Ligand-accelerated vanadium-catalysed epoxidation in water

Article abstract of DOI:10.1039/b509436d

Vanadium-catalysed epoxidation of allylic alcohols, a classical example of ligand-decelerated catalysis, in water it turns into a ligand-accelerated process. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b509436d

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Ligand-accelerated vanadium-catalysed epoxidation in water{
Za¨ınaba Bourhani and Andrei V. Malkov*
Received (in Cambridge, UK) 6th July 2005, Accepted 22nd July 2005
First published as an Advance Article on the web 19th August 2005
DOI: 10.1039/b509436d
employed3,5,6,9 which included VO(i-PrO)3 as a source of V
Vanadium-catalysed epoxidation of allylic alcohols, a classical
example of ligand-decelerated catalysis, in water it turns into a
ligand-accelerated process.
(1 mol%) and anhydrous t-BuOOH as a stoichiometric oxidant.
To take the full advantage of water as a solvent, alternative
V sources and oxidants were assessed. Thus, VOSO4?H2O was
found to be as efficient as the more expensive, commonly
employed VO(i-PrO)3 or VO(acac)2, while (NH4)VO3 proved less
reactive. Furthermore, anhydrous t-BuOOH was replaced with a
70% aqueous solution.
Asymmetric epoxidation of allylic alcohols is regarded as one of
the major tools for introducing chirality into organic molecules.1
Its wide recognition springs from the discovery by Sharpless
and Katsuki of a very efficient process mediated by Ti-tartrate
complexes.2 Another useful methodology, pioneered by Sharpless,3
is based on V-hydroxamate complexes. Attractive features of V
catalysis,4 in contrast to Ti, include low catalyst loading (1 mol%
or less) and high tolerance of air and moisture. However, for more
than two decades it remained in the shadow of Ti catalysis,
until recently, when Yamamoto reported on a new family of
hydroxamic acid ligands5,6 which, in the latest development,7 for
the first time, surpassed the Ti(IV) systems in terms of enantio-
selectivity. However, there is a fundamental difference between the
two methodologies: the Ti-mediated process is accelerated by
ligands, while in the case of V, coordination of ligands results in a
significant deactivation of the catalyst.8 Despite a steady progress
in tackling the ligand deceleration problem,6,7,9 complexes of V
with chiral ligands are still unable to match the rate of epoxidation
exhibited by the non-coordinated vanadyl alkoxides.
Overall, the epoxidation in water proceeded at a lower rate than
in toluene, however, the enantioselectivity was not affected. The
sulfonamide-derived ligands 1 and 2 reacted faster and gave better
conversions than their imido counterpart 3 boosting our earlier
observations of the accelerating effect of the sulfonamide
functionality.9 Remarkably, ligands 2 and 3, sharing the same
tert-leucine framework, produced the opposite enantiomers of the
products (compare entries 2 and 5 with entries 3 and 6) suggesting
that the remote functional group plays a crucial role in shaping up
the transition state which has still not been established in detail.9,11
Carrying out epoxidation in aqueous solution, particularly in
the presence of a Lewis-acidic catalyst, can be complicated by a
competing hydrolytic opening of the epoxide ring, thus affecting
the yield of the target product.12 In this regard, the rate of
epoxidation in water represents an important factor in choosing a
Herein, we wish to report on our finding that in water, V
catalysis turns into a ligand-accelerated process. Employing water
as a solvent offers numerous advantages over traditional organic
solvents.10 Apart from the favourable environmental impact and
low cost, it brings simplification to the synthetic protocols and the
product isolation technique.
A selection of bidentate chiral hydroxamic acids 1–3 employed
in this work are shown in Fig. 1. Compound 1 exhibited the best
reactivity in the series of sulfonamide-derived hydroxamic acids,9
ligand 3 represents a family of imido hydroxamic acids, introduced
by Yamamoto, which were successfully employed in asymmetric
epoxidation of allylic and homoallylic alcohols.6 Hydroxamic acid
2 can be viewed as a hybrid of 1 and 3 sharing the sulfonamide
functionality with 1 while the rest of the molecule duplicates 3.
Geraniol 4 and 2-methylcinnamyl alcohol 5 were chosen as the
model substrates.
Fig. 1 Chiral hydroxamic acids.
Asymmetric epoxidation catalysed by V complexes with ligands
1–3 in toluene was compared against the same reaction in water
(Scheme 1, Table 1). In toluene, the standard conditions were
WestChem, Department of Chemistry, Joseph Black Building,
University of Glasgow, Glasgow, Scotland, UK G12 8QQ.
E-mail: amalkov@chem.gla.ac.uk; Fax: 44 141 330 4888;
Tel: 44 141 330 5943
{ Electronic supplementary information (ESI) available: Synthesis and
characterisation of chiral ligand 3; experimental details of catalytic
epoxidation, characterisation of the products and enantioselectivity
determination. See http://dx.doi.org/10.1039/b509436d/
Scheme 1 Asymmetric epoxidation in toluene and water.
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The epoxidation is likely to proceed in the organic phase, as
water soluble V salts exhibited poor conversion. Hydroxamic acid,
a well-known key structural fragment of natural siderophores,13
coordinates to the V ion and transfers it to the organic phase
where epoxidation is taking place. In these circumstances, the
concentration of the catalytically active V complex will be
controlled by the concentration of the ligand. Once extracted
from water, V remains in the organic layer as a complex with
hydroxamic acid; the aqueous phase turns out to be essentially free
from the metal after the reaction is complete.
Table 1 Asymmetric epoxidation catalysed by V complexes of chiral
hydroxamic acids 1–3 in toluene and water
Toluenea
Waterb
Yield
(%)
ee (%),
config.c
Yield
(%)
ee (%),
config.c
Entry
Ligand
Geraniol (4)
1
2
3
1
2
3
95
93
97
64 (S,S)
66 (S,S)
54 (R,R)
73
60 (S,S)
32 (S,S)
60 (R,R)
52d
22d
2-Methylcinnamyl alcohol (5)
4
5
6
a
1
2
3
90
87
89
62 (S,S)
51 (S,S)
78 (R,R)
79
73
59 (S,S)
46 (S,S)
78 (R,R)
At room temperature, hydrolysis of the epoxide ring became the
prevailing process leading to the corresponding triol in quantitative
yield (entry 6). On the other hand, carrying out reaction at 220 uC,
resulted not only in complete suppression of the undesired
hydrolysis, but also led to increased enantioselectivity (entry 7).
In order to prevent the reaction mixture from freezing at 220 uC,
a 3 : 1 water–methanol mixture was employed. Note that in
methanol alone the epoxidation is very sluggish,9 while in aqueous
solutions methanol content up to 25% is tolerated.
13d
The reaction was carried out in toluene at 220 uC (ligand 1, 2) or
at 0 uC (ligand 3) for 20 h using 5–6 M solution of tert-butyl
hydroperoxide in nonane (1.5 equiv.) as the oxidant, the catalyst was
generated in situ from VO(i-PrO)3 (1 mol%) and the ligand
b
(1.8 mol%). The reaction was carried out in water at 0 uC for 20 h
using 70% aqueous solution of tert-butyl hydroperoxide (1.5 equiv.)
as the oxidant, the catalyst was generated from vanadyl sulfate
hydrate (1 mol%) and the ligand (1.1 mol%). Determined by chiral
c
GC. The absolute configuration of the products was deduced from
their optical rotation and comparison with the literature data.
The efficacy of the protocol was assessed using the epoxidation
of a range of allylic alcohols (Table 3).{ The conditions in each
case were optimised to maximise the yield of the target epoxides.
Despite moderate selectivities, the results can be viewed as a step
towards greener technologies.
d
Conversion rather than yield, determined by GC and 1H NMR.
suitable ligand, as the formation of epoxide should be significantly
faster than its hydrolysis. Both sulfonamide ligands 1 and 2
provided good conversions while keeping hydrolysis to a minimum
(¡5%). Based on better overall performance, the subsequent
experiments were carried out with ligand 1.
In conclusion, we have developed a practical protocol for
V-catalysed asymmetric epoxidation of allylic alcohols in
water. We have demonstrated that in water the process becomes
Next, we investigated the effect of catalyst loading employing
geraniol (4) as a model substrate. The results are summarised in
Table 2. Surprisingly, conversion without a ligand turned out to be
very low (18%) (entry 1) while the ligand alone did not promote
any reaction at all (entry 2). On the other hand, addition of 1 equiv.
of ligand 1 with respect to V resulted in a nearly complete
conversion to the epoxide 5 (entry 4). Furthermore, even at
0.5 equiv. of the ligand content the catalytic system remained
equally effective (entry 3) which represented a reverse trend
compared to the reaction in organic solvents. The process in water
turned into a ligand-accelerated catalysis. As expected, increasing
the ligand/V ratio above 1.5 : 1 reduced the reaction rate as a
result of the formation of VL2 complexes that are known to be
catalytically inactive (entries 8, 9).3,8
Table 3 Asymmetric epoxidation of allylic alcohols in water using V
complex with ligand 1a
Yield ee (%)b
Entry Substrate
1
T/uC t/h (%)
(config.c)
4
220 20 69d
69 (S,S)
2
3
8
5
0
0
60 55e
60 79e
57 (R,R)
59 (S,S)
4
5
9
220 60 92de 72 (+)
Table 2 Effect of ligand–V ratio and temperature on the asymmetric
epoxidation of geraniol (4) in watera
Entry Ligand 1/mol% V/mol% T/uC Conversion (%) ee (%)
1
2
3
4
5
6
7
8
9
a
0
1
0.5
1
1.1
1.1
1.1
1.5
2.5
1
0
1
1
1
1
1
1
1
0
0
0
0
0
18
,1
84
—
—
57
60
60
—
69
61
61
10
11
0
0
60 61
70 (R,R)
63 (S,R)
93
73b
6
60 41e
20 100c
220
69bd
76
a
The reaction was carried out on 1 mmol scale. The catalyst was
generated in situ from vanadyl sulfate hydrate (2 mol%) and ligand 1
0
0
47
b
(2.2 mol%), unless stated otherwise. Determined by chiral GC and
c
chiral HPLC. The absolute configuration of the products was
The reactions were carried out for 20
h
using 70% aqueous
solution of tert-butyl hydroperoxide (1.5 equiv.) as the oxidant; the
catalyst was generated from vanadyl sulfate hydrate and ligand 1.
Isolated yield. Opening of the epoxide took place (ref. 12). The
deduced from their optical rotation and comparison with the
literature data. The reaction was carried out in a 3 : 1 water–
d
b
c
d
e
methanol mixture. The catalyst was generated from vanadyl sulfate
hydrate (3 mol%) and ligand 1 (3.3 mol%).
reaction was carried out in a 3 : 1 water–methanol mixture.
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2 (a) T. Katsuki and K. B. Sharpless, J. Am. Chem. Soc., 1980, 102, 5974;
ligand-accelerated and an excess of the ligand is no longer required.
A range of allylic alcohols were epoxidised with up to 72% ee.
We thank EPSRC for a research grant GR/R86744, and the
University of Glasgow for an additional support.
(b) T. Katsuki and V. S. Martin, Org. React., 1996, 48, 1.
3 (a) R. C. Michaelson, R. E. Palermo and K. B. Sharpless, J. Am. Chem.
Soc., 1977, 99, 1990; (b) K. B. Sharpless and T. R. Verhoeven,
Aldrichim. Acta, 1979, 12, 63.
4 For reviews on V-mediated oxidation, see: (a) A. G. J. Ligtenbarg,
R. Hage and B. L. Feringa, Coord. Chem. Rev., 2003, 237, 89; (b)
C. Bolm, Coord. Chem. Rev., 2003, 237, 245.
5 (a) N. Murase, Y. Hoshino, M. Oishi and H. Yamamoto, J. Org.
Chem., 1999, 64, 338; (b) Y. Hoshino, N. Murase, M. Oishi and
H. Yamamoto, Bull. Chem. Soc. Jpn., 2000, 73, 1653.
6 (a) Y. Hoshino and H. Yamamoto, J. Am. Chem. Soc., 2000, 122,
10452; for a related epoxidation of homoallylic alcohols, see: (b)
N. Makita, Y. Hoshino and H. Yamamoto, Angew. Chem., Int. Ed.,
2003, 42, 941.
7 W. Zhang, A. Basak, Y. Kosugi, Y. Hoshino and H. Yamamoto,
Angew. Chem., Int. Ed., 2005, 44, 4389.
8 (a) K. B. Sharpless, Chem. Tech., 1985, 692; (b) D. J. Berristford,
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ˇ
9 A. V. Malkov, Z. Bourhani and P. Kocovsky´, Org. Biomol. Chem.,
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10 For recent reviews, see: (a) S. Otto and J. B. F. N. Engberts, Org.
Biomol. Chem., 2003, 2809; (b) U. M. Lindstro¨m, Chem. Rev., 2002, 102,
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M. G. Finn, V. V. Fokin, H. C. Kolb and K. B. Sharpless, Angew.
Chem., Int. Ed., 2005, 44, 3275.
Notes and references
{ General procedure for asymmetric epoxidation in water: Vanadyl sulfate
hydrate (3.3 mg, 20 mmol or 5.0 mg, 30 mmol), ligand 1 (10.7 mg, 22 mmol
or 16.0 mg, 33 mmol) and allylic alcohol (1 mmol) were added to distilled
water (3 mL) for the reactions at 0 uC or a 3 : 1 water–methanol solution
(3 mL) for the reactions at 220 uC. The mixture was stirred at room
temperature for 30 min and then cooled to 0 uC or 220 uC. A 70% aqueous
solution of t-BuOOH (0.2 mL, 1.5 mmol) was added and the mixture was
stirred at the same temperature for the period of time indicated in Table 3.
The reaction mixture was then quenched with a concentrated solution of
Na2SO3 (10 mL) and after stirring for 1 h at 0 uC it was extracted with
dichloromethane (2 6 20 mL), the combined organic extracts were dried
over MgSO4 and concentrated in vacuo to give a brown oil. Purification of
the products was accomplished by column chromatography on silica gel
(15 6 3 cm) with a 4 : 1 mixture of n-hexane–ethyl acetate. The absolute
configuration of the epoxide products was assigned by comparison of their
optical rotations with the literature data; the enantiomeric excess was
determined using analysis by chiral GC or HPLC.
11 For mechanistic studies, see: (a) K. P. Bryliakov, E. P. Talsi, C. Bolm
and T. Ku¨hn, New J. Chem., 2003, 27, 609; (b) K. P. Bryliakov and
E. P. Talsi, Kinet. Catal., 2003, 44, 334; (c) K. P. Bryliakov, E. P. Talsi,
S. N. Stas’ko, O. A. Kholdeeva, S. A. Popov and A. V. Tkachev, J. Mol.
Catal. A, 2003, 194, 79.
12 (a) R. M. Hanson, Chem.Rev., 1991, 91, 437; (b) H. R. Tetzlaff and
J. H. Espenson, Inorg. Chem., 1999, 38, 881.
13 For a recent review, see: C. Wandersman and P. Delepelaire, Annu. Rev.
Microbiol., 2004, 58, 611.
1 For overviews, see: (a) T. Katsuki, in Comprehensive Asymmetric
Catalysis, ed. E. N. Jacobsen, A. Pfaltz and H. Yamamoto, Springer-
Verlag, Heidelberg, 1999, vol. 2, p. 621; (b) T. Katsuki, Curr. Org.
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P. A. Ganeshpure, Chem. Rev., 2001, 101, 3499; (e) W. Adam,
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4594 | Chem. Commun., 2005, 4592–4594
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