Enantioselective aldol reaction of silyl ketene acetals promoted by a Lewis base-activated Lewis acid catalyst

Article abstract of DOI:10.1016/j.tetasy.2009.05.028

The enantioselective aldol reaction of a silyl ketene acetal was promoted by chiral phosphine oxide-activated tetrachlorosilane to afford the corresponding adduct in high yield with moderate enantioselectivity.

Full text of DOI:10.1016/j.tetasy.2009.05.028

Tetrahedron: Asymmetry 20 (2009) 1369–1370
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Tetrahedron: Asymmetry
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Enantioselective aldol reaction of silyl ketene acetals promoted by a Lewis
base-activated Lewis acid catalyst
a
a,
Yasushi Shimoda a, Teppei Tando a, Shunsuke Kotani b, , Masaharu Sugiura , Makoto Nakajima
*
*
a Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
b Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto 862-0973, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The enantioselective aldol reaction of a silyl ketene acetal was promoted by chiral phosphine oxide-acti-
vated tetrachlorosilane to afford the corresponding adduct in high yield with moderate
enantioselectivity.
Received 24 April 2009
Accepted 25 May 2009
Available online 29 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
in the presence of a stoichiometric amount of tetrachlorosilane
(Eq. 2) and a catalytic amount of chiral N-oxide. The reaction
The Lewis acid-catalyzed aldol reaction of silyl enol ethers, the
so-called Mukaiyama-type aldol reaction, is an important method
for constructing a C–C bond.1,2 Although various chiral metal com-
plexes have been used in enantioselective aldol reactions to afford
aldol adducts in high stereoselectivities, the emergence of Lewis
base-activated Lewis acid catalysis pioneered by Denmark is a re-
cent topic in this area.3 Upon coordination to a Lewis base, the cen-
tral atom in the Lewis acid (tetrachlorosilane) becomes more
electrophilic and generates a cationic species, which significantly
increases the Lewis acidity (Eq. 1). In this concept, Denmark realized
high stereoselectivities in the enantioselective aldol reactions of si-
lyl enol ethers and silyl ketene acetals by using catalytic amounts of
chiral phosphoramides as activators for stoichiometric amounts of
tetrachlorosilane.4 This catalytic system has been applied to a wide
range of asymmetric reactions, including allylation,5z addition of
isocyanides5b or silyl ketene imines5c and vinylogous aldol reac-
tions.5d However, the Lewis bases used in these reactions have been
restricted to chiral phosphoramides. In our pursuit to develop new
organocatalyses promoted by N-oxides or phosphine oxides,6,7 we
herein report enantioselective aldol reactions promoted by N-oxi-
des or phosphine oxide-activated tetrachlorosilane.
proceeded, but both the chemical yield and enantioselectivity were
OSi
Lewis base (10 mol%)
SiCl4 (1.2 equiv.)
OH
O
Me
ð2Þ
PhCHO
+
OR
Ph
OR
º
CH2Cl2, -78 C, 12 h
Me
Me Me
Table 1
Aldol reaction of silyl ketene acetals derived from methyl isobutyrate with
benzaldehyde
Entry
Lewis basec
R
Si
Yielda (%)
ee%b
1
2
3
4
5
6
7
8
BQNO
BINO
Me
Me
Me
Me
Me
Me
Et
TMS
TMS
TMS
TMS
TMS
TBDMS
TMS
TMS
48
67
96
98
79
98
93
49
0
17
52
7
46
30
48
28
BINAPO
DIOPO
SEGPHOSO
BINAPO
BINAPO
BINAPO
iPr
a
Isolated yields.
b
c
ee’s were determined by HPLC analysis using chiral column (Daicel chiralcel OJ).
BQNO: (S)-3,3-dimethyl-2,20-biquinoline N,N0-dioxide; BINO: (R)-1,10-biiso-
quinoline
N,N0-dioxide;
DIOPO:
2,3-O-isopropylidene2,3-dihydroxy-1,4-
bis(diphenylphosphino)butane dioxide; SEGPHOSO: (S)-5,50-bis(diphenylphos-
phino)-4,40-bibenzodioxole dioxide; BINAPO: (S)-2,20-bis(diphenylphosphino)-1,10-
binaphthalene dioxide.
ð1Þ
unsatisfactory (Table 1, entries 1 and 2). Next we employed chiral
phosphine oxide BINAP dioxide (BINAPO), and found that the reac-
tion proceeded smoothly to afford the aldol adduct with moderate
enantioselectivity (entry 3). Other phosphine oxides, such as SEG-
PHOS dioxide or DIOP dioxide, were tested (entries 4 and 5), but
BINAPO gave the best results.
2. Results and discussion
We initially examined the aldol reaction of benzaldehyde with
the trimethylsilyl ketene acetal derived from methyl isobutyrate
Using BINPO as the Lewis base catalyst, we then investigated
the aldol reactions of various silyl ketene acetal derivatives of
isobutyrate. tert-Butyldimethylsilyl enol ether gave the adduct in
high yield, but with lower enantioselectivity (entry 6). Increasing
* Corresponding authors.
E-mail addresses: kotani@gpo.kumamoto-u.ac.jp (S. Kotani), nakajima@gpo.
kumamoto-u.ac.jp (M. Nakajima).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.05.028

1370
Y. Shimoda et al. / Tetrahedron: Asymmetry 20 (2009) 1369–1370
Table 2
Acknowledgement
Aldol reaction of benzaldehydes with TMS ketene acetal derived from methyl
isobutyrate
This work was supported by a Grant-in-Aid for Scientific Re-
search on Priority Areas ‘Advanced Molecular Transformations of
Carbon Resources’ from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
OTMS
BINAPO (10 mol%)
SiCl4 (1.2 equiv.)
OH
O
Me
RCHO +
(3)
OMe
OMe
Ph
º
CH2Cl2, -78 C, 12 h
Me
Me Me
Entry
R
Yielda (%)
96
92
98
79
83
12c
0
ee, % (conf)b
References
1
2
3
4
5
6
7
Ph
4-BrC6H4
52 (R)
49
62 (R)
67 (R)
35 (R)
0
1. For recent reviews on enantioselective aldol reaction, see: (a) Nelson, S. G.
Tetrahedron: Asymmetry, 1998, 9, 357–389; (b) Gröger, H.; Vogl, E. M.;
Shibasaki, M. Chem. Eur. J. 1998, 4, 1137–1141; (c) Mahrwald, R. Chem. Rev.
1999, 99, 1095–1120; (d) Machajewski, T. D.; Wong, C.-H. Angew. Chem., Int. Ed.
2000, 39, 1352–1374; (e) Palomo, C.; Oiarbide, M.; García, J. M. Chem. Soc. Rev.
2004, 33, 65–75.
2. For recent acid catalyses, see: (a) Hamada, T.; Manabe, K.; Ishikawa, S.;
Nagayama, S.; Shiro, M.; Kobayashi, S. J. Am. Chem. Soc. 2003, 125, 2989–2996;
(b) Saito, S.; Yamamoto, H. Acc. Chem. Res. 2004, 37, 570–579; (c) Akiyama, T.
Chem. Rev. 2007, 107, 5744–5758; (d) Yanagisawa, A.; Arai, T. Chem. Commun.
2008, 1165–1172; (e) Terada, M. Chem. Commun. 2008, 4097–4112.
3. (a) Denmark, S. E.; Wynn, T.; Beutner, G. L. J. Am. Chem. Soc. 2002, 124, 13405–
13407; (b) Denmark, S. E.; Beutner, G. L. Angew. Chem., Int. Ed. 2008, 47, 1560–
1638.
O
P
Ph
4-MeOC6H4
1-Naphthyl
2-Naphthyl
PhCH@CH
PhCH2CH2
Ph
Ph
P
O
—
Ph
BINAPO
a
Isolated yields.
b
ee’s were determined by HPLC analysis using chiral column (Daicel chiralcel OB,
OD or OJ). Absolute configurations were assigned by comparing to the literature
values of [ or retention time in HPLC.
a
]
D
4. (a) Denmark, S. E.; Beutner, G. L.; Wynn, T.; Eastgate, M. D. J. Am. Chem. Soc.
2005, 127, 3774–3789; (b) Denmark, S. E.; Chung, W. Angew. Chem., Int. Ed.
2008, 47, 1867–1892; (c) Denmark, S. E.; Lee, W. Chem. Asian J. 2008, 3, 327–
341.
c
1,4-Adduct was obtained in 88% yield.
5. (a) Denmark, S. E.; Wynn, T. J. Am. Chem. Soc. 2001, 123, 6199–6200; (b)
Denmark, S. E.; Fan, Y. J. Am. Chem. Soc. 2003, 125, 7825–7827; (c) Denmark, S.
E.; Wilson, T. W.; Burk, M. T.; Heemstra, J. R. J. Am. Chem. Soc. 2007, 129, 14864–
14865; (d) Denmark, S. E.; Beutner, G. L. J. Am. Chem. Soc. 2003, 125, 7800–7801.
6. For N-oxide or phosphine oxide-catalyzed reactions, see: (a) Nakajima, M.;
Saito, M.; Shiro, M.; Hashimoto, S. J. Am. Chem. Soc. 1998, 120, 6419–6420; (b)
Nakajima, M.; Yokota, T.; Saito, M.; Hashimoto, S. Tetrahedron Lett. 2004, 45,
61–64; (c) Nakajima, M.; Kotani, S.; Ishizuka, T.; Hashimoto, S. Tetrahedron Lett.
2005, 46, 157–159; (d) Kotani, S.; Hashimoto, S.; Nakajima, M. Synlett 2006,
1116–1118; (e) Sugiura, M.; Sato, N.; Kotani, S.; Nakajima, M. Chem. Commun.
2008, 4309–4311.
the bulkiness of the ester substituent decreased both the chemical
yields and enantiomeric excesses (entries 7 and 8).8
Table 2 summarizes the results obtained with various alde-
hydes and the trimethylsilyl ketene acetal of methyl isobutyrate.9
In every case, the benzaldehyde derivatives smoothly reacted to
produce adducts in high yield. While bromobenzaldehyde and 2-
naphthaldehyde gave lower selectivities, aldehydes with elec-
tron-donating or sterically congested groups gave better enanti-
oselectivities. The highest enantioselectivity was obtained in the
reaction of 1-naphthaldehyde. Although dihydrocinnamaldehyde
did not proceed under these conditions, cinnamaldehyde gave
the 1,4-adduct as the major product, exhibiting an interesting fea-
7. For related catalysis promoted by phosphine oxide-activated tetrachlorosilane,
see: Nakanishi, K.; Kotani, S.; Sugiura, M.; Nakajima, M. Tetrahedron 2008, 64,
6415–6419.
8. Both the E- and Z-enol ethers derived from methyl propionate gave the anti-
adduct as the major product (a mixture of E/Z = 1/7 gave the adduct with syn/
anti = 1/7; a mixture of E/Z = 2/1 gave the adduct with syn/anti = 1/6) with low
enantioselectivities. The stereochemical relationship between the E/Z geometry
and syn/anti selectivity suggests that the reaction mechanism involves acyclic
transition state, as proposed by Denmark (Ref. 3). Trimethylsilyl enol ether
derived from methyl acetate gave a racemic adduct in high yield.
9. Typical experimental procedure: tetrachlorosilane (0.060 mL, 1.2 equiv) in
dichloromethane (1 mL) was added to a solution of BINAPO (16.4 mg, 5 mol %),
benzaldehyde (53 mg) and silyl ketene acetal (0.23 mL, 2.0 equiv) in
dichloromethane over 1 h at ꢀ78 °C, and the mixture was stirred for 12 h at
the same temperature. The reaction was quenched with methanol, and the
mixture was extracted with ethyl acetate. The organic layer was washed with
brine, dried over sodium sulfate and evaporated. Purification by silica gel
column chromatography afforded the adduct (100 mg, 96%). The ee was
determined by chiral HPLC (Daicel chiralcel OJ).
ture of
a phosphine oxide catalyst compared to that of a
phosphoramide.10
3. Conclusion
In conclusion, we have demonstrated the effectiveness of
BINAPO as a catalyst for the aldol reaction of trimethylsilyl ketene
acetals. This is the first example using a phosphine oxide as a Lewis
base to activate a Lewis acid in enantioselective aldol reactions.
Further studies to enhance the enantioselectivity are currently in
progress.
10. Denmark has reported that the phosphoramide-catalyzed reaction of silyl
ketene acetal with cinnamaldehyde gives the aldol adduct in high yield (Ref. 3).
This is the first example of a conjugate addition of silyl ketene acetal promoted
by Lewis base-activated Lewis acid catalyst.