502
Chemistry Letters Vol.37, No.5 (2008)
Vanadium-catalyzed Asymmetric Transcyanation of Aliphatic Aldehydes
with Acetone Cyanohydrin
Junko Takaki, Hiromichi Egami, Kazuhiro Matsumoto, Bunnai Saito, and Tsutomu KatsukiÃ
Department of Chemistry, Faculty of Science, Graduate School, Kyushu University,
33 Hakozaki, Higashi-ku, Fukuoka 812-8581
(Received February 27, 2008; CL-080220; E-mail: katsuscc@mbox.nc.kyushu-u.ac.jp)
The vanadium(V)(salalen) complex prepared in situ from
acetone cyanohydrin.
the corresponding vanadium(IV) complex 4 under aerobic con-
ditions was found to be an excellent catalyst for asymmetric
transcyanation of aliphatic aldehydes with acetone cyanohydrin
as the cyanide source, showing high enantioselectivity of
91–95% ee.
We prepared oxovanadium(IV)(salalen) complexes 1–4
according to the known procedure with a slight modification
(Figure 1)11a,12 and examined cyanation of 3-phenylpropanal
with acetone cyanohydrin in dichloromethane (Table 1). The re-
action was first conducted with complex 1 as a catalyst at room
temperature under a nitrogen atmosphere. The reaction was
rather slow, and the enantioselectivity and yield were poorly re-
producible (Entry 1). Since oxovanadium(V)(salen) complexes
are more efficient catalysts for asymmetric transcyanation than
the corresponding oxovanadium(IV)(salen) complexes8 and an
oxovanadium(IV) complex is oxidized to the corresponding ox-
ovanadium(V) species by molecular oxygen,6,13 we considered
that the catalytically poor oxovanadium(IV) complex 1 was
partly oxidized by contaminating oxygen to a more reactive
oxovanadium(V) species. Therefore, complex 1 was exposed
prior to the reaction with oxygen for 1 h at room temperature
and used for the cyanation in an oxygen atmosphere. As expect-
ed, the reaction proceeded smoothly, though the enantioselectiv-
ity was low (Entry 2).14 However, lowering the reaction temper-
ature to 0 ꢀC remarkably improved the enantioselectivity to 81%
ee, without reducing the yield (Entry 3).15 We speculated
that this cyanation was reversible at room temperature, but the
reverse reaction was significantly suppressed at 0 ꢀC. Indeed,
the exposure of the cyanohydrin of 81% ee to the reaction
Asymmetric cyanation of carbonyl functionalities is one
of the most direct and efficient methods for preparing optically
active cyanohydrins and a large number of highly enantioselec-
tive methods have been developed.1,2 Although the utility of
those reactions is associated with many factors, it largely de-
pends on the cyanide source used. Hydrogen cyanide is inexpen-
sive and the most atom-efficient but it is a highly toxic gas and
requires a special care to use. Today, trimethylsilyl cyanide
(TMSCN) is widely used as the source because its use gives
the corresponding trimethylsilyl ether that does not undergo
reverse cyanation. However, it is expensive, volatile, and still
difficult to handle. Hence, the use of other cyanide sources such
as cyanoformate,3,4 acyl cyanide,4 cyanophosphonate,5 and po-
tassium cyanide3,6 has been examined. In 2000, Maruoka et al.
reported another approach, an enantioselective Meerwein–
Ponndorf–Verley type transcyanation using a commercially
available and manageable acetone cyanohydrin as the cyanide
source.7 Though requiring relatively high catalyst loading and
low reaction temperatures, this approach has an advantage of
providing a non-protected cyanohydrin. The potential of this ap-
proach prompted us to examine the cyanation using an cationic
oxovanadium(V)(salen) complex as the catalyst and we found
that the reaction proceeded in the presence of an appropriate
amine base with moderate to high enantioselectivity.8 A ꢀ-
oxo vanadium complex of cis-ꢁ configuration had been pro-
posed to participate in asymmetric cyanation with a vanadium-
(salen)/TMSCN system by North et al.9 The mechanistic
study of our method also infers the participation of a vanadium
complex of cis-ꢁ configuration.8 On the other hand, in parallel
with this study, we discovered that chiral cis-ꢁ metal(salalen)
complexes exhibited versatile and potent asymmetric cataly-
sis.10,11 Therefore, we were intrigued by vanadium(salalen)
complexes as catalysts for asymmetric transcyanation using
Table 1. Asymmetric cyanation of 3-phenylpropanal with
oxovanadium complexes 1–4a
V(salalen) (10 mol %)
O
NC OH
H
NC OH
+
CH2Cl2, O2, 24 h
Ph
Ph
H
Entry Complex T/ꢀC Yield/%b ee/%c Config.d
1e
2
3
4
5
6
7
8f
9g
1
1
1
1
2
3
4
4
4
rt
rt
0
20–80
>99
>99
38
>99
37
74
>99
99h
2–42
11
81
86
87
89
93
92
R
R
R
R
S
S
S
S
S
À15
0
0
0
0
0
91
aComplexes were exposed prior to the reaction to oxygen
for 1 h at rt and the reaction was carried out on a 0.2 mmol
scale, unless otherwise mentioned. bDetermined by 1H NMR
(400 MHz) analysis. cDetermined by the reported method
*
R2
*
(S,S)-1: R1 = t-Bu, R2 = Me
(R,R)-2: R1 = t-Hex, R2 = Me
(R,R)-3: R1 = t-Bu, R2 = Et
(R,R)-4: R1 = t-Hex, R2 = Et
O
V
N
N
d
(ref. 8). Determined by comparison of the optical rotations
with the literature value. eComplex 1 was used without
pretreatment with oxygen and the reaction was carried out
R1
O
O
R1
R1
R1
f
g
under nitrogen. Reaction time was 36 h. Carried out on a
gram scale for 36 h. Isolated yield.
h
Figure 1. Oxovanadium(IV)(salalen) complexes 1–4.
Copyright Ó 2008 The Chemical Society of Japan
Takaki, Junko
