Divergent preparation of fluoroalkylated sulfilimine and sulfilimino iminium salts

Article abstract of DOI:10.1002/adsc.201000494

We have successfully extended our previously described methodology for the preparation of trifluoromethyl N-acyl sulfilimines to the case of bromodifluoro- and dichlorofluoromethyl derivatives. Attempts to convert such N-acyl sulfilimines to free NH-sulfi

Full text of DOI:10.1002/adsc.201000494

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DOI: 10.1002/adsc.201000494
Divergent Preparation of Fluoroalkylated Sulfilimine and
Sulfilimino Iminium Salts
Cꢀline Urban,a Yohan Macꢀ,a Frꢀdꢀric Cadoret,a Jean-Claude Blazejewski,a
and Emmanuel Magniera,*
a
Institut Lavoisier de Versailles, UMR CNRS 8180, Universitꢀ de Versailles St-Quentin-en-Yvelines, 45, Avenue des
Etats-Unis, 78035 Versailles Cedex, France
Fax : (+33)-1-3925-4452; e-mail: magnier@chimie.uvsq.fr
Received: June 25, 2010; Published online: October 26, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000494.
Abstract: We have successfully extended our previ- tron-withdrawing groups giving structures close to
ously described methodology for the preparation of those of efficient perfluoroalkylating agents. Prelimi-
trifluoromethyl N-acyl sulfilimines to the case of bro- nary experiments showed that these new sulfilimine-
modifluoro- and dichlorofluoromethyl derivatives. based compounds have poor perfluoroalkylating
Attempts to convert such N-acyl sulfilimines to free abilities, demonstrating that the sulfilimine function
NH-sulfilimines failed. However, a strategy based on is not sufficiently activating for that purpose, contra-
the reaction of their direct ditriflyl ketal precursor ry to sulfur(VI) reagents.
with amines allows the isolation of either original
sulfilimino iminium salts using secondary amines or Keywords: electron-deficient compounds; fluorine;
of free NH-sulfilimines using primary amines. The sulfilimines; sulfilimino iminium salts; synthetic
latter were further easily N-functionalized with elec- methods
Introduction
(Figure 1). Perfluoroalkyl sulfoxides and sulfones
have indeed been described as efficient nucleophilic
The introduction of fluorine into organic substrates is perfluoroalkylating reagents,[3] yet recent innovative
a subject of great interest. Numerous studies in this research in this area has highlighted the importance
field have been stimulated by the unrivalled proper- of the perfluoroalkyl sulfoximine structures as new
ties brought about by the presence of this atom.[1] Its electrophilic perfluoroalkylating agents.[4] Interesting-
incorporation into molecules has allowed for progress ly, it is important to notice that the replacement of an
in life sciences (medicinal chemistry and agrochemis- oxygen by a nitrogen atom reverses the behaviour of
try), material sciences, energy and also in catalysis.[2] the reagent.
Despite all these improvements, there are many chal-
However, until our publication concerning the
lenges still remaining for organic chemists, in particu- preparation under very mild conditions of sulfilimines
lar the introduction of perfluoroalkyl groups. The and sulfoximines, access to compounds 2 and 4 was
family of sulfur(IV) and sulfur(VI) derivatives ap- somewhat limited. We disclosed a Ritter-like reaction,
pears to be flexible for this purpose because it has fur- between nitriles and sulfoxides activated by trifluoro-
nished either nucleophilic or electrophilic reagents methanesulfonic anhydride, giving rise to a wide
Figure 1. Sulfoxide, sulfone and sulfoximine perfluoroalkylating reagents.
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Table 1. Preparation of mono- and difluoromethyl acyl sulfil-
AHCTUNGTRENGNiUN mines.
Scheme 1. General preparation of fluorinated acyl sulfil-
ACHTUNGTRENNUNGimines.
Entry[a]
R
R’
RF
Yield [%]
1
2
3
4
5
6
7
8
9
H
Me
Me
Me
Ph
CF2Br
CF2Br
CF2Br
CF2Br
CF2Br
CFCl2
CFCl2
CFCl2
CFCl2
CFCl2
4a
4b
4c
4d
4e
4f
4g
4h
4i
81
83
78
72
55
73
67
64
31
18
range of acyl sulfilimines 4 after hydrolysis of a ditri-
flyl ketal 5 intermediate (Scheme 1).[5] In the same
work, we also described the facile synthesis of per-
fluorinated sulfoximines either by oxidation of pure
sulfilimines 4 or directly in a one-pot process from
sulfoxides.
Recently, Hu and co-workers described the prepa-
ration of a difluoromethyl sulfoximine 1 by copper-
catalyzed nitrene transfer reaction onto the corre-
sponding sulfoxide.[4a] This publication prompted us to
firstly extend our methodology to aryl mono- and di-
fluoromethyl N-functionalized sulfilimines. Secondly,
Me
Br
H
H
H
Me
Br
H
G
ACHTUGNRTNE(NUNG CH2)2Br
Me
Me
Me
Ph
10
H
(CH2)2Br
4j
[a]
See ref.[6] for the preparation of starting sulfoxides.
we wanted to probe the behaviour of a wide range of functionalization of the nitrogen. The main purpose is
fluorinated sulfilimines including newly synthesized the preparation of new perfluoroalkylating reagents
ones under both nucleophilic and electrophilic per- based on enhanced activation of the perfluoroalkyl
fluoroalkylation conditions.
part by the nitrogen substituent. Numerous attempts
at hydrolysis (or reduction) of acylsulfilimines 4
proved, however, to be unsuccessful and only led
either to the parent sulfoxides or to non-fluorinated
products.
Results and Discussion
As a prerequisite we started by studying the prepara-
We thought that a clue to this problem could be
tion of aryl bromodifluoro- and dichlorofluoromethyl found in the synthetic intermediate 5. The challenge
sulfilimines (Table 1). Selected examples of bromodi- was to switch from a simple hydrolysis of 5 (giving
fluoromethyl sulfoxides clearly demonstrated the effi- rise to acyl sulfilimine 4) to the preparation of deriva-
ciency of our approach (entry 1). For these the substi- tives which are more amenable to deprotection by the
tution of the aromatic ring was tolerated (entries 2 choice of a suitable nucleophile able to selectively re-
and 3) as well as the variation of the nitrile (entry 4) place the trifluoromethanesulfonic groups in 5.
including one derivative bearing a terminal bromine
Amongst the possible reagents, amines were first
allowing a further post-functionalization (entry 5). considered as candidates for such a purpose. Interest-
Similar results were obtained with dichlorofluoro- ingly, we found that the compounds formed using pri-
methyl sulfoxides with somewhat lower yields espe- mary amines were totally different from those ob-
cially with nitriles other than acetonitrile (entries 6– tained with secondary amines. In this latter case, we
10). The isolation of aryl difluoromethyl acylsulfili- were pleased to find that addition of amines to the
mines (RF =CF2H) 4 was not really successful. In crude reaction mixture allowed the formation of
spite of a total conversion of the corresponding aryl stable and original sulfilimino iminium salts 6, thus
difluoromethyl sulfoxide, we were unable to isolate, achieving our first goal: the substitution of the bis tri-
in both an acceptable and reproducible yield, the flate moieties (Scheme 2).
target molecule because of its degradation during the
purification on silica gel. For the further synthesis of
sulfoximines, our work hence appears to be comple-
mentary to the copper-based methodology of Hu and
co-workers.[4a]
We next focused our attention on the preparation
of “free sulfilimines”. The isolation of these target
compounds would be of interest, with one of the first
and most important challenges envisioned being the Scheme 2. Treatment with secondary amines.
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Divergent Preparation of Fluoroalkylated Sulfilimine and Sulfilimino Iminium Salts
Table 2. Preparation of sulfilimino iminium salts.
This latter reaction was then optimized. Ideally, the
primary amine should be introduced in a dry form (to
avoid formation of acylsulfilimines 4 by competing
hydrolysis), should be inexpensive and have a low
boiling point (because the amine is used in excess).
Good results were obtained with ammonia and ethyl-
amine but these were later discarded because their
volatility was too high.
Propylamine met the above criteria and hence ap-
peared to be the best candidate. The number of
equivalents needed for the reaction was then studied.
Below a critical value of 15 equivalents, we were not
able to reach total completion of the reaction. This
amount was considered as our standard for the studies
devoted to the scope of this transformation (Table 3).
The reaction was then conducted on a wide range of
aryl fluoroalkyl sulfoxides. Two types of structural
variations were examined: the nature and length of
the fluorinated chains and the substitution of the aro-
matic ring. The gram-scale synthesis of NH-sulfil-
Entry
R
R’
R1
R2
RF
Yield [%]
76
1
2
3
4
5
6
7
8
9
H
H
H
H
Me Et
Me Et
Me
Et
Et
Pr
CFCl2
6a
CF2Br 6b 83
CF3 6c
79[a]
6d 98
H
Me Me Me CF3
Me Me Me Me CF3
Me Me Et
Me Ph
Me Ph
Br
6e
6f
6g
76
91
82
Et
Et
Ph
Et
CF3
CF3
CF3
C4F9
Et
Ph
6h 85
6i 89
Me Et
[a]
Only three equivalents of amine were used.
AHCTUNGTRENNUNG
In the case of secondary amines a short study (entries 7–14) and higher perfluoroalkyl chains. In
showed that at least 4 equivalents of amine relative to spite of a total conversion, the slightly lower yields
the starting sulfoxide were needed in order to ensure observed for mono- and difluorinated groups may be
good yields of salts 6, but that a large excess of amine explained by the fact that compounds 7a–f are rela-
was not detrimental to the yield. The reaction appears tively unstable and partially decomposed during the
very flexible to numerous possible structural varia- purification step on silica gel. The presence of a
tions: substitution of the aromatic ring, the length of methyl substituent on the aromatic group is beneficial
the fluorinated chain (from mono to perfluoralkyl), to the yield whereas the attachment of a halogen de-
the nature of the nitrile and of the secondary amine creased slightly the yield. All these new compounds
(Table 2). All these new compounds were stable, iso-
lated in very good yields and fully characterized. The
examples depicted in Table 2 are representative of the
Table 3. Preparation of “free sulfilimines”.
versatility and the flexibility of this one-pot reaction.
This as yet unknown and original family of molecules
can thus be easily synthesized on demand and may
find useful applications. For instance aryl sulfilimino
iminium salts such as 6h (entry 8) exhibiting many
highly delocalized p electrons, and a high polarity
Entry
R
RF
Yield [%]
could be interesting in molecular electronics with em-
phasis in fluorescence.
1
2
3
4
5
6
7
8
H
CFCl2
CFCl2
CFCl2
CF2Br
CF2Br
CF2Br
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
C4F9
C4F9
C4F9
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
7q
54
46
48
59
64
57
91
99
99
99
88
90
77
79
70
94
70
p-Me
p-Br
H
p-Me
p-Br
H
o-Me
m-Me
p-Me
p-Br
o-Cl
m-Cl
p-Cl
H
Interestingly, the use of a primary amine in a 3:1
stoichiometry also led to the isolation of an iminium
salt 6c (entry 3). However, contrary to the case of sec-
ondary amines and to our delight, when an excess of
primary amine was used a free sulfilimine 7 was iso-
lated instead of a salt 6 (Scheme 3).
9
10
11
12
13
14
15
16
17
p-Me
p-Br
Scheme 3. Treatment with an excess of primary amines.
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Scheme 4. Mechanism proposal with either primary or secondary amines.
are stable once isolated and can be kept for weeks in stitution failed, thus preventing the introduction of
the refrigerator. methyl, benzyl or allyl groups. With all these experi-
Reactions with both secondary and primary amines ments, the conversion of the starting sulfilimines was
can be rationalized by the following mechanism pro- almost quantitative but no fluorinated compound has
posal (Scheme 4). We assume that a first equivalent been observed. We assume therefore that N-alkylated
of amine displaces a trifluoromethanesulfonate of the sulfilimines are not stable enough to be isolated.
ketal 5[7] (trapped by a second equivalent of amine) Metal-catalyzed (Pd and Cu) arylation at nitrogen
to produce the intermediate 9 which quickly evolves under the conditions described for sulfoximines
into the key iminium salt 6. The first part of this proved unsuccessful.[9] No reaction occurred in the
transformation pathway requires at least three equiva- different conditions tested and the starting materials
lents of amine: two for the main process and a third was entirely recovered. Fortunately, the introduction
being consumed by the slight excess of trifluorome- of an electron-withdrawing group was efficient for
thanesulfonic anhydride remaining in the reaction sulfilimine stabilization, as shown by the results sum-
medium. Addition of an amine in this precise amount marized in Table 4. Mild conditions allowed the syn-
then gives rise to the sole isolation of salt 6 whatever thesis of sulfilimines bearing a trifluoromethanesul-
its substitution degree (primary or secondary). On the fonyl group in good (for CF3 series) to acceptable
other hand, the addition of an amine in a large excess yields (for mono- and difluoromethyl series) (en-
showed the greatly diverging behaviour of primary tries 1–3). We next concentrated our efforts on tri-
and secondary amines. With secondary amines, even fluoromethyl derivatives. Tosyl and nosyl derivatives
in excess, nothing else happens and salt 6 is still the as well as nitro, cyano and Boc substituted derivatives
major product. The use of a primary amine allows the were readily obtained (entries 4–8). We also envi-
formation of free sulfilimines 7. As a matter of fact, sioned functionalization of the nitrogen by an aza-Mi-
when R1 and R2 are not hydrogens, compound 6 chael addition. However, reactions attempted with
seems to be stable in the reaction medium and would classic Michael acceptors (acrylonitriles or acrylates)
not evolve further. If however R1 is a hydrogen, a met with poor success even under harsh conditions
prototropic equilibrium can generate molecule 10. (no solvent, high temperature). By contrast, vinyl tri-
The latter can further react with another equivalent decafluorohexyl sulfone showed again its very high
of amine to yield sulfilimine 7 and amidinium 11. This reactivity[10] and the Michael adduct 12i (entry 9) was
mechanism is supported by the isolation and full char- obtained within a very short time and in an excellent
acterization of 11a (R=Ph and R2 =Pr, see Experi- yield. These latter results highlighted the poor nucleo-
mental Section), whose structure is in agreement with philicity of perfluoroalkyl free sulfilimines.
those of previously described analogues.[8] Moreover,
As mentioned in the introduction, the structures of
when the pure isolated salt 6c was treated again with some of the compounds described in this work are
an excess of propylamine it was fully converted into reminiscent of those of efficient fluoroalkylating re-
the corresponding free sulfilimine 7g.
agents described either by Shibata or Hu.[4] It was
With free sulfilimines in hand, different possibilities thus tempting to test the fluoroalkylating ability of
for their N-functionalization were then envisioned. our compounds toward nucleophilic (thiolate, acety-
All attempts at alkylation by direct nucleophilic sub- lide, enolate, phenolate) or also electrophilic (ketone,
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Divergent Preparation of Fluoroalkylated Sulfilimine and Sulfilimino Iminium Salts
Table 4. Functionalization of “free sulfilimines”.
Entry
Reactant
Conditions
R
Yield [%]
1
2
3
4
5
6
7
8
9
7a
7d
7g
7g
7g
7g
7g
7g
7g
Tf2O, pyridine, CH2Cl2
Tf2O, pyridine, CH2Cl2
Tf2O, pyridine, CH2Cl2
TsCl, pyridine, CH2Cl2
NsCl, pyridine, CH2Cl2
HNO3, H2SO4, Ac2O, CH2Cl2
BrCN, Et3N, CH2Cl2
Tf
Tf
Tf
Ts
12a
12b
12c
12d
12e
12f
12g
12h
12i
47
38
84
100
83
66
38
70
83
Ns
NO2
CN
Boc
Boc2O, Et3N, CH2Cl2
À
CH2=CH SO2C6F13, CH2Cl2
ACHTGNUTERNUN(NG CH2)2SO2C6F13
aldehyde, alkene) species. In both cases, the attempts assume that these compounds could be used as novel
with the acyl sulfilimines 4, with iminium salts 6 as ligands for organometallic purposes. Besides, the free
well as with free sulfilimines 7 afforded only at best sulfilimines will be studied as new organocatalysts.
traces amounts of fluoroalkylated products. Although Lastly, these new sulfilimine derivatives will be evalu-
some encouraging results were obtained with trifluor- ated as new pharmacophores for medicinal and agro-
omethanesulfonyl sulfilimines 12a–c, they were not chemistry purposes.
sufficiently clear-cut or high-yielding to warrant fur-
ther extensive study. The best results were achieved
upon condensation of lithium phenylacetylide with
Experimental Section
acylsulfilimine 4a affording bromodifluoromethylphe-
nylacetylene in only 23% conversion, or of lithium 6-
methoxy-2-naphthylacetylide with triflyl sulfilimine
12b giving the corresponding bromodifluoromethyl
derivative in a 22% estimated yield but hardly separa-
ble from the starting material.
General Procedure for the Preparation of Sulfilimine,
as Exemplified by the Reaction of Difluorobromo-
methyl Phenyl Sulfoxide with Acetonitrile
Trifluoromethanesulfonic anhydride (1.7 mL, 9.5 mmol,
1.5 equiv.) was added to a precooled (À158C) mixture of
phenyl bromodifluoromethyl sulfoxide (1.6 g, 6.4 mmol,
1 equiv.) and acetonitrile (0.5 mL, 9.5 mmol, 1.5 equiv.). The
reaction mixture was stirred for one day at À158C, then hy-
drolyzed with water (20 mL), and extracted with CH2Cl2
(3ꢂ50 mL). The combined organic layers were washed with
water (3ꢂ50 mL), dried over MgSO4, and concentrated
under reduced pressure. The residue was purified by flash
chromatography (SiO2, pentane/Et2O 4/6) to give N-(acetyl)
bromodifluoromethyl phenyl sulfilimine (4a) as an orange
powder; yield: 1.5 g (81%); mp 56–588C; 19F NMR
(188 MHz, CDCl3): d=À47.1 and À46.1 (AB syst, J=
Conclusions
We have demonstrated the efficiency of amine trap-
ping for the functionalization of the bis triflate inter-
mediate 5. The great molecular diversity offered by
the judicious choice of the nitrogen derivative allowed
either original sulfilimino iminium salts 6 or free sulf-
ACHTUNGTRENNUNG
7
1
groups afforded stable sulfilimines. Preliminary ex-
periments showed that these sulfilimine-based com-
136 Hz); H NMR (300 MHz, CDCl3): d=2.21 (3H, s), 7.55–
7.61 (2H, m), 7.68 (1H, tt, J=7.5 Hz, J=1.6 Hz), 7.87–7.91
pounds showed poor efficiency regarding perfluoro- (2H, m); 13C NMR (75 MHz, CDCl3): d=24.6, 123.4 (CF2,
dd, J=352 Hz, J=348 Hz), 128.0, 129.2, 129.7, 134.2, 183.3;
anal. calcd. for C9H8BrF2NOS: C 36.50, H 2.72, N 4.73;
found: C 36.59, H 2.73, N 4.73.
alkyl transfer reactions. Nevertheless, the important
variety of sulfilimines described here opens the way,
by simple oxidation, to a wide range of sulfoximines
as new and promising perfluoroalkylating reagents.
These studies are currently under development in our
laboratory. Furthermore, many other applications are
envisioned for these new and original structures. Non-
fluorinated sulfoximines have been extensively de-
scribed as efficient ligands for catalysis[11] and also
N-(Acetyl) bromodifluoromethyl p-tolyl sulfilimine (4b):
White powder; mp 58–608C; 19F NMR (188 MHz, CDCl3):
d= À47.4 and À46.4 (AB syst, J=135 Hz); 1H NMR
(200 MHz, CDCl3): d=2.19 (3H, s), 2.41 (3H, s), 7.36 (2H,
d, J=8.2 Hz), 7.77 (2H, d, J=8.2 Hz); 13C NMR (75 MHz,
CDCl3): d=21.6, 24.7, 123.6 (CF2, dd, J=352 Hz, J=
348 Hz), 124.6, 129.3, 130.5, 145.5, 183.3; MS (pos. ESI, for
more rarely non-fluorinated sulfilimines.[12] We 79Br): m/z=332 (M+Na)+, 641 (2M+Na)+; HR-MS: m/z=
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331.9517, calcd. for C10H1079BrF2NOSNa: 331.9532 (d=
4.5 ppm).
129.6, 129.8, 131.7, 134.4, 135.5, 137.7, 177.5; MS (pos. ESI
for 35Cl): m/z=352 (M+Na)+, 681 (2M+Na)+; HR-MS:
m/z=351.9741, calcd. for C14H1035Cl2FNOSNa: 351.9742
(d=0.3 ppm).
N-(Acetyl) bromodifluoromethyl p-bromophenyl sulfil-
imine (4c): White powder; mp 88–908C; 19F NMR
(188 MHz, CDCl3) d= À47.0 and À46.0 (AB syst, J=
N-(Bromopropylacetyl)
sulfil
dichlorofluoromethyl
phenyl
1
G
136 Hz); H NMR (200 MHz, CDCl3): d=2.21 (3H, s), 7.69–
1
7.79 (4H, m); 13C NMR (75 MHz, CDCl3): d=24.6, 123.2
(CF2, dd, J=353 Hz, J=349 Hz), 127.1, 129.6, 130.5, 133.1,
183.3; MS (pos. ESI, for 79Br): m/z=396 (M+Na)+, 769
d, J=1.4 Hz); H NMR (300 MHz, CDCl3): d=3.09 (2H, t,
J=7.1 Hz), 3.72 (1H, t, J=7.1 Hz), 7.59–7.64 (2H, m), 7.70–
7.76 (1H, m), 7.99 (2H, d, J=7.9 Hz); 13C NMR (75 MHz,
CDCl3): d=28.5, 41.5, 124.9 (CF, d, J=340 Hz), 128.7, 129.6,
129.9, 134.6, 182.1; MS (pos. ESI, for 79Br, 35Cl): m/z=360
(M+H)+, 382 (M+Na)+, 741 (2M+Na)+; HR-MS: m/z=
359.9036, calcd. for C10H1079Br35Cl2FNOS: 359.9028 (d=
2.2 ppm).
(2M+Na)+;
HR-MS:
m/z=395.8481,
calcd.
for
C9H779Br2F2NOSNa: 395.8481 (d=0 ppm).
Bromodifluoromethyl phenyl N-(phenylacetyl) sulfilimine
(4d): Yellow powder; mp 98–1008C; 19F NMR (188 MHz,
CDCl3): d=À46.8 and À45.5 (AB syst, J=135 Hz);
1H NMR (300 MHz, CDCl3): d=7.42–7.49 (2H, m), 7.50–
7.55 (1H, m), 7.60–7.66 (2H, m), 7.70–7.77 (1H, m), 8.02
(2H, d, J=7.7 Hz), 8.26–8.30 (2H, m); 13C NMR (75 MHz,
CDCl3): d=128.0, 128.6 (CF2, dd, J=348 Hz, J=347 Hz),
129.3, 129.4, 129.9, 131.7, 134.3, 135.2, 177.4; anal. calcd. for
C14H10BrF2NOS: C 46.94, H 2.81, N 3.91; found: C 47.03, H
2.94, N 3.86.
General Procedure for the Synthesis of Sulfilimino
Iminium Salts, as Exemplified by the Reaction of
Phenyl Trifluoromethyl Sulfoxide with Acetonitrile
and Dimethylamine
Trifluoromethanesulfonic anhydride (0.3 mL, 1.9 mmol,
1.5 equiv.) was added under argon to a precooled (À158C)
mixture of phenyl trifluoromethyl sulfoxide (0.25 g,
1.3 mmol, 1 equiv.) and acetonitrile (0.1 mL, 1.9 mmol,
1.5 equiv.). The reaction mixture was stirred for 1 d at
À158C, then dimethylamine (0.35 mL, 5.2 mmol, 4 equiv.)
diluted in 2 mL of CH2Cl2 was carefully added to the mix-
ture. After 16 h the reaction was hydrolyzed with water
(5 mL), extracted with CH2Cl2 (3ꢂ15 mL), dried over
MgSO4, and concentrated under reduced pressure. The resi-
due was purified by preparative chromatography (SiO2,
CH2Cl2/methanol, 95/5) to give dimethyl-{1-[(phenyl(tri-
fluoromethyl)-l4-sulfanylidene)amino]ethylidene}ammoni-
um trifluoromethanesulfonate (6d); yield: 0.52 g (98%);
19F NMR (188 MHz, CDCl3): d = À79.0 (3F, s), À67.3 (3F,
Bromodifluoromethyl N-(bromopropylacetyl) phenyl sulf-
ilimine (4e): Yellow powder; mp 56–588C; 19F NMR
(188 MHz, CDCl3): d= -47.0 and À45.8 (AB syst, J=
136 Hz); 1H NMR (200 MHz, CDCl3): d=3.07 (2H, t, J=
7 Hz), 3.71 (2H, t, J=7.1 Hz), 7.56–7.76 (3H, m), 7.93 (2H,
d, J=7.5 Hz); 13C NMR (75 MHz, CDCl3): d=28.4, 41.1,
123.4 (CF2, dd, J=352 Hz, J=347 Hz), 127.7, 129.3, 129.8,
134.4, 181.9; MS (pos. ESI, for 79Br): m/z=410 (M+Na)+,
797 (2M+Na)+; HR-MS: m/z=409.8642, calcd. for
C10H979Br2F2NOSNa 409.8637 (d=1.2 ppm).
N-(Acetyl) dichlorofluoromethyl phenyl sulfilimine (4f):
White powder; mp 84–868C; 19F NMR (188 MHz, CDCl3):
d=À54.3 (1F, d, J=1.4 Hz); 1H NMR (200 MHz, CDCl3):
d=2.23 (3H, s), 7.53–7.74 (3H, m), 7.94–8.00 (2H, m);
13C NMR (75 MHz, CDCl3): d=25.2, 124.9 (CF, d, J=
340 Hz), 129.1, 129.5, 129.8, 134.4, 183.6; anal. calcd. for
C9H8Cl2FNOS: C 40.31, H 3.01, N 5.22; found: C 39.92, H
2.94, N 5.02.
N-(Acetyl) dichlorofluoromethyl p-tolyl sulfilimine (4g):
Yellow powder; mp 68–708C; 19F NMR (188 MHz, CDCl3):
d=À54.7 (1F, d, J=1.4 Hz); 1H NMR (200 MHz, CDCl3):
d=2.21 (3H, s), 2.43 (3H, s), 7.36 (2H, d, J=8.1 Hz), 7.83
(2H, d, J=8.1 Hz); 13C NMR (75 MHz, CDCl3): d=21.6,
25.1, 124.9 (CF, d, J=340 Hz), 125.5, 129.7, 130.2, 145.6,
183.3; anal. calcd. for C10H10Cl2FNOS: C 42.57, H 3.57, N
4.96; found: C 42.65, H 3.68, N 4.89.
N-(Acetyl) p-bromophenyl dichlorofluoromethyl sulfil-
imine (4h): Brown powder; mp 90–928C; 19F NMR
(188 MHz, CDCl3): d=À54.3 (1F, s); 1H NMR (200 MHz,
CDCl3): d=2.21 (3H, s), 7.68–7.74 (2H, m), 7.79–7.86 (2H,
m); 13C NMR (75 MHz, CDCl3): d=25.0, 124.6 (CF, d, J=
341 Hz), 128.0, 129.8, 131.0, 132.8, 183.4; MS (pos. ESI, for
79Br, 35Cl): m/z=346 (M+H)+, 368 (M+Na)+, 691 (2M+
H)+; HR-MS: m/z=345.8880, calcd. for C9H879Br35Cl2FNOS:
345.8871 (d=2.6 ppm).
1
s); H NMR (300 MHz, CDCl3): d = 2.62 (3H, s), 3.33 (3H,
s), 3.36 (3H, s), 7.64–7.73 (2H, m), 7.75–7.82 (1H, m), 8.05
(2H, d, J=7.9 Hz); 13C NMR (75 MHz, CDCl3): d=19.2,
39.8, 41.6, 120.7 (CF3, q, J=321 Hz), 123.2 (CF3, q, J=
329 Hz), 124.5, 129.1, 130.8, 135.9, 173.8; MS (pos. ESI):
m/z=194 (MÀCF3)+, 263 (M)+; HR-MS: m/z=263.0816,
calcd. for C11H14F3N2S: 263.0830 (d=À5.3 ppm).
1-({[DichloroACTHNUTRGNEUNG
(fluoro)methyl]-phenyl-l4-sulfanylidene}ami-
no)ethylidene-diethyl-ammonium trifluoromethanesulfonate
(6a): Brown powder; mp 80–828C; 19F NMR (188 MHz,
CDCl3): d
=
À78.8 (3F, s), À56.3 (1F, s); 1H NMR
(300 MHz, CDCl3): d = 1.15–1.32 (6H, m), 2.64 (3H, s),
3.43–3.72 (3H, m), 3.79–3.96 (1H, m), 7.56–7.68 (2H, m),
7.70–7.80 (1H, m), 8.01 (2H, d, J=8.7 Hz); 13C NMR
(75 MHz, CDCl3): d = 11.8, 12.9, 18.4, 45.2, 46.7, 120.5
(CF3, q, J=320 Hz), 125.0 (CF, d, J=344 Hz), 129.6,
126.0,130.0, 135.8, 172.1; MS (pos. ESI, for Cl35): m/z=222
(MÀCCl2F)+, 323 (M)+; HR-MS: m/z=323.0562, calcd. for
C13H1835Cl2FN2S 323.0552 (d=3.1 ppm).
1-({[BromoACTHNUTRGNEUNG
(difluoro)methyl]-phenyl-l4-sulfanylidene}ami-
no)ethylidene-diethyl-ammonium trifluoromethanesulfonate
(6b): Brown powder; mp 48–508C; 19F NMR (188 MHz,
CDCl3): d=À78.8 (3F, s), À49.5 and À48.5 (AB system, J=
198 Hz); 1H NMR (300 MHz, CDCl3): d=1.22–1.33 (6H,
m), 3.47–3.72 (3H, m), 2.65 (3H, s), 3.81–3.95 (1H, m),
7.61–7.70 (2H, m), 7.74–7.81 (1H, m), 8.01 (2H, d, J=
7.5 Hz); 13C NMR (75 MHz, CDCl3): d=12.1, 13.2, 18.8,
Dichlorofluoromethyl phenyl N-(phenylacetyl) sulfilimine
(4i): 19F NMR (188 MHz, CDCl3): d=À54.0 (1F, s);
1H NMR (300 MHz, CDCl3): d=7.42–7.48 (2H, m), 7.49–
7.55 (1H, m), 7.59–7.66 (2H, m), 7.70–7.76 (1H, m), 8.07–
8.11 (2H, m), 8.28–8.32 (2H, m); 13C NMR (75 MHz,
CDCl3): d=125.4 (CF, d, J=340 Hz), 127.9, 129.4, 129.5,
2810
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2805 – 2814

Divergent Preparation of Fluoroalkylated Sulfilimine and Sulfilimino Iminium Salts
45.4, 47.0, 120.7 (CF3, q, J=328 Hz), 122.8 (CF2, dd, J=
356 Hz, J=346 Hz), 125.5, 129.4, 130.5, 135.9, 172.3; MS
(pos. ESI, for 79Br): m/z=222 (MÀCF2Br)+, 351 (M)+; anal.
calcd. for C14H18BrF5N2O3S2: C 33.54, H 3.62, N 5.59; found:
C 33.91, H 3.73, N 5.61.
1-{[(4-Bromophenyl)(nonafluorobutyl)-l4-sulfanylidene]-
amino]ethylidene-diethyl-ammonium trifluoromethanesulfo-
nate (6i): 19F NMR (188 MHz, CDCl3): d=À126.2 (2F, m),
À119.8 (2F, m), À107.6 (2F, m), À81.0 (3F, t, J=9.6 Hz),
À78.9 (3F, s); 1H NMR (300 MHz, CDCl3): d=1.23–1.33
(6H, m), 2.67 (3H, s), 3.48–3.72 (3H, m), 3.77–3.94 (1H, m),
7.83 (2H, d, J=9.1 Hz), 7.96 (2H, d, J=8.7 Hz); 13C NMR
(75 MHz, CDCl3): d=11.9, 13.0, 18.7, 45.3, 47.1, 123.0,
131.2, 131.7, 133.8, 172.4; MS (pos. ESI, for 79Br): m/z=300
(MÀC4F9)+, 519 (M)+; anal. calcd. for C17H17BrF12N2O3S2: C
30.50, H 2.56, N 4.19; found: C 30.68, H 2.69, N 4.25.
Methyl-(1-{[phenyl(trifluoromethyl)-l4-sulfanylidene]ami-
no}ethylidene)ammonium trifluoromethanesulfonate (6c):
19F NMR (188 MHz, CDCl3) d=À79.0 (3F, s), À67.3 (3F, s);
1H NMR (200 MHz, CDCl3) d=0.95 (3H, t, J=7.4 Hz),
1.60–1.78 (2H, m), 2.61 (3H, s), 3.37–3.63 (2H, m), 7.68–
7.88 (3H, m), 8.07 (2H, d, J=7.6 Hz), 9.42 (1H, br s);
13C NMR (75 MHz, CDCl3) d=11.2, 20.7, 21.1, 44.8, 120.4
(CF3, q, J=317 Hz), 123.0 (CF3, q, J=326 Hz), 124.1, 129.0,
130.8, 136.0, 173.7; MS (pos. ESI): m/z=277 (M)+; HR-MS:
m/z=277.0996, calcd. for C12H16F3N2S: 277.0986 (d=
3.6 ppm).
General Procedure for the Preparation of Free
Sulfilimines, as Exemplified by the Reaction of
Phenyl Trifluoromethyl Sulfoxide with Acetonitrile
Dimethyl-(1-{[p-tolyl(trifluoromethyl)-l4-sulfanylidene]-
Trifluoromethanesulfonic anhydride (2.0 mL, 11.6 mmol,
1.5 equiv.) was added to a precooled (À158C) mixture of
phenyl trifluoromethyl sulfoxide (1.5 g, 7.7 mmol, 1 equiv.)
and acetonitrile (0.6 mL, 11.6 mmol, 1.5 equiv.). The reac-
tion mixture was stirred for one day at À158C, diluted with
CH2Cl2 (5 mL) then hydrolyzed by slow addition of propyl-
amine (9.5 mL, 11.6 mmol, 15 equiv.). The reaction mixture
was stirred for one day at room temperature, then water
(10 mL) was added and the crude mixture extracted with
CH2Cl2 (3ꢂ20 mL). The combined organic layers were
washed with water (3ꢂ20 mL), dried over MgSO4, and con-
centrated under reduced pressure. The residue was purified
by flash chromatography (SiO2, pentane/Et2O 4/6) to give
phenyl trifluoromethyl sulfilimine (7g) as a white powder;
yield: 1.4 g (91%); mp 48–508C; 19F NMR (188 MHz,
amino}ethylidene)ammonium
trifluoromethanesulfonate
(6e): 19F NMR (188 MHz, CDCl3): d=À78.9 (3F, s), À67.7
1
(3F, s); H NMR (300 MHz, CDCl3): d=2.43 (3H, s), 2.58
(3H, s), 3.30 (3H, s), 3.33 (3H, s), 7.45 (2H, d, J=8.1 Hz),
7.90 (2H, d, J=8.5 Hz); 13C NMR (75 MHz, CDCl3): d=
19.0, 21.8, 39.7, 41.4, 120.7 (CF3, q, J=321 Hz), 120.8, 123.1
(CF3, q, J=328 Hz), 129.1, 131.4, 147.6, 173.5; MS (pos.
ESI): m/z=208 (MÀCF3)+, 277 (M)+; HR-MS: m/z=
277.0978, calcd. for C12H16F3N2S: 277.0986 (d=À2.9 ppm).
Diethyl-(1-{[p-tolyl(trifluoromethyl)-l4-sulfanylidene]ami-
no}ethylidene)ammonium trifluoromethanesulfonate (6f):
19F NMR (188 MHz, CDCl3): d=À78.8 (3F, s), À67.5 (3F,
1
s); H NMR (300 MHz, CDCl3): d=1.20–1.30 (6H, m), 2.43
(3H, s), 2.62 (3H, s), 3.46–3.71 (3H, m), 3.73–3.87 (1H, m),
7.46 (2H, d, J=8.7 Hz), 7.91 (2H, d, J=8.3 Hz); 13C NMR
(75 MHz, CDCl3): d=11.9, 13.2, 18.6, 21.8, 45.3, 47.0, 120.7
(CF3, q, J=321 Hz), 120.9, 123.1 (CF3, q, J=328 Hz), 129.2,
131.5, 147.7, 172.4; MS (pos. ESI): m/z=236 (MÀCF3)+, 305
(M)+; HR-MS: m/z=305.1293, calcd. for C14H20F3N2S:
305.1299 (d=À2.0 ppm).
1
CDCl3): d=À74.4 (3F, s); H NMR (200 MHz, CDCl3): d=
1.86 (1H, br s), 7.53–7.66 (3H, m), 7.73–7.78 (2H, m);
13C NMR (75 MHz, CDCl3): d=125.9 (CF3, q, J=1.3 Hz),
128.3 (CF3, q, J=337 Hz), 129.5, 132.5, 135.2; anal. calcd.
for C7H6F3NS: C 43.52, H 3.13, N 7.25; found: C 43.71, H
3.12, N 7.21.
Diethyl-(phenyl-{[p-tolyl(trifluoromethyl)-l4-sulfanylid-
ene]amino}methylene)ammonium trifluoromethanesulfonate
(6g): Brown powder; mp 109–1118C; 19F NMR (188 MHz,
CDCl3): d=À78.7 (3F, s), À66.2 (3F, s); 1H NMR
(300 MHz, CDCl3): d=1.05–1.16 (3H, m), 1.33–1.44 (3H,
m), 2.41 (3H, s), 3.25–3.42 (2H, m), 3.71–3.86 (1H, m),
3.98–4.13 (1H, m), 6.96–7.04 (1H, m), 7.30–7.37 (1H, m),
7.38–7.51 (3H, m), 7.51–7.65 (2H, m), 7.65–7.72 (2H, m);
13C NMR (75 MHz, CDCl3): d=11.9, 13.4, 21.6, 44.4, 48.0,
120.6 (CF3, q, J=321 Hz), 120.5, 122.7 (CF3, q, J=326 Hz),
125.9, 126.1, 128.6, 129.7, 130.1, 130.2, 131.7, 132.0, 148.1,
173.7; MS (pos. ESI): m/z=298 (MÀCF3)+, 367 (M)+; HR-
MS: m/z=367.1438, calcd. for C19H22F3N2S: 367.1450 (d=
3.5 ppm).
N,N’-Dipropylphenylamidinium trifluoromethanesulfonate
(11a): 19F NMR (188 MHz, MeOD): d = À87.7; 1H NMR
(300 MHz, MeOD) d=0.89 (6H, t, J=7.3 Hz), 1.58 (4H,
sextuplet, J=7.3 Hz), 3.15 (4H, t, J=7.0 Hz), 7.37–7.42
(2H, m), 7.46–7.53 (3H, m); 13C NMR (50 MHz, CD3CN)
d=11.6, 24.2, 47.7, 128.4, 129.4, 130.4, 134.5, 161.8; MS (pos.
ESI): m/z=205 (M)+; HR-MS: m/z=205.1693, calcd. for
C13H21N2: 205.1705 (d=À4.8 ppm).
Dichlorofluoromethyl phenyl sulfilimine (7a): Yellow
powder; mp 48–508C; 19F NMR (188 MHz, CDCl3): d=
1
À60.2 (1F, d, J=1.4 Hz); H NMR (200 MHz, CDCl3): d=
2.47 (1H, br s), 7.50–7.66 (3H, m), 7.79–7.84 (2H, m);
13C NMR (75 MHz, CDCl3): d=127.0, 129.0, 129.4 (CF, d,
J=348 Hz), 132.7, 135.8; anal. calcd. for C7H6Cl2FNS: C
37.19, H 2.67, N 6.19; found: C 37.42, H 2.78, N 6.19.
ACHTUNGTRENNUNG
({[p-Tolyl)(trifluoromethyl)-l4-sulfanylidene]amino}-
phenyl-methylene)-diphenyl-ammonium trifluoromethane-
sulfonate (6h): Brown powder; mp 174–1768C; 19F NMR
(188 MHz, CDCl3): d=À78.7 (3F, s), À65.0 (3F, s);
1H NMR (300 MHz, CDCl3): d=2.46 (3H, s), 7.03–7.29
(5H, m), 7.31–7.68 (14H, m); 13C NMR (75 MHz, CDCl3):
d=21.8, 120.4, 120.8 (CF3, q, J=321 Hz), 122.9 (CF3, q, J=
328 Hz), 126.6, 127.5, 128.4, 128.7, 128.8, 129.1, 129.5, 129.5,
129.8, 130.3, 131.7, 132.2, 141.9, 148.1, 177.2; MS (pos. ESI):
m/z=394 (MÀCF3)+, 463 (M)+; HR-MS: m/z=463.1445,
calcd. for C27H22F3N2S: 463.1450 (d=1.1 ppm).
Dichlorofluoromethyl p-tolyl sulfilimine (7b) Yellow
powder; mp 68–708C; 19F NMR (188 MHz, CDCl3): d=
1
À60.4 (1F, d, J=1.4 Hz); H NMR (200 MHz, CDCl3): d=
2.42 (3H, s), 2.50 (1H, br s), 7.34 (2H, d, J=8.1 Hz), 7.68
(2H, dd, J=7.3 Hz, J=1.1 Hz); 13C NMR (75 MHz, CDCl3):
d=21.5, 126.9, 129.5 (CF, d, J=348 Hz), 129.7, 132.7, 143.6;
anal. calcd. for C8H8BrF2NS: C 40.01, H 3.36, N 5.83; found:
C 40.21, H 3.51, N 5.82.
p-Bromophenyl dichlorofluoromethyl sulfilimine (7c):
Orange powder; mp 64–668C; 19F NMR (188 MHz, CDCl3):
Adv. Synth. Catal. 2010, 352, 2805 – 2814
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asc.wiley-vch.de
2811

Cꢀline Urban et al.
FULL PAPERS
1
1
d=À60.3 (1F, s); H NMR (200 MHz, CDCl3): d=2.49 (1H,
À74.3 (3F, s); H NMR (300 MHz, CDCl3): d = 1.98 (1H,
br s for NH), 7.54 (2H, d, J=8.9 Hz), 7.69 (2H, d, J=
8.5 Hz); 13C NMR (75 MHz, CDCl3): d=124.5 (CF3, q, J=
340 Hz), 127.3, 129.8, 133.5, 139.1; MS (pos. ESI, for 35Cl iso-
tope): m/z=228 (M+H)+, 250 (M+Na)+, 477 (2M+Na)+;
HR-MS: m/z=227.9851, calcd. for C7H635ClF3NS: 227.9862
(d=À4.8 ppm).
br s), 7.71 (4H, d, J=0.5 Hz); 13C NMR (75 MHz, CDCl3):
d=127.8, 128.5, 129.2 (CF, d, J=349 Hz), 132.3, 134.8; MS
(pos. ESI, for 79Br, 35Cl): m/z=304 (M+H)+; HR-MS:
m/z=303.8764, calcd. for C7H679Br35Cl2FNS: 303.8765 (d=
0.3 ppm).
Bromodifluoromethyl phenyl sulfilimine (7d): 19F NMR
(188 MHz, CDCl3): d=À52.3 and À51.2 (AB syst, J=
135 Hz); 1H NMR (200 MHz, CDCl3): d=2.16 (1H, br s),
7.52–7.68 (3H, m), 7.73–7.79 (2H, m); 13C NMR (75 MHz,
CDCl3): d=126.4, 129.3, 131.5 (CF2, dd, J=368 Hz, J=
366 Hz), 132.6, 135.8. Due to its relative instability, full char-
acterization of this compound was finalized via its derivative
12b.
m-Chlorophenyl trifluoromethyl sulfilimine (7m): White
powder; mp 48–508C; 19F NMR (188 MHz, CDCl3): d=
1
À73.9 (3F, s); H NMR (300 MHz, CDCl3): d = 2.23 (1H,
br s for NH), 7.44–7.60 (2H, m), 7.63 (1H, d, J=7.5 Hz),
7.77 (1H, s); 13C NMR (75 MHz, CDCl3): d=124.2, 124.5
(CF3, q, J=339 Hz), 126.0, 130.7, 132.8, 136.0, 136.9; MS
(pos. ESI, for 35Cl isotope): m/z=228 (M+H)+, 250 (M+
Na)+, 477 (2M+Na)+; HR-MS: m/z=227.9857, calcd. for
C7H635ClF3NS: 227.9862 (d=À2.2 ppm).
Bromodifluoromethyl p-tolyl sulfilimine (7e): 19F NMR
(188 MHz, CDCl3): d=À52.5 and À51.5 (AB syst, J=
135 Hz); 1H NMR (200 MHz, CDCl3): d=2.11 (1H, br s),
2.44 (3H, s), 7.36 (2H, d, J=8.1 Hz), 7.62 (2H, d, J=
8.2 Hz); 13C NMR (75 MHz, CDCl3): d=21.5, 126.3, 129.9,
131.5 (CF2, dd, J=366 Hz, J=357 Hz), 132.6, 143.4; MS
(pos. ESI, for 79Br): m/z=268 (M+H)+; HR-MS: m/z=
267.9606, calcd. for C8H979BrF2NS: 267.9607 (d=0.4 ppm).
Bromodifluoromethyl p-bromophenyl sulfilimine (7f):
Orange powder; mp 58–608C; 19F NMR (188 MHz, CDCl3):
d=À52.4 and À51.3 (AB syst, J=136 Hz); 1H NMR
(200 MHz, CDCl3): d=2.12 (1H, br s), 7.68 (4H, dd, J=
9.6 Hz, J=8.6 Hz); 13C NMR (75 MHz, CDCl3): d=127.6,
127.9, 131.1 (CF2, dd, J=362 Hz, J=356 Hz), 132.5, 134.8;
MS (pos. ESI, for 79Br): m/z=332 (M+H)+; HR-MS: m/z=
331.8557, calcd. for C7H679Br2F2NS: 331.8556 (d=0.3 ppm).
o-Tolyl trifluoromethyl sulfilimine (7h): Yellow powder;
mp 56–588C; 19F NMR (188 MHz, CDCl3): d=À74.1 (3F,
s); 1H NMR (200 MHz, CDCl3): d=1.86 (1H, br s), 2.52
(3H, s), 7.28–7.32 (1H, m), 7.48 (2H, t, J=4.5 Hz), 7.90
(1H, t, J=4.5 Hz); 13C NMR (75 MHz, CDCl3): d=18.8,
125.3, 127.3, 129.7 (CF3, q, J=295 Hz), 131.2, 132.3, 134.5,
137.6; anal. calcd. for C8H8F3NS: C 46.37, H 3.89, N 6.76;
found: C 46.74, H 3.66, N 6.86.
p-Chlorophenyl trifluoromethyl sulfilimine (7n): White
powder; mp 59–608C; 19F NMR (188 MHz, CDCl3): d=
1
À73.2 (3F, s); H NMR (300 MHz, CDCl3): d=2.22 (1H, br
s for NH), 7.46–7.59 (3H, m), 7.90–7.98 (1H, m); 13C NMR
(75 MHz, CDCl3): d=127.4, 128.0, 130.5, 133.5, 133.7, 134.5;
MS (pos. ESI, for 35Cl isotope): m/z=228 (M+H)+, 250
(M+Na)+, 477 (2M+Na)+; HR-MS: m/z=227.9854, calcd.
for C7H635ClF3NS: 227.9862 (d=À3.5 ppm).
Nonafluorobutyl phenyl sulfilimine (7o): Yellow powder;
mp 48–508C; 19F NMR (188 MHz, CDCl3): d=À126.6 (2F,
m), À121.3 (2F, m), À115.7 (2F, m), À81.3 (3F, tt, J=10 Hz,
1
J=2.4 Hz); H NMR (200 MHz, CDCl3): d=2.12 (1H, br s),
7.52–7.66 (3H, m), 7.74 (2H, d, J=7.9 Hz); 13C NMR
(75 MHz, CDCl3): d=126.6, 129.5, 132.8, 134.7; anal. calcd.
for C10H6F9NS: C 34.99, H 1.76, N 4.08; found: C 35.42, H
1.91, N 4.21.
Nonafluorobutyl tolyl sulfilimine (7p): White powder; mp
89–918C; 19F NMR (188 MHz, CDCl3): d=À126.6 (2F, m),
À121.2 (2F, m), À115.6 (2F, m), À81.3 (3F, t, J=9.6 Hz);
1H NMR (300 MHz, CDCl3): d=2.45 (3H, s), 2.48 (1H, br s
for NH), 7.34 (2H, d, J=7.5 Hz), 7.64 (2H, d, J=8.1 Hz);
13C NMR (75 MHz, CDCl3): d=144.0, 131.2, 130.3, 126.7,
21.5; MS (pos. ESI): m/z=139 (MÀC4F9)+, 358 (M+H)+;
HR-MS: m/z=358.0304, calcd. for C11H9F9NS: 358.0307
(d=0.7 ppm).
m-Tolyl trifluoromethyl sulfilimine (7i): 19F NMR
(188 MHz, CDCl3): d=À74.4 (3F, s); 1H NMR (200 MHz,
CDCl3): d=1.85 (1H, br s), 2.45 (3H, s), 7.32–7.55 (4H, m);
13C NMR (75 MHz, CDCl3): d=21.3, 123.1, 124.8 (CF3, q,
J=338 Hz), 126.1, 129.3, 133.3, 135.2, 139.9; anal. calcd. for
C8H8F3NS: C 46.37, H 3.89, N 6.76; found: C 45.87, H 3.96,
N 6.65.
p-Tolyl trifluoromethyl sulfilimine (7j): Yellow powder;
mp 58–628C; 19F NMR (188 MHz, CDCl3): d=À74.7 (3F,
s); 1H NMR (200 MHz, CDCl3): d=1.81 (1H, br s), 2.41
(3H, s), 7.35 (2H, d, J=8.1 Hz), 7.60 (2H, d, J=8 Hz);
13C NMR (75 MHz, CDCl3): d=21.3, 124.1 (CF3, q, J=
337 Hz), 125.8, 130.1, 131.9, 143.3; MS (pos. ESI): m/z=230
(M+Na)+, 437 (2M+Na)+; HR-MS: m/z=230.0251, calcd.
for C8H8F3NSNa: 230.0227 (d=1.2 ppm).
p-Bromophenyl nonafluorobutyl sulfilimine (7q): White
powder; mp 94–968C; 19F NMR (188 MHz, CDCl3): d=
À126.5 (2F, m), À121.1 (2F, m), À115.2 (2F, m), À81.3 (3F,
1
t, J=9.6 Hz); H NMR (300 MHz, CDCl3): d=2.47 (1H, br
s for NH), 7.62 (2H, d, J=8.3 Hz), 7.72 (2H, d, J=8.5 Hz);
13C NMR (75 MHz, CDCl3): d=127.9, 128.1, 132.8, 133.4;
MS (pos. ESI, for 79Br isotope): m/z=202 (MÀC4F9)+, 421
(M+H)+;
HR-MS:
m/z=421.9245,
calcd.
for
C10H679BrF9NS: 421.9255 (d=2.3 ppm).
General Procedure for the Preparation of Trifluoro-
methanesulfonyl Sulfilimines, as Exemplified by the
Reaction with 7a
p-Bromophenyl trifluoromethyl sulfilimine (7k): White
powder; mp 72–748C; 19F NMR (188 MHz, CDCl3): d=
1
À74.4 (3F, s); H NMR (200 MHz, CDCl3): d=1.80 (1H, br
To a solution of dichlorofluoromethyl phenyl sulfilimine 7a
(0.28 g, 1.2 mmol, 1.0 equiv.) and pyridine (0.30 mL,
3.7 mmol, 3.0 equiv.) in CH2Cl2 (15 mL) was added trifluoro-
methanesulfonic anhydride (0.31 mL, 1.9 mmol, 1.5 equiv.)
at 08C. The mixture was stirred overnight at room tempera-
ture. CH2Cl2 (10 mL) and 1M hydrochloric acid solution
(20 mL) were then added. The phases were separated and
s), 7.64 (2H, d, J=8.5 Hz), 7.74 (2H, d, J=8.5 Hz);
13C NMR (75 MHz, CDCl3): d=124.5 (CF3, q, J=337 Hz),
127.5, 127.6, 132.8, 134.4; anal. calcd. for C7H5BrF3NS: C
30.90, H 1.85, N 5.15; found: C 31.21, H 1.51, N 5.22.
o-Chlorophenyl trifluoromethyl sulfilimine (7l): White
powder; mp 64–668C; 19F NMR (188 MHz, CDCl3): d=
2812
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ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2805 – 2814

Divergent Preparation of Fluoroalkylated Sulfilimine and Sulfilimino Iminium Salts
the aqueous layer extracted with CH2Cl2 (2ꢂ20 mL). The
combined organic phases were dried over magnesium sulfate
and evaporated under vacuum. Purification by a silica gel
preparative plate (SiO2, pentane/Et2O, 8/2) afforded dichlo-
rated under vacuum. Purification on a silica gel preparative
plate (SiO2, pentane/Et2O 7/3) afforded the corresponding
sulfilimine 12e as a white solid; yield: 49 mg (83%); mp 87–
898C; 19F NMR (188 MHz, CDCl3): d=À68.4 (3F, s);
1H NMR (200 MHz, CDCl3): d=7.58–7.74 (6H, m), 7.92–
7.96 (2H, m), 8.24–8.29 (1H, m); 13C NMR (75 MHz,
CDCl3): d=123.4 (CF3, q, J=329 Hz), 124.2, 126.7, 128.2,
130.3, 130.7, 132.3, 132.9, 134.9, 136.2, 147.2; anal. calcd. for
C13H9F3N2O4S2: C 41.27, H 2.40, N 7.40; found: C 41.31, H
2.49, N 7.24.
N-Nitro phenyl trifluoromethyl sulfilimine (12f): To a so-
lution of trifluoromethyl phenyl sulfilimine 7g (47 mg,
0.24 mmol, 1.0 equiv.) in CH2Cl2 (1 mL) was added fuming
nitric acid (10 mL) at 08C. After 15 min, sulfuric acid
(1 drop) and acetic anhydride (0.5 mL) were added to the
mixture, which was stirred overnight at room temperature.
CH2Cl2 (20 mL) and a saturated aqueous solution of sodium
bicarbonate (20 mL) were then added. The phases were sep-
arated and the aqueous layer was extracted with CH2Cl2 (2ꢂ
20 mL). The combined organic phases were dried over mag-
nesium sulfate and evaporated under vacuum. Purification
on a silica gel preparative plate (SiO2, pentane/Et2O, 4:6) af-
forded 12f as a white solid; yield: 38 mg (66%); mp 87–
898C; 19F NMR (188 MHz, CDCl3): d=À60.8 (3F, s);
1H NMR (300 MHz, CDCl3): d=7.68–7.73 (2H, m), 7.81–
7.83 (1H, m), 7.95–7.98 (2H, m); 13C NMR (75 MHz,
CDCl3): d=123.2 (CF3, q, J=328 Hz), 123.3, 129.7, 130.8,
135.9; anal. calcd. for C7H5F3N2O2S: C 35.30, H 2.12, N
11.76; found: C 35.38, H 2.21, N 11.61.
ACHTUNGTRENNUNGrofluoromethyl phenyl N-trifluoromethanesulfonyl sulfili-
mine (12a) as a white solid; yield: 0.21 g (47%); mp 76–
788C; 19F NMR (188 MHz, CDCl3): d=À78.3 (3F, s), À56.6
1
(1F, s); H NMR (300 MHz, CDCl3): d=7.68–7.73 (2H, m),
7.81–7.87 (1H, m), 7.99–8.02 (2H, m); 13C NMR (75 MHz,
CDCl3): d=119.7 (CF3, q, J=322 Hz), 124.9 (CF, d, J=
343 Hz), 127.5, 129.3, 130.3, 135.9; anal. calcd. for
C8H5Cl2F4NO2S2: C 26.83, H 1.41, N 3.91; found: C 26.51, H
1.39, N 3.81.
Bromodifluoromethyl phenyl N-trifluoromethanesulfonyl
sulfilimine (12b): Pale yellow solid; mp 67–698C; 19F NMR
(188 MHz, CDCl3): d=À78.3 (3F, s), À49.1 and À48.7 (AB
1
system, J=132 Hz); H NMR (300 MHz, CDCl3): d=7.69–
7.75 (2H, m), 7.82–7.88 (1H, m), 7.97–8.00 (2H, m);
13C NMR (75 MHz, CDCl3): d=119.7 (CF3, q, J=322 Hz),
123.1 (CF2, app. t, J=354 Hz), 126.8, 128.8, 130.5, 135.8;
anal. calcd. for C8H5BrF5NO2S2: C 24.88, H 1.31, N 3.63;
found: C 25.23, H 1.32, N 3.57.
Phenyl N-(trifluoromethane sulfonyl) trifluoromethyl sulf-
ACHTUNGTRENNUNG
ilimine (12c): Yellow powder; mp 48–508C; 19F NMR
(188 MHz, CDCl3) d=À78.4 (3F, d, J=2.0 Hz), À67.5 (3F,
d, J=2.0 Hz); 1H NMR (300 MHz, CDCl3) d=7.71–7.77
(2H, m) 7.86 (1H, tt, J=7.4 Hz, J=2.0 Hz), 7.97–8.00 (2H,
m); 13C NMR (75 MHz, CDCl3) d=119.7 (CF3, q, J=
320 Hz), 123.0 (CF3, q, J=325 Hz), 125.4, 128.3, 130.8,
135.9; anal. calcd. for C8H5F6NO2S2: C 29.54, H 1.55, N 4.31;
found: C 29.91, H 1.42, N 4.28.
N-Cyanophenyl trifluoromethyl sulfilimine (12g): To a so-
lution of trifluoromethyl phenyl sulfilimine 7g (50 mg,
0.26 mmol, 1.0 equiv.) and triethylamine (73 mL, 0.52 mmol,
2.0 equiv.) in CH2Cl2 (1 mL) was added cyanogen bromide
(41 mg, 0.39 mmol, 1.5 equiv.). The mixture was stirred over-
night at room temperature. CH2Cl2 (20 mL) and 1M hydro-
chloric acid solution (20 mL) were then added. The phases
were separated and the aqueous layer extracted with
CH2Cl2 (2ꢂ20 mL). The combined organic phases were
dried over magnesium sulfate and evaporated under
vacuum. Purification on a silica gel preparative plate (SiO2,
pentane/Et2O, 4/6) afforded 12g as a white solid; yield:
22 mg (38%); mp 97–998C; 19F NMR (188 MHz, CDCl3):
Phenyl N-p-toluenesulfonyl trifluoromethyl sulfilimine
(12d): To a solution of trifluoromethyl phenyl sulfilimine 7g
(0.65 g, 3.4 mmol, 1.0 equiv.) and pyridine (0.5 mL,
10.1 mmol, 3.0 equiv.) in CH2Cl2 (8 mL) was added p-tolue-
nesulfonyl chloride (0.96 g, 5.1 mmol, 1.5 equiv.) at room
temperature. The mixture was heated under reflux and
stirred overnight. CH2Cl2 (20 mL) and 1M of hydrochloric
acid solution (20 mL) were then added. The phases were
separated and the aqueous layer extracted with CH2Cl2 (2ꢂ
20 mL). The combined organic phases were dried over mag-
nesium sulfate and evaporated under vacuum. Purification
by silica gel flash chromatography (SiO2, pentane/Et2O, 4/6)
afforded the corresponding sulfilimine as a white solid;
yield: 1.2 g (100%); mp 101–1038C; 19F NMR (188 MHz,
1
d=À67.5 (3F, s); H NMR (200 MHz, CDCl3): d=7.71 (2H,
t, J=5.1 Hz), 7.82 (1H, t, J=4.9 Hz), 7.97 (2H, d, J=
7.9 Hz); 13C NMR (75 MHz, CDCl3): d=117.8, 123.6 (CF3,
q, J=334 Hz), 126.6, 128.0, 130.6, 135.5; anal. calcd. for
C8H5F3N2S: C 44.04, H 2.31, N 12.84; found: C 44.38, H
2.27, N 12.58.
1
CDCl3): d=À68.2 (3F, s); H NMR (300 MHz, CDCl3): d=
2.38 (3H, s), 7.25 (2H, d, J=7.9 Hz), 7.60–7.66 (2H, m),
7.71–7.73 (1H, m), 7.81 (2H, d, J=8.3 Hz), 7.90–7.93 (2H,
m); 13C NMR (75 MHz, CDCl3): d=21.4, 123.4 (CF3, q, J=
330 Hz), 126.2, 127.2, 128.0, 129.4, 130.3, 134.7, 140.1, 142.6;
anal. calcd. for C14H12F3NO2S2: C 48.41, H 3.48, N 4.03;
found: C 48.48, H 3.48, N 3.94.
N-tert-Butoxycarbonyl phenyl trifluoromethyl sulfilimine
(12h): To a solution of trifluoromethyl phenyl sulfilimine 7g
(30 mg, 0.16 mmol, 1.0 equiv.) and triethylamine (0.13 mL,
0.93 mmol, 6.0 equiv.) in CH2Cl2 (1 mL) was added di-tert-
butyl dicarbonate (0.11 mL, 0.47 mmol, 3.0 equiv.). The mix-
ture was stirred overnight at room temperature. CH2Cl2
(20 mL) and 1M hydrochloric acid solution (20 mL) were
then added. The phases were separated and the aqueous
layer extracted with CH2Cl2 (2ꢂ20 mL). The combined or-
ganic phases were dried over magnesium sulfate and evapo-
rated under vacuum. Purification on a silica gel preparative
plate (SiO2, pentane/Et2O, 7/3) afforded 12h as a white
solid; yield: 32 mg (70%); mp 66–688C; 19F NMR
(188 MHz, CDCl3): d=À67.2 (3F, s); 1H NMR (200 MHz,
N-o-Nitrobenzenesulfonyl phenyl trifluoromethyl sulfil-
ACHTUNGTRENNUNGimine (12e): To a solution of trifluoromethyl phenyl sulfili-
mine 7g (30 mg, 0.16 mmol, 1.0 equiv.) and pyridine (38 mL,
0.47 mmol, 3.0 equiv.) in CH2Cl2 (1 mL) was added o-nitro-
benzenesulfonyl chloride (52 mg, 0.23 mmol, 1.5 equiv.). The
mixture was stirred overnight at room temperature. CH2Cl2
(20 mL) and 1M hydrochloric acid solution (20 mL) were
then added. The phases were separated and the aqueous
layer extracted with CH2Cl2 (2ꢂ20 mL). The combined or-
ganic phases were dried over magnesium sulfate and evapo-
Adv. Synth. Catal. 2010, 352, 2805 – 2814
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2813

Cꢀline Urban et al.
FULL PAPERS
CDCl3): d=1.51 (9H, s), 7.56–7.77 (3H, m), 7.95–7.99 (2H,
m); 13C NMR (75 MHz, CDCl3): d=28.2, 80.8, 123.8 (CF3,
q, J=329 Hz), 127.4, 128.8, 130.0, 134.3, 164.0; anal. calcd.
for C12H14F3NO2S: C 49.14, H 4.81, N 4.78; found: C 49.37,
H 4.91, N 4.58.
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Phenyl N-2-[(tridecafluorohexyl)sulfonyl]ethyl trifluoro-
methyl sulfilimine (12i): To a solution of trifluoromethyl
phenyl sulfilimine 7g (30 mg, 0.16 mmol, 1.0 equiv.) in
CH2Cl2 (1 mL) was added vinyl tridecafluorohexyl sulfone
(64 mg, 0.16 mmol, 1.0 equiv.). The mixture was stirred for
30 min at room temperature. CH2Cl2 (20 mL) and water
(20 mL) were then added. The phases were separated and
the aqueous layer extracted with CH2Cl2 (2ꢂ20 mL). The
combined organic phases were dried over magnesium sulfate
and evaporated under vacuum. Purification on asilica gel
preparative plate (SiO2, pentane/Et2O, 7/3) afforded 12i;
yield: 77 mg, (83%); 19F NMR (188 MHz, CDCl3): d=
À126.6 (2F, m), À123.2 (2F, m), À122.2 (2F, m), À120.8
(2F, m), À113.9 (2F, br t, J=14.8 Hz), À81.2 (3F, tt, J=
10.0 Hz, J=2.5 Hz), À67.5 (3F, s); 1H NMR (200 MHz,
CDCl3): d=3.41–3.69 (2H, m), 3.74–3.98 (2H, m), 7.53–7.72
(3H, m), 7.82–7.86 (2H, m); 13C NMR (75 MHz, CDCl3):
d=44.4, 54.1, 125.3 (CF3, q, J=346 Hz), 127.7, 129.9, 131.8,
133.0; anal. calcd. for C15H9F16NO2S2: C 29.86, H 1.50, N
2.32; found: C 30.01, H 1.48, N 2.34.
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Acknowledgements
Y.M. thanks GlaxoSmithKline and CNRS for financial sup-
port (BDI grant) and C.U. thanks the French Ministry of Re-
search for PhD grant. FranÅois Metz (Rhodia company) is
gratefully acknowledged for the gift of fluorinated reagents
and Drs. Elyane Kizilian, Emmanuel Allard and Sylvain
Marque for mass spectra.
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and Biological Methods, (Eds.: D. Enders, K.-E.
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ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2805 – 2814