Modular chiral thiazolidine catalysts in asymmetric aryl transfer reactions

Article abstract of DOI:10.1016/j.tetasy.2006.10.025

Modular chiral thiazolidine derivatives were synthesized in a single step from inexpensive and commercially available starting materials. These ligands catalyzed enantioselective arylation of different aldehydes using aryl boronic acids as a source of transferable aryl groups. The products were obtained in excellent yields and good enantioselectivities.

Full text of DOI:10.1016/j.tetasy.2006.10.025

Tetrahedron: Asymmetry 17 (2006) 2793–2797
Modular chiral thiazolidine catalysts in asymmetric
aryl transfer reactions
*
Antonio Luiz Braga, Priscila Milani, Fabr ´ı cio Vargas,
M a´ rcio W. Paix a˜ o and Jasquer A. Sehnem
Departamento de Qu ı´ mica, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil
Received 8 September 2006; accepted 19 October 2006
Abstract—Modular chiral thiazolidine derivatives were synthesized in a single step from inexpensive and commercially available starting
materials. These ligands catalyzed enantioselective arylation of different aldehydes using aryl boronic acids as a source of transferable
aryl groups. The products were obtained in excellent yields and good enantioselectivities.
ꢀ
2006 Elsevier Ltd. All rights reserved.
1
. Introduction
background addition thus competes with the enantioselec-
tive pathway, leading to the formation of the racemic prod-
uct. In order to circumvent this problem, diethylzinc was
found to reduce the reactivity of the arylzinc reagent, by
forming PhZnEt, which is less reactive than diphenylzinc
itself. This strategy improves the overall system perfor-
The addition of organometallic reagents to carbonyl
compounds represents an attractive area in current organic
synthesis. The catalytic enantioselective version of this
reaction provides particularly useful access to chiral alco-
hols, which are synthetically important chiral building
blocks for pharmaceutically active compounds. In recent
years, considerable efforts have been made and great pro-
gress achieved in the catalytic enantioselective arylation
mance, since the aryl transfer reaction proceeds slowly
4
when compared to the reaction with Ph Zn alone. Addi-
2
tionally, it accounts for a higher selectivity for the phenyl
transfer and allows the use of a reduced amount of the
expensive diphenylzinc. These two protocols, however,
have a serious drawback. The scope of the aryl group to
be transferred is limited to the phenyl ring, since only
diphenylzinc is a commercially available diarylzinc reagent.
Thus, there is a growing interest in the development of
methods that allow the asymmetric transfer of a broader
range of substituted aryl groups, starting from inexpensive
and readily accessible sources. In this context, an interest-
ing protocol was recently introduced by Bolm, which takes
advantage of the use of boronic acids as the source of the
nucleophilic aryl species, by a boron-to-zinc exchange reac-
1
of aldehydes. Diarylmethanols are key intermediates in
the synthesis of antihistamic agents such as neobenodine,
orphenadrine, carbinoxamine, antimuscarinics, antidepres-
sants, and endothelin antagonists. As a result, the asym-
metric synthesis of optically active arylcarbinols has
attracted much attention due to their high availability as
starting materials.
Among the available methods for the synthesis of chiral
diarylmethanols, the asymmetric addition of arylzinc
showed the advantages of a wide substituent tolerance,
mild reaction conditions, and the use of relatively non-
toxic zinc metal. The initial approach was centered upon
the use of the expensive diphenylzinc as the aryl source.
However, its enantioselective addition to aldehydes is a
challenging endeavor, since this reagent is much more reac-
tive than the well known diethylzinc. The uncatalyzed
5
tion with diethylzinc. This modified methodology broad-
2
ened the scope of such an addition reaction and enabled
synthetic chemists to elaborate functionalized arylzinc
reagents as nucleophiles in salt free conditions.
3
Unfortunately, only a few elegant and efficient catalysts
have been developed for this purpose. The most successful
results toward optically active diarylmethanols have been
6
*
Corresponding author. Tel.: +55 55 32208761; fax: +55 55 32208998;
e-mail: albraga@quimica.ufsm.br
obtained mainly by the use of chiral b-amino alcohols.
In this field, our group recently reported the use of amino
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.10.025

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A. L. Braga et al. / Tetrahedron: Asymmetry 17 (2006) 2793–2797
alcohols in the catalytic asymmetric aryl transfer to alde-
hydes, furnishing the respective carbinols in excellent yields
and enantiomeric excesses. Furthermore, the efficient use
Table 1. Asymmetric phenyl transfer to p-tolualdehyde catalyzed by
thiazolidines 2a–h (20 mol %)
7
OH
of ligands bearing organochalcogen moieties has recently
been reported for this purpose. In most of the previous
1. Toluene, 60 °C, 12 h
8
PhB(OH)2
+
Et2Zn
2. Ligand, tolualdehyde, 12 h, rt
reports concerning the preparation of chiral ligands, multi-
step syntheses are required. Thus, the development of a
new, flexible and easily prepared effective catalysts is an
important challenge for the practical applications of phenyl
transfer reactions.
O
OR1
S
R
NH
2
2
R
2
a-h
Based on our ongoing interest the asymmetric aryl transfer
to aldehydes and the recent reports employing thiazolidines
as catalysts, mainly in the asymmetric addition of diethyl-
zinc to aldehydes, we report herein the behavior of these
compounds as catalysts in the enantioselective arylation
of aldehydes.
a
b
Entry Ligand
R
1
R
2
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
Me
Me
Me
Me
Et
i-Pr Et
i-Pr Et
i-Pr n-Bu
H
Me
Et
–CH
n-Bu
88
93
94
91
91
95
93
97
15
Rac.
56
21
65
51
75
81
9
2
(CH
2
)
3
CH
2
–
2g
2h
2
. Results and discussion
a
Isolated yield.
Determined by HPLC with a chiralcel OD column.
b
In order to obtain a quick and easy access to a wide range
of ligands, a modular system comprised of simple compo-
nents is essential. Thus, an economical synthesis of the
ligands has to be developed, which allows at any step of
the synthesis an easy modification or incorporation of
different moieties into the chiral pool. Chiral thiazolidines
when ligand 2b was used (entry 2). However, ligands 2c
(R = Me, R = Et) and 2e (R = Me, R = n-Bu) were
1
2
1
2
found to be more efficient in this reaction in terms of reac-
tivity and enantioselectivity (entries 3 and 5). Ligand 2d
also gave a poor ee (entry 4). Additionally, the different
substituents attached to the thiazolidine rings also affected
the enantioselectivity on the products. It is quite evident
that catalyst 2h (entry 8) showed a higher enantioselectivity
than the others. We believe that the butyl group has a
greater rotational freedom of movement than other substit-
uents at the thiazolidine ring. Therefore, ligand 2h could
present a larger steric bulk than other ligands near the
nitrogen. We believe that the thiazolidine derivatives tend
to show higher enantioselectivities when they have a larger
steric bulk in the thiazolidine rings. The enantioselectivity
of the catalysts was also affected by their amounts present
in the catalytic reactions. When we used 10 and 5 mol % of
catalyst 2h, the ee decreased to 63% and 41%, respectively.
2
a–h were easily prepared by the condensation of
L-cysteine ester 1 with the corresponding aldehyde or
ketone in good yields as described in Scheme 1.
Initially, in order to find out the best ligands and an opti-
mal procedure, we chose the PhZnEt addition to p-tolual-
dehyde as a model reaction in the presence of 20 mol %
of ligands 2a–h under different conditions. To the best of
our knowledge, this is the first time that ligands containing
an ester as a complexing group have been evaluated in this
asymmetric reaction. The enantiomeric purity of diaryl-
methanol was determined by HPLC analysis with a chiral
stationary phase column (Daicel Chiralcel OD, hexane/
i-PrOH).
As seen in Table 1, the first important conclusion was ob-
served when the substituents at the thiazolidine (R ) moiety
In order to examine the influence of a new stereogenic cen-
ter in this class of compounds, we easily reproduced ligand
2i (Scheme 2). This chiral thiazolidine was prepared by
condensation with benzaldehyde, and then obtained as an
inseparable diastereoisomeric mixture in a ratio of 61:39
2
were first evaluated, while the R position was kept con-
1
stant as a methyl group (Table 1, entries 1–5). For example,
when chiral ligand 2a was employed, the addition product
was obtained in a 15% ee (Table 1, entry 1). However under
the same conditions, the racemic product was obtained
1
0
in favor of the cis diastereoisomer. (2R,4R)-cis-Thiazol-
idine was assigned to be the major diastereomer based on
1
comparison of H NMR data with previous studies re-
ported in the literature. Although the diastereoisomeric
mixture furnished 1-phenyl-propanol in an 80% ee and
O
11
OR1
O
OR1
a or b
HS
S
NH
NH .HCl
1
R2 R2
2
2
H
Ph
O
R1 = Me, Et, i-Pr
R2 = H, Me, Et, n-Bu, CH (CH ) CH
2
H
H
H
H
H
H
S
H
S
Ph
H
O
2
2 3
O
Ph
etanol; AcONa
N
H
N
H
HS NH Cl
3
MeOOC
MeOOC
0
°C; 4 h
a = acetone or paraformaldehyde, K CO CH Cl
2
3,
2
2
1a
b = benzene, ketone, TsOH, Reflux
2icis
2itrans
Scheme 1. One-pot synthesis of chiral ligands 2.
Scheme 2. Synthesis of ligand 2i as a diastereoisomeric mixture.

A. L. Braga et al. / Tetrahedron: Asymmetry 17 (2006) 2793–2797
2795
O
O
Table 2. Catalytic arylation of aldehydes with boronic acids
OH
iso-propanol
HCl(g)
OH
O
1) Toluene, 60 °C, 12 h
Et Zn
2
HS NH2
HS NH Cl
ArB(OH)2
3
Ar
2) 2h (20mol%), aldehyde, r.t., 12 h
3
R
b,c
Entry Boronic acid
Aldehyde
Yield ee (%)
O
a
(
%)
benzene,PTSA
O
H
48 h,reflux
1
2
3
4
PhB(OH)
2
2
97
91
98
97
81 (S)
75 (S)
79 (S)
73 (S)
O
O
CH3
O
S
NH
PhB(OH)
H
OMe
O
4
Scheme 3. Synthesis of ligand 4 with 57% yield.
PhB(OH)2
H
Cl
O
O
CH3
OCH3
Cl
an 84% yield,9b unfortunately, the respective aryl transfer
afforded the diarylcarbinol in an excellent yield (98%),
but essentially in a racemic form.
PhB(OH)
2
2
H
H
5
PhB(OH)
93
56 (S)
We also tried to evaluate the influence of steric hindrance
near to the sulfur atom in the thiazolidine ring. Based on
this, ligand 4 was synthesized starting from D-penicylamine
using the same synthetic methodology, as described in
Scheme 3.
O
O
6
7
PhB(OH)
2
2
97
89
42 (S)
33 (S)
H
H
When the efficiency of thiazolidine 4 was examined in the
present reaction we could see that the steric bulkiness at
the thiazolidine ring strongly affected the enantioselectivity.
The size of the group close to the sulfur atom is also impor-
tant for the outcome of the reaction and a large decrease in
the ee and yield was observed. p-Tolualdehyde was con-
verted into the corresponding (R)-alcohol with a 52% ee
and a 79% yield.
PhB(OH)
S
8
9
PhB(OH)
2
2
63
59
06 (S)
20 (S)
O
PhB(OH)
O
B(OH)2
Reaction temperature does not seem to have a significant
impact on the enantiomeric excess since reactions conduced
at 0 ꢁC afforded the same level of enantioselectivity when
compared to reactions conducted at room temperature,
using ligand 2h. Literature concerning the influence of the
solvent in the present reaction, meant that its performance
was not examined in our catalytic system.4 Surprisingly,
a lower enantioselection and yields were achieved, 71% and
1
0
1
Benzaldehyde
90
99
80 (R)
57 (R)
H CO
3
B(OH)2
1
Benzaldehyde
Cl
a
b
c
a,5
Isolated yield of the corresponding product.
Enantiomeric excesses were determined by chiral HPLC.
Configuration determined by comparison with literature data.
4
8
3%, respectively, with the addition of DiMPEG to this
reaction. This fact may be due to the strong interactions
of DiMPEG and PhZnEt, leading to the delivery of the
phenyl group with a low enantioselectivity.
afforded diarylmethanols in low yields and enantiomeric
excess (Table 2, entries 4–6). These results could be
explained by the higher steric hindrance that the carbonyl
groups present in ortho-substituted benzaldehydes, which
may hinder the formation of a rigid transition state.
With ligand 2h identified as the most effective, we next
examined the scope of our system in reactions with several
aldehydes with diverse electronic and steric properties. The
results of this study are depicted in Table 2.
With regards to the electronic effects, we noted that all
para-substituted aldehydes afforded the same level of
enantioselectivity, showing that the electronic nature of
the substituent in the aldehyde has a small influence on this
reaction. However, when ortho-substituted aldehydes were
employed, electron-withdrawing and electron-donating
groups were screened in the catalytic system, lower ees were
Based on these results, we were able to observe that the
position of the substituent in the aldehyde plays an impor-
tant role in terms of determining enantioselection. para-
Substituted aldehydes underwent aryl addition in a high
enantiomeric excess and nearly quantitative yields (Table
2
, entries 1–3). However, ortho-substituted benzaldehydes

2796
A. L. Braga et al. / Tetrahedron: Asymmetry 17 (2006) 2793–2797
1
3
achieved to the respective products, showing that electronic
effects play an important role in the enantioselective
reaction.
3.26–3.07 (m, 2H).
C NMR (CDCl3, 100 MHz):
d = 170.98; 72.61; 66.49; 56.78; 32.13.
4
.1.2. (R)-Methyl 2,2-dimethylthiazolidine-4-carboxylate 2b.
1
Next, we investigated the possibility of varying the struc-
ture of the boronic acid (Table 2, entries 10 and 11). Elec-
tron-donating groups achieved the same result as phenyl
boronic acid, while electron-withdrawing groups cause a
dramatic decrease in the enantiomeric excess, probably
due to the decrease in the nucleophilicity of the aryl group
to be delivered.
Yield: 96%; H NMR (CDCl , 200 MHz): d = 6.73 (s, 1H);
4
J = 7.0 Hz, 1H); 3.20 (dd, J = 11.06 Hz, J = 8.2 Hz,
1
1
3
3
1
.44–4.37 (m, 1H); 3.82 (s, 3H); 3.5 (dd, J = 11.04 Hz,
2
1
2
1
3
H); 1.80 (s, 3H); 1.69 (s, 3H). C NMR (CDCl3,
00 MHz): d = 173.48; 75.38; 64.03; 53.19; 43.27; 39.82;
0.07.
4
.2. General procedure for the synthesis of compounds 2c–h
In all cases, no ethyl transfer product was formed, which
4
,5
was consistent with other results and related theoretical
In a two neck round-bottomed flask, equipped with
magnetic stirrer and Dean–Stark apparatus and reflux
condenser, were added L-cysteine methyl ester (0.556 g;
1
2
studies. The boronic acid methodology is one of the most
interesting feature employed herein, since both enantio-
mers of a given product can be easily prepared in excellent
yields and good enantiomeric excesses with the same cata-
lyst, just by the appropriate choice of both reaction part-
ners, aryl boronic acid and aldehyde.
3
mmol), 3-pentanone (0.335 g; 4 mmol), para-toluenosulf-
onic acid (catalytic amount), and benzene (30 mL). The
reaction was refluxed for 48 h and then cooled to room
temperature. The solvent was removed under vacuum
and the reminiscent solid was diluted with an aqueous solu-
tion of K CO 20% (15 mL) and extracted with dichloro-
2
3
3. Conclusion
methane (3 · 20 mL). The organic layer was dried with
MgSO and the solvent removed under reduced pressure
4
In conclusion, we have described the asymmetric arylation
of aldehydes in the presence of a catalytic amount of a chi-
ral thiazolidine affording the corresponding diarylmetha-
nols in good yields and enantiomeric excess. The one-step
synthesis of these ligands from L-cysteine ester, combined
with the mild reaction conditions and good enantioselectiv-
ity obtained make this chiral catalyst practically useful for
general synthesis. The importance of a flexible synthetic
methodology, which allows access to a diversity of ligands
making possible a structural tuning of the ligands in order
to obtain a good catalytic performance is also evident.
yielding the desired product. No further purification were
needed.
4
.2.1. (R)-Methyl 2,2-diethylthiazolidine-4-carboxylate 2c.
1
Yield: 71%; H NMR (CDCl , 200 MHz): d = 4.05–3.98
3
1
(m, 1H); 3.37 (s, 3H); 3.28 (dd, J = 10.16 Hz,
2
J = 6.6 Hz, 1H); 2.87–2.77 (m, 1H); 2.33 (s, 1H); 2.01–
1
3
6
.61 (m, 4H); 1.02 (t, J = 7.3 Hz, 3H); 0.91 (t, J = 7.3 Hz,
1
3
H). C NMR (CDCl , 100 MHz): d = 173.24; 84.14;
3
3.66; 43.07; 38.08; 33.62; 31.06; 9.25; 8.99.
4
2
.2.2. (R)-3-Methoxycarbonyl-1-thio-4-azospire[4.5]decane
The importance of this work lies in the fact that this is the
first study involving ester groups in asymmetric catalytic
aryl transfer to aldehydes with PhB(OH) /Et Zn systems.
This study opens a new frontier for the development of
other catalysts with different complexating groups.
1
d. Yield: 63%; H NMR (CDCl , 200 MHz): d = 4.06
3
1
2
(dd, J = 9.34 Hz, J = 6.6 Hz, 1H); 3.78 (s, 3H); 3.29
1
2
2
2
(dd, J = 10.32 Hz, J = 6.6 Hz, 1H); 2.92–2.82 (m, 1H);
13
2
1
3
.39 (s, 1H); 1.90–1.25 (m, 10H). C NMR (CDCl3,
00 MHz): d = 172.10; 81.64; 63.45; 52.30; 40.80; 39.98;
8.05; 25.47; 25.21; 23.63.
4
. Experimental
4
2
.2.3. (R)-Ethyl 2,2-diethylthiazolidine-4-carboxylate
1
e. Yield: 73%; H NMR (CDCl , 200 MHz): d = 4.22
3
1
2
4
.1. General procedure for the synthesis of compounds 2a,b
(q, J = 7.2 Hz, 2H); 3.99 (dd, J = 9.16 Hz, J = 6.7 Hz,
1
2
1H); 3.29 (dd, J = 10.24 Hz, J = 6.6 Hz 1H); 2.86–2.76
In a two neck round-bottomed flask, under argon and
equipped with magnetic stirrer a solution of L-cyteine
methyl ester (1.715 g; 10 mmol) in dry dichloromethane
(
7
3
m, 1H); 2.37 (s, 1H); 2.04–1.61 (m, 4H); 1.29 (t, J =
.1 Hz, 3H); 1.02 (t, J = 7.3 Hz, 3H); 0.91 (t, J = 7.3 Hz,
1
3
H). C NMR (CDCl , 100 MHz): d = 172.27; 84.54;
3
(
10 mL) was added. K CO (4.2 g; 30 mmol) and parafolm-
2 3
64.13; 61.13; 43.48; 38.53; 34.03; 31.39; 9.54; 9.31.
aldehyde (0.45 g; 30 mmol) were then added. The mixture
was stirred for 24 h at room temperature. The crude mix-
ture was then filtered and washed with water (30 mL)
and extracted with dichloromethane (3 · 20 mL). The or-
4
.2.4. (R)-Isopropyl 2,2-diethylthiazolidine-4-carboxylate 2f.
1
Yield: 79%; H NMR (CDCl , 200 MHz): d = 5.08 (sept,
J = 6.2 Hz, 1H); 3.97 (dd, J = 9.28 Hz, J = 6.6 Hz, 1H);
3
3
1
2
ganic layer was dried with MgSO and the solvent removed
1
2
4
.29 (dd, J = 10.34 Hz, J = 6.6 Hz, 1H); 2.81 (dd,
under a reduced pressure yielding the desired product.
1
2
J = 10.24 Hz, J = 9.4 Hz, 1H); 2.27 (s, 1H); 2.05–1.69
m, 4H); 1.29 (d, J = 3.6 Hz, 3H); 1.26 (d, J = 3.6 Hz,
(
4
.1.1. (R)-Methyl thiazolidine-4-carboxylate 2a. Yield:
3H); 1.03 (t, J = 7.3 Hz, 3H); 0.92 (t, J = 7.3 Hz, 3H).
1
13
7
5%;
H
NMR (CDCl3, 200 MHz): d = 4.38 (dd,
C NMR (CDCl , 100 MHz): d = 171.13; 84.80; 68.83;
3
1
2
J = 7.4 Hz, J = 3.5 Hz, 1H); 4.23 (s, 2H); 3.72 (s, 3H);
64.19; 38.85; 34.22; 31.22; 21.59; 21.56; 9.68; 9.47.

A. L. Braga et al. / Tetrahedron: Asymmetry 17 (2006) 2793–2797
2797
4
.2.5. (R)-Methyl 2,2-dibutylthiazolidine-4-carboxylate 2g.
Professor L. A. Wessjohann, Dr. J. Schmidt (IPB,
Germany) for HPLC and HRMS analysis.
1
Yield: 87%; H NMR (CDCl , 200 MHz): d = 4.02 (m,
3
1
2
1
1
1
1
3
H); 3.77 (s, 3H); 3.30 (dd, J = 10.2 Hz, J = 6.6 Hz,
H); 2.88–2.79 (m, 1H); 2.40 (s, 1H); 1.91–1.70 (m, 4H);
1
3
.51–1.31 (m, 8H); 0.96–0.89 (m, 6H). C NMR (CDCl3,
00 MHz): d = 171.74; 83.42; 63.89; 51.91; 41.58; 39.20;
8.41; 27.51; 27.10; 22.67; 22.63; 13.66; 13.59.
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2
.2.6. (R)-Isopropyl 2,2-dibutylthiazolidine-4-carboxylate
1
h. Yield: 71%; H NMR (CDCl , 200 MHz): d = 5.09
3
1
(
sept, J = 6.2 Hz, 1H); 3.98 (dd, J = 7.36 Hz,
2
1
2
J = 6.7 Hz, 1H); 3.30 (dd, J = 10.3 Hz, J = 6.7 Hz,
1
1
H); 2.86–2.76 (m, 2H); 1.91–1.67 (m, 4H); 1.51–1.25 (m,
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3
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4
.3. General procedure for the synthesis of compounds 2i
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d = 7.42–7.20 (m, 10H); 5.76 (s, 1H ); 5.51 (s, 1Htrans);
1
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(
2
cis
4
.19–4.12 (m, 1H ); 3.97–3.89 (m, 1H
); 3.70 (2s, 6H,
C NMR (CDCl3,
cis
trans
3
hedron: Asymmetry 2005, 16, 1367; (d) Fontes, M.; Verda-
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Mu n˜ iz, K. Bioorg. Med. Chem. Lett. 2002, 2, 1795; (g) Bolm,
C.; Kesselgruber, M.; Grenz, A.; Hermanns, N.; Hildebrand,
J. P. New J. Chem. 2001, 25, 13; (h) Huang, W. S.; Pu, L.
Tetrahedron Lett. 2000, 41, 145; (i) Huang, W.-S.; Pu, L. J.
Org. Chem. 1999, 64, 4222.
1
OCH3 cis and trans); 3.43–3.01 (m, 4H).
1
1
5
00 MHz): d = 171.54; 170.95; 140.70; 137.74; 128.05;
27.79; 127.24; 126.88; 126.41; 71.89; 70.31; 64.86; 63.78;
1.89; 51.80; 38.49; 37.51.
4
.4. General procedure for the synthesis of compounds 4
The same procedure was used for the synthesis of com-
pounds 2c–h. Yield: 57%; H NMR (CDCl , 200 MHz):
d = 5.10 (sept, J = 6.2 Hz, 1H); 3.80 (s, 1H); 3.03 (s, 1H);
1
5
6
. Bolm, C.; Rudolph, J. J. Am. Chem. Soc. 2002, 124,
1
1
3
4850.
. (a) Bolm, C.; Rudolph, J.; Schmidt, F. Synthesis 2005, 5, 840;
.85–1.74 (m, 4H); 1.60 (s, 3H); 1.31–1.26 (m, 14H); 1.21
¨
b) Bolm, C.; Oz c¸ ubuk c¸ u, S.; Schmidt, F. Org. Lett. 2005, 7,
(
1
3
(
s, 3H); 0.95–0.90 (m, 6H). C NMR (CDCl , 100 MHz):
1407; (c) Bolm, C.; Rudolph, J.; Hermanns, N. J. Org. Chem.
2004, 69, 3997; (d) Schmidt, F.; Stemmler, R. T.; Rudolph, J.;
Bolm, C. Chem. Soc. Rev. 2006, 35, 454; (e) Kim, J. G.;
Walsh, P. J. Angew. Chem., Int. Ed. 2006, 45, 4175.
3
d = 169.36; 80.48; 72.55; 68.89; 58.87; 42.67; 40.82; 28.86;
2
7.90; 27.86; 27.34; 23.04; 23.00; 21.91; 21.86; 14.03; 13.96.
7
. (a) Braga, A. L.; L u¨ dtke, D. S.; Vargas, F.; Paix a˜ o, M. W.
Chem. Commun. 2005, 2512; (b) Braga, A. L.; L u¨ dtke, D. S.;
Vargas, F.; Schneider, P. H.; Paix a˜ o, M. W.; Schneider, A.;
Wessjohann, L. A. Tetrahedron Lett. 2005, 46, 7827; (c)
Braga, A. L.; Silva, S. J. N.; L u¨ dtke, D. S.; Drekener, R. L.;
Silveira, C. C.; Rocha, J. B. T.; Wessjohann, L. A. Tetra-
hedron Lett. 2002, 43, 7329.
4.5. General procedure for asymmetric aryl transfer
reactions
Diethylzinc (3.6 mmol, toluene solution) was added drop-
wise to a solution of boronic acid (1.2 mmol) in toluene
(
1
(
2 mL) under an argon atmosphere. After stirring for
2 h at 60 ꢁC, a toluene solution of chiral thiazolidine 2i
20 mol %) was introduced. The reaction was stirred for
8. Wu, P.-Y.; Wu, H.-L.; Uang, B.-J. J. Org. Chem. 2006, 71,
833.
an additional 15 min and the aldehyde (0.5 mmol) was sub-
sequently added. After stirring overnight, the reaction was
quenched with water and the aqueous layer was extracted
with dichloromethane.
9. (a) Guan, Y.; Meng, Q.; Li, Y.; He, Y. Tetrahedron:
Asymmetry 2000, 11, 4255; (b) Jin, M. J.; Kim, S. H. Bull.
Korean Chem. Soc. 2002, 23, 509.
1
0. The diastereomeric ratio was be determined by the intensity
1
ratio of two singlets for the C2 proton in the H NMR
spectrum, which is attributed to two diastereomers.
1
1
1. Brunner, H.; Becker, R.; Riepl, G. Organometallics 1984, 3,
Acknowledgements
1
354.
2. (a) Rudolph, J.; Rasmussen, T.; Bolm, C.; Norrby, P.-O.
Angew. Chem., Int. Ed. 2004, 42, 3002; (b) Rudolph, J.; Bolm,
C.; Norrby, P.-O. J. Am. Chem. Soc. 2005, 127, 1548.
The authors gratefully acknowledge CAPES, CNPq, and
FAPERGS for financial support. We are also grateful to