Copper-Catalyzed N -Arylation of Sulfoximines with Arylboronic Acids under Mild Conditions

Article abstract of DOI:10.1055/s-0037-1612216

N -Arylation of sulfoximines with different arylboronic acids, including sterically hindered boronic acids, is achieved using copper(I) iodide and 4-DMAP at room temperature. Moreover, N -arylation of biologically relevant l -methionine sulfoximine is demonstrated for the first time. All these reactions provided the desired products in excellent yields within a short span of time. The optimized reaction conditions are well suited to the task of N -vinylation of sulfoximine with trans -2-phenylvinylboronic acid.

Full text of DOI:10.1055/s-0037-1612216

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–L
paper
A
en
S. Gupta et al.
Paper
Synthesis
Copper-Catalyzed N-Arylation of Sulfoximines with Arylboronic
Acids under Mild Conditions
Surabhi Guptaa
Siddharth Baranwala
Nalluchamy Muniyappanb
Shahulhameed Sabiahb
Jeyakumar Kandasamy*a
R3
CuI (0.1 equiv)
R3
N
S
O
NH
S
DMAP (1.0 equiv)
OH
OH
R1
R2
R1
R2
+
B
MeOH, RT
open air
O
0
0
0
0-0
0
0
3-3
2
8
5-
9
7
1
X
>50 examples
excellent yields
R1, R2 = alkyl, aryl
3 = alkyl, aryl, halogen, OMe, SMe, NO2, etc.
a Department of Chemistry, Indian Institute of
Technology (BHU), 221005 Varanasi, Uttar
Pradesh, India
R
jeyakumar.chy@iitbhu.ac.in
b Department of Chemistry, Pondicherry University,
605014 Pondicherry, India
Received: 07.12.2018
Accepted after revision: 16.01.2019
Published online: 19.02.2019
this method also has some limitations. For example, N-ary-
lation of sulfoximine failed with sterically hindered 2,4,6-
trimethylphenylboronic acid. Moreover, this method also
requires excess amount of arylboronic acids and longer re-
action time.
DOI: 10.1055/s-0037-1612216; Art ID: ss-2018-t0825-op
Abstract N-Arylation of sulfoximines with different arylboronic acids,
including sterically hindered boronic acids, is achieved using copper(I)
iodide and 4-DMAP at room temperature. Moreover, N-arylation of bio-
logically relevant L-methionine sulfoximine is demonstrated for the first
time. All these reactions provided the desired products in excellent
yields within a short span of time. The optimized reaction conditions
are well suited to the task of N-vinylation of sulfoximine with trans-2-
phenylvinylboronic acid.
It is well known that the nitrogen atom in the sulfoxi-
mine possesses poor nucleophilicity when compared with
alkyl secondary amines,12 which usually necessitates differ-
ent reaction conditions for different N-functionalization re-
actions. In this context, we have envisioned that optimizing
the reaction conditions with different copper salts in the
presence of ligands/bases might lead to delightful results
with respect to sterically hindered arylboronic acids. In
continuation of our previous work on sulfoximine chemis-
try,13 here we disclose an efficient method for the N-aryla-
tion of sulfoximines with sterically hindered arylboronic
acids in the presence of copper(I) iodide and 4-DMAP at
room temperature.
At the outset, optimization of the reaction conditions
was investigated with S-methyl-S-phenylsulfoximine (1a)
and sterically hindered 2,4,6-trimethylphenylboronic acid
(2a) in the presence of various copper(I) and copper(II)
salts (10 mol%) in methanol (Table 1, entries 1–5). The de-
sired product was not observed even after 24 hours at room
temperature with Cu(OAc)2, CuSO4, CuCl, CuBr, and CuI. It is
well known that ligands and bases play an important role in
cross-coupling reactions particularly if the substrates are
poorly reactive or sterically hindered.14 Recently, Phukan
and co-workers disclosed the reaction of copper(I) iodide
with 4-DMAP, which provides Cu[(DMAP)4I]I complex in
DMSO.14e This complex shows excellent catalytic activity in
Chan–Lam reactions.14e In fact, we have recently demon-
strated N-alkylation of sulfoximines with alkylboronic acids
in the presence of copper(II) acetate and pyridine.13 In light
of this, N-arylation was performed with copper(II) acetate
in the presence of pyridine as well as 4-DMAP in methanol.
Key words arylation, boronic acid, sulfoximine, catalysis, copper
Sulfoximines are mono-aza analogues of sulfones that
have been of considerable interest in chemistry and biolo-
gy.1 It has been noticed that functionalization of sulfoxi-
mines at the nitrogen center displays interesting biological
and chemical properties. In this context, N-arylsulfoxi-
mines have been explored as efficient chiral ligands in
asymmetric catalysis.2a–e On the other hand, Gnamm et al.
have recently reported that N-arylsulfoximines exhibit in-
teresting physicochemical and in vitro properties that are
significant for drug discovery.1c N-Arylation of sulfoximine
can be achieved with numerous aryl donors3 such as aryl
halides,4 arylboronic acids,5 aryl sulfonates,6 aryl siloxanes,7
arynes,8 diaryliodonium salt,9 etc.,10 in the presence of Cu,
Pd, Fe, and Ni catalysts.
Among them, Bolm’s copper-mediated Chan–Lam11
coupling of sulfoximine with arylboronic acids was found
to be more advantageous from a synthetic perspective.5
This is because the N-arylation takes place at room tem-
perature in the presence of catalytic amount of copper(II)
acetate under mild reaction conditions. Moreover, aryl-
boronic acids are cheap and more accessible and can be eas-
ily stored and handled. Despite having many advantages,
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S. Gupta et al.
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Synthesis
Table 1 Optimization of the Reaction Conditionsa
(89%) within 4 hours under open air (entry 16). Further-
more, N-arylation was investigated with nickel salts such as
NiCl2 and Ni(OAc)2 in the presence of different additives,
which was previously explored in Chan–Lam coupling reac-
tions (entries 17–20).15 These reactions did not provide the
desired product even after 12 hours at room temperature.
Having established the optimized conditions, N-aryla-
tion of different sulfoximines with 2,4,6-trimethylphenyl-
boronic acid (2a) was investigated (Scheme 1). To our de-
light, the substrates bearing linear and branched alkyl
chains underwent N-arylation smoothly and provided the
desired products 3ba and 3ca in 85–87% yields. It is worth
noting that the sterically hindered S-isopropyl-S-phenyl-
sulfoximine also participated in the coupling reaction with
equal efficiency (Scheme 1, 3ca). Moreover, the substitu-
tions on the aryl ring of the sulfoximine (electron-donating
or -withdrawing) did not affect the progress of the reaction
significantly (3da–fa). Encouraged, we further attempted
the N-arylation of S,S-diphenyl, S-benzyl-S-phenyl, S,S-
dibenzyl, and S,S-dialkyl sulfoximines as well as heterocy-
clic sulfoximine with 2,4,6-trimethylphenylboronic acid. To
our delight, all these substrates underwent N-arylation
smoothly in 71–92% yields (3ga–ka). Likewise, other steri-
cally hindered ortho-substituted arylboronic acids such as
2,6-dimethyl- and 2,6-dimethoxyphenylboronic acids also
gave N-arylated products 3ab and 3ac in 84% and 81% yield,
respectively, in 3–4 hours.
Me
N
HO
OH
B
HN
Me
Me
O
Me
Me
Cu salt
S
+
O
Me
S
base
MeOH
RT
Me
Me
1a
2a
3aa
Entry
Catalyst (10 mol%)
Base (1 equiv)
Time (h)
Yield (%)b
1
2
Cu(OAc)2
CuSO4
–
24
24
24
24
24
12
12
12
12
12
12
12
12
12
12
4
n.r
n.r
n.r
n.r
n.r
59
77
n.r
n.r
7
–
3
CuCl
–
4
CuBr
–
5
CuI
–
6
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
CuSO4
Py
7
4-DMAP
DABCO
DBU
8
9
10
11
12
13
14
15
16
17
18
19
20
Et3N
2,2′-bipy
K2CO3
4-DMAP
4-DMAP
4-DMAP
4-DMAP
4-DMAP
4-DMAP
2,2′-bipy/DBU
DBU
n.r
n.r
20
60
69
89
n.r
n.r
n.rc
n.rd
CuCl
Further, we have investigated the N-arylation of differ-
ent sulfoximines with sterically less hindered arylboronic
acids (Scheme 2). 4-Methylphenylboronic acid was chosen
as a common aryl donor and was employed in the coupling
reaction with a variety of sulfoximines under optimized
conditions. To our delight, all these reactions proceeded
smoothly with excellent yields within 2 hours (Scheme 2,
3ad–nd).
CuBr
CuI
NiCl2·6H2O
Ni(OAc)2·4H2O
NiCl2·6H2O
Ni(OAc)2·4H2O
12
12
12
12
a Reaction conditions: 1a (155 mg, 1.0 mmol), 2a (1.5 equiv), copper salt
(0.1 equiv), and base (1.0 equiv) were stirred in MeOH (2 mL) under open
air.
Having explored the substrate scope with different sulf-
oximines, N-arylation with different boronic acids was in-
vestigated (Scheme 3). In this context, S-methyl-S-phenyl-
sulfoximine (1a) was subjected to the coupling reaction
with arylboronic acids bearing different functional groups
under optimized conditions and the results are summa-
rized in Scheme 3. Arylboronic acids having electron-do-
nating (e.g., Et, OMe, and SMe) and -withdrawing groups (F,
Cl, Br, and NO2) at the para or meta positions were success-
fully coupled with sulfoximine 1a in 78–91% yields (Scheme
3, 3ae–an). Further, to investigate the versatility of the de-
veloped methodology, arylboronic acids bearing sensitive
functional groups such as vinyl, formyl, acyl, and nitrile
were employed for N-arylation reactions. To our delight, the
coupling reactions preceded smoothly, giving 40–82%
yields under optimized reaction conditions (3ao–ar). Like-
wise, more conjugated arylboronic acids such as naphthyl-
and biphenylboronic acids also participated in coupling re-
b Isolated yield; n.r. = no reaction.
c Reaction was carried out in MeCN.
d Reaction was carried out in DMSO.
To our delight, the N-arylation proceeded smoothly, and N-
(2,4,6-trimethyl)phenyl-S-methyl-S-phenylsulfoximine
(3aa) was obtained in 59% and 77% yield, respectively (en-
tries 6 and 7).
The reaction was further investigated with various or-
ganic and inorganic bases such as DABCO, DBU, Et3N, 2,2′-
bipyridine and K2CO3 (Table 1, entries 8–12). Unfortunately,
reactions did not proceed well with these additives. Hence,
optimization was further investigated with different copper
salts in the presence of 4-DMAP in methanol at room tem-
perature (entries 13–16). Among all, copper(I) iodide/4-
DMAP system gave the desired product 3aa in high yield
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S. Gupta et al.
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Synthesis
action efficiently (3as–au). Similarly, N-arylation of dialkyl-
sulfoximines was achieved in excellent yields (3me and 3mk).
Methionine sulfoximine (MSO) is a biologically relevant
sulfoximine that plays an important role in drug discov-
ery.16 It is noteworthy that so far no method has been devel-
oped for the N-arylation of methionine sulfoximine. In this
context, protected L-methionine sulfoximine was subjected
to N-arylation with simple as well as sterically hindered
arylboronic acids (Scheme 4). To our delight, N-arylated L-
methionine sulfoximines were obtained in 78–91% yield
Me
HO
OH
B
R4
O
NH
CuI, DMAP
S
R1
+
HO
OH
R2
MeOH
RT
O
B
N
NH
R2
R3
O
R3
O
CuI, DMAP
S
R3
R3
R1
3ad–nd
Me
Me
S
open air
+
R2
N
R1
MeOH, RT
open air
S
1a–n
Me
2d
R2
R1
R4
Me
Me
Me
N
Me
Me
O
O
O
O
N
N
N
N
Me
O
Me
Me
O
Me
Me
O
Me
N
S
S
S
S
N
Me
Et
n-Pr
i-Pr
S
S
S
n-hept
i-Pr
Et
MeO
3ad
(1 h, 91%)
3bd
3cd
3dd
3ba
3ca
3da
(2 h, 90%)
(45 min, 92%)
(45 min, 92%)
(90 min, 87%)
(3 h, 87%)
(6 h, 85%)c
Me
N
Me
Me
Me
Me
Me
N
Me
N
O
S
O
N
O
N
Me
O
Me
O
Me
O
Me
Me
O
Me
N
S
S
S
N
S
Me
Me
S
S
Me
n-Hept
Me
Me
Me
O2N
Br
O2N
Br
3ed
3fd
3gd
3hd
(90 min, 90%)
(1 h, 89%)
(45 min, 92%)
(2 h, 91%)
3ea
3fa
3ga
(3 h, 88%)
(3 h, 87%)
(3 h, 84%)
Me
Me
Me
Me
O
N
N
S
O
Me
Me
N
S
Me
O
Me
N
S
S
O
3id
3jd
CCDC:1848196
(1 h, 84%)
(1 h, 83%)
3ha
3ia
CCDC:1862831
Me
Me
(4 h, 81%)
(4 h, 82%)
Me
Me
Me
N
Me
O
O
N
Me
Me MeO
OMe
N
N
N
S
Me
Me
O
O
Me
Me
S
S
N
N
O
Bn
S
Bu
Et
Bn
Bu
S
S
n-hept
N
S
O
S
N
Me
Me
O
O
Bu
Bu
Et
N
3kd
3ld
3md
(1 h, 91%)
3nd
(90 min,
81%)
(2 h, 93%)
(1 h, 83%)
3ja
3ka
(3 h, 92%)
3ab
(3 h, 84%)
3ac
(4 h, 81%)
(3 h, 71%)
Scheme 1 N-Arylation of sulfoximine 1a using sterically hindered aryl-
boronic acids. Reagents and conditions: Sulfoximine (150 mg, 1 equiv),
arylboronic acid (1.5 equiv), CuI (0.1 equiv), and DMAP (1.0 equiv) were
stirred in MeOH (2 mL) under open air. Isolated yields are shown. For
3ac, arylboronic acid (2.4 equiv) and CuI (0.2 equiv) were used.
Scheme 2 N-Arylation of various sulfoximines using 4-methylphenyl-
boronic acid. Reagents and conditions: Sulfoximine (150 mg, 1 equiv), 4-
methylphenylboronic acid (1.5 equiv), CuI (0.1 equiv), and 4-DMAP (1.0
equiv) were stirred in MeOH (2 mL) under open air. Isolated yields are
shown.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–L

D
S. Gupta et al.
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Synthesis
under optimized conditions (Scheme 4, 4a–d), which re-
veals a great versatility of the developed protocol.
HO
OH
R
B
O
NH
CuI, DMAP
S
R1
O
+
R2
N
R
MeOH
RT
S
R
R1
R2
OH
open air
B
O
OH
OtBu
NHBoc
Et
N
OMe
SMe
O
O
O
S
N
Me
CuI, DMAP
S
Me
OtBu
NHBoc
HN
MeOH, RT
open air
O
N
R
O
O
O
S
N
N
S
S
S
Me
Me
Me
Me
O
O
OtBu
NHBoc
OtBu
NHBoc
3ae
3af
3ag
3ah
(90 min, 78%)
O
S
N
O
S
N
(45 min, 91%)
(60 min, 90%)
(60 min, 91%)
Me
Me
F
Cl
Br
NO2
MeO
OMe
O
N
O
N
O
N
O
4a
4b
N
(5 h, 78%)c
S
S
S
S
(20 min, 91%)
Me
Me
Me
Me
O
O
OtBu
NHBoc
OtBu
NHBoc
3ai
3aj
3ak
3al
(3 h, 83%)
O
O
S
N
(45 min, 86%)
(45 min, 88%)
(45 min, 89%)
Me
S
N
Me
CH2
CHO
Me
Me
Cl
Cl
CF3
O
N
O
N
Me
Br
O
O
N
S
S
N
4c
(6 h, 79%)
4d
(20 min, 89%)
S
S
Me
Me
Me
Me
Scheme 4 N-Arylation of bioactive L-methionine sulfoximine with aryl-
boronic acids. Reagents and conditions: Sulfoximine (150 mg, 1 equiv),
arylboronic acid (1.5 equiv), CuI (0.018 g, 0.1 equiv), DMAP (0.118 g,
1.0 equiv), and MeOH (2 mL) were stirred at RT under open air. Isolated
yields are shown. For 4b, arylboronic acid (2.4 equiv) and CuI (0.2
equiv) were used.
3am
3an
3ao
3ap
( 2 h, 86%)
(2 h, 88%)
(60 min, 82%)
(2 h, 60%)
O
Me
CN
O
N
O
N
O
N
S
O
N
S
S
Me
S
Me
Me
Me
It is also noteworthy that the arylboronic acid surro-
gates such as phenylboronic acid pinacol ester and potassi-
um phenyltrifluoroborate also participated in the coupling
reaction efficiently (Scheme 5). Further, we have attempted
to prepare the N-vinylsulfoximines17 using vinylboronic
3aq
3ar
3as
3at
(2 h, 45%)
(2 h, 40%)
(45 min, 85%)
(45 min, 85%)
Ph
N
Br
N
S
O
O
S
N
Bu
Bu
Bu
S
O
Bu
Me
O
O
B
3au
(90 min, 52%)
3me
(45 min, 92%)
3mk
CuI (0.1 equiv)
O
O
(1 h, 89%)
NH
N
DMAP (1.0 equiv)
S
S
+
(or)
BF3+K–
Scheme 3 N-Arylation of S-methyl-S-phenylsulfoximine (1a) using var-
ious arylboronic acids. Reagents and conditions: Sulfoximine (150 mg, 1
equiv), arylboronic acid (1.5 equiv), CuI (0.1 equiv), and 4-DMAP (1.0
equiv) were stirred in MeOH (2 mL) at RT under open air. Isolated yields
are shown.
Me
Me
MeOH, RT
open air
3 h
1a
3ae
>80%
Scheme 5 N-Arylation with phenylboronic acid surrogates
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–L

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Synthesis
acid. In this context, the optimized reaction conditions
were well suited to the task with N-vinyl-S-methyl-S-phe-
nylsulfoximine being obtained in 84% yield within 45 min-
utes at room temperature (Scheme 6, 3av).
copper(I) iodide and 4-DMAP in methanol at room tem-
perature. A wide range of aryl, alkyl, diaryl, arylbenzyl,
dibenzyl, and dialkyl sulfoximines were N-arylated with
sterically hindered arylboronic acids as well as library of
other substituted arylboronic acids. All reactions took place
at room temperature and provided good to excellent yields
of N-arylsulfoximines in a short span of time. For the first
time, we have also demonstrated the N-arylation of biologi-
cally relevant L-methionine sulfoximine with different aryl-
boronic acids at room temperature. Surprisingly, the opti-
mized reaction was well suited to the task of N-arylation of
sulfoximine with arylboronic acid surrogates and N-vinyla-
tion of sulfoximine with trans-2-phenylvinylboronic acid.
Overall, the current methodology appears to be more gen-
eral from a synthetic point of view, and thereby promises to
find wide applications in organic synthesis.
O
OH
B
O
Me
Me
S
S
CuI, DMAP
OH
N
+
NH
MeOH
RT
1a
2v
3av
45 min, 84%
Scheme 6 N-Vinylation with vinylboronic acid 2v
The mechanism of Chan–Lam coupling reaction is well
documented in the literature. However, the role of 4-DMAP
in the N-arylation of sulfoximine with sterically hindered
arylboronic acid is not clear to us. Based on the previous re-
ports,14 a plausible mechanism has been proposed for N-
arylation of sulfoximine using arylboronic acids (Scheme
7). First, CuI and 4-DMAP provides Cu(II)-complex in situ
under open air.14e This Cu(II) complex undergoes ligand ex-
change with sulfoximine to give the intermediate A. Subse-
quently, arylboronic acid undergoes trans-metalation with
the complex A and forms the intermediate B. Finally, the re-
ductive elimination of B provides the desired N-arylated
product and copper(0) species. Under open air, the reduced
Cu(0) catalyst was re-oxidized to Cu(II) species and the cat-
alytic cycle is resumed.
Starting materials were prepared using either literature procedures or
modified literature procedures.18 Boronic acids were purchased from
Aldrich and Alfa Aesar chemicals. All reactions were performed in
round-bottomed flasks under open air. Solvents and other chemicals
were purchased from commercial sources and used without further
purification. TLC was performed using pre-coated plates contained
from E. Merck (TLC silica gel 60 F254). TLC plates were visualized by
exposure to ultraviolet light (UV), and then further analyzed by using
an I2 chamber or ninhydrin strain. Column chromatography (cc) was
performed on silica gel (60–120 mesh) using an EtOAc/hexane mix-
ture as eluent. 1H and 13C NMR spectra were recorded on a Bruker
Avance 500 MHz NMR spectrometer and mass spectra were mea-
sured on a Waters Quattro Micro V 4.1.
CuI + DMAP
open air
N-Arylation of Sulfoximines with Arylboronic Acids; General
Procedure
[Cu(DMAP)4I]I-Complex
O
A mixture of the respective sulfoximine (150 mg, 1 equiv, for 3aa,
3ba, 3ja, 3ab, 3ac, 3ad-3nd, 3ae-3au, 3me and 3mk) or (200 mg, 1
equiv, for 3ca-3ia and 3ka), CuI (10 mol%), and 4-DMAP (1 equiv) was
stirred in MeOH (2 mL) under open air at RT for 5 min. The appropri-
ate arylboronic acid or arylboronic acid surrogate or vinylboronic acid
(1.5 equiv) was added to the reaction mixture and allowed to stir at
RT. The progress of reaction was monitored by TLC. After completion,
the reaction mixture was diluted with CH2Cl2 and washed with dis-
tilled water, aq NaHCO3, and brine. The organic layer was dried (an-
hyd Na2SO4), filtered, and evaporated on a rotary evaporator. The
crude product was purified by silica gel column chromatography us-
ing EtOAc/hexane as an eluent to obtain the desired products.
R1
S
R2
NH
LnCu(II)
HI
open air
O
R1
S
N Cu(II)Ln
R2
Cu(0)
(A)
R3 B(OH)2
N-(2,4,6-Trimethylphenyl)-S,S-methylphenylsulfoximine (3aa)
Yield: 235 mg (89%); pale yellow oil; cc: 20% EtOAc/hexane; Rf = 0.25.
O
HI
R1
S
R2
N
R3
O
Cu(II)Ln
IR (KBr, film): 1449, 1232, 1221, 749 cm–1
1H NMR (500 MHz, CDCl3):  = 8.14 (d, J = 7.9 Hz, 2 Harom), 7.59 (m, 3
arom), 6.84 (s, 2 Harom), 3.02 (s, 3 H, CH3), 2.33 (s, 6 H, 2 × CH3), 2.23 (s,
.
R1
S
R2
N
R3
(B)
H
(C)
3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 141.4, 138.0, 133.9, 133.1, 132.5,
129.3, 129.2, 128.0, 43.3, 20.8, 20.1.
Scheme 7 Proposed mechanism for N-arylation of sulfoximine with
arylboronic acid
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H20NOS: 274.1226; found:
274.1257.
In conclusion, N-arylation of sulfoximines with aryl-
boronic acid was demonstrated using a catalytic amount of
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Synthesis
N-(2,4,6-Trimethylphenyl)-S,S-heptylphenylsulfoximine (3ba)
N-(2,4,6-Trimethylphenyl)-S,S-methyl(4-nitrophenyl)sulfoximine
(3fa)
Yield: 199 mg (87%); transparent liquid; cc: 10% EtOAc/hexane; Rf =
0.28.
Yield: 276 mg (87%); yellow oil; cc: 5–10% EtOAc/hexane; Rf = 0.32.
IR (KBr, film): 3280, 2936, 1454, 1218, 1123, 991, 754, 688 cm–1
1H NMR (500 MHz, CDCl3):  = 8.02 (d, J = 7.8 Hz, 2 Harom), 7.58 (m, 1
arom), 7.52 (t, J = 7.4 Hz, 2 Harom), 6.78 (s, 2 Harom), 3.30 (m, 1 H, CH2),
3.05 (m, 1 H, CH2), 2.30 (s, 6 H, 2 × CH3), 2.20 (s, 3 H, CH3), 1.77–1.63
(m, 2 H, CH2), 1.58–1.44 (m, 1 H, CH2), 1.23–1.13 (m, 6 H, 3 × CH2, 1 H,
CH2), 0.83–0.78 (m, 3 H, CH3).
.
IR (KBr, film): 3088, 3022, 2998, 2912, 1696, 1518, 1352, 1289, 1098,
1057 cm–1
.
H
1H NMR (500 MHz, CDCl3):  = 8.39 (d, J = 8.9 Hz, 2 Harom), 8.29 (d, J =
8.9 Hz, 2 Harom), 6.82 (s, 2 Harom), 3.12 (s, 3 H, CH3), 2.27 (s, 6 H, 2 ×
CH3), 2.22 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 150.6, 148.2, 137.2, 133.6, 133.1,
129.4, 127.1, 124.6, 43.80, 20.8, 20.1.
13C NMR (125 MHz, CDCl3):  = 140.2, 138.3, 133.7, 132.9, 132.1,
129.2, 129.1, 128.6, 56.4, 31.6, 28.8, 28.4, 23.8, 22.6, 20.8, 20.4, 14.1.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H32NOS: 358.2199; found:
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H19N2O3S: 319.1111;
found: 319.1111.
358.2195.
N-(2,4,6-Trimethylphenyl)-S,S-diphenylsulfoximine (3ga)
N-(2,4,6-Trimethylphenyl)-S,S-isopropylphenylsulfoximine (3ca)
Yield: 259 mg (84%); transparent oil; cc: 10% EtOAc/hexane; Rf = 0.31.
Yield: 279 mg (85%); transparent liquid; cc: 10% EtOAc/hexane; Rf =
0.29.
IR (KBr, film): 3089, 2913, 2874, 2380, 2342, 1461, 1274, 1218, 1138,
1109, 1091, 954, 746 cm–1
.
IR (KBr, film): 3024, 2926, 1519, 1279, 1258, 1087, 1069, 1033 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.94–7.88 (m, 4 Harom), 7.49–7.48 (m, 2
Harom), 7.45–7.40 (m, 4 Harom), 6.72 (s, 2 Harom), 2.20 (s, 6 H, 2 × CH3),
2.16 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 142.4, 137.9, 133.7, 132.4, 132.1,
129.15, 129.10, 128.1, 20.82, 20.5.
1H NMR (500 MHz, CDCl3):  = 7.86 (d, J = 7.8 Hz, 2 Harom), 7.57–7.41
(m, 3 Harom), 6.72 (s, 2 Harom), 3.53–3.42 (m, 1 H, CH), 2.25 (s, 6 H, 2 ×
CH3), 2.16 (s, 3 H, CH3), 1.42 (d, J = 6.8 Hz, 3 H, CH3), 1.19 (d, J = 6.7 Hz,
3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 139.0, 138.9, 132.9, 132.7, 131.4,
129.2, 129.18, 129.12, 58.3, 20.8, 20.7, 17.4, 16.0.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H22NOS: 336.1417; found:
336.1419.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H24NOS: 302.1573; found:
302.1576.
N-(2,4,6-Trimethylphenyl)-S,S-benzylphenylsulfoximine (3ha)
Yield: 260 mg (81%); transparent oil; cc: 5% EtOAc/hexane; Rf = 0.24.
IR (KBr, film): 3053, 2914, 2838, 2352, 2334, 1445, 1286, 1219, 1134,
N-(2,4,6-Trimethylphenyl)-S,S-ethyl(4-methoxyphenyl)sulfoxi-
mine (3da)
1123, 1086, 961, 741 cm–1
.
Yield: 286 mg (90%); transparent oil; cc: 20% EtOAc/hexane; Rf = 0.24.
1H NMR (500 MHz, CDCl3):  = 7.80 (d, J = 7.4 Hz, 2 Harom), 7.56 (t, J =
7.6 Hz, 1 Harom), 7.43 (t, J = 7.9 Hz, 2 Harom), 7.22 (d, J = 7.0 Hz, 1 Harom),
7.15 (t, J = 7.4 Hz, 2 Harom), 6.89 (d, J = 7.7 Hz, 2 Harom), 6.84 (s, 2 Harom),
4.48–4.16 (ABq, J = 13.5 Hz, 4 H, 2 × CH2), 2.36 (s, 6 H, 2 × CH3), 2.24 (s,
3 H, CH3).
IR (KBr, film): 3025, 2929, 1517, 1296, 1178, 1058, 1031, 1024, 990,
764 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.93 (d, J = 8.6 Hz, 2 Harom), 6.98 (d, J =
8.8 Hz, 2 Harom), 6.78 (s, 2 Harom), 3.85 (s, 3 H, CH3), 3.29 (m, 1 H, CH2),
3.04 (m, 1 H, CH2), 2.31 (s, 6 H, 2 × CH3), 2.19 (s, 3 H, CH3), 1.17 (t, J =
7.3 Hz, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 163.3, 138.6, 133.7, 132.0, 131.0,
130.7, 129.1, 114.4, 55.8, 50.8, 20.8, 20.4, 8.7.
NMR (125 MHz, CDCl3):  = 138.6, 138.2, 133.9, 133.2, 132.4, 131.1,
129.7, 129.4, 129.3, 128.9, 128.43, 128.40, 62.8, 20.8, 20.5.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H24NOS: 350.1573; found:
350.1567.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H24NO2S: 318.1522; found:
318.1523.
N-(2,4,6-Trimethylphenyl)-S,S-dibenzylsulfoximine (3ia)
Yield: 274 mg (82%); white solid; mp 131 °C; cc: 5% EtOAc/hexane; Rf
= 0.26.
N-(2,4,6-Trimethylphenyl)-S,S-(4-bromophenyl)methylsulfoxi-
mine (3ea)
IR (KBr, film): 3274, 3111, 3058, 3012, 2986, 2976, 1514, 1445, 1418,
Yield: 264 mg (88%); transparent oil; cc: 10% EtOAc/hexane; Rf = 0.25.
1232, 1125, 1071, 1067, 761, 691, 585 cm–1
.
IR (KBr, film): 3036, 2928, 1586, 1474, 1289, 1214, 1181, 1093, 1033
1H NMR (500 MHz, CDCl3):  = 7.34 (s, 10 Harom), 6.76 (s, 2 Harom),
4.25–4.17 (ABq, J = 12.5 Hz, 4 H, 2 × CH2), 2.19 (s, 3 H, CH3), 2.07 (s, 6
H, 2 × CH3).
13C NMR (125 MHz, CDCl3):  = 138.1, 134.0, 132.5, 131.5, 129.3,
129.1, 128.8, 58.5, 20.8, 19.7.
cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.98 (d, J = 8.5 Hz, 2 Harom), 7.68 (d, J =
8.5 Hz, 2 Harom), 6.82 (s, 2 Harom), 3.02 (s, 3 H, CH3), 2.29 (s, 6 H, 2 ×
CH3), 2.22 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 140.6, 137.8, 133.8, 132.7, 132.6,
129.7, 129.3, 128.3, 43.6, 20.8, 20.1.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H26NOS: 364.1730; found:
364.1732.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H19BrNOS: 352.0365;
found: 352.0367.
N-(2,4,6-Trimethylphenyl)-S,S-dibutylsulfoximine (3ja)
Yield: 177 mg (71%); pale yellow viscous oil; cc: 10% EtOAc/hexane;
Rf = 0.34.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–L

G
S. Gupta et al.
Paper
Synthesis
IR (KBr, film): 3272, 2960, 1724, 1466, 1380, 1242, 1101, 1016, 807,
729 cm–1
13C NMR (125 MHz, CDCl3):  = 142.3, 139.6, 133.3, 131.2, 129.7,
129.6, 128.8, 123.3, 46.0, 20.8.
.
1H NMR (500 MHz, CDCl3):  = 6.79 (s, 2 H), 3.07–2.97 (m, 4 H), 2.27
(s, 6 H), 2.20 (s, 3 H), 1.84–1.78 (m, 4 H), 1.43–1.39 (m, 4 H), 0.92 (t,
J = 7.3 Hz, 6 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H16NOS: 246.0953; found:
246.0940.
13C NMR (125 MHz, CDCl3):  = 138.6, 133.8, 132.1, 129.0, 52.9, 25.7,
N-(4-Methylphenyl)-S,S-ethylphenylsulfoximine (3bd)
22.1, 20.8, 19.9, 13.8.
Yield: 230 mg (92%); brown solid; mp 86 °C; cc: 30% EtOAc/hexane;
HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H30NOS: 296.2048; found:
Rf = 0.24.
296.2078.
IR (KBr, film): 3369, 3057, 2929, 2786, 2359, 2048, 1594, 1487, 1394,
1265, 1193, 1093 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.89 (d, J = 7.9 Hz, 2 Harom), 7.52 (m, 3
Harom), 6.90 (s, 4 Harom), 3.30 (m, 2 H, CH2), 2.18 (s, 3 H, CH3), 1.27 (t, J =
N-(2,4,6-Trimethylphenyl)-S,S-ethyl(2-pyridyl)sulfoximine (3ka)
Yield: 311 mg (92%); transparent liquid; cc: 10% EtOAc/hexane; Rf =
0.30.
7.4 Hz, 3 H, CH3).
IR (KBr, film): 3353, 3034, 2888, 2779, 2364, 2028, 1574, 1477, 1378,
13C NMR (125 MHz, CDCl3):  = 142.5, 137.6, 133.2, 130.9, 129.7,
129.6, 129.5, 123.3, 51.9, 20.8, 7.8.
1259, 1181, 1094, 983, 814 cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.64 (d, J = 4.5 Hz, 1 Harom), 7.78 (d, J =
7.8 Hz, 1 Harom), 7.73 (t, J = 7.6 Hz, 1 Harom), 7.37 (dd, J = 7.4, 4.8 Hz, 1
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H18NOS: 260.1109; found:
260.1102.
H
arom), 6.68 (s, 2 Harom), 3.85 (m, 1 H, CH2), 3.63 (m, 1 H, CH2), 2.14 (s, 3
H, CH3), 2.08 (s, 6 H, 2 × CH3), 1.37 (t, J = 7.3 Hz, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 158.7, 149.7, 137.8, 137.6, 134.0,
N-(4-Methylphenyl)-S,S-phenylpropylsulfoximine (3cd)
Yield: 243 mg (92%); white solid; mp 110 °C; cc: 30% EtOAc/hexane;
132.1, 128.7, 126.3, 122.3, 46.7, 20.7, 19.5, 7.3.
Rf = 0.22.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H21N2OS: 289.1369; found:
289.1366.
IR (KBr, film): 3020, 2923, 1505, 1287, 1263, 1094, 1069, 1034 cm–1
1H NMR (500 MHz, CDCl3):  = 7.89 (d, J = 7.6 Hz, 2 Harom), 7.51 (m, 3
arom), 6.89 (s, 4 Harom), 3.28 (m, 1 H, CH2), 3.23–3.16 (m, 1 H, CH2),
2.17 (s, 3 H, CH3), 1.76 (m, 2 H, CH2), 0.95 (t, J = 7.4 Hz, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 142.5, 140.6, 138.3, 133.2, 130.8,
129.7, 129.5, 123.3, 59.2, 20.8, 16.7, 12.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H20NOS: 274.1266; found:
274.1283.
.
H
N-(2,6-Dimethylphenyl)-S,S-methylphenylsulfoximine (3ab)
Yield: 210 mg (84%); yellow oil; cc: 20% EtOAc/hexane; Rf = 0.48.
IR (KBr, film): 1474, 1272, 1089, 756, 733 cm–1
1H NMR (500 MHz, CDCl3):  = 8.14 (d, J = 7.5 Hz, 2 Harom), 7.59 (m, 3
arom), 7.01 (d, J = 7.4 Hz, 2 Harom), 6.87 (t, J = 7.4 Hz, 1 Harom), 3.03 (s, 3
.
H
H, CH3), 2.36 (s, 6 H, 2 × CH3).
13C NMR (125 MHz, CDCl3):  = 141.4, 140.9, 134.2, 133.2, 129.4,
N-(4-Methylphenyl)-S,S-isopropylphenylsulfoximine (3dd)
128.4, 128.0, 123.3, 43.6, 20.2.
Yield: 230 mg (87%); pale yellow oil; cc: 20% EtOAc/hexane; Rf = 0.34.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H18NOS: 260.1104; found:
IR (KBr, film): 3020, 2923, 1505, 1287, 1263, 1094, 1069, 1034 cm–1
.
260.1093.
1H NMR (500 MHz, CDCl3):  = 7.84 (d, J = 7.5 Hz, 2 Harom), 7.54 (t, J =
7.2 Hz, 1 Harom), 7.47 (t, J = 7.4 Hz, 2 Harom), 6.89 (s, 4 Harom), 3.39 (m, 1
H, CH), 2.17 (s, 3 H, CH3), 1.40 (d, J = 6.6 Hz, 3 H, CH3), 1.26 (d, J = 6.6
Hz, 3 H, CH3).
N-(2,6-Dimethoxyphenyl)-S,S-methylphenylsulfoximine (3ac)
Yield: 228 mg (81%); yellow oil; cc: 40% EtOAc/hexane; Rf = 0.38.
IR (KBr, film): 1449, 1284, 1079, 765 cm–1
1H NMR (500 MHz, CDCl3):  = 8.08 (d, J = 7.7 Hz, 2 Harom), 7.52 (m, 3
arom), 6.87 (t, J = 8.3 Hz, 1 Harom), 6.51 (d, J = 8.3 Hz, 2 Harom), 3.70 (s, 6
.
13C NMR (125 MHz, CDCl3):  = 142.9, 136.2, 133.1, 130.58, 130.55,
129.6, 129.3, 123.2, 57.0, 20.8, 16.4, 15.9.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C16H19NOSNa: 296.1085;
H
H, 2 × CH3), 3.15 (s, 3 H, CH3).
found: 296.1097.
13C NMR (125 MHz, CDCl3):  = 154.4, 143.1, 132.5, 129.1, 127.9,
122.6, 122.5, 105.2, 56.1, 45.9.
N-(4-Methylphenyl)-S,S-heptylphenylsulfoximine (3ed)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H19NO3S: 292.1002; found:
292.0991.
Yield: 186 mg (90%); white solid; mp 76 °C; cc: 10% EtOAc/hexane;
Rf = 0.50.
IR (KBr, film): 3272, 2927, 1445, 1223, 1110, 991, 752, 689 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.90 (d, J = 7.1 Hz, 2 Harom), 7.54–7.46
(m, 3 Harom), 6.90 (s, 4 Harom), 3.34–3.28 (m, 1 H, CH2), 3.24–3.18 (m, 1
H, CH2), 2.17 (s, 3 H, CH3), 1.79–1.78 (m, 1 H, CH2), 1.67–1.65 (m, 1 H,
CH2), 1.33–1.15 (m, 8 H, 4 × CH2), 0.83 (t, J = 6.8 Hz, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 142.5, 138.3, 133.1, 130.8, 130.1,
129.6, 129.52, 129.50, 123.3, 115.4, 57.6, 31.5, 28.8, 28.2, 22.8, 22.6,
20.8, 14.1.
N-(4-Methylphenyl)-S,S-methylphenylsulfoximine (3ad)
Yield: 215 mg (91%); white solid; mp 112–114 °C; cc: 30% EtOAc/hex-
ane; Rf = 0.18.
IR (KBr, film): 3020, 2923, 1498, 1504, 1287, 1263, 1091, 1069, 1034
cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.95 (d, J = 7.8 Hz, 2 Harom), 7.52 (m, 3
arom), 6.90 (s, 4 Harom), 3.20 (s, 3 H, CH3), 2.18 (s, 3 H, CH3).
H
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H13NOS: 330.1886; found:
330.1889.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–L

H
S. Gupta et al.
Paper
Synthesis
N-(4-Methylphenyl)-S,S-(4-methylphenyl)methylsulfoximine
(3fd)
IR (KBr, film): 3054, 2917, 2847, 2364, 2333, 1454, 1298, 1218, 1136,
1101, 1096 743 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.60 (d, J = 7.9 Hz, 2 Harom), 7.49 (t, J =
7.4 Hz, 1 Harom), 7.35 (t, J = 7.6 Hz, 2 Harom), 7.26 (t, J = 7.4 Hz, 1 Harom),
7.18 (t, J = 7.5 Hz, 2 Harom), 6.99–6.91 (m, 6 Harom), 4.51 (ABq, J = 13.7
Hz, 2 H, CH2), 2.20 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 142.5, 136.7, 133.2, 131.4, 131.0,
129.9, 129.8, 129.0, 128.8, 128.6, 128.4, 123.4, 63.3, 20.8.
Yield: 204 mg (89%); pale yellow viscous oil; cc: 20% EtOAc/hexane;
Rf = 0.40.
IR (KBr, film): 3021, 2922, 1505, 1288, 1197, 1093, 1033, 1013 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.82 (d, J = 8.1 Hz, 2 Harom), 7.28 (d, J =
7.9 Hz, 2 Harom), 6.90 (s, 4 Harom), 3.18 (s, 3 H, CH3), 2.38 (s, 3 H, CH3),
2.18 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 144.1, 142.5, 136.6, 131.0, 130.3,
129.7, 128.8, 123.3, 46.2, 21.7, 20.8.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H19NOSNa: 344.1085;
found: 344.1070.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H18NOS: 260.1109; found:
260.1149.
N-(4-Methylphenyl)-S,S-dibenzylsulfoximine (3kd)
Yield: 169 mg (81%); pale yellow solid; mp 86 °C; cc: 20% EtOAc/hex-
ane; Rf = 0.44.
N-(4-Methylphenyl)-S,S-(4-bromophenyl)methylsulfoximine
(3gd)
IR (KBr, film): 3275, 3105, 3062, 3010, 2996, 2908, 1504, 1438, 1406,
1242, 1116, 1063, 1037, 760, 698, 580 cm–1
.
Yield: 191 mg (92%); white solid; mp 150 °C; cc: 30% EtOAc/hexane;
1H NMR (500 MHz, CDCl3):  = 7.34 (d, J = 6.2 Hz, 10 Harom), 7.02–6.96
(m, 4 Harom), 4.31–4.25 (ABq, J = 14.0 Hz, 4 H, 2 × CH2), 2.26 (s, 3 H,
CH3).
13C NMR (125 MHz, CDCl3):  = 142.7, 131.4, 129.9, 129.0, 128.9,
128.7, 123.4, 120.8, 57.5, 20.9.
Rf = 0.36.
IR (KBr, film): 3026, 2926, 1588, 1486, 1288, 1201, 1094, 1030 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.80 (d, J = 8.3 Hz, 2 Harom), 7.62 (d, J =
8.3 Hz, 2 Harom), 6.91 (d, J = 8.1 Hz, 2 Harom), 6.87 (d, J = 8.0 Hz, 2 Harom),
3.20 (s, 3 H, CH3), 2.19 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 141.9, 138.6, 132.9, 131.5, 130.4,
129.8, 128.6, 123.3, 46.1, 20.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H22NOS: 336.1422; found:
336.1408.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H15BrNOS: 324.0058;
found: 324.0056.
N-(4-Methylphenyl)-S,S-ethyl(2-pyridyl)sulfoximine (3ld)
Yield: 213 mg (93%); pale yellow solid; mp 165 °C; cc: 20–30%
EtOAc/hexane; Rf = 0.46.
N-(4-Methylphenyl)-S,S-methyl-(4-nitrophenyl)sulfoximine (3hd)
IR (KBr, film): 3364, 3047, 2898, 2781, 2354, 2038, 1589, 1483, 1388,
Yield: 198 mg (91%); yellow solid; mp 85 °C; cc: 20% EtOAc/hexane;
Rf = 0.28.
1261, 1184, 1091,973, 814, 757 cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.70 (d, J = 4.2 Hz, 1 Harom), 8.08 (d, J =
7.8 Hz, 1 Harom), 7.84 (t, J = 7.7 Hz, 1 Harom), 7.45–7.40 (m, 1 Harom),
6.94–6.86 (m, 4 Harom), 3.65 (dq, J = 14.7, 7.4 Hz, 1 H, CH2), 3.55 (dq, J =
14.7, 7.5 Hz, 1 H, CH2), 2.17 (s, 3 H, CH3), 1.28 (t, J = 7.4 Hz, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 156.6, 150.5, 142.1, 137.9, 131.3,
129.6, 126.8, 124.6, 123.5, 47.9, 20.8, 7.2.
IR (KBr, film): 3094, 3029, 2932, 1529, 1348, 1294, 1089, 1041 cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.33 (d, J = 8.5 Hz, 2 Harom), 8.13 (d, J =
8.5 Hz, 2 Harom), 6.92 (d, J = 8.1 Hz, 2 Harom), 6.86 (d, J = 8.0 Hz, 2 Harom),
3.27 (s, 3 H, CH3), 2.18 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 150.7, 145.9, 141.3, 132.1, 130.3,
130.0, 124.8, 123.4, 45.8, 20.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H17N2OS: 261.1062; found:
261.1073.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H15N2O3S: 291.0803;
found: 291.0804.
N-(4-Methylphenyl)-S,S-dibutylsulfoximine (3md)
N-(4-Methylphenyl)-S,S-diphenylsulfoximine (3id)
Yield: 205 mg (91%); transparent oil; cc: 10% EtOAc/hexane; Rf = 0.38.
Yield: 178 mg (84%); white solid; mp 171 °C; cc: 20% EtOAc/hexane;
Rf = 0.52.
IR (KBr, film): 3272, 3018, 2940, 1724, 1486, 1380, 1242, 1101, 1071,
1036, 807, 729 cm–1
.
IR (KBr, film): 3083, 2905, 2877, 2381, 2341, 1467, 1286, 1208, 1119,
1H NMR (500 MHz, CDCl3):  = 6.99 (d, J = 8.3 Hz, 2 Harom), 6.95 (d, J =
8.3 Hz, 2 Harom), 3.17–3.03 (m, 4 H, 2 × CH2), 2.25 (s, 3 H, CH3), 1.82–
1.76 (m, 4 H, 2 × CH2), 1.44–1.36 (m, 4 H, 2 × CH2), 0.83 (t, J = 7.4 Hz, 6
H, 2 × CH3).
13C NMR (125 MHz, CDCl3):  = 142.8, 131.2, 129.8, 123.6, 51.7, 25.3,
21.9, 20.9, 13.8.
1104, 1093, 748 cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.04 (d, J = 7.6 Hz, 4 Harom), 7.50–7.41
(m, 6 Harom), 7.04 (d, J = 8.0 Hz, 2 Harom), 6.93 (d, J = 7.9 Hz, 2 Harom),
2.19 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 142.0, 141.1, 132.7, 131.1, 129.7,
129.4, 128.7, 123.7, 20.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H26NOS: 268.1735; found:
268.1755.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H18NOS: 308.1109; found:
308.1100.
N-(4-Methylphenyl)-S,S-cyclohexylheptylsulfoximine (3nd)
Yield: 170 mg (83%); yellow oil; cc: 15% EtOAc/hexane; Rf = 0.24.
IR (KBr, film): 3310, 2920, 2875, 2814, 2313, 1981, 1504, 1644, 1450,
N-(4-Methylphenyl)-S,S-benzylphenylsulfoximine (3jd)
Yield: 173 mg (83%); pale yellow solid; mp 148–151 °C; cc: 20%
EtOAc/hexane; Rf = 0.46.
1277, 1129, 1094, 1034, 958, 849, 773, 690 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–L

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1H NMR (500 MHz, CDCl3):  = 6.97 (s, 4 Harom), 3.10–3.04 (m, 2 H,
CH2), 3.02–2.96 (m, 1 H, CH2), 2.33–2.15 (m, 1 H, CH2, 2 H, CH2), 2.24
(s, 3 H, CH3), 1.91–1.89 (m, 2 H, CH2), 1.81–1.75 (m, 2 H, CH2), 1.69 (d,
J = 12.2 Hz, 1 H, CH2), 1.64–1.48 (m, 2 H, CH2), 1.33–1.23 (m, 10 H, 5 ×
CH2), 0.84 (t, J = 6.8 Hz, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 143.3, 130.9, 130.1, 129.7, 123.6,
115.3, 61.7, 48.8, 31.6, 28.9, 28.7, 26.4, 26.0, 25.7, 25.6, 25.3, 22.8,
22.7, 20.9, 14.2.
N-(4-Fluorophenyl)-S,S-methylphenylsulfoximine (3ai)
Yield: 207 mg (86%); white solid; mp 82–86 °C; cc: 40% EtOAc/hex-
ane; Rf = 0.28.
IR (KBr, film): 3053, 3002, 2928, 1445, 1281, 1263, 1208, 1093, 1032,
821, 745, 679 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.87 (d, J = 7.7 Hz, 2 Harom), 7.48 (m, 3
arom), 6.88 (d, J = 8.7, 2 Harom), 6.72 (d, J = 8.7 Hz, 2 Harom), 3.15 (s, 3 H,
H
CH3).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H35NOS: 336.2356; found:
336.2351.
13C NMR (125 MHz, CDCl3):  = 158.3 (d, JC,F = 239.0), 141.0 (d, JC,F
2.6), 139.1, 133.3, 129.6, 128.6, 124.4 (d, JC,F = 7.7 Hz), 115.5 (d, JC,F
22.1 Hz), 46.0.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H13FNOS: 250.0702; found:
250.0687.
=
=
N-Phenyl-S,S-methylphenylsulfoximine (3ae)
Yield: 203 mg (91%); white solid; mp 100–101 °C; cc: 30% EtOAc/hex-
ane; Rf = 0.22.
IR (KBr, film): 3044, 2089, 1614, 1486, 1267, 1202, 1093, 1040 cm–1
.
N-(4-Chlorophenyl)-S,S-methylphenylsulfoximine (3aj)
1H NMR (500 MHz, CDCl3):  = 7.94–7.88 (m, 2 Harom), 7.48 (m, 3 Har-
om), 7.05 (t, J = 7.8 Hz, 2 Harom), 6.94 (d, J = 7.5 Hz, 2 Harom), 6.80 (t, J =
7.3 Hz, 1 Harom), 3.17 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 145.1, 139.7, 133.4, 129.7, 129.2,
128.8, 123.5, 121.9, 46.2.
Yield: 226 mg (88%); white solid; mp 64–66 °C; cc: 40% EtOAc/hex-
ane; Rf = 0.38.
IR (KBr, film): 3064, 3014, 2926, 1487, 1402, 1371, 1291, 1198, 1091,
738, 681 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.91 (d, J = 7.9 Hz, 2 Harom), 7.56 (t, J =
7.3 Hz, 1 Harom), 7.49 (t, J = 7.6 Hz, 2 Harom), 7.02 (d, J = 8.6 Hz, 2 Harom),
6.90 (d, J = 8.6 Hz, 2 Harom), 3.20 (s, 3 H, CH3).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H14NOS: 232.0796; found:
232.0778.
13C NMR (125 MHz, CDCl3):  = 143.8, 139.0, 133.5, 129.7, 129.0,
128.7, 126.8, 124.5, 46.1.
N-(4-Ethylphenyl)-S,S-methylphenylsulfoximine (3af)
Yield: 225 mg (90%); pale yellow oil; cc: 30% EtOAc/hexane; Rf = 0.28.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H13ClNOS: 266.0406;
found: 266.0396.
IR (KBr, film): 3299, 1615, 1517, 1286, 1225, 1090, 1010, 833 cm–1
1H NMR (500 MHz, CDCl3):  = 7.96 (d, J = 7.7 Hz, 2 Harom), 7.53 (m, 3
arom), 6.94 (d, J = 8.4 Hz, 2 Harom), 6.91 (d, J = 8.4 Hz, 2 Harom), 3.20 (s, 3
.
H
N-(4-Bromophenyl)-S,S-methylphenylsulfoximine (3ak)
H), 2.49 (q, J = 7.5 Hz, 2 H, CH2), 1.12 (t, J = 7.6 Hz, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 142.4, 139.7, 137.6, 133.3, 129.6,
Yield: 266 mg (89%); white solid; mp 109–111 °C; cc: 30% EtOAc/hex-
ane; Rf = 0.44.
128.8, 128.5, 123.3, 46.1, 28.2, 15.7.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H18NOS: 260.1109; found:
IR (KBr, film): 3109, 3026, 2926, 1485, 1401, 1267, 1203, 1007, 821,
732 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.91 (d, J = 7.9 Hz, 2 Harom), 7.53 (m, 3
arom), 7.17 (d, J = 8.2 Hz, 2 Harom), 6.85 (d, J = 8.2 Hz, 2 Harom), 3.21 (s, 3
260.1100.
H
N-(4-Methoxyphenyl)-S,S-methylphenylsulfoximine (3ag)
H, CH3).
13C NMR (125 MHz, CDCl3):  = 144.4, 138.9, 133.6, 132.0, 129.7,
Yield: 229 mg (91%); white solid; mp 102–106 °C; cc: 40% EtOAc/hex-
ane; Rf = 0.18.
128.7, 124.9, 114.4, 46.2.
IR (KBr, film): 3012, 2930, 2833, 1513, 1444, 1263, 1239, 1042 cm–1
1H NMR (500 MHz, CDCl3):  = 7.99–7.90 (m, 2 Harom), 7.58–7.47 (m, 3
arom), 6.93 (d, J = 9.0 Hz, 2 Harom), 6.66 (d, J = 9.0 Hz, 2 Harom), 3.67 (s, 3
.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H13BrNOS: 309.9901;
found: 309.9896.
H
H, CH3), 3.19 (s, 3 H, CH3).
N-(4-Nitrophenyl)-S,S-methylphenylsulfoximine (3al)
13C NMR (125 MHz, CDCl3):  = 155.0, 139.7, 138.1, 133.3, 129.6,
Yield: 221 mg (83%); yellow solid; mp 149–150 °C; cc: 40% EtO-
Ac/hexane; Rf = 0.22.
128.9, 124.5, 114.5, 55.5, 45.8.
IR (KBr, film): 3097, 3020, 2913, 1592, 1294, 1050, 1013 cm–1
.
HRMS (ESI-TOF): m/z [M+ H]+ calcd for C14H16NO2S: 262.0902; found:
1H NMR (500 MHz, CDCl3):  = 7.95 (d, J = 8.7 Hz, 2 Harom), 7.91 (d, J =
7.9 Hz, 2 Harom), 7.61 (t, J = 7.3 Hz, 1 Harom), 7.53 (t, J = 7.6 Hz, 2 Harom),
6.97 (d, J = 8.7 Hz, 2 Harom), 3.29 (s, 3 H, CH3).
262.0887.
N-(4-Thiomethylphenyl)-S,S-methylphenylsulfoximine (3ah)
Yield: 209 mg (78%); yellow oil; cc: 20% EtOAc/hexane; Rf = 0.42.
13C NMR (125 MHz, CDCl3):  = 162.3, 152.8, 141.7, 138.2, 134.1,
IR (KBr, film): 3012, 2930, 2833, 1513, 1444, 1263, 1239, 1042 cm–1
.
130.0, 128.5, 126.3, 125.3, 122.5, 115.8, 46.6.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H13N2O3S: 277.0647;
found: 277.0637.
1H NMR (500 MHz, CDCl3):  = 7.93 (d, J = 7.8 Hz, 2 Harom), 7.56 (t, J =
7.2 Hz, 1 Harom), 7.50 (t, J = 7.6 Hz, 2 Harom), 7.04 (d, J = 8.4 Hz, 2 Harom),
6.92 (d, J = 8.4 Hz, 2 Harom), 3.21 (s, 3 H, CH3), 2.35 (s, 3 H, CH3).
N-(3,5-Dichlorophenyl)-S,S-methylphenylsulfoximine (3am)
13C NMR (125 MHz, CDCl3):  = 143.1, 139.3, 133.4, 130.1, 129.7,
Yield: 249 mg (86%); white solid; mp 83 °C; cc: 30% EtOAc/hexane;
128.9, 128.7, 123.9, 46.1, 17.3.
Rf = 0.40.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H16NOS2: 278.0673; found:
IR (KBr, film): 3109, 3026, 2926, 1485, 1401 cm–1
.
278.0693.
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Synthesis
1H NMR (500 MHz, CDCl3):  = 7.91 (d, J = 7.8 Hz, 2 Harom), 7.62–7.51
(m, 3 Harom), 6.87 (s, 2 Harom), 6.81 (s, 1 Harom), 3.22 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 147.5, 138.5, 134.9, 133.9, 129.9,
128.6, 121.8, 121.6, 46.3.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H12Cl2NOS: 300.0017;
found: 300.0011.
N-(4-Cyanophenyl)-S,S-methylphenylsulfoximine (3ar)
Yield: 99 mg (40%); pale yellow oil; cc: 40% EtOAc/hexane; Rf = 0.24.
IR (KBr, film): 3030, 2930, 2217, 1601, 1490, 1298 cm–1
1H NMR (500 MHz, CDCl3):  = 7.91 (d, J = 7.9 Hz, 2 Harom), 7.62 (t, J =
7.4 Hz, 1 Harom), 7.55 (d, J = 7.6 Hz, 2 Harom), 7.35 (d, J = 8.3 Hz, 2 Harom),
6.98 (d, J = 8.3 Hz, 2 Harom), 3.27 (s, 3 H, CH3).
.
13C NMR (125 MHz, CDCl3):  = 150.3, 138.5, 134.0, 133.4, 130.0,
128.6, 123.3, 119.8, 104.1, 46.7.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H13N2OS: 257.0749; found:
257.0737.
N-(3-Trifluoromethylphenyl)-S,S-methylphenylsulfoximine (3an)
Yield: 254 mg (88%); pale yellow oil; cc: 30% EtOAc/hexane; Rf = 0.28.
IR (KBr, film): 3129, 3016, 2936, 1486, 1401 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.98 (d, J = 7.8 Hz, 2 Harom), 7.63 (t, J =
7.3 Hz, 1 Harom), 7.56 (t, J = 7.5 Hz, 2 Harom), 7.28 (d, J = 2.9 Hz, 1 Harom),
7.24–7.09 (m, 3 Harom), 3.28 (s, 3 H, CH3).
N-(1-naphthyl)-S,S-methylphenylsulfoximine (3as)
Yield: 231 mg (85%); brown oil; cc: 30% EtOAc/hexane; Rf = 0.22.
13C NMR (125 MHz, CDCl3):  = 145.8, 138.9, 133.7, 131.4 (q, JC,F = 32
Hz), 129.8, 129.5, 128.7, 126.1, 124.2 (q, JC,F = 272.5 Hz), 120.2 (q, J =
3.7 Hz), 118.3 (q, J = 3.9 Hz), 46.3.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H13F3NOS: 300.0670;
found: 300.0656.
IR (KBr, film): 3065, 3019, 2923, 1511, 1481, 1282, 1191, 1059 cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.54 (d, J = 8.2 Hz, 1 Harom), 7.99 (d, J =
7.9 Hz, 2 Harom), 7.74 (d, J = 7.9 Hz, 1 Harom), 7.56–7.44 (m, 5 Harom),
7.37 (d, J = 8.1 Hz, 1 Harom), 7.16 (t, J = 7.8 Hz, 1 Harom), 7.08 (d, J = 7.4
Hz, 1 Harom), 3.32 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 141.7, 139.4, 134.7, 133.4, 130.2,
129.7, 128.6, 127.9, 126.2, 126.0, 125.2, 124.1, 121.7, 116.6, 46.1.
N-(4-Vinylphenyl)-S,S-methylphenylsulfoximine (3ao)
Yield: 203 mg (82%); pale yellow oil; cc: 30% EtOAc/hexane; Rf = 0.16.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H16NOS: 282.0953; found:
282.0942.
IR (KBr, film): 3022, 2910, 2833, 1622, 1513, 1263, 1239, 1042 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.94 (d, J = 7.8 Hz, 2 Harom), 7.53 (dt, J =
32.7, 7.5 Hz, 3 Harom), 7.16 (d, J = 8.3 Hz, 2 Harom), 6.95 (d, J = 8.3 Hz, 2
N-(2-Naphthyl)-S,S-methylphenylsulfoximine (3at)
H
arom), 6.55 (dd, J = 17.6, 10.9 Hz, 1 H, CH), 5.53 (d, J = 17.6 Hz, 1 H,
Yield: 231 mg (85%); brown solid; mp 91–92 °C; cc: 30% EtOAc/hex-
ane; Rf = 0.26.
CH2), 5.04 (d, J = 10.9 Hz, 1 H, CH2), 3.22 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 145.0, 139.4, 136.6, 133.4, 131.2,
129.7, 128.7, 127.1, 123.3, 111.6, 46.2.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H16NOS: 258.0953; found:
IR (KBr, film): 3012, 2930, 1521, 1499, 1316, 1298, 1246, 1080, 1013
cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.85 (d, J = 7.2 Hz, 2 Harom), 7.54–7.31
(m, 6 Harom), 7.24 (s, 1 Harom), 7.17 (t, J = 6.9 Hz, 1 Harom), 7.10 (d, J = 7.7
Hz, 2 Harom), 3.12 (s, 3 H, CH3).
258.0958.
N-(4-Formylphenyl)-S,S-methylphenylsulfoximine (3ap)
13C NMR (125 MHz, CDCl3):  = 143.0, 139.3, 134.5, 133.4, 129.7,
Yield: 151 mg (60%); pale yellow solid; mp 92–94 °C; cc: 40% EtO-
129.6, 128.86, 128.82, 127.5, 127.0, 126.0, 124.9, 123.8, 118.7, 46.2.
Ac/hexane; Rf = 0.38.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H16NOS: 282.0953; found:
282.0940.
IR (KBr, film): 3001, 2921, 2836, 1688, 1595 cm–1
1H NMR (500 MHz, CDCl3):  = 9.75 (s, 1 Harom), 7.93 (d, J = 7.8 Hz, 2
arom), 7.60 (t, J = 6.9 Hz, 3 Harom), 7.53 (t, J = 7.7 Hz, 2 Harom), 7.05 (d,
.
H
N-(4-Benzylphenyl)-S,S-methylphenylsulfoximine (3au)
J = 8.4 Hz, 2 Harom), 3.28 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 191.3, 152.2, 138.7, 133.9, 131.4,
Yield: 154 mg (52%); white solid; mp 140–141 °C; cc: 30% EtOAc/hex-
ane; Rf = 0.14.
IR (KBr, film): 3015, 3019, 2923, 1599, 1511, 1481, 1281, 836 cm–1
.
130.2, 130.0, 128.6, 123.0, 116.1, 46.7.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H14NO2S: 260.0745; found:
260.0736.
1H NMR (500 MHz, CDCl3):  = 7.99 (d, J = 7.6 Hz, 2 Harom), 7.58 (t, J =
7.3 Hz, 1 Harom), 7.54–7.47 (m, 4 Harom), 7.38–7.33 (m, 4 Harom), 7.24 (t,
J = 7.3 Hz, 1 Harom), 7.07 (d, J = 8.4 Hz, 2 Harom), 3.24 (s, 3 H, CH3).
N-(4-Acetylphenyl)-S,S-methylphenylsulfoximine (3aq)
13C NMR (125 MHz, CDCl3):  = 144.6, 141.0, 139.5, 134.5, 133.4,
Yield: 119 mg (45%); brown solid; mp 86–87 °C; cc: 40% EtOAc/hex-
129.7, 128.7, 127.8, 126.7, 123.6, 46.2.
ane; Rf = 0.22.
IR (KBr, film): 3001, 2911, 2836, 1725, 1597 cm–1
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H18NOS: 308.1109; found:
308.1103.
.
1H NMR (500 MHz, CDCl3):  = 7.92 (d, J = 7.7 Hz, 2 Harom), 7.71 (d, J =
8.5 Hz, 2 Harom), 7.59 (t, J = 7.3 Hz, 1 Harom), 7.52 (t, J = 7.6 Hz, 2 Harom),
6.98 (d, J = 8.5 Hz, 2 Harom), 3.26 (s, 3 H, CH3), 2.45 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3):  = 197.3, 150.7, 138.8, 133.8, 130.7,
130.0, 129.9, 128.6, 122.6, 46.6, 26.4.
N-Phenylethynyl-S,S-methylphenylsulfoximine (3av)
Yield: 209 mg (84%); brown oil; cc: 30% EtOAc/hexane; Rf = 0.36.
IR (KBr, film): 1698, 1636, 1217, 1096, 983, 739, 695 cm–1
1H NMR (500 MHz, CDCl3):  = 7.94 (d, J = 7.3 Hz, 2 Harom), 7.63 (t, J =
6.9 Hz, 1 Harom), 7.57 (t, J = 7.3 Hz, 2 Harom), 7.16 (m, 4 Harom), 7.04 (m, 1
.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H16NO2S: 274.0902; found:
274.0892.
H
arom), 6.90 (d, J = 13.6 Hz, 1 Harom), 6.19 (d, J = 13.6 Hz, 1 Harom), 3.20
(s, 3 H, CH3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–L

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Synthesis
13C NMR (125 MHz, CDCl3):  = 139.4, 138.0, 133.7, 129.9, 129.8,
128.8, 128.5, 125.7, 125.1, 118.3, 45.5.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H16NOS: 258.0953; found:
258.0930.
13C NMR (125 MHz, CDCl3):  = 170.3, 155.5, 145.1, 145.0, 129.44,
129.42, 123.6, 123.5, 122.4, 83.2, 80.4, 52.8, 52.1, 51.1, 50.9, 39.8,
39.7, 28.4, 28.15, 28.11, 27.0.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H34N2O5S: 413.2105;
found: 413.2104.
N-Phenyl-S,S-dibutylsulfoximine (3me)
tert-Butyl 2-[(tert-Butoxycarbonyl)amino]-4-[N-(2,6-dimethoxy-
phenyl)-S-methylsulfonimidoyl]butanoate (4b)
Yield: 197 mg (92%); yellow viscous oil; cc: 10% EtOAc/hexane; Rf =
0.42.
Yield: 219 mg (78%); transparent oil; cc: 40% EtOAc/hexane; product
spot identified on TLC using ninhydrin stain; Rf = 0.24.
IR (KBr, film): 3048, 2097, 1624, 1573, 1479, 1319, 1274, 1201, 1160,
1079, 943, 841 cm–1
.
IR (KBr, film): 3842, 3321, 2976, 2941, 2837, 2641, 2320, 2082, 1717,
1H NMR (500 MHz, CDCl3):  = 7.18 (t, J = 7.8 Hz, 2 Harom), 7.06 (d, J =
7.4 Hz, 2 Harom), 6.91 (t, J = 7.3 Hz, 1 Harom), 3.17–3.06 (m, 4 H, 2 × CH2),
1.83–1.76 (m, 4 H, 2 × CH2), 1.43–1.37 (m, 4 H, 2 × CH2), 0.91 (t, J = 7.3
Hz, 6 H, 2 × CH3).
13C NMR (125 MHz, CDCl3):  = 145.7, 129.2, 123.6, 121.8, 51.8, 25.2,
21.8, 13.7.
1529, 1446, 1271, 1223, 1148, 1087, 853, 766, 744 cm–1
.
1H NMR (500 MHz, CDCl3):  = 6.91 (t, J = 8.2 Hz, 1 Harom), 6.54 (d, J =
8.2 Hz, 2 Harom), 5.42–5.19 (m, 1 H, CH), 4.25 (s, 1 H, NH), 3.81 (s, 6 H,
2 × OCH3), 3.32–3.22 (m, 2 H, SCH2), 3.05 (d, J = 9.0 Hz, 3 H, SCH3), 2.45
(d, J = 5.1 Hz, 1 H, CH2), 2.27–2.22 (m, 1 H, CH2), 1.43 (d, J = 8.2 Hz, 18
H, 6 × CH3).
13C NMR (125 MHz, CDCl3):  = 170.9, 154.9, 123.1, 105.2, 105.1, 82.6,
80.1, 56.2, 53.0, 41.7, 29.9, 28.5, 28.4, 28.1.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H24NOS: 254.1579; found:
254.1571.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H38N2O7S: 473.2316;
found: 473.2315.
N-(4-Bromophenyl)-S,S-dibutylsulfoximine (3mk)
Yield: 250 mg (89%); pale yellow oil; cc: 40% EtOAc/hexane; Rf = 0.38.
IR (KBr, film): 3272, 3020, 2960, 1726, 1476, 1381, 1262, 1101, 1056,
tert-Butyl 2-[(tert-Butoxycarbonyl)amino]-4-(N-mesityl-S-meth-
ylsulfonimidoyl)butanoate (4c)
1002, 807, 729 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.26 (d, J = 8.7 Hz, 2 Harom), 6.93 (d, J =
8.7 Hz, 2 Harom), 3.16–3.04 (m, 4 H, 2 × CH2), 1.81–1.76 (m, 4 H, 2 ×
CH2), 1.43–1.38 (m, 4 H, 2 × CH2), 0.91 (t, J = 7.3 Hz, 6 H, 2 × CH3).
13C NMR (125 MHz, CDCl3):  = 145.1, 132.1, 125.1, 114.4, 52.0, 25.1,
21.8, 13.7.
Yield: 213 mg (79%); transparent oil; cc: 30% EtOAc/hexane; product
spot identified on TLC using ninhydrin stain; Rf = 0.24.
IR (KBr, film): 3845, 3322, 2941, 2817, 2641, 2320, 2082, 1717, 1529,
1446, 1223, 1148, 1047, 853, 744 cm–1
.
1H NMR (500 MHz, CDCl3):  = 6.80 (s, 2 Harom), 5.27–5.20 (m, 1 H,
CH), 4.24 (s, 1 H, NH), 3.33–3.14 (m, 2 H, SCH2), 2.89 (s, 3 H, SCH3),
2.49–2.40 (m, 1 H, CH2), 2.24 (s, 6 H, 2 × ArCH3-o), 2.20 (s, 3 H, ArCH3-
p), 2.17–2.11 (m, 1 H, CH2), 1.44–1.42 (m, 18 H, 6 × CH3).
13C NMR (125 MHz, CDCl3):  = 170.6, 155.6, 138.1, 133.8, 133.7,
132.5, 129.16, 129.14, 83.1, 52.8, 52.3, 51.9, 40.08, 29.8, 28.4, 28.1,
27.4, 20.8, 19.7.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H23BrNOS: 332.0684;
found: 332.0664.
N-Arylation of an L-Methionine Sulfoximine Derivative with Aryl-
boronic Acids; General Procedure
A mixture of L-methionine sulfoximine derivative (200 mg, 0.59
mmol), CuI (11 mg, 10 mol%), and 4-DMAP (72 mg, 0.59 mmol, 1
equiv) was stirred in MeOH (2 mL) at RT for 5 min under open air. Af-
terwards, the appropriate arylboronic acid (0.89 mmol, 1.5 equiv)
was added and the reaction mixture was allowed to stir at RT until
the completion of reaction. The progress of reaction was monitored
by TLC using 20–40% EtOAc/hexane as eluent (ninhydrin stain). After
completion, the mixture was filtered through a pad of Celite and
washed with CH2Cl2, and the CH2Cl2 solution was evaporated on a ro-
tary evaporator. The crude product was purified by silica gel column
chromatography using 10–50% EtOAc/hexane as eluent to obtain the
desired product.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H40N2O5S: 455.2574;
found: 455.2576.
tert-Butyl (2S)-4-[N-(4-Bromophenyl)-S-methylsulfonimidoyl]-2-
[(tert-butoxycarbonyl)amino]butanoate (4d)
Yield: 260 mg (89%); transparent liquid; cc: 40% EtOAc/hexane; prod-
uct spot identified on TLC using ninhydrin stain; Rf = 0.20.
IR (KBr, film): 3845, 3322, 2981, 2856, 2641, 2320, 2082, 1717, 1529,
1476, 1263, 1201, 1142, 1047, 1004, 853, 744 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.28 (d, J = 7.5 Hz, 2 Harom), 6.91 (d, J =
7.7 Hz, 2 Harom), 5.26 (s, 1 H, CH), 4.21 (s, 1 H, NH), 3.33–3.17 (m, 2 H,
SCH2), 3.01 (s, 3 H, SCH3), 2.40–2.35 (m, 1 H, CH2), 2.13–2.06 (m, 1 H,
CH2), 1.42–1.40 (m, 18 H, 6 × CH3).
13C NMR (125 MHz, CDCl3):  = 170.3, 155.5, 144.4, 144.3, 132.3,
132.2, 125.17, 125.14, 115.0, 83.2, 80.4, 52.6, 51.1, 50.9, 39.8, 39.7,
29.8, 28.4, 28.1, 28.0, 27.0.
tert-Butyl 2-[(tert-Butoxycarbonyl)amino]-4-(S-methyl-N-phenyl-
sulfonimidoyl)butanoate (4a)
Yield: 223 mg (91%); transparent oil; cc: 40% EtOAc/hexane; product
spot identified on TLC using ninhydrin stain; Rf = 0.18.
IR (KBr, film): 3845, 3322, 2941, 2817, 2641, 2320, 2082, 1717, 1610,
1529, 1486, 1233, 1202, 1088, 1047, 853, 744 cm–1
.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H33BrN2O5S: 491.1210;
found: 419.1204.
1H NMR (500 MHz, CDCl3):  = 7.19 (t, J = 6.9 Hz, 2 Harom), 7.04 (t, J =
7.0 Hz, 2 Harom), 6.94 (t, J = 7.2 Hz, 1 Harom), 5.26 (s, 1 H, CH), 4.22 (s, 1
H, NH), 3.38–3.16 (m, 2 H, SCH2), 3.03 (s, 3 H, SCH3), 2.43–2.40 (m, 1
H, CH2), 2.20–2.10 (m, 1 H, CH2), 1.41 (d, J = 7.4 Hz, 18 H, 6 × CH3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–L

L
S. Gupta et al.
Paper
Synthesis
Funding Information
(7) Kim, J.; Ok, J.; Kim, S.; Choi, W.; Lee, P. H. Org. Lett. 2014, 16,
4602.
J.K. gratefully acknowledges DST-India (DST/INT/MPG/P-09/2016) and
Max-Planck Society, Germany for financial support through Indo-Max
Planck partner group project. S.G. and S.B. acknowledge IIT (BHU) for
(8) Aithagani, S. K.; Dara, S.; Munagala, G.; Aruri, H.; Yadav, M.;
Sharma, S.; Vishwakarma, R. A.; Singh, P. P. Org. Lett. 2015, 17,
5547.
(9) Vaddula, B.; Leazer, J.; Varma, R. S. Adv. Synth. Catal. 2012, 354,
986.
a research fellowship.
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2014, 16, 2661. (b) Lämmermann, H.; Sudau, A.; Rackl, D.;
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Acknowledgment
J.K. thanks Mr. Albert Pape for a helpful discussion during the manu-
script preparation. J.K. acknowledges Central Instrumentation Facility
Center (CIFC)-IIT BHU for the NMR facilities. S.S and N.M. acknowl-
edge DST-FIST (Pondicherry University) for MASS facilities.
(12) Hendriks, C. M. M.; Bohmann, R. A.; Bohlem, M.; Bolm, C. Adv.
Synth. Catal. 2014, 356, 1847.
Supporting Information
(13) Gupta, S.; Chaudhary, P.; Muniyappan, N.; Sabiah, S.;
Kandasamy, J. Org. Biomol. Chem. 2017, 15, 8493.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1612216.
S
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–L