Synthesis of aryl benzyl NH-sulfoximines

Article abstract of DOI:10.1016/j.tet.2009.10.056

Efficient synthesis and characterisation of a series of aryl benzyl NH-sulfoximines are described. While N-protected versions of aryl benzyl sulfoximines have been previously described, reports of their deprotection are very limited, presumably due to lab

Full text of DOI:10.1016/j.tet.2009.10.056

Tetrahedron 65 (2009) 10660–10670
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Synthesis of aryl benzyl NH-sulfoximines
,
Nicola Barry a, Nicolas Brondel a, Simon E. Lawrence a, Anita R. Maguire b
*
a Department of Chemistry, Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland
b Department of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland
a r t i c l e i n f o
a b s t r a c t
Article history:
Efficient synthesis and characterisation of a series of aryl benzyl NH-sulfoximines are described. While
N-protected versions of aryl benzyl sulfoximines have been previously described, reports of their de-
protection are very limited, presumably due to lability under the typically harsh deprotection conditions
which can be employed with the less reactive aryl alkyl derivatives. Use of N-cyanosulfoximines as key
intermediates overcomes these difficulties leading to an effective synthetic route to these compounds.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 20 July 2009
Received in revised form
29 September 2009
Accepted 15 October 2009
Available online 20 October 2009
1. Introduction
limited. From a review of the literature it appears that the depro-
tection of the aryl alkyl sulfoximines is possible, but the harsh con-
Sulfoximines were first reported in the early 1950s when
Whitehead and Bentley1 discovered that the sulfoximine of methio-
nine was responsible for the toxicity of wheat flour treated with ni-
trogen trichloride. These compounds have attracted considerable
interest in their use as chiral auxiliaries,2 backbones in pseudopep-
tides3 and applications as chiral ligands in asymmetric synthesis.4 A
number of synthetic methods have been described including imina-
tion of the sulfoxide (or sulfide for sulfilimine synthesis) with
hydrazoic acid5 (generated in situ from sodium azide and hydro-
chloric acid) or O-mesitylene sulfonyl hydroxylamine (MSH)6
allowing immediate access to the NH-sulfoximines. Metal cata-
lysed7and non-metal8 nitrene transfer to sulfoxides (and sulfides)
from iminoiodinates, PhI]NR (preformed or generated in situ), has
been extensively investigated in recent years with considerable
success. The imination of the sulfoxides has also proved successful
using electrochemical methods.9 However, these methods lead to the
formation of N-tosyl sulfoximines or related N-protected derivatives,
which can be difficult to convert into the useful NH derivatives.
ditions required for the cleavage of these N-protected derivatives are
not compatible with the more labile benzyl derivatives. The syn-
thesis of N-tosyl benzyl phenyl sulfoximine has been reported7e with
no indication of its deprotection. Bach and Korber11 reported the
synthesis of the N-Boc benzyl phenyl sulfoximine highlighting the
anticipated ease of the removal of the Boc group. However, the paper
describes the deprotection of the N-Boc benzyl methyl sulfoximine,
while deprotection of the N-Boc benzyl phenyl compound is not
described. The deprotection of the electrochemically produced9 N-
phthalimido benzyl phenyl sulfoximine also proved unsuccessful
resulting in decomposition of the starting sulfoximine. Following
these reports, Bolm and Cho10b described the synthesis of aryl benzyl
NH-sulfoximines via a palladium mediated
a-arylation of pre-
existing sulfoximines while further eluding to the difficulties in
accessing these derivatives via the existing methodologies such as
nitrene transfer and deprotection. More recently Bolm’s group7d has
reported increased efficiencies in the nitrene transfer to sulfoxides,
including benzyl phenyl sulfoxide, using iron(II) triflate as a catalyst
but notably the deprotection of the resulting N-nosyl benzyl phenyl
sulfoximine is not described in this paper.
2. Results and discussion
The initial approach considered for the synthesis of aryl benzyl
sulfoximines involved the reaction of the aryl benzyl sulfoxide, 1,
with hydrazoic acid5 generated in situ from sodium azide and
concentrated sulfuric acid, see Scheme 1. This method had been
successfully applied within our group to a wide range of aryl methyl
derivatives but with the aryl benzyl sulfoxide, 1, the desired NH-
sulfoximine, 2, was isolated in 6% yield and required extensive
chromatographic purification from a complex mixture. While aryl
methyl sulfoximines survive the harsh conditions associated with
the nitrene transfer it has been suggested4e,12 that use of more
labile substituents (e.g., secondary alkyl, benzyl) can lead to the
heterolysis of the C–S bond under acidic conditions.
As part of an ongoing research programme focused on crystal
engineering employing chiral organosulfur compounds we required
access to a series of aryl benzyl NH-sulfoximines. Most of the
reported syntheses of NH-sulfoximines to date are based on aryl
alkyl or diaryl systems7a–d,8a with just a handful of reports of aryl
benzyl NH-sulfoximines.10 There are some reports of N-protected
aryl benzyl sulfoximines but reports of their deprotection are
* Corresponding author.
E-mail address: a.maguire@ucc.ie (A.R. Maguire).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.056

N. Barry et al. / Tetrahedron 65 (2009) 10660–10670
10661
some modification (notably use of trifluoroacetic acid in place of
trifluoroacetic anhydride for the hydrolysis step), the route has
proved successful in leading to the series of compounds 4a–8n as
summarised in Table 1.
O
S
O
NH
Ph
NaN3/ conc. H2SO4
CHCl3, 45 °C
Ph
S
Bn
Bn
1
2
NCN
O
R
NCN
R'
Scheme 1.
NBS/tBuOK
m-CPBA/K2CO3
S
Accordingly, Bolm’s procedure7c employing Fe(III) catalysed
nitrene transfer leading to the N-nosyl derivative, 3, was next ex-
plored as summarised in Scheme 2. The efficiency of the trans-
formation proved variable and furthermore attempts to convert the
N-nosyl sulfoximine to the NH-sulfoximine were unproductive. The
investigation of the N-tosyl derivatives was avoided as harsher
conditions are required to cleave the tosyl group (acid hydrolysis
with concentrated sulfuric acid at 25 ꢀC13) relative to the nosyl
group (nucleophilic aromatic substitution with the in situ genera-
S
S
H2NCN
MeOH
EtOH
R
R'
R
R'
(CF3CO)2O
CH2Cl2
O
R
NCOCF3
R'
O
R
NH
tion of thiophenolate from thiophenol and caesium carbonate7c
)
K2CO3
MeOH
S
S
and this was not envisaged to provide a viable route to the desired
aryl benzyl NH-sulfoximines.
R'
Scheme 3.
O
O
NNs
Ph
A series of aryl benzyl sulfides were initially prepared via thio-
Fe(acac)3
S
late alkylation in good yields; while most of the sulfides were
previously reported, two 4g and 4j are novel and were fully char-
acterised during this work. The treatment of the sulfides with NBS,
cyanamine and potassium tert-butoxide in methanol led efficiently
to the series of N-cyanosulfilimines in comparable yields to the
benzyl methyl derivative reported by Bolm.8b Some of these de-
rivatives (5c, 5l, 5m) were recovered cleanly from the reaction
mixtures and were used without further purification, but most of
the compounds (5a, 5b, 5d-5k, 5n) were purified by column
chromatography to remove traces of residual sulfide. Interestingly,
the efficient transformations were observed with the methoxy
substituted compounds 5c, 5l and 5m, presumably related to the
S
NsNH2 / PhI(OAc)2
CH3CN
Bn
Ph
Bn
3
1
Scheme 2.
In 2007 the Bolm group reported a multi-step sequence leading
to NH-sulfoximines via N-cyanosulfilimines,8b see Scheme 3. While
they described the synthesis of benzyl methyl NH-sulfoximine
following this method, the application of this route to aryl benzyl
NH-sulfoximines was not described. It was decided to explore the
application of this route to aryl benzyl NH-sulfoximines and, with
Table 1
Synthesis of aryl benzyl NH-sulfoximines
NCN
O
NH
R'
O
NCN
R'
O
NCONH2
R'
NBS/tBuOK
S
m-CPBA/K2CO3
K2CO3
MeOH
R'X
CF3COOH
CH2Cl2
S
S
S
S
ArSH
NaH (60%) /
K2CO3
H2NCN
MeOH
EtOH
Ar
Ar
Ar
Ar
R'
Ar
R'
4
8
5
6
7
DMF
Ar
R0
No.
% Yield
No.
% Yield
No.
% Yield
No.
% Yield
No.
% Yield
b
b
C6H5
p-FC6H4
C6H5CH2
p-FC6H4CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
4a
da
54c
71c
76c
52c
37c
77c
78
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
75b
68b
83
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
80
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
52
210b
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
17b
38d
67
4b14
4c15
4d16
4e17
4f18
4g
77b
68b
83
70b
45b
41b
54b
d
p-OCH3C6H4
p-BrC6H4
p-NO2C6H4
o-BrC6H4
o-FC6H4
o-ClC6H4
p-ClC6H4
m-FC6H4
m-BrC6H4
o-OCH3C6H4
p-OCH3C6H4
p-FC6H4
75b
75b
75b
60b
58b
78b
63b
88b
83
60b
de
d
41b
df
df
d
d
4h19
4i20
4j
df
d
d
60c
82
63b
69b
69b
16b,g
56b
67b
56b
56b
38b
d
dh
80b
86b
61b
50b
d
4k21
4l22
4m15
4n14
83
69c
78
p-OCH3C6H4CH2
C6H5CH2
70
d
38b
65
55b
a
Commercially available.
After column chromatography.
After recrystallisation.
b
c
d
e
f
Labile on purification by column chromatography.
Crude 1H NMR shows trace amounts of 8e.
Crude 1H NMR shows sulfide as predominant product.
g
h
On repetition, crude 1H NMR showed molar ratio of 4l/5l/6l as 1:2.1:1.
Crude 1H NMR showed decomposition with partial loss of the methoxy groups.

10662
N. Barry et al. / Tetrahedron 65 (2009) 10660–10670
electronic effect of the methoxy substituent. Each of the N-cyano-
sulfilimines is a novel compound, was isolated as a solid and was
fully characterised. They are stable compounds, which are easily
handled and stored without degradation.
achieved by UV light detection (254 nm). Wet flash column chro-
matography was carried out using Merck Silica Gel 60, typically
with a 30:1 ratio of silica to sample.
Microanalysis was performed by The Microanalysis Laboratory,
UCC, Cork, on Perkin–Elmer 240 and Exeter Analytical CE440 ele-
mental analysers. Low resolution mass spectra were recorded on
a Waters Quattro Micro triple quadrupole instrument in electro-
spray ionisation (ESI) mode using 50% acetonitrile/water containing
0.1% formic acid as eluent; samples were made up in acetonitrile.
High resolution precise mass spectra (HRMS) were recorded on
a Waters LCT Premier TOF LC–MS instrument in electrospray ion-
isation (ESI) mode using 50% acetonitrile/water containing 0.1%
formic acid as eluent; samples were made up in acetonitrile. In-
frared spectra were measured as potassium bromide (KBr) discs for
solids or thin films on sodium chloride plates for liquids on a Per-
kin–Elmer Paragon 1000 FT-IR spectrometer. Melting points were
measured on an Electrothermal 9100-Melting Point apparatus and
a uni-melt Thomas Hoover Capillary melting point apparatus and
are uncorrected.
m-CPBA mediated oxidation of the N-cyanosulfilimines to the
analogous N-cyanosulfoximines was undertaken in the presence of
potassium carbonate in ethanol. The yields obtained for most of the
series of the resulting sulfoximines were reasonable following
column chromatography to remove unreacted N-cyanosulfilimine.
However with the ortho substituted derivatives the principal
product observed in each case was the analogous sulfide. It is clear
that the reaction at sulfur is hindered by the adjacent ortho sub-
stituent and removal of the NCN group occurs in an unusual re-
ductive transformation at sulfur in the presence of m-CPBA. The
novel N-cyanosulfoximines 6a–6n were stable solids and were fully
characterised during this work.
Bolm8b described the use of trifluoroacetic anhydride to trans-
form the N-cyanosulfoximines to the analogues N-trifluoroacetyl
compounds followed by hydrolysis using potassium carbonate in
methanol. During this research we found that the use of trifluoro-
acetic acid led to the N-carbamoyl sulfoximines (7a–7e, 7i-7k, 7n),
which are readily deprotected using potassium carbonate in
methanol to yield the ‘free’ NH-sulfoximines (2, 8b–8d, 8i–8k, 8n).
Acidic hydrolysis of N-cyanosulfoximines has precedent.23 With the
activated dimethoxy derivative 7m formation of a complex reaction
mixture was seen during the trifluoroacetic acid hydrolysis in-
dicating that this system was unstable under the reaction condi-
tions. The N-carbamoyl nitro derivative 7e showed only minimal
conversion into the desired NH-sulfoximine 8e. Moderate yields
were obtained in each of the hydrolysis steps and chromatographic
purification was required at each step, except for 8c, to provide pure
compounds for characterisation. Again both the N-carbamoyl de-
rivatives (7a–7e, 7i–7k, 7n) and the NH-sulfoximines (8b–8d, 8i–
8k, 8n) are novel, other than 2, and were fully characterised during
this work. Each of the compounds was solid and the only issue in
handling was with the difluoro derivative 8b, which proved labile
towards chromatography.
4.2. Benzyl phenyl sulfoxide (1)24
Benzyl phenyl sulfide (1.85 g, 9.24 mmol) was stirred in CH2Cl2
(50 mL) at 0 ꢀC. A solution of m-chloroperbenzoic acid (2.07 g, 77%,
9.24 mmol) in CH2Cl2 (40 mL) was added dropwise over 1 h. The
reaction mixture was stirred for an additional 30 min at 0 ꢀC. Sat-
urated NaHCO3 (30 mL) was added and the phases separated. The
organic layer was further washed with NaHCO3 (2ꢁ30 mL), brine
(30 mL), dried and concentrated under reduced pressure to give the
crude product. Purification was carried out by recrystallisation from
hot methanol, which afforded the title compound as a white solid
(1.45 g, 71%), mp 121–122 ꢀC (lit.24 125–126 ꢀC); nmax (KBr)/cmꢂ1
2960, 1597, 1442, 1415, 1036 (S]O stretch), 745 (C–S stretch); dH
(300 MHz) (CDCl3) 3.99 (1H, A of ABsystem, JAB 12.6, one of CH2), 4.09
(1H, B of ABsystem, JAB 12.6, one of CH2), 6.93–7.02 (2H, m, ArH), 7.19–
7.32 (3H, m, ArH), 7.33–7.51 (5H, m, ArH).
4.3. S-Benzyl-S-phenyl-NH-sulfoximine (2)10b
3. Conclusion
To a solution of benzyl phenyl sulfoxide (1) (1.08 g, 5.0 mmol) in
CHCl3 (8 mL) was added sodium azide (1.07 g, 16.5 mmol). Concen-
trated sulfuric acid (2.88 mL) was then added dropwise to the stirred
mixture. Caution: might be explosive. The reaction mixture was then
heated to exactly 45 ꢀC and stirred at this temperature for 16 h. The
reaction mixture was cooled, diluted with water (25 mL) and
extracted with CH2Cl2 (2ꢁ25 mL) (organic layer 1). The remaining
aqueous layer was made basic by the addition of potassium car-
bonate (pH>9). This aqueous layer was then further extracted with
CH2Cl2 (3ꢁ20 mL) (organic layer 2). Organic layers 1 and 2 were
separately washed with brine (20 mL), dried and concentrated under
reduced pressure. Organic layer 1 yielded the unreacted sulfoxide.
Organic layer 2 yielded a complex mixture of products, which after
purification by column chromatography on silica gel using hexane/
ethyl acetate (50:50) to ethyl acetate (100) gave 2 as a white solid
(6%), mp 104–106 ꢀC (lit.21 112–113 ꢀC); dH (300 MHz) (CDCl3) 2.76
(1H, br s, NH), 4.37 (1H, A of ABsystem, JAB 13.5, one of CH2), 4.45 (1H, B
of ABsystem, JAB 13.5, one of CH2), 7.10–7.78 (10H, m, ArH); dC
(75.5 MHz) (CDCl3) 64.6 (CH2, CH2), 124.4, 128.6, 128.8, 128.9 (CH,
4ꢁaromatic CH), 129.4 (C, aromatic C), 131.1, 133.1 (CH, 2ꢁaromatic
CH), 140.3 (C, aromatic C); m/z (ESI) 232 [(MþH)þ].
This multi-step sequence provides ready access to a series of aryl
benzyl NH-sulfoximines bearing a range of substituents on the aryl
rings, failing only when the phenyl ring is para-nitro or ortho
substituted or with highly activated bis(methoxyaryl) compounds.
4. Experimental
4.1. General
All solvents were HPLC grade or were distilled prior to use by the
following methods: dichloromethane from phosphorus pentoxide;
ethyl acetate from potassium carbonate; hexane was distilled prior
to use. Organic phases were dried using anhydrous magnesium
sulfate (MgSO4). All commercial reagents, including m-chloro-
perbenzoic acid, were used without further purification.
1H (400 MHz) NMR spectra were recorded on a Bruker Avance
400 NMR spectrometer and 1H (300 MHz) NMR spectra were
recorded on a Bruker Avance 300 NMR spectrometer in proton
coupled mode. 13C (75.5 MHz) NMR spectra were recorded on
a Bruker Avance 300 NMR spectrometer. All spectra were recorded
at 20 ꢀC in deuterated chloroform (CDCl3) using trimethylsilane
(TMS) as an internal standard. Chemical shifts (dH and dC) are
reported in parts per million (ppm) relative to the TMS signal and
coupling constants are expressed in hertz (Hz).
4.4. Attempted synthesis of S-benzyl-S-phenyl-N-
(p-nitrobenzenesulfonyl)sulfoximine (3)7d
Thin layer chromatography (TLC) was accomplished using pre-
coated silica gel plates (Merck Silica Gel 60 F254). Visualisation was
Benzyl phenyl sulfoxide (1) (0.43 g, 2.0 mmol), p-nitro-
benzenesulfonamide (0.61 g, 3 mmol), diacetoxyiodobenzene

N. Barry et al. / Tetrahedron 65 (2009) 10660–10670
10663
(1.6 equiv) and iron(III) acetylacetonate (0.035 g, 0.1 mmol) were
stirred in acetonitrile (20 mL) at room temperature. The reaction
progress was monitored by TLC. The reaction mixture was con-
centrated under reduced pressure. CH2Cl2 (25 mL) and water
(20 mL) were added and the phases separated. The organic layer
was further washed with water (2ꢁ20 mL), brine (20 mL), dried
and concentrated under reduced pressure to give the crude prod-
uct as a yellow semi-solid (0.27 g). 1H NMR analysis indicated the
presence of a significant amount of benzyl phenyl sulfoxide (1) [dH
(400 MHz) (CDCl3) 4.00 (1H, A of ABsystem, JAB 12.4, one of CH2), 4.11
(1H, B of ABsystem, JAB 12.4, one of CH2)] and trace amounts of the
desired product (3) whose signals are tentatively assigned as dH
(400 MHz) (CDCl3) 4.76 (1H, A of ABsystem, JAB 13.6, one of CH2), 4.83
(1H, B of ABsystem, JAB 14.0, one of CH2). Molar ratio of 1/3 was 1:0.17.
consumed the mixture was poured onto water (20 mL). The phases
were separated and the aqueous layer was further washed with
CH2Cl2 (2ꢁ10 mL). The combined organic layers were washed with
brine (20 mL), dried over MgSO4, filtered and concentrated under
reduced pressure to give the crude product. Purification was carried
out by wet flash chromatography using hexane/ethyl acetate (60:40
to 50:50) as eluent, where necessary.
4.5.5. Procedure E. The N-carbamoylsulfoximine (1 equiv) was
dissolved in methanol (10 mL) and K2CO3 (5 equiv) was added. The
reaction progress was monitored by TLC and once all of the sul-
foximine was consumed, the mixture was concentrated under re-
duced pressure. Water (10 mL) and CH2Cl2 (10 mL) were added to
the reaction residue and the phases separated. The aqueous layer
was further washed with CH2Cl2 (2ꢁ10 mL). The combined organic
layers were washed with brine (20 mL), dried over MgSO4 and
concentrated under reduced pressure to give the crude product.
Purification was carried out by wet flash chromatography using
hexane/ethyl acetate (70:30) to ethyl acetate (100) as eluent, where
necessary.
4.5. General procedures
4.5.1. Procedure A. The thiol (1 equiv) was added dropwise to
a stirred suspension of NaH (1.05 equiv)/K2CO3 (1.05 equiv) in DMF
(15 mL) under N2 at 0 ꢀC. The reaction mixture was stirred for
20 min and the alkyl halide (1 equiv) in DMF (1 mL) was then slowly
added over 20 min. The reaction mixture was stirred for a further
16 h at room temperature. Water (50 mL) and CH2Cl2 (30 mL) were
added and the phases separated. The organic layer was concen-
trated under reduced pressure. The product was dissolved in CH2Cl2
(30 mL), washed with 2 M HCl (3ꢁ20 mL) and brine (20 mL), dried
over MgSO4 and concentrated under reduced pressure to give the
crude product. Purification was carried out either by wet flash
chromatography, using hexane/ethyl acetate (98:2 to 95:5) as elu-
ent, or recrystallisation from a suitable solvent or by a combination
of both methods as indicated for each compound.
4.5.6. 4-Fluorobenzyl-(40-fluorophenyl)-sulfide
(4b)14. Following
procedure A, the reaction of NaH (0.27 g, 60% dispersion in oil,
6.83 mmol), 4-fluorobenzene thiol (0.83 g, 0.69 mL, 6.50 mmol) and
4-fluorobenzyl chloride (0.94 g, 0.78 mL, 6.50 mmol) and sub-
sequent recrystallisation from hot methanol afforded 4b as a white
solid (0.83 g, 54%), mp 46–47 ꢀC (lit.14 44.5–45.5 ꢀC); nmax (KBr)/cmꢂ1
2923,1596,1515,1494,1239, 750 (C–S stretch); dH (300 MHz) (CDCl3)
3.99 (3H, s, CH2), 6.88–7.00 (4H, m, ArH), 7.10–7.19 (2H, m, ArH),
7.20–7.30 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 40.2 (CH2, CH2), 115.7
(CH, d, 2JC–F 21.0, aromatic CH), 116.4 (CH, d, 2JC–F 21.0, aromatic CH),
130.8 (CH, d, 3JC–F 8.3, aromatic CH),133.69,133.73 (C, 2ꢁaromatic C),
134.2 (CH, d, 3JC–F 8.3, aromatic CH),162.3 (C, d,1JC–F 244.5, C–F),162.6
(C, d, 1JC–F 245.3, C–F).
4.5.2. Procedure B8b. The sulfide (1 equiv), cyanamine (1.3 equiv)
and potassium tert-butoxide (1.2 equiv) were stirred in methanol
(10 mL) at room temperature. N-Bromosuccinimide (1.5 equiv) was
added to this solution. The reaction progress was monitored by TLC.
Once the starting sulfide had been consumed, the reaction mixture
was concentrated under reduced pressure. Saturated Na2S2O3 so-
lution (10 mL) and CH2Cl2 (10 mL) were added to the crude mixture
and the phases separated. The aqueous layer was further washed
with CH2Cl2 (2ꢁ10 mL). The combined organic layers were washed
with brine (20 mL), dried over MgSO4 and concentrated under re-
duced pressure to give the crude product. Purification was carried
out by wet flash chromatography using dichloromethane/acetone
(9:1 to 6:1) or hexane/ethyl acetate (60:40) as eluent, where
necessary.
4.5.7. Benzyl-(4-methoxyphenyl)-sulfide (4c)15. Following procedure
A, the reaction of NaH (0.27 g, 60% dispersion in oil, 6.83 mmol),
4-methoxybenzene thiol (0.91 g, 0.81 mL, 6.50 mmol) and benzyl
bromide (1.11 g, 0.92 mL, 6.50 mmol) and subsequent recrystalli-
sation from hot methanol afforded 4c as a white solid (1.07 g, 71%),
mp 47–48 ꢀC (lit.15 48–49 ꢀC); nmax (KBr)/cmꢂ1 2920, 1596, 1571,
1245, 1180, 712 (C–S stretch); dH (300 MHz) (CDCl3) 3.78 (3H, s,
CH3), 3.98 (2H, s, CH2), 6.74–6.83 (2H, m, ArH), 7.14–7.31 (7H, m,
ArH).
4.5.8. Benzyl-(4-bromophenyl)-sulfide (4d)16. Following procedure
D, the reaction of NaH (0.27 g, 60% dispersion in oil, 6.83 mmol), 4-
bromobenzene thiol (1.23 g, 6.50 mmol) and benzyl bromide
(1.11 g, 0.92 mL, 6.50 mmol) and subsequent recrystallisation from
hot methanol afforded 4d as a white solid (1.38 g, 76%), mp 61–
63 ꢀC (lit.16 63–64 ꢀC); nmax (KBr)/cmꢂ1 2923, 1470, 1453, 1111, 711
(C–S stretch); dH (300 MHz) (CDCl3) 4.08 (2H, s, CH2), 7.11–7.18 (2H,
m, ArH), 7.20–7.32 (5H, m, ArH), 7.33–7.39 (2H, m, ArH).
4.5.3. Procedure C8b. N-Cyanosulfilimine (1 equiv) was stirred in
ethanol (20 mL) at 0 ꢀC. m-Chloroperbenzoic acid (77%, 1.5 equiv)
and K2CO3 (3 equiv) were added to the solution. The solution was
allowed to reach room temperature and stirred until TLC indicated
that all of the starting sulfilimine was consumed. The reaction
mixture was concentrated under reduced pressure. Water (10 mL)
and CH2Cl2 (10 mL) were added to the reaction residue and the
phases separated. The aqueous layer was further washed with
CH2Cl2 (2ꢁ10 mL). The combined organic layers were washed with
brine (20 mL), dried over MgSO4 and concentrated under reduced
pressure to give the crude product. Purification was carried out by
wet flash chromatography using hexane/ethyl acetate (60:40) as
eluent, where necessary.
4.5.9. Benzyl-(4-nitrophenyl)-sulfide (4e)17. Following procedure A,
the reaction of K2CO3 (0.58 g, 4.2 mmol), 4-nitrobenzene thiol
(0.62 g, 4.0 mmol) and benzyl bromide (0.68 g, 0.48 mL, 4.0 mmol)
and subsequent recrystallisation from hot methanol afforded 4e as
a yellow solid (0.51 g, 52%), mp 117–120 ꢀC (lit.17 122 ꢀC); nmax (KBr)/
cmꢂ1 1593, 1574, 1508 (asymmetric NO2 stretch), 1333 (symmetric
NO2 stretch), 719 (C–S stretch); dH (300 MHz) (CDCl3) 4.25 (2H, s,
CH2), 7.23–7.42 (7H, m, ArH), 8.06–8.14 (2H, m, ArH).
4.5.4. Procedure D. N-Cyanosulfoximine (1 equiv) was dissolved in
CH2Cl2 (20 mL) and the mixture cooled to 0 ꢀC. Trifluoroacetic acid
(3 equiv) was slowly added to the above solution and the mixture
was allowed to reach room temperature. The reaction progress was
monitored by TLC and once the starting sulfoximine had been
4.5.10. Benzyl-(2-bromophenyl)-sulfide (4f)18. Following procedure
A, the reaction of K2CO3 (0.44 g, 3.15 mmol), 2-bromobenzene thiol
(0.57 g, 0.35 mL, 3.00 mmol) and benzyl bromide (0.51 g, 0.36 mL,

10664
N. Barry et al. / Tetrahedron 65 (2009) 10660–10670
3.00 mmol) and subsequent recrystallisation from hot methanol
afforded 4f as a white solid (0.31 g, 37%), mp 49–50 ꢀC (lit.18 44–
45 ꢀC); nmax (KBr)/cmꢂ1 2912, 1627, 1452, 1435, 718 (C–S stretch); dH
(300 MHz) (CDCl3) 4.15 (2H, s, CH2), 6.99–7.06 (1H, m, ArH), 7.17–
7.39 (7H, m, ArH), 7.52–7.58 (1H, m, ArH).
741 (C–S stretch); dH (300 MHz) (CDCl3) 3.89 (3H, s, CH3), 4.09 (2H,
s, CH2), 6.82–6.89 (2H, m, ArH), 7.15–7.33 (7H, m, ArH).
4.5.17. 4-Methoxybenzyl-(40-methoxyphenyl)-sulfide (4m)15. Follo-
wing procedure A, the reaction of NaH (0.27 g, 60% dispersion in oil,
6.83 mmol), 4-methoxybenzene thiol (0.91 g, 0.81 mL, 6.50 mmol)
and 4-methoxybenzyl chloride (1.02 g, 0.88 mL, 6.50 mmol) affor-
ded, without further purification, 4m as a white solid (1.32 g, 78%),
mp86–89 ꢀC(lit.15 89–90 ꢀC);nmax (KBr)/cmꢂ12923,1612,1596,1515,
1494, 1182, 741 (C–S stretch); dH (300 MHz) (CDCl3) 3.78 (6H, s,
2ꢁCH3), 3.95 (2H, s, CH2), 6.74–6.83 (4H, m, ArH), 7.05–7.15 (2H, m,
ArH), 7.20–7.29 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 41.0 (CH2, CH2),
55.6, 55.7 (CH3, 2ꢁCH3), 114.1, 114.8 (CH, 2ꢁaromatic CH), 126.6 (C,
aromatic C),130.4 (CH, aromatic CH),130.5 (C, aromatic C),134.4 (CH,
aromatic CH), 159.0, 159.5 (C, 2ꢁaromatic C–O).
4.5.11. Benzyl-(2-fluorophenyl)-sulfide (4g). Following procedure A,
the reaction of K2CO3 (0.44 g, 3.15 mmol), 2-fluorobenzene thiol
(0.38 g, 0.32 mL, 3.00 mmol) and benzyl bromide (0.51 g, 0.36 mL,
3.00 mmol) and subsequent recrystallisation from hot methanol
afforded 4g as a white solid (0.50 g, 77%), mp 43–47 ꢀC. (Found: C,
71.53; H, 4.86; S 15.05; F 9.01. C13H11FS requires C, 71.53; H, 5.08; S
14.69; F 8.70%.) nmax (KBr)/cmꢂ1 2918, 1567, 1468, 1446, 741 (C–S
stretch); dH (300 MHz) (CDCl3) 4.10 (2H, s, CH2), 6.98–7.09 (2H, m,
ArH), 7.17–7.30 (7H, m, ArH); dC (75.5 MHz) (CDCl3) 38.4 (CH2, d,
4JC–F 2.3, CH2), 115.6 (CH, d, 2JC–F 21.5, aromatic CH), 122.8 (C, d, 2JC–F
18.0, aromatic C), 124.3 (CH, d, JC–F 3.8, aromatic CH), 127.3, 128.5
(CH, 2ꢁaromatic CH), 128.8 (CH, d, JC–F 7.5, aromatic CH), 128.9 (CH,
aromatic CH), 133.1 (CH, br d, JC–F 1.5, aromatic CH), 137.2 (C, aro-
matic C), 161.7 (C, d, 1JC–F 243.8, C–F).
4.5.18. Benzyl-(4-fluorophenyl)-sulfide (4n)14. Following procedure
A, the reaction of NaH (0.27 g, 60% dispersion in oil, 6.83 mmol),
4-fluorobenzene thiol (0.83 g, 0.69 mL, 6.50 mmol) and benzyl
bromide (1.11 g, 0.92 mL, 6.50 mmol) afforded, without further pu-
rification, 4n as a white solid (0.93 g, 65%), mp 33–34 ꢀC (lit.14 32.5–
33 ꢀC); nmax (KBr)/cmꢂ1 2923,1590,1490, 1230, 708 (C–S stretch); dH
(300 MHz)(CDCl3)4.03(2H, s, CH2), 6.89–6.99(2H, m, ArH), 7.17–7.32
(7H, m, ArH).
4.5.12. Benzyl-(2-chlorophenyl)-sulfide (4h)19. Following procedure
A, the reaction of K2CO3 (0.73 g, 5.25 mmol), 2-chlorobenzene thiol
(0.72 g, 0.57 mL, 5.00 mmol) and benzyl bromide (0.86 g, 0.59 mL,
5.00 mmol) afforded, without further purification, 4h as a yellow
oil (0.91 g, 78%); nmax (KBr)/cmꢂ1 3022, 1576, 1495, 1453, 745 (C–S
stretch); dH (400 MHz) (CDCl3) 4.14 (2H, s, CH2), 7.07–7.40 (9H, m,
ArH).
4.5.19. N-Cyano-S-benzyl-S-phenylsulfilimine (5a). Following pro-
cedure B, the reaction of benzyl phenyl sulfide (1.50 g, 7.5 mmol),
cyanamine (0.41 g, 9.7 mmol), potassium tert-butoxide (1.09 g,
9.0 mmol) and N-bromosuccinimide (2.00 g, 11.0 mmol) in metha-
nol (30 mL) and subsequent purification by column chromatogra-
phy on silica gel using CH2Cl2/acetone (9:1) afforded 5a as a white
solid (1.35 g, 75%); mp 72–73 ꢀC. (Found: C, 69.41; H, 5.02; N, 11.49.
C14H12N2S requires C, 69.97; H, 5.03; N, 11.66%.) nmax (KBr)/cmꢂ1
2918, 2144 (C^N stretch), 1492, 1451, 1165, 1026; dH (300 MHz)
(CDCl3) 4.28 (1H, A of ABsystem, JAB 12.6, one of CH2,), 4.57 (1H, B of
ABsystem, JAB 12.6, one of CH2), 7.11–7.19 (2H, m, ArH), 7.24–7.43 (3H,
m, ArH), 7.48–7.68 (5H, m, ArH); dC (75.5 MHz) (CDCl3) 58.7 (CH2,
CH2), 120.7 (C, C^N), 126.8 (CH, aromatic CH), 127.4 (C, aromatic C),
129.2, 129.7, 130.0, 130.7, 133.2 (CH, 5ꢁaromatic CH), 134.2 (C, aro-
matic C); m/z (ESI) 241 [(MþH)þ]; HRMS (ESI): exact mass calculated
for C14H13N2S [MþH]þ 241.0799, found 241.0803.
4.5.13. Benzyl-(4-chlorophenyl)-sulfide (4i)20. Following procedure
A, the reaction of K2CO3 (0.44 g, 3.15 mmol), 4-chlorobenzene thiol
(0.43 g, 3.00 mmol) and benzyl bromide (0.51 g, 0.36 mL,
3.00 mmol) and subsequent recrystallisation from hot methanol
afforded 4i as a white solid (0.42 g, 60%), mp 52–55 ꢀC (lit.20 49–
50 ꢀC); nmax (KBr)/cmꢂ1 2919, 1495, 1453, 712 (C–S stretch); dH
(400 MHz) (CDCl3) 4.08 (2H, s, CH2), 7.19–7.32 (9H, m, ArH).
4.5.14. Benzyl-(3-fluorophenyl)-sulfide (4j). Following procedure A,
the reaction of K2CO3 (0.44 g, 3.15 mmol), 2-fluorobenzene thiol
(0.38 g, 0.32 mL, 3.00 mmol) and benzyl bromide (0.51 g, 0.36 mL,
3.00 mmol) afforded, without further purification, 4j as a white
solid (0.53 g, 82%), mp 39–41 ꢀC. (Found: C, 71.24; H, 4.78; S 15.13; F
8.99. C13H11FS requires C, 71.53; H, 5.08; S 14.69; F 8.70%.) nmax
(KBr)/cmꢂ1 3029, 1600, 1576, 1495, 1264, 716 (C–S stretch); dH
(400 MHz) (CDCl3) 4.13 (2H, s, CH2), 6.82–6.89 (1H, m, ArH), 6.96–
7.08 (2H, m, ArH), 7.17–7.34 (6H, m, ArH); dC (75.5 MHz) (CDCl3)
4.5.20. N-Cyano-S-(4-fluorobenzyl)-S-(40-fluorophenyl)sulfilimine
(5b). Following procedure B, the reaction of 4-fluorobenzyl-(40-
fluorophenyl)-sulfide (4b) (0.48 g, 2.0 mmol), cyanamine (0.12 g,
2.6 mmol), potassium tert-butoxide (0.27 g, 2.4 mmol) and N-bro-
mosuccinimide (0.53 g, 3.0 mmol) and subsequent purification by
column chromatography on silica gel using dichloromethane/ace-
tone (6:1) afforded 5b as a white solid (0.38 g, 68%), mp 112–115 ꢀC.
(Found: C, 60.80; H, 3.62; N, 10.44; S, 11.64; F 13.32. C14H10F2N2S
requires C, 60.86; H, 3.65; N, 10.14; S, 11.60; F 13.75%.) nmax (KBr)/
cmꢂ1 2144 (C^N stretch), 1597, 1509, 1493, 1233, 1176, 1160, 1014,
835; dH (300 MHz) (CDCl3) 4.26 (1H, A of ABsystem, JAB 13.1, one of
CH2,), 4.50 (1H, B of ABsystem, JAB 12.8, one of CH2), 6.98–7.09 (2H, m,
ArH), 7.09–7.18 (2H, m, ArH), 7.19–7.31 (2H, m, ArH), 7.60–7.71 (2H,
2
38.5 (CH2, CH2), 113.1 (CH, d, JC–F 21.2, aromatic CH), 115.9 (CH, d,
2JC–F 22.8, aromatic CH), 124.7 (CH, d, 4JC–F 2.9, aromatic CH), 127.4,
3
128.6, 128.8 (CH, 3ꢁaromatic CH), 130.1 (CH, d, JC–F 8.6, aromatic
CH), 136.8 (C, aromatic C), 139.0 (C, d, 3JC–F 8.0, aromatic C), 162.8 (C,
d, 1JC–F 246.8, C–F).
4.5.15. Benzyl-(3-bromophenyl)-sulfide (4k)21. Following procedure
A, the reaction of K2CO3 (0.73 g, 5.25 mmol), 3-bromobenzene thiol
(0.95 g, 0.59 mL, 5.00 mmol) and benzyl bromide (0.86 g, 0.59 mL,
5.00 mmol) afforded, without further purification, 4k as awhite solid
(1.16 g, 83%), mp 43–46 ꢀC (lit.21 40–41 ꢀC); nmax (KBr)/cmꢂ1 1574,
1560,1456, 719 (C–S stretch); dH (300 MHz) (CDCl3) 4.12 (2H, s, CH2),
7.07–7.14 (1H, m, ArH), 7.17–7.32 (7H, m, ArH), 7.44 (1H, t, J 2.0, ArH).
2
m, ArH); dC (75.5 MHz) (CDCl3) 57.9 (CH2, CH2), 116.3 (CH, d, JC–F
2
21.8, aromatic CH), 117.6 (CH, d, JC–F 23.2, aromatic CH), 120.5 (C,
4
C^N), 122.8 (C, d, JC–F 3.8, aromatic C), 129.3 (C, aromatic C)
overlapping with 129.3 (CH, d, 3JC–F 9.0, aromatic CH), 132.7 (CH, d,
3JC–F 9.0, aromatic CH), 163.5 (C, d, 1J–F 249.0, C–F), 165.5 (C, d, 1JC–F
255.0, C–F); m/z (ESI) 277 [(MþH)þ]; HRMS (ESI): exact mass cal-
culated for C14H11F2N2S [MþH]þ 277.0611, found 277.0615.
4.5.16. Benzyl-(2-methoxyphenyl)-sulfide (4l)22. Following pro-
cedure A, the reaction of NaH (0.27 g, 60% dispersion in oil,
6.83 mmol), 2-methoxybenzene thiol (0.91 g, 0.79 mL, 6.50 mmol)
and benzyl bromide (1.11 g, 0.92 mL, 6.50 mmol) and subsequent
recrystallisation from hot methanol afforded 4l as a white solid
(1.04 g, 69%), mp 67–68 ꢀC; nmax (KBr)/cmꢂ1 2925, 1575, 1477, 1235,
4.5.21. N-Cyano-S-benzyl-S-(4-methoxyphenyl)sulfilimine (5c). Follo-
wing procedure B, the reaction of benzyl-(4-methoxyphenyl)-
sulfide (4c) (0.46 g, 2.0 mmol), cyanamide (0.11 g, 2.6 mmol),

N. Barry et al. / Tetrahedron 65 (2009) 10660–10670
10665
potassium tert-butoxide (0.27 g, 2.4 mmol) and N-bromosuccin-
imide (0.53 g, 3.0 mmol) afforded, without further purification,
a white solid identified as 5c (0.45 g, 83%), mp 72–75 ꢀC; nmax (KBr)/
cmꢂ1 2360, 2145 (C^N stretch), 1496, 1455, 1260, 1177, 1023, 832;
dH (300 MHz) (CDCl3) 3.86 (3H, s, OCH3), 4.28 (1H, A of ABsystem, JAB
12.3, one of CH2), 4.46 (1H, B of ABsystem, JAB 12.7, one of CH2), 6.94–
7.05 (2H, m, ArH), 7.12–7.19 (2H, m, ArH), 7.26–7.40 (3H, m, ArH),
7.54–7.63 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 55.8 (CH3, CH3 of
OCH3), 58.3 (CH2, CH2), 115.4 (CH, aromatic CH), 124.6, 127.6 (C,
2ꢁaromatic C), 129.08, 129.13, 129.5, 130.7 (CH, 4ꢁaromatic CH),
163.6 (C, aromatic C–O), 1ꢁC^N signal absent; m/z (ESI) 271
[(MþH)þ]; HRMS (ESI): exact mass calculated for C15H15N2OS
[MþH]þ 271.0905, found 271.0904.
1ꢁC^N, 2ꢁaromatic C), 128.3, 129.0, 129.2, 129.9, 130.9, 133.6,
134.0 (CH, 7ꢁaromatic CH), 134.8 (C, aromatic C); m/z (ESI) 319, 321
(1:1) [(MþH)þ].
4.5.25. N-Cyano-S-benzyl-S-(2-fluorophenyl)sulfilimine (5g). Follo-
wing procedure B, the reaction of benzyl-(2-fluorophenyl)-sulfide
(4g) (0.44 g, 2.0 mmol), cyanamine (0.12 g, 2.6 mmol), potassium
tert-butoxide (0.27 g, 2.4 mmol) and N-bromosuccinimide (0.53 g,
3.0 mmol) and subsequent purification by column chromatogra-
phy on silica gel using hexane/ethyl acetate (60:40) afforded 5g as
a white solid (0.31 g, 60%), mp 116–120 ꢀC; nmax (KBr)/cmꢂ1 2982,
2928, 2143 (C^N stretch), 1597, 1584, 1473, 1455, 1153, 1027; dH
(300 MHz) (CDCl3) 4.41 (1H, A of ABsystem, JAB 12.9, one of CH2,),
4.49 (1H, B of ABsystem, JAB 12.6, one of CH2), 7.14–7.46 (7H, m, ArH),
7.55–7.66 (1H, m, ArH), 7.87–7.97 (1H, m, ArH); dC (75.5 MHz)
(CDCl3) 57.7 (CH2, d, 4JC–F 1.7, CH2), 116.5 (CH, d, 2JC–F 20.0, aromatic
CH), 120.4 (C, C^N), 121.9 (C, d, 2JC–F 15.5, aromatic C), 126.1 (CH, d,
JC–F 3.4, aromatic CH),127.1 (C, aromatic C), 127.6, 129.1, 129.9, 130.8
(CH, 4ꢁaromatic CH), 134.9 (CH, d, JC–F 8.0, aromatic CH), 158.5 (C,
4.5.22. N-Cyano-S-benzyl-S-(4-bromophenyl)sulfilimine (5d). Follo-
wing procedure B, the reaction of benzyl-(4-bromophenyl)-sulfide
(4d) (0.56 g, 2.0 mmol), cyanamide (0.11 g, 2.6 mmol), potassium
tert-butoxide (0.27 g, 2.4 mmol) and N-bromosuccinimide (0.53 g,
3.0 mmol) and subsequent purification by column chromatography
on silica gel using dichloromethane/acetone (9:1) afforded 5d as
a white solid (0.48 g, 75%), mp 121–125 ꢀC. (Found: C, 52.49; H,
3.49; N, 8.68; S 10.23. C14H11BrN2S requires C, 52.68; H, 3.47; N,
8.78; S 10.04%.) nmax (KBr)/cmꢂ1 2153 (C^N stretch), 1475, 1454,
1388, 1186, 1066, 1007, 833; dH (300 MHz) (CDCl3) 4.28 (1H, A of
ABsystem, JAB 13.0, one of CH2), 4.54 (1H, B of ABsystem, JAB 13.0, one of
CH2), 7.11–7.20 (2H, m, ArH), 7.26–7.43 (3H, m, ArH), 7.44–7.54 (2H,
m, ArH), 7.60–7.70 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 58.8 (CH2,
CH2), 120.5 (C, C^N), 127.0 (C, aromatic C), 128.1, 129.2, 129.8, 130.8,
133.2 (CH, 5ꢁaromatic CH), 133.1 (C, aromatic C), 1ꢁaromatic C
signal absent; m/z (ESI) 319, 321 (1:1) [(MþH)þ]; HRMS (ESI): exact
mass calculated for C14H1279BrN2S [MþH]þ 318.9905, found
318.9904.
1
d, JC–F 248.3, C–F); m/z (ESI) 259 [(MþH)þ]; HRMS (ESI):
exact mass calculated for C14H12FN2S [MþH]þ 259.0705, found
259.0700.
4.5.26. N-Cyano-S-benzyl-S-(2-chlorophenyl)sulfilimine (5h). Follo-
wing procedure B, the reaction of benzyl-(2-chlorophenyl)-sulfide
(4h) (0.47 g, 2.0 mmol), cyanamide (0.11 g, 2.6 mmol), potassium
tert-butoxide (0.27 g, 2.4 mmol) and N-bromosuccinimide (0.53 g,
3.0 mmol) and subsequent purification by column chromatography
on silica gel using hexane/ethyl acetate (60:40) afforded 5h as
a white solid (0.32 g, 58%), mp 140–142 ꢀC. (Found: C, 61.14; H, 3.96;
N, 10.10; S 11.89; Cl 13.18. C14H11ClN2S requires C, 61.20; H, 4.04; N,
10.20; S 10.67; Cl 12.90%.) nmax (KBr)/cmꢂ1 2973, 2918, 2153 (C^N
stretch),1569,1494,1439,1176,1029; dH (300 MHz) (CDCl3) 4.34 (1H,
Aof ABsystem, JAB 12.9, one of CH2), 4.43 (1H, B of ABsystem, JAB 12.9, one
of CH2), 7.21–7.29 (2H, m, ArH), 7.30–7.44 (3H, m, ArH), 7.45–7.60
(3H, m, ArH), 7.88–7.97 (1H, m, ArH); dC (75.5 MHz) (CDCl3) 57.6
(CH2, CH2), 120.7 (C, C^N), 127.3 (C, aromatic C–Cl), 127.9, 128.6,
129.0, 129.8, 130.4, 130.9 (CH, 6ꢁaromatic CH), 131.7, 132.9 (C,
2ꢁaromatic C), 133.8 (CH, aromatic CH); m/z (ESI) 275, 277 (3:1)
[(MþH)þ]; HRMS (ESI): exact mass calculated for C14H1235ClN2S
[MþH]þ 275.0410, found 275.0400.
4.5.23. N-Cyano-S-benzyl-S-(4-nitrophenyl)sulfilimine (5e). Follo-
wing procedure B, the reaction of benzyl-(4-nitrophenyl)-sulfide
(4e) (0.49 g, 2.0 mmol), cyanamide (0.11 g, 2.6 mmol), potassium
tert-butoxide (0.27 g, 2.4 mmol) and N-bromosuccinimide (0.53 g,
3.0 mmol) and subsequent purification by column chromatography
on silica gel using dichloromethane/acetone (9:1) afforded a yellow
solid identified as 5e (0.43 g, 75%), mp 135–139 ꢀC. (Found: C,
58.71; H, 4.08; N, 14.63; S, 11.38. C14H11N3O2S requires C, 58.93; H,
3.89; N,14.73; S,11.24%.) nmax (KBr)/cmꢂ1 2925, 2146 (C^N stretch),
1606, 1579, 1539 (asymmetric NO2 stretch), 1351 (symmetric NO2
4.5.27. N-Cyano-S-benzyl-S-(4-chlorophenyl)sulfilimine (5i). Follo-
wing procedure B, the reaction of benzyl-(4-chlorophenyl)-sulfide
(4i) (0.35 g, 1.50 mmol), cyanamide (0.08 g, 1.90 mmol), potassium
tert-butoxide (0.20 g, 1.80 mmol) and N-bromosuccinimide (0.40 g,
2.25 mmol) and subsequent purification by column chromatogra-
phy on silica gel using hexane/ethyl acetate (60:40) afforded 5i as
a white solid (0.32 g, 78%), mp 122–125 ꢀC. (Found: C, 61.09; H,
3.85; N, 10.04; S 11.72; Cl 13.21. C14H11ClN2S requires C, 61.20; H,
4.04; N, 10.20; S 10.67; Cl 12.90%.) nmax (KBr)/cmꢂ1 3081, 2157
(C^N stretch), 1570, 1475, 1452, 1187, 1010; dH (300 MHz) (CDCl3)
stretch), 1183, 1012; dH (300 MHz) (CDCl3) 4.33 (1H, A of ABsystem
,
JAB 12.6, one of CH2), 4.62 (1H, B of ABsystem, JAB 12.6, one of CH2),
7.10–7.18 (2H, m, ArH), 7.31–7.46 (3H, m, ArH), 7.74–7.81 (2H, m,
ArH), 8.31–8.39 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 59.4 (CH2,
CH2), 124.8 (CH, aromatic CH), 126.2 (C, aromatic C), 127.8, 129.5,
130.3, 130.8 (CH, 4ꢁaromatic CH), 140.8 (C, aromatic C), 1ꢁC^N
signal absent, 1ꢁaromatic C signal absent; m/z (ESI) 286 [(MþH)þ];
HRMS (ESI): exact mass calculated for C14H12N3O2S [MþH]þ
286.0650, found 286.0655.
4.27 (1H, A of ABsystem, JAB 12.9, one of CH2), 4.56 (1H, B of ABsystem
,
4.5.24. N-Cyano-S-benzyl-S-(2-bromophenyl)sulfilimine (5f). Follo-
wing procedure B, the reaction of benzyl-(2-bromophenyl)-sulfide
(4f) (0.28 g, 1.0 mmol), cyanamide (0.06 g, 1.3 mmol), potassium
tert-butoxide (0.14 g, 1.2 mmol) and N-bromosuccinimide (0.27 g,
1.5 mmol) and subsequent purification by column chromatography
on silica gel using hexane/ethyl acetate (60:40) afforded 5f as
a white solid (0.24 g, 75%), mp 132–133 ꢀC. (Found: C, 52.54; H,
3.41; N, 8.74; S 10.36. C14H11BrN2S requires C, 52.68; H, 3.47; N,
8.78; S 10.04%.) nmax (KBr)/cmꢂ1 2973, 2157 (C^N stretch), 1565,
JAB 12.6, one of CH2), 7.10–7.19 (2H, m, ArH), 7.29–7.44 (3H, m, ArH),
7.45–7.61 (4H, m, ArH); dC (75.5 MHz) (CDCl3) 58.9 (CH2, CH2), 120.4
(C, C^N), 127.0 (C, aromatic C–Cl), 128.1, 129.3, 129.8, 130.3, 130.7
(CH, 5ꢁaromatic CH), 132.5, 139.9 (C, 2ꢁaromatic C); m/z (ESI) 275,
277 (3:1) [(MþH)þ]; HRMS (ESI): exact mass calculated for
C14H1235ClN2S [MþH]þ 275.0410, found 275.0402.
4.5.28. N-Cyano-S-benzyl-S-(3-fluorophenyl)sulfilimine (5j). Follo-
wing procedure B, the reaction of benzyl-(3-fluorophenyl)-sulfide
(4j) (1.10 g, 5.0 mmol), cyanamine (0.28 g, 6.6 mmol), potassium
tert-butoxide (0.69 g, 6.1 mmol) and N-bromosuccinimide (1.37 g,
7.7 mmol) and subsequent purification by column chromatography
on silica gel using hexane/ethyl acetate (60:40) afforded 5j as
1495,1455,1180, 1019; dH (300 MHz) (CDCl3) 4.32 (1H, A of ABsystem
,
JAB 12.9, one of CH2), 4.44 (1H, B of ABsystem, JAB 12.9, one of CH2),
7.23–7.60 (7H, m, ArH), 7.64–7.72 (1H, m, ArH), 7.87–7.95 (1H, m,
ArH); dC (75.5 MHz) (CDCl3) 57.9 (CH2, CH2), 120.7, 120.8, 127.4 (C,

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N. Barry et al. / Tetrahedron 65 (2009) 10660–10670
a white solid (0.81 g, 63%), mp 114–117 ꢀC. (Found: C, 65.23; H, 4.29;
N 10.80; S 12.80; F 7.80. C14H11FN2S requires C, 65.10; H, 4.29; N
10.84; S 12.41; F 7.35%.) nmax (KBr)/cmꢂ1 3027, 2156 (C^N stretch),
1585, 1473, 1418, 1223, 1187, 1079; dH (300 MHz) (CDCl3) 4.28 (1H, A
of ABsystem, JAB 12.6, one of CH2), 4.55 (1H, B of ABsystem, JAB 12.6, one
of CH2), 7.11–7.21 (2H, m, ArH), 7.23–7.45 (6H, m, ArH), 7.46–7.57
(1H, m, ArH); dC (75.5 MHz) (CDCl3) 59.1 (CH2, CH2), 113.9 (CH, d,
121.0, 124.7 (C, 1ꢁC^N, 2ꢁaromatic C),129.1, 132.0 (CH, 2ꢁaromatic
CH), 160.5, 163.5 (C, 2ꢁaromatic C–O); m/z (ESI) 301 [(MþH)þ].
4.5.32. N-Cyano-S-benzyl-S-(4-fluorophenyl)sulfilimine (5n). Follo-
wing procedure B, the reaction of benzyl-(4-fluorophenyl)-sulfide
(4n) (0.65 g, 3.0 mmol), cyanamine (0.16 g, 3.9 mmol), potassium
tert-butoxide (0.40 g, 3.6 mmol) and N-bromosuccinimide (0.80 g,
4.5 mmol) and subsequent purification by column chromatography
on silica gel using hexane/ethyl acetate (60:40) afforded 5n as
a white solid (0.42 g, 55%), mp 121–125 ꢀC; nmax (KBr)/cmꢂ1 2918,
2148 (C^N stretch), 1583, 1491, 1451, 1226, 1180, 1158, 1007; dH
(300 MHz) (CDCl3) 4.27 (1H, A of ABsystem, JAB 12.6, one of CH2,), 4.57
(1H, B of ABsystem, JAB 12.6, one of CH2), 7.05–7.43 (7H, m, ArH),
7.58–7.69 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 58.9 (CH2, CH2), 117.4
2
2JC–F 24.0, aromatic CH), 120.3 (C, C^N), 120.4 (CH, d, JC–F 21.0,
4
aromatic CH), 122.5 (CH, d, JC–F 3.8, aromatic CH), 126.9 (C, aro-
matic C), 129.2, 129.9, 130.7 (CH, 3ꢁaromatic CH), 131.6 (CH, d, 3JC–F
7.5, aromatic CH), 136.3 (C, d, 3JC–F 6.0, aromatic C), 162.9 (C, d, 1JC–F
252.8, C–F); m/z (ESI) 259 [(MþH)þ]; HRMS (ESI): exact mass cal-
culated for C14H12FN2S [MþH]þ 259.0705, found 259.0706.
2
4.5.29. N-Cyano-S-benzyl-S-(3-bromophenyl)sulfilimine (5k). Follo-
wing procedure B, the reaction of benzyl-(3-bromophenyl)-sulfide
(4k) (0.56 g, 2.0 mmol), cyanamide (0.11 g, 2.6 mmol), potassium
tert-butoxide (0.27 g, 2.4 mmol) and N-bromosuccinimide (0.53 g,
3.0 mmol) and subsequent purification by column chromatography
on silica gel using hexane/ethyl acetate (60:40) afforded 5k as
a white solid (0.56 g, 88%), mp 140–143 ꢀC. (Found: C, 52.52; H,
3.21; N, 8.40; S 10.38. C14H11BrN2S requires C, 52.68; H, 3.47; N,
8.78; S 10.04%.) nmax (KBr)/cmꢂ1 2924, 2143 (C^N stretch), 1567,
(CH, d, JC–F 22.5, aromatic CH), 120.5 (C, C^N), 127.0 (C, aromatic
3
C), 129.2 (CH, aromatic CH), 129.4 (CH, d, JC–F 9.8, aromatic CH),
129.6 (C, d, 4JC–F 3.0, aromatic C), 129.8, 130.7 (CH, 2ꢁaromatic CH),
165.5 (C, d, 1JC–F 255.0, C–F); m/z (ESI) 259 [(MþH)þ]; HRMS (ESI):
exact mass calculated for C14H12FN2S [MþH]þ 259.0705, found
259.0704.
4.5.33. N-Cyano-S-benzyl-S-phenyl sulfoximine (6a). Following pro-
cedure C, the reaction of N-cyano-benzyl-phenyl sulfilimine (5a)
(1.30 g, 5.4 mmol), m-chloroperbenzoic acid (1.82 g, 77%, 8.1 mmol)
and K2CO3 (2.24 g, 16.0 mmol) and subsequent purification by col-
umn chromatography using hexane/ethyl acetate (60:40) afforded
6a as a white solid (1.12 g, 80%), mp 169–173 ꢀC; nmax (KBr)/cmꢂ1
2978, 2919, 2197 (C^N stretch), 1448, 1244 (asymmetric SON
stretch), 1185, 1081 (symmetric SON stretch); dH (300 MHz) (CDCl3)
4.62 (2H, s, CH2), 7.01–7.09 (2H, m, ArH), 7.23–7.33 (2H, m, ArH),
7.34–7.43 (1H, m, ArH), 7.49–7.59 (2H, m, ArH), 7.60–7.77 (3H, m,
ArH); dC (75.5 MHz) (CDCl3) 63.4 (CH2, CH2), 112.1 (C, C^N), 125.5 (C,
aromatic C), 128.9, 129.2, 129.7, 130.0, 131.3 (CH, 5ꢁaromatic CH),
133.1 (C, aromatic C), 135.4 (CH, aromatic CH); m/z (ESI) 257
[(MþH)þ]; HRMS (ESI): exact mass calculated for C14H13N2OS
[MþH]þ 257.0749, found 257.0738.
1457, 1151, 1102, 883; dH (300 MHz) (CDCl3) 4.26 (1H, A of ABsystem
,
JAB 12.9, one of CH2), 4.55 (1H, B of ABsystem, JAB 12.6, one of CH2),
7.12–7.20 (2H, m, ArH), 7.30–7.46 (4H, m, ArH), 7.51–7.59 (1H, m,
ArH), 7.66–7.77 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 59.3 (CH2, CH2),
120.3 (C, C^N), 123.9 (C, aromatic C–Br), 125.1 (CH, aromatic CH),
126.8 (C, aromatic C), 129.2, 129.3, 130.0, 130.8, 131.3 (CH,
5ꢁaromatic CH), 136.1 (C, aromatic C), 136.2 (CH, aromatic CH); m/z
(ESI) 319, 321 (1:1) [(MþH)þ]; HRMS (ESI): exact mass calculated
for C14H1279BrN2S [MþH]þ 318.9905, found 318.9897.
4.5.30. N-Cyano-S-benzyl-S-(2-methoxyphenyl)sulfilimine (5l). Follo-
wing procedure B, the reaction of benzyl-(2-methoxyphenyl)-sulfide
(4l) (0.46 g, 2.0 mmol), cyanamide (0.11 g, 2.6 mmol), potassium tert-
butoxide (0.27 g, 2.4 mmol) and N-bromosuccinimide (0.53 g,
3.0 mmol) afforded, without further purification, a white solid
identified as 5l (0.45 g, 83%), mp 72–75 ꢀC. (Found: C, 66.83; H, 5.22;
N, 9.96; S 11.56. C15H14N2OS requires C, 66.64; H, 5.22; N, 10.36; S
11.86%.) nmax (KBr)/cmꢂ1 2924, 2153 (C^N stretch),1585,1479,1453,
1251, 1163, 1130, 1013, 748; dH (300 MHz) (CDCl3) 3.93 (3H, s, OCH3),
4.30 (1H, A of ABsystem, JAB 12.9, one of CH2), 4.40 (1H, B of ABsystem, JAB
12.6, one of CH2), 6.94–7.03 (1H, m, ArH), 7.12–7.42 (6H, m, ArH),
7.49–7.60 (1H, m, ArH), 7.78–7.87 (1H, m, ArH); dC (75.5 MHz) (CDCl3)
56.4 (CH3, CH3 of OCH3), 56.8 (CH2, CH2), 111.4 (CH, aromatic CH),
121.5, 121.9 (C, 1ꢁC^N, 1ꢁaromatic C), 122.3, 127.2 (CH, 2ꢁaromatic
CH), 128.2 (C, aromatic C), 128.8, 129.4, 130.8, 134.0 (CH, 4ꢁaromatic
CH), 155.8 (C, aromatic C–O); m/z (ESI) 271 [(MþH)þ]; HRMS (ESI):
exact mass calculated for C15H15N2OS [MþH]þ 271.0905, found
271.0898.
4.5.34. N-Cyano-S-(4-fluorobenzyl)-S-(40-fluorophenyl)sulfoximine
(6b). Following procedure C, the reaction of N-cyano-S-(4-fluo-
robenzyl)-S-(40-fluorophenyl)sulfilimine (5b) (0.30 g, 1.1 mmol), m-
chloroperbenzoic acid (0.36 g, 77%, 1.6 mmol) and K2CO3 (0.45 g,
3.3 mmol) and subsequent purification by column chromatography
on silica gel using hexane/ethyl acetate (60:40) afforded 6b as
a white solid (0.25 g, 77%), mp 109–114 ꢀC; nmax (KBr)/cmꢂ1 2194
(C^N stretch), 1587, 1509, 1492, 1240 (asymmetric SON stretch),
1191, 1158, 1087 (symmetric SON stretch); dH (300 MHz) (CDCl3)
4.60 (2H, s, CH2), 6.96–7.12 (4H, m, ArH), 7.20–7.31 (2H, m, ArH),
7.61–7.71 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 62.6 (CH2, CH2), 111.2
2
2
(C, C^N), 116.3 (CH, d, JC–F 21.8, aromatic CH), 117.4 (CH, d, JC–F
22.5, aromatic CH), 121.3 (C, d, 4JC–F 3.8, aromatic C), 128.6 (C, d, 4JC–F
3
3.0, aromatic C), 132.2 (CH, d, JC–F 9.8, aromatic CH), 133.2 (CH, d,
3JC–F 9.0, aromatic CH), 163.7 (C, d, 1JC–F 249.8, C–F), 166.9 (C, d, 1JC–F
258.8, C–F); m/z (ESI) 293 [(MþH)þ]; HRMS (ESI): exact mass cal-
culated for C14H11F2N2OS [MþH]þ 293.0560, found 293.0570.
4.5.31. N-Cyano-S-(4-methoxybenzyl)-S-(40-methoxyphenyl)sul-
filimine (5m). Following procedure B, the reaction of 4-methoxy-
benzyl-(40-methoxyphenyl)-sulfide (4m) (0.26 g, 1.0 mmol),
cyanamide (0.06 g, 1.3 mmol), potassium tert-butoxide (0.14 g,
1.2 mmol) and N-bromosuccinimide (0.27 g, 1.5 mmol) afforded,
without further purification, a yellow solid identified as 5m (0.21 g,
70%), mp 114–117 ꢀC. (Found: C, 64.07; H, 5.56; N, 8.92; S 11.07.
C16H16N2O2S requires C, 63.98; H, 5.37; N, 9.33; S 10.67%.) nmax (KBr)/
cmꢂ1 2924, 2141 (C^N stretch), 1615, 1509, 1496, 1256, 1153, 1106,
1021; dH (300 MHz) (CDCl3) 3.79 (3H, s, OCH3), 3.87 (3H, s, OCH3),
4.23 (1H, A of ABsystem, JAB 12.6, one of CH2), 4.50 (1H, B of ABsystem, JAB
12.6, one of CH2), 6.78–6.86 (2H, m, ArH), 6.95–7.11 (4H, m, ArH),
7.53–7.62 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 55.3, 55.7 (CH3, 2ꢁCH3
of OCH3), 58.1 (CH2, CH2), 114.5, 115.4 (CH, 2ꢁaromatic CH), 119.3,
4.5.35. N-Cyano-S-benzyl-S-(4-methoxyphenyl)sulfoximine
(6c). Following procedure C, the reaction of N-cyano-S-benzyl-S-
(4-methoxyphenyl)sulfilimine (5c) (0.40 g, 1.5 mmol), m-chloro-
perbenzoic acid (0.50 g, 77%, 4.5 mmol) and K2CO3 (0.62 g,
4.5 mmol) and subsequent purification by column chromatography
using hexane/ethyl acetate (60:40) afforded 6c as a white solid
(0.29 g, 68%), mp 129–133 ꢀC. (Found: C, 62.65; H, 4.93; N, 9.65; S
10.81. C15H14N2O2S requires C, 62.92; H, 4.93; N, 9.78; S 11.20%.)
nmax (KBr)/cmꢂ1 2965, 2185 (C^N stretch), 1590, 1495, 1247
(asymmetric SON stretch), 1172, 1090 (symmetric SON stretch); dH
(300 MHz) (CDCl3) 3.89 (3H, s, CH3), 4.59 (2H, s, CH2), 6.96 (2H, d, J

N. Barry et al. / Tetrahedron 65 (2009) 10660–10670
10667
9.3, ArH), 7.08 (2H, d, J 8.2, ArH), 7.23–7.44 (3H, m, ArH), 7.54 (2H, d,
J 9.3, ArH); dC (75.5 MHz) (CDCl3) 55.9 (CH3, CH3), 63.5 (CH2, CH2),
112.5 (C, C^N), 115.0 (CH, aromatic CH), 123.5, 125.9 (C, 2ꢁaromatic
C), 128.9, 129.8, 131.3, 131.5 (CH, 4ꢁaromatic CH), 165.1 (C, aromatic
C–O); m/z (ESI) 287 [(MþH)þ]; HRMS (ESI): exact mass calculated
for C15H15N2O2S [MþH]þ 287.0854, found 287.0850.
(symmetric SON stretch); dH (300 MHz) (CDCl3) 4.64 (2H, br s, CH2),
7.04–7.12 (2H, m, ArH), 7.24–7.49 (6H, m, ArH), 7.49–7.60 (1H, m,
ArH); dC (75.5 MHz) (CDCl3) 63.3 (CH2, CH2), 111.6 (C, C^N), 116.6
(CH, d, 2JC–F 24.8, aromatic CH),122.8 (CH, d, 2JC–F 21.8, aromatic CH),
4
125.0 (CH, d, JC–F 3.5, aromatic CH), 125.1 (C, aromatic C), 129.1,
3
130.2, 131.3 (CH, 3ꢁaromatic CH), 131.6 (CH, d, JC–F 7.5, aromatic
CH), 135.2 (C, d, 3JC–F 6.8, aromatic C), 162.5 (C, d, 1JC–F 252.8, C–F);
m/z (ESI) 275 [(MþH)þ]; HRMS (ESI): exact mass calculated for
C14H12FN2OS [MþH]þ 275.0654, found 275.0649.
4.5.36. N-Cyano-S-benzyl-S-(4-bromophenyl)sulfoximine
(6d). Following procedure C, the reaction of N-cyano-S-benzyl-S-
(4-bromophenyl)sulfilimine (5d) (0.40 g, 1.25 mmol), m-chloro-
perbenzoic acid (0.42 g, 77%, 1.88 mmol) and K2CO3 (0.52 g,
3.75 mmol) afforded, without further purification, a white solid
identified as 6d (0.35 g, 83%), mp 141–143 ꢀC. (Found: C, 50.13; H,
3.14; N, 8.26; S 9.83. C14H11BrN2OS requires C, 50.16; H, 3.31; N,
8.36; S 9.57.) nmax (KBr)/cmꢂ1 2918, 2184 (C^N stretch), 1570, 1494,
1246 (asymmetric SON stretch), 1204, 1190, 1070 (symmetric SON
stretch); dH (300 MHz) (CDCl3) 4.63 (2H, s, CH2), 7.04–7.12 (2H, m,
ArH), 7.24–7.50 (5H, m, ArH), 7.63–7.71 (2H, m, ArH); dC (75.5 MHz)
(CDCl3) 63.3 (CH2, CH2), 111.7 (C, C^N), 125.3 (C, aromatic C–Br),
129.1, 130.1, 130.6, 131.3 (CH, 4ꢁaromatic CH), 132.1 (C, aromatic C),
133.1 (CH, aromatic CH); m/z (ESI) 335, 337 (1:1) [(MþH)þ]; HRMS
(ESI): exact mass calculated for C14H1279BrN2OS [MþH]þ 334.9854,
found 334.9859.
4.5.40. N-Cyano-S-benzyl-S-(3-bromophenyl)sulfoximine
(6k). Following procedure C, the reaction of N-cyano-S-benzyl-S-
(3-bromophenyl)sulfilimine (5k) (0.15 g, 0.47 mmol), m-chloro-
perbenzoic acid (0.16 g, 77%, 0.71 mmol) and K2CO3 (0.19 g,
1.41 mmol) and subsequent purification by column chromatogra-
phy on silica gel using hexane/ethyl acetate (60:40) afforded 6k as
a white solid (0.11 g, 69%), mp 120–122 ꢀC; nmax (KBr)/cmꢂ1 2922,
2195 (C^N stretch), 1568, 1455, 1246 (asymmetric SON stretch),
1181, 1077 (symmetric SON stretch); dH (300 MHz) (CDCl3) 4.63
(2H, br s, CH2), 7.03–7.12 (2H, m, ArH), 7.28–7.47 (4H, m, ArH), 7.52–
7.58 (1H, m, ArH), 7.73 (1H, t, J 1.8, ArH), 7.81–7.87 (1H, m, ArH); dC
(75.5 MHz) (CDCl3) 63.5 (CH2, CH2), 123.8, 125.1 (C, 2ꢁaromatic C),
127.7, 129.1, 130.3, 131.0, 131.3, 131.9 (CH, 6ꢁaromatic CH), 135.0 (C,
aromatic C), 138.4 (CH, aromatic CH), 1ꢁC^N signal absent; m/z
(ESI) 335, 337 (1:1) [(MþH)þ]; HRMS (ESI): exact mass calculated
for C14H1279BrN2OS [MþH]þ 334.9854, found 334.9846.
4.5.37. N-Cyano-S-benzyl-S-(4-nitrophenyl)sulfoximine (6e). Follo-
wing procedure C, the reaction of N-cyano-S-benzyl-S-(4-nitro-
phenyl)sulfilimine (5e) (0.38 g, 1.30 mmol), m-chloroperbenzoic
acid (0.44 g, 77%, 1.95 mmol) and K2CO3 (0.54 g, 3.90 mmol) and
subsequent purification by column chromatography using hexane/
ethyl acetate (60:40) afforded 6e as a yellow solid (0.16 g, 41%), mp
145–148 ꢀC; nmax (KBr)/cmꢂ1 2931, 2197 (C^N stretch), 1607, 1533
(asymmetric NO2 stretch), 1494, 1455, 1346 (symmetric NO2
stretch), 1254 (asymmetric SON stretch), 1203, 1174, 1085 (sym-
metric SON stretch); dH (300 MHz) (CDCl3) 4.70 (2H, br s, CH2),
7.05–7.12 (2H, m, ArH), 7.18–7.47 (3H, m, ArH), 7.79–7.86 (2H, m,
ArH), 8.32–8.38 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 63.4 (CH2,
CH2), 124.6 (CH, aromatic CH), 124.7 (C, aromatic C), 129.3, 130.5,
130.8, 131.3 (CH, 4ꢁaromatic CH), 139.0, 151.7 (C, 2ꢁaromatic C),
1ꢁC^N signal absent; m/z (ESI) 302 [(MþH)þ]; HRMS (ESI): exact
mass calculated for C14H12N3O3S [MþH]þ 302.0599,. found
302.0599.
4.5.41. N-Cyano-S-benzyl-S-(2-methoxyphenyl)sulfoximine
(6l). Following procedure C, the reaction of N-cyano-S-benzyl-S-(2-
methoxyphenyl)sulfilimine (5l) (0.30 g, 1.10 mmol), m-chloro-
perbenzoic acid (0.37 g, 77%, 1.65 mmol) and K2CO3 (0.46 g,
3.33 mmol) and subsequent purification by column chromatogra-
phy using hexane/ethyl acetate (1:4) afforded 6l as a white solid
(0.05 g, 16%),y mp 145–148 ꢀC; nmax (KBr)/cmꢂ1 2929, 2186 (C^N
stretch), 1593, 1576, 1481, 1236 (asymmetric SON stretch), 1176,
1059 (symmetric SON stretch); dH (300 MHz) (CDCl3) 4.13 (3H, s,
CH3), 4.80 (1H, A of ABsystem, JAB 13.8, one of CH2), 4.94 (1H, B of
ABsystem, JAB 13.8, one of CH2), 7.01–7.09 (1H, m, ArH), 7.11–7.21 (3H,
m, ArH), 7.22–7.38 (3H, m, ArH), 7.61–7.72 (2H, m, ArH); dC
(75.5 MHz) (CDCl3) 57.0 (CH3, CH3), 60.5 (CH2, CH2), 112.3 (C, C^N),
112.9 (CH, aromatic CH), 120.9 (C, aromatic C), 121.6 (CH, aromatic
CH), 125.7 (C, aromatic C), 128.9, 129.8, 131.1, 131.9, 137.5 (CH,
5ꢁaromatic CH), 157.2 (C, aromatic C–O); m/z (ESI) 287 [(MþH)þ];
HRMS (ESI): exact mass calculated for C15H15N2O2S [MþH]þ
287.0854, found 287.0843.
4.5.38. N-Cyano-S-benzyl-S-(4-chlorophenyl)sulfoximine (6i). Follo-
wing procedure C, the reaction of N-cyano-S-benzyl-S-(4-chloro-
phenyl)sulfilimine (5i) (0.15 g, 0.55 mmol), m-chloroperbenzoic
acid (0.18 g, 77%, 0.83 mmol) and K2CO3 (0.23 g, 1.65 mmol) and
subsequent purification by column chromatography using hexane/
ethyl acetate (60:40) afforded 6i as a white solid (0.10 g, 63%), mp
123–126 ꢀC; nmax (KBr)/cmꢂ1 2920, 2193 (C^N stretch), 1571, 1475,
1247 (asymmetric SON stretch), 1182, 1084 (symmetric SON
stretch); dH (300 MHz) (CDCl3) 4.63 (2H, br s, CH2), 7.03–7.12 (2H,
m, ArH), 7.25–7.45 (3H, m, ArH), 7.46–7.59 (4H, m, ArH); dC
(75.5 MHz) (CDCl3) 63.4 (CH2, CH2), 111.8 (C, C^N), 125.3 (C, aro-
matic C), 129.1, 130.0, 130.1, 130.6, 131.3 (CH, 5ꢁaromatic CH), 131.5,
142.6 (C, 2ꢁaromatic C); m/z (ESI) 291, 293 (3:1) [(MþH)þ]; HRMS
(ESI): exact mass calculated for C14H1235ClN2OS [MþH]þ 291.0359,
found 291.0351.
4.5.42. N-Cyano-S-(4-methoxybenzyl)-S-(40-methoxyphenyl)sulf-
oximine (6m). Following procedure C, the reaction of N-cyano-S-(4-
methoxybenzyl)-S-(40-methoxyphenyl)sulfilimine (5m) (0.15 g,
0.50 mmol), m-chloroperbenzoic acid (0.17 g, 77%, 0.75 mmol) and
K2CO3 (0.21 g, 1.50 mmol) and subsequent purification by column
chromatography using hexane/ethyl acetate (70:30) afforded 6m as
a white solid (0.09 g, 56%), mp 160–164 ꢀC; nmax (KBr)/cmꢂ1 2964,
2184 (C^N stretch), 1611, 1586, 1571, 1247 (asymmetric SON
stretch), 1172, 1090 (symmetric SON stretch); dH (300 MHz) (CDCl3)
3.80 (3H, s, CH3), 3.89 (3H, s, CH3), 4.51 (1H, A of ABsystem, JAB 14.4,
one of CH2), 4.56 (1H, B of ABsystem, JAB 14.1, one of CH2), 6.76–6.84
(2H, m, ArH), 6.92–7.02 (4H, m, ArH), 7.49–7.58 (2H, m, ArH); dC
(75.5 MHz) (CDCl3) 55.3, 55.9 (CH3, 2ꢁCH3), 63.1 (CH2, CH2), 114.3,
115.0 (CH, 2ꢁaromatic CH), 117.6, 123.7 (C, 2ꢁaromatic C), 131.6,
132.7 (CH, 2ꢁaromatic CH), 160.8, 165.1 (C, 2ꢁaromatic C–O),
4.5.39. N-Cyano-S-benzyl-S-(3-fluorophenyl)sulfoximine (6j). Follo-
wing procedure C, the reaction of N-cyano-S-benzyl-S-(3-fluo-
rophenyl)sulfilimine (5j) (0.15 g, 0.58 mmol), m-chloroperbenzoic
acid (0.19 g, 77%, 0.87 mmol) and K2CO3 (0.24 g, 1.74 mmol) and
subsequent purification by column chromatography on silica gel
using hexane/ethyl acetate (60:40) afforded 6j as a white solid
(0.11 g, 69%), mp 130–131 ꢀC; nmax (KBr)/cmꢂ1 2967, 2194 (C^N
stretch), 1593, 1476, 1242 (asymmetric SON stretch), 1179, 1078
y
This reaction was repeated. Crude 1H NMR analysis showed molar ratio of 4l/5l/
6l was 1:2.1:1.

10668
N. Barry et al. / Tetrahedron 65 (2009) 10660–10670
1ꢁC^N signal absent; m/z (ESI) 317 [(MþH)þ]; HRMS (ESI): exact
mass calculated for C16H17N2O3S [MþH]þ 317.0960, found 317.0951.
nmax (KBr)/cmꢂ1 3403 (asymmetric NH2 stretch), 3192 (symmetric
NH2 stretch), 1654 (C]O stretch), 1593, 1499, 1362, 1269 (asym-
metric SON stretch), 1183, 1077 (symmetric SON stretch); dH
(300 MHz) (CDCl3) 3.86 (3H, s, OCH3), 4.74 (1H, A of ABsystem, JAB 13.5,
one of CH2), 4.96 (3H, B of ABsystem overlapping with br s, JAB 13.8, one
of CH2 and NH2), 6.85–6.92 (2H, m, ArH), 6.96–7.03 (2H, m, ArH),
7.18–7.34 (3H, m, ArH), 7.50–7.57 (2H, m, ArH); dC (75.5 MHz)(CDCl3)
55.7 (CH3, OCH3), 62.2 (CH2, CH2), 114.2 (CH, aromatic CH), 128.3 (C,
aromatic C), 128.4, 128.8, 130.9, 131.2 (CH, 4ꢁaromatic CH), 161.7,
163.8 (C, 1ꢁaromatic C–O, 1ꢁC]O); m/z (ESI) 305 [(MþH)þ]; HRMS
(ESI): exact mass calculated for C15H17N2O3S [MþH]þ 305.0960,
found 305.0953.
4.5.43. N-Cyano-S-benzyl-S-(4-fluorophenyl)sulfoximine
(6n). Following procedure C, the reaction of N-cyano-S-benzyl-S-
(4-fluorophenyl)sulfilimine (5n) (0.28 g, 1.08 mmol), m-chlor-
operbenzoic acid (0.36 g, 77%, 1.62 mmol) and K2CO3 (0.45 g,
3.25 mmol) and subsequent purification by column chromatogra-
phy on silica gel using hexane/ethyl acetate (60:40) afforded 6n as
a white solid (0.20 g, 67%), mp 137–139 ꢀC; nmax (KBr)/cmꢂ1 2973,
2193 (C^N stretch), 1592, 1493, 1255 (asymmetric SON stretch),
1157, 1089 (symmetric SON stretch); dH (300 MHz) (CDCl3) 4.63
(2H, br s, CH2), 7.02–7.10 (2H, m, ArH), 7.15–7.44 (5H, m, ArH), 7.58–
7.69 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 63.5 (CH2, CH2), 111.9 (C,
4.5.47. N-Carbamoyl-S-benzyl-S-(4-bromophenyl)sulfoximine
(7d). Following procedure D, the reaction of N-cyano-S-benzyl-S-(4-
bromophenyl)sulfoximine (6d) (0.30 g, 0.89 mmol) and trifluoro-
acetic acid (0.30 g, 0.21 mL, 2.67 mmol) and subsequent purification
by column chromatography on silica gel using hexane/ethyl acetate
(60:40) to ethyl acetate (100) afforded 7d as a white solid (0.13 g,
41%), mp 205–209 ꢀC; nmax (KBr)/cmꢂ1 3488 (asymmetric NH2
stretch), 3164 (symmetric NH2 stretch), 1660 (C]O stretch), 1593,
1570, 1456, 1367, 1218 (asymmetric SON stretch), 1065 (symmetric
SON stretch); dH (300 MHz) (CDCl3) 4.73 (1H, A of ABsystem, JAB 14.3,
one of CH2), 4.87 (2H, br s, NH2) overlapping with 4.91 (1H, B of
ABsystem, JAB 13.8, one of CH2), 6.95–7.05 (2H, m, ArH), 7.18–7.36 (3H,
m,ArH), 7.41–7.51(2H, m, ArH), 7.52–7.61(2H, m, ArH);dC (75.5 MHz)
(CDCl3)62.1 (CH2, CH2),127.6(C, aromatic C),128.6,129.2,130.3,131.2,
132.2 (CH, 5ꢁaromatic CH), 134.9 (C, aromatic C), 161.3 (C, C]O),
1ꢁaromatic C signal absent; m/z (ESI) 353, 355 (1:1) [(MþH)þ];
HRMS (ESI): exact mass calculated for C14H1479BrN2O2S [MþH]þ,
352.9959, found 352.9953.
2
C^N), 117.2 (CH, d, JC–F 23.3, aromatic CH), 125.5 (C, aromatic C),
128.8 (C, d, 4JC–F 3.0, aromatic C), 129.1, 130.1, 131.3 (CH, 3ꢁaromatic
CH), 132.3 (CH, d, 3JC–F 9.8, aromatic CH), 166.9 (C, d, 1JC–F 258.0, C–
F); m/z (ESI) 275 [(MþH)þ]; HRMS (ESI): exact mass calculated for
C14H12FN2OS [MþH]þ 275.0654, found 275.0651.
4.5.44. N-Carbamoyl-S-benzyl-S-phenyl sulfoximine (7a). Following
procedure D, the reaction of N-cyano-S-benzyl-S-phenyl sul-
foximine (6a) (0.09 g, 0.35 mmol) and trifluoroacetic acid (0.12 g,
0.08 mL, 1.05 mmol) and subsequent purification by column chro-
matography using hexane/ethyl acetate (60:40) afforded 7a as
a white solid (0.05 g, 52%), mp 175–178 ꢀC; nmax (KBr)/cmꢂ1 3430
(asymmetric NH2 stretch), 3193 (symmetric NH2 stretch), 1647
(C]O stretch), 1607, 1454, 1203 (asymmetric SON stretch), 1181,
1084 (symmetric SON stretch); dH (300 MHz) (CDCl3) 4.76 (1H, A of
ABsystem, JAB 13.8, one of CH2), 4.93 (3H, B of ABsystem overlapping
with br s, JAB 13.5, one of CH2 and NH2), 6.93–7.02 (2H, m, ArH), 7.15–
7.34 (3H, m, ArH), 7.39–7.50 (2H, m, ArH), 7.55–7.70 (3H, m, ArH); dC
(75.5 MHz) (CDCl3) 62.1 (CH2, CH2), 127.9 (C, aromatic C), 128.5,
128.7, 128.9, 129.0, 131.2, 133.7 (CH, 6ꢁaromatic CH), 135.6 (C, aro-
matic C),161.7 (C, C]O); m/z (ESI) 275 [(MþH)þ]; HRMS (ESI): exact
mass calculated for C14H15N2O2S [MþH]þ 275.0854, found 275.0841.
4.5.48. N-Carbamoyl-S-benzyl-S-(4-nitrophenyl)sulfoximine
(7e). Following procedure D, the reaction of N-cyano-S-benzyl-S-
(4-nitrophenyl)sulfoximine (6e) (0.12 g, 0.4 mmol) and trifluoro-
acetic acid (0.14 g, 0.09 mL, 1.2 mmol) and subsequent purification
by column chromatography on silica gel using hexane/ethyl acetate
(50:50) to ethyl acetate (100) afforded 7e as a yellow solid (0.07 g,
54%), mp 199–201 ꢀC; nmax (KBr)/cmꢂ1 3429 (asymmetric NH2
stretch), 3105 (symmetric NH2 stretch), 2924, 1652 (C]O stretch),
1589,1531 (asymmetric NO2 stretch),1386 (symmetric NO2 stretch),
1346, 1220 (asymmetric SON stretch), 1134, 1080 (symmetric SON
stretch); dH (300 MHz) (CDCl3) 4.76 (1H, A of ABsystem, JAB 13.8, one of
CH2), 4.91 (3H, B of ABsystem overlapping with br s, JAB 13.8, one of
CH2 and NH2), 6.98–7.05 (2H, m, ArH), 7.20–7.38 (3H, m, ArH), 7.77–
7.84 (2H, m, ArH), 8.21–8.29 (2H, m, ArH); dC (75.5 MHz) (CDCl3)
62.1 (CH2, CH2),123.9 (CH, aromatic CH),126.9 (C, aromatic C),128.8,
129.5, 130.2, 131.2 (CH, 4ꢁaromatic CH), 142.1, 150.7 (C, 2ꢁaromatic
C), 160.9 (C, C]O); m/z (ESI) 320 [(MþH)þ]; HRMS (ESI): exact mass
calculated for C14H14N3O4S [MþH]þ 320.0705, found 320.0720.
4.5.45. N-Carbamoyl-S-(4-fluorobenzyl)-S-(40-fluorophenyl)sulf-
oximine (7b). Following procedure D, the reaction of N-cyano-S-(4-
fluorobenzyl)-S-(40-fluorophenyl)sulfoximine (6b) (0.10 g, 0.34
mmol) and trifluoroacetic acid (0.12 g, 0.08 mL, 1.05 mmol) and
subsequent purification by column chromatography on silica gel
using hexane/ethyl acetate (60:40) to ethyl acetate (100) afforded
7b as a white solid (0.06 g, 70%), mp 189–192 ꢀC. (Found: C, 53.48;
H, 3.80; N, 9.09. C14H12F2N2O2S requires C, 54.19; H, 3.90; N, 9.03%.)
nmax (KBr)/cmꢂ1 3492 (asymmetric NH2 stretch), 3169 (symmetric
NH2 stretch), 1661 (C]O stretch), 1588, 1511, 1490, 1361, 1216
(asymmetric SON stretch), 1151, 1081 (symmetric SON stretch); dH
(300 MHz) (CDCl3) 4.73 (1H, A of ABsystem, JAB 13.8, one of CH2), 4.93
(3H, B of ABsystem overlapping with br s, JAB 13.8, one of CH2 and
NH2), 6.88–7.02 (4H, m, ArH), 7.08–7.20 (2H, m, ArH), 7.60–7.70 (2H,
2
m, ArH); dC (75.5 MHz) (CDCl3) 61.3 (CH2, CH2), 115.7 (CH, d, JC–F
4.5.49. N-Carbamoyl-S-benzyl-S-(4-chlorophenyl)sulfoximine
(7i). Following procedure D, the reaction of N-cyano-S-benzyl-S-(4-
chlorophenyl)sulfoximine (6i) (0.08 g, 0.28 mmol) and trifluoro-
acetic acid (0.09 g, 0.06 mL, 0.83 mmol) and subsequent purification
by column chromatography on silica gel using hexane/ethyl acetate
(60:40) to ethyl acetate (100) afforded 7i as a white solid (0.05 g,
56%), mp 213–216 ꢀC; nmax (KBr)/cmꢂ1 3488 (asymmetric NH2
stretch), 3166 (symmetric NH2 stretch), 1661 (C]O stretch), 1592,
1367, 1218 (asymmetric SON stretch), 1085 (symmetric SON
stretch); dH (300 MHz) (CDCl3) 4.74 (1H, A of ABsystem, JAB 13.8, one of
CH2), 4.88 (2H, br s, NH2) overlapping with 4.92 (1H, B of ABsystem, JAB
13.8, one of CH2), 7.00 (2H, d, J 7.2, ArH), 7.18–7.35 (3H, m, ArH), 7.36–
7.45 (2H, m, ArH), 7.50–7.61 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 62.1
(CH2, CH2),127.6 (C, aromatic C),128.6,129.2,129.2,130.2,131.2 (CH,
5ꢁaromatic CH), 134.2, 140.6 (C, 2ꢁaromatic C), 161.4 (C, C]O); m/z
21.8, aromatic CH), 116.4 (CH, d, 2JC–F 22.5, aromatic CH), 123.7 (C, d,
4JC–F 3.8, aromatic C), 131.2 (C, d, 4JC–F 3.0, aromatic C), 131.6 (CH, d,
3JC–F 9.0, aromatic CH), 132.9 (CH, d, 3JC–F 8.3, aromatic CH), 161.4 (C,
C]O), 163.2 (C, d, 1JC–F 248.3, C–F), 166.0 (C, d, 1JC–F 263.3, C–F); dF
(376.5 MHz) 50.15–50.20 (1F, m, aromatic C–F), 58.56–58.62 (1F, m,
aromatic C–F); m/z (ESI) 311 [(MþH)þ]; HRMS (ESI): exact mass
calculated for C14H13F2N2O2S [MþH]þ 311.0666,. found 311.0667.
4.5.46. N-Carbamoyl-S-benzyl-S-(4-methoxyphenyl)sulfoximine
(7c). Following procedureD, the reaction of N-cyano-S-benzyl-S-(4-
methoxyphenyl)sulfoximine (6c) (0.18 g, 0.6 mmol) and trifluoro-
acetic acid (0.21 g, 0.14 mL, 1.8 mmol) and subsequent purification
by column chromatography on silica gel using hexane/ethyl acetate
(60:40) afforded 7c as a white solid (0.08 g, 45%), mp 142–144 ꢀC;

N. Barry et al. / Tetrahedron 65 (2009) 10660–10670
10669
(ESI) 309, 311 (3:1) [(MþH)þ]; HRMS (ESI): exact mass calculated for
C14H1435ClN2O2S [MþH]þ 309.0465, found 309.0468.
(lit.21112–113 ꢀC); nmax (KBr)/cmꢂ13319 (NH stretch), 2925,1493,1445,
1216 (asymmetric SON stretch), 1110, 1084 (symmetric SON stretch),
974; dH (300 MHz) (CDCl3)2.80(1H,brs, NH),4.31(1H, AofABsystem, JAB
13.2, one of CH2), 4.40 (1H, B of ABsystem, JAB 13.2, one of CH2), 7.07–7.16
(2H, m, ArH), 7.23–7.38 (3H, m, ArH), 7.42–7.51 (2H, m, ArH), 7.54–7.63
(1H, m, ArH), 7.73–7.81 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 64.6 (CH2,
CH2), 128.5, 128.8, 128.9, 131.1, 133.1 (CH, 5ꢁaromatic CH), 140.3 (C,
aromatic C),1ꢁaromatic CH signal absent,1ꢁaromatic C signal absent.
4.5.50. N-Carbamoyl-S-benzyl-S-(3-fluorophenyl)sulfoximine
(7j). Following procedure D, the reaction of N-cyano-S-benzyl-S-(3-
fluorophenyl)sulfoximine (6j) (0.09 g, 0.31 mmol) and trifluoro-
acetic acid (0.11 g, 0.07 mL, 0.93 mmol) and subsequent purification
by column chromatography on silica gel using hexane/ethyl acetate
(60:40) to ethyl acetate (100) afforded 7j as a white solid (0.05 g,
56%), mp 134–136 ꢀC; nmax (KBr)/cmꢂ1 3374 (asymmetric NH2
stretch), 3192 (symmetric NH2 stretch), 1648 (C]O stretch), 1593,
1476, 1362, 1222 (asymmetric SON stretch), 1139, 1107 (symmetric
SON stretch); dH (300 MHz) (CDCl3) 4.75 (1H, A of ABsystem, JAB 13.8,
one of CH2), 4.91 (1H, B of ABsystem, JAB 13.8, one of CH2) overlapping
with 4.97 (2H, br s, NH2), 6.96–7.05 (2H, m, ArH), 7.18–7.51 (7H, m,
ArH); dC (75.5 MHz) (CDCl3) 62.1 (CH2, CH2), 116.2 (CH, d, 2JC–F 25.5,
aromatic CH),120.9 (CH, d, 2JC–F 21.0, aromatic CH),124.5 (CH, d, 4JC–F
3.8, aromatic CH),127.5 (C, aromatic C),128.6,129.2 (CH, 2ꢁaromatic
4.5.54. S-(4-Fluorobenzyl)-S-(40-fluorophenyl)-NH-sulfoximine
(8b). Following procedure E, the reaction of N-carbamoyl-S-(4-fluo-
robenzyl)-S-(40-fluorophenyl)sulfoximine (7b) (0.18 g, 0.58 mmol)
and K2CO3 (0.40 g, 2.90 mmol) and subsequent purification by col-
umn chromatography on silica gel using hexane/ethyl acetate (60:40)
afforded 8b as a white solid (0.06 g, 38%), mp 122–124 ꢀC; nmax (KBr)/
cmꢂ1 3269 (NH stretch), 2918, 1602, 1594, 1506, 1496, 1230 (asym-
metric SON stretch), 1086 (symmetric SON stretch); dH (300 MHz)
(CDCl3) 2.78(1H, brs, NH), 4.27 (1H, AofABsystem, JAB 13.8, oneofCH2),
4.35 (1H, B of ABsystem, JAB 13.8, one of CH2), 6.91–7.03 (2H, m, ArH),
7.04–7.19 (4H, m, ArH), 7.68–7.80 (2H, m, ArH); dC (75.5 MHz) (CDCl3)
63.9 (CH2, CH2),115.7 (CH, d, 2JC–F 21.5, aromatic CH),116.2 (CH, d, 2JC–F
22.4, aromatic CH),124.5 (C, d, 4JC–F 3.3, aromatic C),131.7 (CH, d, 3JC–F
9.5, aromatic CH),132.8 (CH, d, 3JC–F 8.5, aromatic CH),163.2 (C, d,1JC–F
247.3, C–F), 165.7 (C, d, 1JC–F 254.2, C–F), 1ꢁaromatic C signal absent;
m/z (ESI) 268 [(MþH)þ]; HRMS (ESI): exact mass calculated for
C13H12F2NOS [MþH]þ 268.0608, found 268.0595.
3
CH), 130.7 (CH, d, JC–F 7.7, aromatic CH), 131.2 (CH, aromatic CH),
3
137.9 (C, d, JC–F 6.9, aromatic C), 161.4 (C, C]O), 162.3 (C, d, 1JC–F
251.25, C–F); m/z (ESI) 293 [(MþH)þ]; HRMS (ESI): exact mass cal-
culated for C14H14FN2O2S [MþH]þ 293.0760, found 293.0761.
4.5.51. N-Carbamoyl-S-benzyl-S-(3-bromophenyl)sulfoximine
(7k). Following procedure D, the reaction of N-cyano-S-benzyl-S-(3-
bromophenyl)sulfoximine (6k) (0.45 g, 1.35 mmol) and trifluoro-
acetic acid (0.46 g, 0.31 mL, 4.00 mmol) and subsequent purification
by column chromatography on silica gel using hexane/ethyl acetate
(60:40) to ethyl acetate (100) afforded 7k as a white solid (0.56 g,
38%), mp 138–140 ꢀC; nmax (KBr)/cmꢂ1 3473 (asymmetric NH2
stretch), 3187 (symmetric NH2 stretch), 1650 (C]O stretch), 1586,
1570, 1456, 1359, 1222 (asymmetric SON stretch), 1141, 1114 (sym-
metric SON stretch); dH (300 MHz) (CDCl3) 4.73 (1H, A of ABsystem, JAB
13.8, one of CH2), 4.91 (1H, B of ABsystem, JAB 13.8, one of CH2) over-
lapping with 4.97 (2H, br s, NH2), 6.95–7.05 (2H, m, ArH), 7.19–7.39
(4H, m, ArH), 7.50–7.61 (1H, m, ArH), 7.67–7.78 (2H, m, ArH); dC
(75.5 MHz) (CDCl3) 62.2 (CH2, CH2), 122.9 (C, aromatic C–Br), 127.3
(CH, aromatic CH), 127.5 (C, aromatic C), 128.6, 129.3, 130.3, 131.2,
131.6, 136.7 (CH, 6ꢁaromatic CH), 137.6 (C, aromatic C), 161.4 (C,
C]O); m/z (ESI) 353, 355 (1:1) [(MþH)þ]; HRMS (ESI): exact mass
calculated for C14H1479BrN2O2S [MþH]þ 352.9955, found 352.9959.
4.5.55. S-Benzyl-S-(4-methoxyphenyl)-NH-sulfoximine (8c). Follo-
wing procedure E, the reaction of N-carbamoyl-S-benzyl-S-(4-
methoxyphenyl)sulfoximine (7c) (0.07 g, 0.23 mmol) and K2CO3
(0.21 g, 1.50 mmol) afforded, without further purification, a white
solid identified as 8c (0.04 g, 67%), mp 96–99 ꢀC. (Found: C, 63.97;
H, 5.78; N, 5.46; S 11.95. C14H15NO2S requires C, 64.34; H, 5.79; N,
5.36; S 12.27%.) nmax (KBr)/cmꢂ1 3313 (NH stretch), 2909, 1595,
1575, 1496, 1455, 1214 (asymmetric SON stretch), 1106, 1078
(symmetric SON stretch); dH (300 MHz) (CDCl3) 2.72 (1H, br s, NH),
3.86 (3H, s, OCH3), 4.28 (1H, A of ABsystem, JAB 13.1, one of CH2), 4.37
(1H, B of ABsystem, JAB 13.3, one of CH2), 6.86–6.94 (2H, m, ArH),
7.07–7.15 (2H, m, ArH), 7.22–7.37 (3H, m, ArH), 7.61–7.70 (2H, m,
ArH); dC (75.5 MHz) (CDCl3) 55.6 (CH3, CH3 of OCH3), 64.9 (CH2,
CH2), 114.0, 128.4, 128.7 (CH, 3ꢁaromatic CH), 129.0 (C, aromatic C),
131.01, 131.04 (CH, 2ꢁaromatic CH), 131.9 (C, aromatic C), 163.4 (C,
aromatic C–O); m/z (ESI) 262 [(MþH)þ]; HRMS (ESI): exact mass
calculated for C14H16NO2S [MþH]þ 262.0902, found 262.0902.
4.5.52. N-Carbamoyl-S-benzyl-S-(4-fluorophenyl)sulfoximine
(7n). Following procedure D, the reaction of N-cyano-S-benzyl-S-(4-
fluorophenyl)sulfoximine (6n) (0.14 g, 0.51 mmol) and trifluoroacetic
acid (0.17 g, 0.12 mL, 1.53 mmol) and subsequent purification by col-
umn chromatography on silica gel using hexane/ethyl acetate (60:40)
to ethyl acetate (100) afforded 7n as a white solid (0.12 g, 80%), mp
155–158 ꢀC; nmax (KBr)/cmꢂ1 3430 (asymmetric NH2 stretch), 3193
(symmetric NH2 stretch), 1648 (C]O stretch), 1592, 1494, 1365, 1244
(asymmetric SON stretch), 1137, 1081 (symmetric SON stretch); dH
(300 MHz) (CDCl3) 4.74 (1H, A of ABsystem, JAB 13.5, one of CH2), 4.88
(2H, br s, NH2) overlapping with 4.94 (1H, B of ABsystem, JAB 13.8, one of
CH2), 6.95–7.03 (2H, m, ArH), 7.05–7.15 (2H, m, ArH), 7.18–7.36 (3H, m,
ArH), 7.57–7.67 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 62.2 (CH2, CH2),
116.2 (CH, d, 2JC–F 22.5, aromaticCH),127.8(C, aromaticC),128.6, 129.1,
131.2 (CH, 3ꢁaromatic CH), 131.6 (CH, d, 3JC–F 9.0, aromatic CH), 161.4
(C, C]O),165.9 (C, d,1JC–F 255.0, C–F),1ꢁaromatic C signalabsent; m/z
(ESI) 293 [(MþH)þ]; HRMS (ESI): exact mass calculated for
C14H14FN2O2S [MþH]þ 293.0750, found 293.0760.
4.5.56. S-Benzyl-S-(4-bromophenyl)-NH-sulfoximine
(8d). Follo-
wing procedure E, the reaction of N-carbamoyl-S-benzyl-S-(4-bro-
mophenyl)sulfoximine (7d) (0.08 g, 0.23 mmol) and K2CO3 (0.16 g,
1.10 mmol) and subsequent purification by column chromatography
on silica gel using hexane/ethyl acetate (70:30) to ethyl acetate (100)
afforded 8d as a white solid (0.04 g, 60%), mp 114–115 ꢀC. (Found: C,
50.07;H,3.79;N,4.37;S10.32. C13H12BrNOSrequiresC,50.33;H, 3.90;
N,4.52;S10.34%.)nmax (KBr)/cmꢂ13240(NHstretch),1571,1495,1466,
1456, 1386, 1228 (asymmetric SON stretch), 1163, 1065 (symmetric
SON stretch); dH (300 MHz) (CDCl3) 2.80 (1H, br s, NH), 4.30 (1H, A of
ABsystem, JAB 13.7, one of CH2), 4.38 (1H, B of ABsystem, JAB 13.3, one of
CH2), 7.08–7.15 (2H, m, ArH), 7.24–7.39 (3H, m, ArH), 7.54–7.63 (4H, m,
ArH); dC (75.5 MHz) (CDCl3) 64.7 (CH2, CH2), 128.4, 128.5 (C,
2ꢁaromatic C), 128.6, 129.0 130.5, 131.1, 132.1 (CH, 5ꢁaromatic CH),
139.6 (C, aromatic C); m/z (ESI) 310, 312 (1:1) [(MþH)þ]; HRMS (ESI):
exact mass calculated for C13H1379BrNOS [MþH]þ 309.9901, found
309.9909.
4.5.53. S-Benzyl-S-phenyl-NH-sulfoximine (2)21. Following pro-
cedure E, the reaction of N-carbamoyl-S-benzyl-S-phenyl sulfoximine
(7a) (0.21 g, 0.76 mmol) and K2CO3 (0.53 g, 3.83 mmol) and sub-
sequent purification by column chromatography using ethyl acetate/
acetone (2:1) afforded 2 as a white solid (0.03 g, 17%), mp 106–110 ꢀC
4.5.57. S-Benzyl-S-(4-chlorophenyl)-NH-sulfoximine (8i). Following
procedure E, the reaction of N-carbamoyl-S-benzyl-S-(4-chloro-
phenyl)sulfoximine (7i) (0.04 g, 0.13 mmol) and K2CO3 (0.09 g,

10670
N. Barry et al. / Tetrahedron 65 (2009) 10660–10670
0.65 mmol) and subsequent purification by column chromatography
on silica gel using hexane/ethyl acetate (60:40) afforded 8i as a white
solid (0.03 g, 86%), mp 98–100 ꢀC; nmax (KBr)/cmꢂ13254 (NH stretch),
2912, 1572, 1470, 1454, 1385, 1230 (asymmetric SON stretch), 1086
(symmetric SON stretch), 1008; dH (300 MHz) (CDCl3) 2.80 (1H, br s,
NH), 4.30 (1H, A of ABsystem, JAB 13.5, one of CH2), 4.39 (1H, B of
ABsystem, JAB 13.5, one of CH2), 7.08–7.15(2H, m, ArH), 7.24–7.45(5H, m,
ArH), 7.63–7.71 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 64.7 (CH2, CH2),
128.4 (C, aromatic C), 128.6, 129.0 129.1, 130.4, 131.1 (CH, 5ꢁaromatic
CH), 139.9 (C, aromatic C), 1ꢁaromatic C signal absent; m/z (ESI) 266,
268 (3:1) [(MþH)þ]; HRMS (ESI): exact mass calculated for
C13H1335ClNOS [MþH]þ 266.0406, found 266.0403.
afforded 8n as a white solid (0.03 g, 38%), mp 107–109 ꢀC; nmax (KBr)/
cmꢂ1 3269 (NH stretch), 2918,1591,1497,1455,1234 (asymmetric SON
stretch),1110 (symmetric SON stretch); dH (300 MHz) (CDCl3) 2.78 (1H,
br s, NH), 4.30 (1H, A of ABsystem, JAB 13.5, one of CH2), 4.39 (1H, B of
ABsystem, JAB 13.5, one of CH2), 7.05–7.17 (4H, m, ArH), 7.24–7.39 (3H, m,
ArH), 7.69–7.80 (2H, m, ArH); dC (75.5 MHz) (CDCl3) 64.9 (CH2, CH2),
2
116.0 (CH, d, JC–F 22.5, aromatic CH), 128.6, 128.9, 131.0 (CH,
3ꢁaromatic CH), 131.7 (CH, d, 3JC–F 9.0, aromatic CH), 165.6 (C, d, 1JC–F
253.5, C–F), 2ꢁaromatic C signal absent; m/z (ESI) 250 [(MþH)þ];
HRMS (ESI): exact mass calculated for C13H13FNOS [MþH]þ 250.0702,
found 250.0711.
References and notes
4.5.58. S-Benzyl-S-(3-fluorophenyl)-NH-sulfoximine (8j). Following
procedure E, the reaction of N-carbamoyl-S-benzyl-S-(3-fluo-
rophenyl)sulfoximine (7j) (0.21 g, 0.72 mmol) and K2CO3 (0.50 g,
3.59 mmol) and subsequent purification by column chromatogra-
phy on silica gel using hexane/ethyl acetate (70:30) afforded 8j as
a white solid (0.11 g, 61%), mp 90–92 ꢀC; nmax (KBr)/cmꢂ1 3318 (NH
stretch), 2924, 1588, 1472, 1456, 1268, 1219 (asymmetric SON
stretch), 1107 (symmetric SON stretch); dH (300 MHz) (CDCl3) 2.82
(1H, br s, NH), 4.36 (1H, A of ABsystem, JAB 13.5, one of CH2), 4.40 (1H, B
of ABsystem, JAB 13.2, one of CH2), 7.09–7.17 (2H, m, ArH), 7.23–7.39
(4H, m, ArH), 7.40–7.50 (2H, m, ArH), 7.53–7.58 (1H, m, ArH); dC
(75.5 MHz) (CDCl3) 64.6 (CH2, CH2),116.3 (CH, d, 2JC–F 24.0, aromatic
1. (a) Bentley, H. R.; McDermott, E. E.; Pace, J.; Whitehead, J. K.; Moran, T. Nature
1950, 165, 150; (b) Whitehead, J. R.; Bentley, H. R. J. Chem. Soc. 1952, 1572.
2. (a) Reggelin, M.; Zur, C. Synthesis 2000, 1; (b) Johnson, C. R. Acc. Chem. Res. 1973,
6, 341; (c) Pyne, S. G. Sulfur Rep. 1992, 12, 57.
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9. Siu, T.; Yudin, A. K. Org. Lett. 2002, 4, 1839.
10. (a) Yoshida, T.; Naruto, S.; Uno, H.; Nishimura, H. Chem. Pharm. Bull. 1982, 30,
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Jansson, J.; Moessner, C.; Bolm, C. Org. Lett. 2004, 19, 3293; (d) Muller, J. F. K.;
Neuberger, M.; Spingler, B. Angew. Chem., Int. Ed. 1999, 38, 3549; (e) Pyne, S. G.;
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2
4
CH), 120.3 (CH, d, JC–F 21.0, aromatic CH), 124.7 (CH, d, JC–F 3.8,
aromatic CH), 128.2 (C, aromatic C), 128.6, 129.0 (CH, 2ꢁaromatic
3
CH), 130.5 (CH, d, JC–F 7.5, aromatic CH), 131.0 (CH, aromatic CH),
3
142.8 (C, d, JC–F 6.0, aromatic C), 162.3 (C, d, 1JC–F 249.8, C–F); m/z
(ESI) 250 [(MþH)þ]; HRMS (ESI): exact mass calculated for
C13H13FNOS [MþH]þ 250.0702, found 250.0712.
4.5.59. S-Benzyl-S-(3-bromophenyl)-NH-sulfoximine
(8k). Follo-
wing procedure E, the reaction of N-carbamoyl-S-benzyl-S-(3-bro-
mophenyl)sulfoximine (7k) (0.21 g, 0.59 mmol) and K2CO3 (0.41 g,
2.97 mmol) and subsequent purification by column chromatogra-
phy on silica gel using hexane/ethyl acetate (70:30) afforded 8k as
a white solid (0.09 g, 50%), mp 110–111 ꢀC; nmax (KBr)/cmꢂ1 3260
(NH stretch), 2915, 1566, 1493, 1454, 1409, 1234 (asymmetric SON
stretch), 1141 (symmetric SON stretch), 1025; dH (300 MHz) (CDCl3)
2.82 (1H, br s, NH), 4.30 (1H, A of ABsystem, JAB 13.5, one of CH2), 4.39
(1H, B of ABsystem, JAB 13.2, one of CH2), 7.09–7.17 (2H, m, ArH), 7.24–
7.41 (4H, m, ArH), 7.63–7.74 (2H, m, ArH), 7.90 (1H, t, J 2.1, ArH); dC
(75.5 MHz) (CDCl3) 64.7 (CH2, CH2), 122.9 (C, aromatic C–Br), 127.4
(CH, aromatic CH), 128.2 (C, aromatic C), 128.6, 129.0, 130.3, 131.1,
131.8, 136.1 (CH, 6ꢁaromatic CH), 142.5 (C, aromatic C); m/z (ESI)
310, 312 (1:1) [(MþH)þ]; HRMS (ESI): exact mass calculated for
C13H1379BrNOS [MþH]þ 309.9901, found 309.9901.
11. Bach, T.; Korber, C. Eur. J. Org. Chem. 1999, 1033.
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4.5.60. S-Benzyl-S-(4-fluorophenyl)-NH-sulfoximine (8n). Following
procedure E, the reaction of N-carbamoyl-S-benzyl-S-(4-fluo-
rophenyl)sulfoximine (7n) (0.10 g, 0.32 mmol) and K2CO3 (0.22 g,
1.62 mmol) and subsequent purification by column chromatography
on silica gel using hexane/ethyl acetate (70:30) to ethyl acetate (100)
24. Capozzi, M. A. M. J. Chem. Soc. 1971, 3018.