One of the most straightforward synthetic procedures for the
preparation of â-hydroxysulfides is the ring opening of epoxides
with thiols in the presence of promoters and/or catalysts.7
However, most of the methods reported consist of Lewis acid
catalysts to perform these reactions under mild conditions, but
these methods suffer with various disadvantages such as drastic
reaction conditions, poor regioselectivity, lower yields, and
undesirable side products by rearrangement of oxiranes and
oxidation of thiols.8
Synthesis of â-Hydroxysulfides from Alkenes
under Supramolecular Catalysis in the Presence
of â-Cyclodextrin in Water
K. Surendra, N. Srilakshmi Krishnaveni, R. Sridhar, and
K. Rama Rao*
Organic Chemistry DiVision-I, Indian Institute of Chemical
Technology, Hyderabad 500 007, India
However, another method commonly used for the straight-
forward synthesis of â-hydroxysulfides involves the thiol-
oxygen cooxidation reactions (TOCOs) of olefins.9 Generally,
the TOCO reaction proceeds on the free-radical-chain pathway.
However, these reactions usually require a base catalyst with a
large excess of thiols and are initiated by UV irradiation or
peroxides. This methodology also suffers with regioselectivity,
lower yields (up to 50%), and undesirable side products. Thus,
in principle, a direct conversion of alkenes into â-hydroxysul-
fides would be a useful contribution to the synthesis of this
functional class. The addition of thiols and various nucleophiles
onto carbon-carbon double bonds proceeds usually in a
Markovnikov or anti-Markovnikov manner.10
ReceiVed April 17, 2006
An environmentally benign and highly efficient procedure
has been developed for the direct one-pot synthesis of
â-hydroxysulfides in good yields under neutral conditions
from alkenes and thiophenols in the presence of aerial oxygen
using â-cyclodextrin in water. This protocol tolerates a wide
variety of functional groups or substrates and does not require
the use of either acid or base catalysts. â-Cyclodextrin can
be recovered and reused for a number of runs without any
loss of activity.
In continuation of our interest in the use of cyclodextrins as
mild and efficient biomimetic catalysts in promoting various
transformations,11 we have attempted the addition of thiols to
alkenes in water in the presence of cyclodextrins.
Cyclodextrins (CDs) are cyclic oligosaccharides possessing
hydrophobic cavities, which bind substrates selectively and
catalyze chemical reactions with high selectivity. They catalyze
reactions by supramolecular catalysis involving reversible
formation of host-guest complexes by noncovalent bonding
as seen in enzymes. Complexation depends on the size, shape,
and hydrophobicity of the guest molecule. We describe, herein,
the remarkable catalytic activity of â-cyclodextrin in the addition
Improving the efficiency of organic synthesis, including
minimizing the energy cost and chemical waste, is a major goal
in synthetic chemistry. In this regard, performing multistep bond
formation and/or bond cleavage in one pot is an attractive
strategy.1 Among various approaches, green chemistry with
water as solvent is becoming important in the present day
organic synthesis.2 Water is a safe, economical, and environ-
mentally benign solvent.3 Water with a recyclable catalyst under
supramolecular catalysis and without the use of any harmful
organic solvents appears to be ideal. We felt the need to apply
the principles of supramolecular catalysis with water as solvent
for the synthesis of â-hydroxysulfides during the course of our
investigations. â-Hydroxysulfides are important building blocks
for the synthesis of higher functionalized organic molecules.4
â-Hydroxysulfides are of great synthetic utility in the field of
pharmaceuticals5 and natural products,6 particularly for the
synthesis of leukotrienes such as LTC4 and LTD4.
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John Wiley: New York, 1974; part 3, p 771. (b) Iida, T.; Yamamoto, N.;
Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1997, 119, 4783. (c) Fringuelli,
F.; Pizzo, F.; Tortoioli, S.; Vassaro, L. J. Org. Chem. 2003, 68, 8248. (d)
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(2) (a) Anastas, P. T.; Warner, J. C. Green Chemistry, Theory and
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Handbook of Green Chemistry & Technology; Clark, J., Macquarrie D.,
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(11) (a) Surendra, K.; Krishnaveni, N. S.; Mahesh, A.; Rao, K. R. J.
Org. Chem. 2006, 71, 2532. (b) Surendra, K.; Krishnaveni, N. S.; Rao, K.
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V. D.; Rao, K. R. J. Org. Chem. 2003, 68, 4994. (d) Surendra, K.;
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10.1021/jo060805a CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/27/2006
J. Org. Chem. 2006, 71, 5819-5821
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