Angewandte
Chemie
DOI: 10.1002/anie.200700949
Asymmetric Epoxidation
Titanium-Catalyzed Asymmetric Epoxidation of Non-Activated
Olefins with Hydrogen Peroxide**
Yuji Sawada, Kazuhiro Matsumoto, and Tsutomu Katsuki*
Asymmetric epoxidation of olefins is a potent method for
synthesizing enantioenriched epoxides that are high-utility
intermediates. Thus, over the past few decades, extensive
research efforts have been devoted to the development of
The development of asymmetric epoxidation of aliphatic
olefins (non-activated olefins) with aqueous hydrogen perox-
ide is a high-priority issue; however, there are just a few
catalysts for the reaction. Although a platinum catalyst was
reported by Strukul and co-workers, it has been applied only
[
1]
catalytic asymmetric epoxidation,
and some excellent
[2]
[3]
[9]
transition-metal catalysts based on titanium, manganese,
to terminal olefins with no a branches. Herein, we describe
[
4]
[5]
vanadium, and molybdenum as well as organocatalysts
asymmetric epoxidation of non-activated olefins with aque-
ous hydrogen peroxide, which was achieved by using
titanium(salalen) complex 1 and had a much wider substrate
scope.
[
6]
such as chiral ketones have been reported. However, these
reactions require oxidants of lower atom-efficiency such as
bulky alkyl hydroperoxides and oxones. From the viewpoint
of green sustainability, the development of asymmetric
epoxidation using aqueous hydrogen peroxide that is low-
cost, highly atom-efficient, easy-to-handle, and ecologically
benign (no production of hazardous waste), has been strongly
We first examined epoxidation of non-activated olefins at
room temperature (Table 1). Yield was sharply sensitive to
substrate concentration, and high yields were obtained at high
[
8a]
concentration. A selectivity of 80% ee was observed in the
epoxidation of non-branched terminal olefins, irrespective of
the presence or absence of a functional group such as ester or
ether and the length of the alkyl substituents (entries 2–5,
Table 1). Reflecting the steric bulk of the alkyl substituent,
epoxidation of vinylcyclohexane showed an improved enan-
tioselectivity of 95% ee (entry 6, Table 1). Z Olefins are also
favorable substrates and asymmetric epoxidation of non-
branched Z olefins showed good enantioselectivity (entries 7–
9, Table 1). Reactions of 1-cyclohexyl-1-alkenes also pro-
ceeded with good enantioselectivities of 73–81% ee, but the
reactions were slow (entries 10 and 11, Table 1). Moreover,
the epoxidation of (Z)-2,2-dimethyl-3-decene exhibited a
high enantioselectivity of 97% ee yet was much slower
[
7]
desired in industry and academic research.
Recently, we found that di-m-oxo titanium(salalen) and di-
m-oxo titanium(salan) complexes serve as efficient catalysts
for asymmetric epoxidation of olefins using aqueous hydro-
[
8]
gen peroxide. The epoxidation of conjugated olefins with
the di-m-oxo titanium(salalen) complex 1 (Figure 1) pro-
ceeded with high turnover numbers (up to 4600) as well as
high to excellent enantioselectivity at room temperature. We
also preliminarily examined epoxidation of 1-octene and
obtained a high enantioselectivity of 82% ee.
(entry 12, Table 1). These results indicate that complex 1
can efficiently differentiate not only the alkyl group and the
hydrogen atom but also methyl and methylene, methylene
and methine, and methylene and quaternary carbons. While a
good enantioselectivity of 70% ee was obtained in the
epoxidation of (Z)-2-pentenyl benzyl ether, the reaction of
(Z)-3-decene was poorly enantioselective, indicating that the
differentiation of simple n-alkyl groups is difficult (entries 13
and 14, Table 1). It is also noteworthy that this asymmetric
epoxidation is stereospecific and no isomerization was
Figure 1. Di-m-oxo titanium(salalen) complex 1.
1
detected in the epoxidation of Z olefins by H NMR analysis
(entries 7–14, Table 1). Furthermore, low catalyst loading of
[
*] Y. Sawada, K. Matsumoto, Prof. T. Katsuki
Department of Chemistry, Faculty of Science
Graduate School, Kyushu University
Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)
Fax: (+81)92-642-2607
1–3 mol% is sufficient for the epoxidation. To our knowledge,
this is the first example showing better than 70% ee in
epoxidation of non-activated Z olefins using aqueous hydro-
[10]
gen peroxide.
With these results, we investigated regio- and enantiose-
lectivity of epoxidation of dienes that have terminal and
internal double bonds. In electrophilic epoxidation, the more
electron-rich C=C bond tends to be epoxidized preferentially.
However, less electron-rich terminal C=C bonds were selec-
E-mail: katsuscc@mbox.nc.kyushu-u.ac.jp
[
**] Financial support (Specially Promoted Research 18002011) from a
Grant-in-Aid for Scientific Research from the Ministry of Education,
Science, and Culture, Japan, is gratefully acknowledged. K.M. is
grateful for a JSPS Research Fellowship for Young Scientists.
tively epoxidized under the present conditions with good to
high regioselectivity (Scheme 1). Although the detailed
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2007, 46, 4559 –4561
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4559