A Simple, Convenient and Expeditious Approach to Cineol 469
phenylselenyl halides [23], PhSeX (X = Cl, Br). In-
tramolecular heterocyclization is the main reaction
in the case of all investigated primary and secondary
alkenols, while tertiary alkenols, under the same ex-
perimental conditions, are not converted into cyclic
products at all by PhSeBr and in a small amount with
PhSeCl.
SCHEME 1
RESULTS AND DISCUSSION
and pyridine (1 mmol) in dry CH2Cl2 (5 cm3) was
added solid PhSeCl (1.1 mmol, 0.212 g) or PhSeBr
(1.1 mmol, 0.260 g) or PhSeI (1,1 mmol, 0.311 g) at
room temperature. The reaction was completed in
few minutes. The pale yellow solution was washed
with 5 cm3 1 M HCl aqueous solution, saturated
NaHCO3, and then brine. The organic layer was dried
(Na2SO4), concentrated, and chromatography was
performed. The product was obtained after the elu-
tion of the traces of diphenyl diselenide from a silica
gel /CH2Cl2 column. All the products were character-
ized and identified on the basis of their spectral data.
The cyclic ether products were known compounds,
and their spectral data had been given previously in
the literature [30]. Reduction was performed accord-
ing to the procedure described earlier [31].
Recently, we presented an approach to cyclic ethers
from tertiary alkenols using PhSeX (X = Cl, Br) in
the presence of pyridine [24]. The procedure works
smoothly resulting in quantitative formation of the
cyclic ethers. Prompted by this finding, we consid-
ered it synthetically interesting and profitable for our
purposes to extend this method to other represen-
tative alkenols in order to describe a general pro-
cedure for a rapid and efficient cyclization reaction
of alkenols with phenylselenyl halides [25,26]. Var-
ious substituted tetrahydrofuran and tetrahydropy-
ran rings were obtained that depended on the struc-
ture of the starting alkenols. Oxidative or reductive
elimination of phenylseleno group gave different un-
saturated or saturated ethers that are constutuents of
many natural and biological active products. In par-
ticular, our attention focused on the development of a
general synthetic route for the preparation of cineol.
It is a matter of fact that cineol (eucalyptol) has a
widespread use (in cough syrups and expectorants,
in perfumery, and flavoring). Available methods for
the preparation of cineol require more steps in the
synthetic process with unsatisfactory yields [27,28],
or isolation from natural products [29]. The most
common approach involves phenylselenoetherifica-
tion of ꢀ-terpineol and a subsequent reduction with
Bu3SnH or by catalytic hydrogenation (H2, Pd/C, or
Ra/Ni in THF at room temperature).
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The cyclization step was carried out by addition
of 1 equivalent of PhSeX (X = Cl, Br, I) at room
temperature to a CH2Cl2 solution of ꢀ-terpineol and
pyridine (in ratio 1:1), and cyclic ether bearing PhSe
group was obtained in quantitative yield (100%).
Reduction of this cyclic ether (elimination of PhSe
group) with Bu3SnH in toluene at 110◦C in the pres-
ence of AIBN gave a 98% yield of the cineol (see
Scheme 1). When the removing of PhSe group was
performed by catalytic hydrogenation with Ra/Ni in
THF at room temperature, the yield of cineol was
lower (94%).
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EXPERIMENTAL
All reactions were carried out on a 1 mmol scale. To
a magnetically stirred solution of alkenol (1 mmol)