Published on the web March 22, 2013
489
Zinc-catalyzed Reduction of Aldehydes with a Hydrosilane Leading
to Symmetric Ethers and Silyl Ethers
Norio Sakai,* Yoshifumi Nonomura, Reiko Ikeda, and Takeo Konakahara
Department of Pure and Applied Chemistry, Faculty of Science and Technology,
Tokyo University of Science (RIKADAI), Noda, Chiba 278-8510
(Received December 31, 2012; CL-121297; E-mail: sakachem@rs.noda.tus.ac.jp)
The efficient reductive etherification of aromatic or aliphatic
Table 1. Examinations of reaction conditions
aldehydes using a reducing system that combines Zn(OTf)2 with
either TMDS or Et3SiH is described. The present reducing
system can also be applied to the hydrosilylation of aromatic
aldehydes having either a strong electron-withdrawing group or
a pyridine ring.
O
CHO
Lewis acid (0.05 equiv)
silane (Si-H: 4 equiv)
Cl
Cl
1
or
CHCl3, rt, 24 h
O-Si
Cl
Cl
1a
1'
Synthesis of ethers is one of the most widely investigated
methods in organic chemistry. Among the various methods
available, the Williamson ether synthesis and its modification
under basic conditions have been widely developed for this
purpose.1 As a further extension of this method, several groups
have demonstrated the combination of a Lewis or Brønsted acid
with a hydrosilane such as BF3-Et3SiH,2 TrClO4-Et3SiH,3 TMSI
or TMSOTf-Et3SiH,4 BiCl3 or BiBr3-Et3SiH,5 SbI3-PhSiH3,6
FeCl3-Et3SiH,7 I2-PMHS [poly(methylhydrosiloxane)],8 TfOH-
Et3SiH,9 and Cu(OTf)2-TMDS (1,1,3,3-tetramethyldisiloxane)10
to promote the reductive homocoupling of carbonyl compounds
or heterocoupling of carbonyl compounds with silyl ethers,
which yields symmetric or unsymmetrical ethers. Reducing
systems consisting of a zinc catalyst and a hydrosilane have also
recently been used in a variety of functional group trans-
formations involving the hydrosilylation of ketones,11 deoxyge-
nation of carbonyl compounds12 or amides,13 and reductive
amination.14
In this context, during further research on the reductive
transformation of a typical functional group with a carbon-
oxygen bond by using a reducing system that combined an
indium compound with a hydrosilane,15 we found that unlike
conventional conversions using a zinc catalyst, as shown above,
a Zn(OTf)2-TMDS or Et3SiH reducing system promoted the
reductive coupling of aromatic and aliphatic aldehydes, afford-
ing symmetric ethers. This type of reducing system could also be
applied to the hydrosilylation of aromatic aldehydes with a
pyridine ring. In this letter, we report the preliminary results of
this transformation.
The reduction of p-chlorobenzaldehyde (1a) with a zinc
catalyst and a hydrosilane was initially examined as a model
reaction (Table 1).16 For example, when the reaction was
conducted with 0.05 equiv of ZnCl2 and 4 equiv (Si-H) of
Et3SiH in CHCl3 at room temperature, the reduction proceeded
in a clean manner to produce the unexpected symmetric ether 1
in 60% yield, with the corresponding silyl ether 1¤ in 20% yield
(Entry 1). ZnI2 was ineffective for the reduction, and most of
the starting aldehyde was recovered (Entry 2). By contrast, a
relatively strong Lewis acid among the zinc catalysts, Zn(OTf)2,
showed high catalytic activity for this reduction (Entries 3-5).
PhSiH3 and TMDS as a hydrosilane showed moderate to good
selectivity, respectively, but a polymer-like PMHS did not
Yield/%a
Entry
Lewis acid
Silane
1
1¤
1
2
3
4
5
6
7c
ZnCl2
ZnI2
Et3SiH
Et3SiH
Et3SiH
PhSiH3
TMDS
PMHS
Et3SiH
60
20
NR
60
66b
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
InBr3
trace
ND
88 (78)
NR
trace
trace
(84)
aGC (isolated) yield. The starting aldehyde was recovered in
25% yield. Bath temperature: 60 °C, reaction time: 1 h.
b
c
afford the desired product (Entry 6). When the reduction was
conducted in a typical coordinate solvent such as CH3CN and
THF, unfortunately, a small amount of silyl ether was obtained
without the ether. On the other hand, when a similar reaction
was performed using InBr3 instead of the zinc catalyst, the
corresponding silyl ether 1¤ was selectively obtained (Entry 7).
Consequently, a reducing system composed of 5 mol % of
Zn(OTf)2 and 4 equiv of TMDS in CHCl3 provided the best
result, but with the isolation of either the ether or the silyl ether,
the conditions using Et3SiH were also acceptable.
With the optimized conditions found in Table 1, the scope
of this reaction was examined with aromatic aldehydes
containing a variety of functional groups (Table 2).17 In all
cases using aromatic aldehydes having either a relatively weak
electron-withdrawing group such as a halogen or an electron-
donating group such as a methyl or methoxy substituent, the
etherification proceeded smoothly, producing the corresponding
symmetric ethers 2-4 in good yields. When the reaction was
conducted with 2-naphthaldehyde or benzaldehyde, the corre-
sponding ethers 5 and 6 were obtained in good yields. On the
other hand, the use of benzaldehyde with an o-methyl substituent
led to a decrease in the yield and recovery of the starting
aldehyde, probably due to steric hindrance.18 By contrast, when
the reaction was carried out using benzaldehydes with a strong
electron-withdrawing group such as a trifluoromethyl, cyano, or
nitro group, contrary to our expectation, the corresponding silyl
ether derivatives 8-10 were selectively obtained via hydro-
silylation.19 Interestingly, although a pyridine ring with a basic
Chem. Lett. 2013, 42, 489-491
© 2013 The Chemical Society of Japan