One-pot indium iodide mediated synthesis of chiral β-seleno amides and selenocysteine derivatives by ring-opening reaction of 2-oxazolines

Article abstract of DOI:10.1002/ejoc.200700671

A set of chiral β-seleno amides were efficiently synthesized by a simple and efficient procedure involving a ring-opening reaction of 2-oxazoline with diorganyl dichalcogenides mediated by indium(I) iodide. As an application, the synthesis of selenocystei

Full text of DOI:10.1002/ejoc.200700671

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200700671
One-Pot Indium Iodide Mediated Synthesis of Chiral β-Seleno Amides and
Selenocysteine Derivatives by Ring-Opening Reaction of 2-Oxazolines
[
a]
[b]
[a]
[b]
Antonio L. Braga,* Fabrício Vargas, Fábio Z. Galetto, Márcio W. Paixão,
[a]
[a]
Ricardo S. Schwab, and Paulo S. Taube
Keywords: Selenium / Nitrogen heterocycles / Oxygen heterocycles / Selenocysteine / Indium
A set of chiral β-seleno amides were efficiently synthesized
by a simple and efficient procedure involving a ring-opening
reaction of 2-oxazoline with diorganyl dichalcogenides medi-
ated by indium(I) iodide. As an application, the synthesis of
selenocysteine derivatives was accomplished.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
Organoselenium compounds have emerged as an excep-
Reduction of Se–Se bonds, especially cleavage of di-
tional class of structures in recent years due to their pivotal phenyl or diaryl diselenides, has recently received much ef-
role in the synthesis of a large number of biological com- fort for the preparation of unsymmetrical diorganyl sele-
pounds (e.g., selenocarbohydrates, selenoamino acids, and nides. Chemical cleavage of Se–Se bonds in diaryl diselen-
selenopeptides) and as important therapeutic compounds ides was realized with reducing agents such as NaBH , Na/
4
[
8]
ranging from antiviral and anticancer agents to naturally NH , Bu SnH, and LiAlH .
3
3
4
occurring food supplements.[ In addition, selenoamino ac-
1]
In recent years, some protocols with indium(I) iodide
ids are important as building blocks for the synthesis of mediated cleavage of diorganyl diselenides were developed
[
2]
[9]
[10]
selenoproteins and because of their potential biological to prepare vinylic selenides, selenoesters, and β-hydroxy
[
11]
activity in, for example, the protection against neurodegen- selenides
erative diseases, such as Parkinson’s and Alzheimer’s dis- diorganyl selenides.
eases. Additionally, there is continuing interest in the de-
with special attention given to unsymmetrical
[
12]
[
3]
We recently developed an indium(I) protocol for the
velopment of new methods for the synthesis of enantiomer- preparation of selenocysteine and selenothreonine deriva-
ically pure amino acids with substituents strategically tives by an aziridine-2-carboxylate ring-opening reaction
placed at side-chain positions with the ability to install un- promoted by in situ generated bis(organoseleno)iodo-
[
13]
saturation. In this context, selenocysteine derivatives indium(III). By this method, a series of selenoamino ac-
mainly phenylselenocysteines) can serve as convenient pre- ids could be synthesized in excellent yields, and these com-
(
[4]
cursors to dehydroamino acids, which are useful electro- pounds displayed some interesting structural diversity.
philic handles for the chemoselective preparation of peptide
We also reported Lewis acid (LA) mediated nucleophilic
ring opening of chiral 2-oxazolines to provide nonracemic
β-seleno amides, and a mechanism was proposed that con-
[
5]
conjugates. Moreover, chiral selenides and diselenides-
containing ligands have been employed as useful catalysts
in various asymmetric transformations.[ Therefore, the de-
velopment of new methods for the introduction of sele-
nium-containing groups into organic molecules,[ particu-
larly in a stereocontrolled manner, remains a significant
challenge.
6]
sisted of an S 2-type pathway to rationalize the formation
N
of the chiral products. In this work, the selenium nucleo-
phile required to open the oxazoline ring was generated by
reduction of the diselenide with sodium borohydride in eth-
7]
[
14]
anol.
Additionally, by this method, it was possible to
synthesize a selenocysteine derivative in moderated yield.
Attempting to disclose further extension of these works,
we examined the reaction between indium(III) chalcogenol-
ates 3, obtained from indium(I) iodide and diorganyl dis-
elenides, and several types of chiral 2-oxazolines 1
[
[
a] Departmento de Química, Universidade Federal de Santa
Maria,
Santa Maria, RS 97105-900, Brazil
Fax: +55-55-3220-8998
(Scheme 1). The work resulted in an efficient synthesis of
E-mail: albraga@quimica.ufsm.br
b] Instituto de Química, Universidade de São Paulo,
São Paulo, SP 05508-900, Brazil
β-seleno amides 2 and selenocysteine derivatives 5 under
mild and neutral conditions.
Eur. J. Org. Chem. 2007, 5327–5331
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5327

A. L. Braga et al.
SHORT COMMUNICATION
Table 1, Entry 3 vs. 2 and 4). By changing the solvent to
toluene, a small decrease in the reaction yield was observed
(Table 1, Entry 5). Concerning the high stability of organic
indium compounds in water relative to other metals, we
evaluated the reaction in EtOH/H O (2:1), but unfortu-
2
nately the product was obtained in low yield (Table 1, En-
try 6). Presumably under these conditions, the indium(III)
selenolates are readily hydrolyzed to produce the corre-
[
9b]
sponding selenol and indium(III) hydroxide.
We also varied the indium salt which promotes the cleav-
age of the Se–Se bond. Thus, the bis(organoseleno)bromo-
indium(III) was generated by reduction of PhSeSePh with
InBr and applied in the ring-opening reaction of 1a to fur-
nish 2a in same yield for dioxane (Table 1, compare En-
tries 7 and 3) and with a small decrease in the yield for
THF and toluene (Table 1, Entries 8 and 9).
Scheme 1. Indium(I) iodide mediated oxazoline ring opening with
diorganoyl diselenides.
Notably, indium selenolate 3 promoted the oxazoline
ring-opening reaction in the absence of a Lewis acid. We
envisage that this fact is probably due to coordination of
the indium(III) complex with the nitrogen atom of the oxaz-
oline moiety (Figure 1), which itself acts as a Lewis acid.[
The preparation of β-seleno amides proceeds through regio-
and chemoselective nucleophilic attack of the organoyl sele-
nide anion at the C5 position of the ring, which leads to
cleavage of the C5–O1 bond and furnishes the desired prod-
uct without any loss of enantiomeric purity, as determined
by chiral HPLC.
Results and Discussion
It is well know that indium(I) compounds, through their
oxidative insertion into a suitable substrate, generate the
corresponding indium(III) derivatives. Thus, complex bis-
13]
(organoylseleno)iodoindium(III) 3 is readily prepared by
the reaction of equimolar amounts of InI and RSeSeR in
[
9,12a,15]
1
,4 dioxane.
Our studies started by the determination of the best sol-
vent in which to perform this reaction by using oxazoline
a and the bis(organoseleno)iodoindium(III) prepared
1
through the reaction between PhSeSePh and InI as shown
in Table 1.
Table 1. Ring-opening reactions of oxazoline 1a with the use of
various solvents.
Figure 1. Proposed mechanism for the oxazoline ring-opening reac-
tion.
With the optimal conditions in hand, the present reac-
tion was extended to a broader range of oxazolines and
diselenides in order to evaluate the scope and limitations of
the mild reaction procedure.
As delineated in Table 2, all the β-seleno amides were
obtained in good-to-excellent yields for all the oxazolines
studied. Concerning the R group, the presence of an elec-
tron-donating group, such as the methoxy group, or an elec-
tron-withdrawing group, such as a chloro atom, in the aro-
matic rings of the diselenides had no significant influence
on the reactivity of the process, as the products were ob-
tained with only a slight decrease in the reaction yield
Entry
Solvent
Yield [%][a]
1
2
3
4
5
6
7
8
9
DCM
THF
1,4-dioxane
MeCN
toluene
EtOH/H O
2
1,4-dioxane
THF
30
94
99
61
81
15
99
89
75
[
[
[
[
b]
c]
c]
c]
toluene
[
a] Yields refer to those of pure isolated products characterized by
spectroscopic methods. [b] EtOH/H O, 2:1. [c] InBr was used.
2
(Table 2, Entries 2 and 3). The reaction was also performed
with dialkyl diselenides as a nucleophilic source of selenium
When dichloromethane was employed as the solvent, the and products 2d–f were furnished in good yields (Table 2,
product was obtained in a very unsatisfactory yield Entries 4–6). The nature of the side chain on the oxazoline
(Table 1, Entry 1). By increasing the polarity and boiling did not play a significant role in terms of conversion to
point of the solvent system (Table 1, Entries 2–4), better re- the desired product, as the results obtained with different
sults were obtained, and the most efficient ring-opening lipophilic groups were quite similar (Table 2, Entries 7 and
process was achieved when 1,4 dioxane was used (99%; 8).
5328
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5327–5331

Synthesis of Chiral β-Seleno Amides and Selenocysteine Derivatives
Table 2. Ring-opening Reaction of oxazolines 1a–c.
Scheme 3. Synthesis of selenocysteine derivatives.
Entry Oxazoline
R1
R
Product, yield [%][a]
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1b
1c
iPr
iPr
iPr
iPr
iPr
iPr
Bn
iBu
Ph
2a, 99
2b, 89
2c, 90
2d, 40
2e, 62
2f, 53
2g, 98
2h, 95
As outlined in Scheme 3, this route may constitute an
attractive option for the preparation of various structurally
diverse selenocysteine derivatives, as the strategy presented
herein does not require the use of protecting groups such
as Boc, Cbz, or Fmoc. It is worth mentioning that phenyl-
selenocysteine derivatives, such as compound 5a, have been
used as precursors for the solid-phase peptide synthesis
6 4
p-MeOC H
p-ClC
Bn
Bu
Et
Ph
Ph
6 4
H
[
a] Yields refer to those of pure isolated products characterized by (SPPS) of selenocysteine-containing peptides, which are
spectroscopic methods.
used for the mild oxidative introduction of dehydro-
[
4a–4c]
alanines.
Conclusions
As a further extension of the present approach, we at-
tempted to synthesize several chiral β-chalcogeno amides,
and the results are summarized in Scheme 2. Chiral β-thio
amides 4a (R = Ph) and 4b (R = Bn) were obtained in
excellent yields, but corresponding tellurium derivative 4c
The present procedure with indium(I) iodide provides a
practical and concise synthesis of a wide range of useful
chiral β-seleno amides 2a–h and their derivatives in an easy,
straightforward, and flexible synthetic route that starts
from chiral 2-oxazolines. This method offers significant im-
provements with regard to operational simplicity, reaction
conditions (neutral medium), and high isolated yields of
products. Most importantly, with the bis(organoylseleno)-
iodoindium(III) complexes 3 we could also achieve the ef-
ficient synthesis of selenocysteine derivatives 5a–c.
(R = Ph) was obtained in low yield.
Experimental Section
General Procedure for the Synthesis of Chiral β-Seleno Amides 2 or
5
: In a 25-mL round-bottomed flask equipped with a reflux con-
denser, under an argon atmosphere, InI (powder, 121 mg,
.5 mmol) was added to a solution of the appropriate diorganyl
0
diselenide (0.5 mmol) in dry 1,4 dioxane (5 mL). The mixture was
allowed to stir until all InI (15–45 min) was dissolved and then
the appropriate oxazoline (0.5 mmol) was added, and the resulting
solution was stirred and heated at reflux for 24 h. The mixture was
quenched with a saturated NH
CH Cl , and the combined organic fractions were collected, dried
with MgSO , and filtered; the solvent was then removed in vacuo
4
Cl solution and extracted with
Scheme 2. Synthesis of chiral β-chalcogeno amides.
2
2
4
to yield crude products 2a–h or 5a–c, which were purified by flash
chromatography.
Because of their potential biological activity, in the last
years some recent and classical successful approaches aimed (S)-N-[3-Methyl-1-(phenylselanyl)butan-2-yl]benzamide (2a): The
at the synthesis of selenocysteines and their derivatives were enantiomeric purity was determined by HPLC analysis (Chiralcel-
–
1
[
16]
OD column; hexane/2-propanol, 90:10; flow rate 1.0 mLmin ; R
isomer t
documented. In this context, a formidable challenge still
remains to develop novel synthetic methods that can permit
the introduction of selenium into optically active amino ac-
ids, which could be widely explored as building blocks for
R R
= 9.33 min; S isomer t = 13.47 min) and found to be
Ͼ99.9%. Yield: 0.171 g (99%). White solid. M.p. 101–103 °C.
α] = +210 (c = 1.0, CH Cl ). H NMR (400 MHz, CDCl ): δ =
D 2 2 3
.60–7.35 (m, 7 H), 7.25–7.19 (m, 3 H), 6.29 (d, J = 8.4 Hz, 1 H),
2
0
1
[
7
[
16c,16d]
the synthesis of seleno peptides and derivatives.
Thus, we also focused our attention on the synthetic useful-
ness of this method by evaluating its viability in the synthe-
4
(
.22 (m, 1 H), 3.25–3.23 (m, 2 H), 2.05–2.00 (m, 1 H), 0.98–0.96
m, 6 H) ppm. C NMR (100 MHz, CDCl ): δ = 167.0, 134.5,
3
32.7, 131.1, 129.9, 129.1, 128.3, 126.9, 126.7, 54.7, 31.7, 31.6, 19.3,
sis of selenocysteine derivatives, and 2-oxazoline-4-carbox- 18.5 ppm. Se NMR (76 MHz, CDCl ): δ = 251.5 ppm. IR (KBr):
13
1
7
7
3
–
1
ylate was employed as the starting material (Scheme 3).
ν˜ = 3313, 2965, 1633, 1533, 1470, 1178, 733, 693 cm . HRMS
Eur. J. Org. Chem. 2007, 5327–5331
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5329

A. L. Braga et al.
SHORT COMMUNICATION
(ESI): calcd. for C18
H
21NNaOSe [M + Na]+ 370.0680; found 132.7, 131,4, 129.7, 129.4, 129.1, 128.6, 128.4, 127.2, 126.7, 126.7,
3
70.0677.
50.8, 39.1, 32.1 ppm. IR (KBr): ν˜ = 3313, 2919, 1641, 1536, 1475,
–
1
1
+
203, 737, 691 cm . HRMS (ESI): calcd. for C22H21NNaOSe [M
Na] 418.0680; found 418.0677.
(
(
S)-N-[1-(4-Methoxyphenylselanyl)-3-methylbutan-2-yl]benzamide
2b): Yield: 0.167g (89%). White solid. M.p. 100–102 °C. [α]
+
2
0
D
=
1
+
99 (c = 1.0, CH
2
Cl ). H NMR (400 MHz, CDCl ): δ = 7.61–7.59 (S)-N-[4-Methyl-1-(phenylselanyl)pentan-2-yl]benzamide (2h): Yield:
2
3
2
0
(m, 2 H), 7.48–7.36 (m, 5 H), 6.75–6.73 (m, 2 H), 6.10 (d, J = 0.171g (95%). White solid. M.p. 99–101 °C. [α]
D
= +65 (c = 1.0,
2 2 3
CH Cl ). H NMR (400 MHz, CDCl ): δ = 7.58–7.17 (m, 10 H),
1
8
2
.8 Hz, 1 H), 4.21–4.15 (m, 1 H), 3.74 (s, 3 H), 3.14 (m, 2 H),
.06–1.99 (m, 1 H), 0.97–0.93 (m, 6 H) ppm. 13C NMR (100 MHz,
6.16 (d, J = 8.4 Hz, 1 H), 4.53–4.48 (m, 1 H), 3.27 (dd, J = 12.6 Hz,
J = 5.2 Hz, 1 H), 3.20 (dd, J = 12.6 Hz, J = 4.6 Hz, 1 H), 1.65–1.46
CDCl
1
2
3
): δ = 167.0, 159.4, 135.6, 134.7, 131.2, 128.4, 126.8, 119.7,
1
3
14.9, 55.1, 54.9, 32.8, 31.7, 19.3, 18.5 ppm. IR (KBr): ν˜ = 3308,
965, 1633, 1551, 1249, 1183, 696 cm . HRMS (ESI): calcd. for
3
(m, 3 H), 0.92–0.89 (m, 6 H) ppm. C NMR (100 MHz, CDCl ): δ
–1
= 166.7, 134.5, 132.6, 131.2, 130.0, 129.2, 128.3, 127.0, 126.7, 47.6,
+
C
19
H23NNaO
2
Se [M + Na] 400.0786; found 400.0777.
43.6, 34.3, 25.0, 22.8, 22.3 ppm. IR (KBr): ν˜ = 3293, 2960, 1628,
–
1
1
552, 1470, 1178, 732, 696 cm . HRMS (ESI): calcd. for
(
(
S)-N-[1-(4-Chlorophenylselanyl)-3-methylbutan-2-yl]benzamide
2c): Yield: 0.171g (90%). White solid. M.p. 122–124 °C. [α]
23NNaOSe [M + Na]+ 384.0837; found 384.0837.
19
C H
2
0
D
=
1
+
189 (c = 1.0, CH
2 2 3
Cl ). H NMR (400 MHz, CDCl ): δ = 7.61– (S)-N-[3-Methyl-1-(phenylthio)butan-2-yl]benzamide (4a): Yield:
2
0
7
=
.59 (m, 2 H), 7.48–7.39 (m, 5 H), 7.16–7.14 (m, 2 H), 6.07 (d, J 0.144g (96%). White solid. M.p. 114–116 °C. [α]
8.0 Hz, 1 H), 4.23–4.17 (m, 1 H), 3.21–3.18 (m, 2 H), 2.05–1.96 CH Cl ). H NMR (400 MHz, CDCl
2 2 3
D
= +45 (c = 1.0,
): δ = 7.63 (d, J = 7.2 Hz, 2
m, 1 H), 0.98 (d, J = 3.2 Hz, 3 H), 0.96 (d, J = 3.2 Hz, 3 H) ppm. H), 7.45–7.34 (m, 5 H), 7.23 (t, J = 7.6 Hz, 2 H), 7.15–7.14 (m, 1
1
(
1
3
C NMR (100 MHz, CDCl
3
): δ = 167.0, 134.4, 134.2, 133.3, 131.3, H), 6.22 (d, J = 8.4 Hz, 1 H), 4.23–4.19 (m, 1 H), 3.23–3.21 (m, 2
1
29.2, 128.4, 128.1, 126.7, 54.7, 32.0, 31.6, 19.4, 18.4 ppm. IR H), 2.10–2.05 (m, 2 H), 0.98 (d, J = 3.6 Hz, 3 H), 0.97 (d, J =
–1
13
(
(
3
KBr): ν˜ = 3298, 2955, 1628, 1546, 1470, 1091, 691 cm . HRMS
ESI): calcd. for C18
82.0479.
3.6 Hz, 3 H) ppm. C NMR (100 MHz, CDCl
134.6, 131.28, 129.7, 129.0, 128.4, 126.8, 126.3, 54.5, 37.0, 30.8,
3
): δ = 167.2, 136.1,
+
H21ClNOSe [M + H] 382.0476; found
19.4, 18.4 ppm. HRMS (ESI): calcd. for C18
Na] 322.1247; found 322.124.
H
21NNaOS [M +
+
(S)-N-[1-(Benzylselanyl)-3-methylbutan-2-yl]benzamide (2d): Yield:
2
0
0.072g (40%). White solid. M.p. 108–110 °C. [α]
D
= +215 (c = 1.0,
): δ = 7.73–7.71 (m, 2 H),
.50–7.43 (m, 3 H), 7.27–7.14 (m, 5 H), 6.11 (d, J = 8.0 Hz, 1 H), 7.22 (m, 10 H), 6.13 (d, J = 8.4 Hz, 1 H), 4.20–4.12 (m, 1 H), 3.75
.15–4.12 (m, 1 H), 3.81 (d, J = 12 Hz, 1 H), 3.76 (d, J = 12 Hz, 1 (d, J = 1.2 Hz, 2 H), 2.70–2.63 (m, 2 H), 2.03–1.86 (m, 1 H), 0.96–
(S)-N-[1-(Benzylthio)-3-methylbutan-2-yl]benzamide (4b): Yield:
0.147g (94%). White solid. H NMR (400 MHz, CDCl ): δ = 7.76–
3
1
1
CH
7
4
2
Cl
2
). H NMR (400 MHz, CDCl
3
1
3
H), 2.84 (dd, J = 12.4 Hz, J = 6.4 Hz, 1 H), 2.74 (dd, J = 12.4 Hz,
3
0.91 (m, 6 H) ppm. C NMR (100 MHz, CDCl ): δ = 167.3, 138.1,
J = 4.8 Hz, 1 H), 1.92–1.87 (m, 1 H), 0.95 (d, J = 4.4 Hz, 3 H), 134.8, 131.4, 129.6, 128.9, 128.6, 128.6, 128.5, 128.4, 127.1, 126.9,
0
1
3
1
.93 (d, J = 4.4 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl
): δ = 53.4, 36.5, 34.1, 31.2, 19.4, 18.4 ppm.
3
67.1, 139.0, 134.8, 131.3, 129.0, 128.8, 128.5, 126.9, 126.8, 53.8,
(
0
S)-N-[3-Methyl-1-(phenyltellanyl)butan-2-yl]benzamide (4c): Yield:
2.0, 27.7, 27.6, 19.4, 18.4 ppm. IR (KBr): ν˜ = 3298, 2965, 1639,
2
0
.050g (25%). Yellow solid. M.p. 79–81 °C. [α]
D
= +55 (c = 1.0,
): δ = 7.72–7.70 (m, 2 H),
.61–7.58 (m, 2 H), 7.45–7.11 (m, 6 H), 6.18 (d, J = 8.4 Hz, 1 H),
–
1
5 2 6 , 1 1 7 8 , 7 3 1 , 6 9 1 c m . H R M S ( E S I ) : c a l c d . fo r
1
2 2 3
CH Cl ). H NMR (400 MHz, CDCl
7
+
C
19
H23NNaOSe [M + Na] 384.0842; found 384.0824.
(
0
S)-N-[1-(Butylselanyl)-3-methylbutan-2-yl]benzamide (2e): Yield:
4.17–4.13 (m, 1 H), 3.26 (dd, J = 12.4 Hz, J = 6.5 Hz, 1 H), 3.21
(dd, J = 12.4 Hz, J = 4.7 Hz, 1 H), 1.95–1.89 (m, 1 H), 0.96 (d, J
.101g (62%). Pale yellow oil. [α]2
): δ = 7.79–7.77 (m, 2 H), 7.51–7.41 (m, 3
H), 6.30 (d, J = 8.4 Hz, 1 H), 4.17–4.10 (m, 1 H), 2.95 (dd, J = (100 MHz, CDCl
0
1
D 2 2
= +118 (c = 1.0, CH Cl ). H
1
3
NMR (400 MHz, CDCl
3
= 6.7 Hz, 3 H), 0.92 (d, J = 6.7 Hz, 3 H) ppm. C NMR
): δ = 167.0, 138.5, 134.6, 131.3, 129.3, 128.4,
127.8, 126.8, 111.2, 55.1, 33.3, 19.4, 18.5, 14.6 ppm. IR (KBr): ν˜ =
3
1
2
2
7
1
1
2.6 Hz, J = 5.8 Hz, 1 H), 2.78 (dd, J = 12.6 Hz, J = 5.0 Hz, 1 H),
.58 (t, J = 7.6 Hz, 2 H), 2.01–1.92 (m, 1 H), 1.65 (q, J = 7.4 Hz,
–
1
3329, 2955, 1643, 1547, 1178, 732, 691 cm . HRMS (ESI): calcd.
H), 1.36 (sex, J = 7.4 Hz, 2 H), 1.01–0.98 (m, 6 H), 0.86 (t, J = for C18
H
21NNaOTe [M + Na]+ 420.0577; found 420.0565.
.4 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl
31.3, 128.5, 126.8, 54.2, 32.7, 31.6, 27.7, 24.8, 22.9, 19.5, 18.5,
): δ = 167.0, 134.8,
3
(
0
R)-Methyl 2-Benzamido-3-(phenylselanyl)propanoate (5a): Yield:
2
0
.127g (70%). White solid. M.p. 74–76 °C. [α]
D
= +35 (c = 1.0,
): δ = 7.61–7.19 (m, 10 H),
.95 (d, J = 7.2 Hz, 1 H), 5.19–5.14 (m, 1 H), 3.55–3.51 (m, 4 H),
–
1
3.4 ppm. IR (film): ν˜ = 3298, 2960, 1634, 1541, 1178, 701 cm .
1
2 2 3
CH Cl ). H NMR (400 MHz, CDCl
6
3
+
HRMS (ESI): calcd. for C16
28.1178.
H26NOSe [M + H] 328.1179; found
3
1
3
.42 (dd, J = 13.6 Hz, J = 4.8 Hz, 1 H) ppm. C NMR (100 MHz,
): δ = 170.7, 166.7, 133.3, 133.2, 131.2, 129.1, 128.5, 128.3,
(
S)-N-[1-(Ethylselanyl)-3-methylbutan-2-yl]benzamide (2f): Yield:
CDCl
127.4, 126.9, 52.6, 52.3, 29.8 ppm. Se NMR (76 MHz, CDCl
.81–7.31 (m, 5 H), 6.33 (d, J = 7.8 Hz, 1 H), 4.21–4.11 (m, 1 H), = 268.5 ppm. IR (KBr): ν˜ = 3359, 3073, 2960, 1741, 1649, 1516,
3
1
77
0
7
2
1
1
1
2
.079g (53%). Pale yellow oil. H NMR (400 MHz, CDCl
3
): δ =
3
): δ
–
1
.88 (dd, J = 16 Hz, J = 5.8 Hz, 2 H), 2.60 (dd, J = 7.4 Hz, J = 1 2 0 8 , 1 1 6 2 , 7 4 2 , 6 8 1 c m . H R M S ( E S I ) : c a l c d . fo r
5 Hz, 2 H), 2.05–1.88 (m, 1 H), 1.38 (t, J = 7.6 Hz, 3 H), 1.12– 17NNaO
Se [M + Na]+ 386.0265; found 386.0261.
.05 (m 6 H) ppm. 13C NMR (100 MHz, CDCl
): δ = 166.78,
C
17
H
3
3
(
R)-Methyl-2-benzamido-3-(4-chlorophenylselanyl) Propanoate (5b):
34.48, 131.08, 128.31, 128.26, 128.00, 127.90, 126.52, 53.82, 31.3,
2
0
Yield: 0.129g (65%). White solid. M.p. 85–87 °C. [α]
1
2
D
= +30 (c =
): δ = 7.60 (d, J = 7.6 Hz,
6.9, 19.2, 18.1, 18.0, 15.5 ppm. HRMS (ESI): calcd. for
1
.0, CH
2
Cl
2
). H NMR (400 MHz, CDCl
3
+
C
14
H
21NNaOSe [M + Na] 322.0688; found 322.0681.
H), 7.50–7.41 (m, 5 H), 7.17–7.15 (m, 2 H), 6.84 (d, J = 7.2 Hz,
(
0
1
S)-N-[3-Phenyl-1-(phenylselanyl)propan-2-yl]benzamide (2g): Yield: 1 H), 5.20–5.16 (m, 1 H) 3.62 (s, 3 H), 3.57 (dd, J = 13.4 Hz, J =
20
13
.193g (98%). White solid. M.p. 148,5–150.5 °C. [α]
D
= +52 (c =
4.5 Hz, 1 H), 3.39 (dd, J = 13.4 Hz, J = 4.4 Hz, 1 H) ppm.
C
1
.0, CH
2
Cl
2
). H NMR (400 MHz, CDCl
3
): δ = 7.53–7.19 (m, 15
NMR (100 MHz, CDCl ): δ = 170.8, 166.7, 135.0, 133.9, 133.3,
3
H), 6.20 (d, J = 7.2 Hz, 1 H), 4.64–4.59 (m, 1 H), 3.24–2.97 (m, 4 131.9, 129.3, 128.5, 126.9, 126.8, 52.9, 52.6, 30.1 ppm. IR (KBr): ν˜
H) ppm. 13C NMR (100 MHz, CDCl
330
): δ = 168.8, 137.3, 134.3,
= 3344, 3067, 2944, 1736, 1644, 1516, 1224, 1091, 809 cm . HRMS
–1
3
5
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5327–5331

Synthesis of Chiral β-Seleno Amides and Selenocysteine Derivatives
(
4
ESI): calcd. for C17
19.9867.
H
16ClNNaO
3
Se [M + Na]+ 419.9876; found
[7] a) A. L. Braga, O. E. D. Rodrigues, M. W. Paixão, H. R. Ap-
pelt, C. C. Silveira, D. P. Bottega, Synthesis 2002, 2338, b)
A. L. Braga, M. W. Paixão, D. S. Lüdtke, C. C. Silveira,
O. E. D. Rodrigues, Org. Lett. 2003, 5, 2635, c) A. L. Braga,
S. J. N. Silva, D. S. Lüdtke, R. L. Drekener, C. C. Silveira,
J. B. T. Rocha, L. A. Wessjohann, Tetrahedron Lett. 2002, 43,
7329, d) A. L. Braga, M. W. Paixão, G. Marin, Synlett 2005,
(
(
(
R)-Methyl-2-benzamido-3-(4-methoxyphenylselanyl) Propanoate
2
0
5c): Yield: 0.133g (68%). White solid. M.p. 79–81 °C. [α]
c = 1.0, CH Cl ). H NMR (400 MHz, CDCl
2 2 3
D
= +38
): δ = 7.64–7.62 (m,
H), 7.53–7.49 (m, 3 H), 7.45–7.40 (m, 2 H), 6.94 (d, J = 7.0 Hz,
1
2
1
3
1
975, e) A. L. Braga, D. S. Lüdtke, E. E. Alberto, J. Braz.
H), 6.78–6.76 (m, 2 H), 5.19–5.16 (m, 1 H), 3.75 (s, 3 H), 3.62 (s,
H), 3.48 (dd, J = 13.3 Hz, J = 4.4 Hz, 1 H), 3.34 (dd, J = 13.3 Hz,
Chem. Soc. 2006, 17, 1, f) A. L. Braga, D. S. Lüdtke, J. A.
Sehnem, E. E. Alberto, Tetrahedron 2005, 61, 11664, g) C.
Santi, T. Wirth, Tetrahedron: Asymmetry 1999, 10, 1019, h) T.
Wirth, Tetrahedron Lett. 1995, 36, 7849, i) T. Wirth, K. J. Kul-
ieke, G. Fragale, Helv. Chim. Acta 1996, 79, 1957, j) J. Sprinz,
M. Kiefer, G. Helmchen, M. Reggelin, G. Huttner, O. Walter,
L. Zsolnai, Tetrahedron Lett. 1994, 35, 1523, k) M. Zielinska-
Blajet, R. Siedlecka, J. Skarzewski, Tetrahedron: Asymmetry
13
J = 5.0 Hz, 1 H) ppm. C NMR (100 MHz, CDCl
3
): δ = 170.9,
66.6, 159.5, 136.1, 131.6, 128.3, 128.2, 126.9, 118.3, 114.8, 55.1,
2.8, 52.4, 30.5 ppm. IR (KBr): ν˜ = 3327, 2951, 1736, 1641,
1
5
1
4
–1
H19NNaO
4
Se [M + Na]+
521 cm . HRMS (ESI): calcd. for C18
16.0379; found 416.0374.
2
007, 18, 131.
Acknowledgments
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Toru, Y. Ueno, Synthesis 1992, 377, c) K. K. Bhasin, N. Singh,
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Published Online: October 1, 2007
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Eur. J. Org. Chem. 2007, 5327–5331
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5331