An Improved Procedure for Phenylselenoetherification of Some Δ5-Alkenols Using Pyridine, Ag2o, and Some Lewis Acids as Catalysts

Article abstract of DOI:10.1002/hc.10227

An improved procedure for intramolecular cyclization of some Δ⁵-alkenols, using PhSeX (X = Cl, Br) has been developed. We found that cyclization can be facilitated in the presence of pyridine, Ag ₂O, and some Lewis acids as catalysts

Full text of DOI:10.1002/hc.10227

Heteroatom Chemistry
Volume 15, Number 2, 2004
A
ꢀ
n Improved Procedure for
Phenylselenoetherification of Some
5
-Alkenols Using Pyridine, Ag O, and Some
2
Lewis Acids as Catalysts
Zorica M. Bugar cˇ i c´ and Biljana M. Mojsilovi c´
Department of Chemistry, University of Kragujevac, Radoja Domanovi c´ a 12, 34 000 Kragujevac,
Serbia
Received 2 October 2003
in monocyclic or polycyclic compounds, fused with
ABSTRACT: An improved procedure for intramolec-
other cyclic ethers or forming spiro systems [2]. The
5
ular cyclization of some ꢀ -alkenols, using PhSeX (X =
presence in nature of molecules with oxygenated het-
Cl, Br) has been developed. We found that cyclization
erocycles is receiving considerable attention consid-
can be facilitated in the presence of pyridine, Ag O,
2
ering their capacity of modification of the transport
and some Lewis acids as catalysts. Thus catalytic
amount of additives (pyridine and Ag O) influences
+
+
2+
of the metal cations Na , K , and Ca through the
lipid membranes [3–6], this activity being responsi-
ble for their antibiotic [3], neurotoxic [7,8], antiviral
2
higher yields but equimolar amount achieves almost
quantitative yield under extremely mild experimental
[9], and cytotoxic action [10,11], and as growth reg-
conditions. In the presence of Lewis acids (ZnCl
2
and
ulators [3,12,13] or inhibitors of the level of choles-
terol in blood [14], etc.
A number of synthetic approaches have been de-
vised in order to construct the cyclic ether moiety,
using a carbon-carbon [15–22] or a carbon-oxygen
FeCl ) high yields of cyclic ether products are obtained
3
with catalytic amounts. ꢀC 2004 Wiley Periodicals, Inc.
Heteroatom Chem 15:146–149, 2004; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.10227
[23–34] cyclization step or modifying cyclic precur-
sor [35–41].
INTRODUCTION
EXPERIMENTAL
During the last years, cyclic ether units are important
synthetic targets in organic and medicinal chemistry
due to their widespread occurrence in many com-
plex natural compounds exhibiting important bio-
logical activity [1]. These units can be found isolated
All reactions were carried out on a 1 mmol
scale. To a magnetically stirred solution of alkenol
(1 mmol) and catalyst (0.1 mmol or 1 mmol) in dry
3
dichloromethane (5 cm ), solid PhSeCl (0.212 g, 1.1
mmol) or PhSeBr (0.260 g, 1.1 mmol) was added
at room temperature. The reaction went to comple-
tion in a few minutes. The pale yellow solution was
washed (in the case of pyridine as a catalyst) with 1
M HCl aqueous solution (5 cm ), saturated NaHCO
Correspondence to: Zorica M. Bugar cˇ i c´ ; e-mail: zoricab@
knez.uis.kg.ac.yu.
Contract grant sponsor: Ministry of Science, Technology and
Development of The Republic of Serbia.
Contract grant number: 1254.
ꢀ
c 2004 Wiley Periodicals, Inc.
3
3
,
and then brine or with saturated NaHCO
3
and water
(in the case of Ag O, ZnCl , and FeCl ). The organic
2
2
3
1
46

5
2
An Improved Procedure for Phenylselenoetherification of Some ꢀ -Alkenols, Ag O, and Some Lewis Acids 147
layer was dried over Na
2
SO
4
, concentrated and chro-
TABLE 1 Yields (%) of Cyclic Ethers 2a–c from the
5
Phenylselenoetherification of Some ꢀ -Alkenols in the Pres-
matographed. The product was obtained after the
eluation of the traces of diphenyl diselenide from
a silica gel-dichloromethane column. All the prod-
ucts were characterized and identified on the basis
of their spectral data. The cyclic ether products were
known compounds, and their spectral data had been
given previously [29].
ence of a Catalytic and Equimolar Amount of Pyridine and
Ag O, and a Catalytic Amount of ZnCl and FeCl
2
2
3
2a
2b
2c
31
54
100
69
96
89
86
0
PhSeCl
PhSeCl, pyridine cat.
PhSeCl, pyridine equ.
81
90
100
98
100
100
100
75
80
86
100
90
100
94
92
PhSeCl, Ag O cat.
2
PhSeCl, Ag O equ.
2
RESULTS AND DISCUSSION
PhSeCl, ZnCl cat.
2
PhSeCl, FeCl cat.
3
In recent years, we have studied intramolecular cy-
PhSeBr
26
4
5
clization of some ꢀ - and ꢀ -alkenols by means of
phenylselenyl halides [30–41], PhSeX (X = Cl, Br).
Intramolecular heterocyclization is the main reac-
tion in the case of all investigated primary and sec-
ondary alkenols, while tertiary alkenols, under the
same experimental conditions, are not converted
into cyclic products at all by PhSeBr and in a small
amount with PhSeCl. Although the additional prod-
ucts are expected, we have found that all investigated
tertiary alkenols in the reaction with PhSeBr [41] af-
forded γ- and δ-bromoalkanols in high yields (about
PhSeBr, pyridine cat.
PhSeBr, pyridine equ.
PhSeBr, Ag2O cat.
79
100
86
98
100
100
63
100
78
97
81
36
100
55
87
78
87
PhSeBr, Ag O equ.
2
PhSeBr, ZnCl cat.
2
PhSeBr, FeCl cat.
91
3
and improved yields compared with phenylselenyl
halides alone.
Also, the additives increased the reaction rate
dramatically; all reactions were completed a few
minutes (without additives reaction time is half an
hour to several hours). Although the reactions in the
90%).
Recently, we presented an approach to cyclic
ethers from tertiary alkenols using PhSeX (X = Cl,
Br) in the presence of pyridine [42]. 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. In this paper,
presence of pyridine and Ag O can be performed in a
2
catalytic manner, we found that almost quantitative
yields were obtained when 1 equivalent amount of
additive was used (Table 1). As we can see from the
results, pyridine shows the best results in the case
of equimolar amount, while Ag O is a better catalyst
2
for this type of cyclization. In the case of the ter-
tiary alkenol with more substituents (1c) the prod-
uct yield decreases because of the effects of steric
hindrance. Depending on the mechanism, this can
indeed be expected. It appears that the presence of
pyridine is beneficial to the cyclization process and
more likely due to its basic properties. Subsequently,
we evaluated the effect of some Lewis acids on the
cyclization process. The results obtained indicate
we wish to present the extension of the method to
5
primary and secondary ꢀ -alkenols and with Ag
2
O,
ZnCl
2
, and FeCl as catalysts. These alkenols afforded
3
tetrahydropyran derivatives, which are commonly
encountered substructures in many natural prod-
ucts showing interesting biological properties, the
most prominent of these being polyether antibiotics
that the presence of ZnCl
cial role in the cyclization process (Table 1). Yields
2
and FeCl plays a cru-
3
(such as monensin, narasin, and tetronomycin), ma-
rine toxins, and pheromones [3]. Hence, of partic-
ular importance is the discovery of the appropriate
experimental conditions under which phenylseleno-
5
cyclization of ꢀ -alkenols would readily be accom-
plished in synthetically useful manner, regardless of
the reagent used. The results of our investigation are
shown in Table 1 and in Scheme 1.
All reactions proceeded to form oxygen hete-
rocycles bearing the phenylseleno moiety. Cycliza-
tion is facilitating by the presence of pyridine, Ag
2
O,
and some Lewis acids (ZnCl and FeCl ). It became
2
3
clear that phenylselenyl halides in combination with
these catalysts usually gave rise to cleaner reactions
SCHEME 1

1
48 Bugar cˇ i c´ and Mojsilovi c´
of the cyclic ether products in the presence of cat-
alytic amount of ZnCl and FeCl are even better than
those obtained with pyridine and Ag O. Even though
PhSeCl in combination with equimolar amount of
ZnCl is known as a strong chlorophenylselenylating
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3
1
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[
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of ZnCl
9%).
We also evaluated the effect of AgOAc on the cy-
2
and FeCl influenced moderate yields (41–
3
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These results are clear evidence that the presence
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2
O, ZnCl
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A speculative rationale explaining the increased
yields of cyclic ether products in the additive-
catalyzed process performed under our conditions
could be the following. All used additives can bound
−
counter ion from reagent (X from PhSeX), increase
−
electrophilicity of PhSe group, and eliminate X as
[
a concurrent of hydroxyl group in cyclization step.
All additives could enhance the nucleophilicity of the
hydroxyl group of the alkenol and also mediate the
stabilization of the oxonium ion intermediates.
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THP-ethers are more advantageous in terms of time
and yield than those previously reported for the same
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This improved procedure for phenyselenoether-
ification should often prove the simplest and supe-
rior to those currently available. As for the yields
of cyclic ethers, the procedure described in this ar-
ticle gave better results than reported procedures.
Accompanied by other merits, such as the mildness
of the reaction conditions and the simplicity of the
experimental procedure, our procedure is the most
attractive one for the conversion of alkenols into ox-
acyclic compounds. Moreover, we are confident that
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