Epoxidation of allylic alcohols in aqueous solutions of non surfactant amphiphilic sugars

Article abstract of DOI:10.1039/b108352j

A variety of cyclic and acyclic allylic alcohols undergo efficient chemo-, regio- and/or stereoselective epoxidations in neutral aqueous solutions of amphiphilic carbohydrates (sucrose, L-arabinose, methyl or ethyl β-D-fructopyranoside) by using dilute hydrogen peroxide in the presence of molybdic or tungstic salts.

Full text of DOI:10.1039/b108352j

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Epoxidation of allylic alcohols in aqueous solutions of non surfactant
amphiphilic sugars
Cécile Denis,a Khalid Misbahi,a Abdelali Kerbal,b Vincent Ferrièresa and Daniel Plusquellec*a
a Ecole Nationale Supérieure de Chimie de Rennes, Synthèses et Activations de Biomolécules, CNRS
UMR 6052, Institut de Chimie de Rennes, Avenue du Général Leclerc F-35700. Rennes, France.
E-mail: daniel.plusquellec@ensc-rennes.fr; Fax: (+33 0) 2 99 87 13 98; Tel: (+33 0) 2 99 87 13 01
b Laboratoire de Chimie Organique, Faculté des Sciences, Dhar Elmehrez, Fès, Morocco
Received (in Cambridge, UK) 14th September 2001, Accepted 15th October 2001
First published as an Advance Article on the web 15th November 2001
A variety of cyclic and acyclic allylic alcohols undergo
efficient chemo-, regio- and/or stereoselective epoxidations
in neutral aqueous solutions of amphiphilic carbohydrates
Carbohydrates 1–3a,b display therefore facial amphiphilicity
and apolar organic compounds are expected to interact in
aqueous media with the hydrophobic regions of these sugars in
order to minimise unfavourable interactions with water. Aque-
ous solutions of amphiphilic carbohydrates are therefore
expected i) to enhance the solubility of allylic alcohols and ii) to
localise and to orientate the organic substrates.
(sucrose,
L
-arabinose, methyl or ethyl b- -fructopyranoside)
D
by using dilute hydrogen peroxide in the presence of
molybdic or tungstic salts.
Epoxides are versatile building blocks for organic synthesis,
because the epoxide group can be readily opened to produce
vicinal functionalities. Chemo-, regio-, diastereo- and enantio-
selective processes have therefore been developed over the last
decades for the synthesis of oxiranes.1 Traditionally, the
conversion of an alkene into an epoxide is performed by using
peroxycarboxylic acids or tert-butyl hydroperoxide in conjunc-
tion with transition metal catalysts in organic solvents.1
Nevertheless the need for reducing the amounts of toxic waste
from chemical processes requires the use of environmentally
friendly solvents and reagents. In this context, intensive efforts
have been developed in the field of organic synthesis in water.2,3
In this communication, we report a novel and very simple route
for epoxidation of allylic alcohols by aqueous hydrogen
peroxide4 in the presence of molybdic or tungstic salts5 in
neutral aqueous solutions of non surfactant amphiphilic car-
bohydrates.
Epoxidations of allylic alcohols (Fig. 2, 1 mmol) were
performed with 30% hydrogen peroxide (10 mmol) in the
presence of molybdic acid or sodium tungstate (0.1 mmol) in
aqueous buffered solutions (20 mL, pH7, phosphate buffer)
Reactions were carried out in water solutions of selected
carbohydrates, e.g. sucrose 1, a-
L
-arabinopyranose 2 and
methyl or ethyl b-
D
-fructopyranoside 3a,b (Fig. 1). Recent
reinvestigation of sucrose conformation in water reveals the
existence of an interresidue water-bridge.6 This conformation
resembles that found in the crystal7 and in polar aprotic
solvents.8 Applying the Oxford Molecular MAD program9 to
that conformation of sucrose revealed the outside section of the
fructose moiety to be hydrophobic in type.10
Fig. 2 Selected allylic alcohols 4–13.
The composition of an equilibrated mixture of -arabinose 2
L
containing 20 mmol (molar solutions) of sugar additives. Indeed
epoxidations were therefore carried out in dilute ~ 2% aqueous
hydrogen peroxide. The reactions were stirred for 12–72 h
(Table 1) at +2 °C and the products were then easily extracted
with diethyl ether and their purity was determined by capillary
GLC analysis. To compare our system with previously
described aqueous solutions of surfactants,13 some epoxidations
were carried out under the same conditions without any
amphiphilic carbohydrate.
Results of the epoxidation of a number of acyclic and cyclic
allylic alcohols are reported in Table 1. Simple allylic alcohols
4–8 (entries 1–6) afforded the corresponding epoxides in high
conversion yields when reactions were performed in the
presence of carbohydrates 1 or 2. It is noteworthy that no enone
formation was observed14 (see for example entry 2) and that
conversion of the less reactive terminal olefin 51 was dramat-
ically enhanced in the presence of sucrose additive (entries 2, 3).
Moreover, under the present conditions, no triol, resulting from
oxirane opening, could be detected.
in water greatly favours pyranoses (60% a, 35% b) over
furanoses (3% a, 2% b) at 25 °C.11 In the most abundant a-
pyranose form, -arabinose 2a is characterised by an arrange-
L
ment of hydroxy, methine and methylene groups which divides
the molecule into hydrophobic and hydrophilic surfaces. This
expectation is clearly corroborated by computation of the
hydrophilicity potential. Moreover, we have synthesised methyl
and ethyl b- -fructopyranosides 3a and 3b, respectively,
D
according to a procedure recently developed in our laboratory.12
In order to extend our investigation on the regioselectivity of
the reaction, geraniol 9 and nerol 10 were chosen as typical
polyolefinic substrates that are sparingly soluble in pure water
Fig. 1 Structure and hydrophobic areas of amphiphilic carbohydrates 1–3.
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Chem. Commun., 2001, 2460–2461
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b108352j

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Table 1 Epoxidation of allylic alcohols with H2O2–metal catalyst in
aqueous neutral solutions of glycosidic additives at + 2 °C
the epoxidation reaction. Some significant results for the
epoxidation of representative cyclic and acyclic allylic alcohols
are listed in Table 2. The data indicate that acyclic alcohols 4–8
gave mixtures of erythro/threo epoxides. Nevertheless, epox-
idation in glycosidic aqueous media generates stereoselectively
erythro enriched epoxy alcohols. This outcome is the same as
for metal catalysed systems in organic solvents but is opposite
to that obtained using peroxyacids in organic media.16
Con-
Metal Reaction version ketone
Entry Alcohol Additive catalyst time (h) (%) ratio
Epoxide: Isolated
yield
(%)
1
2
3
4
5
6
7
8
9
10
11
12b
13
14
15
16
4
5
1
Mo+6
Mo+6
Mo+6
W+6
24
72
72
24
72
72
48
48
24
48
48
48
72
24
48
24
100
78
30
100
92
97
94
98
97
100
100
100
100
70
> 99+1 75
> 99+1a 72
> 99+1 28
95+5 83
> 99+1 83
> 99+1 88
> 99+1 92
> 99+1 92
90+10 80
97+3 86
97+3 85
98+2 84
83+17 80
87+13 66
60+40 68
85+15 67
1
5
—
1
In the case of cyclohex-2-enols 11–13 the epoxidation was
highly stereoselective when compared with the results obtained
by a peracid epoxidation (Table 2). In particular, allylic alcohols
11–12 gave exclusively the product where epoxide and OH
functions are cis to each other when the reactions were
6
7
1
Mo+6
Mo+6
Mo+6
Mo+6
Mo+6
W+6
8
2
9
1
10
11
11
11
11
12
13
13
13
1
performed in aqueous solutions of -fructose derivatives 3a or
D
2
3b in the presence of Mo+6 or W+6 catalyst. Once again,
comparison of cis+trans ratio underlines the role played by
arabinose as additive (entries 7 and 8).
3a
3b
3b
1
W+6
W+6
W+6
The predictable sense of the addition to cyclic olefins can be
rationalised by means of a model where hydrophobic inter-
actions are probably involved between the most hydrophobic
face of the cyclic alcohol and that of sugar additive. These
interactions may account for the enhanced stereoselective
hydroxy directed epoxidation of cyclic allylic alcohols observed
herein.
2
—
3a
Mo+6
Mo+6
Mo+6
72
70
a Oxirane oxidation in CH2Cl2 gave 51+49.14b Recycled aqueous solution
from entry 11.
In conclusion, it was shown that dilute hydrogen peroxide
together with molybdenum(VI) or tungsten(VI) salts is an
efficient system for the chemo-, regio- and stereoselective
epoxidation of allylic alcohols in aqueous solutions of carbohy-
drates characterised by a facial amphiphilicity.
but highly soluble in 1 M sucrose solutions. A site-selective
epoxidation occurred at the least electron-rich allylic double
bond and pure 2,3-epoxy-geraniol and -nerol were isolated in
high yields (entries 7, 8). Unfortunately, epoxidation of geraniol
9 in the presence of sucrose gave 2,3-epoxygeraniol with
modest enantioselectivity (ee = 10% determined by polari-
metry). Our results obtained in neutral media therefore compare
favourably with previous work performed with peracids in
strongly alkaline media13 or with transition metal catalysed
epoxidations in organic solvents.15,16
Notes and references
1 For a review, see for instance: A. S. Rao, in Comprehensive Organic
Synthesis, ed. B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, Vol.
7, pp. 357–387.
Oxidations of six-membered cyclic substrates (Table 1,
entries 9–15) indicated that enone formation competed with
epoxidation. The ratio of oxirane to ketone showed a pro-
nounced dependence on both substrates and reaction conditions
as exemplified by entries 14 and 15. The best chemoselectivities
were attained by using tungsten(VI) catalyst in the presence of
sugar additives. Moreover, it is important to mention that
solutions containing fructosides and catalyst could be recycled
for further experiments without loss of conversion yield,
chemoselectivity and stereoselectivity (entry 12).
The results presented here suggest OH-assisted epoxidation
of allylic alcohols, presumably related to the formation of an
intermediate in which the olefinic alcohol is most likely
coordinated to the metal via the hydroxy group. Such an
intermediate was previously suggested for tungsten catalysed
epoxidations in protic media.16,17 The next step was therefore to
ascertain whether sugar–substrate and/or intermediate inter-
actions were strong enough to promote stereodiscrimination in
2 C. J. Li, Chem. Rev., 1993, 93, 2023; A. Lubineau, J. Augé, H.
Bienaymé and Y. Queneau, Synthesis, 1994, 741; A. Lubineau, Chem.
Ind., 1996, 123.
3 C. Denis, B. Laignel, D. Plusquellec, J. Y. Le Marouille and A. Botrel,
Tetrahedron Lett., 1996, 37, 53.
4 G. Strukul, in Catalytic Oxidation with Hydrogen Peroxide as Oxidant,
Kluwer Academic Publishers, 1992 R. A. Sheldon, in Applied
Homogeneous Catalysis with Organometallic Compounds, ed. B.
Cornils and W. A. Hermans, VCH Weinheim, 1996J. Brinksma, R.
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6 S. Immel and F. W. Lichtenthaler, Liebigs Ann., 1995, 1925; S. B
Engelsen, C. Hervé du Penhoat and S. Pérez, J. Phys. Chem., 1995, 99,
13334.
7 J. C. Hanson, L. C. Sieker and L. H. Jensen, Acta Crystallogr., Sect. B,
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8 J. C. Christofides and D. B. Davies, Chem. Commun., 1985, 1553.
9 MAD V23, Oxford Molecular Ltd, Magdalen Centre, Oxford Science
Park, Oxford OX4 4GA, England.
Table 2 Diastereoselective epoxidations of allylic alcohols in aqueous
neutral solutions of carbohydrates 1–3
10 F. W. Lichtenthaler and S. Immel, Int. Sugar J., 1995, 97, 12.
11 S. A. Galena, M. J. Blandamer and J. B. F. N. Engberts, J. Org. Chem.,
1992, 57, 1995.
12 V. Ferrières, T. Benvegnu, M. Lefeuvre, D. Plusquellec, G. Mackenzie,
M. J. Watson, J. A Haley, J. W. Goodby, R. Pindak and M. K. Durbin,
J. Chem. Soc., Perkin Trans. 2, 1999, 951.
dra
mCPBA or
Metal
catalyst (cis+trans)
erythro+threo analogues
Entry
Substrate Additive
(lit.)
13 F. Fringuelli, R. Germani, F. Pizzo, F. Santinelli and G. Sanelli, J. Org.
Chem., 1992, 57, 1198; M. Nakaruma, N. Tsutsui and T. Takeda,
Tetrahedron Lett., 1984, 25, 3231.
1
2
3
4
4
5
1
Mo+6
Mo+6
Mo+6
Mo+6
W+6
68+32
68+32
30+7013
38+6214
36+6414
(95+5)18
(95+5)18
1
8
1
2
62+38
14 B. E. Rossiter, T. R. Verhoeven and K. B. Sharpless, Tetrahedron Lett.,
1979, 4733; W. Adam, F. Prechtl, M. J. Richter and A. K. Smerz,
Tetrahedron Lett., 1993, 34, 8427.
11
11
12
12
13
13
(99+1)
3a or 3b
( > 99+1)
(95+5)
5
6
7
8
1
W+6
15 K. B. Sharpless and R. C. Michaelson, J. Am. Chem. Soc., 1973, 95,
3a or 3b
W+6
Mo+6
Mo+6
( > 99+1)
(94+6)
6136.
2
—
(90+10)
16 K. B. Sharpless and T. R. Verhoeven, Aldrichimica Acta, 1979, 12,
63.
(89+11)
17 D. Prat and R. Lett, Tetrahedron Lett., 1986, 27, 707; D. Prat, B.
Delpech and R. Lett, Tetrahedron Lett., 1986, 27, 711.
18 P. Chantemps and J. L. Pierre, Tetrahedron, 1976, 32, 549.
a dr: diastereoisomeric ratio were determined by GLC. erythro/threo refers
to acyclic substrates whereas cis/trans to cyclic products.
Chem. Commun., 2001, 2460–2461
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