Highly regioselective ring opening of oxiranes with phenoxides in the presence of β-cyclodextrin in water

Article abstract of DOI:10.1021/jo034194n

Highly regioselective ring opening of oxiranes to β-hydroxy ethers with phenoxides has been achieved in impressive yields in the presence of β-cyclodextrin as catalyst and water as solvent.

Full text of DOI:10.1021/jo034194n

SCHEME 1
High ly Regioselective Rin g Op en in g of
Oxir a n es w ith P h en oxid es in th e P r esen ce
of â-Cyclod extr in in Wa ter †
K. Surendra, N. Srilakshmi Krishnaveni,
Y. V. D. Nageswar, and K. Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical
Technology, Hyderabad- 500 007, India
ramaraok@iict.res.in
The best choice appeared to be through supramolecular
catalysis involving cyclodextrins with water as solvent
since such reactions do not generate any toxic waste
products (Scheme 1).
Received February 13, 2003
Abstr a ct: Highly regioselective ring opening of oxiranes to
â-hydroxy ethers with phenoxides has been achieved in
impressive yields in the presence of â-cyclodextrin as catalyst
and water as solvent.
Cyclodextrins 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. Complex-
ation depends on the size, shape, and hydrophobicity of
the guest molecule. Thus mimicking of biochemical
selectivity, which is due to orientation of the substrate
by complex formation positioning only certain region for
favorable attack, will be superior to chemical selectivity,
which involves random attack due to intrinsic reactivity
of the substrate at different regions. Our earlier expertise
in the field of biomimetic modeling of organic chemical
reactions involving cyclodextrins11 prompted us to at-
tempt the regioselective ring opening of oxiranes with
phenoxides in the presence of â-cyclodextrin (â-CD) as
this is one of the most useful synthetic transformations
with a variety of applications.
The reaction was carried out by the in situ formation
of the â-CD complex of the epoxide (1) in water followed
by the addition of phenoxide (2) and stirring for 8 h at
60 °C to give the corresponding â-hydroxy ethers (3) in
impressive yields. Several examples illustrating this
simple and practical methodology are summarized in
Table 1. The reaction goes smoothly at 60 °C without the
formation of any side products or rearrangements. These
reactions also take place at room temperature to give the
corresponding â-hydroxy ethers but the reaction times
were longer (18-24 h). The catalyst â-cyclodextrin can
be easily recovered and reused. These reactions do not
proceed in the absence of cyclodextrin. The compounds
were characterized by 1H NMR, mass, IR, and elemental
analysis or otherwise compared with the known com-
pounds.10 The stereochemistry of the ring-opened prod-
ucts (19-21) has been assigned trans configuration by
comparison with the known compounds.12
There is continued interest in the regioselective ring
opening of oxiranes to â-hydroxy ethers due to their
significance as valuable synthetic intermediates in a
variety of pharmaceuticals.1 Oxiranes are well-known
carbon electrophiles and their synthetic potential is
enhanced by their ability to undergo regioselective ring-
opening reactions2 with various nucleophiles such as
CN-,3 N3-,4 NO3-,5 halides,6 amines,7 thiols,8 etc.
The most straightforward synthesis of â-hydroxy ethers
consists of the ring opening of glycidol with phenols in
the presence of tertiary amines or under alkaline condi-
tions at 80-130 °C.9 However, there is a recent report of
the synthesis of a variety of hydroxy ethers with phe-
noxide anions in micellar media with use of Ce(OTf)4.10
Even in this methodology, regioisomers were obtained
and the yields reported were particularly lower when the
reaction was carried out in aqueous medium. Thus, there
is a need for a widely applicable approach preferably with
water as a solvent, which is gaining increasing impor-
tance in present day organic synthesis.
† IICT communication no. 030410.
(1) (a) Wright, J . L.; Gregory, T. F.; Heffner, T. G.; MacKenie, R.
G.; Pugsley, T. A.; Meulen, S. V.; Wise, L. D. Bioorg. Med. Chem. Lett.
1997, 1377. (b) Baker, N. R.; Byrne, N. R.; Byrne, N. G.; Economide,
A. P.; J aveld, T. Chem. Pharm. Bull. 1995, 1045. (c) Kirkup, M. P.;
Rizvi, R.; Shankar, B. B.; Duggar, S.; Clader, J .; McCombie, S. W.;
Lin, S.; Yumibe, N.; Huie, K.; Heek, M.; Compton, D. S.; Davis, H. R.;
McPhail, A. T. Bioorg. Med. Chem. Lett. 1996, 2069.
(2) (a) Parker, R. E.; Isaacs, N. S. Chem. Rev. 1959, 59, 737. (b)
Bonini, C.; Righi, G. Synthesis 1994, 225. (c) Paknikar, S. K.; Kirtane.
J . G. Tetrahedran 1983, 39, 2323. (d) Smith, J . G. Synthesis 1984, 629.
(3) (a) Fulop, F.; Huber, I.; Bernath, G.; Honing, H.; Seyfer-
wesserthal, P. Synthesis 1991, 43. (b) Iranpoor, N.; Shekarriz, M.
Synth. Commun. 1999, 29, 2249. (c) Ciaccio, J . A.; Stanescu, C.;
Bontemps, J . Tetrahedron Lett. 1992, 33, 1431. (d) Chini, M.; Crotti,
P.; Favero, L.; Macchia, F. Tetrahedron Lett. 1991, 32, 4775. (e) Chini,
M.; Crotti, P.; Favero, L.; Macchia, F.; Pineschi, M. Tetrahedron Lett.
1994, 35, 433.
(4) Scriveni, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88.
(5) (a) Iranpoor, N.; Salehi, P. Tetrahedron 1995, 51, 909. (b)
Iranpoor, N.; Zeynizadeh, B. Synthesis 1999, 29, 1071. (c) Iranpoor,
N.; Tarrian, T.; Movahedi, Z. Synthesis 1996, 1473.
(6) (a) Bonini, C.; Righi, G. Synthesis 1994, 225. (b) Reference 11a
and references therein.
(7) Reddy, L. R.; Reddy, M. A.; Bhanumathi, N.; Rao, K. R. New J .
Chem. 2001, 25, 221 and references therein.
(8) Yadav, J . S.; Reddy, B. V. S.; Gakul, B. Chem. Lett. 2002, 906.
(9) Chem, J .; Shum, W. Tetrahedron Lett. 1995, 36, 2379.
(10) Iranpoor, N.; Firouzabadi, H.; Safavi, A.; Shekarriz, M. Synth.
Commun. 2002, 32, 2287.
These reactions do take place with R-CD as well with
the same regioselectivity and sterochemistry; however,
â-CD was chosen as the catalyst since it is inexpensive
(11) (a) Reddy, M. A.; Surendra, K.; Bhanumathi, N.; Rao, K. R.
Tetrahedron 2002, 58, 6003. (b) Reddy, M. A.; Bhanumathi, N.; Rao,
K. R. Tetrahedron Lett. 2002, 43, 3237. (c) Reddy, M. A.; Bhanumathi,
N.; Rao, K. R. Chem. Commun. 2001, 1974. (d) Reddy, L. R.; Bhanu-
mathi, N.; Rao, K. R. Chem. Commun. 2000, 2321. (e) Reddy, L. R.;
Reddy, M. A.; Bhanumathi, N.; Rao, K. R. Synlett 2000, 339. (f) Reddy,
M. A.; Reddy, L. R.; Bhanumathi, N.; Rao, K. R. New J . Chem. 2001,
25, 359. (g) Reddy, M. A.; Reddy, L. R.; Bhanumathi, N.; Rao, K. R.
Chem. Lett. 2001, 246.
10.1021/jo034194n CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/16/2003
4994
J . Org. Chem. 2003, 68, 4994-4995

TABLE 1. Rin g Op en in g of Oxir a n es w ith P h en oxid e in P r esen ce of â-CD in Wa ter
a
b
All the products were characterized by 1H NMR, IR, and mass spectroscopy. Isolated yields after purification.
and easily accessible. Though inclusion complexation
takes place in situ during the reaction, the complexes
have been isolated and characterized by powder X-ray13
Exp er im en ta l Section
Ma ter ia ls. Oxiranes were either purchased commercially or
synthesized15a and phenoxides were synthesized as reported in
the literature.15b
1
and H NMR studies.14 Here, the role of CD appears to
Gen er a l P r oced u r e. â-Cyclodextrin (1 mmol) was dissolved
in water (25 mL) at 60 °C, and epoxide (1 mmol) dissolved in
acetone (2 mL) was added slowly with stirring. After 15 min at
that temperature, sodium phenoxide(1 mmol) was added and
stirred for 8 h at 60 °C. The organic material was extracted with
ethyl acetate. The organic phase was separated, filtered, and
washed with brine. The organic phase was then dried (Na2SO4)
and filtered and the solvent was removed under vacuum. The
crude product was purified by silica gel column chromatography
with ethyl acetate:hexane (2:8) as eluent.
be not only to activate the oxiranes but also to promote
highly regioselective ring opening due to inclusion com-
plex formation with cyclodextrin in this new biomimetic
methodology.
Thus, it has been shown for the first time that
â-hydroxy ethers with high synthetic potential can be
made in a biomimetic fashion with high regioselectivity
from the easily accessible oxiranes and inexpensive
phenoxides in the presence of â-cyclodextrin in water.
Further potential applications of this reaction are under
study.
Su p p or tin g In for m a tion Ava ila ble: Experimental data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(12) Shigeki, M.; Das, J .; Roels, J .; Vogl, E. M.; Yamamoto, N.; Iida,
T.; Yamaguchi, K.; Shibasaki, M. J . Am. Chem. Soc. 2000, 122, 2252.
(13) Szejtli, J .; Osa, T. Comprehensive Supramolecular Chemistry;
Pergamon: Oxford, U.K. 1996; Vol. 3, p 253.
J O034194N
(15) (a) Stephenson, O. J . Chem, Soc. 1954, 1571. (b) Kornblum,
N.; Lurie, A. P. J . Am. Chem. Soc. 1959, 81, 2705.
(14) Demarco, P. V.; Thakkar, A. L. Chem. Commun. 1970, 2.
J . Org. Chem, Vol. 68, No. 12, 2003 4995