Reductive etherification of carbonyl compounds with alkyl trimethylsilylethers using polymethylhydrosiloxane (PMHS) and catalytic B(C 6F5)3

Article abstract of DOI:10.1016/j.tetlet.2004.05.061

A facile synthesis of symmetrical and unsymmetrical ethers is achieved by reductive coupling of carbonyl compounds with alkoxysilanes. This reaction is performed using inert polymethylhydrosiloxane as the hydride source and B(C ₆F₅)<

Full text of DOI:10.1016/j.tetlet.2004.05.061

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5497–5499
Reductive etherification of carbonyl compounds with alkyl
trimethylsilylethers using polymethylhydrosiloxane (PMHS)
and catalytic B(C6F5)3
q
S. Chandrasekhar,* G. Chandrashekar, B. Nagendra Babu, K. Vijeender and
K. Venkatram Reddy
Organic Chemistry Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 2 March 2004; revised 28 April 2004; accepted 7 May 2004
Abstract—A facile synthesis of symmetrical and unsymmetrical ethers is achieved by reductive coupling of carbonyl compounds
with alkoxysilanes. This reaction is performed using inert polymethylhydrosiloxane as the hydride source and B(C6F5)3 as the
catalytic activator of the PMHS.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Ethers are generally prepared by O-alkylation of alkox-
ides under basic conditions using various alkyl halides.1
Chloroimidates have also been used for etherification
reagents under acidic conditions.2 Alternatively, reduc-
tive coupling between carbonyl compounds in the pres-
ence of trialkylsilane has been used for symmetric ethers
as communicated by Doyle and co-workers.3 Other
popular methods include Noyori’s trimethylsilyl triflate
catalyzed reaction of acetals4 and the use of Mukai-
yama’s trityl perchlorate catalyst.5 Olah and co-workers
have reported a more general synthesis of both sym-
metric and unsymmetrical ethers catalyzed by TMSI.6
High pressure hydrogenation of carbonyl compounds in
the presence of alcohols7 and trimethylsilane mediated
reductive etherification,8;9 are other useful protocols.
Our research group has a long term programme on the
utilization of polymethylhydrosiloxane (PMHS),10 a sili-
con industry by-product as a safe source of hydride.
Towards this end, the results pertaining to reductive
etherification of carbonyl compounds with alkoxytri-
methylsilanes are presented herein.
methylhydrosiloxane (2 equiv) in dichloromethane, to
give the ether in 85% yield (Scheme 1). This success
promoted us to expose the aldehyde to other TMS ethers
(Table 1, entry 1). In all cases, uniformly consistent
results were obtained. 4-Nitrobenzaldehyde also partic-
ipated in the reaction without affecting the nitro group.
Mechanistically, we believe, coordination of the car-
bonyl compound with B(C6F5)3 followed by formation
of an acetal intermediate, which abstracts hydride from
PMHS to release the product is involved. In a general-
ization to other TMS ethers and carbonyl compounds,
the benzyl alcohol TMS ether was exposed to aceto-
phenone (entry 2) to yield 2-phenylethyl benzyl ether
without any cleavage of the benzyl ether, which is typ-
ical of PMHS in presence of Pd–C. Entry 4 [(4-meth-
oxybenzyloxy)trimethylsilane] demonstrates the stability
of a conjugated olefinic system with product yields
always over 70%. A natural product substrate, a steroid
TMS ether (entry 7), and a terpene (entry 6) also
R"
Initially trimethyl(3-phenylpropoxy)silane was subjected
to reductive etherification with benzaldehyde in the
presence of 1 mol % B(C6F5)3 catalyst and poly-
O
OTMS
R'
R"'
O
B(C6F5)3 (1 mol%)
+
R"
R"'
R
PMHS
DCM, r.t
R'
R
q IICT communication no 040212.
R, R" = Alkyl, Aryl
R', R"' = Alkyl, H
* Corresponding author. Tel.: +91-40-27193434; fax: +91-40-271605-
12; e-mail: srivaric@iict.res.in
Scheme 1.
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.05.061

5498
S. Chandrasekhar et al. / Tetrahedron Letters 45 (2004) 5497–5499
Table 1. Reductive etherification of carbonyl compounds with alkyl trimethylsilyl ethers using PMHS and B(C6F5)3
Entry
Substrates
Product
Yield (%)a
I
II
p-MeOC6H4CHO
C6H5CHO
C6H11CHO
R1OPMB
85
85
81
84
88
R1
OTMS
R1OBn
)
1
R1OCH2C6H11
R1OCH2C6H4-p-NO2
R1O(CH2)3C6H5
R1 =
p-NO2C6H4CHO
3-C6H5CH2CH2CHO
OTMS
2
3
C6H5COCH3
C6H5COCH3
78
70
OBn
OTMS
OTMS
OPMB
MeO
MeO
CH2OPMB
4
5
CHO
75
p-MeOC6H4CHO
C6H5CHO
C6H11CHO
R2OPMB
R2OBn
R2OCH2C6H11
80
83
82
R2
OTMS
(
OTHP
R2 =
R3
OTMS
)
6
p-MeOC6H4CHO
C6H5CHO
C6H11CHO
R3OPMB
R3OBn
R3OCH2C6H11
82
82
80
R3 =
R4
OTMS
7
p-MeOC6H4CHO
C6H5CHO
C6H11CHO
R4OPMB
R4OBn
R4OCH2C6H11
85
90
80
R4 =
(
a Isolated yields of the product is after purified by column chromatography.
furnished the corresponding ethers with both aliphatic
and aromatic aldehydes with excellent yields.
References and notes
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2169; (b) Brosa, C.; Ferrer, J. C.; Malet, C.; Amezaga, J.
J. Org. Chem. 1989, 54, 3984; (c) Eberle, M. K.; Nuninger,
F. Tetrahedron Lett. 1994, 35, 6477; (d) Davis, R.;
Muchowski, J. M. Synthesis 1982, 987.
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1981, 1240; (b) White, J. D.; Reddy, G. N.; Spessard, G.
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In conclusion, PMHS in the presence of 1 mol %
B(C6F5)3 has been proved to be a useful system for
reductive etherification of carbonyl compounds with
various TMS ethers.
General experimental procedure. To a stirred solution of
the carbonyl compound (2 mmol) and the TMS ether
(2 mmol) in dry dichloromethane (5 mL) was added
B(C6F5)3 (10 mg, 0.02 mmol) and PMHS (240 mg,
4 mmol). The reaction mixture was stirred at room
temperature for 5 h. After completion of the reaction,
water was added to the reaction mixture, which was
extracted with dichloromethane (3 · 5 mL). The com-
bined organic layers were washed with brine, dried over
anhydrous Na2SO4, concentrated in vacuo and purified
by column chromatography.
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