One-pot synthesis of β-amino/β-hydroxy selenides and sulfides from aziridines and epoxides

Article abstract of DOI:10.1055/s-0029-1216960

Diaryl disulfides and diselenides undergo facile cleavage on treatment with rongalite (sodium hydroxymethanesulfinate) to generate the corresponding thiolate and selenolate species in situ, which effect the ring opening of aziridines and epoxides in a reg

Full text of DOI:10.1055/s-0029-1216960

PAPER
3267
One-Pot Synthesis of b-Amino/b-Hydroxy Selenides and Sulfides from
Aziridines and Epoxides
O
ne-PotSynthesis
e
of
b
-Amin
n
o/
b
-Hydroxy
k
Selenides an
a
d Sulfidestaraman Ganesh, Srinivasan Chandrasekaran*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India
Fax +91(80)23602423; E-mail: scn@orgchem.iisc.ernet.in
Received 14 April 2009; revised 17 June 2009
diselenides or from selenocyanates followed by coupling
with an alkyl halide in one pot, since most of the selenols
are unstable and are oxidized spontaneously to the corre-
sponding diselenides in air. Reducing agents, such as
Abstract: Diaryl disulfides and diselenides undergo facile cleavage
on treatment with rongalite (sodium hydroxymethanesulfinate) to
generate the corresponding thiolate and selenolate species in situ,
which effect the ring opening of aziridines and epoxides in a regio-
selective manner. A simple, mild, cost-effective protocol has been NaBH4, Na/NH3, Bu3SnH, and LiAlH4, have been used
for the synthesis of selenides.9 Ranu et al. developed an
developed to prepare b-amino and b-hydroxy sulfides and selenides
in a one-pot operation.
indium(I) iodide mediated cleavage of diaryl diselenides
and diaryl disulfides.10
Key words: b-amino selenide, b-amino sulfide, b-hydroxy selen-
ide, b-hydroxy sulfide, rongalite, aziridine, epoxide
Generally, b-amino or b-hydroxy sulfides and selenides
are prepared using the same methodology starting from an
amino alcohol, followed by conversion of the hydroxy
In recent years the synthesis of peptidomimetic molecules
group into a good leaving group and subsequent nucleo-
has become an increasingly popular area in the field of
philic substitution with thiolate or in situ generated sele-
drug design.1 Specifically, synthetic routes to sulfanyl-
nolate.11 Later, aziridines and epoxides were found to be
and selanyl-substituted unnatural amino acids and its de-
the best starting materials to prepare these analogues in a
rivatives, which are the building blocks for the synthesis
stereo- and regiocontrolled manner.12 Wakselman et al.
of modified thio- and seleno-proteins,2 have attracted at-
demonstrated the synthesis of perfluoroalkyl sulfides by
tention due to their interesting structural and biological
the treatment of perfluoroalkyl halides with an organic
properties. The seleno-proteins play an important role in
disulfide mediated by rongalite.13 Tang et al. reported the
metabolic processes, glutathione peroxidase (GPx) for ex-
synthesis of alkyl aryl sulfides mediated by sodium
ample, acts as a peroxide scavenger.3a In addition to the
dithionite, sodium thiosulfate, or rongalite (sodium hy-
droxymethanesulfinate, 1) and compared the rates and
percentage of conversion and it was found that rongalite
interesting properties of thio- and seleno- proteins, simple
organosulfur and organoselenium compounds exhibit
many useful biological and medicinal properties.4 They
is the most efficient reducing agent for disulfides and for
are generally targeted as compounds with antioxidant, an-
the synthesis of sulfides.14
titumor, and antimicrobial activity and many of these
Following these literature reports, we attempted the syn-
thesis of b-amino and b-hydroxy chalcogenides in a one-
pot process mediated by rongalite. Herein, we report our
comprehensive study on the aziridine/epoxide ring open-
ing with sulfur and selenium nucleophiles derived from
disulfides/diselenides in the presence of rongalite (sodium
hydroxymethanesulfinate, 1), which led to an efficient
synthesis of b-amino- and b-hydroxy selenides and sul-
fides from the corresponding diselenides and disulfides
under mild conditions (Scheme 1).
compounds are competitive inhibitors for target proteins.3
Apart from the biological applications, enantiomerically
pure b-amino or b-hydroxy sulfides and selenides are ex-
cellent ligands for transition-metal-based asymmetric ca-
talysis.5 Keeping in mind the wide range of applications of
these analogues, general synthetic methodologies to pre-
pare sulfur- and selenium-containing derivatives of amino
acids in a simple, efficient, stereoregulated manner is
greatly appreciated and remains a challenge. A myriad of
work has been devoted towards the synthesis of these
analogues.6
Reaction of enantiopure N-tosylaziridine 2 with diphenyl
diselenide (3a) mediated by rongalite (1) was carried out
by the addition of 3a (0.5 equiv) to a well-stirred solution
of aziridine 2 in N,N-dimethylformamide, followed by the
addition of potassium carbonate (2 equiv) and rongalite
(1, 3 equiv) at room temperature (20 min) resulting in the
regioselective ring opening of the aziridine 2 to form the
expected b-amino selenide 4a in 98% yield15 (Scheme 2).
Unsymmetrical sulfides are generally prepared from alkyl
halides by nucleophilic substitution of thiols in the pres-
ence of a base and a suitable solvent.7 A number of transi-
tion-metal-catalyzed coupling reactions have been
developed to synthesize these sulfides, which are shown
to be mild and selective.8 Introduction of the selenium
moiety is generally carried out by reductive cleavage of
A mechanism has been proposed for the reduction of di-
selenide 3a followed by the ring opening of aziridine 2
(Scheme 3).14b Rongalite when treated with a base decom-
SYNTHESIS 2009, No. 19, pp 3267–3278
Advanced online publication: 21.08.2009
DOI: 10.1055/s-0029-1216960; Art ID: T07409SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
9
–
poses to formaldehyde and HSO2 , which transfers a sin-

3268
V. Ganesh, S. Chandrasekaran
PAPER
O
S
OH
1
NHTs
Ts
N
NaO
X
X
X
X
R1
+
R2
(0.5 equiv)
R2
2
R1
K2CO3, DMF
r.t.
O
S
OH
1
OH
NaO
O
R1
+
R2
(0.5 equiv)
R2
K2CO3, DMF
r.t.
2
R1
X = selenium (24 examples)
X = sulfur (24 examples)
Scheme 1 General scheme for the synthesis of b-amino and b-hydroxy selenides and sulfides
ONa
HO
S
NHTs
1
O
NTs
Ph
Se
Se Se
Ph
K2CO3, DMF
r.t., 20 min
4a
2
3a
98%
Scheme 2 Nucleophilic ring opening of 2 with diphenyl diselenide (3a) mediated by 1
ONa
base
HO
S
HSO2– Na+
HCHO
+
O
SET
SET
.
HSO2– Na+
Se
Se
.
Se Se
HSO2
3a
X
Y
.
.
Se
H+
SO2
Se
HSO2
X
Y
NHTs
Ts
N
Ph
Se
Ph
Se
2
Scheme 3 Mechanism for the formation of b-amino selenides
gle electron to the diselenide resulting in the formation of ing to the corresponding b-amino selenides 4b–f, respec-
a radical anion intermediate. The intermediate may spon- tively, in excellent yield. In the case of 2-(4,5-
taneously disproportionate into a radical X and anionic dihydrooxazol-2-yl)-substituted diselenide 3d the cleav-
species Y. The selenium radical X further gets reduced to age was slower relative to the other diselenides due to
anionic species Y, by another single electron transfer steric crowding at the ortho-position. The 4,5-dihydro-
(SET). The attack of Y on aziridine in a regioselective oxazol-2-yl group is a masked carboxylic acid and it can
manner at the less hindered carbon gives the desired b- be deprotected after the reaction.17 An aliphatic diselenide
amino selenide.
like dibenzyl diselenide (3g) failed to react with rongalite
to give the selenolate even after stirring for 24 hours at
room temperature.
The mildness of the reaction conditions and the excellent
yield obtained encouraged us to explore the scope and
generality of the methodology. A wide range of dise- To expand the scope of this methodology, we decided to
lenides 3b–g were selected to study the ring-opening reac- study the reactivity of other aziridines bearing different
tion with phenylalanine-derived aziridine 2. All diaryl functionalities and complexity in the structure, with
diselenides were synthesized from the corresponding diphenyl diselenide (3a). The reaction of aziridines 5a–j18
anilines by a diazotization, selenocyanation, and reduc- with diphenyl diselenide (3a) mediated by rongalite (r.t.,
tion sequence.16 The results of our study are summarized 20 min), resulted in the formation of the corresponding b-
in Table 1. Diselenides 3b–f reacted with aziridine 2 lead- amino selenides 6a–j in excellent yield (Table 2).
Synthesis 2009, No. 19, 3267–3278 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of b-Amino/b-Hydroxy Selenides and Sulfides
3269
Table 1 Synthesis of Phenylalanine-Derived b-Amino Selenides 4
Entry
1
Reactant
R-Se-Se-R
Product
Time
Yield (%)
NHTs
Se
Ts
Ph
N
20 min
98
97
Ph
3a
2
2
4a
NHTs
Ph
Se
Me
2
3
30 min
30 min
3b
4b
NHTs
Ph
Se
2
2
2
93
89
95
3c
4c
O
N
O
NHTs
N
4
5
60 min
20 min
Ph
Se
3d
3e
4d
NHTs
Ph
Se
Cl
Cl
4e
NHTs
Ph
Se
O2N
6
7
2
2
20 min
24 h
94
–
NO2
3f
4f
no reaction
3g
Table 2 Synthesis of b-Amino Selenides 6 from Diphenyl Diselenide (3a) and Various Aziridines
Entry
Reactanta
Product
Time (min)
20
Yield (%)
Ts
N
NHTs
SePh
96
1
SePh
NHTs
(1.1:1)b
Ph
Ph
Ph
6a
6a¢
5a
TsN
OH
2
3
30
40
94
95
Se
OH
NHTs
5b
6b
Ts
N
Se
NHTs
5c
6c
Synthesis 2009, No. 19, 3267–3278 © Thieme Stuttgart · New York

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V. Ganesh, S. Chandrasekaran
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Table 2 Synthesis of b-Amino Selenides 6 from Diphenyl Diselenide (3a) and Various Aziridines (continued)
Entry
4
Reactanta
Product
Time (min)
40
Yield (%)
Ts
N
92
90
Se
NHTs
NHTs
5d
6d
Ts
N
5
6
40
30
Se
5e
6e
SePh
NHTs
Ts
N
83
OH
OH
(1:1.7)b
OH
NHTs
SePh
5f
6f¢
6f
NHTs
7
8
30
30
92
94
NTs
NTs
SePh
5g
6g
NHTs
SePh
5h
5i
6h
SePh
NHTs
SePh
86
NTs
9
30
45
(1:1.8)b
NHTs
6i
6i¢
Cbz
N
10
95
Ph
Se
Ph
NHCbz
5j
6j
a Compounds 5a–i are racemic and the relative stereochemistry is represented, 5j was derived enantiomerically pure from L-phenylalanine.
b Based on 1H NMR integration values.
Styrene-derived aziridine 5a reacted with diphenyl dise- When propylene oxide was treated with diphenyl dise-
lenide (3a) to give an inseparable mixture of regioisomers lenide (3a) and rongalite, the reaction proceeded cleanly
6a and 6a¢ in the ratio 1.1:1.19 The regioisomers arise due (DMF, r.t., 20 min) to give the b-hydroxy selenide 8a in
to similar reactivity profile of the less hindered carbon and 87% yield (Scheme 4).
the benzylic center. The aziridines 5b–h underwent facile
ring opening in the usual manner at the less hindered car-
ONa
HO
S
bon center to give the desired products 6b–h. In the case
of the trisubstituted aziridine 5f, the reaction gave a 1.7:1
regioisomeric mixture of products 6f/6f¢. This can be ex-
plained on the basis of the competition of nucleophilic at-
tack in a SN1 like pathway at the tertiary center and SN2
fashion at the secondary center. The same kind of regio-
isomeric mixture 6i/6i¢ is obtained in the methylcyclohex-
ene-derived aziridine 5i. Since deprotection of the tosyl
group involves harsh conditions, the same methodology
has been demonstrated using benzyloxycarbonyl (Cbz)
OH
1
O
O
+
Se Se
SePh
K2CO3, DMF
r.t., 20 min
8a
87%
7a
3a
Scheme 4 Nucleophilic ring opening of epoxides with diphenyl
diselenide (3a) mediated by 1
The scope of the methodology was further investigated by
protected aziridine 5j. The Cbz-protected aziridine 5j un- using various epoxides to study the reactivity. The ep-
derwent ring opening smoothly in 45 minutes to give the oxides 7b–h were treated with diphenyl diselenide (3a)
b-amino selenide 6j in 95% yield.
and rongalite under the same conditions leading to the for-
mation of b-hydroxy selenides 8b–h in excellent yields
(Table 3). Ring opening in the case of styrene oxide (7b),
The versatility of the reaction was explored further by ex-
tending the methodology to the ring opening of epoxides.
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One-Pot Synthesis of b-Amino/b-Hydroxy Selenides and Sulfides
3271
Table 3 Synthesis of b-Hydroxy Selenides 8 from Diphenyl Diselenide (3a) and Various Epoxides
Entry
1
Reactanta
Product
Time (min)
20
Yield (%)
97
OH
O
Se
Ph
Ph
7b
8b
OH
O
2
3
4
20
20
20
95
91
95
SePh
SePh
7c
8c
O
OH
p-NO2BzO
p-NO2BzO
8d
8e
7d
OH
O
O
O
SePh
7e
OH
O
5
30
94
SePh
7f
8f
OH
O
O
SePh
6
7
30
30
93
92
PhSe
PhSe
O
OH
7g
7h
8g
SePh
Br
OH
8h
a All compounds except 7d were racemic, p-NO2Bz = p-nitrobenzoyl.
(unlike the styrene-derived aziridine 5a) resulted in a sin- As in the case of diselenides, disulfides can also undergo
gle regioisomer 8b in 95% yield following the SN2 path- reductive cleavage in the presence of rongalite. The reac-
way exclusively. The reaction was further extended to bis- tion was carried out by the addition of diphenyl disulfide
epoxides, to give bis-selenides. The reaction of bis-ep- (9a, 0.5 equiv) to a solution of phenylalanine-derived azir-
oxide 7g yielded the corresponding bis-selenide 8g (93%). idine 2 in N,N-dimethylformamide, followed by the addi-
The bis-selenide 8g is an important precursor for making tion of potassium carbonate (2 equiv). The mixture was
the trans-furofuran moiety in the total synthesis of (–)-ku- stirred vigorously followed by the addition of rongalite (3
mausallene.20 Similarly, in the reaction of epibromohy- equiv).15 The reaction proceeded smoothly (20 min) to
drin 7h, the corresponding bis-selenide 8h was obtained give the corresponding b-amino sulfide 10a as the sole
in 92% yield.
product in 96% yield (Scheme 5). The facile reactivity
and the excellent yield obtained encouraged us to explore
the reaction with various disulfides to check the generality
of this methodology.
Having demonstrated the ability of rongalite to cleave the
diselenide bond and its application to the synthesis of b-
amino selenides and b-hydroxy selenides, the chemistry
was extended to the synthesis of b-amino sulfides and b- Phenylalanine-derived aziridine 2 was taken as a standard
hydroxy sulfides by reductive cleavage of diaryl disul- and reacted with various organic disulfides. The reaction
fides.
of disulfides 9b–f with aziridine 2 mediated by rongalite
ONa
HO
S
NHTs
1
O
NTs
Ph
S
+
S
S
Ph
K2CO3, DMF
r.t., 20 min
2
9a
10a
96%
Scheme 5 Nucleophilic ring opening of 2 with diphenyl disulfide (9a) mediated by 1
Synthesis 2009, No. 19, 3267–3278 © Thieme Stuttgart · New York

3272
V. Ganesh, S. Chandrasekaran
PAPER
Table 4 Synthesis of Phenylalanine-Derived b-Amino Sulfides 10
Entry
1
Reactant
R-S-S-R
Product
Time
Yield (%)
NHTs
S
Ts
Ph
N
20 min
96
96
92
Ph
9a
2
2
10a
NHTs
Ph
S
Me
2
3
4
30 min
30 min
20 min
9b
10b
NHTs
Ph
S
N
2
2
N
9c
10c
NHTs
Ph
S
Cl
94
Cl
9d
10d
NHTs
Ph
S
O2N
5
6
2
2
20 min
24 h
95
–
NO2
9e
9f
10e
no reaction
gave the corresponding b-amino sulfides 10b–e in excel- Following the efficient ring opening of aziridines, the re-
lent yield (Table 4). As in the case of dibenzyl diselenide action was extended to study the ring opening of epoxides.
(3g), dibenzyl disulfide (9f) also failed to react with azir- To compare the reactivity differences between the seleni-
idine 2 even after 24 hours.
um and sulfur nucleophiles, the same set of epoxides were
taken for the study. Initially, propylene oxide 7a was
treated with diphenyl disulfide (9a) and rongalite in N,N-
dimethylformamide to give 12a as the sole product in
93% yield (Scheme 6). The reaction of various epoxides
7b–h with diphenyl disulfide (9a) and rongalite gave the
corresponding b-hydroxy sulfides 12b–h in excellent
yields (Table 6).
The methodology was further extended to various aziri-
dines. The aziridines 5a–k were treated with diphenyl di-
sulfide (9a, 0.5 equiv) followed by the addition of
potassium carbonate and rongalite and the reaction (r.t.,
20 min) resulted in the formation of b-amino sulfides
11a–k in excellent yields (Table 5). In the case of styrene-
derived aziridine 5a, the reaction led to a regioisomeric
mixture of b-amino sulfides 11a/11a¢ in 1:1 ratio with a
total yield of 96%.
ONa
HO
S
OH
1
O
O
The aziridines 5d,e underwent ring opening smoothly
from the less hindered side. Since the isopropyl group
blocks the approach of the incoming nucleophile, the nu-
cleophile attacks at the less hindered side of the aziridine
to give 10d,e as the sole products in excellent yield. With
trisubstituted aziridine 5f, a regioisomeric mixture of b-
amino sulfides 11f and 11f¢ were formed in 90% yield in
the ratio 3:1. Cbz-protected aziridine 5j was successfully
converted into Cbz-b-amino sulfide 11j in 96% yield,
which can be converted into the free amine by simple
deprotection.
+
S
S
SePh
K2CO3, DMF
r.t., 20 min
12a
93%
7a
9a
Scheme 6 Nucleophilic ring opening of epoxides with diphenyl
disulfide (9a) mediated by 1
In summary, reductive cleavage of diaryl disulfides and
diselenides mediated by rongalite followed by the ring
opening of aziridines provides an easy access to b-amino
sulfides and b-amino selenides in a stereospecific and re-
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One-Pot Synthesis of b-Amino/b-Hydroxy Selenides and Sulfides
3273
Table 5 Synthesis of b-Amino Sulfides 11 from Diphenyl Disulfide (9a) and Various Aziridines
Entry
1
Reactanta
Product
Time (min)
20
Yield (%)
Ts
N
NHTs
SPh
96
SPh
NHTs
(1:1)b
Ph
Ph
Ph
11a
11a¢
5a
TsN
OH
2
3
4
30
40
40
94
95
94
92
S
OH
NHTs
5b
11b
Ts
N
S
NHTs
5c
11c
Ts
N
S
NHTs
5d
11d
Ts
N
5
6
40
30
S
NHTs
5e
11e
SPh
NHTs
Ts
N
90
OH
OH
(3:1)b
OH
NHTs
SPh
5f
11f
11f¢
NHTs
7
8
30
30
92
93
NTs
SPh
5g
11g
NHTs
NTs
NTs
SPh
5h
5i
11h
SPh
NHTs
89
9
SPh
30
(4:1)b
NHTs
11i
11i¢
Cbz
N
10
11
45
30
96
94
Ph
S
Ph
NHCbz
5j
11j
NHTs
NTs
SPh
5k
11k
a Compounds 5a–i, 5k are racemic and the relative stereochemistry is represented, 5j was derived enantiomerically pure from L-phenylalanine.
b Based on the 1H NMR integration values.
gioselective manner under mild conditions in a one-pot high yield. The reaction has been extended further to the
operation. The methodology would be of interest due to ring opening of epoxides in a stereospecific and regiose-
the cost-effective and metal-free reaction conditions and
Synthesis 2009, No. 19, 3267–3278 © Thieme Stuttgart · New York

3274
V. Ganesh, S. Chandrasekaran
PAPER
lowed by K2CO3 (0.4 mmol, 2 equiv) and rongalite (1, 0.6 mmol, 3
equiv). The mixture was stirred at r.t. for 30–60 min (TLC monitor-
ing). After complete consumption of the starting material, H2O was
added to quench the reaction and it was extracted with CH2Cl2 (2 ×
10 mL). The organic layer was separated and dried (anhyd Na2SO4).
The crude product was purified by column chromatography (silica
gel).
Table 6 Synthesis of b-Hydroxy Sulfides 12 from Diphenyl Disul-
fide (9a) and Various Epoxides
Entry
Reactanta
Product
Time Yield
(min) (%)
OH
O
S
Ph
1
20
97
Ph
(S)-1-Phenyl-3-(4-tolylselanyl)-N-tosylpropan-2-amine (4b)
Colorless oil; yield: 97%; Rf = 0.3 (EtOAc–hexanes, 2:8).
7b
[a]D25 –52.9 (c 2, CHCl3).
12b
OH
O
IR (neat): 3280, 3027, 2922, 1598, 1492, 1330, 1158, 1093, 806,
615 cm–1.
2
3
4
20
20
20
94
91
93
SPh
7c
1H NMR (300 MHz, CDCl3): d = 7.41 (d, J = 6.3 Hz, 2 H), 7.30 (d,
J = 6.0 Hz, 2 H), 7.16–7.15 (m, 3 H), 7.1–7.05 (m, 4 H), 6.93–6.91
(m, 2 H), 4.83 (d, J = 5.1 Hz, 1 H), 3.52–3.45 (m, 1 H), 3.07 (dd,
J = 3.3, 9.6 Hz, 1 H), 2.94 (dd, J = 4.8, 10.2 Hz, 1 H), 2.80–2.71 (m,
1 H), 2.37 (s, 3 H), 2.34 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 143.0, 137.3, 136.8, 136.5, 133.3,
130.0, 129.4, 129.2, 128.5, 126.9, 126.6, 125.3, 54.5, 40.2, 33.1,
21.5, 21.1.
12c
12d
O
OH
p-NO2BzO
SPh
p-NO2BzO
7d
OH
O
O
O
SPh
7e
12e
77Se NMR (75 MHz, CDCl3): d = 236.096.
OH
HRMS: m/z [M + Na]+ calcd for C23H25N2NaO2SSe: 482.0669;
O
5
30
93
found: 482.0669.
SPh
7f
12f
(S)-1-(1-Naphthylselanyl)-3-phenyl-N-tosylpropan-2-amine
(4c)
Colorless oil; yield: 93%; Rf = 0.4 (EtOAc–hexanes, 2:8).
[a]D25 –67.3 (c 1, CHCl3).
IR (neat): 3276, 3054, 2923, 1498, 1328, 1158, 767, 748, 665 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.27–8.24 (m, 1 H), 7.88–7.81 (m,
2 H), 7.69 (d, J = 6.0 Hz, 1 H), 7.57–7.52 (m, 2 H), 7.37 (t, J = 39.0
Hz, 1 H), 7.34 (m, 2 H), 7.16–7.11 (m, 3 H), 6.88 (d, J = 8.4 Hz, 4
H), 4.76 (d, J = 7.2 Hz, 1 H), 3.53–3.42 (m, 1 H), 3.10 (dd, J = 4.5,
12.9 Hz, 1 H), 2.99 (dd, J = 6.6, 13.8 Hz, 1 H), 2.83–2.76 (m, 2 H),
2.26 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 142.9, 136.6, 136.5, 134.1, 132.8,
129.5, 129.3, 129.2, 128.7, 128.6, 128.4, 127.4, 126.8, 126.7, 126.6,
126.3, 125.8, 54.5, 40.3, 32.7, 31.4.
OH
O
O
SPh
6
7
30
30
94
94
PhS
PhS
O
OH
7g
7h
12g
SPh
Br
OH
12h
a All compounds except 7d were racemic; p-NO2Bz = p-nitrobenzoyl.
lective manner for the synthesis of b-hydroxy sulfides and
selenides in excellent yields.
77Se NMR (75 MHz, CDCl3): d = 181.220.
HRMS: m/z [M + Na]+ calcd for C26H25NNaO2SSe: 518.0669;
All reactions were carried out in oven-dried apparatus using dry sol-
vents under anhydrous conditions, unless otherwise noted. Reaction
mixtures were stirred magnetically unless otherwise stated. Com-
mercial grade solvents were distilled and dried according to litera-
ture procedures.21 Analytical TLC was performed on commercial
plates coated with silica gel GF254 (0.25 mm). Silica gel (230–400
mesh) was used for column chromatography. Melting points deter-
mined are uncorrected. Yields refer to chromatographically and
spectroscopically (1H NMR) homogeneous materials, unless other-
wise stated. IR spectra were recorded on a FT-IR spectrometer.
NMR spectra were recorded on 300 or 400 MHz instruments and
chemical shifts are cited with respect to SiMe4 as internal (1H and
13C) and Me2Se (77Se) as external standard. High resolution mass
spectra (HR-MS) were recorded on an electro-spray mass spectro-
meter. All novel compounds were fully characterized. All known
compounds had spectroscopic data consistent with the literature:
4a,22a 6a,21b 6b,22b 6h,22b 8a,12d 8b,22d 8h,22e 10a,12a 10d,12c 11a,12a
11c,12c 11g,12a 11h,12a 11j,22f 11k,22g 12a,22h 12b,22i 12f,22j 12h.22k
r.t. = 28 °C.
found: 518.0668.
(S)-1-[2-(5,5-Dimethyl-4,5-dihydrooxazol-2-yl)phenylselanyl]-
3-phenyl-N-tosylpropan-2-amine (4d)
Colorless oil; yield: 89%; Rf = 0.3 (EtOAc–hexanes, 3:7).
[a]D25 –34.1 (c 1, CHCl3).
IR (neat): 3281, 2968, 2960, 1646, 1455, 1314, 1157, 1030, 963,
813, 733, 655 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.70 (m, 1 H), 7.45 (d, J = 6.0 Hz,
2 H), 7.26–7.19 (m, 6 H), 7.05–7.0 (m, 4 H), 5.74 (d, J = 5.4 Hz, 1
H), 4.10 (s, 2 H), 3.62–3.57 (m, 1 H), 3.02–2.92 (m, 3 H), 2.76 (dd,
J = 4.8, 9.9 Hz, 1 H), 2.32 (s, 3 H), 1.45 (s, 3 H), 1.44 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 162.1, 143.4, 137.5, 133.1, 131.4,
131.3, 130.4, 129.9, 129.4, 129.1, 127.3, 127.2, 126.2, 79.4, 69.1,
59.6, 41.5, 32.3, 29.1, 29.0, 22.0.
77Se NMR (75 MHz, CDCl3): d = 255.64.
HRMS: m/z [M + Na]+ calcd for C27H30N2NaO3SSe: 565.104;
b-Amino Selenides or b-Hydroxy Selenides; General Procedure
To a well-stirred soln of aziridine or epoxide (0.2 mmol, 1 equiv) in
DMF (2 mL) was added the diselenide (0.1 mmol, 0.5 equiv) fol-
found: 565.1035.
Synthesis 2009, No. 19, 3267–3278 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of b-Amino/b-Hydroxy Selenides and Sulfides
77Se NMR (75 MHz, CDCl3): d = 294.45.
3275
(S)-1-(4-Chlorophenylselanyl)-3-phenyl-N-tosylpropan-2-
amine (4e)
Yield: 95%; mp 62 °C; Rf = 0.4 (EtOAc–hexanes, 2:8).
[a]D25 –54.4 (c 2, CHCl3).
HRMS: m/z [M + Na]+ calcd for C19H25NNaO2Se: 434.0669; found:
434.0676.
(3R*,4S*)-2-Methyl-4-(phenylselanyl)-N-tosylpentan-3-amine
(6d)
Colorless oil; yield: 92%; Rf = 0.3 (EtOAc–hexanes, 1:9).
IR (neat): 3282, 2924, 1598, 1475, 1325, 1159, 1090, 813, 743, 700,
665 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41 (d, J = 7.8 Hz, 2 H), 7.31 (d,
J = 8.4 Hz, 2 H), 7.22–7.03 (m, 7 H), 6.93–6.90 (m, 2 H), 4.88 (d,
J = 6.9 Hz, 1 H), 3.51–3.36 (m, 1 H), 3.12 (dd, J = 4.8, 12.9 Hz, 1
H), 2.94 (dd, J = 6.3, 13.8 Hz, 1 H), 2.87–2.69 (m, 2 H), 2.38 (s, 3
H).
13C NMR (75 MHz, CDCl3): d = 143.2, 136.3, 134.1, 129.5, 129.3,
129.1, 128.6, 128.4, 126.9, 126.7, 126.4, 54.4, 40.2, 33.11, 21.5.
IR (neat): 3480, 2962, 2939, 2784, 1626, 1600, 1443, 1325, 1164,
1090, 1033, 747, 667 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.69 (d, J = 8.1 Hz, 2 H), 7.40–
7.37 (m, 2 H), 7.31–7.17 (m, 5 H), 4.94 (d, J = 9.9 Hz, 1 H), 3.36
(ddd, J = 0.1, 0.9, 4.5 Hz, 1 H), 3.15–3.06 (m, 1 H), 2.38 (s, 3 H),
2.09–1.99 (m, 1 H), 1.38 (d, J = 7.5 Hz, 3 H), 0.84 (d, J = 5.1 Hz, 6
H).
13C NMR (75 MHz, CDCl3): d = 143.0, 138.6, 134.4, 129.6, 129.4,
129.0, 127.7, 126.9, 63.0, 45.4, 29.9, 21.5, 21.0, 20.4, 17.3, 16.9.
77Se NMR (75 MHz, CDCl3): d = 245.881.
HRMS: m/z [M + Na]+ calcd for C22H22ClNNaO2SSe: 502.0123;
found: 502.0121.
77Se NMR (75 MHz, CDCl3): d = 363.35.
(S)-1-(4-Nitrophenylselanyl)-3-phenyl-N-tosylpropan-2-amine
(4f)
HRMS: m/z [M + Na]+ calcd for C19H25NNaO2SSe: 434.0669;
found: 434.0646.
Yield: 94%; mp 117 °C; Rf = 0.5 (EtOAc–hexanes, 4:6).
(3R*,4R*)-2-Methyl-4-(phenylselanyl)-N-tosylpentan-3-amine
(6e)
Yield: 90%; mp 65 °C; Rf = 0.3 (EtOAc–hexanes, 1:9).
[a]D25 –66.0 (c 1, CHCl3).
IR (neat): 3447, 3295, 1596, 1574, 1513, 1343, 1158, 1066, 851
cm–1.
IR (neat): 3288, 2963, 2873, 1598, 1437, 1327, 1157, 1093, 1031,
814, 741, 667 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.06–8.04 (m, 2 H), 7.47–7.26 (m,
2 H), 7.21–7.11 (m, 5 H), 6.95–6.93 (m, 2 H), 4.88 (d, J = 5.4 Hz, 1
H), 3.57–3.53 (m, 1 H), 3.29 (dd, J = 3.6, 9.9 Hz, 1 H), 3.07 (dd,
J = 5.1, 9.9 Hz, 1 H), 2.93 (dd, J = 5.1, 7.5 Hz, 1 H), 2.78–2.73 (m,
2 H), 2.38 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 146.3, 143.5, 140.4, 136.5, 136.0,
129.6, 129.2, 128.8, 127.9, 127.0, 12.9, 123.9, 54.4, 40.4, 32.1,
21.5.
1H NMR (300 MHz, CDCl3): d = 7.87 (d, J = 8.1 Hz, 2 H), 7.54–
7.51 (m, 2 H), 7.30–7.22 (m, 5 H), 4.84 (d, J = 6.3 Hz, 1 H), 3.53
(dd, J = 3.0, 4.2 Hz, 1 H), 3.18–3.11 (m, 1 H), 2.39 (s, 3 H), 1.96–
1.80 (m, 1 H), 1.25 (d, J = 6.9 Hz, 3 H), 0.80 (d, J = 7.2 Hz, 3 H),
0.75 (d, J = 6.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 142.9, 138.7, 135.3, 129.4, 129.0,
128.4, 127.8, 126.9, 64.8, 44.0, 31.6, 21.4, 20.6, 20.3, 19.5.
77Se NMR (75 MHz, CDCl3): d = 271.059.
HRMS: m/z [M + Na]+ calcd for C22H22N2NaO4SSe: 513.0364;
77Se NMR (75 MHz, CDCl3): d = 342.3.
HRMS: m/z [M + Na]+ calcd for C19H25NNaO2SSe: 434.0669;
found: 513.0364.
found: 434.0682.
4-(Phenylselanyl)-3-(tosylamino)butan-1-ol (6b)
Colorless oil; yield: 94%; Rf = 0.3 (EtOAc–hexanes, 3:7).
(1R*,2R*)-2-(Phenylselanyl)-N-tosylcyclopentan-3-amine (6g)
Colorless oil; yield: 92%; Rf = 0.4 (EtOAc–hexanes, 2:8).
IR (neat): 3475, 2961, 2939, 2789, 1616, 1600, 1493, 1325, 1204,
1093, 1023, 745, 667 cm–1.
IR (neat): 3273, 2978, 2853, 1590, 14, 1356, 1150, 1190, 1030, 823,
746, 663 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.66 (d, J = 7.8 Hz, 2 H), 7.38 (d,
J = 7.8 Hz, 2 H), 7.36–7.18 (m, 5 H), 5.13 (d, J = 4.2 Hz, 1 H),
3.38–3.28 (m, 2 H), 2.43 (s, 3 H), 2.16–2.01 (m, 2 H), 1.70–1.42 (m,
4 H).
13C NMR (75 MHz, CDCl3): d = 143.3, 136.9, 135.0, 129.6, 128.9,
128.0, 127.8, 127.2, 60.0, 47.3, 31.6, 30.7, 21.9, 21.5.
77Se NMR (75 MHz, CDCl3): d = 352.8.
HRMS: m/z [M + Na]+ calcd for C18H21NNaO2SSe: 418.0356;
1H NMR (300 MHz, CDCl3): d = 7.58 (d, J = 8.4, Hz, 2 H), 7.41–
7.38 (m, 2 H), 7.30–7.19 (m, 5 H), 5.29 (d, J = 8.4 Hz, 1 H), 3.83–
3.76 (m, 1 H), 3.69–3.55 (m, 2 H), 3.09 (dd, J = 3.6, 12.9 Hz, 1 H),
2.69 (dd, J = 6.9, 12.9 Hz, 1 H), 2.41 (s, 3 H), 2.18 (s, 1 H), 1.88–
1.78 (m, 1 H), 1.66–1.55 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 143.5, 138.5, 133.1, 129.7, 129.3,
127.4, 127.0, 58.9, 51.1, 36.5, 34.1, 21.5.
77Se NMR (75 MHz, CDCl3): d = 243.28.
HRMS: m/z [M + Na]+ calcd for C17H21NNaO3SSe: 422.0305;
found: 418.0349.
found: 422.0304.
(S)-N-(Benzyloxycarbonyl)-1-phenyl-3-(phenylselanyl)propan-
3-amine (6j)
Yield: 95%; mp 74 °C; Rf = 0.6 (EtOAc–hexanes, 2:8).
[a]D25 +15.1 (c 1, CHCl3).
IR (neat): 3287, 3030, 2928, 1700, 1511, 1253, 1024, 738, 696 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.49–7.1 (m, 15 H), 5.02 (s, 2 H),
4.94 (d, J = 6.9 Hz, 1 H), 4.15–4.12 (m, 1 H), 3.05 (d, J = 3.3 Hz, 2
H), 2.90 (d, J = 7.2 Hz, 2 H).
(3R*,4S*)-4-(Phenylselanyl)-N-tosylhexan-3-amine (6c)
Yield: 95%; mp 62 °C; Rf = 0.5 (EtOAc–hexanes, 3:7).
IR (neat): 3475, 2961, 2939, 2789, 1616, 1600, 1493, 1325, 1204,
1093, 1023, 745, 667 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.63 (d, J = 8.4 Hz, 2 H), 7.38–
7.18 (m, 7 H), 5.2 (d, J = 9.6 Hz, 1 H), 3.40–3.31 (m, 1 H), 2.83 (td,
J = 3.3, 6.5 Hz, 1 H), 2.40 (s, 3 H), 1.77–1.64 (m, 2 H), 1.61–1.50
(m, 1 H), 1.36–1.21 (m, 1 H), 0.96–0.84 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 143.1, 133.9, 129.7, 129.5, 129.4,
129.2, 127.5, 126.9, 58.3, 57.4, 28.2, 24.2, 21.5, 13.0, 10.6.
13C NMR (75 MHz, CDCl3): d = 155.5, 137.2, 132.8, 129.3, 129.2,
128.5, 128.4, 128.0, 127.9, 127.1, 126.6, 66.6, 52.2, 40.2, 32.5.
Synthesis 2009, No. 19, 3267–3278 © Thieme Stuttgart · New York

3276
V. Ganesh, S. Chandrasekaran
PAPER
b-Amino Sulfides/b-Hydroxy Sulfides; General Procedure
77Se NMR (75 MHz, CDCl3): d = 240.56.
To a well-stirred soln of aziridine or epoxide (0.2 mmol, 1 equiv) in
DMF (2 mL) was added the disulfide (0.1 mmol, 0.5 equiv) fol-
lowed by K2CO3 (0.4 mmol, 2 equiv) and rongalite (1, 0.6 mmol, 3
equiv). The mixture was stirred at r.t. for 30–60 min (TLC monitor-
ing). After complete consumption of the starting material, H2O was
added to quench the reaction and it was extracted with CH2Cl2 (2 ×
10 mL). The organic layer was separated and dried (anhyd Na2SO4).
The crude product was further purified by column chromatography
(silica gel).
HRMS: m/z [M + Na]+ calcd for C23H23NNaO2Se: 448.0792; found:
448.08.
1-(Phenylselanyl)hex-5-en-1-ol (8c)
Colorless oil; yield: 95%; Rf = 0.5 (EtOAc–hexanes, 2:8).
IR (neat): 3417, 3073, 2927, 1640, 1578, 1477, 1427, 1072, 1022,
912, 736, 691 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.54 (m, 2 H), 7.27–7.24 (m, 3 H),
5.83–5.72 (m, 1 H), 4.98–4.92 (m, 2 H), 3.72–3.66 (m, 1 H), 3.12
(dd, J = 3.6, 12.9 Hz, 1 H), 2.89 (dd, J = 8.7, 12.9 Hz, 1 H), 2.22–
2.07 (m, 2 H), 1.66–1.59 (m, 2 H).
(S)-1-Phenyl-3-(2-pyridylsulfanyl)-N-tosylpropan-2-amine
(10c)
Yield: 92%; mp 63°C; Rf = 0.5 (EtOAc–hexanes, 3:7).
[a]D25 –63.4 (c 1, CHCl3).
13C NMR (75 MHz, CDCl3): d = 138.0, 133.0, 129.3, 129.2, 127.2,
114.9, 69.4, 37.0, 35.6, 30.0.
77Se NMR (75 MHz, CDCl3): d = 233.71.
HRMS: m/z [M + Na]+ calcd for C12H16NaOSe: 279.0264; found:
IR (neat): 3278, 3062, 2924, 1666, 1581, 1454, 1332, 1159, 1092,
739, 665 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.44–8.42 (m, 1 H), 7.93 (d,
J = 4.2 Hz, 1 H), 7.56 (d, J = 8.4 Hz, 2 H), 7.49 (dt, J = 2.1, 7.2 Hz,
1 H), 7.31–7.05 (m, 9 H), 3.61–3.52 (m, 1 H), 4.23 (dd, J = 4.2, 13.5
Hz, 1 H), 3.03 (dd, J = 7.5, 14.7 Hz, 1 H), 2.97–2.88 (m, 2 H), 2.36
(s, 3 H).
279.0264.
(R)-2-Methyl-1-(4-nitrobenzoyl)-3-(phenylselanyl)propan-2-ol
(8d)
Colorless oil; yield: 91%; Rf = 0.4 (EtOAc–hexanes, 3:7).
13C NMR (75 MHz, CDCl3): d = 158.5, 148.9, 142.7, 137.5, 136.4,
[a]D25 +11.5 (c 2, CHCl3).
IR (neat): 3472, 3056, 2978, 1725, 1526, 1274, 1104, 718 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.26 (d, J = 8.7 Hz, 2 H), 8.11 (d,
J = 8.7 Hz, 2 H), 7.58–7.54 (m, 2 H), 7.21–7.19 (m, 3 H), 4.36 (d,
J = 11.1 Hz, 1 H), 4.31 (d, J = 11.1 Hz, 1 H), 3.32 (d, J = 12.6 Hz,
1 H), 3.18 (d, J = 12.6 Hz, 1 H), 2.48 (s, 1 H), 1.42 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 164.2, 150.6, 135.0, 133.0, 130.7,
130.1, 129.2, 127.4, 123.5, 71.5, 70.8, 39.4, 24.7.
77Se NMR (75 MHz, CDCl3): d = 228.01.
HRMS: m/z [M + Na]+ calcd for C17H17NNaO5Se: 418.017; found:
129.5, 128.5, 127.0, 126.6, 122.7, 120.2, 56.7, 41.9, 33.8, 21.4.
HRMS: m/z [M + Na]+ calcd for C21H22N2NaO2S2: 421.1020;
found: 412.1016.
(S)-1-(4-Nitrophenylsulfanyl)-1-phenyl-N-tosylpropan-2-amine
(10e)
Yield: 95%; mp 121 °C; Rf = 0.4 (EtOAc–hexanes, 3:7).
[a]D25 –62.1 (c 1, CHCl3).
IR (neat): 3263, 2923, 1578, 1511, 1336, 1154, 1089, 741, 662 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.08 (d, J = 9 Hz, 2 H), 7.48 (d,
J = 8.1 Hz, 2 H), 7.27–7.18 (m, 5 H), 6.99 (d, J = 6.3 Hz, 2 H),
6.98–6.95 (m, 2 H), 4.90 (d, J = 6.9 Hz, 1 H), 3.59–3.48 (m, 1 H),
3.30 (dd, J = 4.5, 13.8 Hz, 1 H), 3.08–2.93 (m, 2 H), 2.77 (dd,
J = 6.9, 13.8 Hz, 1 H), 2.37 (s, 3 H).
418.0184.
1-(Allyloxy)-3-(phenylselanyl)propan-2-ol (8e)
Colorless oil; yield: 95%; Rf = 0.6 (EtOAc–hexanes, 2:8).
IR (neat): 3436, 3073, 2860, 1578, 1478, 1421, 1108, 929, 736, 691
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.53–7.50 (m, 2 H), 7.26–7.21 (m,
2 H), 5.92–5.79 (m, 1 H), 5.28–5.14 (m, 2 H), 3.96–3.88 (m, 3 H),
3.54–3.43 (m, 2 H), 3.12–2.86 (m, 2 H), 2.85 (d, J = 4.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 145.6, 145.3, 143.5, 136.4, 135.9,
129.6, 128.8, 127.0, 126.9, 126.7, 123.9, 53.8, 39.7, 36.4, 21.5.
HRMS: m/z [M + Na]+ calcd for C22H22N2NaO4S2: 465.0919;
found: 465.0914.
13C NMR (75 MHz, CDCl3): d = 134.3, 132.6, 129.6, 129.1, 127.0,
117.2, 72.7, 69.4, 31.8.
4-(Phenylsulfanyl)-(tosylamino)butan-1-ol (11b)
Colorless oil; yield: 94%; Rf = 0.3 (EtOAc–hexanes, 3:7).
77Se NMR (75 MHz, CDCl3): d = 242.423.
HRMS: m/z [M + Na]+ calcd for C12H16NaO2Se: 295.0213; found:
IR (neat): 3483, 3293, 2966, 3931, 2874, 1635, 1598, 1440, 1325,
1159, 1093, 1033, 747, 667 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.56 (d, J = 8.1 Hz, 2 H), 7.19–
7.13 (m, 7 H), 5.40 (d, J = 8.1 Hz, 1 H), 3.73 (ddd, J = 3.3, 9.0, 11.7
Hz, 1 H), 3.56–3.45 (m, 2 H), 3.06 (dd, J = 4.2, 14.1 Hz, 1 H), 2.68
(dd, J = 7.2, 14.1 Hz, 1 H), 2.33 (s, 3 H), 1.86–1.71 (m, 2 H), 1.60–
1.49 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 143.5, 137.2, 135.2, 129.8, 129.7,
129.1, 127.0, 126.6, 59.0, 39.1, 35.5, 21.5.
295.0211.
(2R*,3R*)-1,4-Bis(phenylselanyl)butane-2,3-diol (8g)
Yield: 93%; mp 76°C; Rf = 0.5 (EtOAc–hexanes, 4:6).
IR (neat): 3417, 3173, 2927, 1428, 1032, 1022, 920, 746, 687 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.49–7.44 (m, 2 H), 7.25–7.21 (m,
3 H), 3.74 (dd, J = 5.4, 8.1 Hz, 1 H), 3.06–3.04 (m, 2 H), 2.93 (d,
J = 5.4 Hz, 1 H).
HRMS: m/z [M + Na]+ calcd for C16H19NNaO3S2: 360.0704; found:
360.0712.
13C NMR (75 MHz, CDCl3): d = 132.9, 129.1, 129.0, 127.2, 71.3,
33.1, 32.6.
(3R*,4S*)-2-Methyl-4-(phenylsulfanyl)-N-tosylpentan-3-amine
(11d)
Colorless oil; yield: 94%; Rf = 0.3 (EtOAc–hexanes, 1:9).
77Se NMR (75 MHz, CDCl3): d = 244.61.
HRMS: m/z [M + Na]+ calcd for C16H18NaO2Se2: 424.9535; found:
424.9544.
IR (neat): 3483, 3293, 2966, 3931, 2874, 1635, 1598, 1440, 1325,
1159, 1093, 1033, 747, 667 cm–1.
Synthesis 2009, No. 19, 3267–3278 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of b-Amino/b-Hydroxy Selenides and Sulfides
3277
1H NMR (300 MHz, CDCl3): d = 7.72 (d, J = 8.4 Hz, 2 H), 7.26–
7.19 (m, 7 H), 4.97 (d, J = 9.9 Hz, 1 H), 3.41–3.34 (m, 1 H), 3.14–
3.06 (m, 1 H), 2.39 (s, 3 H), 2.11–1.99 (m, 1 H), 1.23 (d, J = 6.9 Hz,
3 H), 0.88–0.84 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 143.0, 138.7, 135.0, 131.8, 129.4,
128.9, 127.0, 62.5, 48.7, 29.3, 21.5, 21.0, 19.2, 17.6.
13C NMR (75 MHz, CDCl3): d = 135.5, 134.2, 129.5, 128.9, 126.2,
117.2, 72.3, 72.2, 68.9, 37.3.
HRMS: m/z [M + Na]+ calcd for C12H16NaO2S: 247.0769; found:
247.0784.
(2R*,3R*)-1,4-Bis(phenylsulfanyl)butane-2,3-diol (12g)
Colorless oil; yield: 94%; Rf = 0.5 (EtOAc–hexanes, 4:6).
HRMS: m/z [M + Na]+ calcd for C19H25NNaO2S2: 386.1224; found:
386.1223.
IR (neat): 3483, 3293, 2966, 3931, 2874, 1635, 1598, 1440, 1325,
1159, 1093, 1033, 747, 667 cm–1.
(3R*,4R*)-2-Methyl-4-(phenylsulfanyl)-N-tosylpentan-3-amine
(11e)
Yield: 92%; mp 67°C; Rf = 0.3 (EtOAc–hexanes, 1:9).
1H NMR (300 MHz, CDCl3): d = 7.34–7.16 (m, 5 H), 3.73 (dd,
J = 5.4, 8.7 Hz, 1 H), 3.12–3.07 (m, 2 H), 3.91 (d, J = 5.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 134.8, 129.9, 129.0, 126.6, 70.2,
38.1.
HRMS: m/z [M + Na]+ calcd for C16H18NaO2S2: 424.9535; found:
424.9544.
IR (neat): 3289, 2965, 2929, 1598, 1439, 1327, 1160, 1093, 1025,
909, 748, 665 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.69 (d, J = 8.4 Hz, 2 H), 7.39–
7.31 (m, 2 H), 7.31–7.22(m, 5 H), 4.87 (d, J = 9.0 Hz, 1 H), 3.47
(ddd, J = 3.0, 4.2, 22.2 Hz, 1 H), 3.22–3.15 (m, 1 H), 2.39 (s, 3 H),
2.02–1.88 (m, 1 H), 1.16 (d, J = 7.2 Hz, 3 H), 0.8 (d, J = 6.9 Hz, 3
H), 0.77 (d, J = 6.9 Hz, 3 H).
Acknowledgment
V.G. thanks CSIR, New Delhi for a Shyama Prasad Mukherjee Fel-
lowship and S.C.N. thanks DST, New Delhi for a JC Bose National
Fellowship.
13C NMR (75 MHz, CDCl3): d = 143.0, 138.6, 134.3, 132.5, 129.4,
128.4, 127.3, 126.9, 63.9, 47.4, 30.4, 21.4, 20.7, 19.4, 19.2.
HRMS: m/z [M + Na]+ calcd for C19H25NNaO2S2: 386.1224; found:
386.1235.
References
1-(Phenylsulfanyl)hex-5-en-2-ol (12c)
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(b) Chakraborty, T. K.; Ghosh, S.; Jayaprakash, S. Curr.
Med. Chem. 2002, 9, 421.
(2) (a) Moroder, R. J. J. Pept. Sci. 2005, 11, 187. (b) Pegoraro,
S.; Fiori, S.; Cramer, J.; Rudolph-Böhner, S.; Moroder, L.
Protein Sci. 1999, 8, 1605. (c) Fiori, S.; Pegoraro, S.;
Rudolph-Böhner, S.; Cramer, J.; Moroder, L. Biopolymers
2000, 53, 550.
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2003, 125, 13455. (c) Nogueria, C. W.; Zeni, G.; Roch,
J. B. T. Chem. Rev. 2004, 104, 6255.
Colorless oil; yield: 94%; Rf = 0.4 (EtOAc–hexanes, 2:8).
IR (neat): 3409, 2912, 1640, 1584, 1480, 1439, 1069, 1025, 912,
738, 691 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.40–7.19 (m, 5 H), 5.86–5.73 (m,
1 H), 5.05–4.94 (m, 2 H), 3.73–3.65 (m, 1 H), 3.15 (dd, J = 3.6, 14.1
Hz, 1 H), 2.85 (dd, J = 9.0, 14.1 Hz, 1 H), 2.5 (d, J = 3 Hz, 1 H),
2.29–2.07 (m, 2 H), 1.66–1.59 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 138.0, 135.3, 130.0, 129.0, 126.6,
115.0, 68.9, 42.1, 35.1, 29.9.
HRMS: m/z [M + K]+ calcd for C12H16NaOS: 247.0559; found:
247.0564.
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Todaro, L. J.; Coffen, D. L. J. Org. Chem. 1992, 57, 851.
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N. C. M. W.; Kellogg, R. M. Tetrahedron: Asymmetry 1994,
5, 31. (c) Jin, M. J.; Ahn, S. J.; Lee, K. S. Tetrahedron Lett.
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(R)-2-Methyl-1-(4-nitrobenzoyl)-3-(phenylsulfanyl)propan-2-ol
(12d)
Yield: 91%; mp 52°C; Rf = 0.4 (EtOAc–hexanes, 3:7).
[a]D25 +6.0 (c 2, CHCl3).
IR (neat): 3483, 3293, 2966, 3931, 2874, 1635, 1598, 1440, 1325,
1159, 1093, 1033, 747, 667 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.26 (d, J = 7.2 Hz, 2 H), 8.14 (d,
J = 7.2 Hz, 2 H), 7.44–7.41 (m, 2 H), 7.27–7.13 (m, 3 H), 4.36 (d,
J = 11.4, 1 H), 4.30 (d, J = 11.4 Hz, 1 H), 3.32 (d, J = 12 Hz, 1 H),
3.20 (d, J = 12 Hz, 1 H), 2.73 (s, 1 H), 1.40 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 164.3, 150.6, 136.1, 135.0, 130.7,
130.2, 129.1, 126.8, 123.5, 71.9, 70.4, 44.4, 24.3.
HRMS: m/z [M + Na]+ calcd for C17H17NNaO5S: 370.0725; found:
370.0724.
1-(Allyloxy)-3-(phenylsulfanyl)propan-2-ol (12e)
Colorless oil; yield: 93%; Rf = 0.6 (EtOAc–hexanes, 2:8).
IR (neat): 3435, 3914, 3860, 1584, 1481, 1439, 1108, 930, 739, 691
cm–1.
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1H NMR (300 MHz, CDCl3): d = 7.39–7.35 (m, 2 H), 7.29–7.24 (m,
2 H), 7.20–7.15 (m, 1 H), 5.91–5.80 (m, 1 H), 5.28–5.15 (m, 2 H),
3.98–3.87 (m, 3 H), 3.53 (dd, J = 4.2, 9.9 Hz, 1 H), 3.47 (dd, J = 6.0,
9.9 Hz, 1 H), 3.11 (dd, J = 6.0, 13.8 Hz, 1 H), 3.03 (dd, J = 4.2, 13.8
Hz, 1 H), 2.91 (d, J = 4.5 Hz, 1 H).
Synthesis 2009, No. 19, 3267–3278 © Thieme Stuttgart · New York

3278
V. Ganesh, S. Chandrasekaran
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Synthesis 2009, No. 19, 3267–3278 © Thieme Stuttgart · New York