Heterogeneous asymmetric epoxidation of cis-allylic alcohols: Use of polymer-supported Ti(IV)-catalyst

Article abstract of DOI:10.1016/S0957-4166(98)00188-8

Heterogeneous asymmetric epoxidation of cis-allylic alcohols with titanium isopropoxide and tert-butyl hydroperoxide has been achieved using a branched/crosslinked poly(tartrate ester) ligand. The enantioselectivities and chemical yields obtained are at l

Full text of DOI:10.1016/S0957-4166(98)00188-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 2019–2022
Heterogeneous asymmetric epoxidation of cis-allylic alcohols:
use of polymer-supported Ti(IV)-catalyst
Jaana K. Karjalainen,a Osmo E. O. Hormi a,∗ and David C. Sherrington b
aDepartment of Chemistry, University of Oulu, PO Box 333, FIN-90570 Oulu, Finland
bDepartment of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street,
Glasgow, G1 1XL, Scotland, UK
Received 8 April 1998; accepted 12 May 1998
Abstract
Heterogeneous asymmetric epoxidation of cis-allylic alcohols with titanium isopropoxide and tert-butyl hydro-
peroxide has been achieved using a branched/crosslinked poly(tartrate ester) ligand. The enantioselectivities and
chemical yields obtained are at least comparable to low molecular weight tartrate ligands. © 1998 Published by
Elsevier Science Ltd. All rights reserved.
The asymmetric epoxidation of alkenes is central to many of the recent developments in the stereo-
selective synthesis of chiral molecules.1 Our earlier studies have established the advantages of using
a polymer-supported Ti(IV)-catalyst in the epoxidation of trans-allylic alcohols.2–4 In line with our
continuing interest in this area, we have now undertaken the investigation of the epoxidation of cis-allylic
alcohols.
Allylic alcohols having a cis-3-substituent are typically the most sluggish of allylic alcohols to be
epoxidised.5 Using the conventional low molecular weight Sharpless tartrate–titanium isopropoxide
system these cis-allylic alcohols give variable enantiofacial selectivity.6 Nevertheless, asymmetric epoxi-
dation of these substrates is effective and in most cases the enantiomeric purity is at least 80%.
The numerous attractive features of a polymer-supported asymmetric organic synthesis are well recog-
nised. For example the isolation of the chiral product, free of the chiral catalyst or auxiliary, is simplified.
In addition many successful chiral catalytic systems are moisture or air-sensitive organometallic species
and polymer-supported analogues can be used and be recovered more easily without exposure to water
and/or air.7
We have previously reported on the synthesis of branched/crosslinked poly(tartrate ester)s and have
studied the use of these optically active poly(tartrate ester) ligands in asymmetric epoxidations of trans-
allylic alcohols with titanium tetraisopropoxide and tert-butyl hydroperoxide.3,4 In the present paper
∗
Corresponding author. E-mail: Osmo.Hormi@oulu.fi
0957-4166/98/$19.00 © 1998 Published by Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00188-8

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we would like to report the results obtained using these branched poly(tartrate ester)s as ligands in the
epoxidation of cis-allylic alcohols.
The branched/crosslinked polyester 3 was prepared by condensation polymerisation of L-(+)-tartaric
acid and 1,8-octanediol as shown in Scheme 1.3 The degree of branching/crosslinking was determined as
described before by 1H NMR.4 We have previously pointed out that a high level of branching/crosslinking
of the polymer ligand inhibits the enantioselective epoxidation of trans-allylic alcohols.4 Accordingly we
have now used poly(tartrate ester)s having a degree of branching of 10%, 14% and ꢀ15% in epoxidations
of cis-allylic alcohols.
Scheme 1.
Table 1 shows the results obtained. As expected, the reaction times needed to achieve significant
conversion were longer than in the epoxidation of trans-allylic alcohols. After one week the conversion
varied between 20–51% depending on the substrate. The results of the asymmetric epoxidation of cis-2-
penten-1-ol are shown in entries 1 and 2. Using a polymer ligand having a 10% degree of branching the
conversion was 51% after 7 days in a freezer and the enantioselectivity of the reaction was high (86%).
The enantioselectivity dropped significantly (48% ee) using the crosslinked polymer ligand. Using the
monomeric diethyltartrate–titanium isoproxide system the reported yield was 60% with 80% ee.8 The
results of asymmetric epoxidation of cis-2-hexen-1-ol (entry 4) are also comparable to the results using
the monomeric analogue. The conversion was 48% after 6 days with 80% ee. The polymer ligand having
a 14% degree of branching (entry 5) resulted in better enantioselectivity than the low molecular weight
tartrate ligand (DMT, entry 6). Using stoichiometric levels of diisopropyl tartrate–titanium isopropoxide
the reported conversion was 60% with 80% ee.9
The rate of epoxidation of cis-4-benzyloxy-2-buten-1-ol was the slowest (entries 7–9). The conversion
after 7 days was only 20% and the enantioselectivity of the reaction was 66–68%. In the reported
enantioselectivity using L-(+)-diethyl tartrate as the ligand varied from 85% (for catalytic levels) to as
high as 92% (for stoichiometric levels).6,10 In the present work the monomeric dimethyl tartrate–titanium
isopropoxide system was used to compare with a polymeric analogue.11 The results are shown in
Table 1. Generally the polymer ligand 3 gives better enantioselectivity than the monomeric dimethyl
tartrate ligand. The high level of branching/crosslinking (ꢀ15%) of the polymer ligand inhibits the
enantioselective epoxidation of cis-allylic alcohols.
The recovery of polymer-catalyst by simple filtration aids the isolation of products. The complex work-
up required in the Sharpless procedure is considerably simplified, and foaming emulsions are avoided.
One of the attractive features of using these polymer-supported catalysts is that a large excess of catalyst
can be used to accelerate reactions and yet the work-up and isolation of product remains very simple.
Indeed all the reactions were found to proceed much better with substrate:Ti:tartrate ratios in the range
100:100:200 to 100:200:400 i.e. using roughly stoichiometric levels of Ti and tartrate. However the
systems remain catalytic in that TBHP needs to be activated by the Ti/tartrate complex.
In summary, we have demonstrated that using polymer-supported Sharpless catalyst in the asymmetric
epoxidation of cis-allylic alcohols the results obtained are comparable with, or better than, those achieved
by using the optimised conventional low molecular weight ligand. The enantioselectivies obtained vary

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Table 1
Comparison of DMT and polyester 3 prepared from L-(+)-tartaric acid in the asymmetric epoxidation
of cis-2-allylic alcohols with TBHP (2 equiv.) and Ti(OPri)4 in CH2Cl2 at −20°C12
from 66–86% with reasonable chemical yields (up to 57%) using the polymer ligand having a degree of
branching of 10%–14%. The crosslinked polymer ligand resulted in remarkably lower enantioselectivity
(38–48% ee) with reasonable chemical yields. A large excess of polymer-supported catalyst can be used
to improve reaction rates while avoiding added complications in the work-up.
It could also be interesting to investigate the circulation of the polymeric catalyst but, so far, we have
made no thorough study to reuse the catalyst.
Acknowledgements
JKK acknowledges financial support from the Neste Oy Foundation, Finland which made this work
possible.
References
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3. Karjalainen, J. K.; Hormi, O.; Sherrington, D. C. Molecules, 1998, 3, 51–59.
4. Karjalainen, J. K.; Hormi, O.; Sherrington, D. C. Accepted for publication in Tetrahedron: Asymmetry.

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5. Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis; Ed. Ojima, I., VCH Publishers, Inc., 1993; pp.
103–158.
6. Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109,
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7. Hodge, P. Polymer-supported Asymmetric Organic Synthesis in Innovation and Perspectives in Solid Phase Synthesis; Ed.
R. Epton; SPCC UK, 1990; pp. 273–292.
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9. (a) Mori, K.; Nakazono, Y. Tetrahedron, 1986, 42(23), 6459. (b) Nicolaou, K. C., Webber, S. E. J. Chem. Soc., Chem.
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10. Katsuki, T.; Lee, A. W. M.; Ma, V. S. J. Org. Chem. 1982, 47(7), 1373.
11. The esters used conventionally in Sharpless epoxidations are dimethyl, diethyl and diisopropyl tartrates, and, with a few
subtle exeptions, all are equally effective at inducing asymmetry. See for example Johnson, R. A.; Sharpless, K. B. In
Comprehensive Organic Synthesis, Vol. 7, Eds. Trost, B. M., Fleming, I., Ley, S. V. Pergamon Press, Oxford 1991, pp.
389–436
12. General procedure for asymmetric epoxidation: The literature procedure for the epoxidation of allylic alcohols was
followed with modifications. An oven-dried three-necked round-bottomed flask equipped with a magnetic stirbar, nitrogen
inlet, septum and bubbler was charged with 4 Å powdered, activated molecular sieves, polymer-ligand 3 and dry CH2Cl2.
The flask was cooled to −20°C and Ti(O-i-Pr)4 (via syringe) was added dropwise with stirring. The reaction mixture was
stirred at −20°C and after about one hour, 2 equiv. of TBHP in iso-octane was added with a syringe at a moderate rate. The
resulting mixture was stirred at −20°C for at least one hour. The substrate (dissolved in dry CH2Cl2) was added dropwise
with a syringe, being careful to maintain the reaction temperature between −15°C and −20°C. The mixture was stirred for
an additional 3–12 hours at −15°C to −20°C. The reaction mixture was stored in a freezer for approximately one week.
The reaction was monitored by gas chromatography (GC) using dodecane as an internal standard. The polymer was filtered
and the reaction mixture washed thoroughly with CH2Cl2. Workup was then performed. The crude product was purified
by flash-chromatography (eluent: petrol ether (40°C–60°C):diethyl ether=1:1) and analysed by 1H NMR, GC and HRMS.
All compounds showed satisfactory spectroscopic and analytical data. The enantioselectivity of the epoxide was measured
by 1H NMR analysis of the derived MTPA ester in benzene-d6 or by HPLC using a chiral Chiralpak AS 25 cm×0.46 cm
column together with a Chiralpak AS 5 cm×0.46 cm pre-column (RI-detection, eluent: n-hexane:isopropanol=9:1, flow
rate: 0.5 ml/min).