One-Pot Synthesis of Aryl- and Alkyl S-Perfluoroalkylated NH-Sulfoximines from Sulfides

Article abstract of DOI:10.1002/chem.201805055

A general efficient one-pot synthesis of S-perfluoroalkylated NH-sulfoximines from sulfides has been developed using phenyliodine diacetate (PIDA) and ammonium carbamate. Remarkable rate enhancement with trifluoroethanol was observed, presumably due to H-bonding effects. These mild and metal-free conditions are compatible with -CH₂F, -CFCl₂, -CF₂H, -CF₂Br, -C₄F₉, and -CF₃ groups, in both the alkyl- and aryl series. Based on a ¹⁹F NMR analysis, a λ⁶-acetoxysulfanenitrile intermediate was proposed.

Full text of DOI:10.1002/chem.201805055

A Journal of
Accepted Article
Title: One-pot Synthesis of Aryl- and Alkyl S-Perfluoroalkylated NH-
Sulfoximines from Sulfides
Authors: Slim Chaabouni, Jean-François Lohier, Anne-Laure
Barthelemy, Thomas Glachet, Elsa Anselmi, Guillaume
Dagousset, Patrick Diter, Bruce Pégot, Emmanuel Magnier,
and Vincent Reboul
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201805055
Link to VoR: http://dx.doi.org/10.1002/chem.201805055
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10.1002/chem.201805055
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COMMUNICATION
One-pot Synthesis of Aryl- and Alkyl S-Perfluoroalkylated
NH-Sulfoximines from Sulfides
Slim Chaabouni,[a] Jean-François Lohier,[a] Anne-Laure Barthelemy,[b] Thomas Glachet,[a] Elsa Anselmi,[b]
Guillaume Dagousset,[b] Patrick Diter,[b] Bruce Pégot,[b] Emmanuel Magnier*[b] and Vincent Reboul*[a]
Abstract:
A
general
efficient
one-pot
synthesis
of
combination of sodium azide in sulfuric acid or oleum) first
reported by Yagupolskii’s group in 1984 (Scheme 1b).[14] By
adaptating these conditions (dilution with dichloromethane or
chloroform), this methodology could be applied to a fluoromethyl
group[4b] as well as in the aliphatic series.[15] However, this
reactions remained difficult to handle due to the explosiveness
and toxicity of these reagents. To circumvent this issue, Magnier
reported a safer three steps synthesis starting from sulfoxides
through a Ritter type reaction (mediated by Tf2O and acetonitrile)
which allowed the synthesis of NH-sulfoximines after oxidation
and subsequent deprotection of the nitrogen (Scheme 1c).[16] This
procedure also suffers from drawbacks: its inefficiency in the
S-alkyl series as well as with S-fluoromethyl chains.
Regarding the growing interest for S-perfluoroalkyl sulfoximines,
there is an urgent need to tackle the limitations previously
mentioned, as well as a common one: the use of a sulfoxide as
the starting material. In the context of an exponential growth of
methodologies to prepare the SCF3 moiety,[17] the use of this
group as a substrate would be a fantastic advantage.
S-perfluoroalkylated NH-sulfoximines from sulfides has been
developed using PIDA and ammonium carbamate. Remarkable rate
enhancement with trifluoroethanol was observed, presumably due to
H-bonding effects. These mild and metal-free conditions are
compatible with -CH2F, -CFCl2, -CF2H, -CF2Br, -C4F9 and -CF3 groups,
in both the alkyl- and aryl series. Based on a 19F NMR analysis, a
l6-acetoxysulfanenitrile intermediate was proposed.
Since their discovery in 1950 by Bentley and Whitehead,[1]
NH-sulfoximines, the mono-aza analogues of sulfones, have
attracted much attention as illustrated by their wide application in
organic synthesis, and their promising properties for medicinal
chemistry.[2] The interest in the S-fluorinated sulfoximines has
grown in recent years, owing to their very peculiar properties.[3]
Shibata first demonstrated their ability to transfer the
perfluoroalkyl group to nucleophiles, and was followed by
others.[4] Fluorinated sulfoximines can furthermore act as
nucleophiles as performed by Hu,[5] or radical transfer agents.[6]
They are also employed as ortho-directing groups,[7] building
blocks for liquid crystals[8] and as powerful electron withdrawing
entities.[9] However, the principal drawback to their development
is still the lack of general preparation methods. If remarkable
efforts were made in the recent past to develop efficient syntheses
of non-fluorinated sulfoximines, it is important to point out that
these methodologies can hardly be transposed to the fluorinated
series.[10] This is mainly explained by the poor nucleophilicity of
the sulfur atom. Bolm confirmed the ineffective nitrene transfer to
phenyl trifluoromethyl sulfide and its corresponding sulfoxide and
We report herein a general, safe, one-pot and metal-free
preparation of aryl- and alkyl NH-sulfoximines from the
corresponding sulfides and applicable to a wide range of
fluorinated chains (Scheme 1d). A mechanistic investigation of
this reaction was also performed.
a) First synthesis by Shreeve's group from perfluorinated sulfoxide
O
NH
O
NH3
S
+
2 NH4Cl
S
RF
R'F
RF
R'F
F
F
b) Yagupolskii's work: from sulfoxide
O
thus developed
a
three step synthesis of N-protected
O
NH
R = Ar: NaN3, H2SO4
trifluoromethyl sulfoximines.[11] The same tendency was observed
by Luisi and Bull during the metal-free nitrene transfer to
4-bromophenyl trifluoromethyl sulfoxide.[12] The first synthesis of
fluorinated NH-sulfoximines was described by Shreeve’s group by
using sulfur oxydifluorides and ammonia.[13] Unfortunately, this
method was limited to the bis(perfluoroalkyl) series (Scheme 1a).
To date, the most straightforward synthesis is the reaction (by the
S
S
R
RF
R
RF
R = Alk: NaN3, H2SO4, CH2Cl2
c) Magnier's work: from sulfoxide
Ac
O
N
S
Tf2O
O
NH
1) KMnO4
2) HCl
S
S
Ar
RF
CH3CN
Ar
RF
Ar
RF
d) This work: one pot reaction from sulfide
PhI(OAc)2
NH2-CO2NH4
O
NH
S
S
R
RF
R
RF
CF3CH2OH
[a]
[b]
Dr. S. Chaabouni, J.-F. Lohier, T. Glachet and Dr. V. Reboul
Normandie Univ, LCMT, ENSICAEN, UNICAEN, CNRS, 14000
Caen, France
E-mail: vincent.reboul@ensicaen.fr
A.-L. Barthelemy, Dr. E. Anselmi, Dr. G. Dagousset,Dr. P. Diter,
Dr. B. Pégot and Dr. E. Magnier
Scheme 1. Preparation of NH-fluorinated sulfoximines
Institut Lavoisier de Versailles, UMR 8180, Université de Versailles-
Saint-Quentin. 78035 Versailles Cedex, France
E-mail:emmanuel.magnier@uvsq.fr
The group of Reboul recently developed an efficient synthesis
of non-fluorinated NH-sulfoximines from sulfides using
phenyliodine diacetate (PIDA) and ammonium carbamate (AC).
with methanol as the solvent.[18] However, when the reaction was
Supporting information for this article is given via a link at the end of
the document.
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10.1002/chem.201805055
Chemistry - A European Journal
COMMUNICATION
conducted in this solvent using trifluoromethyl phenyl sulfide 1a,
phenyl group, the conversion was lower and the yields dropped
to 47% for 2b and 65% for 2c. On the other hand, the
phenylsulfide 1d bearing a 4-methoxy substituent, led to an
excellent yield of 78% (2d). The same reaction conditions were
then applied to the challenging alkyl series. We were delighted to
obtain very high yields starting from sulfides containing an alkyl
chain (with 2, 3 or 6 carbon atoms) ending in a phenyl (2e; 95%),
benzyloxy (2f; 80%), cyano (2g; 80%), phenylester (2h; 70%) or
phenylcyano (2i; 72%) group. However, with benzylic sulfide (2j
and 2k) groups, the acid hydrolysis led to decomposition of both
sulfoximines. Consequently, this step was not performed and
moderate yields were obtained. Sulfoximine 2n, bearing an NH-
indole group, was also obtained in 48% yield from NBoc-indole
protected sulfide.
only traces of the desired NH-sulfoximine 2a were detected by 19
F
NMR analysis of the crude product and sulfide 1a was recovered
(Table 1, entry 1). We reasoned that increasing the electrophilicity
of the hypervalent iodine species could enhance the reactivity.
With BF3.Et2O, described as an efficient activator,[19] no
conversion was observed (entry 2). We next investigated the use
of highly polar and strong hydrogen-bond donating solvents.[20]
Hexafluoro-isopropanol (HFIP) led to complete conversion but
also to a messy crude mixture (Table 1, entry 3). In contrast, we
were delighted to find that trifluoroethanol (TFE) led to the
formation of sulfoximine 2a in 52% yield (Table 1, entry 4). Adding
nucleophilic additives such as methanol or water to the reaction
mixture (Table 1, entries 5-7) did not improve the yield.
Table 2. Reaction scope with various aryl- and alkyl trifluoromethyl sulfidesa,b
Table 1. Optimization of reaction conditions using sulfide 1a
NH
NAc
NH
O
O
O
PIDA (2.1 equiv)
AC (1.5 equiv)
NH
NAc
O
O
a
b
S
S
+
R
CF3
S
S
S
+
Ph
CF3
S
S
R
CF3
R
CF3
R
CF3
Ph
CF3
Ph
CF3
solvent, additive
rt, time
1
2
3
2
1a
2a
3a
a: PIDA (2.1 equiv), AC (1.5 equiv), TFE, rt, 3 h then PIDA (1 equiv), AC (1 equiv), 3 h
b: HCl, CH3CN, rt, 12 h
Entry
Solvent, additive
Time
[h]
Conversion;
Yield of
2a/3a ratio [%][a]
7; nd
2a [%][a]
2a: 85%[a][b] (88/12)[c]
R = H
NH
O
S
NH
O
2e: 95%
(84/16)
R = NO2
R = Br
2b: 47% [67%] (89/11)
2c: 65% [76%] (84/16)
2d: 78% (87/13)
Ph
S
1
2
3
4
5
6
7
8
9
10
MeOH
3
traces
nd
CF3
( )3
CF3
R
R = OMe
CH2Cl2, BF3.Et2O
HFIP
3
0; nd
MeO2C
NH
NH
NH
O
O
O
3
97; nd
traces
52
2f: 80%
(84/16)
2g: 89%
(87/13)
BnO
S
NC
S
S
( )3
( )6
( )2
CF3
CF3
2h: 70%
CF3
TFE
3
59; 88/12
30; 90/10
52; 88/12
53; 88/12
85; 88/12
100; 88/12
0; nd
(85/15)
1:1 MeOH/TFE
1:9 MeOH/TFE
1:9 H2O/TFE
TFE
3
27
F
NC
NH
O
S
NH
O
S
NH
O
2i: 72%
(84/16)
S
CF3
3
47
( )2
CF3
CF3
2j: 53%[d]
(83/17)
2k: 40%[d]
(100/0)
NH
3
46
O
O
S
N
CF3
6[b]
3+3[c]
3
75
F3CO
NH
O
S
NH
O
S
2l: 56%[d]
O
CF3
TFE
83[d]
nd
CF3
(85/15)
N
H
TFE, PIFA[e]
N
O
2n: 48% [76%][e]
2m: 68% (88%)
[a] Estimated by 19F NMR with PhOCF3 as internal standard. [b] PIDA
(3.1 equiv) and AC (2.5 equiv) were used. [c] Addition of PIDA and AC
(1 equiv) to the reaction mixture after 3 h. [d] Isolated yield of 2a after
acid hydrolysis (HCl/CH3CN). [e] PIFA was used instead of PIDA.
2l
(79/21)
(86/14)
[a] Isolated yields. Full conversion was almost always obtained, otherwise
indicated in square brackets. [b] Reaction performed on 12 mmole scale.
[c] Ratio of NH and NAc sulfoximines measured by 1H or 19F NMR analysis of
the crude mixture indicated in brackets. [d] Isolated yield without acid hydrolysis.
[e] The NBoc indole deprotection occurred during the acid hydrolysis at 80°C.
When the reaction time was extended to 6 h with the utilization
of an excess of PIDA/AC (3 equiv/2.5 equiv), the conversion rose
to 85% (Table 1, entries 8). Full conversion was achieved by
adding 1 equiv of each reagent after 3 h (Table 1, entry 9). The
use of TFE systematically delivered a constant ratio of molecules
2a/3a (see the mechanistic discussion). To avoid tedious
separation, the crude mixture was directly treated with HCl 6 M in
acetonitrile in order to deprotect 3a (full conversion after 12 h).[4e]
Using those optimized conditions, sulfoximine 2a was isolated in
83% yield.[21] However, when phenyliodine ditrifluomethylacetate
(PIFA) was used instead of PIDA, no reaction occurred (Table 1,
entry 10). With these conditions in hand, the scope of the reaction
was evaluated in the trifluoromethyl series (Table 2).
As a first progress status, our methodology allowed a mild
one-pot transformation of alkyl and aryl trifluoromethyl thioethers
into the corresponding sulfoximines. In light of these results, we
anticipated that our sulfoximination reaction could be applied to
other perfluoroalkyl series (Table 3). Sulfoximines bearing a
nonafluorobutyl group were indeed prepared in both the alkyl (4c)
and aryl series (4a, 4b[22]) with good yields. With sulfides bearing
a CF2Br group, excellent yields were obtained with a phenyl (5a;
87%), a tolyl (5b; 76%) or a 4-MeOC6H4 (5c; 86%) group as well
as with an aliphatic substrate (5d, 49%). X-ray structure of 5b
reveals an anti staggered conformation between the bromine and
the tolyl group.
The scalability of the reaction was first demonstrated by
conducting the reaction with 1a on a 12 mmol scale without
erosion of the yield. With electron withdrawing groups on the
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Table 3. Reaction scope with various aryl- and alkyl fluorinated sulfidesa,b
sulfoximines (Figure 1). We also observed a doublet (purple, at –
118.2 ppm) and another AMX system (2 dd in red at –114.2 and
–120.1 ppm). These latter signals gradually disappeared over
time (Figure 1, top) in favour of the two sulfoximines. Close
examination of the HRMS spectrum of the crude product,
revealed a mass corresponding to the sulfoximine 10 bearing a
[I+Ph] on the nitrogen atom. The structure of compound 10 was
undoubtedly confirmed by mixing sulfoximine NH-7b with PIDA.
The CF2H group in 19F NMR spectrum appeared as a doublet
(surprisingly the two fluorine atoms are magnetically equivalent at
–118.2 ppm). Consequently, we assigned this purple signal to the
sulfoximine 10. This compound 10 is very sensitive to hydrolysis
and slowly led to the corresponding NH-sulfoximine 7b. Its
formation can also explain the need for an excess of PIDA. The
last species detected by NMR showed a AMX system (red colour
in figure 1). Its concentration remains low and stable during the
first 5 hours before final disappearance.
NH
RF
NAc
RF
NH
RF
O
O
O
a
b
S
+
R
RF
S
S
S
R
R
R
a: PIDA (2.1 equiv), AC (1.5 equiv), TFE, rt, 3 h
then PIDA (1 equiv), AC (1 equiv), 3 h
b: HCl, CH3CN, rt, 12 h
NH
O
S
NH
O
R = H
4a: 77%[a] (85/15)[b]
4c: 63% [86%]
(89/11)
S
C4F9
( )11
C4F9
R = Br 4b: 46% [66%]
(87/13[c]
)
R
NH
O
NH
O
5a: 87% (83/17)
5b: 76% (83/17)
R = H
CF2Br R = Me
S
S
S
( )11
CF2Br
5b
R = MeO 5c: 86%
5d: 49%
(87/13)
R
R
(84[c]/16)
NH
CFCl2
O
NH
O
R = H
6a: 88% (78/22)
S
( )7
CFCl2
R = Br
6b: 33% [45%]
(81/19)
6b
6c: 81%
(87/13)
NH
O
7a: 74% 82%[d]
(75/25)
NH
O
R = H
S
S
CF2H
Ph
S
( )3
CF2H
R = MeO 7b: 58%, 88%[d]
(78/22)
7c: 64%, 68%[d]
(87/13)
R
R
7b
NH
CH2F
O
8a: 28% 80%[d] (86/14)
8b: 42%, 89%[d] (82/18[c]
R = Me
R = H
)
[a] Isolated yields. Full conversion was almost always obtained, otherwise
indicated in square brackets. [b] Ratio of NH and NAc sulfoximines measured
by 1H or 19F NMR analysis of the crude mixture indicated in brackets. [c] X-Ray
was obtained. [d] Reaction performed in MeOH.
Monofluoro dichloro thioethers proved also to be efficient
substrates as illustrated by the synthesis of aryl (6a, 6b) and alkyl
sulfoximines (6c). The reactivity with the challenging
difluoromethyl and fluoromethyl moieties was more surprising.
The difluorinated substrates gave rise to the S-aryl sulfoximines
7a-b and S-alkyl sulfoximine 7c with good yields. Quite
unexpectedly the latter was improved with methanol as the
solvent. This result was even more pronounced with the
fluoromethyl phenyl thioether. With TFE, a moderate yield of 42%
of sulfoximine 8a was obtained whereas with methanol, the
sulfoximines 8a and 8b[22] were isolated in excellent yields of 80%
and 89% respectively. These last conditions, which were already
described for the non-fluorinated series,[18] were only efficient for
these two S-difluoromethyl and S-monofluoromethyl substrates
with an emphasis for the latter.[23] In other cases, TFE is essential.
This last remark suggests a different pathway between the non-
fluorinated thioethers and the perfluoroalkylated ones.
Consequently, special attention was paid to the reaction
mechanism.
Ph
I
N
O
N
OAc
NH
NAc
O
S
O
S
S
H
H
H
S
H
F
F
F
F
F
F
F
F
O
O
O
O
NH-7b
NAc-7b
9
10
Figure 1. 19F NMR spectra (CDCl3, 564 MHz, –20°C) of reaction mixture over
time, selected region (d = –113 to –124 ppm).
This intermediate possess an asymmetric sulfur atom. Based
on our previous experience,[18] its structure was assigned to
sulfanenitrile
mechanism. It starts with the initial formation of an activated
nitrene, mediated by TFE, able to react with
9 and allowed us to propose the following
perfluoroalkylthioethers (Scheme 2). As this species has a very
short life time, no observation by NMR analysis was successful.
We postulate that a H-bonded adduct between the TFE and PIDA
led to the formation of the [PhI(OAc)]+ cation A. In the presence
of ammonia, nitrene B should be formed, as described by Luisi
and Bull[24] and by Reboul,[18] in the non-fluorinated series.[25] The
TFE would also be involved in the formation of the activated
nitrene [PhI+N] C through H-bonding. The reaction of the latter
with the sulfur atom gives rise to a sulfilimine D, undetected by
Monitoring of the reaction by 19F NMR analysis (in TFE at 0°C)
as well as by mass spectrometry was undertaken (Figure 1). The
(4-methoxyphenyl) difluoromethyl thioether was chosen as the
model substrate because of its peculiarly remarkable NMR
signals. Both expected sulfoximines, NH-7b and NAc-7b,
possess two diastereotopic fluorine atoms. After one minute of
reaction, we thus observed the rapid formation of NH-7b (AB part
of ABX system in blue at –121.8 and –119.3 ppm) and NAc-7b
(AMX system in green, 2 dd at –115.4 and –122.7 ppm)
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COMMUNICATION
[1]
[2]
a) Bentley, J. K. Whitehead, J. Chem. Soc. (D) 1950, 2081-2082; b) H.
R. Bentley, E. E. McDermott, J. Pace, J. K. Whitehead, and T. Moran,
Nature 1950, 165, 150.
NMR analysis. The nucleophilic attack of an acetate anion on this
short lived species (SN2 type reaction, Scheme 2, red arrows)
delivers the observed sulfanenitrile intermediate F. Subsequent
attack of TFE on the latter account for the formation of the NH-
For reviews on sulfoximes: a) C. R. Johnson, Acc. Chem. Res. 1973, 6,
341; b) S. G. Pyne, Sulfur reports 1999, 21, 281; c) M. Reggelin, C. Zur,
Synthesis 2000, 1; d) U. Lücking, Angew. Chem. Int. Ed. 2013, 52, 9399;
Angew. Chem. 2013, 125, 9570.
sulfoximine
as
proved
by
the
presence
of
the
trifluoroethanolacetate G[26] (observed in the crude mixture). Last,
the NH-sulfoximine can react either with the PIDA (formation of
H) or with the sulfanenitrile F according to the isolated mixture of
NH and NAc sulfoximines. Although not proved by our
experimental observations, a second pathway cannot be totally
ruled out. The formation of a thiazynium E should be possible via
a SN1 like mechanism from sulfilimine D (Scheme 2, purple
arrows), as proposed by Yoshimura.[27] Considering the poor
nucleophilicity of trifluoroethanol, the thiazynium E would evolve
into sulfanenitrile F instead of F’.
[3]
[4]
For reviews on fluorinated sulfoximes: a) V. Bizet, R. Kowalczyk, C. Bolm,
Chem. Soc. Rev. 2014, 43, 2426; b) X. Shen, J. Hu, Eur. J. Org. Chem.
2014, 4437; c) A.-L. Barthelemy, E. Magnier, C. R. Chimie 2018, 21, 711.
a) S. Noritake, N. Shibata, S. Nakamura, T. Toru, M. Shiro, Eur. J. Org.
Chem. 2008, 3465; b) Y. Nomura, E. Tokunaga, N. Shibata, Angew.
Chem. Int. Ed. 2011, 50, 1885; Angew. Chem. 2011, 123, 1925; c) Y.-D
Yang, X. Lu, G. Lu, E. Tokunaga, S. Tsuzuki, N. Shibata, ChemistryOpen
2012, 1, 221; d) G. K. S. Prakash, Z. Zhang, F. Wang, C. Ni, G. A. Olah,
J. Fluorine. Chem. 2011, 132, 792; e) B. Pégot, C. Urban, A. Bourne, T.
N. Le, S. Bouvet, J. Marrot, P. Diter, E. Magnier, Eur. J. Org. Chem. 2015,
3069.
X = AcO or CF3CH2O
[5]
a) M. L. Boys, E. W. Collington, H. Finch, S. Swanson, J. F. Whitehead,
Tetrahedron Lett. 1988, 29, 3365; b) W. Zhang, F. Wang, J. Hu, Org. Lett.
2009, 11, 2109; c) W. Zhang, W. Huang, J. Hu, Angew. Chem. Int. Ed.
2009, 48, 9858; Angew. Chem. 2009, 121, 10042; d) W. Zhang, J. Hu,
Adv. Synth. Catal. 2010, 352, 2799; e) X. Shen, W. Zhang, L. Zhang, T.
Luo, X. Wan, Y. Gu, J. Hu, Angew. Chem. Int. Ed. 2012, 51, 6966; Angew.
Chem. 2012, 124, 7072; f) X. Shen, W. Zhang, C. Ni, Y. Gu, J. Hu, J. Am.
Chem. Soc. 2012, 134, 16999; g) X. Shen, W. Miao, C. Ni, J. Hu, Angew.
Chem. Int. Ed. 2014, 53, 775; Angew. Chem. 2014, 126, 794; h) X. Shen,
Q. Liu, T. Luo, J. Hu, Chem. Eur. J. 2014, 20, 6795.
F3C
F3C
H
O
H
O
O
OAc
N
X
N
NH3
TFE
O
O
Ph
I
Ph
I
X
Ph
O
I
Ph
I
A
B
Nitrene
C Activated
nitrene
OAc
N
O
N
CF3
TFE
S
S
R RF
SN1 like
(disfavored)
R
RF
Ph
I
E
S
F' (not detected)
R
RF
N
CF3
O
AcO
S
F3C
R
RF
OAc
[6]
a) Y. Arai, R. Tomita, G. Ando, T. Koike, M. Akita, Chem. Eur. J. 2016,
22, 1262; b) N. Noto, T. Koike, M. Akita, J. Org. Chem. 2016, 81, 7064;
c) M. Daniel, G. Dagousset, P. Diter, P.-A. Klein, B. Tuccio, A.-M.
Goncalves, G. Masson, E. Magnier, Angew. Chem. Int. Ed. 2017, 56,
3997; Angew. Chem. 2017, 129, 4055
TFE
(favored)
O
O
AcN
R
HN
R
F
D
H
O
S
S
SN2 like
O
H
RF
RF
O
AcO
CF3
N
PIDA
G
S
R
RF
I
O
N
Ph
F
[7]
[8]
[9]
T.-N. Le, P. Diter, B. Pégot, C. Bournaud, M. Toffano, R. Guillot, G. Vo-
Thanh, E. Magnier, Org. Lett. 2016, 18, 5102.
H
S
R
RF
AcO
Scheme 2. Proposed mechanism.
P. Kirsch, M. Lenges, D. Kuehne, K.-P. Wanczek, Eur. J. Org. Chem.
2005, 797.
a) F. Terrier, E. Magnier, E. Kizilian, C. Wakselman, E. Buncel, J. Am.
Chem. Soc. 2005, 127, 5563; b) C. Rouxel, C. Le Droumaguet, Y. Macé,
S. Clift, O. Mongin, E. Magnier, M. Blanchard-Desce, Chem. Eur. J. 2012
18,12487.
In summary, we have reported the first direct synthesis of
fluorinated NH-sulfoximines from sulfides in both the alkyl and aryl
series. A diverse set of important functional groups were well
tolerated. Remarkable reactivity enhancement with TFE was
observed. In agrochemical and medicinal chemistry, the use of
fluorinated sulfoximines has been neglected for a long time[28] and
we expect this methodology will be used in order to increase
chemical diversity. Further investigations to expand the reactivity
of such species are also in progress in our laboratories.
[10] A single example of NTs-sulfoximine was reported by oxidative imination
of difluoromethyl phenyl sulfoxide (with PhI=NTs in the presence of
catalytic amount of copper triflate). See reference 5b
[11] R. Kowalczyk, A. J. F. Edmunds, R. G. Hall, C. Bolm, Org. Lett. 2011, 13,
768.
[12] M. Zenzola, R. Doran, L. Degennaro, R. Luisi, J. A. Bull, Angew. Chem.
Int. Ed. 2016, 55, 7203; Angew. Chem. 2016, 128, 7319.
[13] a) D. T. Sauer, J. M. Shreeve, Inorg. Chem. 1972, 11, 238; b) T. Abe, J.
M. Shreeve, Inorg. Chem. 1981, 20, 2432; c) T. Abe, J. M. Shreeve, Inorg.
Chem. 1981, 20, 2894; d) T. Abe, J. M. Shreeve, J. Chem. Soc., Chem.
Commun. 1981, 242.
Acknowledgements
[14] a) N. V Kondratenko, O. A. Radchenko, L. M. Yagupolskii, Zh. Org. Khim.
1984, 20, 2250; b) N. V. Kondratenko, V. I. Popov, O. A. Radchenko, N.
V. Ignat’ev, L. M. Yagupolskii, Zh. Org. Khim. 1986, 22, 1716.
[15] E. Magnier, C. Wakselman, Synthesis 2003, 565.
[16] a) Y. Mace, C. Urban, C. Pradet, J. Marrot, J.-C. Blazejewski, E. Magnier,
Eur. J. Org. Chem. 2009, 3150; b) B. Pegot, C. Urban, P. Diter, E.
Magnier, Eur. J. Org. Chem. 2013, 7800.
S.C. thanks Labex Synorg and Labex Charmmmat for
a
postdoctoral fellowship. A.-L.B. thanks the French Ministry of
Research for a doctoral fellowship. We gratefully acknowledge Dr.
K. Wright for the improvement of the English manuscript, K.
Jarsalé for HRMS analysis, H. Elsiblani and R. Legay for 1H NMR
studies.
[17] X.-H. Xu, K. Matsuzaki, N. Shibata, Chem. Rev. 2015, 115, 731.
[18] J.-F. Lohier, T. Glachet, H. Marzag, A.-C. Gaumont, V. Reboul, Chem.
Commun. 2017, 53, 2064.
[19] S. Izquierdo, S. Essafi, I. Del Rosal, P. Vidossich, R. Pleixats, A.
Vallribera, G. Ujaque, A. Lledós, A. Shafir, J. Am. Chem. Soc. 2016, 138,
12747.
Keywords: fluorinated NH-sulfoximines • PIDA • iodonitrene •
thiazynium • λ6–sulfanenitrile
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[20] I. Colomer, C. Batchelor-Mcauley, B. Odell, T. J. Donohoe, R. G.
Compton, J. Am. Chem. Soc. 2016, 138, 8855.
[21] Sulfoximine 2a was also obtained from the corresponding sulfoxide but
in a lower yield of 51% using the optimized conditions.
[22] The X-ray structure of the corresponding N-Ac sulfoximine was obtained.
See Supporting Information.
[23] We rationalized theses results considering the poor nucleophilicity of the
sulfur atom when a trifluoromethylthio group is present.
[24] A. Tota, M. Zenzola, S. J. Chawner, S. S. John-Campbell, C. Carlucci, G.
Romanazzi, L. Degennaro, J. A. Bull, R. Luisi, Chem. Commun. 2017,
53, 348.
[25] The formation of the iodonitrene (B or C) is not observed when PIFA and
ammonium carbamate (or ammonia) were mixed in MeOH (no formation
of N2).
[26] In 19F NMR analysis, the chemical shift of trifluoroethanolacetate is
characteristic with a triplet at –74 ppm.
[27] T. Yoshimura, E. Tsukurimichi, H. Kita, H. Fujii, C. Shimasaki, Bull. Chem.
Soc. Jpn. 1990, 63, 1764.
[28] Selected references: a) M. Kahraman, S. Sinishtaj, P. M. Dolan, T. W.
Kensler, S. Peleg, U. Saha, S. S. Chuang, G. Bernstein, B. Korczak, G.
H. Posner, J. Med. Chem. 2004, 47, 6854; b) U. Lücking, R. Jautelat, M.
Krüger, T. Brumby, P. Lienau, M. Schäfer, H. Briem, J. Schulze, A.
Hillisch, A. Reichel, A. M. Wengner and G. Siemeister, ChemMedChem
2013, 8, 1067; c) C. M. M. Hendriks, J. Hartkamp, S. Wiezorek, A.-D.
Steinkamp, G. Rossetti, B. Lüscher, C. Bolm, Bioorg. Med. Chem. Lett.
2017, 27, 2659.
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Slim Chaabouni, Jean-François Lohier,
Anne-Laure Barthelemy, Thomas
Glachet, Elsa Anselmi, Guillaume
Dagousset, Patrick Diter, Bruce Pégot,
Emmanuel Magnier* and Vincent
Reboul*
Page No. – Page No.
One-pot Synthesis of Aryl- and Alkyl
S-Perfluoroalkylated NH-Sulfoximines
from Sulfides
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