An efficient route to phenylselenoethers in the presence of Ag2O

Article abstract of DOI:10.1007/s00706-007-0661-y

An efficient protocol for the preparation of phenylselenoethers from unsaturated alcohols using phenylselenenyl halides at room temperature was developed. The procedure employs phenylselenenyl chloride and bromide, some Δ ⁴- and Δ ⁵-

Full text of DOI:10.1007/s00706-007-0661-y

Monatshefte fu¨r Chemie 138, 985–988 (2007)
DOI 10.1007/s00706-007-0661-y
Printed in The Netherlands
An Efficient Route to Phenylselenoethers in the Presence of Ag2O
ꢀ
ˇ ´ ´
Zorica M. Bugarcic , Vera M. Divac, and Mariana P. Gavrilovic
Department of Chemistry, Faculty of Science, University of Kragujevac, Kragujevac, Serbia
Received February 1, 2007; accepted (revised) February 9, 2007; published online July 20, 2007
# Springer-Verlag 2007
Summary. An efficient protocol for the preparation of phe-
tion step or modifying cyclic precursor. Among them,
nylselenoethers from unsaturated alcohols using phenylse-
lenenyl halides at room temperature was developed. The
procedure employs phenylselenenyl chloride and bromide,
some D4- and D5-alkenols and Ag2O, as an additive, to generate
the tetrahydropyrans or tetrahydrofurans. This method permits
the preparation of cyclic phenylselenoethers in high yields and
under extremely mild conditions.
cyclofunctionalization of unsaturated alcohols is a
very popular reaction providing easy access to cyclic
ethers. In many respects selenocyclofunctionalization
has the advantage that the introduction of the hetero-
atom, the manipulation of the obtained product, and
the removal of the function are facilitated by simple
and mild condition [15–23]. This methodology has
also been extended to more complex systems having
alcohol and double bond functions.
Keywords. Additive; Alcohol; Cyclization; Phenylselen-
oetherification.
In 1973 the biochemical role of selenium in mam-
mals has been established. It has been found that it
is part of the active site of the antioxidant enzyme
glutation peroxidase [24, 25]. During the next decade
came the explosive growth in the use of organoselen-
ium compounds. Very soon it has been found that
the phenylselenenyl groups are very good electrophi-
lic reagents in organic synthesis, and in reactions with
olefinic bonds they very often produce regio- and
stereoselective products.
Introduction
Substituted tetrahydrofuran and tetrahydropyran
ring systems are common structural units found in
many bioactive natural products. Consequently, the
development of strategies for the stereocontrolled
synthesis of substituted tetrahydrofurans and tetra-
hydropyrans is an area of considerable ongoing in-
terest [1, 2]. The presence in Nature of molecules
with oxygenated heterocycles is receiving significant
attention considering their capability to transport the
metallic cations Naþ, Kþ, and Ca2þ through lipid
membranes [3–6]. This activity is responsible for
their antibiotic [3], neurotoxic [7, 8], antiviral [9], and
cytotoxic action [10, 11] and as growth regulators
[3, 12, 13] or inhibitors of the level of cholesterol
in blood [14], etc.
Results and Discussion
In recent years, we have been interested in the
synthesis of oxygenated heterocyclic rings via intra-
molecular cyclization of alkenols by means of phe-
nylselenenyl halides [18], PhSeX (X ¼ Cl, Br). We
have reported that intramolecular heterocyclization is
the main reaction in the case of all investigated pri-
mary and secondary alkenols, while tertiary alkenols
under the same experimental conditions are not con-
verted into cyclic products at all by PhSeBr and in
A number of synthesis approaches have been de-
vised in order to construct the cyclic ether moiety using
either a carbon–carbon or a carbon–oxygen cycliza-
ꢀ
Corresponding author. E-mail: zoricab@kg.ac.yu

ˇ ´
Z. M. Bugarcic et al.
986
only a small amount with PhSeCl. Recently, we
have found an approach to cyclic ethers from tertiary
alkenols using PhSeX (X ¼ Cl, Br) in the presence
of pyridine [19, 22]. We found that pyridine as
additive enables fast and facile cyclization and very
high yields of cyclic ethers were obtained.
The present paper describes an easy access to cyc-
lic ethers, THP or THF type, bearing a phenylseleno
moiety in which the yields exceed 70% (in some
cases 90%) and with a little or no purification re-
quired. The procedure works smoothly resulting in
almost quantitative formation of the cyclic ethers
in the presence of Ag2O as the catalyst. The results
of our investigation are displayed in Tables 1 and 2
and in Schemes 1, 2, and 3. The results obtained
show that all reactions proceeded to form oxygen
heterocycles bearing the phenylseleno moiety in
high yields. The cyclization using a stoichometric
amount of Ag2O was completed faster than those
using a catalytic amount. On the other hand, the
reaction without a catalyst in some cases (8b–8e)
did not afford the desired product in practical yield
Table 1. Phenylselenoetherification of some D4-alkenols in the presence of a catalytic and equimolar amount of Ag2O,
Aꢁ ꢁ ꢁPhSeCl, Bꢁ ꢁ ꢁPhSeBr
Substrate
Products
Yields of cyclic ether products=%a
A
A=Ag2O
cat.
A=Ag2O
eq.
B
B=Ag2O
cat.
B=Ag2O
eq.
5a
5b
5c
5d
5e
6a
6b
6c
6d
69
92
86
72
81
97
99
90
93
95
99
100
95
97
99
63
64
47
75
65
86
88
65
90
88
94
95
90
92
95
7e
a
Isolated yields of D4-alkenols [18]
Scheme 1
Scheme 2

Efficient Route to Phenylselenoethers
987
Table 2. Phenylselenoetherification of some D5-alkenols in the presence of a catalytic and equimolar amount of Ag2O,
Aꢁ ꢁ ꢁPhSeCl, Bꢁ ꢁ ꢁPhSeBr
Substrate
Products
Yields of cyclic ether products=%a
A
A=Ag2O
cat.
A=Ag2O
eq.
B
B=Ag2O
cat.
B=Ag2O
eq.
8a
8b
8c
8d
8e
9a
9b
9c
9d
9e
81
80
31
33
30
98
90
69
71
68
100
100
96
97
87
75
26
0
0
0
86
78
55
59
54
98
97
87
88
81
a
Isolated yields of D5-alkenols [18]
Scheme 3
(9b–9e). Cyclization is facilitated by the presence
of Ag2O. Also, the additive caused a dramatic in-
crease in the reaction rate. All reactions were finished
within a few minutes (without additives reaction
time is half an hour to several hours). As we can see
from the results in Tables 1 and 2, primary (5a, 5b)
and secondary (5c) D4-alkenols with a terminal dou-
ble bond as well as D4-alkenols with a terminally
monosubstituted double bond (5d) afford regiose-
lectively the five-membered cyclic ethers (6a, 6b,
6c, and 6d). The D4-alkenol 5e with (E)-configura-
tion in contrast to 5d ((Z)-configuration) affords the
six-membered cyclic ether 7e as a unique product
(Table 1, Scheme 2). The yields of cyclic ethers
are higher by about 20% in comparision with yields
without additive.
To extend the generality of this reaction, cyclization
of various primary, secondary, and tertiary D5-al-
kenols was carried out under optimized conditions,
the results are displayed in Table 2 and in Scheme 3.
These alkenols gave tetrahydropyrans, which are
commonly encountered substructures in many natu-
ral products showing interesting biological properties,
the most prominent of these being polyether antibiot-
ics such as monensin, narasin, and tetronomycin [3].
Hence, of particular importance is the discovery of
the appropriate experimental conditions under which
phenylselenocyclization of D5-alkenols would readily
be accomplished in synthetically useful yields, regard-
less of the reagent used. Cyclization of these alkenols
was complete in a short time, producing the corre-
sponding derivatives 9a–9e in good to excellent yields.
All reactions proceeded to form six-membered
oxygen heterocycles bearing the phenylseleno moiety.
It is in accordance with the ionic mechanism of this
reaction (Scheme 1) and may be ascribed to the ther-
modynamic stability of the cyclized product. Cycli-
zation is facilitated by the presence of Ag2O. Yields
of products are higher and reaction time is shorter.
Catalytic amounts of the additives cause higher yields,
but an equimolar amount gives almost quantitative
yields. Alkenols 8a and 8b reacted very fast and in
very high yields (in the case of PhSeCl and equimo-
lar amount of additive yields are quantitative) but in
the case of alkenols with larger substituents as in 8c,
8d, and 8e, the yields decreased due to steric hin-
drance. Depending on the mechanism, this can indeed
be expected. Obtained results are clear evidence that
the presence of Ag2O increase the yield of the cyclic
ether products. The results are strongly supported by

ˇ ´
Z. M. Bugarcic et al.: Efficient Route to Phenylselenoethers
988
the fact that the additive can bind the counter ion from
the reagent (Xꢂ from PhSeX), increase electrophilicity
of the PhSe group facilitating the subseqent nucleo-
philic attack of the oxygen to form the desired ether,
and eliminates Xꢂ as a concurrent of the hydroxyl
group in the cyclization step.
Acknowledgements
This work was funded by the Ministry of Science, Technology
and Development of the Republic of Serbia (Grant: 142 008B).
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All reactions were carried out on a 1 mmol scale. To a magnet-
ically stirred solution of 1 mmol alkenol and 0.1 mmol or
1 mmol catalyst in 5 cm3 dry CH2Cl2 0.212 g solid PhSeCl
(1.1mmol) or 0.260g PhSeBr (1.1 mmol) were added at room
temperature. The reaction went to completion within a few
minutes. The pale yellow solution was washed with saturated
NaHCO3 and H2O. The organic layer was dried over Na2SO4,
concentrated, and chromatographed. The product was obtained
after the eluation of traces of diphenyl diselenide from a silica
gel-CH2Cl2 column. All products were characterized and iden-
tified on the basis of their spectral data [18].
´
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