tion catalysts in the presence of aqueous H2O2 because they
resist both oxidative and hydrolytic degradation.3c The good
performance of these POM catalysts with aqueous H2O2,3g,h
notably their tolerance of water, prompted us to use sandwich
POMs as epoxidation catalysts in combination with organic
hydroperoxides, which are often superior to those by H2O2
in regard to selectivity.4 Unfortunately, catalytic hydroper-
oxide oxidations are not well-suited for the manufacture of
fine chemicals in multipurpose plant equipment because of
the low process efficiency due to catalyst deactivation by
adventitious water.5 We report our unprecedented results on
the use of [ZnW(VO)2(ZnW9O34)2]12- as a highly active
catalyst for the selective epoxidation of allylic alcohols by
hydroperoxides.6 Stimulated by the high enantioselectivity
that we have obtained recently in the asymmetric Weitz-
Scheffer epoxidation of R,â enones by enantiopure hydro-
peroxides,7 notably the sterically demanding TADDOL-
derived hydroperoxide TADOOH,7b we also present here the
first POM-catalyzed asymmetric epoxidation of allylic al-
cohols by TADOOH.
catalyzed oxidations,8c and the racemic [1-(4-chlorophen-
yl)]ethyl hydroperoxide (4a) as oxygen donor (Table 1). This
Table 1. Catalytic Oxidation of Mesitylol (1a) by the Various
Transition-Metal-Substituted Polyoxometalates with the Racemic
Hydroperoxide 4a
selectivitya
tempb convna mba
diastereo
entry
M
(°C)
(%)
(%)
2a :3a
(threo:erythro)
1
2
3
4
5
6
7
8
OV(IV)
OV(IV)
Mn(II)
Ru(III)
Fe(III)
Zn(II)
20
50c
50
50
50
50
50
50
>95
>95
85
94
18
8
18
12
>95 >95:5
>95 >95:5
91:9
91:9
90:10
90:10
94:6
95:5
92:8
95:5
85
70
95
90
92
95
90:10
70:30
90:10
85:15
93:7
First an extensive screening of various transition-metal-
substituted sandwich-type POMs, namely [ZnWM2(ZnW9-
O34)2]q- or M-POM (M ) OVIV, MnII, RuIII, FeIII, ZnII, PdII,
and PtII, q ) 10-12), was conducted with racemic hydro-
peroxides. The reactions were carried out in a 1,2-dichlo-
roethane solution of the POMs, obtained by extraction from
an aqueous solution of their alkali metal derivatives, through
the addition of Aliquat 336 as a lipophilic quaternary
ammonium salt. No meticulous precautions were taken to
exclude water, other than brief drying over Na2SO4 (see
Supporting Information).
Pd(II)
Pt(II)
88:12
a Conversions (allylic alcohol), material balances, and product ratios were
determined by 1H NMR analysis of the crude reaction mixture, ca. 5% error
of the stated value. b For entries 3-8, 0.02 mol % of catalyst loading was
employed; no conversion was observed at 20 °C. c Reaction time was 6 h.
screening revealed that the oxovanadium(IV)-substituted
POM, namely [ZnW(VO)2(ZnW9O34)2]12- or OdV(IV)-
POM, was the most reactive and selective catalyst for the
epoxidation of allylic alcohols (Table 1). High yields were
obtained within 24 h at 20 °C (entry 1) or within 6 h at 50
°C (entry 2), with only 0.01 mol % of POM catalyst.
Although the sandwich-type POM [ZnW(VO)2(ZnW9-
O34)2]12- has been known for some time,9 apparently it had
hitherto not been used for catalytic epoxidations. Our results
on the epoxidation of a variety of substituted allylic alcohols
1 by the racemic (1-phenyl)ethyl hydroperoxide (4b) with
the OdV(IV)-POM catalyst are collected in Table 2. As is
evident, the secondary allylic alcohol 1a (entry 1) afforded
the epoxy alcohol in high diastereoselectivity (threo:erythro
91:09). The usual undesirable allylic oxidation (CH insertion)
was not observed, which manifests the high chemoselectivity
of this reaction. With tert-butyl hydroperoxide (Table 2, entry
2) instead of (1-phenyl)ethyl hydroperoxide (4b), a lower
conversion (65%) was obtained under identical reaction
conditions. 2-Cyclohexen-1-ol (1b) was found to be less
reactive than the acyclic allylic alcohols and gave selectively
the cis-epoxy alcohol 2b (entry 3), but a higher (50 °C)
temperature was necessary for complete conversion of the
allylic substrate. Significant in regard to regioselectivity is
1-methylgeraniol (1c) with two types of double bonds, which
gave only the 3,4 epoxide in excellent yield and high
diastereoselectivity (entry 4). Similarly, the primary allylic
Mesitylol (1a) was chosen as model substrate, which is
an established probe for the assessment of the chemoselec-
tivity (epoxidation versus allylic oxidation)8a,b and diaste-
reoselectivity (threo versus erythro epoxidation) in metal-
(3) For leading examples in catalysis, see: (a) Hill, C. L.; Brown, R. B.
J. Am. Chem. Soc. 1986, 108, 536-538. (b) Mansuy, D.; Bartoli, J. F.;
Battioni, P.; Lyon, D. K.; Finke, R. G. J. Am. Chem. Soc. 1991, 113, 7222-
7226. (c) Neumann, R.; Gara, M. J. Am. Chem. Soc. 1995, 117, 5066-
5074. (d) Bo¨sing, M.; No¨h, A.; Loose, I.; Krebs, B. J. Am. Chem. Soc.
1998, 120, 7252-7259. (e) Mizuno, N.; Nozaki, C.; Kiyoto, I.; Misono,
M. J. Am. Chem. Soc. 1998, 120, 9267-9272. (f) Weiner, H.; Finke, R. G.
J. Am. Chem. Soc. 1999, 121, 9831-9842. (g) Adam, W.; Alsters, P. L.;
Neumann, R.; Saha-Mo¨ller, C. R.; Sloboda-Rozner, D.; Zhang, R. Synlett
2002, 12, 2011-2014. (h) Adam, W.; Alsters, P. L.; Neumann, R.; Saha-
Mo¨ller, C. R.; Sloboda-Rozner, D.; Zhang, R. J. Org. Chem. In press.
(4) Sheldon, R. A.; Kochi, J. K. Metal-Catalyzed Oxidations of Organic
Compounds; Academic Press: New York, 1981; pp 48-62.
(5) For example, even in the presence of molecular sieves, the Sharpless-
Katsuki epoxidation still requires 5-10 mol % of Ti catalyst to protect the
latter from adventitious water; see: Johnson, R. A.; Sharpless, K. B. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley: New York, 2000;
pp 231-280.
(6) Hydroperoxides such as tert-butyl hydroperoxide are known to serve
as the oxygen source for POM-catalyzed oxidations; however, these
epoxidations are of limited success in view of the low reactivity and, in
most cases, undesirable radical-type reactions, see: (a) Faraj, M.; Hill, C.
L. J. Chem. Soc., Chem. Commun. 1987, 1487-1489. (b) Neumann, R.;
Khenkin, A. M. Inorg. Chem. 1995, 34, 5753-5760.
(7) (a) Adam, W.; Rao, P. B.; Degen, H.-G.; Saha-Mo¨ller, C. R. J.
Am. Chem. Soc. 2000, 122, 5654-5655. (b) Aoki, M.; Seebach, D. HelV.
Chim. Acta 2001, 84, 187-207.
(8) (a) Adam, W.; Hajra, S.; Herderich M.; Saha-Mo¨ller, C. R. Org. Lett.
2000, 2, 2773-2776. (b) Adam, W.; Herold, M.; Hill, C. L.; Saha-Mo¨ller,
C. R. Eur. J. Org. Chem. 2002, 941-946. (c) Adam, W.; Wirth, T. Acc.
Chem. Res. 1999, 32, 703-710.
(9) The synthesis and X-ray structure of oxovanadium(IV) POM is
known; see: Tourne´, C. M.; Tourne´, G. F.; Zonnevijlle, F. J. Chem. Soc.,
Dalton Trans. 1991, 143-155.
726
Org. Lett., Vol. 5, No. 5, 2003