Bismuth trichloride catalyzed efficient reductive etherification of carbonyl compounds with alcohols: A novel method for preparation of symmetrical and unsymmetrical ethers

Article abstract of DOI:10.1246/cl.2002.248

The reductive homocoupling of a carbonyl compound and heterocoupling of a carbonyl compound with a non-protected alcohol were both effected smoothly at room temperature with triethylsilane in the presence of a catalytic amount of bismuth trichloride to afford the corresponding ethers in good yields.

Full text of DOI:10.1246/cl.2002.248

248
Chemistry Letters 2002
Bismuth Trichloride Catalyzed Efficient Reductive Etherification of Carbonyl Compounds
with Alcohols: A Novel Method for Preparation of Symmetrical and Unsymmetrical Ethers
Makoto Wada,ꢀ Sonoe Nagayama, Kaori Mizutani, Ryoichi Hiroi, and Norikazu Miyoshi
Department of Chemistry, Faculty of Integrated Arts and Sciences, The University of Tokushima,
1-1 Minamijosanjima, Tokushima 770-8502
(Received October 25, 2001; CL-011051)
The reductive homocoupling of a carbonyl compound and
Table 1. Ether synthesis using carbonyl compounds and Et3SiH
in the presence of BiCl3
a
heterocoupling of a carbonyl compound with a non-protected
alcohol were both effected smoothly at room temperature with
triethylsilane in the presence of a catalytic amount of bismuth
trichloride to afford the corresponding ethers in good yields.
The preparation of ethers is limited in practical sense to
Williamson’s etherification involving alkylation of an alkoxy
anion with analkyl halide underbasic conditions. However, olefin
formation sometimes occurs under these basic conditions, thus it
is desired to develop a useful method for the synthesis of
symmetrical and unsymmetrical ethers under non-basic condi-
tions.
Suzuki and we have shown that bismuth bromide can
efficiently catalyze the cyanation of carbonyl compounds and
acetals.1 Komatsu and Suzuki described the catalytic utility of
this salt for the reductive homocoupling of carbonyl compounds
and heterocoupling of a carbonyl compound with an alkoxysilane
by using triethylsilane to afford the corresponding symmetrical
and unsymmetrical ethers, respectively.2 Although similar
etherifications of carbonyl compounds with alkoxysilanes3;4 or
alcohol THP ethers5 via trialkylsilane reduction have already
been developed, there are few methods which involve a simple
process using non-protected alcohols.6
We now wish to report a convenient method for preparation
of symmetrical and unsymmetrical ethers from aldehydes and
aldehydes—non-protected alcohols, respectively, by the promo-
tion of triethylsilane (Et3SiH) and bismuth trichloride (BiCl3).
be used at all as a substrate.
Our results indicate several synthetic utilities of the present
reaction: 1) It is noteworthy that equimolar amount of aldehydes
and non-protected alcohols give the high yields of the
corresponding ethers with Et3SiH and BiCl3 under mild
conditions. 2) This is a convenient method for the preparation
of various alcohols protected by synthetic useful protecting
group. a) By the use of benzyl alcohol, benzaldehyde is
reductively converted to dibenzyl ether (Table 2, Entry 3). b)
When benzaldehyde is employed as a carbonyl component,
alcohols are directly transformed to the corresponding benzyl
ethers (Table 2, Entries 1–5 and Entry 16). 3) Reductive
etherification of benzaldehyde proceeds chemoselectively with
3-phenyl-1-propanol (80% yield) even if acetophenone is present
in the reaction mixture, and acetophenone is recovered intact.
4) An aldehyde containing a hydroxyl group (Table 1, Entry 4)
and an alcohol containing a carboxyl group (Table 2, Entry 16)
are usable as a substrate without a protection of their functional
groups, which contribute to the overall synthetic efficiency
because the tedious protection–deprotection process can be
Similarly to the results obtained by Suzuki,2 various
symmetrical ethers are synthesized under mild reaction condi-
tions as shown in the eq 1. Some of the results are summarized in
Table 1. Benzaldehyde (Entry 1) and aliphatic aldehydes (Entries
2 and 3) reacted smoothly to afford the corresponding
symmetrical ethers in good yields. As for ketones, sterically
hindered one (Entry 7) afforded only a trace of the expected ether,
and the starting ketone was recovered. It is noteworthy that the
corresponding symmetrical ether was obtained from 3-hydro-
xybenzaldehyde without the protection of the hydroxyl group. As
shown in Table 2, various aldehydes coupled smoothly with
primary and secondary alcohols in good yields (Entries 1–12),
while ketones gave the coupling products in low yields as the
ketones were recovered (Entries 13–15).7 The benzaldehyde–
phenol reaction gave no product and tert-butyl alcohol could not
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
249
Table 2. Ether synthesis using carbonyl compounds and alcohols by BiCl3 and Et3SiHa
Debruyn, and D. A. Kooistra, J. Am. Chem. Soc., 94, 3659 (1972). b)
It was reported that exposure of hydroxy ketones to excess Et3SiH
and TMSOTf resulted in the formation of oxepane. K. C. Nicolaou,
C. K. Hwang, and D. A. Nugiel, J. Am. Chem. Soc., 111, 4136
(1989).
simplified.
The mechanism of the present reaction is considered via
hemiacetal6 or hemiacetal-type3 compound as described in the
literature. In conclusion, we have developed a new convenient
method for the preparation of ethers from carbonyl compounds
and non-protected alcohols under non-basic conditions.
7
A typical procedure for the synthesis of benzyl 3-phenylpropyl
ether by the benzaldehyde—3-phenyl-1-propanol reaction is
described as follows: Bismuth trichloride (73.0mg, 0.23 mmol)
was placed in a 50ml two-necked flask and dried in vacuo by
heating. CH2Cl2 (5 ml) was added under nitrogen and to the
resulting suspension were added benzaldehyde (104.7 mg,
0.99 mmol) and 3-phenyl-1-propanol (162.3 mg, 1.20 mmol) using
a syringe. Then Et3SiH (163.0mg, 1.4 mmol) was added and the
reaction mixture was stirred for 3 h at room temperature. The
reaction mixture was quenched with a saturated aqueous ammo-
nium chloride solution, and the organic materials were extracted
with Et2O (20 ml ꢁ 3). After drying the ether layer over anhydrous
Na2SO4, the solvent was evaporated in vacuo. The residue was
purified by thin layer chromatography on silica gel (hexane:ethyl
acetate ¼ 10 : 1) to give benzyl 3-phenylpropyl ether (195.7 mg,
93%).
References and Notes
1
N. Komatsu, M. Uda, H. Suzuki, T. Takahashi, T. Domae, and M.
Wada, Tetrahedron Lett., 38, 7215 (1997).
2
N. Komatsu, J-Y. Ishida, and H. Suzuki, Tetrahedron Lett., 38, 7219
(1997).
3
4
J.-I. Kato, N. Iwasawa, and T. Mukaiyama, Chem. Lett., 1985, 743.
S. Hatakeyama, H. Mori, K. Kitano, H. Yamada, and M. Nishizawa,
Tetrahedron Lett., 35, 4367 (1994).
5
6
T. Suzuki, K. Ohashi, and T. Oriyama, Synthesis, 1999, 1561.
a) Synthesis of ethers by the reduction of aldehydes and ketones by
triethylsilane inalcoholic acidic media has beenreported. However,
a molar excess of sulfuric acid or trifluoroacetic acid to aldehydes
and ketones is used in an excess of alcohols. M. P. Doyle, D. J.