Catalytic asymmetric epoxidation of allylic alcohols using a renewable hydroperoxide

Article abstract of DOI:10.1016/S0040-4039(02)01110-3

Sharpless modified asymmetric epoxidation of allylic alcohols can be successfully performed using an easily accessible and renewable tertiary furyl hydroperoxide in the presence 20 mol% of the chiral Ti(O-i-Pr)₄/L-DIPT/MS 4 ? system.

Full text of DOI:10.1016/S0040-4039(02)01110-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5629–5631
Catalytic asymmetric epoxidation of allylic alcohols using a
renewable hydroperoxide†
Alessandra Lattanzi,* Patrizia Iannece and Arrigo Scettri
Dipartimento di Chimica, Universita` di Salerno, Via S. Allende 84081 I Baronissi, Salerno, Italy
Received 22 March 2002; accepted 10 June 2002
Abstract—Sharpless modified asymmetric epoxidation of allylic alcohols can be successfully performed using an easily accessible
,
and renewable tertiary furyl hydroperoxide in the presence 20 mol% of the chiral Ti(O-i-Pr)4/L-DIPT/MS 4 A system. © 2002
Elsevier Science Ltd. All rights reserved.
Chiral epoxides are important intermediates in organic
synthesis and the development of new methodologies
for their preparation is a subject of intensive research.1
pure hydroperoxides.6 Interestingly, if the alkyl
hydroperoxide is used in enantiopure form,7 a coopera-
tive effect of the chiral ligand and hydroperoxide has
been observed, but it is difficult to predict the successful
combination of both in order to achieve the highest ee
in the product.
For the epoxidation of allylic alcohols, interesting pro-
cedures have been reported using vanadium catalysts
and hydroxamic acids derivatives,2 but the Sharpless
protocol with titanium tetraisopropoxide and tartrate
esters ligands3 is still the most employed, furnishing the
epoxides with very high enantiomeric excess. Regardless
of the metal-catalyzed methodology, the structure of
the hydroperoxide4 plays a significant role in influenc-
ing the level of enantioselectivity achievable for this
process. As a consequence some investigations have
been reported in the literature concerning the employ-
ment of structurally different alkyl hydroperoxides.4,5 It
has been observed that tertiary alkyl and aryl hydroper-
oxides assure the highest ee’s in the product. In this
respect, for the vanadium-chiral hydroxamic acid
methodology, the triphenylmethyl hydroperoxide2c
proved to be more efficient than the commercial tert-
butyl hydroperoxide (TBHP). In the catalytic Sharpless
epoxidation TBHP and cumene hydroperoxide (CHP)
were reported to reproduce the high level of enantiose-
lectivity found under stoichiometric loadings of the
chiral catalyst.3b Another interesting aspect, scarcely
investigated so far, was the employment of optically
We previously reported on the synthesis and the reac-
tivity of highly functionalized furyl hydroperoxides8 as
oxygen donors in the Sharpless epoxidation of allylic
alcohols. Furthermore, in the same process, racemic
secondary hydroperoxides can be kinetically resolved
and enantiomerically enriched furyl hydroperoxides and
furyl alcohols were isolated. With stoichiometric
amounts of the chiral catalyst, high ee’s for the epox-
ides were achieved when using
a tertiary furyl
hydroperoxide. Unfortunately, when trying substoichio-
metric amounts of the chiral catalyst a dramatic drop in
the enantioselectivity was observed.
n-BuLi, -78 °C
R1
THF
R2
R
R
O
O
R
O
OH
R1
R2
1
> 80%
H2O2, H+
DME, rt
R1
R1
R2
R2
R
O
O
Keywords: asymmetric epoxidation; alkyl hydroperoxides; titanium;
allylic alcohols.
OOH
OH
2
1
* Corresponding author. Tel.: +39-089-965374; fax: +39-089-965296;
e-mail: lattanzi@unisa.it
> 60%
†
Dedicated to the memory of Professor Guido Sodano who deceased
on June 2001.
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01110-3

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A. Lattanzi et al. / Tetrahedron Letters 43 (2002) 5629–5631
order of addition of the reagents and in particular the
allylic alcohol and the alkyl hydroperoxide, can affect
the enantioselectivity.3 When the oxidant 2a was added
before geraniol in the experimental procedure, a
reduced yield and slightly lower ee were observed (entry
3).
With the intention of producing an easily accessible
class of furyl hydroperoxides9 to use in asymmetric
oxidation processes, very recently, our investigations
focused on the synthesis of structurally simple furyl
hydroperoxides.10 We succeeded in our goal with a
two-step sequence which allowed us to obtain furyl
hydroperoxides of type 2 (R=Me, H; R1=H, Me;
R2=alkyl, Me) (Scheme 1) with an overall yield ]50%.
Compounds 2 proved to be stable and could be isolated
by silica gel chromatography.11
Hence having proved successful under stoichiometric
conditions, hydroperoxide 2a was reacted in the pres-
ence of catalytic molar loadings of Ti(O-i-Pr)4/
L-DET
0.20/0.30 with respect to 3 (Table 2).
The tertiary furyl hydroperoxide 2a (R=H; R1=R2=
Me, overall yield 65%), which can be considered a
heteroaromatic equivalent of CHP, has been success-
fully used12 under catalytic conditions in Uemura’s13
modified procedure of asymmetric sulfoxidation. Then,
we thought it would be interesting to study the poten-
tial use of this oxidant in the asymmetric epoxidation.
A catalytic procedure is highly desirable for different
reasons: Lewis acid sensitive epoxides can be synthe-
sized in higher yields, easier isolation work up is needed
and less consuming reagents protocol can be applied.
We were delighted to observe that the level of asymmet-
ric induction was still high when 20 mol% of the chiral
catalyst was employed for the epoxidation of geraniol
Herein we report that high enantioselectivity can be
achieved in the asymmetric Sharpless epoxidation
employing the tertiary hydroperoxide 2a, but more
importantly the level of asymmetric induction is main-
tained high using catalytic conditions.
(entry 1).
be a better ligand than
L
-Diisopropyl tartrate (
L-DIPT) turned out to
L
-DET, in fact, a significant
improvement of ee was observed for 2,3-epoxygeraniol
(entry 2). A variety of double bond substituted allylic
alcohols treated under catalytic conditions, using
L-
Some preliminary runs, under stoichiometric condi-
tions, were carried out in order to evaluate the reactiv-
ity and the efficiency of the tertiary furyl hydroperoxide
2a in the asymmetric epoxidation of allylic alcohols
(Table 1).
DIPT as ligand, were converted to the epoxides in good
yield and very high ee. In some examples the ee mea-
sured was higher than the one obtained with the use of
TBHP/L
-DET3b (entry 4). Not surprisingly, the epoxi-
dation of nerol (entry 7) furnished the epoxide with
moderate ee.
Geraniol and trans 2-methyl-3-phenyl-prop-2-en-1-ol
were epoxidized in high yield and ee as shown, respec-
tively, in entries 1 and 2. It has been reported that the
In the Sharpless epoxidation, cis allylic alcohols react
slowly compared to trans allylic alcohols, moreover,
Table 1. Asymmetric epoxidation with 2a under stoichiometric conditionsa

A. Lattanzi et al. / Tetrahedron Letters 43 (2002) 5629–5631
5631
Table 2. Asymmetric epoxidation with 2a under catalytic conditionsa
considerably lower ee’s for the corresponding cis epox-
Yamamoto, H. J. Org. Chem. 1999, 64, 338; (d) Hoshino,
Y.; Yamamoto, H. J. Am. Chem. Soc. 2000, 122, 10452;
(e) Bolm, C.; Ku¨hn, T. Synlett 2000, 6, 899.
3. (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980,
102, 5974; (b) Gao, Y.; Hanson, R. M.; Klunder, J. M.;
Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem.
Soc. 1987, 109, 5765.
ides are reported.4
In conclusion, furyl hydroperoxide 2a can be consid-
ered an efficient oxidant in the asymmetric Sharpless
epoxidation of allylic alcohols.
4. (a) Finn, M. G.; Sharpless, K. B. In Asymmetric Synthe-
sis; Morrison, J. D., Ed.; Academic Press: New York,
1985; p. 247; (b) Rossiter, B. E. In Asymmetric Synthesis;
Morrison, J. D., Ed.; Academic Press: New York, 1985;
p. 193.
5. Adam, W.; Korb, M. N. Tetrahedron: Asymmetry 1997,
8, 1131.
6. Aoki, M.; Seebach, D. Helv. Chim. Acta 2001, 84, 187
and references cited therein.
The enantioselectivity is maintained high under cata-
lytic loadings of the chiral catalyst and the epoxides are
generally obtained with ee’s >90%. This modified proce-
dure of catalytic Sharpless epoxidation is an example of
resource-saving protocol. Unlike cumyl alcohol, which
is a side-product of the epoxidation when using CHP
as oxidant, the furyl alcohol 1a (Table 1) can be
recovered by flash chromatography and recycled as
starting material for the synthesis of hydroperoxide 2a
according to Scheme 1.
7. Bolm, C.; Beckmann, O.; Ku¨hn, T.; Palazzi, C.; Adam,
W.; Rao, P. B.; Saha-Mo¨ller, C. R. Tetrahedron: Asym-
metry 2001, 12, 2441.
8. (a) Lattanzi, A.; Iannece, P.; Scettri, A. Tetrahedron Lett.
1999, 40, 3899; (b) Lattanzi, A.; Bonadies, F.; Scettri, A.
Tetrahedron: Asymmetry 1997, 8, 2141.
Acknowledgements
We are grateful to MURST and CNR for financial
9. The synthesis of highly functionalized furyl hydroperox-
ides used as oxygen donors in Ref. 8b requires four
synthetic steps.
support.
10. Massa, A.; Palombi, L.; Scettri, A. Tetrahedron Lett.
2001, 42, 4577.
References
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