Dicationic ((-)-sparteine)palladium-catalyzed enantioselective aldol reaction of aldehydes with 1-phenyl-1-trimethylsilyloxyethene, proceeding via a palladium enolate

Article abstract of DOI:10.1016/j.tetlet.2006.04.068

A dicationic ((-)-sparteine)palladium complex underwent a superior catalytic enantioselective aldol reaction of aldehydes with 1-phenyl-1-trimethylsilyloxyethene performing satisfactorily, starting with ((-)-sparteine)PdCl₂ and AgSbF₆

Full text of DOI:10.1016/j.tetlet.2006.04.068

Tetrahedron Letters 47 (2006) 4453–4456
Dicationic ((ꢀ)-sparteine)palladium-catalyzed enantioselective
aldol reaction of aldehydes with 1-phenyl-1-trimethylsilyloxyethene,
proceeding via a palladium enolate
*
Syun-ichi Kiyooka, Yushi Takeshita, Yoshinori Tanaka,
Takafumi Higaki and Yosuke Wada
Department of Materials Science, Faculty of Science, Kochi University, Akebono-cho, Kochi 780-8520, Japan
Received 13 March 2006; revised 7 April 2006; accepted 10 April 2006
Abstract—A dicationic ((ꢀ)-sparteine)palladium complex underwent a superior catalytic enantioselective aldol reaction of alde-
hydes with 1-phenyl-1-trimethylsilyloxyethene performing satisfactorily, starting with ((ꢀ)-sparteine)PdCl
2 6
and AgSbF as catalyst
˚
precursors (1 mol % loading) in the presence of 3 A molecular sieves over the reaction.
Ó 2006 Elsevier Ltd. All rights reserved.
1
Significant progress in modern aldol reactions has been
limited to utilizing late transition metal enolates for
aldol reactions since the pioneering work on rhodium
O-bound enolates obtained by metathesis of the corre-
such pre-formed complexes for the dicationic ((R)-
BINAP)palladium-catalyzed enantioselective aldol reac-
tion of benzaldehyde with 1-phenyl-1-trimethylsilyloxy-
ethene 1 to give (R)-2 in a perfect yield with a similar
2
3
sponding silyl enol ethers was reported. The first late
level to the reported enantioselectivity (Eq. 1). By apply-
transition metal-catalyzed enantioselective aldol reac-
tion had to await the appearance of the cationic
BINAP-palladium catalysts. The successive studies
ing the practical one-pot procedure, we have started to
search other chiral ligand systems in which this aldol
reaction would be effective. We disclose herein that dicat-
ionic ((ꢀ)-sparteine)palladium complex is quite useful
for the purpose proposed in this research; this is the first
example of the dicationic palladium-catalyzed enantio-
selective aldol reaction with a chiral dinitrogen bidentate
alkyl ligand. Perhaps the most phenomenal aspect of this
is that sparteine serves as an alternative for BINAP in
spite of the extreme differences in their structure.
3
4
found an effective method generating the chiral palla-
dium enolates from the corresponding silyl enol ethers
by using effective starting palladium complexes: Pd aqua
complexes and binuclear Pd hydroxo complexes. How-
ever, other remarkable developments related to the field
have not been reported until now. We have recently
5
found a practical reaction procedure without utilizing
(
(R)-BINAP)PdCl (1 mol%)
2
2
AgSbF6
TMSO
Ph
O
HO
O
OTMS
Ph
H+
3A molecular sieves
ð1Þ
PhCHO
+
Ph
Ph
Ph
dried DMF
1
rt, overnight
(
R
)-2: 98%, Er 88 : 12
Numerous chiral ligands, useful for a variety of Pd-cata-
lyzed enantioselective reactions, are known, of which
chiral oxazoline derivatives were found to be especially
*
0
Corresponding author. Fax: +81 88 844 8359; e-mail: kiyooka@cc.
kochi-u.ac.jp
6
,7
effective. In searching for effective ligands other than
040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.04.068

4454
S. Kiyooka et al. / Tetrahedron Letters 47 (2006) 4453–4456
O
O
N
O
O
70
6
2
N
N
N
60
Ph
Ph
N
Ph
Ph
52
5
0
I
II
O
O
Ph
Ph
N
2
7
3
0
Ph
Ph
21
III
20
Scheme 1. Commercially available chiral oxazoline ligands tentatively
used.
0
.10
0.25
0.50
1.00
BINAP, we preliminarily adapted commercially avail-
able chiral oxazoline derivatives, I, II, and III, to the
Quantity (mL) of solvent DMF (scaled to 1 mmol reaction)
8
reaction under consideration, as depicted in Scheme 1.
The corresponding catalyst precursors were prepared
from the above oxazoline derivatives and PdCl2-
Figure 1. Remarkable effects of DMF quantity on the yields in the
cationic ((ꢀ)-sparteine)palladium-catalyzed enantioselective aldol
reaction (reaction time: 12 h) of benzaldehyde with 1 along with the
same enantiomeric ratio (92:8).
(
CH CN) . However, the Pd-catalyzed aldol reactions
3 2
of benzaldehyde with 1, starting with the (chiral oxazo-
line ligand)palladium chloride complexes, led to un-
favorable results in that the expected enantioselectivity
was not observed at all. On the basis that the above
ligands exhibited such unpredictable behavior, we could
draw a conclusion that the transient dicationic palladium
The reaction of benzaldehyde with silyl nucleophile 1 in
the presence of ((ꢀ)-sparteine)palladium complex was
investigated using the one-pot procedure, mentioned
above. After detailed investigation, we became aware
of the apparently different dependence that yield had
on the solvent dilution in both reactions using sparteine
and BINAP: the reaction with sparteine gave relatively
good yields when the quantity of solvent DMF was more
limited than the reaction with BINAP. The total use of
DMF (0.25 mL) in the reaction with sparteine (1 mol %
catalyst loading) was appropriate for the 1 mmol scale
of the substrate, in comparison with the effective use of
DMF (1 mL) under similar reaction conditions with BI-
NAP, as shown in Figure 1. According to the optimized
solvent quantity, the reaction (1 mol % catalyst loading)
of benzaldehyde with 1 resulted in a fairly good yield of
(S)-aldol product with high % ee, as shown in Eq. 2. In
addition, it was found that long reaction time improved
the % yield. The dicationic palladium species having
9
complexes with these ligands might be more labile
than the expected stable coordination states, in which
the two nitrogen atoms are fixed to the same side (cis
configuration) toward the palladium atom in com-
plexation. Then, we directed much of our attention
to N,N-bidentate ligands, having an inherently rigid
cis structure. Consequently, (ꢀ)-sparteine was selected;
the preparation of ((ꢀ)-sparteine)PdCl , with respect to
2
the catalytic kinetic resolution of secondary alcohols as
a neutral catalyst in aerobic oxidation, has been re-
1
0
ported. The palladium complex was obtained by mix-
ing PdCl (CH CN) and (ꢀ)-sparteine in acetone and
2
3
2
could be converted in situ to the corresponding dicat-
ionic species (Scheme 2).
(
(-)-sparteine)PdCl (1 mol%)
2
2
AgSbF6
TMSO
Ph
O
HO
O
OTMS
Ph
H+
3
A molecular sieves
PhCHO
+
ð2Þ
Ph
Ph
)-2: 62%, Er 92 : 8
S)-2: 72%, Er 92 : 8
Ph
dried DMF, rt
1
1
2 h / (
S
4
8 h / (
N,N-bidentate ligand (sparteine) was revealed to work
well, not inferior to the case of P,P-bidentate ligand (BI-
NAP). The dilution causes only the lowering of the yield
without leading to any detectable loss in the % ee so that
excess DMF would disturb the in situ regeneration of the
active catalyst species. Conclusively, that is characteristic
of this dinitrogen ligand but the electronic effect on the
dicationic palladium has not been made clear to date.
(
-)-sparteine + PdCl (CH CN)
2 3 2
2
+
acetone
2
SbF6-
N
N
(
(-)-sparteine)PdCl2 + 2AgSbF6
DMF
Pd
DMF
DMF
Scheme 2. A procedure toward the dicationic ((ꢀ)-sparteine)palladium
The typical procedure (1 mol % catalyst loading) is as
catalyst.
follows: Onto
a
mixture of ((ꢀ)-sparteine)PdCl2

S. Kiyooka et al. / Tetrahedron Letters 47 (2006) 4453–4456
4455
˚
17 mg, 0.04 mmol) and 3 A molecular sieves (dried over
Table 1. Dicationic ((ꢀ)-sparteine)Pd-catalyzed enantioselective aldol
(
a
reaction of a variety of aldehydes with 1 (Eq. 3)
an open flame, cooled under reduced pressure, and
stored under Ar) (powder: 120 mg), DMF11 (0.2 mL)
was added and the suspension was stirred for 15 min,
the color then become yellow brown. A DMF solution
b
Entry Aldehydes
Products Yields Er
(%)
c
c
c
1
2
3
4
5
6
7
8
9
0
1
p-Methylbenzaldehyde
3
64
54
72
75
67
53
53
28
15
72
75
91:9 (84:16)
70:30
87:13
94:6
80:20
92:8 (88:12)
82:18
76:24
69:31
91:9
(
0.2 mL) of AgSbF (28 mg, 0.08 mmol) was added to
6
p-Methoxybenzaldehyde
o-Methoxybenzaldehyde
p-Phenylbenzaldehyde
Cinnamaldehyde
3-Phenylpropionaldehyde
Phenylethanaldehyde
Isobutyraldehyde
Pivalaldehyde
1-Naphthylaldehyde
2-Naphthylaldehyde
4
the resulting mixture, followed by precipitation of AgCl.
The color of the solution changed to being slight yellow.
A mixture of benzaldehyde (0.41 mL, 4.0 mmol) and
silyl nucleophile 1 (1.24 mL, 6.0 mmol) was added in
one portion to the solution. The resulting solution was
stirred for 12 h. During the term the color of the solu-
tion gradually changed to black. The formation of the
silylated aldol product was indicated from the corres-
5
6
7
8
9
10
11
12
13
1
1
96:4 (81:19)
ponding spot (R ; 0.65) on TLC (20% AcOEt/n-hexane).
f
a
The reaction was carried out according to the typical procedure
1 mol % catalyst loading) described in text: ((ꢀ)-sparteine)palladium
chloride (0.04 mmol), AgSbF (0.08 mmol), benzaldehyde (4 mmol),
(6 mmol), DMF (0.4 mL), and 3 A molecular sieves (120 mg).
Enantiomeric ratios determined by chiral HPLC (Chiralcel OD).
The data (parentheses) given from the corresponding (BINAP)Pd-
catalyzed reaction (Eq. 2).
The reaction was quenched by the addition of 10% aq
HCl (5 mL) and diethyl ether (10 mL). After stirring
for 10 min, the deprotected aldol was extracted with
diethyl ether (10 mL, twice). The organic layers were
(
6
˚
1
b
c
dried over anhydrous MgSO . After the ether had
4
evaporated, the residue was purified by flash column
chromatography (SiO ) (10% AcOEt/n-hexane) to give
2
5
61 mg of the (S)-isomer in a 62% yield. The optical
purity was determined by HPLC analysis with DAICEL
CHIRALPAC OD-H (5% 2-propanol/n-hexane) to be
also found to decrease the corresponding selectivity
(entries 7, 8, and 9).
8
3% ee (R , (S): 20 min and (R): 23 min).
fs
(
(-)-sparteine)PdCl (1 mol%)
2
2
AgSbF6
TMSO
R
O
HO
O
OTMS
Ph
H+
3
A molecular sieves
ð3Þ
RCHO
+
Ph
R
Ph
dried DMF
1
rt, overnight
3 ~ 13
The results of the dicationic ((ꢀ)-sparteine)palladium-
catalyzed enantioselective aldol reaction (1 mol % cata-
lyst loading) of a variety of aldehydes with 1 are shown
in Table 1 (Eq. 3). The yields were generally slightly low-
SbF6-
*
DMF
N
Pd
N
2+
SbF -
6
H
O
H
HSbF6
5
er than the case with BINAP. As was previously men-
Me
Me
Me
H
TMSOH
tioned, the decrease in yield might be owing to the
labile character of the dicationic (sparteine)palladium
complex against the solvent DMF. Conversely, the
enantiomeric ratios were apparently higher than the case
of BINAP. The steric demands of sparteine at the active
catalytic center might play a more suitable role for enan-
tioselective induction. The aldehyde, having a methoxy
substituent, led to a considerable reduction not only in
the % yield, but also in the enantiomeric ratio presum-
ably via transition states involving different complex-
ations because of the methoxy substituent’s ability to
preferentially coordinate with the cationic palladium
center (entry 2). However, there was no prevailing ten-
dency for o-methoxybenzaldehyde (entry 3). The alde-
hydes, composed of extended p electron systems, were
prone to enhance the enantioselectivity (entries 4, 10,
and 11). Although reactions with primary aldehydes
having a phenyl moiety produced satisfactory yields
Si
O
Ph
H
*
DMF
SbF -
N
Pd
6
TMSO
O
N
O
*
R
Ph
H
Ph
RCHO
H
OTMS
H
R
Ph
*
O
H
N
H
DMF
Pd
O
*
N
Pd
N
SbF6-
SbF6-
N
H
O
O
Ph
(
entries 6 and 7), the reaction with aliphatic aldehydes
*
R
H
Ph
decreased the yields and, in addition, the branching at
a of these aldehydes seriously suppressed the yields
Scheme 3. A plausible mechanism for the catalytic cycle of the dicationic
((ꢀ)-sparteine)palladium-catalyzed enantioselective aldol reaction.
(
entries 8 and 9). The effects on the steric bulkiness were

4456
S. Kiyooka et al. / Tetrahedron Letters 47 (2006) 4453–4456
N
O
Pd
B
N
O
N
O
O
Pd
N
N
N
Pd
H
<
A
H
I (chair form)
II (boat form)
Scheme 4. The most vacant space A toward the background of (ꢀ)-sparteine and the preferential boat conformer for the transition state assembly at A.
1
As reported in the study using the H NMR experiment
under the improved practicable reaction conditions. The
reaction is effective even with a 1 mol % catalyst loading.
4
,5
of the reaction with BINAP, the singlet resonances at
.40 and 4.62 ppm, correlated to the vinyl methylene
4
protons of the O-bound palladium enolate, were also
1
observed in the H NMR spectra of the species in situ
Acknowledgment
formed from (sparteine)PdCl (1 equiv) and AgSbF (2
2
6
˚
equiv) in the presence of 3 A molecular sieves in
This work was supported by a Grant-in-Aid for Scien-
tific Research from Japan Society for the Promotion
of Science.
DMF-d . This observation reveals that the reaction with
7
(
ꢀ)-sparteine proceeds via a similar active intermediate
like that found in the reaction with BINAP. Both enan-
tioselective reactions can be presumably explained by
the same mechanism, as shown in Scheme 3. On the
basis of the 16-electron square-planar geometry, charac-
teristic of dicationic palladium complexes, we can esti-
mate an adequate transition state assembly leading to
the (3S)-configuration of the product aldol. The bottom
part is more open than the upper part of the N–Pd–N
plane, owing to the inherent steric bulkiness of (ꢀ)-spar-
teine, as depicted in Scheme 4. The A part, namely, the
right side of the bottom part, seemingly provides the
most suitable space available for the aldol condensation
process. The high enantioselectivity to S may be
achieved via a cyclic model, consisting of the palladium
enolate, pre-formed at the vacant A space, and the benz-
aldehyde, coordinated after substituting a solvent DMF,
in the square-plane containing the cationic Pd atom.
The bulky part of the sparteine near the palladium
center considerably affects the geometry of the palladium
enolate and allows trans orientation between the Pd
atom and the phenyl part with respect to its O–C bond.
In addition, the bulkiness also synchronously prevents
the approach of the phenyl part of the benzaldehyde
and leads to trans orientation between the Pd atom
and the phenyl part. Consequently, a boat-like con-
former (II) might be more preferential than a chair-like
one (I) as a cyclic model in the transition state assembly.
References and notes
1
2
. Modern Aldol Reactions; Mahrwald, R., Ed.; WILEY-
VCH: Weinheim, 2004.
. Slough, G. A.; Bergman, R. G.; Heathcock, C. H. J. Am.
Chem. Soc. 1989, 111, 938–949, and references cited
therein.
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1995, 60, 2648–2649, and references cited therein; Sode-
oka, M.; Tokunoh, R.; Miyazaki, F.; Hagiwara, E.;
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3
4
5
6
7
. Sodeoka, M.; Hamashima, Y. Bull. Chem. Soc. Jpn. 2005,
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8, 941–956.
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Tetrahedron Lett. 2006, 47, 3959–3962.
. Tietze, L. F.; Ila, H.; Bell, H. P. Chem. Rev. 2004, 104,
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151–4202.
3
4
0
0
8. I: 2,2 -Bis[(4S)-4-benzyl-2-oxazoline], II: 2,2 -methylene-
*
*
bis[(4R,5S)-4,5-diphenyl-2-oxazoline], and III: [R(R ,R )]-
(+)-2,2 -isopropylidenebis(4-benzyl-2-oxazoline)
purchased from Aldrich.
0
were
9
. Nesper, R.; Pregosin, P. S.; P u¨ ntener, K.; W o¨ rle, M. Helv.
Chim. Acta 1993, 76, 2239–2249.
0. Ferreira, E. M.; Stoltz, B. M. J. Am. Chem. Soc. 2001, 123,
725–7726; Mueller, J. A.; Jensen, D. R.; Sigmam, M. S.
J. Am. Chem. Soc. 2002, 124, 8202–8203; Trend, R. M.;
Stoltz, B. M. J. Am. Chem. Soc. 2004, 126, 4482–4483.
1. DMF (water content: 0.005%) was purchased from Kanto
Chemical and distilled (60–65 °C/20 mmHg) from CaH
prior to use.
1
1
7
In conclusion, (ꢀ)-sparteine was found to be quite suit-
able as a chiral bidentate ligand for the chiral dicationic
palladium-catalyzed enantioselective aldol reactions
2