Ephedrine-based diselenide: A promiscuous catalyst suitable to mimic the enzyme glutathione peroxidase (GPx) and to promote enantioselective C-C coupling reactions

Article abstract of DOI:10.1039/c2ob25539a

The ephedrine-based diselenide appears as a new promiscuous catalyst, able to generate optically active alcohols by addition of organozinc to aldehydes (up to 97% ee), and shows powerful GPx like activity, reducing H₂O ₂ to water in only 16.33 min (eleven times faster than PhSeSePh).

Full text of DOI:10.1039/c2ob25539a

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PAPER
Ephedrine-based diselenide: a promiscuous catalyst suitable to mimic the
enzyme glutathione peroxidase (GPx) and to promote enantioselective C–C
coupling reactions†
Letiére C. Soares,a Eduardo E. Alberto,b Ricardo S. Schwab,c Paulo S. Taube,d Vanessa Nascimento,d
Oscar E. D. Rodriguesa and Antonio L. Braga*d
Received 12th March 2012, Accepted 27th June 2012
DOI: 10.1039/c2ob25539a
The ephedrine-based diselenide appears as a new promiscuous catalyst, able to generate optically active
alcohols by addition of organozinc to aldehydes (up to 97% ee), and shows powerful GPx like activity,
reducing H2O2 to water in only 16.33 min (eleven times faster than PhSeSePh).
The growing field of research of selenoproteins combined with
essential physicochemical properties of selenium has promoted
growing interest in the chemistry and biochemistry of selenium
compounds.1 High impact studies have determined that selenium
plays a pivotal role in glutathione peroxidase enzymes (GPx),
which protect organisms from oxidative stress, inherent from
oxygen metabolism.2 Additionally, it has been employed as an
important agent in cancer prevention, immunology, aging, male
reproduction, neurodegenerative diseases, including Alzheimer’s
and Parkinson’s disease, and other physiological processes.3
Since the discovery that selenium plays a paramount role
in GPx enzymes, synthetic developments and design of new
chalcogen-based catalytic antioxidants have attracted consider-
able attention.4
Small molecule organoselenium compounds have emerged as
excellent candidates to act as GPx mimics, due to their well-
known ability to undergo a two-electron redox cycle between
chalcogen(II) and (IV) species.5 On the other hand, in recent
years, increasing application of chiral selenium compounds as
ligands in metal-catalyzed enantioselective transformations has
been witnessed.6 One of the most important challenges in this
field is the development of new chiral ligands for the enantio-
selective addition of organozinc reagents to carbonyl compounds.
This reaction is one of the most important protocols used to
generate a new carbon–carbon bond in an asymmetric manner.7
Two reactions are notable in this regard: the addition of aryl
boronic acids and the addition of diethylzinc to aldehydes.8,9
Much effort has been directed toward the design of new chiral
ligands, which give access to optically active alcohols, acknow-
ledged as important precursors for pharmacologically and bio-
logically active compounds.10
Although selenium catalysts have been successfully used in
the addition of diethylzinc to aldehydes, to the best of our
knowledge, only a few examples have appeared in the literature
describing the application of chiral selenium compounds acting
as effective ligands for the addition of boronic acids to carbonyl
compounds, involving the coordination of the selenium moiety
with the metallic center.11–13 Some chiral selenium compounds
have shown good activity in asymmetric transformations, such
as the enantioselective addition of diethylzinc to aldehydes,14
1,4-addition of Grignard reagents to enones15 and asymmetric
allylic substitution catalyzed by palladium.16
Design and screening of new ligands derived from ephedrine
and its analogues have been explored in numerous asymmetric
reactions.17 The structural characteristics of ephedrine, such as
the presence of two chiral centers directly attached to coordi-
nation centers and the easy introduction of new functionalities,
make this chiral pool an excellent candidate for application in
asymmetric transformations.
In this context, and continuing our interest in the development
of chiral organochalcogen compounds with tailored biological
importance and their application as ligands in asymmetric syn-
thesis, we describe herein the preparation of a new series of
selenium compound derivatives from (−)-ephedrine (Scheme 1)
and their application in asymmetric carbon–carbon bond for-
mation as well as GPx mimics.
aNanoBio, Dpto de Química, CCNE, Universidade Federal de Santa
Maria, Santa Maria, RS, Brazil
bChemistry Department, The State University of New York at Buffalo,
Buffalo, NY, USA
cInstituto de Química, Universidade Federal do Rio Grande do Sul,
Porto Alegre, RS, Brazil
dLaboratório de Síntese de Substâncias de Selênio Bioativas CFM,
Departamento de Química, Universidade Federal de Santa Catarina,
Florianópolis, SC, Brazil. E-mail: albraga@qmc.ufsc.br;
Tel: +55 (48) 37216427
Chiral selenium compounds 2 and 3a–d were readily pre-
pared, in one step, affording the ligands in satisfactory yields
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2ob25539a
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Table 1 Optimization of reaction conditions.
Entry
Ligand (load)
Time (h)
T (°C)
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
8
3a (10 mol%)
3b (10 mol%)
3c (10 mol%)
3c (10 mol%)
3c (10 mol%)
3d (10 mol%)
2 (10 mol%)
1 (10 mol%)
2 (20 mol%)
2 (5 mol%)
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
25
25
25
0
−20
0
0
0
0
0
85
90
91
93
96
98
94
89
99
99
93
—
—
51
70
59
85
92
40
93
86
80
Scheme 1 Reagents and conditions: (i) 1 (1 mmol), THF (10 mL),
Et3N (1.2 mmol), MsCl (1 mmol), 0 °C, 30. (ii) Li2Se2 (2 mmol) in
THF (5 mL), overnight. (iii) Na[RSeB(OEt)3] (1 mmol), in THF (5 mL),
r.t. 12 h.
(Scheme 1). Mesylation of amino alcohol 1 “in situ”, followed
by subsequent reaction with Li2Se2 or a sodium selenolate
derivative, allowed the preparation of 2 in 53% yield and 3a–d
in 56–83% isolated yields.
9
10
11
2 (2.5 mol%)
0
The ability of the synthesized catalysts to promote carbon–
carbon bond formation in an enantioselective manner was evalu-
ated firstly with the addition of boronic acids to aldehydes. To
this aim, phenyl boronic acid was used, as a source of nucleophi-
lic aryl species, along with 4-tolualdehyde in the presence of
10 mol% of ligands 3a–d or 2 (Table 1). The initial experiments
were carried out using the compounds 3a and 3b as chiral induc-
tors. Although the product was obtained in 85 and 90% yield,
respectively, after 1.5 h at r.t., in both experiments no enantio-
meric excess was observed (entries 1 and 2). Interestingly, sele-
noester 3c, under the same conditions, provided the product in
91% yield and with 51% of ee (entry 3).
A detailed analysis of Table 1 shows that the enantioselectivity
was influenced by the temperature. For instance, using ligand 3c
at 0 °C the enantiomeric excess reached 70% with a slight
increase in the yield (entry 4). On the other hand, when the reac-
tion temperature was decreased to −20 °C, the product was
achieved in 96% yield and the selectivity was decreased to 59%
(entry 5). Thus, the reaction carried out at 0 °C was established
as the optimal condition for this protocol.
Following these observations and in view of obtaining a more
effective catalyst, the use of other synthesized ligands was tested.
Analyzing Table 1, it is possible to verify that compound 3d
showed higher selectivity compared to selenoester 3c, affording
the desired product in near quantitative yield and with 85% of
enantiomeric excess (entries 6 and 4). Furthermore, improved
results in this testing reaction were obtained using the diselenide
2. This compound showed excellent catalyst activity for this
reaction, affording the desired product in 94% yield and with
92% ee (entry 7). A direct comparison between our designed
catalyst 2 and alkylated ephedrine 1 was also performed and,
encouragingly, the diselenide 2 was a much more effective cata-
lyst for this transformation (entries 7 and 8).
Another set of experiments was also performed to optimize
the amount of ligand 2 necessary to accomplish the reaction
efficiently. An increase in the amount of 2 to up to 20 mol%
proved to be ineffective, since the enantiomeric excess observed
was at the same level obtained for the reaction using 10 mol% of
2 (entry 9). Some success was obtained by decreasing the cata-
lyst loading to 5 and 2.5 mol%. While the yields were not
affected, there was a slight decrease in the ee (entries 10 and 11).
With these results it was possible to determine the optimal cata-
lyst load as 10 mol%.
a Yields for pure isolated products. b Calculated by HPLC analysis.
Table 2 Boronic acid addition to aldehydes catalyzed by 2.
Entry
Ar1
Ar2
Yielda (%)
eeb,c (%)
1
2
3
4
5
6
7
8
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
2-MeC6H4
4-MeC6H4
2-OMeC6H4
4-OMeC6H4
2-ClC6H4
4-ClC6H4
2-MeC6H4
4-MeC6H4
2-ClC6H4
4-ClC6H4
2-OMeC6H4
4-OMeC6H4
C6H5
C6H5
C6H5
C6H5
C6H5
91
93
85
74
97
84
80
70
60
98
50
76
97(R)
91(R)
89(R)
90(R)
88(S)
87(R)
75(S)
85(S)
45(R)
83(S)
77(S)
71(S)
9
10
11
12
C6H5
a Yields for pure isolated products. b Calculated by HPLC analysis. c The
relative configuration was determined by literature comparison.12b
Given that diselenide 2 proved to be the most effective catalyst
for the addition of phenyl boronic acid to 4-tolualdehyde, we
next examined the scope of addition of boronic acids to different
aldehydes using diselenide 2. Initially, phenyl boronic acid was
employed as a source of aryl species and substituted aldehydes
(Table 2). Our results showed that electronic and steric effects in
the tested aldehydes have only a slight influence on the course of
this reaction. It was found that all substituted aldehydes afforded
products in the same range of yields and with high levels of
enantioselectivity (entries 1–6). The best result was obtained for
2-tolualdehyde, affording the respective product in 91% yield
and 97% ee (entry 1). Next, we investigated the aryl transference
of different aryl boronic acids to benzaldehyde (entries 7–12).
A small decrease in terms of the yield and enantioselectivity was
observed employing para-substituted boronic acids in compari-
son with the first set of experiments. Moreover, the reactions
were strongly affected by the use of ortho-substituted boronic
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Table 3 Asymmetric addition of diethylzinc to benzaldehyde.
Entry
Ligand (mol%)
T (°C)
Yielda (%)
eeb (%)
Scheme 2
1
2
3
4
5
6
7
3c (10)
3d (10)
2 (10)
3d (10)
3d (10)
3d (5)
25
25
25
0
−20
−20
−20
57
82
71
68
66
61
64
91
92
86
89
93
90
89
3d (2.5)
a Yields for pure isolated products. b Calculated by HPLC analysis.
acids. In most cases a decrease in the yield was observed. This
pattern could be attributed to ineffective transmetalation between
Et2Zn and substituted phenyl boronic acid due to the steric and
electronic effects of the substituent.
Encouraged by these results, we also evaluated the efficiency
of the most effective ligands in the addition of diethylzinc to
aldehydes. Different reaction conditions were screened in a view
to improve the efficiency of the system (Table 3). Reactions
carried out with 10 mol% of ligands 3c, 3d and 2 were tested
and all of them showed good results for the addition of diethyl-
zinc to benzaldehyde (entries 1–3). To the compounds tested,
catalyst 3d showed improved efficiency, furnishing 1-phenyl-1-
propanol in 82% yield and 92% ee at 25 °C (entry 2). Other
reaction conditions, such as the temperature and the amount of
3d, were analyzed in order to establish the best protocol for this
reaction.
As shown in Table 3, a decrease from 10 to 5 and 2.5 mol% at
−20 °C caused just a slight decrease in terms of enantiomeric
excess, however, the reaction yields were significantly affected
(entries 5, 6 and 7).
The mechanism for this reaction is similar to that described in
the literature involving selenium compounds, where the active
species is a selenolate generated in the reaction medium. In fact,
we postulated that diselenide can be cleaved in the presence of
diethylzinc leading to the formation of a selenolate (active
species) and a selenoether.13
Fig. 1 GPx like behavior of catalysts 2, 3a, 3c and PhSeSePh.
Table 4 GPx like activity of organoselenium catalysts 2, 3a, 3c and
PhSeSePh.
Entry
Catalysta,b
T50 c (min)
Relative activity
1
2
3
4
PhSeSePh
2
3a
3c
187.28 ( 7.53)
16.33 ( 1.30)d
244.27 ( 25.05)
48.75 ( 5.47)
1.0
11.5
0.8
3.8
a Values of T50 were corrected for the uncatalyzed background reaction.
b MeOH (1 mL); catalyst (0.05 mM); PhSH (5 mM); H2O2 (10 mM).
c T50 is the time required, in minutes, to reduce the thiol concentration
by 50% after the addition of H2O2. d Data in parentheses: experimental
error.
Indeed, this hypothesis was confirmed by performing a reac-
tion involving the ligand 3d in the presence of diethylzinc, under
the same conditions employed in our methodology (Scheme 2).
As expected, after completion of the experiment, it was poss-
ible to obtain the diselenide 2, which was derived from the oxi-
dation of active species. The compound 2 was purified and
compounds carrying chelating groups such as amines, amides or
alcohols near to selenium.18 According to this, we decided to
investigate the GPx like activity of the new ephedrine derivatives
2, 3a and 3c.
The GPx like activity of the synthesized compounds was
monitored according to the method reported by Iwaoka and
Tomoda.19 In this method, the reduction of hydrogen peroxide,
using PhSH as the thiol cofactor, is followed spectrophotometri-
cally due to the increase in the absorbance at 305 nm relative to
the formation of diphenyl disulfide (Fig. 1).
All tested compounds showed catalytic activity in this screen-
ing, promoting the oxidation of thiophenol as compared to the
control reaction in the absence of a catalyst. The time required
to reduce the concentration of the thiol to a half (T50) is depicted
in Table 4. For comparison purposes, diphenyl diselenide
(PhSeSePh), a well known GPx like mimic,18a was used as a
1
identified by nuclear magnetic resonance of H, 13C and 77Se.
The importance of formation of selenolate in the addition of
organometallic species to aldehydes explains the lack of activity
shown by the respective selenides 3a and 3b. These catalysts
cannot coordinate effectively with Zn due to the lower Lewis
basicity character of the Se atom compared to the diselenide
catalyst 2 or its precursor 3d.
From a biological point of view, the structural feature of our
designed compounds became attractive. Numerous reports have
described the positive influence in the GPx like activity of
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3 L. Flohe and W. A. Pryor, Free Radicals in Biology, Academic Press,
New York, 1982.
standard catalyst in our study and its activity was arbitrarily
ascribed as 1.0 (entry 1).
4 (a) H. Sies, Angew. Chem., Int. Ed., 1986, 25, 1058; (b) G. Mugesh and
H. B. Singh, Chem. Soc. Rev., 2000, 29, 347; (c) G. Mugesh and
W. W. Mont, Chem.–Eur. J., 2001, 7, 1365; (d) G. Mugesh, W. W. Mont
and H. Sies, Chem. Rev., 2001, 101, 2125; (e) C. Jacob, G. I. Giles,
N. M. Giles and H. Sies, Angew. Chem., Int. Ed., 2003, 42, 4742;
(f) C. W. Nogueira, G. Zeni and J. B. T. Rocha, Chem. Rev., 2004, 104,
6255; (g) E. E. Alberto, V. Nascimento and A. L. Braga, J. Braz. Chem.
Soc., 2010, 21, 2032; (h) K. P. Bhabak and G. Mugesh, Acc. Chem. Res.,
2010, 43, 1408; (i) E. E. Alberto, L. C. Soares, J. H. Sudati,
A. C. A. Borges, J. B. T. Rocha and A. L. Braga, Eur. J. Org. Chem.,
2009, 4211; ( j) D. J. Press and T. G. Back, Org. Lett., 2011, 13, 4104;
(k) K. Satheeshkumar and G. Mugesh, Chem.–Eur. J., 2011, 17, 4849;
(l) V. Nascimento, E. E. Alberto, W. D. Tondo, D. Dambrowski,
M. R. Detty, F. Nome and A. L. Braga, J. Am. Chem. Soc., 2012, 134,
138.
5 (a) G. P. Chen and D. M. Ziegler, Arch. Biochem. Biophys., 1994, 312,
566; (b) T. P. M. Akerboom, H. Sies and D. M. Ziegler, Arch. Biochem.
Biophys., 1995, 316, 220; (c) M. Iwaoka and S. Tomoda, Chem. Lett.,
2000, 1400; (d) M. Iwaoka, T. Takahashi and S. Tomoda, Heteroat.
Chem., 2001, 12, 293; (e) C. Jacob, G. I. Giles, N. M. Giles and H. Sies,
Angew. Chem., Int. Ed., 2003, 42, 4742; (f) V. Silva, M. M. Woznichak,
K. L. Burns, K. B. Grant and S. W. May, J. Am. Chem. Soc., 2004, 126,
2409; (g) N. Metanis, E. Keinan and P. E. Dawson, J. Am. Chem. Soc.,
2006, 128, 16684; (h) M. Iwaoka, F. Kumakura, M. Yoneda, T. Nakahara,
K. Henmi, H. Aonuma, H. Nakatani and S. Tomoda, J. Biochem., 2008,
144, 121; (i) K. B. Sharpless, K. M. Gordon, R. F. Lauer, D. W. Patrick,
S. P. Singer and M. W. Young, Chem. Scr., 1975, 8A, 9; ( j) H. J. Reich,
Acc. Chem. Res., 1979, 12, 22; (k) M. R. Detty, P. B. Merkel and
S. K. Powers, J. Am. Chem. Soc., 1988, 110, 5920; (l) M. R. Detty,
Organometallics, 1991, 10, 702.
6 For reviews, see: (a) T. Wirth, Tetrahedron, 1999, 55, 1; (b) T. Wirth,
Angew. Chem., Int. Ed., 2000, 39, 3741; (c) A. L. Braga, D. S. Lüdtke,
F. Vargas and R. C. Braga, Synlett, 2006, 1453; (d) A. L. Braga,
D. S. Lüdtke and F. Vargas, Curr. Org. Chem., 2006, 10, 1921;
(e) A. L. Braga, M. W. Paixão and M. Godoi, Dalton Trans., 2011, 40,
11347.
7 (a) R. Noyori, Asymmetric Catalysis in Organic Synthesis, John Wiley &
Sons, New York, 1994; (b) B. Goldfuss, Synthesis, 2005, 14, 2271.
8 For addition of boronic acids see: (a) S. D. Lüdtke, A. D. Wouters,
G. H. G. Trossini and H. A. Stefani, Eur. J. Org. Chem., 2010, 2351;
(b) A. L. Braga, M. W. Paixão, B. Westermann, P. H. Schneider and
A. W. Ludger, J. Org. Chem., 2007, 73, 2879; (c) W. Ping-Yu,
W. Hsyueh-Liang and U. Biing-Jiun, J. Org. Chem., 2005, 71, 833;
(d) C. Bolm, N. Hermanns, J. P. Hildebrand and K. Muñiz, Angew.
Chem., Int. Ed., 2000, 39, 3465; (e) C. Bolm and J. Rudolph, J. Am.
Chem. Soc., 2002, 124, 14850; (f) C. Bolm, N. Hermanns,
M. Kesselgruber, J. P. Hildebrando and G. Raabe, Angew. Chem., Int.
Ed., 2001, 40, 1488.
Not surprisingly, selenide 3a was the poorer catalyst in this set
of experiments (entry 3). The lower catalytic activity of this com-
pound, T50 of 244 min, is the result of the sluggish oxidation of
the selenide with H2O2. Conversely, a different scenario is
observed for catalysts 2 and 3c. Ephedrine derivative 3c with a
labile selenoester functionality allows the formation in situ of the
correspondent selenolate, which impacts substantially its activity.
Compared to the standard PhSeSePh, catalyst 3c showed cataly-
tic performance aproximately 4-fold higher. Moreover, disele-
nide 2 promoted the reduction of the concentration of PhSH to a
half in just 16.3 min (entry 2). The increased activity of this
compound, 11.5-fold higher than PhSeSePh, is attributed to the
beneficial interactions between selenium and the nitrogen moiety
in the course of the reaction.20
In summary, we have described in this paper the preparation
of new chiral selenium ligands derived from (−)-ephedrine in
only one step in good yields. The ephedrine-based diselenide
was revealed to be an important example of a synthesized pro-
miscuous catalyst, with activity as GPx mimics and the enantio-
selective addition of organozinc to aldehydes, acting as a redox
element or a metal ligand.
In a comparison study, diselenide 2 proved to be a much
better catalyst than the parent aminoalcohol ephedrine 1 for
enantioselective carbon–carbon bond formations. Our designed
catalysts were found to be convenient for use in the enantioselec-
tive aryl transfer addition of boronic acids to aldehydes, as well
as the addition of diethylzinc to aldehydes, allowing the pre-
paration of the desired chiral alcohols in good to excellent yields
and high enantiomeric excess.
The ephedrine-based diselenide was also efficiently used as a
GPx mimic, catalyzing the reduction of H2O2 to water at the
expense of thiophenol using as little as 1 mol%. This diselenide
significantly accelerated the reaction exhibiting a T50 of
16.33 min, while only a marginal accelerating effect was
observed for the already known GPx mimic, PhSeSePh, which
showed a T50 of 187.28 min. This opens a new perspective of
using this kind of compound in medicine, since it could act as a
redox element or a metal ligand with potential application as
mimics or inhibitors of enzymes.
9 For addition of diethylzinc see: (a) S. M. Cerero, B. L. Maroto and
T. C. Engel, Eur. J. Org. Chem., 2010, 1717; (b) A. R. Abreu,
M. M. Pereira and J. C. Bayón, Tetrahedron Lett., 2010, 66, 743;
(c) P. Salehi, M. Dabiri, G. Kozehgary and M. Baghbanzadeh, Tetra-
hedron: Asymmetry, 2009, 20, 2609; (d) J. A. Groeper, S. R. Hitchcock,
J. M. Standard and S. Banerjee, Tetrahedron: Asymmetry, 2009, 20, 2154;
(e) S. Lésniak, M. Rachwalski, E. Sznajder and P. Kielbasínski, Tetra-
hedron: Asymmetry, 2009, 20, 2311.
Acknowledgements
We are grateful to INCT-Catálise, CNPq, CAPES and FAPESC
10 (a) N. Sperber, D. Paga, E. Schwenk and M. Sherlock, J. Am. Chem.
Soc., 1949, 71, 887; (b) A. F. Harms and W. T. J. Nauta, Med. Pharm.
Chem., 1960, 2, 57; (c) K. Meguro, M. Aizawa, T. Sohda, Y. Kawamatsu
and A. Nagaoka, Chem. Pharm. Bull., 1985, 33, 3787; (d) F. Toda,
K. Tanaka and K. Koshiro, Tetrahedron: Asymmetry, 1991, 2, 873;
(e) S. Stanev, R. Rakovska, N. Berova and G. Snatzke, Tetrahedron:
Asymmetry, 1995, 6, 183; (f) M. Bota, V. Summa, F. Corelli, G. D. Pietro
and P. Lombardi, Tetrahedron: Asymmetry, 1996, 7, 1263; (g) E. J. Corey
and C. J. Heldal, Tetrahedron Lett., 1996, 37, 4837.
11 (a) A. L. Braga, H. R. Appelt, P. H. Schneider, C. C. Silveira and
L. A. Wessjohann, Tetrahedron: Asymmetry, 1999, 10, 1733;
(b) A. L. Braga, O. E. D. Rodrigues, M. W. Paixão, H. R. Appelt, C.
C. Silveira and D. P. Bottega, Synthesis, 2002, 2338; (c) T. Wirth and
C. Santi, Tetrahedron: Asymmetry, 1999, 10, 1019; (d) T. Wirth, Tetra-
hedron Lett., 1995, 36, 7849.
for financial support.
References
1 (a) C. Paulmier, Selenium Reagents and Intermediates in Organic Syn-
thesis, Pergamon Press, Oxford, 1986; (b) T. G. Back, Organoselenium
Chemistry. A Practical Approach, Oxford University Press, Oxford,
1999; (c) E. E. Alberto and A. L. Braga, Selenium and Tellurium Chem-
istry
– From Small Molecules to Biomolecules and Materials,
ed. W. J. Derek, L. Risto, Springer-Verlag, Berlin, 2011.
2 (a) H. Sies, Oxidative Stress: Introductory Remarks, Academic Press,
London, 1985; (b) H. Sies, Angew. Chem., Int. Ed., 1986, 25, 1058;
(c) T. C. Stadtman, J. Biol. Chem., 1991, 266, 16257; (d) F. Ursini and
R. Paoletti, Oxidative Processes and Antioxidants, Raven Press,
New York, 1994.
12 (a) C. M. Bolm, A. Kesselgruber, N. Grenz Hermmanns and
J. P. Hildebrand, New J. Chem., 2001, 25, 13; (b) R. S. Schwab,
6598 | Org. Biomol. Chem., 2012, 10, 6595–6599
This journal is © The Royal Society of Chemistry 2012

View Article Online
L. C. Soares, L. Dornelles, O. E. D. Rodrigues, M. W. Paixão, M. Godoi
and A. L. Braga, Eur. J. Org. Chem., 2010, 3574.
13 A. L. Braga, M. W. Paixão, D. S. Lüdtke, C. C. Silveria and
O. E. D. Rodrigues, Org. Lett., 2003, 5, 2635.
Y. Jiang, M. C. K. Choi and A. S. C. Chan, Tetrahedron: Asymmetry,
2002, 1, 809; (e) A. L. Braga, H. R. Appelt, P. H. Schneider,
C. C. Silveira and L. A. Wessjohann, Tetrahedron: Asymmetry, 1999, 10,
1733; (f) M. W. Paixão, M. Godoi, C. R. B. Rhoden, B. Wesstermann,
L. Wessjohann, D. S. Lüdtke and A. L. Braga, J. Mol. Catal.A: Chem.,
2007, 261, 120; (g) J. Myung-Jong, M. S. Shaheen, L. Dong-Hwan and
Q. Huili, Org. Lett., 2008, 10, 1235.
14 (a) A. L. Braga, H. R. Appelt, P. H. Schneider, C. C. Silveira and
L. A. Wessjohann, Tetrahedron: Asymmetry, 1999, 10, 1733;
(b) A. L. Braga, O. E. D. Rodrigues, M. W. Paixão, H. R. Appelt,
C. C. Silveira and D. P. Bottega, Synthesis, 2002, 2338; (c) T. Wirth and
C. Santi, Tetrahedron: Asymmetry, 1999, 10, 1019; (d) T. Wirth, Tetra-
hedron Lett., 1995, 36, 7849.
15 A. L. Braga, S. J. N. Silva, D. S. Lüdtke, R. L. Drekener, C. C. Silveira,
J. B. T. Rocha and L. A. Wessjohann, Tetrahedron Lett., 2002, 43, 7329.
16 (a) P. H. Scheneider, H. S. Schrekker, C. C. Silveira, L. A. Wessjohann
and A. L. Braga, Eur. J. Org. Chem., 2004, 2715; (b) A. L. Braga,
M. W. Paixão, P. Milani, C. C. Silveira, O. E. D. Rodrigues and
E. F. Alves, Synlett, 2004, 1297.
17 For some examples see: (a) S. C. A. Chan, P. Li and P. Tong, Tetra-
hedron: Asymmetry, 2001, 12, 2301; (b) J. Kang, J. W. Kim, J. W. Lee,
D. S. Kim and J. I. Kim, Bull. Korean Chem. Soc., 1996, 17, 1135;
(c) M.-J. Jin, S.-J. Ahn and K.-S. Lee, Tetrahedron: Asymmetry, 1996,
37, 8767; (d) L. Gong, A. Mi, H. Zhang, X. Li, G. Chem, X. Cui,
18 (a) S. R. Wilson, P. A. Zucker, R. R. C. Huang and A. Spector, J. Am.
Chem. Soc., 1989, 111, 5936; (b) V. Galet, J. L. Bernier, J. P. Hénichart,
D. Lesieur, C. Abadie, L. Rochette, A. Lindenbaum, J. Chalas,
J. F. R. Faverie, B. Pfeiffer and P. Renard, J. Med. Chem., 1994, 37,
2903; (c) G. Mugesh, A. Panda, H. B. Singh, N. S. Punekarb and
R. J. Butcher, Chem. Commun., 1998, 2227; (d) G. Mugesh, A. Panda,
H. B. Singh, N. S. Punekar and R. J. Butcher, J. Am. Chem. Soc.,
2001, 123, 839; (e) S. K. Tripathi, U. Patel, D. Roy, R. B. Sunoj,
H. B. Singh, G. Wolmershäuser and R. J. Butcher, J. Org. Chem.,
2005, 70, 9237.
19 M. Iwaoka and S. Tomoda, J. Am. Chem. Soc., 1994, 116, 2557.
20 For a recent review about selenium–heteroatom nonbonding interactions
see: A. J. Mukherjee, S. S. Zade, H. B. Singh and R. B. Sunoj, Chem.
Rev., 2010, 110, 4357.
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