Reductive etherification of aldehydes photocatalyzed by dicarbonyl pentamethylcyclopentadienyl iron complexes

Article abstract of DOI:10.1016/j.tetlet.2012.07.038

The reductive etherification of aldehydes can be performed by the reaction with dialkylmethylsilanes in the presence of new iron(II) piano-stool catalysts of general formula Cp^*Fe(CO)₂Ar (Cp ^* = η⁵-C₅Me₅; Ar = Ph, 4-C₆H₄OCH₃, 4-C₆H₄CH ₃, Fc). This transformation is promoted by UV light and affords a simple route for the preparation of unsymmetrical alkyl ethers.

Full text of DOI:10.1016/j.tetlet.2012.07.038

Tetrahedron Letters 53 (2012) 5015–5018
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Reductive etherification of aldehydes photocatalyzed by dicarbonyl
pentamethylcyclopentadienyl iron complexes
Gilles Argouarch a, , Guillaume Grelaud a,b, Thierry Roisnel c, Mark G. Humphrey b, Frédéric Paul a
⇑
a Institut des Sciences Chimiques de Rennes, Organométalliques: Matériaux et Catalyse, UMR CNRS 6226, Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France
b Research School of Chemistry, Australian National University, Canberra, ACT 0200, Australia
c Institut des Sciences Chimiques de Rennes, Centre de Diffractométrie X, UMR CNRS 6226, Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The reductive etherification of aldehydes can be performed by the reaction with dialkylmethylsilanes in
the presence of new iron(II) piano-stool catalysts of general formula Cp⁄Fe(CO)2Ar (Cp⁄ =
g
5-C5Me5;
Received 14 May 2012
Revised 4 July 2012
Accepted 10 July 2012
Available online 15 July 2012
Ar = Ph, 4-C6H4OCH3, 4-C6H4CH3, Fc). This transformation is promoted by UV light and affords a simple
route for the preparation of unsymmetrical alkyl ethers.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Reductive etherification
Silanes
Iron catalysis
Piano-stool complexes
In recent years, there has been continuing interest in the cata-
lyzed reductive etherification of carbonyl compounds because
the ether linkage is one of the most important functional groups
in organic chemistry.1–13 This valuable transformation involves
the use of organosilanes with aldehydes or ketones in the presence
of a Lewis acid catalyst, carried out under very mild reaction con-
ditions to limit the formation of side products (in contrast to more
classical methods such as the Williamson synthesis), and thus give
symmetrical or unsymmetrical ethers in high yields. Typically, car-
bonyl compounds are converted into mixed ethers with trimethyl-
silyl ethers (or the corresponding unprotected alcohol) as the
alkoxy source and triethylsilane as the reductant (Scheme 1).
Various Lewis acids, ranging from metal salts such as InCl3,3
R"OTMS
or
O
Et3SiH
Cat.
OR"
R'
+
R
R'
R
R"OH
Scheme 1. Synthesis of unsymmetrical ethers by reductive etherification of
carbonyl compounds.
or Diels–Alder and other cycloaddition reactions.14 Interest in
these molecules is currently growing due to the abundance,
sustainability, and non-toxicity of iron, in conjunction with the
versatility and selectivity of iron complexes in catalysis.15 With
the last-mentioned in mind, we have now prepared and fully
characterized a series of piano-stool iron(II)
r–aryl complexes of
general formula Cp⁄Fe(CO)2Ar and found that representatives of a
family of such molecules display good catalytic activity for the
UV-promoted reductive etherification of aromatic and aliphatic
aldehydes.
FeCl3,4 BiCl3,8 or Cu(OTf)2 to metal-free species such as TMSI,11
7
TMSOTf,10 or triflic acid,1 have been examined and proved to be
efficient catalysts in this reductive coupling. However, we believe
that despite the diversity and the usefulness of the previous cata-
lytic systems, development of practical and original procedures for
this transformation remains desirable.
The iron precatalysts Cp⁄Fe(CO)2Ar (Ar = Ph (2); (4-C6H4OCH3)
(3); (4-C6H4CH3) (4); Fc (5)) were synthesized as shown in Scheme
2. When treated with phenyllithium or lithiobenzene derivatives,
the readily accessible iodo precursor Cp⁄Fe(CO)2I (1)16 undergoes
a substitution reaction to give the desired complexes 2–4. A similar
reaction of 1 with monolithioferrocene, prepared according to the
procedure of Mueller–Westerhoff,17 gives the homodinuclear iron
product 5. After purification, these compounds were obtained as
air-stable yellow solids in fair to good yields.
Half-metallocene iron(II) carbonyl complexes incorporating
[CpFe(CO)n] or [Cp⁄Fe(CO)n] fragments (n = 1 or 2; Cp: cyclopenta-
dienyl =
g g
5-C5H5; Cp⁄: pentamethylcyclopentadienyl = 5-C5Me5)
have been used as Lewis acid catalysts since the early 1980s for
various organic transformations such as C–C bond formation,
reduction of carbonyl compounds, living radical polymerization,
While considerable recent efforts have been focused on opti-
mizing the syntheses of a wide range of parent CpFe(CO)2Ar deriv-
atives,18 the metathesis of 1 with aryllithium reagents that we
⇑
Corresponding author. Tel.: +33 02 23 23 59 61; fax: +33 02 23 23 69 39.
E-mail address: gilles.argouarch@univ-rennes1.fr (G. Argouarch).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.038

5016
G. Argouarch et al. / Tetrahedron Letters 53 (2012) 5015–5018
Table 1
Catalytic behavior of iron complexes 2–5
OEt2
1) (EtO)2MeSiH, DCM
Fe
I
Fe
R
+
Li
R
CHO
0 °C to rt
OC
OC
ν
O
cat. [Fe], h , 4 h
OC
OC
Br
Br
2
2) Hydrolysis
1
R = H (67%)
3 R = OCH3 (60%)
4 R = CH3 (42%)
Runa
Catalyst
Yieldb (%)
THF
0 °C to rt
1
2
3
4
5
None
0
FcLi
2
3
4
5
88
93
95
88
Fe
OC
Fe
OC
a
All reactions were carried out with 2 mmol of 4-bromobenzaldehyde, 1.5 equiv
of silane, and 0.02 equiv of the catalyst.
5 (63%)
Scheme 2. Synthesis of precatalysts 2–5.
b
Isolated yields.
is the solvent of choice for this reaction; in comparison, acetonitrile
or toluene gives poor conversions even after longer reaction times.
(3) Attempts performed under various conditions without UV light
were unsuccessful. (4) The diethoxymethylsilane provides the eth-
oxy group of the isolated ether and presumably acts as the hydride
source during the reaction, since the substrate was recovered when
diphenylsilane was used in its place.
Next, the scope and limitations of this iron-catalyzed reductive
etherification were investigated with 3 as the model catalyst and a
variety of aromatic aldehydes under the same reaction conditions
(Table 2, runs 1–9). Benzaldehyde (run 1) and its alkylated (run
6) or halogenated (runs 2, 4 and 7) derivatives were well tolerated.
When methyl 4-formylbenzoate was used, etherification of the
aldehyde was followed by saponification of the ester and the cor-
responding benzoic acid product was formed (run 8), but a slight
modification of the hydrolysis step allowed to maintain the ester
group in the final product (run 9). Surprisingly, when substrates
with strong electron-releasing or electron-withdrawing functional
groups were tested (runs 3 and 5), the catalytic activity of 3 was
lost. Efforts to understand and to overcome these substituent ef-
fects (which were also observed with 2, 4, and 5) have so far been
unsuccessful.
When dimethoxymethylsilane was used in this reaction (runs
10–14), the expected benzyl methyl ether derivatives were iso-
lated in excellent yields. Particularly noteworthy is that the more
sterically hindered o-tolualdehyde also gave the desired product
in almost quantitative yield (run 14). Furthermore, we have found
that this reaction is similarly effective for aliphatic aldehydes such
as undecyl aldehyde (run 15) or phenylacetaldehyde (run 16), but
with these substrates the hydrolysis step must be avoided to pre-
vent any decomposition of the ether formed, and was replaced by a
chromatographic purification.
have employed possibly constitutes the most straightforward
route to the molecules depicted here although, to the best of our
knowledge, only one representative of this family, that is Cp⁄Fe(-
CO)2(2,6-C6H3F2), has been previously synthesized following this
protocol.19 The new complexes were readily identified by the usual
spectroscopies and satisfactory high-resolution mass spectrometry
and elemental analyses were obtained. The crystal structures of 2–
5 were unequivocally determined by X-ray diffraction analyses, as
illustrated for 5 in Figure 1, and can be described as distorted
three-legged piano-stool iron complexes with bond lengths and
angles within the previously established ranges.16 They are essen-
tially symmetrical with respect to the plane bisecting the Fe(CO)2
unit.
We then investigated the catalytic activity of iron carbonyl com-
pounds 2–5 for the reaction of aldehydes with functional silanes
under irradiation. First, 4-bromobenzaldehyde as the model sub-
strate was treated with 1.5 equiv of diethoxymethylsilane under
UV light, in the presence of complexes 2–5 at a catalytic loading
of 2 mol % (Table 1). After 4 h of irradiation, full conversion of the
aldehyde was achieved and only 1-bromo-4-(ethoxymethyl)ben-
zene was isolated in high yields following hydrolysis (runs 2–5).
The following comments can be made: (1) No reaction is ob-
served in the absence of catalyst (run 1). (2) Methylene chloride
We believe that the mechanism of this photocatalyzed process
can be considered to proceed via an hemiacetal-type intermedi-
ate.12,13 The active Lewis acid catalysts certainly originate from
the photochemical decarbonylation of the precatalysts 2–5 to give
16-electron intermediates of general formula [Cp⁄Fe(CO)Ar], and
not from the cleavage of the
r-bonded aryl ligand leading to the
cationic [Cp⁄Fe(CO)2]+ fragment. Indeed, the photolabilization of
CO ligands in Cp⁄Fe(CO)2X architectures has been established pre-
viously,19,20 and when the THF adduct [Cp⁄Fe(CO)2(THF)][PF6]21
was employed in the reaction, no transformation occurred.
In conclusion, we have found a new photoinduced reaction for
the preparation of unsymmetrical ethers from both aromatic and
aliphatic aldehydes. For the first time, stable iron(II) carbonyl com-
plexes activated upon UV irradiation were employed in this reduc-
tive etherification. The main advantages of this protocol are rapid
and clean conversion of the substrates under mild reaction condi-
tions, low catalytic loadings, and the necessity for only one silane
reagent.
Figure 1. Molecular diagram of compound 5 at the 40% probability level. All
hydrogen atoms have been omitted for clarity. Selected bond distances (Å) and
angles (deg): Fe(1)–C(11) 1.752(2), Fe(1)–C(13) 1.760(2), Fe(1)–C(21) 1.985(0),
C(11)–O(12) 1.152(2), C(13)–O(14) 1.148(2), Fe(1)–Cp⁄centroid 1.729, Fe(2)–Cpcentroid
1.653, C(11)–Fe(1)–C(13) 96.48(9), C(11)–Fe(1)–C(21) 90.57(8), C(13)–Fe(1)–C(21)
90.81(8), O(12)–C(11)–Fe(1) 177.2(5), O(14)–C(13)–Fe(1) 177.7(4), C(21)–Fe(1)–
Cp⁄
120.31, C(11)–Fe(1)–Cp⁄
124.58, C(13)–Fe(1)–Cp⁄
124.74.
centroid
centroid
centroid

G. Argouarch et al. / Tetrahedron Letters 53 (2012) 5015–5018
5017
Table 2
Screening of the reaction using 3 as the catalyst
3 (2 mol %)
+
(R'O)2MeSiH
R
R
OR'
O
DCM, hν, 4 h
Runa
1
Substrate
CHO
Silane
Product
Yieldb (%)
O
O
(EtO)2MeSiH
70
84
CHO
2
3
’’
’’
Br
Br
CHO
O
0
O2N
O2N
CHO
O
4
5
6
7
’’
’’
’’
’’
91
Cl
Cl
CHO
O
Trace
73
MeO
Me
MeO
Me
F
CHO
O
CHO
O
78
F
CHO
CHO
O
O
O
8
’’
94
Me
HO2C
O
O
9c
’’
75
98
O
Me
Me
O
O
CHO
CHO
O
O
10
(MeO)2MeSiH
Br
Br
11
12
13
’’
’’
’’
99
82
90
Me
Me
CHO
O
O
CHO
O
Cl
Cl
CHO
O
14
’’
99
70
70
O
15d
16d
(EtO)2MeSiH
’’
9
9
O
CHO
a
b
c
All reactions were carried out with 2 mmol of the substrate, 1.5 equiv of silane, and 0.02 equiv of 3.
Isolated yields.
To avoid saponification of the product, the hydrolysis step was modified.
Purification of the crude product by chromatography instead of hydrolysis.
d
Acknowledgments
Supplementary data
G.G. thanks Region Bretagne for partial support of a PhD scholar-
ship. The CNRS (PICS program N° 5676 & ANR 2010-BLAN-7191) is
acknowledged for financial support. M.G.H. thanks the ARC for an
Australian Professorial Fellowship.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
07.038.

5018
G. Argouarch et al. / Tetrahedron Letters 53 (2012) 5015–5018
T.; Itazaki, M.; Nakazawa, H. Organometallics 2011, 30, 3461–3463; (c) Krishna
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