Synthesis of ethers from esters via Fe-catalyzed hydrosilylation

Article abstract of DOI:10.1039/c2cc32142d

Triiron dodecacarbonyl allows for the selective reduction of esters into the corresponding ethers. This protocol has a wide substrate scope. In addition, cholesteryl pelarogonate has been reduced under the reaction conditions with an excellent yield.

Full text of DOI:10.1039/c2cc32142d

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COMMUNICATION
Synthesis of ethers from esters via Fe-catalyzed hydrosilylationw
Shoubhik Das, Yuehui Li, Kathrin Junge and Matthias Beller*
Received 23rd March 2012, Accepted 13th September 2012
DOI: 10.1039/c2cc32142d
Triiron dodecacarbonyl allows for the selective reduction of
esters into the corresponding ethers. This protocol has a wide
substrate scope. In addition, cholesteryl pelarogonate has been
reduced under the reaction conditions with an excellent yield.
Due to the unique chemo- and regioselectivity of silanes, more
recently catalytic hydrosilylations have become increasingly
popular in organic synthesis.10,11 Unfortunately, similar to
catalytic hydrogenations the majority of the known transition
metal-based catalysts in hydrosilylations lead only to alcohols.12
Nevertheless, few examples of catalytic hydrosilylation to ethers
with Mn,13 Ti,14 Ru15 and In-based16 catalysts are known.
However, still these procedures need further improvement
as they use either expensive silanes such as PhSiH3 or large
amounts of catalysts or have limited substrate scope.
Aliphatic and aromatic ethers represent valuable building
blocks for fine chemicals as well as polymers and dyes.1 In
addition, this structural motif is also found in a number of
pharmaceuticals and agrochemicals. The most common approach
for the synthesis of ethers makes use of nucleophilic substitution
reactions of alkoxides with alkyl halides/sulfonates under basic
conditions (Williamson synthesis).2 In addition, acid-promoted
condensations of alcohols,3 and for aromatic ethers Buchwald–
Hartwig cross-coupling reactions are frequently applied.4 Despite
these achievements, the development of novel methods for the
synthesis of ethers continues to be an active area of research.5
Among the different possible starting materials for ether synthesis,
carboxylic esters constitute promising candidates. It is well known
that they can be prepared in a benign manner. Subsequent
catalytic hydrogenation would allow for a salt-free synthesis of
ethers. Unfortunately, so far a general methodology for this
transformation is not known (Scheme 1).
Recently, Fe-based complexes allowed for considerable
inventions in catalysis.17,18 Apart from the abundant availability
of iron, the often low toxicity and the bio-mimetic nature of the
pre-catalysts make iron an ideal candidate for catalysis.19 Based
on our previous studies of the reduction of carboxylic amides to
amines and esters to alcohols,20,21 herein we report the first iron-
catalyzed hydrosilylation of esters to ethers.
Initially, the reaction of 2-phenethyl acetate to give the ether
1 was investigated as a model system to identify and optimize
critical reaction parameters (Table 1). Apart from testing
different pre-catalysts and ligands also various silanes were
employed. By performing the reaction in toluene at 100 1C in
the absence of any catalyst no conversion was observed
(Table 1, entry 1). Similarly, in the presence of 10 mol% of
different iron(II) salts and complexes no activity is found
(Table 1, entries 2–5, 9 and 10). However, applying tetra-
methyldisiloxane (TMDS) in the presence of plain Fe3(CO)12
the reaction gave the desired (2-ethoxyethyl)benzene 1 in 90%
yield (Table 1, entry 8). In addition to TMDS, other silanes
such as PhSiH3, Ph2SiH2, (EtO)3SiH, and PMHS were also
tested for this reduction. From a mechanistic point of view it is
important to note that in none of the latter cases appreciable
activity was found using triiron dodecacarbonyl as a catalyst
(Table 1, entries 11, 16–18). Other previously reported Zn(II)-
and Cu(II)-based catalysts were also applied in the model
reaction but again in none of the cases any activity was
observed (Table 1, entries 12–14). With respect to the mechanism,
we believe that this iron-catalyzed reduction of esters to ethers
proceeds similarly to the reduction of amides recently proposed
by Nagashima and co-workers.22 At first, thermolysis of
Fe3(CO)12 should generate the coordinatively unsaturated
Fe(CO)3 fragment which is believed to be the ‘‘real’’ active species
in the catalytic cycle. This fragment is formed more easily from
the triiron cluster compared to Fe(CO)5 and Fe2(CO)9 or other
iron carbonyl complexes (Table 1, entries 6–10). Subsequent
double oxidative addition of the Si–H groups of TMDS will form
Instead, recent work showed that the corresponding alcohols
are obtained.6 On the other hand, the reduction of esters and
thioesters to ethers is feasible using stoichiometric amounts of
LiAlH4,7 DIBAL8 or organotin hydrides.9 Drawbacks of these
protocols are the price of the reductants, necessity of additives,
air and moisture sensitivity of the stoichiometric organometallic
reagents. Regarding their reduction potential, organosilanes are
in between highly reactive metal hydrides and inert hydrogen.
Advantageously, their activity can be controlled both by the
substituents on the silicone centre as well as by catalysts,
e.g. transition metal complexes, Lewis acids or Lewis bases.
Scheme 1 Possible synthesis of ethers from esters.
Leibniz-Insitut fur Katalyse e.V., Albert-Einstein-Straße 29a, 18059,
¨
Rostock, Germany. E-mail: matthias.beller@catalysis.de;
Fax: +49 381-1281-50000
w Electronic supplementary information (ESI) available: General
information, advanced results, experimental procedures and analytical
data. See DOI: 10.1039/c2cc32142d
c
10742 Chem. Commun., 2012, 48, 10742–10744
This journal is The Royal Society of Chemistry 2012

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Table 1 Iron-catalyzed hydrosilylation of 2-phenylethyl acetate:
variation of catalysts and optimization of reaction conditionsa
Table 2 Iron-catalyzed reduction of estersa
Yieldb [%]
Entry
Esters
Ethers
Entry
Catalyst [mol%]
Silane
Solvent Yieldb [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
—
TMDSc
TMDS
TMDS
TMDS
TMDS
TMDS
TMDS
TMDS
TMDS
TMDS
PMHSd
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
—
—
—
—
—
10
25
90
—
—
35
—
—
—
32
5
1
2
85c
85
Fe(OAc)2 (10)
Fe(BF4)2Á6H2O (10)
Fe(OTf)2 (10)
Fe(NO3)2 (10)
Fe(CO)5 (10)
3
4
5
6
7
78
70
70
75
70
Fe2(CO)9 (10)
Fe3(CO)12 (10)
Fe(CO)3(COT) (10)
CpFe2(CO)4 (10)
Fe3(CO)12 (10)
Zn(OAc)2 (10)
Zn(OTf)2 (10)
Cu(OTf)2 (10)
Fe3(CO)12 (10)
Fe3(CO)12 (10)
Fe3(CO)12 (10)
Fe3(CO)12 (10)
Fe3(CO)12 (5)
Fe3(CO)12 (2.5)
Fe3(CO)12 (10)
Fe3(CO)12 (10)
(EtO)2MeSiH Toluene
TMDS
TMDS
Ph2SiH2
Et3SiH
PhMe2SiH
Ph2MeSiH
TMDS
TMDS
TMDS
TMDS
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
p-Xylene
Dioxane
19
15
78
33
90
61
8
9
60
85
a
Reaction conditions: ester (1.0 mmol), catalyst, silane (3 mmol),
b
solvent (3 mL), 2 h, 100 1C. Determined by GC with hexadecane as
an internal standard. TMDS = tetramethyldisiloxane. 1 mmol
PMHS = 0.06 mL.
c
d
10
11
12
50
60
70
a disilaferracyclic intermediate. Hydrosilylation of the carbo-
nyl group of the ester forms the O-silylated species. After
reductive eliminations the desired ether and siloxane are
produced. This proposed catalytic cycle is in agreement with
the special activity of TMDS compared to monosilanes.
Once suitable reaction conditions were identified for the
model system, next the scope and limitations of this first iron-
catalyzed reduction of esters to ethers were explored. As
shown in Table 2, 19 different aromatic and aliphatic esters
are reduced smoothly to the corresponding ethers (Table 2).
Different aromatic, aliphatic, and alicyclic esters are reduced
under the optimized reduction conditions to give the respective
ethers in 50–85% yield. In none of the cases we observed the
formation of alcohols. Comparing entries 6 and 7 in Table 2
there is no difference between electron-withdrawing and electron-
donating substituents on the aryl ring. As shown by the reduction
of benzofuranone it is also possible to synthesize cyclic ethers by
this methodology (Table 2, entry 8). From a synthetic point of
view the synthesis of non-symmetric aliphatic ethers using this iron
catalyst is interesting, too (Table 2, entries 11–18). Expediently, the
model reaction was easily scaled up to the 50 mmol-scale to
provide 90% of the desired product. After having demonstrated
the synthesis of various aliphatic ethers in good yield we
investigated the reduction of different steroid esters. As an
example the hydrosilylation of cholesteryl nonanoate, also called
cholesteryl pelargonate, was performed (Table 2, entry 19). The
starting material is an industrially applied liquid crystal material,
which is also used for cosmetic applications.
13
14
15
16
17
18
70
71
72
70
73
70
19
70
a
Reaction conditions: esters (1 mmol), Fe3(CO)12 (10 mol%), TMDS
b
(3 mmol), toluene (3 mL). All are isolated yields except entries 8,
11–17 (here GC yields were obtained using hexadecane as an internal
c
standard). In all the cases of isolated yields, the silane was destroyed
after the reaction by adding 3 mL of 2 M solution of sodium hydroxide
for 3 h. Then, the products were purified by column chromatography.
double bond and provided the corresponding ether in 70%
isolated yield. In summary, we developed the first iron-catalyzed
reduction of esters to ethers using TMDS and plain iron carbonyl
In the presence of 10 mol% triiron dodecacarbonyl selective
reduction of the ester group took place without touching the
c
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complexes. Moderate to good yields of 19 different ethers were
obtained starting from aromatic, aliphatic and alicyclic esters.
Clearly, this procedure can be still further improved with
respect to substrate scope and reaction conditions. Never-
theless, we believe it represents a significant step towards the
development of a general methodology for the challenging
transformation of esters into ethers.
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10744 Chem. Commun., 2012, 48, 10742–10744
This journal is The Royal Society of Chemistry 2012