(μ-Hydroxo)-platinum complex-catalyzed enantioselective aldol reaction of aldehydes with 1-methoxy-2-methyl-1-(trimethylsilyloxy)propene in DMF

Article abstract of DOI:10.1016/j.tetlet.2008.01.041

[((R)-BINAP)Pt(μ-OH)]₂·2OTf catalyzed the enantioselective aldol reaction of aldehydes with 1-methoxy-2-methyl-(1-trimethylsilyloxy)propene at room temperature in dry DMF in high yields with enantioselectivity up to 92%. This is a versatile exa

Full text of DOI:10.1016/j.tetlet.2008.01.041

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1589–1592
(l-Hydroxo)-platinum complex-catalyzed enantioselective aldol
reaction of aldehydes with 1-methoxy-2-methyl-1-
(trimethylsilyloxy)propene in DMF
Syun-ichi Kiyooka *, Satoshi Matsumoto, Masafumi Kojima, Kazuyuki Sakonaka,
Hirofumi Maeda
Department of Materials Science, Faculty of Science, Kochi University, Akebono-cho, Kochi 780-8520, Japan
Received 3 December 2007; revised 3 January 2008; accepted 10 January 2008
Available online 15 January 2008
Abstract
[((R)-BINAP)Pt(l-OH)]2ꢀ2OTf catalyzed the enantioselective aldol reaction of aldehydes with 1-methoxy-2-methyl-(1-trimethyl-
silyloxy)propene at room temperature in dry DMF in high yields with enantioselectivity up to 92%. This is a versatile example of the
catalytic enantioselective aldol reaction using a silyl ketene acetal promoted by (l-hydroxo)-platinum complexes under mild conditions.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Enantioselective aldol reaction; (l-Hydroxo)-platinum complex
Although late transition metal complex-catalyzed
enantioselective aldol reactions are expected for industrial
processes, the effective catalytic systems have not been
developed yet.1 The preceding results were quite limited
to group 10 metal-catalyzed reactions (palladium2 and
platinum3). We have recently reported a practically simpli-
fied reaction procedure available for the dicationic (BIN-
AP)- and (sparteine)-palladium-catalyzed aldol reactions
with 1-phenyl-(1-trimetylsilyloxy)ethene, in situ providing
an active catalyst from ((R)-BINAP)- or ((ꢁ)-sparteine)-
in dry DMF.4 However, the palladium-catalyzed aldol
reactions do not work well with silyl ketene acetals, which
are advantageous for the sequential aldol strategy in con-
structing 1,3-diol frameworks in natural products because
it allows preparation of the next aldehyde by the direct
reduction of the ester moiety in the aldol products.5 On
the other hand, a silyl ketene acetal, 1-methoxy-2-methyl-
(1-trimethylsilyloxy)propene 1, underwent the platinum-
catalyzed aldol reaction as reported merely by Fujimura,3
where an active platinum cationic species was prepared
in situ from a Pregosin complex,6 3,5-di-tert-butylsalicyl-
aldehyde-chelating (BINAP)platinum(II) complexes, accord-
ing to the Strukul method7 by treatment with HOTf and
lutidine in CH2Cl2. The in situ formed catalyst (5 mol %
loading) led the aldol reaction of benzaldehyde with 1 in
CH2Cl2 at ꢁ25 °C (21 h) to give the corresponding aldol
in a quantitative yield with 59% ee, although high enantio-
selectivity was achieved in the reaction with linear
aliphatic aldehydes. The valid structure of the active
platinum catalyst has not been elucidated yet. In addition,
alternative cationic catalysts can also be formed in situ
from (BINAP)PtCl2 and AgX, but the behavior is different
from the above in some reactions.8 It is obvious that the
catalytic reaction with isolated complexes is advantageous
more than that with in situ formed6 catalysts or catalyst
precursors with regard to the simplicity of handling cata-
lysts and the reproducibility of the results.9 Then, we inves-
tigated the platinum-catalyzed enantioselective aldol
reaction by utilizing the known platinum complexes as
˚
PdCl2 and AgSbF6 in the presence of 3 A molecular sieves
*
Corresponding author. Tel.: +81 88 884 8295; fax: +81 88 844 8359.
E-mail address: kiyooka@cc.kochi-u.ac.jp (S. Kiyooka).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.041

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S. Kiyooka et al. / Tetrahedron Letters 49 (2008) 1589–1592
the starting catalysts. We disclose herein the (l-hydroxo)-
platinum complex-catalyzed enantioselective aldol reaction
with 1 in DMF. Some platinum complexes furnished with
BINAP auxiliary are known: [((R)-BINAP)Pt(l-OH)]2ꢀ
2BF4 was used for enantioselective Baeyer–Villiger oxida-
tions of cyclic ketones with hydrogen peroxide7b and
[((R)-BINAP)Pt(H2O) (OTf)]ꢀOTf was provided for ligand
exchange reactions.10 Thus, we first chose l-hydroxo-
platinum complex 211 and monoaqua-platinum complex
312 as the catalysts having the same counter anion for the
platinum-catalyzed enantioselective aldol reaction, as
depicted in Figure 1.
described in Ref. 13. The enantioselectivity in the reactions
using 2 was remarkably affected by theꢁ counter anions
(entries 1, 2, 3, 5): The two anions, BF4 and PF6ꢁ, are
prone to give relatively lower % ee.14 The optimized reac-
tion (rt, 12 h, DMF) in the presence of ((R)-BINAP)-2-
OTf (5 mol % on Pt) resulted in a high yield (86%) with a
high enantioselectivity (84% ee). When ((R)-BINAP)-2-
SbF6 was used in CH2Cl2, the enantioselectivity was con-
siderably reduced (entry 4). Apparently, DMF is suitable
for the reaction as likely emphasized in the case of the cor-
responding Pd-catalyzed reaction.2,4 However, the quantity
of DMF also affected both the % yield and the % ee:
Increasing from 0.3 mL to 1.5 mL of DMF seriously
reduced them on the 1 mmol scale reaction (entry 6). More-
over, lower loading of the catalyst (1 mol %) could not
The results are shown in Table 1 on the platinum com-
plex-catalyzed enantioselective aldol reaction of benzalde-
hyde with 1 in DMF; the experimental details are
Ph
P
Ph
P
Ph
Ph
Ph
Pt
Ph
Ph
H
O
OTf
+
P
-
-
Pt
OTf
Pt
Ph
2OTf
H
P
Ph
P
Ph
P
O
H
O
H
Ph
Ph
μ-hydroxo complex 2
monoaqua complex 3
O
P(Ph)
P(Tol)
P(Tol)
P(Xylil)
O
O
O
P(Ph)
P(Ph)
2
2
2
2
2
P(Ph)
P(Xylil)
2
2
2
(R)-H -BINAP
(R)-SEGPHOS
(S)-Tol-BINAP
(S)-Xylyl-BINAP
8
Fig. 1. Structures of platinum complexes and chiral auxiliary used in this study.
Table 1
Platinum complex-catalyzed enantioselective aldol reaction of benzaldehyde with 1-methoxy-2-methyl-(1-trimethylsilyloxy)propene 1 in DMFa
a All reactions were carried out at rt with stirring under Ar: benzaldehyde (1.0 mmol), 1 (2.0 mmol), Pt complex (5 mol %) in DMF (0.3 mL), as described
in Ref. 13.
b
Isolated yields.
c
The % ee values were determined with HPLC (Daicel Chiralcel OD-H).
CH2Cl2 was used.
DMF (1.5 mL) was used.
Pt (1 mol %) was used.
d
e
f
g
The opposite configuration.

S. Kiyooka et al. / Tetrahedron Letters 49 (2008) 1589–1592
1591
maintain the selectivity obtained in the 5 mol % reaction
(entry 7). With respect to the above results on DMF, the
transition assembly determining the selectivity is supposed
to be susceptible to the role of the solvent DMF. Structural
effects of chiral modified BINAP ligands were examined in
place of BINAP under the same conditions. Only (R)-SEG-
PHOS was capable of providing the aldol product of nearly
the same selectivity as (R)-BINAP, and the other three
ligands were not favored (entries 8–11). The complex,
((R)-BINAP)-3-OTf, underwent the reaction under similar
conditions to give the aldol in a moderate yield with a
moderate % ee but how the structure of the starting cata-
lysts influences the reaction rate and selectivity is unclear
(entry 12).
Table 2 illustrates the structural effects of the substrate-
aldehydes on reactivity and selectivity in the dicationic
((R)-BINAP)-2-OTf-catalyzed enantioselective aldol reac-
tion with 1 which was carried out with the typical proce-
dure in DMF. Both aromatic aldehydes having electron-
attracting and -releasing substituents gave comparable
results on the yield and % ee with benzaldehyde. A typical
primary aliphatic aldehyde, hydrocinnamaldehyde, led to
superior enantioselectivity. As long as 1 is used as a silyl
nucleophile, ((R)-BINAP)-2-OTf plays a reliable role in
the platinum-catalyzed enantioselective aldol reaction over
a wide range of aldehydes, having a phenyl functional
group. A linear aliphatic aldehyde, heptanal, underwent
the reaction in a low yield but a high % ee (entry 7) while
secondary aldehydes did not work under the reaction
conditions in analogy with Fujimura’s case.
In conclusion, our practically simplified mild procedure,
starting with a known complex ((R)-BINAP)-2-OTf, turned
out to be available for the platinum-catalyzed enantioselec-
tive aldol reaction of a variety of aldehydes with a silyl
ketene acetal 1. Studies with other silyl ketene acetals for
acyclic stereoselection accompanying high enantioselectivi-
ty are in progress. Mechanistic studies of whether the reac-
tion in question proceeds in a Lewis acid catalyzed manner
or through a pathway involving platinum enolates are also
under investigation.
Acknowledgments
We thank the Takasago International Corporation for
the generous gift of (R)-SEGPHOS and (R)-H8-BINAP.
This work was supported by a Grant-in-Aid for Scien-
tific Research from Japan Society for the Promotion of
Science.
References and notes
Table 2
[((R)-BINAP)Pt(l-OH)]2-2OTf-catalyzed enantioselective aldol reaction
of a variety of aldehydes with 1a
1. Modern Aldol Reactions; Mahrwald, R., Ed.; Wiley-VCH: Weinheim,
2004.
Me
Me
OTMS
OMe
((R)-BINAP)-2-OTf (5 mol%)
2. (a) Sodeoka, M.; Ohrai, K.; Shibasaki, M. J. Org. Chem. 1995, 60,
2648; (b) Sodeoka, M.; Tokunoh, R.; Miyazaki, F.; Hagiwara, E.;
Shibasaki, M. Synlett 1997, 463; (c) Sodeoka, M.; Hamashima, Y.
Bull. Chem. Soc. Jpn. 2005, 78, 941.
RCHO +
DMF, rt, 12 h
1
3. Fujimura, O. J. Am. Chem. Soc. 1998, 120, 10032.
TMSO
R
O
HO
O
4. (a) Kiyooka, S.-i.; Hosokawa, S.; Tsukasa, S. Tetrahedron Lett. 2006,
47, 3959; (b) Kiyooka, S.-i.; Takeshita, Y.; Tanaka, Y.; Higaki, T.;
Wada, Y. Tetrahedron Lett. 2006, 47, 4453.
5. Iterative enantioselective aldol reactions using silyl ketene acetals for
constructing 1,3-polyols. An example: Kiyooka, S.-i.; Shahid, K. A.;
Goto, F.; Okazaki, M.; Shuto, Y. J. Org. Chem. 2003, 68, 7967.
6. Anktin, C.; Pregosin, P. S.; Bachechi, F.; Mura, P.; Zambonelli, I. J.
Organomet. Chem. 1981, 222, 175.
7. (a) Gusso, A.; Baccin, C.; Pinna, F.; Struckul, G. Organometallics
1994, 13, 3442; (b) Strukul, G.; Varagnolo, A.; Pinna, F. J. Mol.
Catal. A: Chem. 1997, 117, 413; (c) Paneghetti, C.; Gavagnin, R.;
Pinna, F.; Strukul, G. Organometallics 1999, 18, 5057; (d) Pignat, K.;
Vallotto, J.; Pinna, F.; Strukul, G. Organometallics 2000, 19, 5160.
8. Enantioselective Baeyer–Villiger oxidation: Ref. 7b and enantioselec-
tive Diels–Alder reaction: Ghosh, A. K.; Matsuda, H. Org. Lett. 1991,
1, 2157.
H+
Ph
R
Ph
Me Me
Me Me
4b~g
Entry
1
Aldehydes
Products
Yields (%)
% ee
81
4b
82
Me
CHO
2
3
4
4c
4d
4e
89
89
92
82
79
82
CHO
NO2
CHO
CHO
9. Unpublished results, Kiyooka, S.-i.; Matsumoto, S.: The dicationic
species in situ formed from ((S)-BINAP)PtCl2 and AgPF6 in the
˚
presence of 3 A molecular sieves, according to the procedure used in
CHO
CHO
5
6
4f
77
72
the Pd enolate studies (Ref. 4), underwent the enantioselective aldol
reaction in a good performance on yield and enantioselectivity.
10. Stang, P. T.; Olenyuk, B.; Arif, A. M. Organometallics 1995, 14, 5281.
11. [((R)-BINAP)Pt(l-OH)]2ꢀ2OTf was prepared according to the syn-
thetic procedure for the corresponding BF4 congener reported by
4g
4h
82
92
90
Strukul (Ref. 7b): 31P NMR (160 MHz, CDCl3) d 3.64 (JPtꢁP
=
7
23b
CHO
3625 Hz).
a
The reaction was carried out according to the typical procedure
described in Ref. 13.
12. [((R)-BINAP)Pt(H2O)(OTf)]ꢀOTf was prepared according to the
procedure of Stang (Ref. 10): 31P NMR (160 MHz, CDCl3) d 2.71
(JPtꢁP = 4020 Hz).
b
The reaction time was 24 h.

1592
S. Kiyooka et al. / Tetrahedron Letters 49 (2008) 1589–1592
13. A typical procedure (5 mol % catalytic reaction) is as follows: To a
mixture of [((R)-BINAP)Pt(l-OH)]2ꢀ2OTf (49 mg, 0.025 mmol:
0.05 mmol on Pt) in dry DMF (0.3 mL) was added silyl nucleophile
1 (405 lL, 2.0 mmol) at rt under Ar. After the solution was stirred at
room temperature for 10 min, benzaldehyde (102 lL, 1.0 mmol) was
added. The solution was stirred for 12 h. The formation of the
silylated aldol product was checked by the use of the corresponding
spot (Rf, 0.70) on TLC (20% AcOEt/n-hexane). The reaction was
quenched upon 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 (20 mL ꢂ 2). The organic layer was dried over
anhydrous MgSO4. The solvent was evaporated in vacuo to give a
crude residue. The crude residue was purified by flash column
chromatography (SiO2) (10% AcOEt/n-hexane) to give 178 mg in a
86% yield. 1H NMR (400 MHz, CDCl3) d 1.11 (s, 3H), 1.15 (s, 3H),
2.17 (s, 3H), 3.08 (d, J = 4.16 Hz, 1H), 3.73 (s, 3H), 4.90 (d,
J = 4.16 Hz, 1H), 7.35–7.28 (m, 5H). The optical purity of the
Komura, M.; Matsuo, H.; Nakano, M. J. Org. Chem. 1991, 56, 2276.
The reported data of 4a: Kobayashi, S.; Ishitani, H.; Yamashita, Y.;
Ueno, M.; Shimizu, H. Tetrahedron 2001, 57, 861: Zirconium-
catalyzed enantioselective aldol reaction, (S)-isomer of 97% ee: ½aꢃD
25
+5.70 (c 2.49, MeOH). Fu, F.; Teo, Y.-C.; Loh, T.-P. Tetrahedron
Lett. 2006, 47, 4267: Indium-catalyzed enantioselective aldol reaction,
(S)-isomer of 64% ee: [a]D +13.43 (c 8.43, CH2Cl2). The enantiomeric
excesses in Tables 1 and 2 were determined by HPLC analysis
employing a DAICEL CHIRALCEL OD-H and DJ-H columns: Rf
values (flow rate, 1 mL/ min) of the products; 4a (OD-H, 0.7%
2-propanol/n-hexane) t1 = 60 min (major) and t2 = 66 min (minor):
(OJ-H, 2% 2-propanol/n-hexane) t1 = 20 min (major) and t2 = 27 min
(minor); 4b (OD-H, 1% 2-propanol/n-hexane) t1 = 29 min (major)
and t2 = 47 min (minor); 4c (OD-H, 5% 2-propanol/n-hexane)
t1 = 30 min (major) and t2 = 38 min (minor); 4d (OD-H, 5% 2-pro-
panol/n-hexane) t1 = 34 min (major) and t2 = 47 min (minor); 4e
(OD-H, 1% 2-propanol/n-hexane) t1 = 101 min (major) and
t2 = 134 min (minor); 4f (OD-H, 1% 2-propanol/n-hexane) t1 =
63 min (major) and t2 = 92 min (minor); 4g (OD-H, 2% 2-propanol/
n-hexane) t1 = 19 min (major) and t2 = 35 min (minor); 4h
(OD-H, 0.5% 2-propanol/n-hexane) t1 = 9 min (major) and t2 =
12 min (minor).
product was determined by HPLC analysis with
a DAICEL
CHIRALCEL OD-H column to be 84% ee. The optical rotation
22
was measured to be ½aꢃD +21.50 (c 2.0, CH2Cl2). Although the
absolute configuration of the product 4a was not reported in Ref. 3,
we decided it with the other products as follows: The absolute
configurations were assigned in comparison with the authentic
samples, which were prepared by our chiral oxazaborolidinone-
catalyzed enantioselective aldol reactions: Kiyooka, S.-i.; Kaneko, Y.;
14. [((R)-BINAP)Pt(l-OH)]2ꢀ2BF4 has been used only once under similar
reaction conditions (ꢁ25 °C, CH2Cl2) but the reaction failed miser-
ably (27% yield, 16% ee) (Ref. 3).