Modular chiral selenium-containing oxazolines: Synthesis and application in the palladium-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1016/j.tet.2005.09.044

A new series of modular chiral selenium-containing oxazolines has been synthesized from inexpensive and commercially available l-serine and l-aspartic acid. These new compounds were evaluated as chiral ligands in the palladium-catalyzed asymmetric allylic

Full text of DOI:10.1016/j.tet.2005.09.044

Tetrahedron 61 (2005) 11664–11671
Modular chiral selenium-containing oxazolines: synthesis
and application in the palladium-catalyzed asymmetric
allylic alkylation
*
Antonio L. Braga, Diogo S. Lu¨dtke, Jasquer A. Sehnem and Eduardo E. Alberto
´
Departamento de Quımica, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
Received 23 July 2005; revised 13 September 2005; accepted 15 September 2005
Available online 3 October 2005
Abstract—A new series of modular chiral selenium-containing oxazolines has been synthesized from inexpensive and commercially
available L-serine and L-aspartic acid. These new compounds were evaluated as chiral ligands in the palladium-catalyzed asymmetric allylic
alkylation reaction, furnishing the product in high enantiomeric excess, using Cs2CO3/CH2Cl2 as the base/solvent system.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
backbone.7,8 Some of these ligands are shown in Figure 1
and all of them have been successfully employed in the
enantioselective allylation reaction.
The preparation of new and efficient enantiopure ligands
providing a chiral environment to metals for asymmetric
catalysis is currently one of the major challenges in
synthetic organic chemistry. Among the transition metal-
catalyzed reactions known to form carbon–carbon and
carbon-heteroatom bonds, the palladium-catalyzed allylic
substitution stands out as one of the most valuable synthetic
tools available.1 The development of effective chiral ligands
for this process has grown steadily over the past few years
since several new catalysts have been successfully
employed for asymmetric induction in this reaction.
Among the wide variety of catalysts designed, hetero-
bidentate ligands play an important role once they capitalize
upon the difference in electronic character of the two donor
atoms to exert a stereoelectronic bias upon intermediate
p-allyl complexes. Stereoelectronically, the palladium-allyl
terminus opposite to the more powerful acceptor atom will
be longer; hence, more susceptible to cleavage as a result of
nucleophilic attack.2
Figure 1. Oxazoline ligands for palladium-catalyzed allylic alkylations.
Mixed S,N-ligands have also been extensively studied in
palladium-catalyzed allylic substitutions. Various sulfur-
containing oxazolines were reported to act as chiral
catalysts in this reaction.9 Ferrocenyl-oxazolines incorpor-
ating a thioether moiety were applied to such a process as
well.10 A series of sulfur-imine mixed donors, derived from
amino acids has also been described to induct high degrees
of enantioselectivity in the allylation reaction.11 Our group
has recently published the synthesis of cysteine and
methionine-derived N,S-ligands and its application to
asymmetric allylations.12
In this context, chiral bidentate ligands, equipped with an
oxazoline framework and a soft donor heteroatom, have
been the subject of research of many groups. The pioneering
chiral phosphine-oxazolines developed by Pfaltz,3
Helmchen,4 and Williams5 are by far the most widely
studied6 and have served as inspiration for the design of
many other heterobidentate P,N ligands with an oxazoline
Keywords: Selenium; Catalyst; Oxazolines; Ligands.
*
Corresponding author. Tel.: C55 55 3220 8761; fax: C55 55 3220 8998;
e-mail: albraga@quimica.ufsm.br
On the other hand, chiral organoselenium compounds have
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.044

A. L. Braga et al. / Tetrahedron 61 (2005) 11664–11671
11665
attracted much attention of organic chemists over the last
decade, and are now a very important tool for stereo-
selective transformations.13 These compounds have found
use in the stereoselective ring opening of epoxides,14 anti-
stereoselectivity and Markownikoff regioselectivity in the
electrophilic selenenylation of alkenes.15 Most importantly,
chiral diselenides have been employed as useful ligands in
various asymmetric transformations such as asymmetric
hydrosilylation of acetophenone,16 enantioselective diethyl-
zinc addition to aldehydes,17,18 and 1,4 addition of Grignard
reagents to enones.19
Ligand 2a was obtained by esterification of both carboxyl
groups of aspartic acid, followed by acylation at nitrogen
with benzoyl chloride. The diester 6 was cleanly reduced to
the diol 723 which was treated, without further purification,
with TsCl in dichloromethane using triethylamine as base.
The ditosylated intermediate immediately cyclizes to the
entropically favored oxazoline 8.7c The organoselenium
functionalization took place again by nucleophilic displace-
ment of the tosylate leaving group by a phenyl selenide
anion generated by reduction of PhSeSePh with NaBH4 in a
3:1 mixture of THF and ethanol.
In the course of our current interest in chiral organoselenium
mediated asymmetric transformations,18,19 and as only few
examples of chiral ligands containing a selenium atom
coordinated to palladium have been described,20 we decided
to prepare a new class of chiral oxazoline ligands 1 and 2
(Fig. 2) with an organoselenium moiety as a soft donor,
starting from an easily available and inexpensive chiral
pool. These chiral selenium-containing oxazolines had their
efficiency examined as catalysts in the enantioselective
palladium-catalyzed allylic alkylation reaction.
Ligands 2b–h were prepared in a similar way as 2a by
nucleophilic displacement of tosylate leaving group with the
selenide anion generated by reaction of the corresponding
diorganoyl diselenide with NaBH4 in THF/EtOH. The
desired oxazolinyl selenides were obtained with yields
ranging from 77 to 97% (Scheme 2).
Figure 2. Selenium-containing oxazolines 1 and 2.
2. Results and discussion
Ligands 1 and 2 were synthesized starting from natural
amino acids L-serine and L-aspartic acid, respectively.
Oxazolinyl selenide 1 was prepared by the sequence
shown in Scheme 1. First, esterification of L-serine with
SOCl2/MeOH, followed by cyclization of the resulting ester
with ethyl chlorobenzimidate resulted in the corresponding
oxazolinyl ester 3 in 85% yield for the two steps.21 The ester
was further reduced to the alcohol 4, which was treated with
TsCl in dichloromethane affording the tosylate 5 in good
yield.22 Thus the desired oxazolinyl selenide was obtained
by nucleophilic displacement with PhSeSePh/NaBH4 in a
3:1 mixture of THF/ethanol as solvents.
Scheme 2. Synthesis of ligands 2a–h.
Structural variations at R2 positions were also introduced.
Thus, we prepared tosylates 10 and 11 in a similar way to 8,
and they were further submitted to substitution with
phenylselenolate anion to afford oxazolinyl selenide 2i
and 2j (Scheme 3).
Scheme 3. Synthesis of ligands 2i–j.
One of the major advantages of the strategy developed is its
modular construction and, thus, modifications in the
structure of the catalysts can be easily introduced. This
characteristic is important for the fine-tuning of the catalytic
activity and for a deeper understanding of the steric and
electronic effects in the reaction outcome (Fig. 3). More-
over, it is interesting to point out that, for the first time, an
organoselenium group is attached to a sp3 carbon in a ligand
designed for palladium-catalyzed allylic alkylations. This
structural feature is highly interesting, since it facilitates the
Scheme 1. Synthesis of ligand 1.

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A. L. Braga et al. / Tetrahedron 61 (2005) 11664–11671
with diminished yields. A plausible explanation for this
account is that the presence of the electron-withdrawing
group reduces the ability of the selenium to coordinate to
palladium, which would account for the lowering in the
yields of 9 (see entries 4 and 7). When catalyst 2d bearing an
electron-donating group was employed, an ee of 75% was
obtained (entry 5).
Figure 3. Modular construction of chiral selenium-containing oxazolines.
introduction of the selenium atom into the framework of the
molecule thus permiting a highly flexible strategy for steric
and electronic modifications at R1 position.
Steric effects seem to be crucial in our catalytic system. The
increase of the bulk around selenium causes a negative
effect in the enantioselectivity of the reaction. This can be
easily evidenced by a dramatic decrease in the ee by using
ligand 2g, which has an t-Bu substituent directly attached to
selenium (entry 6). A more pronounced effect can be seen
when the highly encumbered ligand 2e was employed. A
poor yield of 9 was achieved and interestingly the opposite
enantiomer was formed with a very low enantioselectivity
of only 6% (entry 6).
With this set of ligands in hand, we turned our attention to
investigate their potential in the palladium-catalyzed
asymmetric allylic alkylation.
We studied the alkylation reaction of racemic 1,3-diphenyl-
2-propenyl acetate with sodium dimethyl malonate, using
the chiral selenium-containing oxazolines 1 and 2 as chiral
ligands (10 mol%) in the presence of [Pd(h3-C3H5)Cl]2
(2.5 mol%) in THF as solvent. The results of these studies
are summarized in Table 1.
The influence of the sterics at the oxazoline ring was also
evaluated. When the phenyl group in 2a was replaced by
bulkier ones such as in the case of 2i and 2j, a decrease in the
ee was detected (entries 10 and 11). 2i gave an ee of 58%
and in the case of ligand 2j an essentially racemic product
was obtained (5% ee, entry 11).
Table 1.
All ligands furnished the alkylated product with the (R)
configuration as the major product, except for ligand 2e,
which furnished a slight excess of the opposite enantiomer.
The stereochemistry of 9 was assigned by comparison of the
sign of optical rotation with literature data.7b
#
Ligand
R1
R2
Yield
(%)a
ee
(%)b
1
2
3
4
5
6
7
8
1
—
Ph
—
Ph
Ph
Ph
Ph
Ph
Ph
Ph
71
99
93
85
81
67
83
91
89
68
63
23
85
79
63
75
6c
54
37
70
58
5
2a
2b
2c
2d
2e
2f
2g
2h
2i
CH2Ph
4-ClPh
4-MeOPh
2,4,6-Me3Ph
3-CF3Ph
t-Bu
Me
Ph
Ph
A plausible explanation for such a high difference in the
level of enantioselection showed between 1 and 2a can be
found in the difference of the bite angle of the chiral ligand.
It is known that as the length of the tether in bidentate
ligands is increased, the bite angle can be increased as
well.9b,24 This increase places the chiral environment of the
ligand closer to the allyl system and it may result in greater
asymmetric induction. So, as ligand 2a has a longer side
chain, it coordinates to palladium in a greater bite angle.
This behavior results in closer proximity of the oxazoline
moiety to the allyl unit and, hence, greater enantioselectivity
should be observed in comparison with ligand 1 (Fig. 4).
9
10
11
Ph
4-t-BuPh
t-Bu
2j
a Isolated yields.
b Determined by HPLC with a Daicel Chiralcel OD column, hexane/
isopropanol 99:1; 0.5 mL/min; 254 nm.
c The opposite enantiomer was obtained.
Ligand 1 furnished quite disappointing results, once the
alkylation product was obtained with poor enantio-
selectivity. On the other hand, ligands of type 2 performed
much more successfully.
Ligand 2a has proven to be more efficient than 1, giving the
alkylated product in 85% ee (Table 1, entry 2). We could
observe that the nature of the group attached to the selenium
atom plays an important role in the enantioselection event.
The catalyst 2b with a benzyl substituent at selenium was
tested, but no increase in the ee could be achieved (entry 3).
Since the best result was obtained using catalyst 2a, which
has R1ZPh, we attempted to test ligands with several
different substituents at the aromatic ring of the organo-
selenium moiety. Ligands with electron-withdrawing
groups like chlorine (2c) and trifluormethyl (2f) at the
selenium donor were also evaluated. Unfortunately, a
decrease in the enantioselectivity was observed together
Figure 4. Effect of the bite angle.
Attempts to study the loading of the catalyst used were also
performed. As depicted in the Figure 5, quantities of 15, 10,
5, and 2.5 mol% of chiral ligand 2a were employed in the
asymmetric allylic alkylation. The best results were
obtained by using 10 mol% of 2a and 2.5 mol% of the
palladium source. This amount corresponds to a 2:1 ratio of
ligand to palladium. Changing this ratio to 1:1, by lowering
the amount of 2a to 5 mol%, a decrease of the ee to 78% was
observed. Moreover, a dramatic decrease in the ee was
verified when 2.5 mol% of the ligand was used.

A. L. Braga et al. / Tetrahedron 61 (2005) 11664–11671
11667
ee was observed when toluene was used instead of
dichloromethane (compare entries 9 and 10).
In order to propose a plausible explanation of the
stereoselectivity observed, a schematic reaction pathway
is shown in Scheme 4.25
Figure 5. Variation in the amount of 2a in the presence of 2.5 mol% of
[Pd(h3-C3H5)Cl]2.
The results obtained with ligand 2a encouraged us to
continue our search to find out some improvements in the
reaction conditions using this catalyst. The results of these
studies are summarized in Table 2.
Table 2. Effect of the base/solvent system in the asymmetric allylic
alkylation
Entry
Base
Solvent
Time
(h)
Yield
(%)a
ee
(%)b
1c
2
BSA/KOAc CH2Cl2
BSA/KOAc CH2Cl2
BSA/KOAc CH2Cl2
BSA/KOAc CH3CN
BSA/KOAc Toluene
24
24
24
24
24
24
24
2
71
97
93
95
63
99
96
99
99
49
23
81
79
79
66
85
85
85
91
32
Scheme 4. Plausible reaction pathways for the asymmetric allylic
alkylation.
3d
4
Taking into analogy the previous work of Anderson where
he proposes that the attack of the nucleophile occurs trans to
a nitrogen donor,11b which is the contrary of that expected
for a nitrogen–sulfur chelate complex, we assumed that our
system behaves in a similar way, that is, the nucleophile
attacks preferentially at the allylic position trans to the Pd–N
bond in the p-allylpalladium complex.
5
6
NaH
NaH
THF
THF
7d
8
Cs2CO3
Cs2CO3
Cs2CO3
CH2Cl2
CH2Cl2
Toluene
9d
10
10
24
a Isolated yields.
b Determined by HPLC with a Daicel Chiralcel OD column, hexane/
isopropanol 99:1; 0.5 mL/min; 254 nm.
Since (R)-9 is the major product of the alkylation reaction of
racemic 1,3-diphenyl-2-propenyl acetate with dimethyl
malonate, the reaction appears to proceed preferentially
via the intermediate (A) in the equilibrium depicted in
Scheme 4.
c Reaction carried out using 1 as ligand.
d Reaction was carried out at 0 8C.
We examined the effect of another base/solvent system and
results are depicted in Table 2. Changing the base from NaH
to N,O-bis(trimethylsilyl)acetamide (BSA) and the solvent
from THF to dichloromethane, a decrease in the ee was
observed (entries 2 and 3). Another change to a more polar
solvent, acetonitrile, and to the apolar toluene, did not result
in any improvement (see entries 4 and 5). When using
acetonitrile the ee of the product did not change
significantly. With toluene, however, the enantioselectivity
decreased to 66% ee.
The steric repulsion in the intermediate (A) between a
phenyl terminus of the allylic substrate arranged in a ‘W’
orientation and the selenophenyl group seems to be smaller
than the repulsion of the phenyl ring attached to the
2-position of the oxazoline ring and the phenyl moiety in
structure (B), which is disposed in a ‘M’ orientation.
These disfavoring steric interactions, which are present in
intermediate (B) would lead to a predominance of the
intermediate (A) in the equilibrium and explain the
stereoselectivity observed in favor of (R)-9 (Scheme 4).
On the other hand, employing cesium carbonate as base and
performing the reaction in dichloromethane, the reaction
proceeded smoothly and the product was isolated in 85% of
enantiomeric excess and full conversion after only 2 h at
room temperature (entry 8). The use of these conditions
gave the same ee of product 9 when compared to the NaH/
THF system; however, the reaction goes to completion in
much reduced reaction time. On decreasing the temperature
to 0 8C, the reaction took 10 h to completion and, to our
delight the ee of 9 increased to 91% (entry 9). Again,
reducing the polarity of the solvent proved to negatively
influence the reaction outcome, since a dramatic drop in the
3. Conclusions
In summary, we have described herein a new class of chiral
selenium-containing oxazoline chiral ligands, which were
prepared in a concise and flexible synthetic route in good
yields. This flexibility permits the preparation of a wide
range of compounds with varied steric and electronic
combination of substituents. This feature confers to this

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A. L. Braga et al. / Tetrahedron 61 (2005) 11664–11671
class of compounds a modular character allowing the
synthesis of small libraries of new chiral selenium
compounds.
4.1.2. (S)-(2-phenyl-4,5-dihydrooxazol-4-yl)methyl
4-methylbenzenesulfonate 5.29 Under an argon atmos-
phere, TsCl (0.420 g, 2.2 mmol) was added in one portion,
at 0 8C, to a solution of alcohol 4 (0.354 g, 2 mmol) in
dichloromethane (5 mL) and Et3N (0.6 mL, 4 mmol) in the
presence of a catalytic amount of DMAP (25 mg, 10 mol%).
The mixture was then stirred for 24 h at room temperature
diluted with CH2Cl2 (30 mL) and washed with saturated
NaCl(aq) (20 mL). The organic layer was dried with MgSO4,
filtered and the solvent evaporated. The crude product was
purified by flash chromatography eluting with a mixture of
hexanes–ethyl acetate (80/20). Yield: 77%; [a]2D4 C56.6 (c
1.0, EtOH); 1H NMR (CDCl3, 400 MHz): dZ7.86–7.79 (m,
2H), 7.77–7.69 (m, 2H), 7.49–7.20 (m, 5H), 4.55–4.38 (m,
2H), 4.33–4.19 (m, 2H), 4.05–3.96 (m, 1H), 2.39 (s, 3H);
13C NMR (CDCl3, 100 MHz): dZ166.0, 145.0, 132.5,
131.8, 129.9, 128.4, 128.3, 128.0, 127.0, 70.8, 69.8, 65.1,
21.7.
Additionally, these compounds were systematically
screened as chiral ligands in the asymmetric palladium-
catalyzed allylic alkylation of racemic 1,3-diphenyl-2-
propenyl acetate with dimethyl malonate. We were able to
identify among the set of ligands prepared, a catalyst that
can effectively promote the allylic alkylation reaction in
high ee. This approach demonstrates the importance of the
easy access to modification in the structure of the chiral
ligand in order to readily identify an efficient ligand for a
given catalytic setup through a correct combination of
structural and electronic properties of the catalyst and
refinement of reaction conditions.
We also believe that this modular approach, which permits
ready access of a range of new chiral selenium compounds,
may have significant importance in the design of new Se,
N-ligand systems for application in asymmetric catalysis.
4.1.3. (S)-2-(2-phenyl-4,5-dihydrooxazol-4-yl)ethyl
4-methylbenzenesulfonate 8.7c Under an argon atmos-
phere, TsCl (2.88 g, 15 mmol) was added in one portion to a
solution of diol 7 (1.045 g, 5 mmol) in dichloromethane
(50 mL) and Et3N (4.2 mL, 30 mmol) at 0 8C. The mixture
was then stirred for 24 h and slowly warmed to 25 8C. The
reaction mixture was diluted with CH2Cl2 (50 mL) and
washed with 1 M HCl(aq) (20 mL), saturated NaHCO3(aq)
(20 mL) and saturated NaCl(aq) (20 mL). The organic layer
was dried with MgSO4, filtered, and concentrated. The
crude product was purified by flash chromatography eluting
with a mixture of hexanes–ethyl acetate (70/30). Yield:
75%; [a]2D4 K59 (c 2.0, CHCl3); 1H NMR (CDCl3,
400 MHz): dZ7.86 (d, JZ8.4 Hz, 2H), 7.79 (d, JZ
8.4 Hz, 2H), 7.46–7.30 (m, 5H), 4.48–4.44 (m, 1H), 4.35–
4.23 (m, 3H), 4.04–4.00 (m, 1H), 2.42 (s, 3H), 2.03–1.97
(m, 2H); 13C NMR (CDCl3, 100 MHz): dZ164.01, 144.75,
132.76, 131.37, 129.78, 128.29, 128.22, 128.15, 127.83,
72.28, 67.88, 63.34, 34.98, 21.54.
4. Experimental
4.1. General procedures
1
Melting Points are uncorrected. H and 13C NMR spectra
were recorded at 400 and 100 MHz, respectively, with
tetramethylsilane as internal standard. High-resolution mass
spectra were recorded on a Bruker BioApex 70e FT-ICR
(Bruker Daltonics, Billerica, USA) instrument in ESI-mode.
Column chromatography was performed using Merck Silica
Gel (230–400 mesh) following the methods described by
Still.26 Thin-layer chromatography (TLC) was performed
using Merck Silica Gel GF254, 0.25 mm thickness. For
visualization, TLC plates were either placed under
ultraviolet light, or stained with iodine vapor, or acidic
vanillin. THF was dried over sodium benzophenone ketyl
and distilled prior to use. Dichloromethane and acetonitrile
were distilled from phosphorus pentoxide. All other
solvents were used as purchased unless otherwise noted.
Racemic 1,3-diphenyl-3-acetoxyprop-1-ene was prepared
according to literature procedure.27 Compounds 3,21 6 and
77c were prepared by the procedures described in the cited
references.
4.1.4. (S)-2-(2-tert-butyl-phenyl-4,5-dihydrooxazol-4-yl)
ethyl 4-methylbenzenesulfonate 10. This compound was
prepared in the same method used for 8, starting from (S)-2-
tert-butyl-benzoylamino-1,4-butanediol (0.795 g, 3 mmol).
1
Yield 55%; [a]D20 K56 (c 0.6, CH2Cl2); H NMR (CDCl3,
400 MHz): dZ7.80 (d, JZ8.4 Hz, 4H), 7.40 (d, JZ8.4 Hz,
2H), 7.31 (d, JZ8.4 Hz, 2H), 4.47–4.42 (m, 1H), 4.33–4.23
(m, 3H), 4.03–3.99 (m, 1H), 2.42 (s, 3H), 2.01–1.96 (m,
2H), 1.30 (s, 9H); 13C NMR (CDCl3, 100 MHz): dZ164.11,
154.91, 144.67, 133.02, 129.78, 128.05, 127.85, 125.19,
124.60, 72.22, 67.91, 63.36, 35.07, 34.87, 31.08, 21.52;
HRMS m/z calcd for C22H27O4NSCHC402.1729, found
402.1733.
4.1.1. (R)-(2-phenyl-4,5-dihydrooxazol-4-yl)methanol
4.28 Under an argon atmosphere, sodium borohydride
(0.760 g, 20 mmol) was added, at 0 8C, to a solution of
oxazolinyl ester 3 (1.025 g, 5 mmol) in dry ethanol (20 mL).
The reaction was then stirred for 12 h under reflux and after
this time, cooled to room temperature, diluted with CH2Cl2
(30 mL) and washed with saturated NaCl(aq) (20 mL). The
organic layer was dried with MgSO4, filtered and the solvent
removed under vacuum. Alcohol 4 was used without further
4.1.5. (S)-2-(2-tert-butyl-4,5-dihydrooxazol-4-yl)ethyl
4-methylbenzenesulfonate 11.30 This compound was
prepared in the same method used for 8, starting from (S)-
2-trimethyl-acetylamino-1,4-butanediol (0.567 g, 3 mmol).
purification. Yield 87%; [a]2D0 C35 (c 0.42, CHCl3); H
1
NMR (CDCl3, 400 MHz): dZ7.81–7.79 (m, 2H), 7.43–7.26
(m, 3H), 4.44–4.30 (m, 3H), 3.93 (dd, J1Z11.6 Hz, J2Z
4.0 Hz, 1H), 3.63 (dd, J1Z11.6 Hz, J2Z4 Hz, 1H), 2.89 (s,
1H); 13C NMR (CDCl3, 100 MHz): dZ165.45, 131.38,
128.24, 128.14, 126.95, 69.17, 68.00, 63.60; HRMS m/z
calcd for C10H11O2NC NaC200.0682, found 200.0683.
1
Yield 62%; [a]D20 K54 (c 0.6, CH2Cl2); H NMR (CDCl3,
400 MHz): dZ7.78 (d, JZ8.4 Hz, 2H), 7.34 (d, JZ8.4 Hz,
2H), 4.26–4.07 (m, 4H), 3.85–3.81 (m, 1H), 2.44 (s, 3H),
1.89–1.86 (m, 2H), 1.16 (s, 9H); 13C NMR (CDCl3,
100 MHz): dZ174.32, 144.62, 132.44, 129.75, 128.74,

A. L. Braga et al. / Tetrahedron 61 (2005) 11664–11671
11669
1
71.94, 67.72, 62.69, 34.89, 32.93, 27.17, 21.39; HRMS m/z
calcd for C16H24O4NSCHC326.1416, found 326.1420.
CH2Cl2); H NMR (CDCl3, 400 MHz): dZ7.92 (d, JZ
7.2 Hz, 2H), 7.49–7.39 (m, 5H), 6.81 (d, JZ8.8 Hz, 2H),
4.47–4.35 (m, 2H), 4.00–3.96 (m, 1H), 3.78 (s, 3H), 3.02–
2.91 (m, 2H), 2.07–1.99 (m, 1H), 1.96–1.89 (m, 1H); 13C
NMR (CDCl3, 100 MHz): dZ163.60, 159.21, 135.47,
131.19, 128.17, 128.13, 127.64, 119.60, 114.71, 72.09,
66.44, 55.12, 36.47, 25.10; HRMS m/z calcd for C18H19O2-
NSeCHC362.0648, found 362.0653.
4.2. General procedure for the synthesis of ligands 1
and 2
Under an argon atmosphere, sodium borohydride was added
to a solution of the diorganoil diselenide (0.55 mmol) in
THF (4 mL). Ethanol (2 mL) was then dropwise added and
the clear solution formed was stirred at room temperature
for 10 min. After this time a THF (1 mL) solution of the
appropriate oxazolinyl tosylate (1 mmol) was added
dropwise. After stirring for 24 h at room temperature, the
reaction mixture was quenched with aqueous saturated
NH4Cl (10 mL) and extracted with CH2Cl2 (3!15 mL).
The combined organic layers were dried with MgSO4,
filtered, and concentrated. The crude product was purified
by flash chromatography first eluting with hexanes and then
with a mixture of hexanes–ethyl acetate (80/20).
4.2.6. (S)-4-(2-(mesitylselanyl)ethyl)-2-phenyl-4,5-di-
hydrooxazole 2e. Yield: 88%; [a]2D0 K35 (c 0.5, CH2Cl2);
1H NMR (CDCl3, 400 MHz): dZ7.91 (d, JZ8.0 Hz, 2H),
7.47–7.36 (m, 3H), 6.91 (s, 2H), 4.46–4.44 (m, 1H), 4.36–
4.32 (m, 1H), 3.99–3.95 (m, 1H), 2.82–2.77 (m, 2H), 2.53
(s, 6H), 2.25 (s, 3H), 1.98–1.86 (s, 1H), 1.84–1.83 (m, 1H);
13C NMR (CDCl3, 100 MHz): dZ163.54, 142.95, 137.91,
131.15, 128.40, 128.37, 128.34, 127.65, 127.31, 72.04,
66.69, 36.65, 24.42, 24.62, 20.80; HRMS m/z calcd for
C20H23ONSeCHC374.1011, found 374.1017.
4.2.1. (S)-2-phenyl-4-(phenylselanylmethyl)-4,5-di-
hydrooxazole 1. Yield: 91%; [a]2D0 K15 (c 0.5, CH2Cl2);
1H NMR (CDCl3, 400 MHz): dZ7.90 (d, JZ7.2 Hz, 2H),
7.56–7.53 (m, 8H), 4.53–4.46 (m, 2H), 4.25–4.22 (m, 1H),
3.42–3.38 (m, 1H), 2.95–2.89 (m, 1H); 13C NMR (CDCl3,
100 MHz): dZ164.66, 133.02, 131.47, 129.15, 128.29,
128.29, 128.27, 127.48, 127.28, 72.53, 66.58, 32.73; HRMS
m/z calcd for C16H15ONSeCHC318.0392, found 318.0391.
4.2.7. (S)-2-phenyl-4-(2-(3-(trifluoromethyl)phenyl-
selanyl)-ethyl)-4,5-dihydrooxazole 2f. Yield: 80%; [a]D20
K59 (c 0.5, CH2Cl2); 1H NMR (CDCl3, 400 MHz): dZ7.93
(d, JZ7.2 Hz, 2H), 7.74 (s, 1H), 7.46 (d, JZ7.2 Hz, 1H),
7.42–7.35 (m, 5H), 4.51–4.49 (m, 1H), 4.47–4.41 (m, 1H),
4.03–4.00 (m, 1H), 3.19–3.16 (m, 1H), 3.13–3.11 (m, 1H),
2.05–1.99 (m, 2H); 13C NMR (CDCl3, 100 MHz): dZ
163.89, 135.17, 131.59, 131.34, 131.32 (q, JZ32.1 Hz),
129.26, 128.55, 128.51, 128.26, 128.22, 127.58, 123.43 (q,
JZ3.8 Hz), 72.11, 66.36, 36.37, 23.92; HRMS m/z calcd for
C18H16ONSeCHC400.0442, found 400.0421.
4.2.2. (S)-2-phenyl-4-(2-(phenylselanyl)ethyl)-4,5-di-
hydrooxazole 2a. Yield: 97%; [a]2D0 K57 (c 0.55,
1
CH2Cl2); H NMR (CDCl3, 400 MHz): dZ7.93 (d, JZ
7.16 Hz, 2H), 7.52–7.37 (m, 5H), 7.26–7.20 (m, 3H), 4.48–
4.37 (m, 2H), 4.02–3.98 (m, 1H), 3.14–2.99 (m, 2H), 2.10–
2.01 (m, 1H), 2.00–1.94 (m, 1H); 13C NMR (CDCl3,
100 MHz): dZ165.88, 132.48, 131.24, 130.04, 129.14,
128.21, 128.17, 127.99, 126.74, 72.12, 66.46, 36.45, 24.04;
HRMS m/z calcd for C17H17ONSeC NaC354.0366, found
354.0367.
4.2.8. (S)-4-(2-(tert-butylselanyl)ethyl)-2-phenyl-4,5-
dihydrooxazole 2g. Yield: 77%; [a]2D0 K75 (c 0.5,
CH2Cl2); H NMR (CDCl3, 400 MHz): dZ7.94 (d, JZ
7.12 Hz, 2H), 7.47–7.38 (m, 3H), 4.53–4.49 (m, 1H), 4.39–
4.36 (m, 1H), 4.07–4.03 (m, 1H), 2.79–2.71 (m, 2H), 2.08–
2.04 (m, 1H), 1.97–1.94 (m, 1H), 1.46 (s, 9H); 13C NMR
(CDCl3, 100 MHz): dZ163.63, 131.19, 128.20, 128.19,
127.74, 72.25, 66.95, 38.86, 37.09, 32.46, 17.91; HRMS m/z
calcd for C15H21ONSeC NaC334.0672, found 334.0680.
1
4.2.3. (S)-4-(2-(benzylselanyl)ethyl)-2-phenyl-4,5-di-
hydrooxazole 2b. Yield: 87%; [a]2D0 K58 (c 0.5,
1
CH2Cl2); H NMR (CDCl3, 400 MHz): dZ7.93 (d, JZ
4.2.9. (S)-4-(2-(methylselanyl)ethyl)-2-phenyl-4,5-di-
hydrooxazole 2h. Yield: 79%; [a]2D0 K82 (c 0.55,
7.2 Hz, 2H), 7.45–7.36 (m, 3H), 7.29–7.17 (m, 5H), 4.42–
4.38 (m, 1H), 4.33–4.29 (m, 1H), 3.96–3.92 (m, 1H), 3.78
(s, 2H), 2.62–2.59 (m, 2H), 2.04–1.95 (m, 1H), 1.90–1.81
(m, 1H); 13C NMR (CDCl3, 100 MHz): dZ163.33, 139.07,
131.02, 128.59, 128.19, 128.01, 127.91, 127.50, 126.39,
71.87, 66.30, 36.38, 26.79, 19.56; HRMS m/z calcd for
C18H19ONSeCNaC368.0563, found 368.0526.
1
CH2Cl2); H NMR (CDCl3, 400 MHz): dZ7.94 (d, JZ
7.2 Hz, 2H), 7.47–7.38 (m, 3H), 4.53–4.49 (m, 1H), 4.42–
4.38 (m, 1H), 4.07–4.03 (m, 1H), 2.72–2.67 (m, 2H), 2.07–
1.95 (m, 5H); 13C NMR (CDCl3, 100 MHz): dZ163.68,
131.24, 128.22, 128.18, 127.69, 72.18, 66.52, 36.42, 21.20,
4.05; HRMS m/z calcd for C12H15ONSeCHC270.0386,
found 270.0397.
4.2.4. (S)-4-(2-(4-chlorophenylselanyl)ethyl)-2-phenyl-4,
5-dihydrooxazole 2c. Yield: 90%; [a]2D0 K48 (c 0.55,
CH2Cl2); 1HNMR(CDCl3, 400 MHz):dZ7.93(d,JZ7.2 Hz,
2H), 7.47–7.40 (m, 5H), 7.22 (d, JZ8.4 Hz, 2H), 4.50–4.45
(m, 1H), 4.40–3.37 (m, 1H), 4.02–3.98 (m, 1H), 3.11–3.01 (m,
2H), 2.05–1.95 (m, 2H); 13C NMR (CDCl3, 100 MHz): dZ
163.73, 133.76, 132.93, 131.27, 129.11, 128.23, 128.21,
128.15, 127.56, 72.06, 66.36, 36.36, 24.08; HRMS m/z calcd
for C17H16ONSeClCHC366.0154, found 366.0163.
4.2.10. (S)-2-(4-tert-butylphenyl)-4-(2-(phenylselanyl)
ethyl)-4,5-dihydrooxazole 2i. Yield: 93%; [a]2D0 K51 (c
0.55, CH2Cl2); H NMR (CDCl3, 400 MHz): dZ7.85 (d,
1
JZ8.4 Hz, 2H), 7.50 (d, JZ7.2 Hz, 2H), 7.41 (d, JZ
8.4 Hz, 2H), 7.26–7.23 (m, 3H), 4.47–4.39 (m, 2H), 4.01–
3.98 (m, 1H), 3.10–3.01 (m, 2H), 2.06–2.04 (m, 1H), 1.98–
1.96 (m, 1H), 1.32 (s, 9H); 13C NMR (CDCl3, 100 MHz):
dZ163.69, 154.68, 132.42, 130.08, 128.98, 127.98, 126.71,
125.17, 124.81, 71.97, 66.42, 36.48, 34.83, 31.08, 23.68;
HRMS m/z calcd for C21H25ONSeCHC388.1168, found
388.1179.
4.2.5. (S)-4-(2-(4-methoxyphenylselanyl)ethyl)-2-phenyl-
4,5-dihydrooxazole 2d. Yield: 91%; [a]2D0 K48 (c 0.55,

11670
A. L. Braga et al. / Tetrahedron 61 (2005) 11664–11671
4.2.11. (S)-2-tert-butyl-4-(2-(phenylselanyl)ethyl)-4,5-
dihydrooxazole 2j. Yield: 90%; [a]2D0 K26 (c 0.55,
CH2Cl2); H NMR (CDCl3, 400 MHz): dZ7.48 (d, JZ
References and notes
1
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7.6 Hz, 2H), 7.27–7.21 (m, 3H), 4.26–4.21 (m, 1H), 4.16–
4.13 (m, 1H), 3.84–3.80 (m, 1H), 3.01–2.97 (m, 1H), 2.95–
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4.3. General procedure for the asymmetric allylic
alkylation with NaH/THF
A THF (1 mL) solution of [Pd(h3-C3H5)Cl]2 (10 mg,
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Acknowledgements
The authors gratefully acknowledge CAPES, CNPq and
FAPERGS for financial support. CAPES is also acknowl-
edged for providing a PhD fellowship to D. S. L.
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