Synthesis of chiral β-chalcogen amine derivatives and Gram-positive bacteria activity

Article abstract of DOI:10.1016/j.tet.2012.09.049

Efficient ring opening reaction between aziridines and diphenyl dichalogenides using HCl, Zn° in ionic liquid is disclosed, affording chiral β-chalcogen amines derivatives in good yields under mild reaction condition. The ionic liquid was further reused f

Full text of DOI:10.1016/j.tet.2012.09.049

Tetrahedron 68 (2012) 10444e10448
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of chiral
activity
b-chalcogen amine derivatives and Gram-positive bacteria
,
a
a
a
Josimar Vargas a, Senthil Narayanaperumal b , Kashif Gul , Bruno B. Ravanello , Luciano Dornelles ,
*
Letiere C. Soares a, Camilla F.S. Alves c, Taiane Schneider c, Rodrigo de A. Vaucher c, Roberto C.V. Santos c,
,
Oscar E.D. Rodrigues a
*
a Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, Brazil
Deˇ partamento de Química, Universidade Federal de Sao Carlos, Sao Carlos, Brazil
Ciencias da Saude, Laboratorio de Microbiologia, Centro Universitario Franciscano, Santa Maria, Brazil
b
~
~
c
ꢀ
ꢀ
ꢀ
a r t i c l e i n f o
a b s t r a c t
Efficient ring opening reaction between aziridines and diphenyl dichalogenides using HCl, Znꢀ in ionic
liquid is disclosed, affording chiral b-chalcogen amines derivatives in good yields under mild reaction
condition. The ionic liquid was further reused four times without the loss of its efficiency. The chiral
chalcogenoamines showed antimicrobial activity against Gram-positive bacteria strains.
Ó 2012 Elsevier Ltd. All rights reserved.
Article history:
Received 30 June 2012
Received in revised form 31 August 2012
Accepted 11 September 2012
Available online 25 September 2012
1. Introduction
aziridines afford the corresponding chiral
derivatives.
b-chalcogen amine
Development of methods for stereocontrolled synthesis of chiral
-chalcogen amine derivative continues to receive significant at-
However, these methods all possess one or more of the fol-
lowing disadvantages, including prolonged reaction time, suffered
from the fact that a Lewis acid or strong base was necessary to
effect the reaction, or the requirement for costly, air-sensitive
substances.
b
tention. They have generally targeted as compounds with antioxi-
dant, antitumour, and antimicrobial activities and many of these
compounds are competitive inhibitors for target proteins.1 In ad-
dition to the interesting properties of thio- and seleno-proteins,
simple organosulfur and organoselenium compounds exhibit sev-
eral useful biological and medicinal applications.2 Besides, syn-
thetic methods for preparation of seleno-cysteine,3 selenium-based
peptides,4 selenoglycosides,5 seleno-nucleosides6 and other im-
portant natural compounds7 is an intensive current research area.
Moreover, chiral selenide and diselenides containing ligands offer
attractive and practical options in the development of asymmetric
transformations.8
Keeping in mind the wide range of applications of these ana-
logues, general and recyclable synthetic methodologies to prepare
sulfur- and selenium-containing derivatives of amino acids in
a simple, efficient, stereo-regulated manner is greatly appreciated
and remains as a highly challenging and desiring endeavour.
Room-temperature ionic liquids are currently attracting con-
siderable scientific interest on several fronts. Ionic liquids (ILs) are
low melting organic salts composed solely of cations and anions,
which make them highly tunable for specific applications.15 Ionic
liquids are noted to have a number of unique properties16 and these
behaviours have been shown to have a large number of applica-
tions. Moreover, ionic liquids have received considerable attention
due to their ability to serve as effective reaction media for a wide
range of organic reactions and other applications in chemistry.17 By
modifying the structure of the cations or anions of ionic liquids, it
has been shown that their properties can be altered in order to
influence the outcomes of reactions. On other hand, Gram-positive
infections are associated to high rates of morbidity and mortality.18
For instance, Listeria monocytogenes causes serious localized and
generalized infections in humans and a variety of other vertebrates,
including domesticated and wild birds as well mammals.19 Bacillus
cereus is also a Gram-positive, rod-shaped, spore-forming aerobe
commonly found in soil and many other sources, is a cause of food
The development of new methods for the introduction of sulfur-
and selenium-containing groups into organic molecules, remains
a significant challenge. In this context, ring opening reaction of
aziridines with chalcogen nucleophiles provides an useful protocol
to synthesize chiral
b-chalcogen amine derivatives using organic
solvents.9
Substantial number of reports have been appearing in the lit-
erature describing the reductive cleavage of SeS/SeeSe bonds,
employing NaBH4,10 Zn,11 Zn/InCl3,12 InI13 and others,14 which
generate chalcogen nucleophiles upon further reaction with
* Corresponding authors. E-mail address: rodriguesoed@gmail.com (O.E.D.
Rodrigues).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.09.049

J. Vargas et al. / Tetrahedron 68 (2012) 10444e10448
10445
poisoning and can occasionally be responsible for surgical wound
infection, pneumonia and meningitis in compromised patients. In
this context, the development of new and modulate compounds for
antimicrobial activity could afford an important point for biological
applications and this way we reported the synthesis of chiral b-
organochalcogen amines and the Gram-positive bacteria
evaluation.
Fig. 1. Room-temperature ionic liquids.
2. Results and discussion
Analyzing Table 1, the desired b-seleno amine 2a was obtained
In the course of our ongoing research towards the synthesis and
application of organochalcogen compounds in organic synthesis
and searching for the biological and synthetic importance of chiral
in a good yield using [bmim]BF4 at 80 ꢀC. When [bmim]BF4 was
used at room temperature, the desired product was not observed
(Table 1, entries 1 and 2), the same was observed when the reaction
was conducted without HCl (Table 1, entry 3). While other ionic
liquids such as [bmim]PF6, [bmmim]BF4, [bpy]BF4 were effective for
the transformation, they were less efficient than [bmim]BF4 (Table
1, entries 4e6). The amount of zinc required to promote the com-
pletion of the reaction was also evaluated. The reaction with
0.6 equiv of zinc showed similar results, leading to the desired
product 2a in excellent yields as well (Table 1, entry 7). In addition,
ionic liquids could increase the aziridine ring opening due to the
Lewis acid ability of these compounds. This could be observed,
comparing the more effectivity of the [bmim]BF4 compared to
[bmmim]BF4 (Table 1, entries 2 and 6) and additionally, HCl also
appears as an important catalyst for this aziridine ring opening.
Lower yield was observed by using conventional organic solvents
such as THF, CH2Cl2 and CH3CN under reflux temperature as com-
pared to [bmim]BF4 (Table 1, entries 1, 8e10). Hence, the optimal
conditions for the ring opening of aziridines using diphenyl dis-
b
-organochalcogen amine and their derivatives, it is reported in
this paper a simple and efficient methodology for the synthesis of
chiral -organochalcogen amine derivatives from the ring opening
b
reaction of aziridines with diphenyl dichalcogenides using HCl
(1 M), Zn in ionic liquid and the biological evaluation of the syn-
thesized compounds as antimicrobial agent, as depicted in
Scheme 1.
Scheme 1. Synthesis of chiral b-organochalcogen amines.
elenide with 0.5 equiv of Zn related to diselenide, 10
mL HCl in
In order to identify the optimal reaction conditions, N-Ts pro-
tected aziridine 1a derived from -phenyl alanine, diphenyl dis-
elenide and HCl (1 M) was chosen as a test substrate.
[bmim]BF4 (0.5 mL) at 80 ꢀC affording the chiral
b-seleno amine
L
derivatives. In order to demonstrate the generality of this method,
it was investigated the scope of this reaction to prepare a variety of
We carried out the reaction employing N-Ts protected aziridine
chiral
b-seleno amine derivatives from N-protected aziridines 1aeg
1a, with PhSeSePh, 0.5 equiv of zinc dust and 10
liquid (0.5 mL) under different conditions to get the desired chiral
-seleno amine 2a, as summarized in Table 1. Firstly, it was per-
mL HCl in ionic
derived from
L-phenyl alanine,
L-valine,
L-leucine and
L
-isoleucine
as depicted in Table 2.
b
formed a series of experiments with four different ionic liquids
(Fig. 1) in order to check the influence of these in the reaction
course.
Table 2
Synthesis of chiral b-chalcogenoamine derivatives
Table 1
Screening of reaction conditions
Entry
R
Reactant
PGa
Product
Yieldb (%)
1
2
3
4
5
6
7
8
Bn
1a
Ts
Ts
2a
3a
2b
3b
2c
3c
2d
3d
2e
3e
2f
90
78
88
70
73
75
85
70
76
66
62
60
67
Bn
1b
1c
1d
1e
1f
Boc
Boc
Boc
Boc
Ts
Ts
Ts
Ts
Ts
Entry
Ionic liquida
Temp (ꢀC)
Time (h)
Yieldb (%)
i-Pr
i-Pr
1
[bmim]BF4
[bmim]BF4
[bmim]BF4
[bmim]PF6
[bpy]BF4
[bmmim]BF4
[bmim]BF4
THF
rt
80
80
80
80
80
80
Reflux
Reflux
Reflux
2
2
2
4
4
4
2
12
12
12
d
2
90
d
3c
4
76
50
64
92
56
38
44
9
i-Bu
s-Bu
s-Bu
5
10
11
12
13
6
7d
8
Ts
Boc
3f
2g
1g
9
10
CH2Cl2
CH3CN
a
Reaction time for PG¼Boc, 120 min; PG¼Ts, 90 min.
b
Yields refer to pure isolated products and characterized by 1H and 13C NMR.
Ionic liquids were prepared by the available literature procedure17h,l and were
subjected to vacuum before use (except [bmim]BF4, which was acquired from
ALDRICH).
a
As shown in Table 2, it was possible to verify that the respective
chiral b-seleno amine derivatives were obtained in good to excel-
lent yields from different N-protected aziridines. In general, N-Ts
afforded better yields than the N-Boc protected aziridines (for
b
Yields refer to pure isolated products and characterized by 1H and 13C NMR.
c
Without HCl.
d
Zn dust (0.6 equiv).

10446
J. Vargas et al. / Tetrahedron 68 (2012) 10444e10448
instance, see Table 2, entries 2 and 4). The R group derived from the
aminoacid side showed a small steric effect, allowing slightly better
yields to the small groups. As a further extension of our protocol, it
was applied the same reaction conditions employed for the prep-
3. Conclusion
In summary, reductive cleavage of diphenyl disulfides and dis-
elenides mediated by zinc and HCl in ionic liquid followed by the
aration of chiral
b-seleno amino derivatives to prepare a series of
ring opening of aziridines provides an easy access to chiral
b-amino
chiral -sulfur amino derivatives.
b
sulfides and -amino selenides in a stereospecific and regiose-
b
The reaction of aziridines 1aef with diphenyl disulfide medi-
ated by zinc in ionic liquid and HCl resulted to the formation of the
corresponding chiral b-amino sulfides 3aef in good to excellent
yield (Table 2, entries 1e12), showing a similar behaviour for the
selenide aziridine ring opening.
Continuing our efforts to provide synthetic methods that are
more benign at an environmental point of view, it was attempted to
reuse the ionic liquid/[bmim]BF4, which was one of the prime ob-
jectives in our quest. In this regard, it was performed a set of ex-
periments aiming to reuse the reaction medium, Fig. 2. After
completion of the reaction, ionic liquid/[bmim]BF4 was recovered
(see Supplementary data) and subjected to another run, affording
the corresponding product in good yield. This process was repeated
four more times affording the desired product in a close range of
yield.
lective manner under mild conditions with good skeletal diversity
in a one-pot process. The methodology would be of interest due to
the cost-effective, mild reaction conditions and good to excellent
yields were obtained in a short time. We believe that this method
reported in this study would greatly contribute to environmentally
greener protocol since the solvent/ionic liquid would be reused up
to four successive runs besides safer processes. Current efforts are
directed at gaining a deeper understanding of some of the funda-
mental principles dictating the reactivity of these systems, as well
as extending their utility by expanding the substrate scope.
4. Experimental
4.1. General procedure for the synthesis of chiral b-chalcogen
amine derivatives (2aeg and 3aef)
In a Schlenk flask, under argon atmosphere, diphenyl dichal-
cogenide (0.5 mmol) and zinc dust (0.5 mmol) were added to
[bmim]BF4 (0.5 mL) at 80 ꢀC. The reaction mixture was allowed to
stir for 10 min to solubilize the diphenyl dichalcogenide and af-
terwards 10 mL HCl (1 M) was added. Then, the mixture was
allowed to stir for 5 min and aziridine (1 mmol) was slowly added.
The reaction mixture was allowed to stir for suitable reaction time
(monitored by TLC and assisted by visual observation). The mixture
was then extracted with ether (3ꢁ20 mL), and the combined ether
extract was washed with brine, dried (MgSO4), and evaporated to
leave the crude product. Purification by column chromatography
over silica gel (hexane/ethyl acetate 95:5), furnished the pure chiral
b-chalcogen amino derivatives 2aeg and 3aef.
Fig. 2. Reuse of ionic liquid/[bmim]BF4.
4.1.1. (S)-4-Methyl-N-(1-phenyl-3-(phenylselanyl)propan-2-yl) ben-
zenesulfonamide (2a).22 Yield 90%; 1H NMR (400 MHz, CDCl3):
In connection with the synthetic approach, compounds 2f and
3f were evaluated for their efficacy as antimicrobial agents (Table
3). From the results of disc diffusion and microdilution
method20,21 (see Supplementary data), was observed an activity
against Gram-positive bacteria strains, especially L. monocytogenes,
B. cereus and Paenibacillus species (Table 3). Comparing these re-
sults to those obtained with standard antibiotics, compounds 2f
and 3f produced a lower inhibition to that produced by Amikacin
(see Supplementary data).
d
¼7.43e7.39 (m, 4H), 7.27e7.09 (m, 9H), 6.93e6.91 (m, 2H), 4,72 (d,
J¼7.2 Hz, 1H), 3.55e3.48 (m, 1H), 3.12 (dd, 1J¼12.83 Hz, 2J¼4.54 Hz,
1H), 2.95 (dd, 1J¼14.42 Hz, 2J¼6.48 Hz, 1H), 2.82 (dd, 1J¼12.83 Hz,
2J¼7.21 Hz, 1H), 2.74 (dd, 1J¼14.42 Hz, 2J¼7.21 Hz, 1H), 2.37 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3):
d
¼143.13, 136.68, 136.45, 132.92,
129.51, 129.24, 128.61, 127.29, 126.96, 126.72, 54.49, 40.29, 32.87,
21.47 ppm.
4.1.2. (S)-tert-Butyl 1-phenyl-3-(phenylselanyl) propan-2-ylcar-
bamate (2b).9c Yield 88%; 1H NMR (400 MHz, CDCl3):
d
¼7.51e7.48
Table 3
(m, 2H), 7.29e7.12 (m, 8H), 4.70e4.66 (m, 1H), 4.09e4.06 (m, 1H),
Antimicrobial activities of 2f and 3f
3.04e3.01 (m, 2H), 2.87e2.82 (m, 2H), 1.38 (s, 9H) ppm; 13C NMR
Microorganisms
Source
MIC compounds (mg/mL)
(100 MHz, CDCl3):
128.40, 126.99, 126.44, 80.98, 38.21, 32.77, 28.24, 27.81 ppm.
d
¼154.96, 137.48, 132.74, 129.29, 129.09, 128.68,
2f
3f
Bacillus cereus
ATCC9634
ATCC7644
Environmental isolate 1100
Environmental isolate 550
1100
1100
1100
1100
1100
1100
1100
1100
Listeria monocytogenes
Paenibacillus alginolyticus
Paenibacillus azotofixans
Paenibacillus gluconolyticus Environmental isolate 550
Paenibacillus thiaminolyticus Environmental isolate 550
4.1.3. (S)-tert-Butyl 3-methyl-1-(phenylselanyl)butan-2-ylcarbamate
(2c).22 Yield 73%; 1H NMR (200 MHz, CDCl3):
d
¼7.55e7.50 (m, 2H),
7.26e7.23 (m, 3H), 4.60e4.55 (m, 1H), 3.69e3.59 (m, 1H), 3.07 (d,
J¼5.6 Hz, 2H), 1.94e1.77 (m, 1H), 1.42 (s, 9H), 0.91e0.87 (m, 6H)
ppm; 13C NMR (100 MHz, CDCl3):
79.10, 55.64, 32.41, 31.69, 28.33, 19.43, 17.97 ppm.
d
¼155.54, 132.93, 129.05, 126.99,
Despite the moderate activity, the structural simplicity, easy
preparation and modulate character of the synthesis may allow this
methodology as an alternative basis for the preparation of new
antimicrobial agents class and the results illustrate, up to our
knowledge, for the first time an antimicrobial effect of chiral
chalcogenoamines.
4.1.4. (S)-4-Methyl-N-(3-methyl-1-(phenylselanyl)butan-2-yl)benze-
nesulfonamide (2d).14d Yield 85%; 1H NMR (400 MHz, CDCl3):
d
¼7.62 (d, J¼8.4 Hz, 2H), 7.37e7.35 (m, 2H), 7.26e7.17 (m, 5H), 4.82
(d, J¼6.4 Hz, 1H), 3.23e3.17 (m, 1H), 3.06 (dd, 1J¼12.8 Hz, 2J¼4.8 Hz,
1H), 2.74 (dd, 1J¼12.8 Hz, 2J¼6.6 Hz, 1H), 2.38 (s, 3H), 2.01e1.93 (m,
1H), 0.81 (d, J¼6.8 Hz, 3H), 0.76 (d, J¼6.8 Hz, 3H) ppm; 13C NMR

J. Vargas et al. / Tetrahedron 68 (2012) 10444e10448
10447
(100 MHz, CDCl3):
127.05, 58.57, 31.64, 30.68, 21.49, 19.01, 17.44 ppm.
d
¼143.19, 137.65, 133.07, 129.54, 129.15, 127.29,
3.44e3.33 (m, 1H), 3.14 (dd, 1J¼4.0 Hz, 2J¼13.6 Hz, 1H), 2.75 (dd,
1J¼6.8 Hz, 2J¼13.2 Hz,1H), 2.39 (s, 3H),1.49e1.40 (m, 2H),1.34e1.26
(m, 1H), 0.79 (d, J¼6.4 Hz, 3H), 0.59 (d, J¼6.0 Hz, 3H) ppm; 13C NMR
4.1.5. (S)-4-Methyl-N-(4-methyl-1-(phenylselanyl)pentan-2-yl)ben-
(CDCl3, 100 MHz)
d
¼143.38, 137.57, 135.39, 130.18, 129.55, 128.95,
zenesulfonamide (2e).23 Yield 76% ; 1H NMR (400 MHz, CDCl3):
127.07, 126.56, 51.22, 43.37, 39.94, 24.33, 22.88, 21.51, 21.46 ppm;
20
d
¼7.60 (d, J¼8.4 Hz, 2H), 7.42e7.40 (m, 2H), 7.29e7.21 (m, 3H), 7.18
[a
]
ꢂ47 (c 1.0, ethyl acetate). ESI-HRMS calcd for C19H25NO2S2
D
(d, J¼8.4 Hz, 2H), 4.86 (d, J¼8.4 Hz, 1H), 3.46e3.38 (m, 1H), 3.10 (dd,
1J¼12.2 Hz, 2J¼3.6 Hz, 1H), 2.73 (dd, 1J¼12.2 Hz, 2J¼6.8 Hz, 1H), 2.38
(s, 3H), 1.48e1.36 (m, 2H), 1.29e1.23 (m, 1H), 0.77 (d, J¼6.4 Hz, 3H),
364.1413 (MþþH), found, m/z 364.1394.
4.1.13. 4-Methyl-N-((2S,3S)-3-methyl-1-(phenylthio)pentan-2-yl)
0.59 (d, J¼6.0 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3):
d
¼142.19,
benzenesulfonamide (3f). Yield 60%; 1H NMR (400 MHz, CDCl3):
137.65, 133.19, 129.52, 129.08, 127.23, 126.98, 51.54, 43.82, 34.65,
24.30, 22.76, 21.52, 21.43 ppm.
d
¼7.66 (d, J¼8.4 Hz, 2H), 7.28e7.15 (m, 7H), 4.86 (d, J¼8.0 Hz, 1H),
3.29e3.21 (m, 1H), 2.98 (dd, 1J¼6.0 Hz, 2J¼13.6 Hz, 1H), 2.83 (dd,
1J¼6.0 Hz, 2J¼13.6 Hz, 1H), 2.38 (s, 3H), 1.84e1.73 (m, 1H), 1.46e1.37
(m, 1H), 1.09e0.97 (m, 1H), 0.82e0.76 (m, 6H) ppm; 13C NMR
4.1.6. 4-Methyl-N-((2S,3S)-3-methyl-1-(phenylselanyl)pentan-2-yl)
benzenesulfonamide (2f).23 Yield 62%; 1H NMR (CDCl3, 400 MHz)
(CDCl3, 100 MHz)
d
¼143.20, 137.50, 135.23, 129.81, 129.49, 128.91,
d
¼7.64 (d, J¼8.0 Hz, 2H), 7.34e7.32 (m, 2H), 7.26e7.18 (m, 5H), 4.88
127.10, 126.44, 56.98, 36.74, 36.14, 24.40, 21.46, 14.87, 11.64 ppm;
20
(d, J¼8.4 Hz, 1H), 3.30e3.24 (m, 1H), 2.99 (dd, 1J¼5.6 Hz, 2J¼12.8 Hz,
1H), 2.77(dd,1J¼6 Hz, 2J¼12.4 Hz,1H), 2.39 (s, 3H),1.74e1.68 (m,1H),
1.45e1.36 (m, 1H), 1.04e0.98 (m, 1H), 0.80e0.76 (m, 6H) ppm; 13C
[a
]
þ24 (c 1.0, ethyl acetate). ESI-HRMS calcd for C19H25NO2S2
D
364.1399 (MþþH), found, m/z 364.1394.
NMR (CDCl3, 100 MHz)
129.08, 127.24, 127.06, 57.52, 37.52, 31.10, 24.44, 21.47, 14.96,
11.38 ppm.
d
¼143.6, 137.58, 133.04, 129.51, 129.35,
Acknowledgements
We are grateful to CNPq, CAPES, TWAS and FAPERGS (PRONEM
11/2080-9), for financial support.
4.1.7. tert-Butyl-(2S,3S)-3-methyl-1-(phenylselanyl)pentan-2-
ylcarbamate (2g).23 Yield 67%
;
1H NMR (CDCl3, 200 MHz)
Supplementary data
d
¼7.54e7.50 (m, 2H), 7.26e7.21 (m, 3H), 4.6e4.5 (m, 1H), 3.75e3.7
(m, 1H), 3.1e3.0 (m, 1H), 1.67e1.57 (m, 2H), 1.42 (s, 9H), 1.17e0.95
Synthetic procedures and compounds characterization data.
Supplementary data associated with this article can be found in the
online version, at http://dx.doi.org/10.1016/j.tet.2012.09.049.
(m, 2H), 0.9e0.84 (m, 6H) ppm; 13C NMR (CDCl3, 50 MHz)
d
¼155.49, 133.12, 129.06, 129.05, 127.07, 71.88, 38.44, 32.1, 28.38,
27.76, 15.43, 11.37 ppm.
References and notes
4.1.8. (S)-4-Methyl-N-(1-phenyl-3-(phenylthio)propan-2-yl)benze-
nesulfonamide (3a).24 Yield 78%; 1H NMR (CDCl3, 400 MHz)
d
¼7.44
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(d, J¼8 Hz, 2H), 7.29e7.16 (m, 8H), 7.10 (d, J¼8 Hz, 2H), 6.97e6.94
(m, 2H), 4.66 (d, J¼6.8 Hz, 1H), 3.52e3.47 (m, 1H), 3.15 (dd,
1J¼6.4 Hz, 2J¼13.6 Hz, 1H), 2.98 (dd, 1J¼6.4 Hz, 2J¼13.8 Hz, 1H),
2.87e2.75 (m, 2H), 2.38 (s, 3H) ppm; 13C NMR (CDCl3, 100 MHz)
d
¼143.16, 136.67, 136.35, 134.97, 129.68, 129.51, 129.26, 129.03,
128.62, 126.96, 126.74, 126.48, 53.91, 39.43, 38.02, 21.46 ppm.
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~
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4.1.9. (S)-tert-Butyl 1-phenyl-3-(phenylthio)propan-2-ylcarbamate
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F.; Galetto, F. Z.; Paixao, M. W.; Schwab, R. S.; Taube, P. S. Eur. J. Org. Chem. 2007,
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(3b).25 Yield 70%; 1H NMR (CDCl3, 400 MHz)
d
¼7.35e7.33 (m,
~
2H), 7.30e7.15 (m, 8H), 4.68e4.66 (m, 1H), 4.10e4.04 (m, 1H),
3.09e3.01 (m, 2H), 2.91e2.86 (m, 2H), 1.39 (s, 9H) ppm; 13C NMR
€
~
(CDCl3, 100 MHz)
128.16, 126.62, 125.19, 79.5, 57.2, 40.08, 39.61, 28.40 ppm.
d
¼155.16, 138.0, 136.35, 129.26, 128.79, 128.81,
4.1.10. (S)-tert-Butyl 3-methyl-1-(phenylthio)butan-2-ylcarbamate
(3c).26 Yield 75%; 1H NMR (CDCl3, 200 MHz)
d
¼7.41e7.18 (m, 5H),
€
4.61e4.56 (m, 1H), 3.70e3.67 (m, 1H), 3.08 (d, J¼6.0 Hz, 2H),
1.97e1.87 (m, 1H), 1.43 (s, 9H), 1.01e0.88 (m, 6H) ppm; 13C NMR
(CDCl3, 50 MHz)
37.57, 30.83, 28.35, 22.44, 19.13 ppm.
d
¼155.79, 130.84, 129.70, 128.93, 126.21, 68.96,
~
8. For a comprehensive review about the use of chiral organoselenium com-
pounds in asymmetric catalisys see: (a) Wirth, T. Tetrahedron 1999, 55, 1e28;
4.1.11. (S)-4-Methyl-N-(3-methyl-1-(phenylthio)butan-2-yl)benze-
nesulfonamide (3d).27 Yield 70%; 1H NMR (400 MHz, CDCl3):
d¼7.66
€
(b) Wirth, T. Angew. Chem., Int. Ed. 2000, 39, 3740e3749; (c) Braga, A. L.; Ludke,
€
D. S.; Vargas, F.; Braga, R. C. Synlett 2006, 1453e1466; (d) Braga, A. L.; Ludtke, D.
(d, J¼8.4 Hz, 2H), 7.27e7.19 (m, 7H), 4.87 (d, J¼8.4 Hz, 1H),
3.23e3.17 (m, 1H), 3.06 (dd, 1J¼4.8 Hz, 2J¼13.6 Hz, 1H), 2.78 (dd,
1J¼6.8 Hz, 2J¼13.2 Hz, 1H), 2.38 (s, 3H), 2.09e2.02 (m, 1H), 0.83 (d,
J¼7.2 Hz, 3H), 0.77 (d, J¼6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
S.; Vargas, F. Curr. Org. Chem. 2006, 10, 1921e1938; (e) Freudendahl, D. M.;
Shahzad, S. A.; Wirth, T. Eur. J. Org. Chem. 2009, 1649e1664.
€
~
~
9. (a) Braga, A. L.; Ludtke, D. S.; Paixao, M. W.; Rodrigues, O. E. D. Org. Lett. 2003, 5,
2635e2638; (b) Braga, A. L.; Paixao, M. W.; Marin, G. Synlett 2005, 1675e1678;
(c) Braga, A. L.; Schneider, P. H.; Paixao, M. W.; Deobald, A. M.; Peppe, C.;
~
d
¼143.23, 137.63, 135.29, 129.75, 129.52, 128.94, 127.09, 126.43,
Bottega, D. P. J. Org. Chem. 2006, 71, 4305e4307; (d) Braga, A. L.; Schwab, R. S.;
Alberto, E. E.; Salman, S. M.; Vargas, J.; Azeredo, J. B. Tetrahedron Lett. 2009, 50,
2309e2311; (e) Salman, S. M.; Narayanaperumal, S.; Schwab, R. S.; Bender, C. R.;
Rodrigues, O. E. D.; Dornelles, L. RSC Adv. 2012, 2, 8478e8482.
57.95, 36.62, 29.62, 21.47, 18.89, 17.11 ppm.
4.1.12. (S)-4-Methyl-N-(4-methyl-1-(phenylthio)pentan-2-yl)benze-
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(d, J¼8.0 Hz, 2H), 7.23e7.19 (m, 7H), 4.74 (d, J¼7.6 Hz, 1H),
d
¼7.63

10448
J. Vargas et al. / Tetrahedron 68 (2012) 10444e10448
ꢀ
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