336
Chemistry Letters Vol.38, No.4 (2009)
Dibutyltin Dibromide-catalyzed Trimethylsilylcyanation of Aldehydes and Imines
Akira Yanagisawa,Ã Takuya Matsumoto, Takayoshi Arai, and Kazuhiro Yoshida
Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522
(Received January 28, 2009; CL-090094; E-mail: ayanagi@faculty.chiba-u.jp)
Table 1. Screening of tin catalysts in trimethylsilylcyanation of benzalde-
hyde (2a) with cyanotrimethylsilane (3)a
Dibutyltin dibromide efficiently catalyzes addition of tri-
methylsilyl cyanide to aldehydes and aldimines. Various tri-
methylsilylated cyanohydrins and ꢀ-aminonitriles are obtained
in moderate to high yield by this method.
tin catalyst (0.1 equiv)
CH2Cl2, r.t., 24 h
O
OSiMe3
+
Me3SiCN
3 (2 equiv)
Ph
H
Ph
CN
2a
4a
Entry
Tin catalyst
Yield/%b
Organotin(IV) reagents such as trialkyltin enolates and allyl-
ic trialkyltins are known to have moderate nucleophilicity and
have been often utilized for carbon–carbon bond forming reac-
tions; however, their use in organic synthesis is somewhat limit-
ed because of their toxicity.1 To overcome this difficulty, we at-
tempted to develop the above-mentioned reactions promoted by
a catalytic amount of organotin(IV) compounds and as a result,
we found an aldol reaction of alkenyl trichloroacetates catalyzed
by dibutyltin dimethoxide, which is efficiently recycled with the
assistance of methanol.2 By taking advantage of this catalytic
system, the Mannich-type reaction of aldimines3 and the
Michael addition to p-benzoquinone4 have been also achieved.
As for these reactions, noteworthy is the fact that organotin(IV)
enolates are generated catalytically and immediately undergo
addition to the corresponding electrophiles. In addition, we have
found a dibutyltin oxide-catalyzed allyl-transfer reaction from
tertiary homoallylic alcohols to aldehydes, in which a catalytic
amount of an allylic tin compound is formed in situ.5 Our interest
in the catalytic ability of these organotin(IV) compounds has led
us to undertake a further investigation of related tin species.
Here, we wish to describe a cyanation of aldehydes and imines
with trimethylsilyl cyanide catalyzed by dibutyltin dibromide
(Scheme 1).
Cyanohydrins are versatile synthetic intermediates for di-
verse natural products, which are further transformable into ꢀ-
hydroxycarboxylic acids or ꢀ-hydroxyketones.6 In order to con-
struct the cyanohydrin moiety efficiently, various metal catalysts
have been applied to silylcyanation of aldehydes.7 As for orga-
notin(IV) compounds, tributyltin cyanide has been found to cat-
alyze addition of triethylsilyl cyanide to aldehydes8 and relevant
acylcyanation.9 In 1996, Whitesell and Apodaca have reported
that dibutyltin dichloride is an effective catalyst for trimethyl-
silylcyanation of aldehydes and ketones in the absence of sol-
vent.10 They measured a 1:1 mixture of Bu2SnCl2 and Me3SiCN
in CDCl3 by 1H NMR at room temperature and detected
Me3SiCl (ca. 5%) which suggests a tin cyanide as a catalytically
active species. This result prompted us to examine Bu2SnBr2 (1),
which is anticipated to show higher catalytic activity than that of
Bu2SnCl2.11 So, we carried out a reaction of benzaldehyde (2a)
with Me3SiCN (3) in the presence of 10 mol % Bu2SnBr2 (1) in
CH2Cl2 under more diluted conditions than Whitesell’s condi-
1
2
3
4
5
Bu2SnBr2 (1)
Bu2SnCl2
Bu2Sn(OMe)2
Bu2SnO
Bu3SnBr
52
14
3
3
<1
aThe reaction was carried out employing cyanotrimethylsi-
lane (3, 2 equiv), benzaldehyde (2a, 1 equiv), and tin catalyst
(0.1 equiv) in CH2Cl2 at room temperature for 24 h. bIsolated
yield.
Table 2. Solvent effect on trimethylsilylcyanation of benzaldehyde (2a)
with cyanotrimethylsilane (3) catalyzed by Bu2SnBr2 (1)a
Bu2SnBr2 (1, 0.1 equiv)
O
OSiMe3
+
Me3SiCN
solvent, r.t., 24 h
Ph
H
Ph
CN
3 (2 equiv)
2a
4a
Entry
Solvent
Yield/%b
1
2
3c
4
5
6
7
CH2Cl2
THF
THF
MeCN
DMF
52
78
<1
62
<1
<1
<1
MeOH
Toluene
aThe reaction was carried out employing cyanotrimethylsi-
lane (3, 2 equiv), benzaldehyde (2a, 1 equiv), and dibutyltin
dibromide (1, 0.1 equiv) in a specified solvent at room tem-
perature for 24 h. bIsolated yield. cBu2SnCl2 was used as a
catalyst instead of Bu2SnBr2 (1).
tions and compared its catalytic activity with other organotin(IV)
reagents (Table 1). As a result, Bu2SnBr2 (1) afforded the
desired trimethylsilylated cyanohydrin 4a in 52% yield in the
reaction at room temperature for 24 h (Entry 1). In contrast,
Bu2SnCl2 indicated lower reactivity under similar reaction con-
ditions (Entry 2). Bu2Sn(OMe)2 and Bu2SnO, which were effec-
tive catalysts for the aforementioned aldol reaction2 and allyl-
transfer reaction,5 had almost no catalytic activity in the present
cyanation (Entries 3 and 4).
In order to obtain a more satisfactory yield, we then inves-
tigated solvent effects (Table 2). Among the solvents tested,
THF was found to furnish a higher yield than that given in
CH2Cl2 (Entries 1 and 2), while Bu2SnCl2 did not promote the
cyanation at all in the former solvent (Entry 3). Acetonitrile
was also a promising solvent (Entry 4), however, use of DMF,
MeOH, and toluene resulted in totally unacceptable yields
(Entries 5–7).
X
OSiMe3
CN
NHR2
CN
cat. Bu2SnBr2
THF, r.t.
+
or
Me3SiCN
R1
X = O, NR2
H
R1
R1
Scheme 1. Bu2SnBr2-catalyzed cyanation of aldehydes and imines.
Copyright Ó 2009 The Chemical Society of Japan