Angewandte
Chemie
DOI: 10.1002/anie.200705624
Iron Catalysis
Iron-Catalyzed Enantioselective Hydrosilylation of Ketones**
Nadim S. Shaikh, Stephan Enthaler, Kathrin Junge, and Matthias Beller*
Dedicated to Professor Wolfgang A. Herrmann on the occasion of his 60th birthday
Noteworthy efforts have been devoted to the development of
efficient catalytic asymmetric reductions employing benign
and environmentally available biometals such as iron, zinc,
and copper. The preparation of enantiomerically pure secon-
dary alcohols is of special significance because these inter-
mediates constitute valuable building blocks for the manu-
facture of pharmaceuticals, agrochemicals, and advanced
we disclose our results on an improved and general iron-
catalyzed asymmetric hydrosilylation of ketones (Table 1).
Our recent study on the hydrosilylation of aldehydes
revealed that Fe(OAc)2 in the presence of electron-rich
Table 1: Ligand screening for the asymmetric hydrosilylation of aceto-
[a]
phenone with Fe(OAc) –ligand.
2
[1]
materials. Catalytic asymmetric hydrogenation of prochiral
[2]
ketones is the most direct route to optically active alcohols,
however, hydrosilylation of carbon–carbon and carbon–
heteroatom bonds is a promising alternative to asymmetric
hydrogenation because of the mild conditions and operational
[
b]
[c]
Entry
Ligand
Yield [%]
ee [%]
[
3]
simplicity.
The earliest reports on hydrosilylation appeared three
1
2
3
4
5
6
7
8
9
(S)-binap
(R)-(S)-josiphos
(S,S)-diop27
(S,S)-chiraphos
(S)-quinap96
(S,S)-deguphos
(R)-binaphane
(R,R)-Me-duphos
(S,S)-Et-duphos
(S,S)-iPr-duphos
(S,S)-Me-duphos
>99
74
1
1
[
4]
decades ago, and known asymmetric hydrosilylations of
14
[
5]
prochiral ketones rely on precious metals such as rhodium,
5
0
[
6]
[7]
ruthenium, and iridium. Less expensive metals such as
8
[
8]
[9]
[10]
[11]
titanium, zinc, tin,
and copper
have also been
68
78
92
>99
99
7
5
explored. Each method has its virtues as well as its limitations.
The limitations include either the cost of the metal catalyst,
the toxicity of the residual metal in the product, the opera-
tional difficulties (e.g. low temperatures ranging from À50 to
À708C), or the use of complex ligand systems.
69 (S)
77 (R)
7
1
1
0
1
>99
75 (R)
[
a] General conditions: Fe(OAc) (5 mol%), ligand (10 mol%), aceto-
phenone (0.5 mmol), (EtO) MeSiH (2 equiv), THF (2 mL), 658C.
Absolute configuration of the secondary alcohol was determined by
comparison of the optical rotation to reported values (see Supporting
Information). (S,S)-diop=(4S,5S)-(+)-4,5-bis(dipheny1phosphino)me-
2
Recently, we started a program to develop more sustain-
able catalysts by replacing precious metals with nonprecious
metals. In accord with the concept of “cheap metals for noble
2
[
12]
tasks”,
the possible uses of iron catalysts are especially
[
13]
attractive. Iron is the second most abundant metal available
and plays an important role in biology. Despite the many
thyI-2,2-dimethyl-1,3-dioxolane;
(S,S)-chiraphos=(2S,3S)-(À)-bis(di-
[14]
phenylphosphino)butane; (R)-binaphane=(R,R)-(À)-1,2,-bis{(R)-4,5-
dihydro-3H-binaptho[1,2-c:2’,1’-e]phosphino}benzene. [b] Determined
by GC-FID methods with diethyleneglycol dimethyl ether as an internal
standard. FID=flame inonization detection. [c] Determined by GC
methods with a chiral column.
[
15]
advantages and recent attention to iron catalysis, it remains
undeveloped compared to other transition metals (e.g. Ru,
Rh, Pd, and Ir etc.), particularly in the field of asymmetric
catalysis. To the best of our knowledge there is only one
report by Nishiyama ând Furuta on the development of
iron-catalyzed asymmetric hydrosilylation. They used multi-
dentate nitrogen ligands and reported enantioselectivities of
up to 79%. The scope of this work can be expanded; herein,
[
16]
phosphine ligands and hydrosilanes forms an active cata-
lyst. On the basis of these findings we turned our attention
to the asymmetric reduction of ketones.
[
17]
Initially, several chiral ligands were tested for the
reduction of acetophenone to 1-phenylethanol by using a
given set of conditions and selected phosphines (Table 1 and
Figure 1). Privileged ligands such as (S)-2,2’-bis(diphenyl-
phosphino)-1,1’-binaphthyl ((S)-binap), (R)-1-[(S)-2-diphe-
nylphosphino)ferrocenyl]ethyldicyclohexylphosphine ((R)-
[
*] Dr. N. S. Shaikh, Dr. S. Enthaler, Dr. K. Junge, Prof. Dr. M. Beller
Leibniz-Institut für Katalyse e.V.
Universität Rostock
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
Fax: (+49)381-1281-5000
(S)-josiphos), (S)-1-[2-(diphenylphosphino)-1-naphthyl]iso-
E-mail: matthias.beller@catalysis.de
quinoline ((S)-quinap), (S,S)-l-benzyl-3,4-bis-(diphenylphos-
phino)pyrrolidine ((S,S)-deguphos), and binaphthyl derived
systems, such as L1 and L2, gave good to excellent con-
versions of acetophenone (68–99%), but poor enantioselec-
tivities (0–14% ee). A 25% ee is observed for L3, indicating
the need for a more basic phosphorus atom to give increased
[
**] N.S.S. thanks the Alexander von Humboldt Foundation (Bonn,-
Germany) for a postdoctoral research fellowship. We gratefully
acknowledge Evonik (formerly Degussa) for the precious gift of
ligands L5–L12.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2008, 47, 2497 –2501
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2497