Vanadium-catalyzed asymmetric epoxidation of homoallylic alcohols

Article abstract of DOI:10.1021/ja067495y

New chiral bishydroxamic acids were synthesized and tested as chiral ligands in the vanadium-catalyzed asymmetric epoxidation of homoallylic alcohols to provide good yields and high enantioselectivities. Copyright

Full text of DOI:10.1021/ja067495y

Published on Web 12/21/2006
Vanadium-Catalyzed Asymmetric Epoxidation of Homoallylic Alcohols
Wei Zhang and Hisashi Yamamoto*
Department of Chemistry, UniVersity of Chicago, 5735 South Ellis AVenue, Chicago, Illinois 60637
Received October 19, 2006; E-mail: yamamoto@uchicago.edu
Catalytic asymmetric epoxidation of olefins is very useful for
the synthesis of enantiomerically enriched epoxides, which are
versatile building blocks for the synthesis of natural products and
biologically active substances. There are many efficient protocols
to mediate the epoxidation of allylic alcohols to provide satisfactory
yields and enantioselectivities.1 However, very limited catalyst
systems can be used for the asymmetric epoxidation of homoallylic
alcohols and those substrates in which olefin is located further from
the hydroxy group. Sharpless asymmetric epoxidation, which was
efficient for allylic alcohols, could not provide homoallylic alcohols
Scheme 1. Asymmetric Epoxidation of Allylic Alcohols and
Homoallylic Alcohols by Vanadium and BHA Complexes
2,3
with satisfactory enantioselectivities. The protocol reported by
our group, which used vanadium and R-amino acid-based hydrox-
amic acid ligands to perform the asymmetric epoxidation of
homoallylic alcohols, was found to be efficient.4 Unfortunately,
however, the enantioselectivities of trans and cis-substituted olefins
were not satisfactory. Thus, there has been no truly efficient catalytic
asymmetric epoxidation of homoallylic alcohols reported. Recently,
we reported a vanadium-catalyzed epoxidation of allylic alcohols
,5
Table 1. Screening of Ligands
with newly designed bishydroxamic acid (BHA) ligands (1a and
6
1
b), which has the following features: (1) high enantioselectivity
for a wide scope of allylic alcohols, (2) less than 1 mol % catalyst
loading, (3) mild reaction conditions, and (4) use of aqueous tert-
butyl hydroperoxide (TBHP) as an achiral oxidant instead of
anhydrous TBHP7 (Scheme 1). Herein, we report a new modified
BHA ligand that is suitable for highly enantioselective vanadium-
catalyzed epoxidation of homoallylic alcohols.
-9
Initial experimental modification showed that cumene hydrop-
eroxide (CHP) was better than TBHP to facilitate and complete
the transformation, and toluene was used as solvent to inhibit
cyclization of the produced epoxide to the corresponding tetrahy-
drofuran byproduct (Scheme 1), One mol % catalyst loading was
enough to perform the reaction at room temperature. Reaction
proceeded smoothly, and moderate enantioselectivity as well as
good yield was achieved on 2a when ligand 1b was used (Table 1,
entry 1). With this promising result in hand, new ligands based on
a
1b were synthesized. The enantioselectivity was increased to 90%
All reactions were carried out in toluene in the presence of 1.5 equiv
b
of cumene hydroperoxide (CHP) (88%) unless otherwise indicated. Isolated
ee with 1c. Finally, 1d, which was introduced with a more hindered
substituted phenyl group, was found to be excellent for the reaction;
yield after chromatographic purification. c Enantiomeric excess values were
determined by chiral HPLC (AD-H), and the detailed information is provided
in the Supporting Information.
96% ee was obtained on 2a, while the rate of the reaction was also
facilitated (Table 1).
Scheme 2. Kinetic Resolution of Homoallylic Alcohols
The scope of the reaction was investigated with 1d under the
modified conditions. Gratifyingly, both trans- and cis-substituted
epoxides were achieved with virtually complete enantioselectivities
and satisfactory yields.
With the successful results of the asymmetric epoxidation of
homoallylic alcohols, this catalyst system was applied to the kinetic
resolution of these alcohols with outstanding selectivities (4a, 4b)
(
Scheme 2). Both the starting homoallylic alcohols and epoxy
10
alcohols were obtained with satisfactory enantiopurity. It should
also be noted that this kinetic resolution gave us an opportunity to
generate asymmetric carbon in a completely new scheme. In fact,
starting homoallylic alcohols can be synthesized efficiently using
preexisting chemistry of allylic anions.11
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10.1021/ja067495y CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Scope of Substrates
References
(
1) For recent reviews, see: (a) Katsuki, T. In ComprehensiVe Asymmetric
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(
7) For recent reports on chiral vanadium catalyst for epoxidation, see: (a)
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a
All reactions were carried out in toluene in the presence of 1.5 equiv
(
9) For mechanistic study on vanadium-hydroxamic acid oxidation, see: (a)
Bryliakov, K. P.; Talsi, E. P. Kinet. Katal. 2003, 44, 334. (b) Bryliakov,
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b
of cumene hydroperoxide (CHP) (88%) unless otherwise indicated. Isolated
yield after chromatographic purification. Enantiomeric excess values were
determined by either chiral HPLC or chiral GC, and the detailed information
is provided in the Supporting Information.
c
The absolute configurations of 3c and 3f were determined as
(
3R,4R) and (3R,4S), respectively, by comparison of reported optical
2b,3b,12
rotation.
In summary, we have designed a new chiral bishy-
droxamic acid ligand, which has been shown to be excellent for
the vanadium-catalyzed asymmetric epoxidation and kinetic resolu-
tion of homoallylic alcohols. Further studies focusing on broader
application of our chiral vanadium-hydroxamic acid complexes
to wider scope are ongoing.
(
10) (a) Enantiomeric excess values were determined by chiral GC analysis,
and the detailed information is provided in Supporting Information. The
absolute configurations of 4a and 4b were determined as (R) and (R),
respectively, by comparison of retention times (GC analysis) of the
absolute configuration known compounds (9a, 9b), which were prepared
by the following reported sequence: Ehrlich, G.; Kalesse, M. Synlett 2005,
4, 655. Detailed information is provided in Supporting information. (b)
For the stereoselective epoxidation of homoallylic alcohols, see: Mihelich,
E. D.; Daniels, K.; Eickhoff, D. J. J. Am. Chem. Soc. 1981, 103, 7690.
Acknowledgment. Support for this research was provided by
the SORST project of the Japan Science and Technology Agency
(JST), National Institutes of Health (NIH) GM068433-01, Merck
(11) Kende, A. S.; Toder, B. H. J. Org. Chem. 1982, 47, 167.
Research Laboratories, and a starter grant from the University of
Chicago.
(
12) To explain these enantioselectivities, as well as those of kinetic resolutions,
we proposed a possible model of the asymmetric epoxidation of homoal-
lylic alcohol catalyzed by the complex of vanadium and ligand 1d, which
is provided in the Supporting Information.
Supporting Information Available: Representative experimental
procedures and spectral data for 1c and 1d. This material is available
free of charge via the Internet at http://pubs.acs.org.
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