Highly efficient catalytic system for hydrosilylation of ketones with iron(II) acetate-thiophenecarboxylate

Article abstract of DOI:10.1016/j.tetlet.2007.11.002

A combination of a catalyst derived from ferrous acetate and sodium thiophene-2-carboxylate efficiently promoted hydrosilylation of aromatic and aliphatic ketones to give the corresponding secondary alcohols in high yields with extremely high selectivity.

Full text of DOI:10.1016/j.tetlet.2007.11.002

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 110–113
Highly efficient catalytic system for hydrosilylation of ketones
with iron(II) acetate–thiophenecarboxylate
Akihiro Furuta and Hisao Nishiyama*
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Chikusa, Nagoya 464-8603, Japan
Received 13 September 2007; revised 31 October 2007; accepted 1 November 2007
Available online 4 November 2007
Abstract—A combination of a catalyst derived from ferrous acetate and sodium thiophene-2-carboxylate efficiently promoted
hydrosilylation of aromatic and aliphatic ketones to give the corresponding secondary alcohols in high yields with extremely high
selectivity.
Ó 2007 Elsevier Ltd. All rights reserved.
Efficient reduction of simple ketones to secondary alco-
hols is an important subject for organic synthesis.1 Potent
methods for the reduction to meet social demands such as
environmentally sound and inexpensive ones have been
quested continuously. In this context, we have recently
reported catalytic hydrosilylation of ketones with iron
catalysts, which consist of commercially available
Fe(OAc)2 and a nitrogen-based ligand, N,N,N0,N0-tetra-
methylethylenediamine (TMEDA) (Scheme 1).2 However,
the selectivity of hydrosilylative reduction giving the
desired secondary alcohols largely fluctuated to recover
the starting ketones (ca. 2–50%) derived from dehydro-
genative silylation depending on substrate ketones.
In general, metal-catalyzed hydrosilylation of ketones A
thus also suffers from dehydrogenative silylation to form
silyl enol ether C, which regenerates the starting ketone A
after hydrolytic work up (Scheme 2).
the sulfur atom making preferable bonding to iron atom
not only as shown in some enzymes but also organo-
metallic iron complexes.3 We have focused on thiophene
derivatives as ligands. First, we confirmed that ferrous
acetate itself gave only a trace amount of reduction
product (Table 1, entry 1). Next, we examined thiophene
3a as a ligand to find that hydrosilylation of 4-phenyl-
phenyl methyl ketones 1 with 5 mol % of ferrous acetate
and diethoxymethylsilane (2.0 equiv) took place, but it
gave the reduction product 2 in only 15% of the yield
at 65 °C for 24 h (Scheme 3, entry 2 of Table 1), where
85% of the starting ketone remained unreacted and
was recovered. Addition of dithiophene 3b and thio-
phenecarboxylic acid 3c also did not work well (entries
3 and 4). However, when we adopted sodium thio-
phene-2-carboxylate (3d, STC) as an additive, we even-
tually found almost complete selectivity in high yield
(entry 5). Where, the conversion was 100%, and no start-
ing ketone was recovered. In place of (EtO)2MeSiH,
During our continuous search for efficient ligands for
catalytic hydrosilylation, we have been fascinated with
Metal cat.
R3Si-H
5 mol% Fe(OAc)2
Ph
H
Me2NCH2CH2NMe2
Ph
(EtO)2MeSiH
+
CH3
CH3
OH
O
O
O
THF, 65 °C, 20 h
SiR3
SiR3
O
work up with H3O+
A
B
C
2
1
94 % (recovered 1, 3%)
H3O+
H
Scheme 1. Iron–TMEDA catalyst for hydrosilylation of ketones.
+
O
O
H
Keywords: Iron; Thiophene; Hydrosilyation; Ketone; Reduction.
D
A
*
Corresponding author. Fax: +81 52 789 3209; e-mail: hnishi@
apchem.nagoya-u.ac.jp
Scheme 2. Metal-catalyzed hydrosilylation of ketones.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.002

A. Furuta, H. Nishiyama / Tetrahedron Letters 49 (2008) 110–113
Table 1. Iron-catalyzed hydrosilylation of ketonesa
111
Entry
Metal salt (mol %)
Ligand (mol %)
°C/h
Yield of 2 (%)
Recovered ketone 1 (%)
1
2
3
4
5
6c
7
8
9
Fe(OAc)2 (5)
Fe(OAc)2 (5)
Fe(OAc)2 (5)
Fe(OAc)2 (5)
Fe(OAc)2 (5)
Fe(OAc)2 (5)
Fe(OAc)2 (2)
—
—
65/24
65/24
65/24
65/24
65/24
65/24
65/36
65/24
65/24
65/24
4
15
10
20
99
90
98
No react
No react
No react
94b
85b
89b
76b
0
3a (10)
3b (10)
3c (10)
3d (10)
3d (10)
3d (4)
3d (10)
3d (10)
3d (10)
7d
0
—
—
—
FeCl3 (5)
Fe(acac)3 (5)
10
a 4-Phenylphenyl methyl ketone (1) (1.0 mmol), THF (3 mL), (EtO)2MeSiH (2.0 mmol).
b Ketone 1 remained unreacted and then recovered.
c PMHS (ca 2.0 mmol) in place of (EtO)2MeSiH.
d Conversion was ca 100%. The ketone was recovered after hydrolysis.
of the ketone, respectively (entry 11). Benzyl ketone
4m, phenethyl ketone 4n and 2-tridecanone (4o) effi-
ciently gave only the secondary alcohols (entries 13–15).
5 mol% Fe(OAc)2
ligand
Ph
Ph
(EtO)2MeSiH
CH3
CH3
OH
THF, 65 °C
work up with H3O+
O
Comparing to our previous results with Fe(OAc)2/
TMEDA catalyst,2 the yields and the selectivity
described here in Table 2 were extremely improved; for
representative examples with Fe(OAc)2/TMEDA cata-
lyst and (EtO)2MeSiH, the substrate ketones [yield (%)
of the corresponding secondary alcohol/yield (%) of
recovered ketone]; 4g [67/31], 4j [89/10], 4k [55/42], 4m
[48/51] and 4n [88/5] (Chart 1).
2
1
R
S
S
S
S
R = CO2H
R = CO2Na
3a
3b
3c
3d
Scheme 3. Iron–thiophene derivatives catalyzed hydrosilylation of
ketones.
In turn, a,b-unsaturated ketones 6 were examined under
the same condition to give mainly the corresponding
1,2-reduction products in 93% of 7a with a small
amount of 1,4-reduction product (Scheme 4). Chalcone
6b resulted in lower yield (57%).
polymethylhydrosiloxane (PMHS) worked similarly but
formed some amounts of the starting ketone after
hydrolysis (entry 6). The reduction with 2 mol % of
Fe(OAc)2 sufficiently proceeded for 36 h to give 2 in
98% (entry 7). We also confirmed that in the absence
of Fe(OAc)2, only STC did not cause the hydrosilylation
(entry 8). The combination of FeCl3 and Fe(acac)3 with
STC showed no catalytic activity (entries 9 and 10).
Thus, we have found that almost complete selective
reduction of ketones with the catalyst derived from fer-
rous acetate and sodium thiophene-2-carboxylate and
diethoxymethylsilane as a hydrogen donor.
Table 2. Iron-catalyzed hydrosilylation of other ketonesa
Entry
Ketone
Alcohol
Reaction
time (h)
Yield (%)
(recovered)
1
4a
4b
4c
4d
4e
4f
5a
5b
5c
5d
5e
5f
24
24
24
19
24
24
40
24
24
24
40
48
24
20
24
96 (0)
95 (4)c
97 (<1)c
99 (0)
98 (0)
97 (0)
89 (5)d
95 (0)
94 (0)
99 (0)
93 (3)d
96 (4)d
94 (0)
99 (0)
97 (0)
2b
3b
4
5
6b
7
Under the standard condition adopted for entry 5 in
Table 1, other ketones were subjected to the hydrosily-
lation to furnish the corresponding secondary alcohols
(Table 2). Substituted acetophenones 4a–f were reduced
in high yields 95–99% of 5a–f (conversion = 100%) with
no formation of starting ketones after acidic work up
except p-methoxyphenyl ketone and p-phenoxyphenyl
ketone (Table 2, entries 1–6). Ester and bromo groups
survived under the reduction condition. Although
b-acetonaphthone (4h) was efficiently reduced, a-aceto-
naphthone (4g) resulted in a decrease of the yield to
89% and regeneration of the ketone (5%) (entries 7
and 8). Alkyl phenyl ketones 4i and 4j were reduced to
94% and 99%, respectively (entries 9 and 10). a-Tetra-
lone (4k) was reduced to 93% giving a small amount
4g
4h
4i
5g
5h
5i
8
9
10
11
12
13b
14
15
4j
5j
4k
4l
5k
5l
4m
4n
4o
5m
5n
5o
a Ketone (1.0 mmol), Fe(OAc)2 (5.0 mol %), STC 3d (10 mol %),
(EtO)2MeSiH (2.0 mmol), THF (3.0 mL), 65 °C.
b Work up was performed with TBAF (1 M, 1 mL) and KF (2 mmol)
instead of aq HCl.
c Conversion was almost 100%. The ketone was detected after work up.
d The ketone remained unreacted.

112
A. Furuta, H. Nishiyama / Tetrahedron Letters 49 (2008) 110–113
R
R
CH3
CH3
OH
O
O
O
OH
4j
5j
R = H
R = H
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
R = OCH3
R = OPh
R = CO2CH3
R = Br
R = OCH3
R = OPh
R = CO2CH3
R = Br
OH
OH
4k
4l
5k
5l
OCH3
CH3
O
OCH3
CH3
OH
4f
5f
O
H3CO
H3CO
O
OH
CH3
CH3
4m
5m
H3C
O
H3C
OH
4g
5g
CH3
CH3
CH3
OH
CH3
CH3
OH
4n
5n
O
O
O
4h
4i
5h
5i
n-C5H11
n-C5H11
OH
n-C11H23
n-C11H23
CH3
OH
O
4o
5o
Chart 1.
carboxylate catalyst for the transfer hydrogenation
(Scheme 5, a) and hydrogenation of ketone (Scheme 5,
b). The transfer hydrogenation with ketone 1 with
Fe(OAc)2 (5 mol %), STC (10 mol %) and NaOt-Bu
(30 mol %) in isopropyl alcohol proceeded to give alco-
hol 2 in only 23% yield (unreacted ketone, 66% recov-
ered) at 65 °C for 24 h. At 80 °C for 24 h, the yield
increased to 69% yield (recovered ketone, 28%). Under
molecular hydrogen atmosphere (6 atm), a very weak
acceleration was observed to form alcohol 2 in 30% yield
(recovered ketone, 70%) at 65 °C for 24 h. Therefore, we
conclude that the iron–thiophenecarboxylate system
proved to be not so sufficient for transfer hydrogenation
and hydrogenation.
5 mol% Fe(OAc)2
10 mol% STC
(EtO)2MeSiH
R
R
THF, 65 °C
work up with H3O+
O
OH
6a
6b
7a 93% (1,4-reduction = 2%)
7b 57% (1,4-reduction = 11%)
R = Me
R = Ph
Scheme 4. Iron-catalyzed hydrosilylation of a,b-unsaturated ketone.
In terms of iron-catalyzed reduction of ketones, transfer
hydrogenation with iron–phosphine catalysts has been
reported by Beller and co-workers.4 In addition, Casey
and Guan recently reported an iron–hydroxycyclopenta-
dienyl complex for hydrogenation of ketones.5 These
works prompted us to check an ability of iron–thiophene-
In summary, we have thus found a highly efficient method
for catalytic hydrosilylation of ketones with iron–thio-
phenecarboxylate.6 At this stage, although we cannot
clearly explain the effect of thiophenecarboxylate
(STC), we think that one or two STC moieties can
strongly bind to iron as a bidentate ligand through S
atom and COOꢀ skeleton to prevent from undesirable
dehydrogenative silylation.7
Ph
Ph
a) and b)
CH3
CH3
OH
O
1
2
a) Fe(OAc)2 (5 mol%) ,STC 3d (10 mol%),
NaO-t-Bu (30 mol%), i-PrOH (3 ml):
Acknowledgements
65 °C, 24 h, 2 (23%), recovered 1 (66%)
80 °C, 24 h, 2 (69%), recovered 1 (28%)
This work was partly supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan
(460:18065011), the Japan Society for the Promotion
of Science (18350049) and Mitsubishi Foundation.
b) Under the same condition of a, H2 (6 atm):
65°C, 24 h, 2 (30%), recovered 1 (70%).
Scheme 5. Iron-catalyzed transfer hydrogenation and hydrogenation.

A. Furuta, H. Nishiyama / Tetrahedron Letters 49 (2008) 110–113
113
(%) of 2/recovered 1], Pd(OAc)2 [15/76], Sn(OAc)2 [18/80],
Co(OAc)2 [37/58] and Cu(OAc)2 [no react]. On the other
hand, the set of Zn(OAc)2 and STC exhibited high activity
[98/0]. Under the same standard reaction condition (at
65 °C, 10 h), p-methoxybenzaldehyde was also reduced to
p-methoxybenzyl alcohol in 96% yield.
References and notes
1. As reviews for hydrosilylation including asymmetric catal-
ysis: Carpentier, J.-F.; Bette, V. Curr. Org. Chem. 2002, 6,
913; Riant, O.; Mostefai, N.; Courmarcel, J. Synthesis 2004,
2943.
7. Typical procedure. Hydrosilylation of methyl 4-phenylphenyl
2. Nishiyama, H.; Furuta, A. Chem. Commun. 2007, 760.
3. For chiral sulfur-containing ligands, as review: Pellissier, H.
Tetrahedron 2007, 63, 1297; For new thiophene-containing
ligands: Albano, V. G.; Bandini, M.; Barbarella, G.;
Melucci, M.; Monari, M.; Piccinelli, F.; Tommasi, S.;
Umani-Ronchi, A. Chem. Eur. J. 2006, 12, 667; For enzyme
models containing sulfur skeletons: Volbeda, A.; Fontecil-
la-Camps, J. C. Coord. Chem. Rev. 2005, 249, 1609; For
examples: Justice, A. K.; Linck, R. C.; Rauchfuss, T. B.;
Wilson, S. R. J. Am. Chem. Soc. 2004, 126, 13214; Li, Z.;
Ohki, Y.; Tatsumi, K. J. Am. Chem. Soc. 2005, 127, 8950.
4. Enthaler, S.; Hagemann, B.; Erre, G.; Junge, K.; Beller, M.
Chem.-Asian J. 2006, 1, 598.
ketone (1):
A mixture of ferrous acetate (8.7 mg,
0.05 mmol), ketone 1 (196 mg, 1.0 mmol), sodium thio-
phene-2-carboxylate (3d) (15.0 mg, 0.10 mmol) in absolute
THF (3.0 mL) was stirred for ca 10 min at 65 °C to form an
orange homogenous solution. Then, (EtO)2MeSiH
(0.32 mL, 2.0 mmol) was added by a syringe. The mixture
was stirred at 65 °C for 24 h. After confirming consumption
of 1 by TLC examination, aq HCl (2 N, 2 mL) was added at
0 °C. The mixture was extracted with ethyl acetate, and the
extract was dried over Na2SO4. After concentration, the
residue was purified by silica-gel column chromatography
to give the desired alcohol 2 (196 mg, 0.99 mmol) in 99%
1
yield. The product was analyzed by H and 13C NMR. 2-
5. Casey, C. P.; Guan, H. J. Am. Chem. Soc. 2007, 129, 5816.
6. Other metal acetates (5 mol %) in the combination with
STC were examined to show lower catalytic activity: [yield
Thiophenecarboxylic acid sodium salt was purchased from
Aldrich (28897-7) and Wako (325-75571).