Enantioselective aldol reaction of trimethoxysilyl enol ethers with aldehydes catalyzed by p-Tol-BINAP·AgF complex

Article abstract of DOI:10.1055/s-2001-9715

New catalytic asymmetric Mukaiyama-type aldol reaction using trimethoxysilyl enol ethers was achieved using p-Tol-BINAP·AgF complex as a catalyst. High syn- and enantioselectivities were obtained both from the E- and Z-silyl enol ethers.

Full text of DOI:10.1055/s-2001-9715

LETTER
69
Enantioselective Aldol Reaction of Trimethoxysilyl Enol Ethers with
Aldehydes Catalyzed by p-Tol-BINAP·AgF Complex
Akira Yanagisawa, Yoshinari Nakatsuka, Kenichi Asakawa, Hiromi Kageyama, Hisashi Yamamoto*
Graduate School of Engineering, Nagoya University, CREST, Japan Science and Technology Corporation (JST)
Chikusa, Nagoya 464-8603, Japan
Fax +81-52-789-3222; E-mail: yamamoto@cc.nagoya-u.ac.jp
Received 30 October 2000
Table 1 Asymmetric Aldol Reaction of Cyclohexanone-Derived
Abstract: New catalytic asymmetric Mukaiyama-type aldol reac-
tion using trimethoxysilyl enol ethers was achieved using p-Tol-BI-
NAP·AgF complex as a catalyst. High syn- and enantioselectivities
were obtained both from the E- and Z-silyl enol ethers.
Trimethoxysilyl Enol Ether with Benzaldehyde Catalyzed by Various
a
BINAP·AgF Complexes
OSi(OMe)3
+
chiral phosphine·AgF
O
OH
*
Key words: enantioselective aldol reaction, silyl enol ethers, alde-
hydes, BINAP·silver(I) complex, asymmetric catalysis
(10 mol%)
PhCHO
*
Ph
MeOH
The Mukaiyama aldol reaction is a favorite method for the
synthesis of -hydroxy carbonyl compounds. Although a
P(3,5-Me2C6H3)2
P(3,5-Me2C6H3)2
PR2
PR2
1
variety of chiral Lewis acid catalysts have been developed
for the asymmetric reaction of trialkylsilyl enol ethers or
ketene trialkylsilyl acetals with carbonyl compounds,1
most of those used are main-group metal (B, Zn, Sn, etc.)
compounds or first row-transition metal (Ti, Cu, etc.)
compounds, and the use of second or third row-transition
metal compounds such as silver catalysts has received lit-
,2
(S)-3,5-Xylyl-BINAP
(R)-p-Tol-BINAP (R = 4-MeC6H4)
R)-p-tBuC6H4-BINAP (R = 4-tBuC6H4)
(
3
,4
5
tle attention. In a previous paper, we showed a new cat-
alytic asymmetric Sakurai-Hosomi allylation reaction
using the p-Tol-BINAP·AgF complex. We describe here
a new example of catalytic asymmetric aldol condensa-
tion using trimethoxysilyl enol ethers and p-Tol-BI-
6
NAP·AgF complex (eq 1).
a
Unless otherwise noted, the reaction was carried out using chiral
phosphine·AgF complex (10 mol%), cyclohexanone-derived trime-
thoxysilyl enol ether (1 equiv), and benzaldehyde (1 equiv) in MeOH.
Isolated yield. Determined by H NMR analysis. The value corre-
OSi(OMe)3
O
OH
*
b
c
1
d
R2
cat. p-Tol-BINAP·AgF
4
R1
+ R CHO
R1
*
R4
sponds to the major diastereomer. Determined by HPLC analysis
CH3OH
R2 R3
e
R3
(Chiralcel OD-H, Daicel Chemical Industries, Ltd.). 5 mol% of the
catalyst was used.
Equation 1
The mechanism of the present catalytic reaction has not
been fully elucidated; however, the BINAP·AgF complex
is thought to behave as a chiral Lewis acid catalyst rather
than a silver enolate based on the following NMR results.
When trimethoxysilyl enol ether of cyclohexanone was
treated with an equimolar mixture of (R)-BINAP·AgF
Using various BINAP derivatives, we studied the enanti-
oselectivity of this process; yields, syn/anti ratios, and
enantiomeric excesses of the products obtained by the re-
action of cyclohexanone-derived trimethoxysilyl enol
ether with benzaldehyde under the influence of 10 mol%
of various BINAP derivative-AgF complexes in MeOH
which are shown in Table 1. Among the BINAP deriva-
complex and DMF in CD OD at room temperature, peaks
3
of the silyl enol ether disappeared and a set of new peaks
ascribable to the 1-cyclohexenyl group appeared, while
7
tives examined, (R)-p-Tol-BINAP was found to provide
peaks of (MeO) SiF and cyclohexanone were not ob-
3
the most satisfactory result (entry 3). Use of (R)-p-
served at all. These observations are a positive proof that
none of the silver enolate was generated. Furthermore, we
found that when an (R)-BINAP was added to an
7
tBuC H -BINAP resulted in a higher yield with slightly
6
4
better ee, although the syn/anti ratio decreased (entry 5).
equimolar amount of AgF in CD OD at room tempera-
3
ture, a considerable amount of 2:1 complex [FAB- and
Synlett 2001, No. 1, 69–72 ISSN 0936-5214 © Thieme Stuttgart · New York

7
0
A. Yanagisawa et al.
LETTER
+
ESI-MS: m/z 1353 (M - F)] was formed accompanied by
a 1:1 complex (eq 2). The 2:1 complex was found to have
no reactivity in the present aldol reaction. The formation
of the undesired 2:1 complex, however, can be suppressed
to some extent by introducing a bulky substituent at the
para-position of the phenyl groups of BINAP. Indeed,
Table 2 Diastereo- and Enantioselective Aldol Reaction of Trime-
thoxysilyl Enol Ethers with Aldehydes Catalyzed by (R)-p-Tol-BI-
NAP·AgF Complex
a
(
R)-p-Tol-BINAP and (R)-p-tBuC H -BINAP provided
6 4
higher chemical yields than did (R)-BINAP (compare en-
tries 1, 3, and 5 in Table 1).
PPh2
+
AgF
CD3OD, RT
PPh2
1:1 mixture
Ph
P
Ph
P
Ph
P
PhPh
Ph
AgF
Ph
0.5
Ag
P
P
P
F
PhPh
Ph
Ph
Ph
1:1 complex
2:1 complex
+
0.5 AgF
a
Unless otherwise specified, the reaction was carried out using (R)-
p-Tol-BINAP·AgF (10 mol%), trimethoxylsilyl enol ether (1 equiv),
Equation 2
b
c
and aldehyde (1 equiv) in MeOH at -78 °C for 4 h. Isolated yield.
1
d
Determined by H NMR analysis. The value corresponds to the ma-
jor diastereomer. Determined by HPLC analysis (Chiralcel OB-H or
Table 2 summarizes the results obtained for the reaction
of (E)- and (Z)-silyl enol ethers with various aldehydes
under the influence of 10 mol% of (R)-p-Tol-BINAP·AgF
in MeOH. All the reaction of cyclohexanone-derived (E)-
trimethoxysilyl enol ether resulted in remarkable syn- and
e
OD-H, Daicel Chemical Industries, Ltd.). The reaction was perfor-
f
med using 3 mol% of (R)-p-Tol-BINAP and 5 mol% of AgF. The
g
reaction was performed at -78 °C for 4 h, then at -40 °C for 4 h. The
reaction was performed using 1.2 mol% of (R)-p-Tol-BINAP and
h
2
mol% of AgF. The reaction was performed at -78 °C for 2 h, then
enantioselectivities with aromatic aldehydes (entries 1-
i
1
at -40 °C for 2 h, and finally at -20 °C for 2 h. Determined by H
8
6
). We found that a 0.6:1 mixture of (R)-p-Tol-BINAP
NMR analysis of the MTPA ester of the product.
and AgF gave the desired 1:1 complex without formation
of the unreactive 2:1 complex, and thus, when the amount
of (R)-p-Tol-BINAP was reduced to 3 mol%, the aldol
product was still formed in high yield without any loss of
optical purity even at 40 °C (entries 2 and 3). However,
use of less than 2 mol% of the catalyst resulted in a lower
yield and ee (entry 4). In contrast, tert-butyl ethyl ketone-
derived (Z)-silyl enol ether gave the syn product almost
exclusively with high enantioselectivity up to 97% ee in
combination not only with aromatic aldehydes but also
with , -unsaturated aldehyde (entries 7-11). In the reac-
tion with cinnamaldehyde, only a 1,2-adduct was ob-
served (entry 11).
that trimethoxysilyl enol ethers reacted with aldehydes,
syn-selectively irrespective of the E/Z stereochemistry in
the presence of BINAP·AgF catalyst, the cyclic transition-
state structures A and B shown in Figure can be postulated
as models for the aldol reaction. In these models, the BI-
NAP·AgF complex coordinates as a chiral Lewis acid to
both an aldehyde and a silyl enol ether to form a six-mem-
bered cyclic structure, which is further stabilized by the
adjacent four-membered ring formed by AgF and tri-
methoxysiloxy group.10 Thus, from the E-enol ether, the
syn-aldol adduct can be selectively obtained via a boat-
like transition-state structure A, whereas model B pos-
From the aforementioned NMR results and the facts that
9
AgF obviously activated trimethoxysilyl enol ethers and
H
P
P
OH
O
H
P
P
R1
H
Ag
Ag
R3
O
F
R3
R1
R3
F
O
O
R2
Si(OMe)3
R2
syn
H
O
Si(OMe)3
E
Z
R1
A (boat form)
R2
B (chair form)
Figure 1 Probable Cyclic Transition-state Structures
Synlett 2001, No. 1, 69–72 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Enantioselective Aldol Reaction of Trimethoxysilyl Enol Ethers
71
sessing a chair conformation connects the Z-enol ether to of the syn isomer (87% ee): [ ]25 = +109.5 (c = 1.0,
D
the syn product. These models are different from those CHCl ); elemental analysis calcd for C H O : C 76.44,
3
13 16
2
proposed for asymmetric allylation by allylic H 7.90; found: C 76.10, H 8.23. Other physical and spec-
5
1
13
trimethoxysilanes which are anticipated to proceed via tral data (TLC, IR, H NMR, and C NMR) were identical
six-membered cyclic transition-state structures including with those in the literature.1
a BINAP-coordinated allylic silver. The difference in
1b,14
structure is probably due to whether or not the transmetal-
lation to allylic silvers or silver enolates occurs prior to
Acknowledgement
condensation with aldehydes.
We thank Takasago International Corporation for its generous gift
of (R)-p-Tol-BINAP and (S)-3,5-Xylyl-BINAP. A.Y. also acknow-
ledges financial support from the Naito Foundation and Takeda Sci-
ence Foundation.
In summary, we have demonstrated a novel example of
asymmetric Mukaiyama aldol reaction with trimethoxysi-
lyl enol ethers catalyzed by the p-Tol-BINAP·AgF com-
plex. We previously showed that BINAP·AgOTf complex
is a good catalyst for the asymmetric aldol reaction of tri-
References and Notes
1
1
alkyltin enolates, however, the reaction has the disad-
vantage of requiring the use of toxic trialkyltin
compounds, and silyl enol ethers do not react with alde-
hydes in the presence of this chiral silver(I) catalyst. Main
features of our new process are: (1) the procedure can be
performed without any difficulty employing readily avail-
able chemicals and can provide various optically active
(1) Review: Gennari, C. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon
Press: Oxford, U.K., 1991; Vol. 2, p 629.
(
2) Reviews for catalytic asymmetric aldol reactions using silyl
enol ethers or ketene silyl acetals: (a) Bach, T. Angew. Chem.
Int. Ed. Engl. 1994, 33, 417. (b) Hollis, T. K.; Bosnich, B. J.
Am. Chem. Soc. 1995, 117, 4570. (c) Braun, M. In Houben-
Weyl: Methods of Organic Chemistry; Helmchen, G.,
-
hydroxy ketones with high enantioselectivity up to 97%
Hoffmann, R. W., Mulzer, J., Schaumann, E., Eds.; Georg
Thieme Verlag: Stuttgart, 1995; Vol. E 21, p 1730. (d) Nelson,
S. G. Tetrahedron: Asymmetry 1998, 9, 357. (e) Gröger, H.;
Vogl, E. M.; Shibasaki, M. Chem. Eur. J. 1998, 4, 1137.
ee; (2) remarkable syn selectivity is observed for the reac-
tion independent of the E/Z stereochemistry of the silyl
enol ethers; (3) this process is less damaging to the envi-
ronment since less toxic trimethoxysilyl enol ether and
MeOH are used as a reagent and solvent, respectively.
Further work is now in progress on the catalytic aldol re-
action and the detailed reaction mechanism.
(
f) Mahrwald, R. Chem. Rev. 1999, 99, 1095. (g) Arya, P.;
Qin, H. Tetrahedron 2000, 56, 917. (h) Machajewski, T. D.;
Wong, C.-H. Angew. Chem. Int. Ed. Engl. 2000, 39, 1353.
3) Chiral rhodium catalysts: (a) Reetz, M. T.; Vougioukas, A. E.
Tetrahedron Lett. 1987, 28, 793. Chiral palladium catalysts:
(
(
6
b) Sodeoka, M.; Ohrai, K.; Shibasaki, M. J. Org. Chem. 1995,
0, 2648. (c) Sodeoka, M.; Tokunoh, R.; Miyazaki, F.;
A representative experimental procedure is given by the
reaction of trimethoxysilyl enol ether of cyclohexanone
with benzaldehyde catalyzed by (R)-p-Tol-BINAP·AgF
complex (entry 3 in Table 1 and entry 1 in Table 2). A
mixture of AgF (13.0 mg, 0.102 mmol) and (R)-p-Tol-BI-
NAP (67.9 mg, 0.100 mmol) was dissolved in dry MeOH
6 mL) under argon atmosphere and with direct light ex-
cluded, and stirred at 20 °C for 10 min. To the resulting
solution were added dropwise benzaldehyde (100 µL,
.98 mmol) and (1-cyclohexenyloxy)trimethoxysilane
Hagiwara, E.; Shibasaki, M. Synlett 1997, 463. (d) Sodeoka,
M.; Shibasaki, M. Pure Appl. Chem. 1998, 70, 414. (e) Fujii,
A.; Sodeoka, M. Tetrahedron Lett. 1999, 40, 8011. See also:
(f) Hagiwara, E.; Fujii, A.; Sodeoka, M. J. Am. Chem. Soc.
1
998, 120, 2474. (g) Fujii, A.; Hagiwara, E.; Sodeoka, M. J.
Am. Chem. Soc. 1999, 121, 5450. Chiral platinum catalysts:
h) Fujimura, O. J. Am. Chem. Soc. 1998, 120, 10032.
(
(
(
4) Recent examples of direct catalytic asymmetric aldol
reactions of aldehydes with unmodified ketones are also
noteworthy: (a) Yamada, Y. M. A.; Yoshikawa, N.; Sasai, H.;
Shibasaki, M. Angew. Chem. Int. Ed. Engl. 1997, 36, 1871.
(b) Yamada, Y. M. A.; Shibasaki, M. Tetrahedron Lett. 1998,
0
(
1
2
220.4 mg, 1.01 mmol) successively at 78 °C. After be-
ing stirred for 4 h at this temperature, the mixture was
treated with brine (2 mL) and solid KF (ca. 1 g) at ambient
temperature for 30 min. The resulting precipitate was fil-
tered off by a glass filter funnel filled with Celite and sil-
ica gel. The filtrate was dried over Na SO4 and
3
9, 5561. (c) Yoshikawa, N.; Yamada, Y. M. A.; Das, J.;
Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1999, 121, 4168.
d) List, B.; Lerner, R. A.; Barbas, C. F., III. J. Am. Chem. Soc.
000, 122, 2395. (e) Notz, W.; List, B. J. Am. Chem. Soc.
2000, 122, 7386.
(
2
®
2
concentrated in vacuo after filtration. The residual crude
product was purified by column chromatography on silica
gel (1:5 ethyl acetate/hexane as the eluant) to afford a
mixture of aldol adducts (156.5 mg, 78% yield) as white
solids. The syn/anti ratio was determined to be 84/16 by
H NMR analysis. The enantioselectivities of the syn and
anti isomers were determined to be 87% ee and 48% ee,
respectively, by HPLC analysis using a chiral column
(5) Yanagisawa, A.; Kageyama, H.; Nakatsuka, Y.; Asakawa, K.;
Matsumoto, Y.; Yamamoto, H. Angew. Chem. Int. Ed. 1999,
38, 3701.
(
6) Yamagishi and co-workers independently examined the
BINAP·silver(I)-catalyzed asymmetric Mukaiyama aldol
reaction using trimethylsilyl enol ethers and found that the
1
reaction was accelerated by BINAP·AgPF in DMF
6
containing a small amount of water to give the aldol product
with high enantioselectivity: Ohkouchi, M.; Yamaguchi, M.;
Yamagishi, T. Enantiomer 2000, 5, 71.
(
Chiralcel OD-H, Daicel Chemical Industries, Ltd., hex-
ane/i-PrOH = 9/1, flow rate = 0.5 mL/min): tsyn-minor
13.4 min, tsyn-major = 14.5 min, tanti-major = 16.1 min
2S,1’R), tanti-minor = 22.2 min (2R,1’S). The absolute con-
figurations of the syn isomers are not known. Spectral data
(
7) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.;
Kumobayashi, H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J.
Org. Chem. 1986, 51, 629. (R)- and (S)-p-Tol-BINAP are
commercially available (AZmax).
=
(
Synlett 2001, No. 1, 69–72 ISSN 0936-5214 © Thieme Stuttgart · New York

7
2
A. Yanagisawa et al.
LETTER
(
8) Aliphatic aldehydes were inactive under the standard reaction
conditions. For example, the reaction with hydrocinnam-
aldehyde gave the aldol product in less than 1% yield at -78 °C
for 4 h.
(12) The trimethoxysilyl enol ether of cyclohexanone was prepared
by 1,4-hydrosilylation of 2-cyclohexen-1-one with
1
3
(MeO) SiH catalyzed by (Ph P) RhCl or (Ph P) RhH. Tert-
3
3
3
3
4
butyl ethyl ketone-derived trimethoxysilyl enol ether was
prepared by treating the ketone with LDA in ether followed by
(
9) The aldol product was obtained only in 3% yield when the
reaction of (1-cyclohexenyloxy)trimethoxysilane with
benzaldehyde was carried out in the presence of 10 mol% of
silylation with (MeO) SiCl.
3
(13) (a) Ojima, I.; Kogure, T. Organometallics 1982, 1, 1390.
(b) Zheng, G. Z.; Chan, T. H. Organometallics 1995, 14, 70.
(14) (a) Juaristi, E.; Beck, A. K.; Hansen, J.; Matt, T.;
Mukhopadhyay, T.; Simson, M.; Seebach, D. Synthesis 1993,
1271. (b) Denmark, S. E.; Winter, S. B. D.; Su, X.; Wong, K.-
T. J. Am. Chem. Soc. 1996, 118, 7404. (c) Denmark, S. E.;
Wong, K.-T.; Stavenger, R. A. J. Am. Chem. Soc. 1997, 119,
2333.
(
R)-BINAP·AgOTf in THF at -78 °C ~ r.t. for 12 h.
(
10) Bottoni, Tagliavini, and coworkers have suggested similar
eight-membered cyclic transition-state models for BF3-
promoted addition of allylsilanes to aldehydes: Bottoni, A.;
Costa, A. L.; Tommaso, D. D.; Rossi, I.; Tagliavini, E. J. Am.
Chem. Soc. 1997, 119, 12131.
(
11) (a) Yanagisawa, A.; Matsumoto, Y.; Nakashima, H.;
Asakawa, K.; Yamamoto, H. J. Am. Chem. Soc. 1997, 119,
9319. (b) Yanagisawa, A.; Matsumoto, Y.; Asakawa, K.;
Yamamoto, H. J. Am. Chem. Soc. 1999, 121, 892.
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