892
J. Am. Chem. Soc. 1999, 121, 892-893
Enantioselective Aldol Reactions Catalyzed by Tin
Methoxide and BINAP‚Silver(I) Complex
Akira Yanagisawa, Yukari Matsumoto, Kenichi Asakawa, and
Hisashi Yamamoto*
Graduate School of Engineering, Nagoya UniVersity
CREST, Japan Science and Technology Corporation (JST)
Chikusa, Nagoya 464-8603, Japan
ReceiVed August 10, 1998
Aldol reaction is a useful method of preparing â-hydroxy
carbonyl compounds and has attracted a great deal of attention
1
from synthetic organic chemists. Organotin(IV) enolates, existing
usually in O-Sn form and/or C-Sn form, are versatile nucleo-
philes which exhibit high reactivity toward various electrophiles
and can react with aldehydes in the absence or presence of a Lewis
Figure 1. A possible catalytic cycle.
2
acid; however, the aldol process has the disadvantage of requiring
the stoichiometric use of toxic trialkyltin compounds. We report
here the first example of the aldol reaction using a catalytic
amount of tin enolate and the asymmetric version with BINAP‚
silver(I) catalyst.
3
Reaction of enol acetate 1 (R ) CH ) with trialkyltin methoxide
is a convenient route to trialkyltin enolate 2 without the
3
contamination by lithium halides (Figure 1). Trialkyltin enolate
2
has been reported to undergo aldol condensation with aldehydes
4
even at low temperature. We envisaged that if the aldol product
could further react with a coexisting enol ester 1 to give the tin
3
enolate 2 and ester 4, the aldol reaction might proceed catalyti-
cally.
Figure 2. An alternative possible catalytic cycle.
Thus, we initially examined the exchange reaction between
cyclohexanone-derived enol acetate and tributyltin methoxide to
3
room temperature for 12 h; however, the aldol product was
obtained in only 16% yield. As a consequence, the reaction
between the tin alkoxide of aldol adduct and the enol trichloro-
acetate was found to progress sluggishly. We then verified another
determine the optimal reaction conditions (eq 1). In the reaction
at -20 °C and even at 0 °C, the formation of tin enolate was not
observed at all. In marked contrast, the corresponding enol
5
possibility of tin-catalyzed reaction (Figure 2). First, R SnOMe
trichloroacetate was nearly quantitatively transformed into the
3
reacts with an enol trichloroacetate 5 to generate the trialkyltin
enolate 2 and methyl trichloroacetate. Subsequently, the tin enolate
tributyltin enolate of cyclohexanone within 30 min at -20 °C
eq 1).6
(
2
can be added to an aldehyde to give the aldol adduct 3. Finally,
protonolysis of the alkoxide by MeOH regenerates the tin
methoxide. The rate of methanolysis is regarded as the key to
success in the catalytic cycle.
Thus, when 10 mol % of tributyltin methoxide was slowly
added to an equimolar mixture of the cyclohexanone-derived enol
(
7) The tributyltin alkoxide of aldol adduct was found to react with MeOH
1
1
1
9
below -20 °C by H NMR analysis. We further performed Sn NMR
experiments to investigate whether a pentacoordinate structure of the tin aldol
product exists and contributes to its higher reactivity toward MeOH or not.
We thus chose the 1-trichloroacetoxy cyclohexene as a substrate
for the catalytic aldol reaction. The enol trichloroacetate was
treated with benzaldehyde in the presence of 10 mol % of
tributyltin methoxide in dry THF at -20 °C for 8 h and then at
1
19
3 4
The Sn NMR spectrum (111.9 MHz, CDCl , room temperature, Me Sn; δ
0
.0 ppm) of the tin alkoxide showed two peaks at δ 101.9 (anti) and 100.7
4c
ppm (syn) with an anti/syn ratio of 23/77. These signals, however, appeared
at a field almost similar to that of tributyltin methoxide (δ 108-110 ppm),
2
b
(1) Reviews: (a) Heathcock, C. H. In ComprehensiVe Organic Synthesis;
which is regarded as a tetracoodinate tin compound.
Trost, B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press: Oxford,
U.K., 1991; Vol. 2, p 133 and related chapters. (b) Braun, M. In Houben-
Weyl: Methods of Organic Chemistry; Helmchen, G., Hoffmann, R. W.,
Mulzer, J., Schaumann, E., Eds.; Georg Thieme Verlag: Stuttgart, 1995; Vol.
E 21, p 1603.
(8) Yanagisawa, A.; Nakashima, H.; Ishiba, A.; Yamamoto, H. J. Am. Chem.
Soc. 1996, 118, 4723.
(9) Examples of catalytic asymmetric aldol reactions with silyl enol ethers
or ketene silyl acetals, reviews: (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., 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) Gr o¨ ger, H.; Vogl, E. M.; Shibasaki,
M. Chem. Eur. J. 1998, 4, 1137. Notable recent communications: (f) Chen,
C.-T.; Chao, S.-D.; Yen, K.-C.; Chen, C.-H.; Chou, I.-C.; Hon, S.-W. J. Am.
Chem. Soc. 1997, 119, 11341. (g) Kr u¨ ger, J.; Carreira, E. M. J. Am. Chem.
Soc. 1998, 120, 837. (h) Denmark, S. E.; Stavenger, R. A.; Wong, K.-T. J.
Org. Chem. 1998, 63, 918. Related catalytic asymmetric Mannich-type
reactions: (i) Hagiwara, E.; Fujii, A.; Sodeoka, M. J. Am. Chem. Soc. 1998,
120, 2474. (j) Ferraris, D.; Young, B.; Dudding, T.; Lectka, T. J. Am. Chem.
Soc. 1998, 120, 4548. Examples of direct catalytic asymmetric aldol reactions
of aldehydes with unmodified ketones: (k) Yamada, Y. M. A.; Yoshikawa,
N.; Sasai, H.; Shibasaki, M. Angew. Chem., Int. Ed. Engl. 1997, 36, 1871. (l)
Yamada, Y. M. A.; Shibasaki, M. Tetrahedron Lett. 1998, 39, 5561.
(
2) Reviews: (a) Pereyre, M.; Quintard, J.-P.; Rahm, A. Tin in Organic
Synthesis; Butterworth: London, 1987; p 286. (b) Davies, A. G. Organotin
Chemistry; VCH: Weinheim, 1997; p 185.
(3) (a) Pereyre, M.; Bellegarde, B.; Mendelsohn, J.; Valade, J. J. Organomet.
Chem. 1968, 11, 97. (b) Lutsenko, I. F.; Baukov, Y. I.; Belavin, I. Y. J.
Organomet. Chem. 1970, 24, 359. (c) Kobayashi, K.; Kawanisi, M.; Hitomi,
T.; Kozima, S. Chem. Lett. 1984, 497. Tributyltin enolates should be purified
by distillation immediately before use.
(4) (a) Shenvi, S.; Stille, J. K. Tetrahedron Lett. 1982, 23, 627. (b) Labadie,
S. S.; Stille, J. K. Tetrahedron 1984, 40, 2329. (c) Kobayashi, K.; Kawanisi,
M.; Hitomi, T.; Kozima, S. Chem. Lett. 1983, 851.
(
5) Libman, J.; Sprecher, M.; Mazur, Y. Tetrahedron 1969, 25, 1679.
(
6) Methyl trichloroacetate has been reported to be hydrolyzed in aqueous
alkaline solution faster than methyl acetate, see: Barthel, J.; B a¨ der, G.;
Schmeer, G. Z. Phys. Chem. 1968, 62, 63.
1
0.1021/ja982857q CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/15/1999