A mild and efficient biomimetic synthesis of α-hydroxymethylarylketones from oxiranes in the presence of β-cyclodextrin and NBS in water

Article abstract of DOI:10.1016/S0040-4039(02)00433-1

α-Hydroxymethylarylketones can be synthesized in good yields from easily accessible epoxides in the presence of β-cyclodextrin and NBS in water. This method is a direct, one-pot, synthesis under mild conditions using water as solvent and has many advantages over existing methodologies.

Full text of DOI:10.1016/S0040-4039(02)00433-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3237–3238
A mild and efficient biomimetic synthesis of
a-hydroxymethylarylketones from oxiranes in the presence of
†
b-cyclodextrin and NBS in water
M. Arjun Reddy, N. Bhanumathi and K. Rama Rao*
Organic Chemistry Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 2 January 2002; revised 18 February 2002; accepted 1 March 2002
Abstract—a-Hydroxymethylarylketones can be synthesized in good yields from easily accessible epoxides in the presence of
b-cyclodextrin and NBS in water. This method is a direct, one-pot, synthesis under mild conditions using water as solvent and
has many advantages over existing methodologies. © 2002 Elsevier Science Ltd. All rights reserved.
a-Hydroxymethylarylketones are widely used synthetic
reactions. These reactions involve supramolecular cataly-
sis through reversible formation of host–guest com-
plexes with the substrates by non-covalent bonding.
Complexation depends on the size, shape and hydro-
phobicity of the guest molecule. Thus, biochemical-like
selectivity which exhibits shape and substrate selectivity
with the reactions being carried out in water will be
superior to chemical selectivity. These attractive fea-
tures of cyclodextrins in the biomimetic modelling of
chemical reactions prompted us to investigate the reac-
tion of styrene epoxide:b-cyclodextrin complexes with
NBS in water. The complexes were formed with b-
cyclodextrin since it is the most accessible and least
expensive of the cyclodextrins. The catalyst can also be
recovered and reused.
intermediates of considerable significance in organic
1
and medicinal chemistry. In view of their importance
as versatile intermediates, a number of methods such as
2
3
the oxidation of enolates using dioxygen ( O ), oxida-
2
3
4
tion of epoxides and diols, synthesis from a-hydroxy
ketone dimethylacetals using iodobenzene diacetate–
potassium hydroxide–methanol followed by oxidation,
partial reduction of 1,2-diketones etc. have been
5
6
reported. However there are still severe limitations with
these methodologies such as the use of anhydrous
organic solvents, moisture sensitive and hazardous
reagents, complex catalysts, low yields etc. In view of
these limitations, there is still a need for a mild and
widely applicable alternative approach using water as
the solvent, which is environmentally benign.
In general these reactions were carried out as follows:
the inclusion complexes were prepared by adding the
epoxide (1, 1 mmol) in acetone (1 ml) to an aqueous
solution of b-cyclodextrin (1 mmol) at 60°C and the
solution was allowed to cool to room temperature
(Scheme 1). Then NBS (1.5 mmol) was added and the
mixture stirred at room temperature for 24 h. The
In our efforts to develop biomimetic approaches for
chemical reactions involving cyclodextrins (CD), we
were trying to synthesize optically active bromohydrins
by the opening of styrene epoxide-b-cyclodextrin com-
plexes with NBS in water. These conditions resulted in
the unexpected and exclusive formation of a-
hydroxyketones.
7
H
O
O
Cyclodextrins which are cyclic oligosaccharides possess-
ing hydrophobic cavities mimic enzymes in their ability
to bind substrates selectively and to catalyze chemical
O
NBS, H2O
RT, 24 h
OH
R
R
1
2
Keywords: oxiranes; NBS; b-cyclodextrin; H O; biomimetic; a-
2
R= H, Br, Cl, Me and NO2
hydroxymethylarylketones.
*
Corresponding author. E-mail: ramaraok@iict.ap.nic.in
IICT Communication No: 01.10.05.
†
Scheme 1.
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00433-1

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M. Arjun Reddy et al. / Tetrahedron Letters 43 (2002) 3237–3238
product was extracted with ethyl acetate and purified
by column chromatography on silica gel. The yields
obtained were good to excellent (Table 1). Higher yields
were obtained when electron-donating substituents
were present on the aromatic ring. All the products
In conclusion, we have demonstrated for the first time
that a-hydroxymethylarylketones can be synthesized in
a biomimetic fashion directly from easily accessible
epoxides in the presence of cyclodextrin and NBS using
water as the solvent. This approach may be considered
as simple with high potential for future applications.
1
were fully characterized by H NMR, IR and mass
spectroscopic data and by comparison with known
8
compounds. These CD mediated water based reactions
benefit from mild conditions and are also useful from
the practical point of view of not having to handle
flammable, anhydrous solvents and toxic reagents.
Acknowledgements
M.A.R. thanks the CSIR, New Delhi for the award of
a research fellowship.
The mechanism of a-hydroxyketone formation may be
postulated as follows: the fact that these reactions do
not take place in the absence of cyclodextrin and that
the starting epoxide is intact indicates the essential role
of cyclodextrin. The cyclodextrin appears to activate
not only the epoxide but also further catalyzes the
reaction through the formation of cyclodextrin hypo-
bromite (from NBS and water) as observed by Breslow
in the chlorination of anisole with sodium hypochlor-
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