ORGANIC
LETTERS
2003
Vol. 5, No. 1
85-87
Catalytic Enantioselective Epoxidation of
Homoallylic Alcohols by Chiral
Zirconium Complexes
Takahiro Okachi, Norio Murai, and Makoto Onaka*
Department of Chemistry, Graduate School of Arts and Sciences, The UniVersity of
Tokyo, Komaba, Meguro, Tokyo 153-8902, Japan
Received November 10, 2002
ABSTRACT
Catalytic enantioselective epoxidation of homoallylic alcohols using Zr(Ot-Bu)4 and tartrate ester (or tartramide) has been developed. In the
Zr(Ot-Bu)4/diisopropyl tartrate-catalyzed epoxidation, the reverse of the enantiofacial preference was observed, depending on the Zr/ligand
ratios of 1:1 or 1:2.
Asymmetric epoxidation of olefins is a powerful tool for the
production of enantiomerically enriched epoxides that are
versatile building blocks for the synthesis of natural products
and biologically active substances. A variety of efficient
methods have been developed.1-6 The first practical asym-
metric epoxidation was performed with allylic alcohols using
t-BuOOH (TBHP) and stoichiometric amounts of Ti-tartrate
complexes,2 and afterward, the epoxidation was improved
in a catalytic way.3
In contrast, when the Ti-tartrate-TBHP system was
extended to the epoxidation of homoallylic alcohols, the rate
of epoxidation was much slower and the enantiomeric
purities of the resulting epoxides were lower, ranging from
27 to 55% ee.7 Katsuki et al. also reported the asymmetric
epoxidation of homoallylic alcohols using Zr(On-Pr)4 and
tartramide derivatives: the ee of an epoxide from a cis-
homoallylic alcohol was improved to 77% ee (25% yield),
while other homoallylic alcohols gave poor results.8 Here
we report a catalytic asymmetric epoxidation of various
homoallylic alcohols using chiral zirconium complexes.
Initially, we carried out the epoxidation of trans-3-hexen-
1-ol (1a) with cumene hydroperoxide (CHP) using Zr(Ot-
Bu)4 and tartrate ester (or tartramide). The epoxidation using
stoichiometric amounts of Zr(Ot-Bu)4 and diisopropyl L-
tartrate (DIPT) proceeded smoothly, and the corresponding
epoxy alcohol (2a) was obtained in 78% yield with 88% ee
in the short period of 1.0 h (Table 1, entry 1). Another
combination of Zr(Ot-Bu)4 and dibenzyl L-tartramide (DBTA)
also accelerated the reaction even at the lower temperature
of -40 °C to give satisfactory results of 90% yield and 87%
ee (Table 1, entry 2). Interestingly, the enantiofacial prefer-
ence of the two reactions was opposite to that observed in
the aforementioned epoxidation by Sharpless and Katsuki.7,8
(1) For recent reviews on highly enantioselective epoxidation of allylic
alcohols, see: (a) Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; VCH: New York, 1993; Chapter 4.1. (b) Katsuki,
T.; Martin, V. S. Org. React. 1996, 48, 1.
(2) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974.
(3) Hanson, R.; Sharpless, K. B. J. Org. Chem. 1986, 51, 1922.
(4) For recent reviews on metal-catalyzed highly enantioselective ep-
oxidation of unfunctionalized olefins, see: (a) Jacobsen, E. N. In Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993; Chapter 4.2.
(b) Collman, J. P.; Zhang, X.; Lee, V. J.; Uffelman, J. I. Science 1993,
261, 1404. (c) Katsuki, T. Coord. Chem. ReV. 1995, 140, 189. (d)
Mukaiyama T. Aldrichimica Acta 1996, 29, 59.
(5) For recent reviews on asymmetric epoxidation of electron-deficient
olefins, see: Porter, M. J.; Skidmore, Chem. Commun. 2000, 1215.
(6) For recent reviews on chiral ketone-catalyzed asymmetric epoxidation,
see: (a) Denmark, S. E.; Wu, Z. Synlett 1999, 847. (b) Frohn, M.; Shi, Y.
Synthesis 2000, 1979.
(7) Bryant, E. R.; Sharpless, K. B. J. Org. Chem. 1984, 49, 3707.
(8) Ikegami, S.; Katsuki, T.; Yamaguchi, M. Chem. Lett. 1987, 83.
10.1021/ol027261t CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/11/2002