Phenylselenoetherification of Some Δ5-Alkenols in the Presence of Pyridine, Ag2O, and AgOAc as Additives

Article abstract of DOI:10.1007/s00706-002-0596-2

An improved procedure for intramolecular cyclization of some Δ ⁵-aikenols using PhSeX (X=Cl, Br) was developed. We found that cyclization can be facilitated in the presence of pyridine, Ag₂O, and AgQAc as additives. Thus, a catalytic

Full text of DOI:10.1007/s00706-002-0596-2

Monatshefte f€ur Chemie 134, 1359–1363 (2003)
DOI 10.1007/s00706-002-0596-2
Phenylselenoetherification of Some
D5-Alkenols in the Presence of Pyridine,
Ag2O, and AgOAc as Additives
ꢀ
ˇ ´ ´
Zorica M. Bugarcic and Marijana Gavrilovic
University of Kragujevac, Faculty of Science, Department of Chemistry,
YU-34 000 Kragujevac, Yugoslavia
Received October 21, 2002; accepted (revised) November 13, 2002
Published online August 28, 2003 # Springer-Verlag 2003
Summary. An improved procedure for intramolecular cyclization of some D5-alkenols using PhSeX
(X ¼ Cl, Br) was developed. We found that cyclization can be facilitated in the presence of pyridine,
Ag2O, and AgOAc as additives. Thus, a catalytic amount of additive influenced higher yields and
equimolar amounts achieved almost quantitative yields under extremely mild experimental conditions.
The effect of the halide ion of the selenylating reagent was not significant.
Keywords: Additives; Alkenols; Cyclization; Heterocycles; Phenylselenyl halides.
Introduction
During the last years, cyclic ethers have attracted considerable attention due to
their occurrence in several groups of natural compounds exhibiting important
biological activities [1]. These units can be found in monocyclic or polycyclic
compounds, fused with other cyclic ethers or forming spiro systems [2]. The
presence of molecules with oxygenated heterocycles in nature is receiving con-
siderable attention thinking of their capacity of transport modification of Naþ ,
Kþ , and Ca2 þ .cations 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 cholesterol level in blood
[14].
A number of synthetic approaches have been devised in order to construct the
cyclic ether moiety, using a carbon–carbon [15–22] or a carbon–oxygen [23–34]
cyclization step, or modifying a cyclic precursor [35–41].
ꢀ
Corresponding author. E-mail: zoricab@knez.uis.kg.ac.yu

ꢀ ꢁ ꢁ
Z. M. Bugarcic and M. Gavrilovic
1360
Results and Discussion
In recent years we have studied the intramolecular cyclizations of some D4- and
D5-alkenols by means of benzeneselenenyl halides PhSeX (X ¼ Cl, Br) [29, 40–
42]. Intramolecular heterocyclization is the main reaction in the case of all inves-
tigated primary and secondary alkenols, whereas tertiary alkenols, under the same
experimental conditions are not converted into cyclic products at all by PhSeBr,
however, in low yields with PhSeCl. Although additional products are expected,
we have found that all investigated tertiary alkenols in the reaction with PhSeBr
[41] afforded ꢀ- and ꢁ-bromoalkanols in high yields (about 90%).
Recently [42], we have presented an approach to cyclic ethers from tertiary alke-
nols using PhSeX (X ¼ Cl, Br) in the presence of pyridine. We found that the yields of
the cyclic ethers are quantitative. In this paper, we present the extension of the meth-
odology to primary and secondary D5-alkenols and with Ag2O and AgOAc as addi-
tives. These alkenols have given tetrahydropyrans, which are commonly encountered
substructures in many natural products showing interesting biological properties, the
most prominent of these being polyether antibiotics 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 can
readily be accomplished in synthetically useful yields, regardless of the reagent used.
The results of our investigation are shown in Tables 1 and 2 and in Scheme 1.
All reactions proceeded to form six-membered oxygen heterocycles bearing the
phenylseleno moiety. This is in accordance with the ionic mechanism of this reac-
tion and may be ascribed to the thermodynamic stability of the cyclized product.
Cyclization is facilitated by the presence of pyridine, Ag2O, and AgOAc. Thus,
yields of products are higher and reaction times are shorter. Catalytic amounts of
additives influence higher yields, but an equimolar amount gives almost quantita-
tive yields. As we can see from Tables 1 and 2, pyridine shows the best results if an
equimolar amount is used and Ag2O is the best catalyst for this type of cyclization.
It appears that the presence of pyridine is beneficial to the cyclization process due
to its basic properties. All additives could enhance the nucleophilicity of the hydrox-
yl group of the alkenol and also mediate the stabilization of the oxonium ion
intermediates. In the case of alkenols with larger substituents as in 1c, 1d, and
1e, the product yields go down regarding to the effects of steric hindrance. Depend-
ing on the mechanism, this can indeed be expected.
Table 1. Phenylselenoetherification of some D5-alkenols in the presence of catalytic amounts of
pyridine, Ag2O, and AgOAc. A ꢁ ꢁ ꢁ PhSeCl, B ꢁ ꢁ ꢁ PhSeBr
Substrates Products Yields of cyclic ether products=%
A
A=py A=Ag2O A=AgOAc
B
B=py B=Ag2O B=AgOAc
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
81 90
80 86
31 54
33 56
30 51
98
90
69
71
68
86
83
35
40
34
75 79
26 63
86
78
55
59
54
77
32
27
30
29
0
0
0
36
38
35

Phenylselenoetherification of Some D5-Alkenols
1361
Table 2. Phenylselenoetherification of some D5-alkenols in the presence of equimolar amounts of
pyridine, Ag2O, and AgOAc. A ꢁ ꢁ ꢁ PhSeCl, B ꢁ ꢁ ꢁ PhSeBr
Substrates Products Yields of cyclic ether products=%
A
A=py A=Ag2O A=AgOAc
B
B=py B=Ag2O B=AgOAc
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
81 100
80 100
31 100
33 100
100
100
96
89
85
58
60
54
75 100
26 100
98
97
87
88
81
80
62
42
45
40
0
0
0
100
100
85
97
30
93
87
Scheme 1
This improved procedure for phenylselenoetherification should often prove the
simplest and superior to those currently available. As for the yields of cyclic ethers,
the procedure described in this article gave better results than reported synthesis.
Accompanied by other merits, such as the mildness of the reaction conditions and
the simplicity of the experimental procedure, our synthesis is the most attractive
one for the conversion of alkenols into oxacyclic compounds.
Experimental
Gas–liquid chromatography (GLC) analysis was performed with a Deni instrument, model 2000 with
capillary apolar columns. 1H and 13C NMR spectra were run in CDCl3 on a Varian Gemini 200 MHz
NMR spectrometer. IR spectra were obtained with Perkin-Elmer Model 137B and Nicolet 7000 FT
spectrophotometers. Microanalyses were performed by Dornis and Colbe. Thin-layer chromatography
(TLC) was carried out on 0.25 mm E. Merck precoated silica gel plates (60F-254) using UV light for
visualization. For column chromatography, E. Merck silica gel (60, particle size 0.063–0.200mm) was
used.
General Procedure
All reactions were carried out on a 1 mmol scale. To a magnetically stirred solution of 1 mmol of
alkenol and 0.1 mmol or 1 mmol of additive in 5 cm3 of dry CH2Cl2 was added 0.212 g of solid PhSeCl
(1.1mmol) or 0.260 g of PhSeBr (1.1mmol) at room temperature. The reaction went to completion in a

ꢀ ꢁ ꢁ
Z. M. Bugarcic and M. Gavrilovic
1362
few minutes. The pale yellow solution was washed (in the case of pyridine as additive) with 5 cm3 of
1 M aqueous HCl solution, saturated NaHCO3 solution, and then brine or with saturated NaHCO3
solution and H2O (in the case of Ag2O and AgOAc). The organic layer was dried (Na2SO4), concen-
trated, and chromatography was performed. The product was obtained after elution of traces of
diphenyl diselenide from a silica gel column using CH2Cl2 as eluent. All the products were character-
ized and identified on the basis of their spectral data. The cyclic ether products are known compounds,
and their spectral data have been given previously [29].
Acknowledgments
This work was founded by the Ministry of Science, Technologies, and Development of the Republic of
Serbia (Grant: 1254).
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