of these results we became interested in the iron-catalyzed
hydrosilylation of carbonyl compounds.
Here, we report for the first time our investigations, which
result in a highly chemoselective reduction of aldehydes with
broad substrate scope.
higher catalyst loading (15 mol %, 20 mol % ligand) and
temperature (85 °C). Other iron salts of Fe(II) as well as
Fe(III) showed very little or no activity (Table 1, entries 6-9,
12, 14-16). Fe(OAc)2 was chosen for further studies as it
is easy to handle, for example, can be handled/weighed in
air. There was no conversion when the reaction was carried
out at room temperature using Fe(OAc)2/PCy3/PMHS system.
Further screening of ligands (Table 2) revealed that a more
As shown in Table 1, several commercially available iron
Table 1. Iron-Catalyzed Hydrosilylation of Benzaldehydea
a
Table 2. Hydrosilylation of Benzaldehyde Using Fe(OAc)2
entry
ligand
silane
yield(%)b
1
2
3
4
5
6
7
PCy3
PCy3
PCy3
PCy3
PCy3
tBu3P
PMHS
(EtO)2MeSiH
Ph2SiH2
PhSiH3
Ph2MeSiH
PMHS
98
95c
64
83
<1
61
10
entry
catalyst
Fe(acac)2
Fe(OAc)2
Fe(OAc)2
Fe(OAc)2
Fe(OAc)2
FeCl2
temp (°C)
yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
65
65
65
rt
18
90c
98
0
75
10
0
2-(Di-tert-butylphosphino)-1- PMHS
phenyl-1H-pyrrole
PPh3
Di-1-adamantyl-n-
butyl-phosphine
DPPC
50
65
65
65
65
65
85
65
65
65
65
65
8
9
PMHS
PMHS
9
<1
FeI2
FeF2
2
FeCl3 (anhydrous)
Fe(ClO4)3
Fe(ClO4)3
Fe(III)citrate
Fe(BF4)2.6H2O
Fe(acac)3
FeBr2
25
10
57d
<1
92
5
10
11
12
PMHS
PMHS
PMHS
15
2
3
DPPM
DPPE
a Unless otherwise stated, the reactions were performed at 65 °C for 16
h with benzaldehyde (0.5 mmol) in THF (2 mL) using silane (1.6 equiv) or
PMHS (3 equiv). Iron catalyst 5 mol % and ligand 10 mol % were used.
b Yield of 1b determined by GC-FID using diethyleneglycol dimethyl ether
as an internal standard. DPPC, 1,2-bis(diphenyl-phosphino)cyclohexane;
DPPM, bis(diphenylphosphino)methane; DPPE, bis(diphenylphosphino)et-
hane. c Reaction was run for 4 h.
15
21
Fe(OSO2CF3)2
a Reactions were conducted with benzaldehyde (0.5 mmol), unless stated,
iron salt (5 mol %), PCy3 (10 mol %) in THF (2 mL) using PMHS (3
equiv), for 16 h. b Determined by GC-FID using diethylene glycol dimethyl
ether as an internal standard. c Reaction run using 5 mol % ligand. d Reaction
run using 15 mol % catalyst and 20 mol % ligand.
basic phosphine is required for good conversion (e.g., Table
2, entries 1-4 and 6), although to our surprise the hindered
di-1-adamantyl-n-butylphosphine does not show any reactiv-
ity (Table 2, entry 9). Use of other mono- or bidentate ligands
showed very little or no activity at all. Among the tested
hydrosilanes, diethoxymethylsilane and phenylsilane gave
good yields of benzyl alcohol via formation of the corre-
sponding silyl ether intermediates (Table 2, entries 2-4).10
The most inexpensive polymeric hydrosilane, PMHS (3
equiv) proved to be ideal for this catalyst system. Moreover,
diethoxymethylsilane gave similar results (95%, 4 h, Table
2, entry 2).
The order of reactivity of hydrosilanes with the present
catalyst system is observed as PMHS g (EtO)2MeSiH >
PhSiH3 > Ph2SiH2 > Ph2MeSiH (Table 2, entries 1-5). After
optimization, we were able to demonstrate the generality of
our practical hydrosilylation with several aromatic aldehydes
(Table 3).
salts were tested in the presence of tricyclohexyl-phosphine
as a ligand and polymethylhydrosiloxan (PMHS)9 for the
hydrosilylation of benzaldehyde. In this model reaction
benzaldehyde is converted to (polymeric) silyl ether inter-
mediates, which upon basic workup afforded benzyl alcohol.
At 65 °C Fe(OAc)2 and Fe(BF4)2‚6H2O proved to be most
reactive (Table 1, entries 2, 3, and 13). Iron perchlorate
(hydrate) gave benzyl alcohol in moderate yield (57%) at
(7) (a) Anilkumar, G.; Bitterlich, B.; Gelalcha, F. G.; Tse, M. K.; Beller,
M. Chem. Commun. 2007, 289-291. (b) Bitterlich, B.; Anilkumar, G.;
Gelalcha, F. G.; Spilker, B.; Grotevendt, A.; Jackstell, R.; Tse, M. K.; Beller,
M. Chem. Asian J. 2007, 2, 521-529. (c) Gelalcha, F. G.; Bitterlich, B.;
Anilkumar, G.; Tse, M. K.; Beller, M. Angew. Chem, Int. Ed. 2007, 46,
7293-7296.
(8) (a) Kischel, J.; Jovel, I.; Mertins, K.; Zapf, A.; Beller, M. Org. Lett.
2006, 8, 19-22. (b) Iovel, I.; Mertins, K.; Kischel, J.; Zapf, A.; Beller, M.
Angew. Chem., Int. Ed. 2005, 44, 3913-3917.
(9) PMHS was discovered as a stoichiometric reductant with reduced
toxicity and reagent cost: (a) Barr, K. J.; Berki, S. C.; Buchwald, S. L. J.
Org. Chem. 1994, 59, 4323. For a review on PMHS see: (b) Lawrence, N.
J.; Drew, M. D.; Bushell, S. M. J. Chem. Soc., Perkin Trans. 1 1999, 3381-
3391. For the use of PMHS in hydrosilylation (c) Mimoun, H. J. Org. Chem.
1999, 64, 2582-2589. The first example of iron with PMHS in the presence
of NaBH4 for the reduction of carbonyl: (d) Mimoun, H. Patent WO 96/
12694, Firmenich S. A., 1995. (e) Hansen, M. C.; Buchwald, S. L. Org.
Lett. 2000, 2, 713-715. (f) Jurkauskas, V.; Sadighi, P.; Buchwald, S. L.
Org. Lett. 2003, 5, 2417-2420.
The duration of the reaction was unoptimized; however,
no product was formed in the first 3 h in the case of
benzaldehyde (monitored by GC for entries 1, 3-5). In most
(10) According to GC-MS analysis of the reaction mixture the corre-
sponding silyl ethers (m/z ) 240, 290, 214; Table 2, entries 2-4,
respectively) were detected. Ph2MeSiH was inert under the present reaction
conditions.
5430
Org. Lett., Vol. 9, No. 26, 2007