The reductive etherification of carbonyl compounds using polymethylhydrosiloxane activated by molecular iodine

Article abstract of DOI:10.1016/j.tetlet.2009.10.063

Aldehydes and ketones undergo a smooth reductive etherification by polymethylhydrosiloxane (PMHS) in the presence of a catalytic amount of molecular iodine under mild conditions to afford the corresponding symmetrical ethers in excellent yields. This new reagent system (PMHS/I₂) provides a simple and convenient route for the preparation of symmetrical ethers from carbonyl compounds.

Full text of DOI:10.1016/j.tetlet.2009.10.063

Tetrahedron Letters 51 (2010) 46–48
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The reductive etherification of carbonyl compounds using
polymethylhydrosiloxane activated by molecular iodine
*
J. S. Yadav , B. V. Subba Reddy, K. Shiva Shankar, T. Swamy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Aldehydes and ketones undergo a smooth reductive etherification by polymethylhydrosiloxane (PMHS)
in the presence of a catalytic amount of molecular iodine under mild conditions to afford the correspond-
ing symmetrical ethers in excellent yields. This new reagent system (PMHS/I2) provides a simple and con-
venient route for the preparation of symmetrical ethers from carbonyl compounds.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 13 September 2009
Revised 10 October 2009
Accepted 14 October 2009
Available online 17 October 2009
Keywords:
Polymethylhydrosiloxane
Molecular iodine
Carbonyl compounds
Reductive etherification
Ethers
The formation of carbon–oxygen bond is one of the most widely
used functional group transformations in organic synthesis.1,2 The
classical methods for the preparation of ethers are the Williamson
and Wurtz’s synthesis.3,4 The reductive etherification is one of the
direct and simple method for the synthesis of symmetrical ethers.
Typically, Lewis acids such as boron trifluoride, trifluoroacetic acid,
ferric chloride and trimethylsilyltriflate are employed as catalysts
for the reductive etherification of carbonyl compounds with trieth-
ylsilane.5,6 Doyle et al. have reported an acid promoted reductive
coupling of carbonyl compounds with trialkylsilanes as a route to
symmetrical ethers.7 This method requires several-fold excess of
strong Bronsted acids, often used as solvents which limit its poten-
tial use in large scale synthesis. Other reagents such as pyridine–
borane/trifluoroacetic acid and solid super acids/trialkylsilanes
have also been employed for the reductive etherification of alde-
hydes to furnish symmetrical and unsymmetrical ethers.8 How-
ever, many of these reagents are corrosive, moisture sensitive
and are required in stoichiometric amounts. Therefore, the devel-
opments of simple and cost-effective reagents that are more effi-
cient and provide convenient procedures with improved yields
are desirable.
form several organic transformations using stoichiometric levels
to catalytic amounts. Owing to advantages associated with this
eco-friendly catalyst, molecular iodine has been explored as a pow-
erful reagent in organic synthesis.10
In continuation of our interest on the catalytic use of molecular
iodine for various organic transformations,11 we herein report a
mild, convenient and rapid method for the reductive etherification
of both aldehydes and ketones with polymethylhydrosiloxane
(PMHS), using a catalytic amount of elemental iodine. Initially,
we attempted the reductive etherification of benzaldehyde (1)
with PMHS (2) in the presence of
a catalytic amount of
(2.5 mol %) molecular iodine. The reaction was complete within
30 min and the desired product, dibenzyl ether 3a was obtained
in 90% yield (Scheme 1).
This result provided incentive for further study with various
aldehydes such as phenylacetaldehyde, 2-phenylpropanaldehyde
and 3-phenylpropanaldehyde. Interestingly, these aldehydes re-
acted equally well with PMHS to provide the corresponding sym-
metrical ethers (Table 1, entries b–d). In case of entry c, the
product was obtained as a diastereomeric mixture in 1:1 ratio
which was confirmed by GC and also by comparison with authentic
In recent years, molecular iodine has gained importance as
inexpensive, non-toxic and a readily available catalyst for various
organic transformations affording the corresponding products with
high selectivity in excellent yields.9 The mild Lewis acidity associ-
ated with iodine enhanced its usage in organic synthesis to per-
O
I2
CH2Cl2 , rt
O
H
+
PMHS
3a
2
1
* Corresponding author. Tel.: +91 40 27193030; fax: +91 40 27160387.
E-mail address: yadavpub@iict.res.in (J.S. Yadav).
Scheme 1. Preparation of dibenzyl ether.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.063

J. S. Yadav et al. / Tetrahedron Letters 51 (2010) 46–48
47
Table 1
PMHS/I2-Promoted reductive etherification of carbonyl compounds
Entry
Carbonyl compounds (1)
Ethers (3)a
Reaction time (min)
30
Yieldb (%)
90
O
H
O
a
H
O
O
b
c
35
30
86
Me
Me
Me
H
O
82c
O
H
O
O
d
e
25
30
85
88
O
O
CH3
H3C
H
H3C
O
O
OMe
MeO
f
20
89
H
MeO
O
H
OMe
OMe
O
MeO
g
35
35
87
87
O
H
O
OMe
MeO
MeO
h
H
O
O
i
30
85
OH
Cl
OH
OH
Cl
O
O
Cl
j
25
45
86
82
H
O
Me
O
Me
Me
O
Me
Me
k
H
Me
Me
Me
Me
O
H
l
40
87
OPh
OPh
OPh
O
Me Me
O
m
n
30
30
85d
70
Me
O
O
O
O
o
p
15
15
84
O
O
86d
a
b
c
All products were characterized by IR, 1H, 13C NMR and mass spectroscopy.
Yield refers to pure products after chromatography.
The product was obtained as a diastereomeric mixture in 1:1 ratio which was determined by GC.12
A single diastereomer was formed.2
d
samples.12 Similarly, substituted aromatic aldehydes such as
p-methylbenzaldehyde, p-anisaldehyde, o-anisaldehyde, m-anisal-
dehyde, m-hydroxybenzaldehyde, p-chlorobenzaldehyde, 2,4,6-tri-
methylbenzaldehyde and m-phenoxybenzaldehyde were converted
into their corresponding symmetrical ethers in high yields by using
this procedure (Table 1, entries e–l). Next, we examined the reactiv-
ity of ketones such as acetophenone and cyclohexanone. Ketones
Me Me
O
O
I2
PMHS
Me
+
CH2Cl2, rt
3m
Scheme 2. Preparation of di-2-phenethyl ether.

48
J. S. Yadav et al. / Tetrahedron Letters 51 (2010) 46–48
also participated well in this reaction (Table 1, entries m and n,
Scheme 2).
References and notes
The products were characterized by 1H, 13C NMR, IR and mass
spectrometry and also by comparison with authentic compounds.8
In cases of entries m and p, a single diastereomer was obtained,
which was confirmed by 1H NMR spectrum of the crude products
and also by comparison with authentic samples.2 The reactions
are operationally simple and highly efficient for the production
of symmetrical ethers from carbonyl compounds. There are several
advantages in the use of iodine as the catalyst for this transforma-
tion, which include high yields of products, operational simplicity,
enhanced rates, cleaner reaction profiles and easy availability of
the catalyst at low cost. In addition, the reaction conditions are
amenable for scale-up. Among various catalysts such as Sc(OTf)3,
Yb(OTf)3, Ce(OTf)3, In(OTf)3 InCl3 and InBr3 employed for this
conversion, molecular iodine was found to be the most effective
catalyst in terms of yields and reaction rates. As solvent, dichloro-
methane gave the best results. The scope and generality of this pro-
cess is illustrated with respect to various carbonyl compounds and
the results are presented in Table 1.13
Mechanistically, it is known that iodine may react with PMHS to
produce trimethylsilyl iodide which might be responsible for initi-
ating the reaction and unstable reducing reagent, which rapidly re-
acts with carbonyl compounds to promote the reduction.9a To test
this hypothesis; we carried out the reaction with trimethylsilyl io-
dide (0.25 equiv) and PMHS under otherwise identical conditions.
The products were identical to those that were obtained with io-
dine. However, the products were obtained in low to moderate
yields (45–60%) when TMSI was employed as the catalyst. Thus,
the combination of PMHS and 2.5 mol % of molecular iodine
(PMHS/I2) was found to be effective for this conversion. The use
of molecular iodine as a catalyst for the activation of polymethyl-
hydrosiloxane (PMHS), which is an inexpensive and soluble hydro-
gen source, for the reduction of carbonyl compounds makes this
quite simple, more convenient and practical.
1. Olah, G. A.; Rochin, C. J. Org. Chem. 1987, 52, 701.
2. Sassaman, M. B.; Kotian, K. D.; Surya Prakash, G. K.; Olah, G. A. J. Org. Chem.
1987, 52, 4314.
3. Wurtz, A. Ann. Chem. 1856, 46, 222.
4. March, J.. Advanced Organic Chemistry: Reactions, Mechanisms and Structure, 2nd
ed.; McGraw-Hill Book Company: New York, 1978. 357.
5. (a) Postema, M. H. D. Tetrahedron 1992, 48, 8545; (b) West, C. T.; Donnelly, S. J.;
Kooistra, D. A.; Doyle, M. P. J. Org. Chem. 1973, 38, 2675; (c) Doyle, M. P.;
DeBruyn, D. J.; Donnelly, S. J.; Kooistra, D. A.; Odubela, A. A.; West, C. T.;
Zonnebelt, S. M. J. Org. Chem. 1974, 39, 2740.
6. (a) Doyle, M. P.; West, C. T. J. Org. Chem. 1975, 40, 3821; (b) Doyle, M. P.; West,
C. T. J. Org. Chem. 1975, 40, 3829; (c) Doyle, M. P.; West, C. T. J. Org. Chem. 1975,
40, 3835; (d) Iwanami, K.; Yano, K.; Oriyama, T. Chem. Lett. 2007, 36, 38.
7. Doyle, M. P.; DeBruyn, D. J.; Kooistra, D. A. J. Am. Chem. Soc. 1972, 94, 3659.
8. (a) Kikugawa, Y. Chem. Lett. 1979, 415; (b) Olah, G. A.; Yamato, T.; Iyer, P. S.;
Prakash, G. K. S. J. Org. Chem. 1986, 51, 2826.
9. (a) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.; Swamy, T. Tetrahedron Lett. 2005,
46, 2687; (b) Huang, G.; Isobe, M. Tetrahedron 2001, 57, 10241; (c) Tsukiyama,
T.; Peters, S. C.; Isobe, M. Synlett 1993, 413; (d) Hosokawa, S.; Kirschbaum, B.;
Isobe, M. Tetrahedron Lett. 1998, 39, 1917; (e) Tsukiyama, T.; Isobe, M.
Tetrahedron Lett. 1992, 33, 7911.
10. (a) Togo, H.; Iida, S. Synlett 2006, 2159; (b) Banik, B. K.; Fernandez, M.; Alvarez,
C. Tetrahedron Lett. 2005, 46, 2479; (c) Kartha, K. P. R.; Ballell, L.; Bilke, J.;
McNeil, M.; Field, R. A. J. Chem. Soc., Perkin. Trans. 1 2001, 770; (d) Koreeda, M.;
Houston, T. A.; Shull, B. K.; Klemke, E.; Tuinman, R. J. Synlett 1995, 90; (e) Vaino,
R. K.; Szarek, W. A. Synlett 1995, 1157; (f) Lipshutz, B. H.; Keith, J. Tetrahedron
Lett. 1998, 39, 2495; (g) Ko, S.; Sastry, M. N. V.; Lin, C.; Yao, C. F. Tetrahedron
Lett. 2005, 46, 5771.
11. (a) Yadav, J. S.; Reddy, B. V. S.; Hashim, S. R. J. Chem. Soc., Perkin. Trans. 1 2000,
3082; (b) Yadav, J. S.; Reddy, B. V. S.; Sabitha, G.; Reddy, G. S. K. K. Synthesis
2000, 1532; (c) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Rao, K. V. J. Chem. Soc.,
Perkin. Trans. 1 2002, 1401; (d) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Chand, P.
K.; Prasad, A. R. Synlett 2001, 1638; (e) Yadav, J. S.; Reddy, B. V. S.; Narayana
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13. Experimental procedure: To
a mixture of benzaldehyde (0.212 g, 2 mmol)
and polymethylhydrosiloxane (0.390 g, 6 mmol, Sigma Aldrich) in dichloro-
methane (10 mL) was added 2.5 mol % of iodine at 0 °C under nitrogen
atmosphere. The reaction mixture was stirred at room temperature for
specified time in Table 1. After complete conversion, as indicated by TLC, the
reaction mixture was diluted with water (10 mL) and washed with Na2S2O3
solution and extracted with dichloromethane (2 Â 15 mL). The organic layers
were dried over anhydrous Na2SO4 and purified by column chromatography on
silica gel (Merck, 100–200 mesh, 1% ethyl acetate in n-hexanes) to afford pure
In conclusion, iodine has proved to be an effective catalyst for
the reductive etherification of various aldehydes with polymethyl-
hydrosiloxane under extremely mild conditions. This method de-
scribes a novel use of molecular iodine for the activation of
polymethylhydrosiloxane to provide symmetrical ethers from car-
bonyl compounds. The procedure is very simple, quick and conve-
nient which may find use in organic synthesis.
ether. Spectral data for selected products: 3a: liquid, IR (KBr):
1490, 1197, 769 cmÀ1 1H NMR (200 MHz, CDCl3): d 4.52 (s, –O–CH2Ph, 4H),
7.21–7.35 (m, Ar-H, 10H). 13C NMR (50 MHz, CDCl3): d 75.1, 127.4, 128.2, 129.4,
132.3. ESI-MS: m/z (%): 199 (M+1). Compound 3f: Liquid, IR (KBr): 2925, 1635,
1219, 1054, 772 cmÀ1 1H NMR (200 MHz, CDCl3): d 3.80 (s, –O–CH3, 6H), 4.58 (s,
m 2934, 1631,
.
m
.
–O–CH2Ph, 4H), 6.85 (d, J = 8.6 Hz, m-Ar-H, 4H), 7.25 (d, J = 8.6 Hz, p-Ar-H, 4H).
13C NMR (50 MHz, CDCl3): d 55.5, 79.5, 114.3, 129.5, 131.2, 159.5. ESI-MS: m/z
(%): 259(M+1). Compound 3j: Solid, mp 54–55 °C, IR (KBr):
1195, 775 cmÀ1 1H NMR (200 MHz, CDCl3): d 4.41 (s, –O–CH2Ph, 4H), 7.25–7.34
(m, Ar-H, 8H). 13C NMR (50 MHz, CDCl3): d 71.2, 128.8, 129.3, 131.8, 138.5. ESI-
MS: m/z (%): 268 (M+1). Compound 3m: Liquid, IR (KBr): 2923, 1618, 1218,
m 2996, 1633, 1439,
.
m
Acknowledgment
771 cmÀ1 1H NMR (200 MHz, CDCl3): d 1.66 (d, J = 7.0 Hz, –CHCH3, 6H), 4.24 (q,
.
J = 7.0 Hz, –CHCH3, 2H), 7.19–7.37 (m, Ar-H, 10H).13C NMR (50 MHz, CDCl3): d
26.1, 80.1, 126.6, 127.8, 128.7, 145.4. ESI-MS: m/z (%): 227(M+1).
S.S. and T.S. thank CSIR, New Delhi for the award of fellowships.