J. Am. Chem. Soc. 1999, 121, 2641-2642
2641
A New Bifunctional Asymmetric Catalysis: An
Efficient Catalytic Asymmetric Cyanosilylation of
Aldehydes
One of the key issues for designing a Lewis acid-Lewis base
catalyst is how to prevent the internal complexation of these
moieties. Molecular modeling studies suggested that 1 would
avoid such a problem, because the coordination of the Lewis base,
attached to the 3,3′-position of the binaphthol, to the internal
aluminum seemed to be torsionally unfavorable. When consider-
ing 2, however, which has an ethylene linker, the internal
coordination seemed to be quite stable without strain. In ac-
cordance with this expectation, the reaction of TMSCN with
benzaldehyde 5h, catalyzed by 2 (9 mol %), proceeded slowly at
Yoshitaka Hamashima, Daisuke Sawada, Motomu Kanai, and
Masakatsu Shibasaki*
Graduate School of Pharmaceutical Sciences
The UniVersity of Tokyo
Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
-
40 °C (37 h) and gave the cyanohydrin 6h in only 4% yield
after hydrolysis. In this case, strong intramolecular coordination
of the phosphine oxide should reduce the Lewis acidity of the
aluminum, therefore diminishing the catalytic efficiency of 2.
However, a solution of 1 (9 mol %), 5h, and TMSCN, at -40
ReceiVed NoVember 11, 1998
Developing efficient asymmetric catalytic addition reactions
1
to carbonyl compounds is an intensely studied area. The catalysis
°
C (37 h), afforded 6h in 91% yield. Therefore, in the case of 1,
by chiral Lewis acids activating the electrophile is among the
most successful approaches.1 Recently, chiral Lewis bases
coordinating to and activating silylated nucleophiles have been
the intramolecular binding of the phosphine oxide to the aluminum
seems to be labile enough to allow coordination of the aldehyde
to the aluminum. Conversion of 6h to the corresponding ethoxy-
carbonate, followed by chiral HPLC analysis, revealed that 6h
2
introduced into this field. We have been involved in developing
a new asymmetric catalyst from the concept of multifunctional
catalysis,3 whereby activation of substrates and nucleophiles
occurs simultaneously at the Lewis acid and the Br o¨ nsted base
moieties in the catalyst, thus affording high enantioselectivities
in a variety of reactions. Therefore, it seemed rational to design
a new bifunctional asymmetric catalyst consisting of Lewis acid
and Lewis base moieties, which activate both electrophiles and
8
had 87% ee. The absolute configuration was determined to be S
by optical rotation.7d
Encouraged by the result of benzaldehyde with catalyst 1, we
next investigated the reaction of aliphatic aldehydes. Surprisingly,
aliphatic aldehydes afforded very low ee values: 5a gave S-6a
in 90% yield and in 9% ee; 5c gave S-6c in 80% yield and in
8
2
5% ee. We anticipated that there would be competition between
4
nucleophiles at defined positions simultaneously. Using this
two reaction pathways in the case of the more reactive aliphatic
aldehydes. The desired pathway involves the dual interaction
between the Lewis acid and the aldehyde and between the Lewis
base and TMSCN, whereas the undesired pathway involves mono-
activation by the Lewis acid. We assumed that these two pathways
could differ more significantly if the Lewis acidity of the catalyst
was decreased, and so we investigated the effect of additives
which coordinate to the aluminum to reduce its Lewis acidity.
Moreover, the additive could change the geometry of aluminum
concept, we designed the chiral Lewis acid-Lewis base catalyst
. We assumed that the aluminum would work as a Lewis acid
1
to activate the carbonyl group, and the oxygen atom of the
phosphine oxide would work as a Lewis base to activate the
silylated nucleophiles.5 We report herein that catalyst 1 is a
,6
7
highly efficient catalyst for the cyanosilylation of aldehydes with
broad generality, affording products in excellent chemical yields
and excellent enantioselectivities.
9
from tetrahedral to trigonal bipyramidal, which should allow the
phosphine oxide to exist in a more favorable position relative to
the aldehyde. After several attempts, we found that electron
1
0,11
donating phosphine oxides had a beneficial effect on ee.
the case of 5a, the ee values of 6a significantly increased from
% to 41% and 56% by the addition of 36 mol % of CH P(O)-
Ph and Bu P(O), respectively. Further improvement of ee (up to
7%) was achieved by the slow addition of TMSCN (10 h), via
syringe pump, in the presence of Bu P(O) (Table 1, entry 1). In
the case of 5h, however, addition of Bu P(O) resulted in a very
In
9
3
2
3
9
(
1) (a) Noyori, R. Asymmetric Catalysis In Organic Synthesis; John Wiley
Sons: New York, 1994. (b) Catalytic Asymmetric Synthesis; Ojima, I.,
Ed.; VCH: New York, 1993.
2) (a) Denmark, S. E.; Su, X.; Nishigaichi, Y. J. Am. Chem. Soc. 1998,
3
&
3
sluggish reaction, affording only a trace amount of the product.
However, the reaction proceeded in 98% yield and in 96% ee in
(
1
20, 12990-12991. (b) Nakajima, M.; Saito, M.; Shiro, M.; Hashimoto, S. J.
Am. Chem. Soc. 1998, 120, 6419-6420. (c) Iseki, K.; Mizuno, S.; Kuroki,
the presence of CH
O) as the additive for aliphatic and R,â-unsaturated aldehydes,
and CH P(O)Ph as the additive for aromatic aldehydes.
This catalyst is practical and has a broad generality with respect
3 2 3
P(O)Ph (entry 7). Therefore, we used Bu P-
Y.; Kobayashi, Y. Tetrahedron Lett. 1998, 39, 2767-2770.
(
(
3) Shibasaki, M.; Sasai, H.; Arai, T. Angew. Chem., Int. Ed. Engl. 1997,
3
6, 1236-1256.
3
2
(4) (a) Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. Engl. 1998, 37,
1
3
5
986-2012. (b) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991,
0, 49-69. (c) Kobayashi, S.; Tsuchiya, Y.; Mukaiyama, T. Chem. Lett. 1991,
41-544.
1
2
to the variety of aldehydes that can be used (Table 1). Since
cyano groups can be easily converted into carboxyl groups, this
(5) We have found that phosphine oxides promote the cyanosilylation of
aldehydes: TMSCN reacted with 5a to give 6a in 81% yield in the presence
of 40 mol % of Bu P(O) at ambient temperature for 7.5 h. In the absence of
Bu P(O), the yield was 12% under the same conditions. At -40 °C for 40 h,
however, the reaction did not proceed at all.
6) As phosphines catalyze the cyanosilylation of aldehydes (Kobayashi,
S.; Tsuchiya, Y.; Mukaiyama, T. Chem. Lett. 1991, 537-540), we first
(8) The products of the opposite configuration were generally obtained by
3 (9 mol %) (-40 °C, 37 h): 5g gave R-6g (50% yield and 12% ee); 5a gave
R-6a (56% yield and 10% ee); 5c gave R-6c (36% yield and 4% ee) with 3.
(9) (a) Ooi, T.; Kagoshima, N.; Maruoka, K. J. Am. Chem. Soc. 1997, 119,
5754-5755. (b) Murakata, M.; Jono, T.; Mizuno, Y.; Hoshino, O. J. Am.
Chem. Soc. 1997, 119, 11713-11714.
3
3
(
investigated 3,3′-phosphinomethylbinaphthol (X ) PPh
2
). However, the
(10) Addition of ether, dimethyl sulfoxide, H u¨ nig base, or acetonitrile gave
lower ee values. Since the reaction pathway involving activation by the external
phosphine oxide is negligible at -40 °C (ref 5), only an internal phosphine
oxide can function as an activator of TMSCN, because the phosphine oxide
exists at the appropriate position close to TMSCN in the reactive complex.
(11) The reaction rate in the presence of the additive phosphine oxide is
naphthol moieties of this ligand were partly silylated during the reaction,
whereas catalyst 1 was stable against silylation under the reaction conditions.
(
7) (a) Hwang, C.-D.; Hwang, D.-R.; Uang, B.-J. J. Org. Chem. 1998, 63,
6
5
4
1
762-6763. (b) Bolm, C.; M u¨ ller, P.; Harms, K. Acta Chem. Scand. 1996,
0, 305-315. (c) Corey, E. J.; Wang, Z. Tetrahedron Lett. 1993, 34, 4001-
004. (d) Hayashi, M.; Miyamoto, Y.; Inoue, T.; Oguni, N. J. Org. Chem.
993, 58, 1515-1522. (e) Nitta, H.; Yu, D.; Kudo, M.; Mori, A.; Inoue, S. J.
slower than that in the absence of the additive (the relative reaction rate; kadditive
no-additive ) 0.6, in the reaction of 6a in the presence or absence of Bu P(O)),
as expected from the lower Lewis acidity.
/
k
3
Am. Chem. Soc. 1992, 114, 7976-7975.
1
0.1021/ja983895c CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/04/1999