Modular chiral β-selenium-, sulfur-, and tellurium amides: synthesis and application in the palladium-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1016/j.tet.2007.10.086

A series of modular chiral β-chalcogen amides have been efficiently synthesized from inexpensive and easily available 2-oxazolines. All the selenium, sulfur, and tellurium compounds were evaluated as chiral ligands in the palladium-catalyzed asymmetric al

Full text of DOI:10.1016/j.tet.2007.10.086

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 392e398
www.elsevier.com/locate/tet
Modular chiral b-selenium-, sulfur-, and tellurium amides: synthesis and
application in the palladium-catalyzed asymmetric allylic alkylation
*
Fabrıcio Vargas , Jasquer A. Sehnem, Fabio Z. Galetto, Antonio L. Braga
*
´
Departamento de Qu´ımica, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
Received 20 July 2007; received in revised form 13 October 2007; accepted 23 October 2007
Available online 25 October 2007
Abstract
A series of modular chiral b-chalcogen amides have been efficiently synthesized from inexpensive and easily available 2-oxazolines. All the
selenium, sulfur, and tellurium compounds were evaluated as chiral ligands in the palladium-catalyzed asymmetric allylic alkylation. The
corresponding alkylated products were obtained in excellent enantiomeric excess, using BSA/CH2Cl2 as the base/solvent system.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Selenium; Sulfur; Tellurium; Chiral catalyst; Palladium; Asymmetric allylic alkylation
1. Introduction
Many chiral organochalcogenides have also demonstrated
their utility in this process.8
The search for new and properly designed chiral ligands in
asymmetric catalysis is currently one of the major challenges
in synthetic organic chemistry.1 Thus, a practical, modular,
and concise strategy should be applied to facilitate the prepa-
ration of a wide range of enantiopure ligands from easily avail-
able starting materials.
Chiral nitrogen compounds bearing an organochalcogen
moiety and their metal complexes have been frequently em-
ployed as effective catalysts in various enantioselective trans-
formations.2 For instance, selenium- and sulfur-containing
chiral ligands have been reported as efficient catalysts in sev-
eral different enantioselective reactions, such as the enantiose-
lective diethylzinc3 and alkynylzinc4 addition to aldehydes,
and conjugate addition to enones.5
Following our interest in the preparation and application of
chiral organochalcogen compounds in asymmetric transforma-
tions, we report in this full account the behavior of a modular
series of selenium-, sulfur-, and tellurium-chalcogen amides
starting from chiral 2-oxazolines, as depicted in the retrosyn-
thetic analysis (Fig. 1). All the b-organochalcogen amides
had their efficiency examined as chiral ligands in the enantio-
selective palladium-catalyzed asymmetric allylic alkylation
reaction.
2. Results and discussion
The modular chiral b-chalcogen amides were rapidly syn-
thesized starting from 2-oxazolines as inexpensive and easily
Among the transition metal-catalyzed reactions, the palla-
dium-catalyzed allylic alkylation is a versatile, widely used
process in organic synthesis for the enantioselective formation
of carbonecarbon and carboneheteroatom bonds.6 Moreover,
it is an interesting process in the synthesis of optically active
small molecules and in the total synthesis of natural products.7
R1
R1
O
R2Y
R2Y
HN
Ph
+
O
N
Ph
-chalcogen amide
ligands
* Corresponding authors. Tel.: þ55 55 3220 8761; fax: þ55 55 3220 8998.
E-mail address: albraga@quimica.ufsm.br (A.L. Braga).
Figure 1. Retrosynthetic analysis of the chiral b-chalcogen amides.
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.086

F. Vargas et al. / Tetrahedron 64 (2008) 392e398
393
accessible chiral pool starting materials. According to our pre-
vious communication,9 the respective reaction proceeds
through the formation of an oxazolinium intermediate,10 and
the regio- and chemoselective nucleophilic attack of the chal-
cogenide at the C(5) position of the chiral 2-oxazoline leads to
the C(5)eO(1) bond cleavage, furnishing the corresponding
chiral b-chalcogen amide without any racemization, as deter-
mined by chiral HPLC.11 Thus, the most efficient ring-opening
process was achieved when the chalcogenide was generated in
situ in the presence of NaBH4 as reducting agent, THF/EtOH
(3:1) as the solvent and 1 equiv of freshly distilled TMSCl as
a Lewis acid. The first study of the scope and limitations of the
ring-opening reaction was conducted in the presence of sele-
nium nucleophiles using the chiral 2-phenyl oxazoline 1a
(R1¼i-Pr) as model starting material (Table 1).
ethers, and ester moieties were prepared in excellent yields
according to this convenient method (Table 1, entries 9e13).
Based on the successful approach developed in the prepara-
tion of a wide range of chiral b-selenium amides by ring-open-
ing reaction we decided to extend our studies in order to
prepare a series of chiral organochalcogenide compounds us-
ing sulfur and tellurium nucleophilic species. Thus, different
b-thio and b-tellurium amides were obtained in a similar
way, as depicted in Table 2.
The corresponding chiral b-thio amides 3aee were ob-
tained with yields ranging from 68 to 83% (Table 2, entries
1e5). As observed with selenium nucleophiles, the ring-open-
ing reaction also tolerates the presence of different R1 groups
at the oxazoline ring (Table 2, entries 1e3) as well as substit-
uents attached at the aromatic ring of the organosulfur moiety
(Table 2, entries 4 and 5). The present reaction was also eval-
uated in the presence of a phenyltellurolate, furnishing the de-
sired chiral b-telluro amide 4 in 52% yield (Table 2, entry 6).
With the chiral compounds 2, 3, and 4 in hand, we turned
our attention to an investigation of their potential as ligands
in the palladium-catalyzed asymmetric allylic alkylation. We
then decided to evaluate the behavior of the catalysts under
conditions previously developed by us9 for the chiral b-seleno
amide 2a. Thus, the catalytic asymmetric reaction, using stan-
dard substrates, was performed using the chiral b-chalcogen
amide (5 mol %) and [Pd(h3-C3H5)Cl]2 (2.5 mol %) in the
presence of CH2Cl2 and BSA/KOAc as a solvent/base system,
as summarized in Table 3.
As shown in Table 1, the chiral organoselenium compounds
2aeh were synthesized in good to excellent yields (Table 1,
entries 1e8), except for dibutyl diselenide, which furnished
the corresponding product 2d in lower yield (Table 1, entry
4). The ring-opening reaction permits a series of different R1
groups attached to the oxazoline ring, as the respective prod-
ucts were obtained in up to 93% yield (Table 1, entries
1e3). The present method also tolerates organodiselenides
bearing hindered substituents (R2¼2,4,6-Me3Ph) as well as
electron-withdrawing (R2¼p-ClPh) and electron-donating groups
(R2¼p-MeOPh), furnishing the corresponding chiral organo-
selenides in excellent yields (Table 1, entries 6e8). Moreover,
different chiral b-seleno amides containing sulfides, alcohols,
We observe that the ligands 2aeh afforded the alkylated
product (R)-7a in similar chemical yield and in up to 98%
ee (Table 3, entries 1e8). The catalytic process tolerates dif-
ferent alkyl (R2¼Bu and Bn) and aryl groups (R2¼2,4,6-
Me3Ph, p-ClPh, and p-MeOPh) attached at the selenium
atom, showing that variations in the steric and electronic prop-
erties do not reduce the ability of the selenium coordinate to
the palladium atom. However, ligands 2iem bearing different
functional groups had a negative effect in the asymmetric re-
action, furnishing the respective racemic alkylated products
in very low yields (Table 3, entries 9e13).
Table 1
Preparation of chiral b-seleno amides by ring-opening reaction of 2-oxazolines
R1
R1
R2Se
O
N
NHBz
2a-i
Ph
1a-d
TMSCl, THF, 30 min.
R2SeSeR2/NaBH4, THF/EtOH (3:1)
reflux, 24 h
R1
R1
R2Se
N
O
NHBz
2j-m
Ph
1e-h
Table 2
Preparation of chiral b-thio and b-telluro amides by ring-opening reaction of
2-oxazolines
Entry
Oxazoline
R1
R2
2, Yielda,b (%)
R1
R1
TMSCl, THF
1
1a
1b
1c
1a
1a
1a
1a
1a
1d
1e
1f
i-Pr
i-Bu
Ph
Ph
2a, 93
2b, 82
2c, 84
2d, 27
2e, 71
2f, 79
2g, 82
2h, 84
2i, 72
2j, 90
2k, 78
2l, 87
2m, 51
R2Y
30 min.
2
O
N
NHBz
R2YYR2/NaBH4
THF/EtOH (3:1)
reflux, 24 h
3
Bn
i-Pr
Ph
Bu
Ph
1a-c
3a-e, 4
4
5
i-Pr
i-Pr
Bn
2,4,6-Me3Ph
6
Entry
Oxazoline
R1
R2
Y
Product, yielda,b (%)
7
i-Pr
i-Pr
p-ClPh
p-MeOPh
Ph
8
1
2
3
4
5
6
a
1a
1b
1c
1a
1a
1a
i-Pr
i-Bu
Bn
Ph
Ph
S
3a, 83
3b, 74
3c, 70
3d, 68
3e, 76
4, 52
9
(CH2)2SMe
CH2OH
CH2OBn
CH2OEt
CO2Me
S
10
11
12
13
a
Ph
Ph
Ph
S
i-Pr
i-Pr
i-Pr
o-ClPh
p-MeOPh
Ph
S
1g
1h
Ph
Ph
S
Te
Isolated yield of the corresponding product.
TMSCl was freshly distilled.
Isolated yield of the corresponding product.
TMSCl was freshly distilled.
b
b

394
F. Vargas et al. / Tetrahedron 64 (2008) 392e398
Table 3
Palladium-catalyzed asymmetric allylic alkylation with 2jem
O
O
2.5 mol% [Pd(η3-C3H5)Cl]2
OAc
5 mol% ligand
MeO
Ph
OMe
MeO2C
CO2Me
R1
+
BSA/KOAc
CH2Cl2, 24 h, r.t.
Ph
Ph
Ph
5a
6a
(R)-7a
R1
R2Se
R2Se
HN
Ph
HN
Ph
2a-i
2j-m
O
O
Entry
Ligand
R1
R2
Yielda (%)
eeb (%)
1
2a
2b
2c
2d
2e
2f
i-Pr
i-Bu
Bn
Ph
Ph
97
95
90
96
94
89
96
96
12
15
13
12
08
98
89
88
97
96
91
95
96
d
d
d
d
d
2
3
Ph
Bu
4
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
5
Bn
2,4,6-Me3Ph
6
7
2g
2h
2i
p-ClPh
p-MeOPh
Ph
8
9
(CH2)2SMe
CH2OH
10
11
12
13
a
2j
Ph
Ph
2k
2l
CH2OBn
CH2OEt
CO2Me
Ph
Ph
2m
Isolated yields.
Determined by HPLC with a Daicel Chiralcel OD column, hexane/isopropanol 99:1; 0.5 mL/min; 254 nm.
b
The chiral organosulfur catalysts 3aee and the organotellu-
4, entry 1) . As noted with the respective selenium-containing
analogues, the asymmetric reaction in the presence of the chi-
ral sulfur catalysts also tolerates diverse alkyl groups (R1¼
i-Pr, i-Bu, Bn) as well as aryl groups (R2¼o-ClPh, p-MeOPh)
attached to the sulfur moiety.
The chiral b-tellurium amide 4 was also evaluated in our
catalytic system under the optimal conditions. Thus, the de-
sired product was obtained in 39% yield and 59% ee (Table
4, entry 6). Despite the moderate yield obtained for the
rium 4 compounds were also evaluated in the present catalytic
reaction under the same reaction conditions, as depicted in
Table 4. This study allowed us to make a direct comparison
of the ability of selenium, sulfur, and tellurium to complex
with palladium and to catalyze the asymmetric alkylation
reaction.
The sulfur-derived catalysts 3aee delivered the alkylated
products in good to excellent yields and in up to 86% ee (Table
Table 4
Palladium-catalyzed asymmetric allylic alkylation with 3aee and 4
O
O
2.5 mol% [Pd(η3-C3H5)Cl]2
OAc
Ph
MeO
Ph
OMe
5 mol% ligand
MeO2C
CO2Me
+
Ph
BSA, KOAc
CH2Cl2, 24 h, r.t.
Ph
5a
6a
(R)-7a
R1
R2Y
HN
Ph
3a-e
O
Entry
Ligand
R1
R2
Y
Yielda (%)
eeb (%)
1
2
3
4
5
6
a
3a
3b
3c
3d
3e
4
i-Pr
i-Bu
Bn
Ph
Ph
Ph
S
94
79
77
79
84
39
86
83
72
74
80
59
S
S
i-Pr
i-Pr
i-Pr
o-ClPh
p-MeOPh
Ph
S
S
Te
Isolated yields.
Determined by HPLC with a Daicel Chiralcel OD column, hexane/isopropanol 99:1; 0.5 mL/min; 254 nm.
b

F. Vargas et al. / Tetrahedron 64 (2008) 392e398
395
Table 5
Palladium-catalyzed asymmetric allylic alkylation with 2a and 3a
Ph
Ph
Se
Se
Ph
Nu
Pd
Ph
Pd
2.5 mol%
N
N
R4
*
[Pd(η3-C3H5)Cl]2
Ph
R3O2C
CO2R3
R3O2C
CO2R3
Ph
O
OAc
O
Ph
5 mol% ligand 2a or 3a
Ph
Ph
+
R4
6a-d
Ph
Ph
BSA/KOAc
CH2Cl2, 24 h, r.t.
Ph
Nu
(A)
(B)
5a
7a-d
O
O
O
O
6a : R3 = Me, R4 = H 6b : R3 = Et, R4 = H
6c : R3 = Et, R4 = Et 6d : R3 = Et, R4 = Ph
PhY
MeO
OMe
MeO
Ph
OMe
NHBz
Y = Se, S
Ph
Ph
Ph
(R)-7a
major product
(S)-7a
Entry
Y
Malonate
Yielda (%)
eeb,c (%)
1
2
3
4
5
6
7
8
a
Se
S
6a
6a
6b
6b
6c
6c
6d
6d
97
94
95
89
83
61
89
68
98
86
93
84
69
48
82
66
Scheme 1. Plausible reaction pathways for the palladium-catalyzed asymmet-
ric allylic alkylation.
Se
S
Attack of the nucleophile on the p-allylpalladium complex
is believed to take place trans to the better p-acceptor. Thus,
we propose that the attack of the nucleophile occurs trans to
a selenium donor in a nitrogeneselenium chelate complex,
i.e., the nucleophile attacks preferentially at the allylic posi-
tion trans to the PdeSe bond in the p-allylpalladium complex.
Because the major product obtained is (R)-7, the reaction
appears to proceed preferentially via the intermediate (A) in
the equilibrium depicted in Scheme 1. Intermediate (A), where
the allyl group is disposed in a ‘W’ orientation, seems to be
more stable than intermediate (B), where the allyl moiety is
arranged in a ‘M’ conformation. We believed that the major
interaction that accounts for the difference in the stability of
both intermediates would be the steric repulsion between the
phenyl terminus of the allylic substrate and the phenyl group
attached to the amide, in intermediate (B). This unfavorable
interaction would explain the predominance of intermediate
(A) in the equilibrium and the stereoselectivity observed in
favor of (R)-7 (Scheme 1).
Taking into consideration the probable influence of the
group attached at the amide group in the formation of the in-
termediates (A) and (B), we decided to make a structural mod-
ification on the general framework of the catalysts and insert
a bulkier group than a phenyl ring in the amide position.
Thus, we prepared the corresponding chiral organochalcoge-
nide amides 2n and 3f by ring-opening reaction of the oxazo-
line 1i with phenylselenolate and phenylthiolate in 87 and
75% yields, respectively (Scheme 2).
Se
S
Se
S
Isolated yields.
Determined by chiral HPLC analysis.
For entries 1e4, the product has an R configuration. For entries 5e8, the
b
c
absolute configuration of the product was not determined.
alkylated product, to the best of our knowledge, this is the first
time that an organic telluride has been used as ligand for this
kind of transformation.
In addition, we have chosen the most efficient selenium-
and sulfur-containing chiral catalysts 2a and 3a (R1¼i-Pr
and R2¼Ph) in the palladium-catalyzed asymmetric allylic al-
kylation to evaluate them in the presence of substituted malo-
nates, as shown in Table 5. Thus, we could observe that the
ligands furnished the respective alkylated products with differ-
ent enantioselectivities, and in good to excellent yields. For
instance, when diethylmalonate 6b was employed as a nucleo-
phile in the asymmetric reaction, comparable results were
obtained to the reactions using dimethylmalonate under the
same conditions (Table 5, compare entries 1e2 and entries
3e4). However, when substituted malonates 6c (R4¼Et) and
6d (R4¼Ph) were employed in the catalytic reaction, the de-
sired products were obtained in lower yields and in up to
82% ee (Table 5, entry 7), demonstrating that the presence
of different groups in the R4 position shows a negative effect
in the formation of a new carbonecarbon bond with a high
level of enantioselectivity.
The chiral organochalcogenide amides 2n and 3f bearing
a bulkier group at the amide moiety (4-t-BuPh) were evaluated
We also note that in all cases presented herein the chiral
b-selenium amides have proven to be more efficient than the
respective chiral sulfur- and tellurium-containing analogues.
This observation of a difference in the behavior among the
chalcogenide donors provides evidence for the higher ability
of selenium to complex with palladium, leading to a superior
level of enantioselection.
O
N
TMSCl, THF
30 min.
i-Pr
Y
HN
PhYYPh/NaBH4
THF/EtOH (3:1)
reflux, 24 h
O
In order to propose a plausible explanation of the stereose-
lectivity observed, a schematic reaction pathway between the
dimethylmalonate and the allylic acetate in the presence of
the chiral ligand 2a is shown in Scheme 1.
2n Y = Se 87%
3f Y = S 75%
1i
Scheme 2. Preparation of chiral ligands 2n and 3f.

396
F. Vargas et al. / Tetrahedron 64 (2008) 392e398
O
O
2.5 mol% [Pd(η3-C3H5)Cl]2
5 mol% ligand 2n or 3f
OAc
Ph
MeO
Ph
OMe
MeO2C
6a
CO2Me
+
Ph
BSA/KOAc
CH2Cl2, 24 h, r.t.
Ph
5a
(R)-7a
i-Pr
i-Pr
Se
S
HN
HN
O
O
2n
3f
95% yield
98% ee
94% yield
91% ee
Scheme 3. Palladium-catalyzed asymmetric allylic alkylation with 2n and 3f.
as ligands in the palladium-catalyzed asymmetric allylic alkyl-
ation under same reaction conditions (Scheme 3).
internal standard. High resolution mass spectra were recorded
on a Brucker BioApex 70e FT-ICR (Bruker Daltonics, Biller-
ica, USA) instrument in ESI-mode. Column chromatography
was performed using Merck Silica Gel (230e400 mesh) fol-
lowing the methods described by Still.12 Thin layer chroma-
tography (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 io-
dine vapor or acidic vanillin. THF was dried over sodium ben-
zophenone ketyl and distilled prior to use. Dichloromethane
and acetonitrile were distilled from phosphorus pentoxide.
All other solvents were used as purchased unless otherwise
noted. Oxazolines were prepared according to the procedures
described in the literature.13 Racemic 1,3-diphenyl-3-acetoxy-
prop-1-ene was prepared according to literature procedure.14
Compounds 2aem were prepared according to the procedure
described in the literature.9
As observed in Scheme 3, the chiral selenium-containing li-
gand 2n, equipped with a 4-t-BuPh group attached to the am-
ide functional group, furnished similar results when compared
with the ligand bearing a phenyl group at the amide moiety 2a,
affording the corresponding alkylated product (R)-7a with the
same level of enantioselectivity (98%) and in comparable
chemical yield. However, the chiral sulfur-containing ana-
logue ligand 3f proved to be more efficient than 3a, delivering
the desired product (R)-7a with a slight improvement in the
enantiomeric excess (91%). Thus, this experimental result sup-
ports the proposed reaction pathway (Scheme 1) through the
more stable intermediate (A), which leads to the major product
with the (R) configuration.
3. Conclusions
In summary, we have described an extensive study concern-
ing the preparation of chiral b-selenium-, sulfur-, and tellu-
rium amides in a short, high yielding synthetic route and
with a modular approach by ring-opening reaction of 2-oxazo-
lines. Furthermore, all the compounds were evaluated as chiral
ligands for the palladium-catalyzed asymmetric allylic alkyl-
ation of racemic 1,3-diphenyl-2-propenyl acetate with malo-
nates. The corresponding alkylated products were achieved
in good to excellent yields and in up to 98% ee. The best re-
sults were obtained with the chiral b-selenium amide 2a, com-
pared to the other organochalcogenide ligands. More
interestingly, for the first time an organic telluride has been
used for this kind of transformation. This result demonstrates
the higher ability of selenium to complex with palladium com-
pared to other chalcogens and thus is an interesting feature for
the design of new ligands containing the chalcogen atom.
4.2. General procedure for the synthesis of chiral
b-chalcogen amides
Under an argon atmosphere, freshly distilled TMSCl
(1 mmol) was added to a solution of the appropriate oxazoline
(1 mmol) in dry THF (4 mL). The mixture was allowed to stir
for at least 30 min. The chalcogenide anion was generated by
reaction of the corresponding diorgano dichalcogenide
(0.6 mmol) with NaBH4 (1.5 mmol) in a mixture of THF
(1.5 mL) and EtOH (0.5 mL) and transferred to the flask con-
taining the oxazolium intermediate. The resulting solution was
stirred for 24 h under reflux. The mixture was quenched with
a saturated NH4Cl solution, extracted with CH2Cl2 and the
combined organic fractions were collected, dried over
MgSO4, and filtered. The solvent was removed in vacuo yield-
ing the crude products, which were purified by flash
chromatography.
4. Experimental
4.2.1. (S )-4-tert-Butyl-N-(3-methyl-1-(phenylselanyl)butan-
2-yl)benzamide 2n
4.1. General procedures
Yield 87%; white solid; mp 126e128 ꢀC; [a]D20 þ68 (c 1.0,
1
CH2Cl2); H NMR (CDCl3, 400 MHz) d 7.57e7.50 (m, 4H),
7.40e7.38 (m, 2H), 7.20e7.18 (m, 3H), 6.14 (d, J¼8.8 Hz,
1H), 4.23e4.21 (m, 1H), 3.26e3.21 (m, 2H), 2.02e2.00 (m,
2H), 1.32 (s, 9H), 0.97e0.95 (m, 6H); 13C NMR (CDCl3,
All compounds were isolated after column chromatography
and showed purity >95% by NMR analysis. Melting points
1
are uncorrected. H and 13C NMR spectra were recorded at
400 and 100 MHz, respectively, with tetramethylsilane as

F. Vargas et al. / Tetrahedron 64 (2008) 392e398
397
100 MHz) d 166.9, 154.7, 132.8, 131.7, 130.0, 129.1, 127.0,
126.6, 125.3, 54.5, 34.8, 31.9, 31.7, 31.1, 19.4, 18.5;
HRMS-ESI m/z calcd for C22H29NOSeþNaþ 426.1306, found
426.1301.
(CDCl3, 100 MHz) d 167.1, 159.0, 134.7, 133.4, 131.2,
128.3, 126.7, 126.1, 114.7, 55.1, 54.6, 38.9, 30.8, 19.2, 18.4;
HRMS-ESI m/z calcd for C19H23NO2SþNaþ 352.1341, found
352.1340.
4.2.2. (S )-N-(3-Methyl-1-(phenylthio)butan-2-yl)benzamide
3a
4.2.7. (S )-4-tert-Butyl-N-(3-methyl-1-(phenylthio)butan-2-yl)-
benzamide 3f
Yield 83%; white solid; mp 114e116 ꢀC; [a]D20 þ45 (c 1.0,
Yield 75%; white solid; mp 119e121 ꢀC; [a]D20 þ62 (c 0.5,
1
1
CH2Cl2); H NMR (CDCl3, 400 MHz) d 7.60e7.55 (m, 2H),
CH2Cl2); H NMR (CDCl3, 400 MHz) d 7.63 (d, J¼7.2 Hz,
2H), 7.45e7.34 (m, 5H), 7.23 (t, J¼7.6 Hz, 2H), 7.15e7.14
(m, 1H), 6.22 (d, J¼8.4 Hz, 1H), 4.23e4.19 (m, 1H), 3.23e
3.21 (m, 2H), 2.10e2.05 (m, 2H), 0.98 (d, J¼3.6 Hz, 3H),
0.97 (d, J¼3.6 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
d 167.2, 136.1, 134.6, 131.2, 129.7, 129.0, 128.4, 126.8,
126.3, 54.4, 36.9, 30.7, 19.3, 18.4; HRMS-ESI m/z calcd for
C18H21NOSþNaþ 322.1247, found 322.1248.
7.41e7.37 (m, 4H), 7.25e7.18 (m, 3H), 6.13 (d, J¼8.4 Hz,
1H), 4.24e4.20 (m, 1H), 3.24e3.22 (m, 2H), 2.08e2.07 (m,
1H), 1.32 (s, 9H), 0.99e0.95 (m, 6H); 13C NMR (CDCl3,
100 MHz) d 167.1, 154.8, 132.8, 131.8, 129.7, 129.2, 126.6,
126.3, 125.4, 54.3, 37.1, 34.8, 31.1, 30.8, 19.4, 18.3; HRMS-
ESI m/z calcd for C22H29NOSþNaþ 378.1862, found 378.1859.
4.2.8. (S )-N-(3-Methyl-1-(phenyltellanyl)butan-2-yl)-
benzamide 4
4.2.3. (S )-N-(4-Methyl-1-(phenylthio)pentan-2-yl)-
benzamide 3b
Yield 52%; yellow solid; mp 79e81 ꢀC; [a]D20 þ55 (c 1.0,
Yield 74%; white solid; mp 108e110 ꢀC; [a]D20 þ25 (c 1.0,
1
CH2Cl2); H NMR (CDCl3, 400 MHz) d 7.72e7.70 (m, 2H),
1
CH2Cl2); H NMR (CDCl3, 400 MHz) d 7.60 (d, J¼7.2 Hz,
7.61e7.58 (m, 2H), 7.45e7.11 (m, 6H), 6.18 (d, J¼8.4 Hz,
1H), 4.17e4.13 (m, 1H), 3.26 (dd, J¼12.4 Hz, J¼6.5 Hz, 1H),
3.21 (dd, J¼12.4 Hz, J¼4.7 Hz, 1H), 1.95e1.89 (m, 1H), 0.96
(d, J¼6.7 Hz, 3H), 0.92 (d, J¼6.7 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) d 166.9, 138.4, 134.6, 131.2, 129.2, 128.4,
127.7, 126.8, 111.1, 55.1, 33.3, 19.3, 18.5, 14.5; HRMS-ESI
m/z calcd for C18H21NOTeþNaþ 420.0577, found 420.0565.
2H), 7.45e7.33 (m, 5H), 7.25e7.21 (m, 2H), 7.14e7.12 (m,
1H), 6.16 (d, J¼8.4 Hz, 1H), 4.50e4.48 (m, 1H), 3.25e3.20
(m, 2H), 1.67e1.55 (m, 3H), 0.93e0.90 (m, 6H); 13C NMR
(CDCl3, 100 MHz) d 166.9, 136.2, 134.5, 131.3, 129.5, 129.0,
128.4, 126.8, 126.2, 47.6, 42.7, 39.2, 25.0, 22.8, 22.2; HRMS-
ESI m/z calcd for C19H23NOSþNaþ 336.1392, found 336.1389.
4.2.4. (S )-N-(1-Phenyl-3-(phenylthio)propan-2-yl)-
benzamide 3c
4.3. General procedure for the palladium-catalyzed
asymmetric allylic alkylation
Yield 70%; white solid; mp 151e153 ꢀC; [a]D20 þ26 (c 1.0,
1
CH2Cl2); H NMR (CDCl3, 400 MHz) d 7.54 (d, J¼8.0 Hz,
Under an argon atmosphere, a solution of [Pd(h3-C3H5)Cl]2
(2.5 mol %) and chiral ligand (5 mol %) in CH2Cl2 (2 mL) was
stirred for 30 min at room temperature. Subsequently, a solu-
tion of rac-1,3-diphenyl-2-propenyl acetate (0.5 mmol), dia-
lkyl malonate (1.5 mmol), N,O-bis(trimethylsilylacetamide)
(BSA) (1.5 mmol), and KOAc (cat. quantity) was added.
The resulting solution was stirred for 24 h. The mixture was
quenched with a saturated NH4Cl solution, extracted with
CH2Cl2 and the combined organic fractions were collected,
dried over MgSO4, and filtered. The solvent was removed in
vacuo yielding the respective alkylated products 7aed, which
were purified by flash chromatography.
2H), 7.40e7.16 (m, 13H), 6.24 (d, J¼8.4 Hz, 1H), 4.61e4.58
(m, 1H), 3.19e3.05 (m, 4H); 13C NMR (CDCl3, 100 MHz)
d 166.2, 137.1, 135.6, 134.2, 131.4, 129.5, 129.4, 129.1,
128.8, 128.6, 128.4, 126.7, 126.4, 50.5, 38.8, 36.9; HRMS-
ESI m/z calcd for C22H21NOSþNaþ 370.1236, found 370.1234.
4.2.5. (S )-N-(1-(2-Chlorophenylthio)-3-methylbutan-2-yl)-
benzamide 3d
Yield 68%; white solid; mp 116e118 ꢀC; [a]D20 þ49 (c 0.5,
1
CH2Cl2); H NMR (CDCl3, 400 MHz) d 7.74 (d, J¼7.2 Hz,
2H), 7.54e7.44 (m, 4H), 7.38 (d, J¼8.0 Hz, 1H), 7.24e7.22
(m, 1H), 7.16e7.14 (m, 1H), 6.24 (d, J¼8.0 Hz, 1H), 4.32e
4.25 (m, 1H), 3.36e3.27 (m, 2H), 3.24e3.15 (m, 1H),
1.00e0.96 (m, 6H); 13C NMR (CDCl3, 100 MHz) d 167.3,
135.1, 134.5, 131.4, 129.9, 129.7, 128.5, 127.3, 127.1,
126.8, 54.0, 35.8, 30.5, 19.5, 18.4; HRMS-ESI m/z calcd for
C18H20NOClSþNaþ 356.0846, found 356.0844.
Acknowledgements
The authors gratefully acknowledge CNPq, CAPES, and
FAPERGS for financial support. F.V. thanks CNPq for
a Ph.D. fellowship.
4.2.6. (S )-N-(1-(4-Methoxyphenylthio)-3-methylbutan-2-yl)-
benzamide 3e
References and notes
Yield 76%; white solid; mp 95e97 ꢀC; [a]D20 þ77 (c 0.5,
1
1. Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley and
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CH2Cl2); H NMR (CDCl3, 400 MHz) d 7.64 (d, J¼6.8 Hz,
2H), 7.47e7.35 (m, 5H), 6.77 (d, J¼8.4 Hz, 2H), 6.17 (d,
J¼8.8 Hz, 1H), 4.17e4.13 (m, 1H), 3.73 (s, 3H), 3.12e3.10
(m, 2H), 2.08e2.03 (m, 1H), 0.96e0.88 (m, 6H); 13C NMR
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~
1999, 10, 1019; (c) Braga, A. L.; Rodrigues, O. E. D.; Paixao, M. W.;
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Tetrahedron: Asymmetry 1993, 4, 1785; (j) Allen, J. V.; Coote, S. J.;
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~
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Net, G.; Ruiz, A.; Claver, C.; Woodward, S. Tetrahedron: Asymmetry
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Milani, P.; Silveira, C. C.; Rodrigues, O. E. D.; Alves, E. F. Synlett
2004, 1297.
9. (a) Braga, A. L.; Vargas, F.; Sehnem, J. A.; Braga, R. C. J. Org. Chem.
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´
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isopropanol 90:10, flow rate 1.0 mL/min), R isomer (tR¼9.33 min), S
isomer (tR¼13.47 min), and found to be >99.9%.
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