Sulfoximines
N-Functionalization of S-Perfluoroalkylated Aryl Sulfoximines
Yohan Macé,a,b Céline Constant-Urban,a Sébastien Bouvet,a Bruce Pégot,a Chloée Bournaud,b Martial Toffano,b
Giang Vo-Thanh,*b Patrick Diter,a Emmanuel Magnier*a
a
Institut Lavoisier de Versailles (ILV), UMR CNRS 8180, Université de Versailles, St Quentin en Yvelines, 45 avenue des Etats-Unis,
78035 Versailles Cedex, France
E-mail: emmanuel.magnier@uvsq.fr
b
Laboratoire de Catalyse Moléculaire, Institut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), UMR CNRS 8182,
Université Paris-Sud 11, 91405 Orsay Cedex, France
E-mail: giang.vo-thanh@u-psud.fr
Received: 27.02.2013; Accepted after revision: 02.04.2013
In contrast to non-fluorinated sulfoximines, which have
been studied extensively,1 access to the S-perfluoroalkyl-
ated analogues was, since 1986, strictly limited to the ef-
ficient, but quite cumbersome, synthesis as described by
Abstract: N-Acylated perfluoroalkylated sulfoximines are synthe-
sized easily from the corresponding free NH-sulfoximines on reac-
tion with acid chlorides. This mild procedure is extended to diacid
chlorides for the preparation of dimeric N-bridged sulfoximines and
to reactions with chloroformates, carbamoyl chlorides, chlorothio- Yagupolskii and co-workers.13 In 2009, we proposed a
noformates and thiocarbamoyl chlorides as electrophiles.
more friendly construction of S-perfluoroalkyl sulfoxi-
mines,14 whereas Bolm and co-workers have described an
Key words: fluorinated sulfoximines, acylation, carbamoylation,
ureas, N-bridged sulfoximines
access to N-protected S-trifluoromethyl substituted sulf-
oximines.15 Our general and versatile methodology allows
the production of a wide range of free NH-sulfoximines in
two steps from the corresponding perfluoroalkyl arylsulf-
oxides (Scheme 1).
Sulfoximines are very fascinating and intriguing com-
pounds in organic chemistry. This sulfur(VI) group is
structurally similar to a sulfone moiety, but the replace-
ment of one of the oxygen atoms with a nitrogen has im-
portant electronic and structural consequences, and
expands significantly the utility of this particular moiety.1
The presence of the nitrogen atom allows additional func-
tionalization (vide infra) and increases the electron-
withdrawing ability of the sulfoximine group. Also, the
chirality of these groups (centered on the sulfur atom) is a
major feature of their applications. Sulfoximines have
been widely employed as reagents in asymmetric synthe-
sis,2 as ligands in enantioselective metal catalysis and in
organocatalysis.3 They have also demonstrated potential
in medicinal chemistry4 and in crop sciences.5 The state-
of-art was, until recently, more limited to S-perfluoroal-
kylated sulfoximines, however, a growing number of ap-
plications have since emerged. These compounds have
been described as strongly electron-withdrawing substitu-
ents,6 as building blocks in liquid crystals7 and as efficient
reagents for perfluoroalkyl group transfer.8 Sulfoximine
derivatives have been employed successfully for the elec-
trophilic introduction of trifluoro- and monofluoromethyl
moieties by Shibata,9 difluoromethyl groups by Hu,10 and
bromodifluoro- and dichloromethyl by our group.11 In
2012, Hu expanded the applications of perfluoroalkylated
sulfoximines and showed that mono- and difluoromethyl
derivatives were efficient reagents for the nucleophilic
transfer of perfluorinated units.12
O
NH
RF
O
R
R
S
S
1. MeCN, Tf2O, 12 h, –15 °C
RF
2. KMnO4, H2O, 18 h
3. HCl (6 M), MeCN, 18 h
1
2a–g
49–81%
RF = CF3, C4F9, CF2Br, CFCl2
R = H, Me, Cl
Scheme 1 Previous synthesis of free NH-sulfoximines
Compounds 2 represent a common platform for various
applications, which can be finely-tuned by appropriate
choice of the group attached to the nitrogen atom. For ex-
ample, we have shown that in the case of electrophilic per-
fluoroalkylating reagents, the reactivity was specific to
the fluorinated moiety being delivered.11 Also, an investi-
gation of the coupling reactions between compounds 2
and aryl iodides or bromides, induced by a copper cata-
lyst, revealed an obvious difference with the non-haloge-
nated derivatives.16 During this study, we noticed that the
quantities of catalyst required were greater than those
used in the non-fluorinated series. These results clearly
showed the need for a comprehensive investigation devot-
ed to the N-functionalization of fluorinated sulfoximines.
In continuation of our research on the synthesis of com-
plex sulfoximines, we describe herein our studies devoted
to the direct introduction of various acyl groups (Scheme
2). The knowledge we have acquired in the field of perflu-
oroalkylated sulfoximines indicated that these substrates
were unstable under basic conditions. The challenge of
SYNTHESIS 2013, 45, 1505–1512
Advanced online publication: 08.05.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338440; Art ID: SS-2013-Z0163-OP
© Georg Thieme Verlag Stuttgart · New York

1506
Y. Macé et al.
PAPER
this present study was to find conditions that would toler-
ate the reactivity of our uncommon complex systems.
Table 1 N-Acylation of Free NH-Sulfoximines
R2
O
O
NH
RF
O
R1
R2COCl, Et3N
N
R1
S
X
S
X
RF
N
O
NH
RF
DMAP (cat.)
CH2Cl2, 5 h
0 °C to r.t.
O
R
R
Y
S
S
Y
Cl
RF
2a–g
4–16
base
X = O, S
Y = R1, OR1, NR1
Entry Substrate R1
RF
R2
Product Yield
(%)a
2a–g
2
Scheme 2 A general route for the N-acylation of sulfoximines
1
2
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
H
H
H
H
H
H
H
CF3
CF3
CF3
CF3
CF3
CF3
CF3
Ph
4
5
100
96
97
97
74
91
49
100
93
97
98
95
93
PhCH2
Me
Harmata et al. have reported a smooth and convenient
method for the direct acylation of free NH-sulfoximines
from a carboxylic acid in the presence of a catalytic
amount of boric acid.17 One of the advantages of this
methodology was the direct isolation of the coupling
product 3 in good yield (up to 80%, Scheme 3). However
with our perfluoroalkylated substrates, no reaction oc-
curred, despite changing the reaction conditions (solvent,
temperature, classical heating or microwave activation,
catalytic or stoichiometric amounts of boric acid). The
starting fluorinated sulfoximine was always recovered
without any trace of N-acylation.
3
6
4
t-Bu
7
5
MeOCOCH2
8
6
Ph(CH2)3
C9H19
Ph
9
7
10
11
12
13
14
15
16
8
4-Me
2-Cl
4-Cl
H
CF3
9
CF3
Ph
10
11
12
13
CF3
Ph
O
CF2Br
CFCl2
C4F9
Ph
B(OH)3 (0.8 equiv)
O
NH
O
OPh
+
O N
H
Ph
S
OPh
toluene
Δ, 24 h
Ph
Me
HO
S
Ph
Me
2g
H
Ph
3
80%
a Yield of isolated product.
Scheme 3 Direct coupling reaction of a sulfoximine with a carbox-
ylic acid catalyzed by boric acid
(Table 1, entry 4) or electron-withdrawing (Table 1, entry
5) groups. A moderate 49% yield was obtained in the case
of decanoyl chloride (Table 1, entry 7) due to the difficul-
ties encountered during purification. The presence of sub-
stituents on the aromatic ring of the sulfoximines was not
detrimental to the yield (Table 1, entries 8–10), nor was
the nature of the perfluoroalkyl chain (Table 1, entries 11–
13). All the products were stable and have been fully char-
acterized.
Although very simple and easy to run, the previous syn-
thetic method, in our hands, could not be extrapolated to
electron-poor systems. The lower reactivity of the nitro-
gen is one of the most plausible explanations for this dis-
appointing result, which again pointed toward the
particular reactivity of these compounds.
Other procedures have also been reported in the literature
for the acylation of non-fluorinated sulfoximines.18 We
thus turned our attention toward a milder pathway, with-
out direct deprotonation of the nitrogen atom. Compound
2a was treated with one equivalent of benzyl chloride
along with one equivalent of triethylamine in the presence
of a catalytic amount of 4-(N,N-dimethylamino)pyridine
(DMAP) to afford N-acylated compound 4 in quantitative
yield (Table 1, entry 1). The order of the introduction of
each reagent was crucial to the success of this transforma-
tion.
Encouraged by these results, we extended our study to the
synthesis of N-bridged sulfoximines obtained by the reac-
tion of 2a with various diacyl chlorides (Scheme 4). A
slight modification of our procedure (pyridine was used as
the base instead of triethylamine) afforded the desired
compounds in moderate to good yields (54–79%).
O
O
O
O
O
S
O
S
O
NH
(
)
n
Cl
Cl
( )
n
CF3
N
N
F3C
S
CF3
DMAP (cat.)
To investigate the scope of this procedure, several acyl
chlorides and sulfoximines were tested. A large panel of
different electrophiles was engaged in the reaction. The
product N-acylated sulfoximines were isolated in good
yields (74–100%) with benzyl (Table 1, entry 2), alkyl
(Table 1, entries 3 and 6), sterically hindered tertiary alkyl
CH2Cl2, pyridine
0 °C to r.t., 5 h
2a
n = 0: 17 79%
n = 2: 18 58%
n = 3: 19 54%
n = 4: 20 55%
Scheme 4 Synthesis of N-bridged sulfoximines
Synthesis 2013, 45, 1505–1512
© Georg Thieme Verlag Stuttgart · New York

PAPER
N-Functionalization of S-Perfluoroalkylated Aryl Sulfoximines
1507
These novel structures appear attractive due to their po- entries 1–7). Each transformation delivered novel, stable
tential applications as ligands in metal catalysis. Closely sulfoximines in good to excellent yields. Varying the na-
related molecules (non-fluorinated bis-sulfoximines ture of the fluorinated moiety (Table 2, entries 8–10) did
linked by an alkyl tether) have been used as ligands in pal- not affect the yield adversely, and allowed the construc-
ladium-catalyzed allylic alkylations.19 The latter were tion of functionalized sulfoximines bearing mono-, di-
prepared by reduction of the carbonyl group of acetylated and nonafluoroalkyl moieties. We also increased the
sulfoximines with dimethylsulfide borane complex. We structural diversity of our targets with various electro-
next tested this protocol with our substrates, but unfortu- philes. Carbamoyl chloride (Table 2, entries 11 and 12)
nately, unreacted starting materials were recovered. This chlorothionoformate (Table 2, entry 13) and thiocarbam-
was the case with several other mild reducing agents oyl chloride (Table 2, entry 14) reacted successfully with
(borane, silane or boron trifluoride–diethyl etherate com- S-trifluoromethyl sulfoximines to afford new sulfur(VI)
plex), whereas more potent reagents (lithium aluminum skeletons in good yields. The lower reactivity of the car-
hydride or diisobutylaluminum hydride) led to the forma- bamoyl chlorides was accompanied by an increase in the
tion of degradation compounds with loss of the fluorinat- reaction time. Heating by classical or non-conventional
ed moiety. We assume that these negative results are the (microwaves) methods did not improve the yield and led
consequence of the deactivation of the acyl function due to degradation compounds.
to the electron-withdrawing properties of the sulfoximine
Thus, we have obtained novel ureas and thioureas in sat-
moiety. Further studies on this topic are ongoing in our
isfactory yields. These products may have applications as
group, but their details fall beyond the scope of this arti-
ligands, organocatalysts and as new key structures for
chemical or agrochemical targets.
cle.
Finally, we focused our efforts on the extension of the
scope of our protocol through the reaction of perfluoroal-
kylated sulfoximines with other acyl electrophiles (Table
In summary, we have described an efficient and mild pro-
cedure for the N-functionalization of S-perfluoroalkylated
sulfoximines, despite the presence of the fluorinated
2). The conditions previously used with acid chlorides
group, which deactivates the imino sulfanyl group and
were also suitable for the coupling reactions with various
makes the compound highly sensitive to a base. The meth-
aliphatic, allylic and aromatic chloroformates (Table 2,
od has been extended to the synthesis of ureas, thioureas
Table 2 N-Functionalization of Sulfoximines with Heteroelectrophiles
X
Y
O
NH
RF
O
N
R
Y
Cl, Et3N
R
S
S
X
RF
DMAP (cat.)
CH2Cl2, 5 h
0 °C to r.t.
2a,b,e–g
21–34
Entry
Substrate
R
RF
X
Y
Product
Yield (%)a
1
2
2a
2a
2a
2a
2a
2a
2a
2e
2f
H
H
H
H
H
H
H
H
H
H
H
CF3
O
O
O
O
O
O
O
O
O
O
O
O
S
i-BuO
21
22
23
24
25
26
27
28
29
30
31
32
33
34
100
100
93
CF3
EtO
3
CF3
MeO
4
CF3
BnO
77
5
CF3
Cl(CH2)2O
allyl-O
Cl3CCH2O
Cl3CCH2O
Cl3CCH2O
Cl3CCH2O
Me2N
64
6
CF3
85
7
CF3
91
8
CF2Br
CFCl2
C4F9
CF3
79
9
94
10
11
12
13
14
2g
2a
2b
2a
2a
64
82b
64b
60
4-Me
H
CF3
Me2N
CF3
C6F5O
H
CF3
S
Me2N
62b
a Yield of isolated product.
b Reaction over 5 d instead of 5 h.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1505–1512

1508
Y. Macé et al.
PAPER
HRMS (EI): m/z [M + Na]+ calcd for C15H12F3NO2SNa: 350.0433;
found: 350.0423 (δ = 3 ppm).
and C2-symmetric bis-sulfoximines. Further investiga-
tions are currently underway in our laboratory toward the
use of these latter substrates as ligands in metal catalysis.
Anal. Calcd for C15H12F3NO2S: C, 55.04; H, 3.67; N, 4.28. Found:
C, 54.92; H, 3.78; N, 4.28.
N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]acetamide
All reactions were conducted under an argon atmosphere in a fresh-
ly distilled solvent, unless otherwise stated. CH2Cl2 was distilled
over calcium hydride. Reactions were monitored by 19F NMR spec-
troscopy, or by thin-layer chromatography (TLC) on Merck silica
gel 60 F254, with the components being visualized under UV light
(254 nm). Column chromatography was performed using Merck sil-
ica gel 60 mesh (40–63 m). Melting points were determined using
a Büchi Tottoli apparatus. NMR spectra were recorded on Bruker
AC 200 or AC 300 spectrometers in CDCl3. The internal reference
was the residual peak of CHCl3 (7.27 ppm) for 1H NMR (200 or 300
MHz), the central peak of CDCl3 (77 ppm) for 13C NMR (75 or 50
MHz) and internal CFCl3 (0 ppm) for 19F NMR (188 MHz) spectra.
Chemical shifts (δ) are given in ppm and standard abbreviations are
used to describe the signal multiplicities. Low-resolution mass
spectrometry and high-resolution mass spectrometry (HRMS) were
performed using a Xevo Qtof Waters spectrometer at ILV,
Versailles. Elemental analyses were performed in Gif sur Yvette
(ICSN) using a Perkin Elmer CHN 2400 analyzer.
(6)
Yield: 116 mg (97%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 2.2 (s, 3 H), 7.6 (t, J = 8.0 Hz, 2
H), 7.7 (t, J = 7.5 Hz, 1 H), 8.0 (d, J = 7.7 Hz, 2 H).
1
13C NMR (75 MHz, CDCl3): δ = 26.8, 124.0 (q, JC–F = 328 Hz),
130.0, 130.1, 130.2, 136.5, 178.6.
19F NMR (188 MHz, CDCl3): δ = –74.9 (s, 3 F).
HRMS (EI): m/z [M + Na]+ calcd for C9H8F3NO2SNa: 274.0120;
found: 274.0121 (δ = –1.3 ppm).
Anal. Calcd for C9H8F3NO2S: C, 43.03; H, 3.21; N 5.58. Found: C,
43.19; H, 3.35; N, 5.61.
2,2-Dimethyl-N-[oxo-phenyl(trifluoromethyl)-λ6-sulfanyli-
dene]propanamide (7)
Yield: 136 mg (97%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 1.0 (s, 9 H), 7.4 (t, J = 8.5 Hz, 2
H), 7.6 (t, J = 7.5 Hz, 1 H), 7.8 (d, J = 7.7 Hz, 2 H).
N-Acylated Sulfoximines; General Procedure
The sulfoximine (1 equiv, 0.5 mmol) and acid chloride (1.1 equiv,
0.55 mmol) were dissolved in anhyd CH2Cl2 (10 mL) under Ar at
0 °C. A catalytic amount of DMAP (0.1 equiv, 0.05 mmol) and
Et3N (1.2 equiv, 0.6 mmol) were added, and the mixture was stirred
for 5 h at r.t. H2O (10 mL) was added and the resulting mixture ex-
tracted with CH2Cl2 (3 × 20 mL). The combined organic layers
were dried over MgSO4, filtered and concentrated under reduced
pressure. The residue was purified by flash chromatography (pen-
tane–Et2O, 7:3) to give the N-acylated sulfoximine.
13C NMR (75 MHz, CDCl3): δ = 27.3, 42.0, 124.0 (q, 1JC–F = 328
Hz), 130.0, 130.8, 136.0, 186.9.
19F NMR (188 MHz, CDCl3): δ = –74.5 (s, 3 F).
HRMS (EI): m/z [M + Na]+ calcd for C12H14F3NO2SNa: 316.0590;
found: 316.0584 (δ = 1.9 ppm).
Methyl 3-Oxo-3-{[oxo-phenyl(trifluoromethyl)-λ6-sulfanyli-
dene]amino}propanoate (8)
Yield: 123 mg (74%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 3.5 and 3.6 (AB system, J = 16 Hz,
2 H), 3.7 (s, 3 H), 7.6 (t, J = 8.2 Hz, 2 H), 7.7 (t, J = 7.7 Hz, 1 H),
8.0 (d, J = 7.9 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 45.9, 52.7, 120.0 (q, 1JC–F = 328
Hz), 129.5, 130.1, 130.2, 136.4, 167.3, 173.5.
19F NMR (188 MHz, CDCl3): δ = –75.5 (s, 3 F).
HRMS (EI): m/z [M + Na]+ calcd for C11H10F3NO4SNa: 332.0175;
found: 332.0168 (δ = 1.9 ppm).
N-Bis-acylated Sulfoximines; General Procedure
The sulfoximine (1 equiv, 0.5 mmol) and diacyl chloride (0.5 equiv,
0.25 mmol) were dissolved in anhyd CH2Cl2 (10 mL) under Ar at
0 °C. Py (1.2 equiv, 0.6 mmol) and a catalytic amount of DMAP
(0.1 equiv, 0.05 mmol) were added, and the mixture was stirred for
5 h at r.t. H2O (10 mL) was added and the resulting mixture extract-
ed with CH2Cl2 (3 × 20 mL). The combined organic layers were
dried over MgSO4, filtered and concentrated under reduced pres-
sure. The residue was purified by flash chromatography (pentane–
Et2O, 7:3) to give the N-bis-acylated sulfoximine.
N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]-4-phenyl-
butanamide (9)
Yield: 162 mg (91%); colorless oil.
N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]benzamide
(4)
Yield: 150 mg (100%); colorless oil.
1H NMR (200 MHz, CDCl3): δ = 2.0 (quin, J = 7.4 Hz, 2 H), 5.5 (t,
J = 7.2 Hz, 2 H), 2.7 (t, J = 7.2 Hz, 2 H), 7.0–7.4 (m, 5 H), 7.7 (t,
J = 7.9 Hz, 2 H), 7.8 (t, J = 7.4 Hz, 1 H), 8.0 (d, J = 7.5 Hz, 2 H).
1H NMR (300 MHz, CDCl3): δ = 7.5 (t, J = 7.3 Hz, 2 H), 7.6 (t, J =
7.5 Hz, 1 H), 7.7 (t, J = 7.3 Hz, 2 H), 7.85 (t, J = 7.7 Hz, 1 H), 8.1
(d, J = 7.7 Hz, 2 H), 8.2 (d, J = 7.9 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 120.3 (q, 1JC–F = 328 Hz), 128.2,
129.8, 130.1, 130.3, 133.1, 133.9, 136.1, 172.9.
19F NMR (188 MHz, CDCl3): δ = –74.9 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C14H11F3NO2S: 314.0457;
found: 314.0452 (δ = 1.7 ppm).
13C NMR (75 MHz, CDCl3): δ = 26.8, 35.0, 38.9, 120.3 (q, 1JC–F
=
327 Hz), 125.9, 128.3, 128.5, 130.0, 130.1, 136.0, 141.6, 181.0.
19F NMR (188 MHz, CDCl3): δ = –74.6 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C17H17F3NO2S: 356.0932;
found: 356.0934 (δ = 0.6 ppm).
N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]decanamide
N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]-2-phenyl-
acetamide (5)
Yield: 157 mg (96%); brown oil.
(10)
Yield: 90 mg (49%); yellow oil.
1H NMR (200 MHz, CDCl3): δ = 0.9 (t, J = 6.5 Hz, 3 H), 1.2–1.5
(m, 12 H), 1.7 (quin, J = 6.8 Hz, 2 H), 2.5 (t, J = 7.0 Hz, 2 H), 7.7
(t, J = 7.2 Hz, 2 H), 7.9 (t, J = 7.3 Hz, 1 H), 8.0 (d, J = 7.8 Hz, 2 H).
1H NMR (300 MHz, CDCl3): δ = 3.7 and 3.75 (AB system, J = 14.5
Hz, 2 H), 7.1–7.3 (m, 5 H), 7.5 (t, J = 7.3 Hz, 2 H), 7.7 (q, J = 7.5
Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 14.1, 22.6, 25.2, 29.2, 29.1, 29.4,
1
13C NMR (75 MHz, CDCl3): δ = 46.8, 120.2 (q, JC–F = 328 Hz),
1
31.8, 39.7, 120.3 (q, JC–F = 329 Hz), 129.9, 130.0, 130.6, 135.9,
127.0, 128.5, 129.6, 130.0, 130.1, 130.2, 134.8, 136.1, 178.9.
19F NMR (188 MHz, CDCl3): δ = –75.1 (s, 3 F).
181.5.
19F NMR (188 MHz, CDCl3): δ = –74.7 (s, 3 F).
Synthesis 2013, 45, 1505–1512
© Georg Thieme Verlag Stuttgart · New York

PAPER
N-Functionalization of S-Perfluoroalkylated Aryl Sulfoximines
1509
HRMS (EI): m/z [M + H]+ calcd for C17H25F3NO2S: 364.1558;
found: 364.1554 (δ = –1.1 ppm).
N-[(1,1,2,2,3,3,4,4,4-nonafluorobutyl)-oxo-(phenyl)-λ6-sulfa-
nylidene]benzamide (16)
Yield: 215 mg (93%); white crystalline solid; mp 86 °C.
N-[Oxo-(p-tolyl)(trifluoromethyl)-λ6-sulfanylidene]benzamide
1H NMR (300 MHz, CDCl3): δ = 7.5 (t, J = 7.0 Hz, 2 H), 7.6 (t, J =
7.3 Hz, 1 H), 7.7 (t, J = 8.0 Hz, 2 H), 7.8 (t, J = 7.0 Hz, 1 H), 8.1 (d,
J = 8.0 Hz, 2 H), 8.2 (d, J = 7.5 Hz, 2 H).
(11)
Yield: 164 mg (100%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 2.5 (s, 3 H), 7.5 (t, J = 8.0 Hz, 4
H), 7.6 (t, J = 7.3 Hz, 1 H), 8.0 (d, J = 8.7 Hz, 2 H), 8.3 (d, J = 8.7
Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 128.3, 128.4, 129.8, 130.0, 130.1,
130.6, 131.1, 133.2, 133.7, 133.9, 136.3, 172.5 (d, 4JC–F = 2 Hz).
19F NMR (188 MHz, CDCl3): δ = –81.0 (s, 3 F), –105.6 and –111.8
(AB system, J = 362 Hz, 2 F), –118.8 and –121.5 (AB system, J =
450 Hz, 2 F), –125.2 and –127.2 (AB system, J = 434 Hz, 2 F).
HRMS (EI): m/z [M + H]+ calcd for C17H11F9NO2S: 464.0361;
found: 464.0352 (δ = 2 ppm).
1
13C NMR (75 MHz, CDCl3): δ = 21.9, 120.4 (q, JC–F = 326 Hz),
128.3, 129.9, 130.2, 130.9, 133.2, 134.2, 148.1, 173.1.
19F NMR (188 MHz, CDCl3): δ = –75.3 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C15H13F3NO2S: 328.0614;
found: 328.0618 (δ = –1.2 ppm).
N,N′-Bis[oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]oxam-
ide (17)
N-[(2-Chlorophenyl)-oxo-(trifluoromethyl)-λ6-sulfanyli-
dene]benzamide (12)
Yield: 93 mg (79%); white crystalline solid; mp 100 °C.
Yield: 161 mg (93%); pale yellow oil.
1H NMR (200 MHz, CDCl3): δ = 7.6–7.8 (m, 4 H), 7.8 (t, J = 7.3
Hz, 2 H), 8.1 (t, J = 7.9 Hz, 4 H).
1H NMR (300 MHz, CDCl3): δ = 7.5 (t, J = 7.3 Hz, 2 H), 7.5–7.6
(m, 3 H), 7.7 (t, J = 7.3 Hz, 1 H), 8.2 (d, J = 8.4 Hz, 2 H), 8.3 (d, J =
8.0 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 120.3 (q, 1JC–F = 328 Hz), 128.2,
129.9, 133.2, 133.5, 134.3, 134.4, 136.7, 172.9.
19F NMR (188 MHz, CDCl3): δ = –72.8 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C14H10ClF3NO2S: 348.0067;
found: 348.0059 (δ = 2.4 ppm).
13C NMR (75 MHz, CDCl3): δ = 120.1 (q, 1JC–F = 328 Hz), 120.2 (q,
1JC–F = 328 Hz), 129.7, 130.3, 136.6, 166.0, 166.1.
19F NMR (188 MHz, CDCl3): δ = –75.1 (s, 3 F), –75.2 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C16H11F6N2O4S2: 473.0064;
found: 473.0064 (δ = 0 ppm).
N,N′-Bis[oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]bu-
tanediamide (18)
Yield: 72 mg (58%); white crystalline solid; mp 122 °C.
1H NMR (200 MHz, CDCl3): δ = 2.8–3.0 (m, 4 H), 7.5–7.8 (m, 6
H), 8.1 (t, J = 7.7 Hz, 4 H).
N-[(4-Chlorophenyl)-oxo-(trifluoromethyl)-λ6-sulfanyli-
dene]benzamide (13)
Yield: 168 mg (97%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 7.3–7.7 (m, 5 H), 8.1 (d, J = 8.0
Hz, 2 H), 8.2 (d, J = 8.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 120.1 (q, 1JC–F = 328 Hz), 128.3,
128.8, 129.8, 130.3, 130.5, 131.5, 133.3, 134.5, 143.5, 172.7.
19F NMR (188 MHz, CDCl3): δ = –74.9 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C14H10ClF3NO2S: 348.0067;
found: 348.0064 (δ = –0.4 ppm).
13C NMR (75 MHz, CDCl3): δ = 34.4, 34.5, 120.1 (q, 1JC–F = 329
1
Hz), 120.2 (q, JC–F = 328 Hz), 129.4, 129.9, 130.0, 130.1, 130.3,
130.4, 135.9, 136.0.
19F NMR (188 MHz, CDCl3): δ = –75.0 (s, 3 F), –75.8 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C18H15F6N2O4S2: 501.0377;
found: 501.0374 (δ = –0.6 ppm).
N,N′-Bis[oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]pen-
tanediamide (19)
N-{[Bromo(difluoro)methyl]-oxo-(phenyl)-λ6-sulfanyli-
dene}benzamide (14)
Yield: mg (54%); white crystalline solid; mp 81 °C.
Yield: 184 mg (98%); yellow crystalline solid; mp 97 °C.
1H NMR (200 MHz, CDCl3): δ = 1.1 (quin, J = 7.2 Hz, 2 H), 2.6 (t,
J = 7.3 Hz, 4 H), 7.7 (t, J = 7.4 Hz, 4 H), 7.8 (t, J = 7.4 Hz, 2 H), 7.9
(d, J = 7.2 Hz, 4 H).
1H NMR (300 MHz, CDCl3): δ = 7.5 (t, J = 7.7 Hz, 2 H), 7.6 (t, J =
7.5 Hz, 1 H), 7.7 (t, J = 7.5 Hz, 2 H), 7.8 (t, J = 7.5 Hz, 1 H), 8.1 (d,
J = 7.9 Hz, 2 H), 8.2 (d, J = 7.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 20.7, 38.5, 120.3 (q, 1JC–F = 327
13C NMR (75 MHz, CDCl3): δ = 121.1 (dd, J = 342, 346 Hz), 128.2,
1
Hz), 124.1 (q, JC–F = 329 Hz), 129.4, 130.0, 130.1, 130.3, 136.1,
129.6, 129.9, 130.6, 132.9, 134.2, 135.9, 172.5 (d, 4JC–F = 2 Hz).
180.6.
19F NMR (188 MHz, CDCl3): δ = –54.8 and –57.4 (AB system, J =
212 Hz, 2 × 1 F).
HRMS (EI): m/z [M + H]+ calcd for C14H11BrF2NO2S: 373.9656;
found: 373.9652 (δ = 1.1 ppm).
19F NMR (188 MHz, CDCl3): δ = –74.6 (s, 3 F), –74.7 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C19H17F6N2O4S2: 515.0534;
found: 515.0535 (δ = 0.2 ppm).
N,N′-Bis[oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]hex-
anediamide (20)
N-{[Dichloro(fluoro)methyl]-oxo-(phenyl)-λ6-sulfanyli-
dene}benzamide (15)
Yield: 73 mg (55%); colorless oil.
Yield: 97.4 mg (95%); yellow crystalline solid; mp 83 °C.
1H NMR (200 MHz, CDCl3): δ = 1.6–1.9 (m, 4 H), 2.6 (t, J = 6.8
Hz, 4 H), 7.7 (t, J = 7.5 Hz, 4 H), 7.8 (t, J = 7.4 Hz, 2 H), 8.1 (d, J =
7.7 Hz, 4 H).
1H NMR (300 MHz, CDCl3): δ = 7.5 (t, J = 7.7 Hz, 2 H), 7.6 (t, J =
7.5 Hz, 1 H), 7.7 (t, J = 7.5 Hz, 2 H), 7.8 (t, J = 7.5 Hz, 1 H), 8.1 (d,
J = 8.3 Hz, 2 H), 8.2 (d, J = 7.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 123.5 (d, 1JC–F = 339 Hz), 128.2,
129.7, 129.8, 130.0, 131.2, 132.9, 134.4, 135.9, 172.5.
19F NMR (188 MHz, CDCl3): δ = –60.8 (s, 1 F).
HRMS (EI): m/z [M + H]+ calcd for C14H11Cl2FNO2S: 345.9866;
found: 345.9852 (δ = –3.6 ppm).
13C NMR (75 MHz, CDCl3): δ = 24.6, 39.2, 120.3 (q, 1JC–F = 329
Hz), 126.5 (q, 1JC–F = 329 Hz), 130.0, 130.1, 130.5, 135.9, 180.9.
19F NMR (188 MHz, CDCl3): δ = –74.6 (s, 6 F).
HRMS (EI): m/z [M + H]+ calcd for C20H19F6N2O4S2: 529.0690;
found: 529.0684 (δ = –1.1 ppm).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1505–1512

1510
Y. Macé et al.
PAPER
O-iso-Butyl N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfanyli-
dene]carbamoate (21)
Yield: 146 mg (100%); colorless oil.
O-Allyl N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]car-
bamoate (26)
Yield: 127 mg (85%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 0.8 (dd, J = 2.7 Hz, J = 6.7 Hz, 6
H), 1.9 (hept, J = 6.7 Hz, 1 H), 3.9 (d, J = 6.7 Hz, 2 H), 7.6 (t, J =
8.3 Hz, 2 H), 7.7 (t, J = 7.5 Hz, 1 H), 8.0 (d, J = 7.7 Hz, 2 H).
1H NMR (300 MHz, CDCl3): δ = 4.6 (d, J = 5.8 Hz, 2 H), 5.2 (2 dd,
J
AX = 10.4 Hz, JBX = 17.1 Hz, JAB <1.0 Hz, 2 H), 5.9 (ddt, J = 5.8
Hz, JAX = 10.4 Hz, JBX = 17.1 Hz, 1 H), 7.7 (t, J = 7.7 Hz, 2 H), 7.9
(t, J = 7.5 Hz, 1 H), 8.1 (t, J = 7.6 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 67.8, 118.8, 120.3 (q, 1JC–F = 327
13C NMR (75 MHz, CDCl3): δ = 18.9, 27.7, 73.4, 120.3 (q, 1JC–F
329 Hz), 130.1, 130.3, 136.3, 156.2.
=
Hz), 130.0, 130.4, 131.6, 136.4, 156.0.
19F NMR (188 MHz, CDCl3): δ = –74.2 (s, 3 F).
MS (ES): m/z (%) = 294 [M + H]+, 189, 126 [PhSOH]+.
19F NMR (188 MHz, CDCl3): δ = –74.4 (s, 3 F).
HRMS (EI): m/z [M + Na]+ calcd for C12H14F3NO3SNa: 332.0539;
found: 332.0523 (δ = 4.6 ppm).
HRMS (EI): m/z [M + H]+ calcd for C11H11F3NO3S: 294.0412;
found: 294.0406 (δ = –2.0 ppm).
O-Ethyl N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfanylidene]car-
bamoate (22)
Yield: 119 mg (100%); yellow oil.
O-(2,2,2-Trichloroethyl) N-[Oxo-phenyl(trifluoromethyl)-λ6-
sulfanylidene]carbamoate (27)
Yield: 174 mg (91%); waxy solid.
1H NMR (200 MHz, CDCl3): δ = 4.7 and 4.8 (AB system, J = 12.0
Hz, 2 H), 7.7 (t, J = 7.2 Hz, 2 H), 7.9 (t, J = 7.5 Hz, 1 H), 8.1 (d, J =
7.6 Hz, 2 H).
1H NMR (300 MHz, CDCl3): δ = 1.2 (t, J = 7.2 Hz, 3 H), 4.1 (q, J =
7.2 Hz, 2 H), 7.6 (t, J = 7.5 Hz, 2 H), 7.7 (t, J = 7.0 Hz, 1 H), 8.0 (t,
J = 8 Hz, 2 H).
1
13C NMR (75 MHz, CDCl3): δ = 14.0, 63.2, 120.3 (q, JC–F = 329
Hz), 130.2, 130.3, 130.5, 136.4, 156.3.
1
19F NMR (188 MHz, CDCl3): δ = –74.1 (s, 3 F).
13C NMR (75 MHz, CDCl3): δ = 75.8, 94.5, 120.0 (q, JC–F = 326
Hz), 130.2, 130.4, 136.7, 154.6.
19F NMR (188 MHz, CDCl3): δ = –74.7 (s, 3 F).
HRMS (EI): m/z [M + Na]+ calcd for C10H10F3NO3SNa: 304.0226;
found: 304.0221 (δ = 1.4 ppm).
HRMS (EI): m/z [M + H]+ calcd for C10H8F3Cl3NO3S: 383.9243;
found: 383.9252 (δ = 2.6 ppm).
O-Methyl N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfanyli-
dene]carbamoate (23)
Yield: 124 mg (93%); colorless oil.
O-(2,2,2-Trichloroethyl) N-{[Bromo(difluoro)methyl]oxo-phe-
nyl-λ6-sulfanylidene}carbamoate (28)
Yield: 176 mg (79%); waxy solid.
1H NMR (300 MHz, CDCl3): δ = 3.8 (s, 3 H), 7.6–7.9 (m, 3 H), 8.1
(d, J = 11.0 Hz, 2 H).
1
13C NMR (75 MHz, CDCl3): δ = 54.0, 120.3 (q, JC–F = 327 Hz),
130.0, 130.4, 136.4, 156.8.
19F NMR (188 MHz, CDCl3): δ = –73.7 (s, 3 F).
1H NMR (300 MHz, CDCl3): δ = 4.7 and 4.8 (AB system, J = 12.0
Hz, 2 H), 7.7 (t, J = 7.3 Hz, 2 H), 7.9 (t, J = 7.5 Hz, 1 H), 8.1 (d, J =
7.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 75.6, 94.6, 120.8 (dd, J = 345, 346
Hz), 129.0, 130.0, 130.8, 136.4, 154.5.
19F NMR (188 MHz, CDCl3): δ = –54.6 and –56.6 (AB system, J =
210 Hz, 2 F).
MS (ES): m/z (%) = 290 [M + Na]+, 268 [M + H]+, 236 [M –
OCH3]+, 151.
HRMS (EI): m/z [M + H]+ calcd for C9H9F3NO3S: 268.0255; found:
268.0266 (δ = 4.1 ppm).
MS (ES): m/z (%) = 467 [M + Na]+, 444 [M + H]+, 296 [M –
OCH2CCl3]+, 151.
O-Benzyl N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfanyli-
dene]carbamoate (24)
HRMS (EI): m/z [M + H]+ calcd for C10H8F2NO3SCl3Br: 443.8442;
found: 443.8436 (δ = –1.4 ppm).
Yield: 131 mg (77%); colorless oil.
1H NMR (200 MHz, CDCl3): δ = 5.1 and 5.2 (AB system, J = 12.1
Hz, 2 H), 7.3 (s, 5 H), 7.6 (t, J = 7.2 Hz, 2 H), 7.8 (t, J = 7.5 Hz, 1
H), 8.0 (d, J = 8.5 Hz, 2 H).
O-(2,2,2-Trichloroethyl) N-{[Dichloro(fluoro)methyl]oxo-phe-
nyl-λ6-sulfanylidene}carbamoate (29)
Yield: 157 mg (94%); waxy solid.
1H NMR (300 MHz, CDCl3): δ = 4.7 and 4.8 (AB system, J = 12.0
Hz, 2 H), 7.7 (m, 3 H), 8.1 (d, J = 8.2 Hz, 2 H).
1
13C NMR (75 MHz, CDCl3): δ = 68.6, 120.0 (q, JC–F = 327 Hz),
127.2, 128.1, 128.3, 129.6, 129.9, 135.2, 136.3, 155.9.
19F NMR (188 MHz, CDCl3): δ = –74.5 (s, 3 F).
1
13C NMR (75 MHz, CDCl3): δ = 75.5, 94.7, 123.3 (d, JC–F = 338
HRMS (EI): m/z [M + H]+ calcd for C15H13F3NO3S: 344.0568;
found: 344.0566 (δ = –0.6 ppm).
Hz), 129.4, 129.8, 131.5, 136.3, 154.5.
19F NMR (188 MHz, CDCl3): δ = –60.2 (s, 1 F).
O-(1-Chloroethyl) N-[Oxo-phenyl(trifluoromethyl)-λ6-sulfa-
MS (ES): m/z (%) = 439 [M + Na]+, 415 [M + H]+, 268 [M –
nylidene]carbamoate (25)
OCH2CCl3]+, 125 [PhSO]+.
Yield: 101 mg (64%) as a mixture of two diastereomers; colorless
oil.
1H NMR (200 MHz, CDCl3): δ = 1.8 (dd, J = 5.8 Hz, J = 3.1 Hz, 3
H), 6.5 (q, J = 5.9 Hz, 1 H), 7.7 (t, J = 7.4 Hz, 2 H), 7.9 (t, J = 7.3
Hz, 1 H), 8.1 (d, J = 7.7 Hz, 2 H).
HRMS (EI): m/z [M + H]+ calcd for C10H8FNO3SCl5: 415.8652;
found: 415.8650 (δ = –0.5 ppm).
O-(2,2,2-Trichloroethyl) N-[(1,1,2,2,3,3,4,4,4-nonafluorobutyl)-
oxo-phenyl-λ6-sulfanylidene]carbamoate (30)
Yield: 154 mg (64%); waxy solid.
13C NMR (75 MHz, CDCl3): δ = 24.9, 83.7, 120.0 (q, JC–F = 326
1
Hz), 129.2, 130.3, 136.7, 154.2.
19F NMR (188 MHz, CDCl3): δ = –74.0 (s, 3 F), –74.8 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C10H10F3NO3SCl: 316.0022;
found: 316.0031 (δ = 2.8 ppm).
1H NMR (300 MHz, CDCl3): δ = 4.7 and 4.8 (AB system, J = 11.9
Hz, 2 H), 7.7 (t, J = 6.0 Hz, 2 H), 7.9 (t, J = 6.0 Hz 1 H), 8.2 (d, J =
7.6 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 75.9, 94.5, 130.1, 130.9, 136.8,
154.1.
Synthesis 2013, 45, 1505–1512
© Georg Thieme Verlag Stuttgart · New York

PAPER
N-Functionalization of S-Perfluoroalkylated Aryl Sulfoximines
1511
19F NMR (188 MHz, CDCl3): δ = –81.1 (s, 3 F), –106.3 and –109.6
(AB system, J = 362 Hz, 2 F), –118.8 and –121.5 (AB system, J =
444 Hz, 2 F), –125.5 and –127.1 (AB system, J = 434 Hz, 2 F).
HRMS (EI): m/z [M + H]+ calcd for C13H8F9NO3SCl3: 533.9147;
found: 533.9148 (δ = –0.2 ppm).
References
(1) (a) Johnson, C. R. Acc. Chem. Res. 1973, 6, 341. (b) Pyne, S.
G. Sulfur Rep. 1999, 21, 281. (c) Reggelin, M.; Zur, C.
Synthesis 2000, 1.
(2) For selected examples, see: (a) Pyne, S. G.; Dong, Z.;
Skelton, B. W.; White, A. H. J. Org. Chem. 1997, 62, 2337.
(b) Reggelin, M.; Heinrich, T. Angew. Chem. Int. Ed. 1998,
37, 2883. (c) Bosshammer, S.; Gais, H.-J. Synthesis 1998,
919. (d) Paquette, L. A.; Gao, Z.; Ni, Z.; Smith, G. F. J. Am.
Chem. Soc. 1998, 120, 2543. (e) Harmata, M.; Pavri, N.
Angew. Chem. Int. Ed. 1999, 38, 2419. (f) Bolm, C.;
Kesselgruber, M.; Muñiz, K.; Raabe, G. Organometallics
2000, 19, 1648. (g) Reddy, R. R.; Gais, H.-J.; Woo, C.-W.;
Raabe, G. J. Am. Chem. Soc. 2002, 124, 10427.
1,1-Dimethyl-3-[oxo-phenyl-(trifluoromethyl)-λ6-sulfanyli-
dene]urea (31)
Yield: 115 mg (82%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 2.9 (s, 3 H), 3.1 (s, 3 H), 7.7 (t, J =
7.1 Hz, 2 H), 7.8 (t, J = 7.4 Hz, 1 H), 8.0 (d, J = 7.5 Hz, 2 H).
1
13C NMR (75 MHz, CDCl3): δ = 35.5, 37.8, 120.4 (q, JC–F = 327
Hz), 129.7, 130.1, 131.5, 135.5, 157.5.
19F NMR (188 MHz, CDCl3): δ = –74.0 (s, 3 F).
(h) Virolleaud, M.-A.; Sridharan, V.; Mailhol, D.; Donne,
D.; Bressy, C.; Chouraqui, G.; Commeiras, L.; Coquerel, Y.;
Rodriguez, J. Tetrahedron 2009, 65, 9756. (i) Yadav, M. R.;
Rit, R. K.; Sahoo, A. K. Chem. Eur. J. 2012, 18, 5541.
(3) For selected examples, see: (a) Langner, M.; Bolm, C.
Angew. Chem. Int. Ed. 2004, 43, 5984. (b) Harmata, M.
Chemtracts 2003, 16, 660. (c) Okamura, H.; Bolm, C. Chem.
Lett. 2004, 33, 482. (d) Sedelmeier, J.; Hammerer, T.; Bolm,
C. Org. Lett. 2008, 10, 917. (e) Lu, S.-M.; Bolm, C. Adv.
Synth. Catal. 2008, 350, 1101. (f) Frings, M.; Bolm, C. Eur.
J. Org. Chem. 2009, 4085. (g) Frings, M.; Atodiresei, I.;
Wang, Y.; Runsink, J.; Raabe, G.; Bolm, C. Chem. Eur. J.
2010, 16, 4577. (h) Frings, M.; Thomé, I.; Bolm, C. Beilstein
J. Org. Chem. 2012, 8, 1443.
HRMS (EI): m/z [M + Na]+ calcd for C10H11F3N2O2SNa: 303.0391;
found: 303.0393 (δ = 0.7 ppm).
1,1-Dimethyl-3-[oxo-(p-tolyl)(trifluoromethyl)-λ6-sulfanyli-
dene]urea (32)
Yield: 94 mg (64%); colorless oil.
1H NMR (200 MHz, CDCl3): δ = 2.5 (s, 3 H), 2.9 (s, 3 H), 3.1 (s, 3
H), 7.6 (d, J = 8.0 Hz, 2 H), 7.9 (d, J = 8.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 21.7, 35.5, 37.8, 120.4 (q, 1JC–F
=
327 Hz), 128.2, 130.2, 130.5, 147.2, 157.6.
19F NMR (188 MHz, CDCl3): δ = –74.5 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C11H14F3N2O2S: 295.0728;
found: 295.0726 (δ = –0.7 ppm).
(4) (a) Chen, X. Y.; Park, S. J.; Buschmann, H.; De Rosa, M.;
Bolm, C. Bioorg. Med. Chem. Lett. 2012, 22, 4307. (b) Park,
S. J.; Buschmann, H.; Bolm, C. Bioorg. Med. Chem. Lett.
2011, 21, 4888. (c) Lu, D.; Vince, R. Bioorg. Med. Chem.
Lett. 2007, 17, 5614. (d) Kahraman, M.; Sinishtaj, S.; Dolan,
P. M.; Kensler, T. W.; Peleg, S.; Saha, U.; Chuang, S. S.;
Bernstein, G.; Korczak, B.; Posner, G. H. J. Med. Chem.
2004, 47, 6854. (e) Chen, X. Y.; Buschmann, H.; Bolm, C.
Synlett 2012, 23, 2808. (f) Park, S. J.; Baars, H.; Mersmann,
S.; Buschmann, H.; Baron, J. M.; Amann, P. M.; Czaja, K.;
Hollert, H.; Bluhm, K.; Redelstein, R.; Bolm, C.
O-(2,3,4,5,6-Pentafluorophenyl) N-[Oxo-phenyl-(trifluoro-
methyl)-λ6-sulfanylidene]carbamothioate (33)
Yield: 125.8 mg (60%); white crystalline solid; mp 80 °C.
1H NMR (300 MHz, CDCl3): δ = 7.7 (t, J = 7.7 Hz, 2 H), 7.9 (t, J =
8.0 Hz, 1 H), 8.0 (t, J = 7.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 119.7 (q, 1JC–F = 325 Hz), 127.3,
130.6, 137.1, 142.7 (m), 192.5.
19F NMR (188 MHz, CDCl3): δ = –76.3 (s, 3 F), –152.4 (m, 2 F),
–157.6 (s, 1 F), –162.9 (m, 2 F).
HRMS (EI): m/z [M + Na]+ calcd for C14H5F8NO2S2Na: 457.9526;
found: 457.9520 (δ = 1.4 ppm).
ChemMedChem 2013, 8, 217.
(5) (a) Zhu, Y.; Loso, M. R.; Watson, G. B.; Sparks, T. C.;
Rogers, R. B.; Huang, J. X.; Gerwick, B. C.; Babcock, J. M.;
Kelley, D.; Hegde, V. B.; Nugent, B. M.; Renga, J. M.;
Denholm, I.; Gorman, K.; DeBoer, G. J.; Hasler, J.; Meade,
B. T.; Thomas, J. D. J. Agric. Food Chem. 2011, 59, 2950.
(b) Sparks, T. C.; DeBoer, G. J.; Wang, N. X.; Hasler, J. M.;
Loso, M. R.; Watson, G. B. Pestic. Biochem. Physiol. 2012,
103, 159.
(6) (a) Terrier, F.; Magnier, E.; Kizilian, E.; Wakselman, C.;
Buncel, E. J. Am. Chem. Soc. 2005, 127, 5563. (b) Rouxel,
C.; Le Droumaguet, C.; Macé, Y.; Clift, S.; Mongin, C.;
Magnier, E.; Blanchard-Desce, M. Chem. Eur. J. 2012, 18,
12487.
1,1-Dimethyl-3-[oxo-phenyl-(trifluoromethyl)-λ6-sulfanyli-
dene]thiourea (34)
Yield: 92 mg (62%); colorless oil.
1H NMR (200 MHz, CDCl3): δ = 3.3–3.4 (m, 6 H), 7.6–7.8 (m, 3
H), 8.0 (d, J = 8.0 Hz, 2 H).
1
13C NMR (75 MHz, CDCl3): δ = 40.4, 42.2, 119.8 (q, JC–F = 319
Hz), 129.9, 130.2, 131.5, 135.2, 182.9.
19F NMR (188 MHz, CDCl3): δ = –77.7 (s, 3 F).
HRMS (EI): m/z [M + H]+ calcd for C10H12F3N2OS2: 297.0343;
found: 297.0351 (δ = 2.7 ppm).
(7) Kirsch, P.; Lengues, M.; Kühne, D.; Wanczek, K.-P. Eur. J.
Org. Chem. 2005, 797.
Acknowledgment
(8) Macé, Y.; Magnier, E. Eur. J. Org. Chem. 2012, 2479.
(9) (a) Noritake, S.; Shibata, N.; Nakamura, S.; Toru, T.; Shiro,
M. Eur. J. Org. Chem. 2008, 3465. (b) Nomura, Y.;
Tokunaga, E.; Shibata, N. Angew. Chem. Int. Ed. 2011, 50,
1885. (c) Yang, Y.-D.; Lu, X.; Liu, G.; Tokunaga, E.;
Tsuzuki, S.; Shibata, N. ChemistryOpen 2012, 1, 221.
(10) (a) Zhang, W.; Wang, F.; Hu, J. Org. Lett. 2009, 11, 2109.
(b) Zhang, W.; Huang, W.; Hu, J. Angew. Chem. Int. Ed.
2009, 48, 9858.
Y.M. thanks UniverSUD PRES for financial support and C.C.-U. is
grateful to the French Ministry of Research for a PhD grant.
François Metz (Rhodia-Solvay) is gratefully acknowledged for the
gift of fluorinated reagents, and Jean-Claude Blazejewski for
helpful discussions.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
(11) Urban, C.; Cadoret, F.; Blazejewski, J.-C.; Magnier, E. Eur.
J. Org. Chem. 2011, 4862.
nnfomartit
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1505–1512

1512
Y. Macé et al.
PAPER
(12) (a) Shen, X.; Zhang, W.; Luo, T.; Wan, X.; Gu, Y.; Hu, J.
Angew. Chem. Int. Ed. 2012, 51, 6966. (b) Shen, X.; Zhang,
W.; Ni, C.; Gu, Y.; Hu, J. J. Am. Chem. Soc. 2012, 134,
16999.
(13) Kondratenko, N. V.; Popov, V. I.; Radchenko, O. A.;
Ignatev, N. V.; Yagupolskii, L. M. Zh. Org. Khim. 1986, 22,
1716.
(14) Macé, Y.; Urban, C.; Pradet, C.; Marrot, J.; Blazejewski,
J.-C.; Magnier, E. Eur. J. Org. Chem. 2009, 3150.
(15) Kowalczyk, R.; Edmunds, A. J. F.; Hall, R. G.; Bolm, C.
Org. Lett. 2011, 13, 768.
(16) Macé, Y.; Pégot, B.; Guillet, R.; Bournaud, C.; Toffano, M.;
Vo-Thanh, G.; Magnier, E. Tetrahedron 2011, 67, 7575.
(17) Garimallaprabhakaran, A.; Harmata, M. Synlett 2011, 361.
(18) (a) Virolleaud, M.-A.; Sridharan, V.; Maihol, D.; Bonne, D.;
Bressy, C.; Chouraqui, G.; Commeiras, L.; Coquerel, Y.;
Rodriguez, J. Tetrahedron 2009, 65, 9756; and references
cited therein . (b) Cho, G. Y.; Bolm, C. Org. Lett. 2005, 7,
1351. (c) Hackenberger, C. P. R.; Raabe, G.; Bolm, C.
Chem. Eur. J. 2004, 10, 2942. (d) Siu, T.; Yudin, A. Org.
Lett. 2002, 4, 1839. (e) Lemasson, F.; Gais, H.-J.; Runsink,
J.; Raabe, G. Eur. J. Org. Chem. 2010, 2157. (f) Bolm, C.;
Kaufmann, D.; Zehnder, M.; Neuburger, M. Tetrahedron
Lett. 1996, 23, 3985.
(19) (a) Bolm, C.; Simic, O.; Martin, M. Synlett 2001, 1878.
(b) Bolm, C.; Hackenberger, C. P. R.; Simic, O.; Verrucci,
M.; Mueller, D.; Bienewald, F. Synthesis 2002, 879.
Synthesis 2013, 45, 1505–1512
© Georg Thieme Verlag Stuttgart · New York