An improved phenylselenoetherification of pent-4-en-1-ol

Article abstract of DOI:10.1007/s00706-006-0581-2

The procedure employs phenylselenyl chloride or bromide, pent-4-en-1-ol, and additives, like pyridine and silver(I) salts, to generate the cyclic ether of tetrahydrofuran type in high yields. A catalytic amount of additive leads to higher yields, but equi

Full text of DOI:10.1007/s00706-006-0581-2

Monatshefte fu¨r Chemie 138, 149–151 (2007)
DOI 10.1007/s00706-006-0581-2
Printed in The Netherlands
An Improved Phenylselenoetherification of Pent-4-en-1-ol
ꢀ
ˇ ´ ´
Zorica M. Bugarcic , Marijana P. Gavrilovic, and Vera M. Divac
Department of Chemistry, Faculty of Science, University of Kragujevac, Kragujevac, Serbia
Received July 5, 2006; accepted (revised) July 25, 2006; published online January 10, 2007
# Springer-Verlag 2007
Summary.The procedure employs phenylselenyl chloride or
[23–34] cyclization step, or modifying a cyclic pre-
cursor [35–41].
bromide, pent-4-en-1-ol, and additives, like pyridine and sil-
ver(I) salts, to generate the cyclic ether of tetrahydrofuran type
in high yields. A catalytic amount of additive leads to higher
yields, but equimolar amounts achieved almost quantitative
yields under extremely mild experimental conditions. The
effect of the halide ion of the selenylating reagent is not sig-
nificant.
Results and Discussion
In recent years, we have studied the intramolecular
cyclization of some D4- and D5-alkenols by means
of benzeneselenyl halides PhSeX (X ¼ Cl, Br) [29,
40–42]. Intramolecular heterocyclization is the main
reaction in the case of all investigated primary and
secondary alkenols, while tertiary alkenols, under
the same experimental conditions are not converted
into cyclic products at all by PhSeBr and in a small
amount by PhSeCl. Although the addition 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 alkenols 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 methodol-
ogy to pent-4-en-1-ol (1) and with Ag2O and AgOAc
as additives. This alkenol yields the tetrahydrofuran
ring, which is a commonly encountered substruc-
ture in many natural products showing interesting
biological properties. The results of our investigation
are shown in Table 1 and Scheme 1. These results
show that all reactions proceeded to form oxygen
heterocycles bearing the phenylseleno moiety in
high yields (Table 1).
Keywords. Additive;Alcohol;Cyclization;Phenylselenoether-
ification; Furan.
Introduction
During the last years, cyclic ethers have attracted
considerable attention due to their occurrence in sev-
eral groups of natural compounds exhibiting im-
portant 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 het-
erocycles in nature is receiving considerable atten-
tion considering their capacity of modification of the
transport of the Naþ, Kþ, and Ca2þ 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 reg-
ulators [3, 12, 13] or inhibitors of the level of cho-
lesterol in blood [14].
A number of synthesis approaches have been
devised in order to construct the cyclic ether moiety
using a carbon–carbon [15–22] or a carbon–oxygen
ꢀ
Corresponding author. E-mail: zoricab@knez.uis.kg.ac.yu

ˇ ´
Z. M. Bugarcic et al.
150
1
Table 1. Phenylselenoetherification of pent-4-en-1-ol without
additive (a) and in the presence of a catalytic (A) and equimo-
lar (B) amount of pyridine (b), Ag2O (c), and AgOAc (d)
columns. H 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. Thin-layer chromatography (TLC) was
carried out on 0.25mm E. Merck precoated silica gel plates
(60F-254) using UV light for visualization. For column chro-
matography, E. Merck silica gel (60, particle size 0.063–
0.200 mm) was used.
alkenol product
Yields of cyclic products=%
PhSeCl PhSeBr
a
b
c
d
a
b
c
d
1
2
A
B
69 97 99 96 63 95 97 92
69 100 97 92 63 100 95 90
General Procedure
All reactions were carried out on a 1 mmol scale. To a mag-
netically stirred solution of alkenol 1 (1mmol) and 0.1mmol
or 1 mmol additive in 5 cm3 dry CH2Cl2 was added 0.212g
solid PhSeCl (1.1mmol) or 0.260 g PhSeBr (1.1mmol) at
room temperature. The reaction went to completion within a
few minutes. The pale yellow solution was washed (in the
case of pyridine as an additive) with 5 cm3 1 M HCl aqueous
solution, saturated NaHCO3, and then brine, or with saturated
NaHCO3 and H2O (in the case of Ag2O and AgOAc). The
organic layer was dried (Na2SO4), concentrated, and chroma-
tography was performed. The product was obtained after elu-
tion of traces of diphenyl diselenide from a silica gel column
using CH2Cl2. All the products were characterized and iden-
tified on the basis of their spectral data. The cyclic ether
product 2 is a known compound. Its spectroscopic data has
been given previously [29].
Scheme 1
Cyclization is facilitated by the presence of pyri-
dine, Ag2O, and AgOAc. Yields of products are higher
and reaction time is shorter. Catalytic amounts of addi-
tives lead to higher yields, but an equimolar amount
gives almost quantitative yields. As we can see from
Table 1, pyridine shows the best results in the case of
an equimolar amount, and Ag2O is the best catalyst for
this type of cyclization. The cyclization using a stoi-
chometric amount of Ag2O was completed faster than
by using catalytic amounts only. 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 hydroxyl group of
the alkenol and also mediate the stabilization of the
oxonium ion intermediates. On the other hand, the
reaction without a catalyst did not afford the desired
product in practical yield. Also, the additive caused a
dramatic increase in reaction rate. Thus, the reactions
were completed in a few minutes (without additives
the reaction time is half an hour to several hours).
This improved procedure for phenyselenoetherifi-
cation should prove simpler and superior to those
currently available. As for the yields of cyclic ethers,
the procedure described gave better results than re-
ported 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 conver-
sion of alkenols into oxacyclic compounds.
Acknowledgements
This work was founded by the Ministry of Science, Technol-
ogies and Development of the Republic of Serbia (Grant: 142
008B).
References
[1] Yasumoto T, Murata M (1993) Chem Rev 93: 1897
[2] Faulkner D (1997) J Nat Prod Rep 14: 259
[3] Wesley JW (1982) Polyether Antibiotics Naturally
Occurring Acid Ionophores, Marcel Decker, New York,
Vols I and II
[4] Painter GR, Presman BC (1982) Top Curr Chem 101: 83
[5] Still WC, Hauck P, Kempf D (1987) Tetrahedron Lett
28: 2817
[6] Smith PW, Still WC (1988) J Am Chem Soc 110: 7917
[7] Shimizu Y, Marine Natural Products, Scheuer P (1978)
Academic press, New York, Vol I, p 1
[8] Ellis S (1985) Toksikon 23: 469
[9] Sakemi S, Higa T, Jefford CW, Bernardinelli G (1986)
Tetrahedron Lett 27: 4287
[10] Suzuki T, Suzuki A, Furusaki T, Matsumoto A, Kato A,
Imanaka Y, Kurosawa E (1985) Tetrahedron Lett 26:
1329
[11] Corley DG, Herb RR, Moore E, Scheuer PJ, Paul VJ
(1988) J Org Chem 53: 3644
[12] Cohran VM (1958) Physiology of Fungi, Wiley, New
York
Experimental
Gas–liquid chromatography (GLC) analysis was performed
with a Deni instrument, model 2000 with capillary apolar
[13] Schreiber SL, Kelly SE, Porco JA, Sanmakia T, Suh EM
(1988) J Am Chem Soc 110: 6210

An Improved Phenylselenoetherification
151
´
´
[14] Gonzalez AG, Martin JD, Martin VS, Norte M, Perez R,
Ruano JZ, Drexler SA, Clardy J (1982) Tetrahedron 38:
1009
[29] Konstantinovic S, Bugarcic Z, Milosavljevic S, Schroth
G, Mihailovic MLJ (1992) Liebigs Ann Chem 261
[30] Gung BW, Francis MB (1993) J Org Chem 58: 6177
[31] Mukai C, Ikeda Y, Sugimoto Y, Hanaoka M (1994)
Tetrahedron Lett 35: 2179
[15] Ravelo JL, Regueiro A, Martin JD (1992) Tetrahedron
Lett 33: 3389
[16] Hoffmann RW, Mu¨nster I (1995) Tetrahedron Lett 36:
1431
[32] Mukai C, Sugimoto Y, Ikeda Y, Hanaoka M (1994)
Tetrahedron Lett 35: 2183
[17] Alvarez E, Diaz MT, Hanxing L, Martin JD (1995) J Am
Chem Soc 117: 1437
[33] Palazoin JM, Martin VS (1995) Tetrahedron Lett 36:
3549
[18] Clark JS, Kettle JG (1997) Tetrahedron Lett 38: 127
[19] Inoue M, Sasaki M, Tachibana K (1997) Tetrahedron
Lett 38: 1611
[20] Berger D, Overman LE, Renhowe PA (1997) JAm Chem
Soc 119: 2446
[21] Crimmins MT, Choy AL (1997) J Org Chem 62: 7548
[22] Nicolaou KC, Prasad CVC, Hwang CK, Duggan ME,
Veale CA (1989) J Am Chem Soc 111: 5321
[23] Nicolaou KC, Prasad CVC, Somers PK, Hwang CK
(1989) J Am Chem Soc 111: 5330
[24] Nicolaou KC, Prasad CVC, Somers PK, Hwang CK
(1989) J Am Chem Soc 111: 5335
[25] Cooper AJ, Salomon RG (1990) Tetrahedron Lett 31:
3813
[26] Suzuki T, Sato O, Hirama M (1990) Tetrahedron Lett 31:
4747
[34] Paquette LA, Sweeney TJ (1990) J Org Chem 55:
1703
[35] Nicolaou KC, McGarry DG, Somers PK, Kim BH,
Ogilvie WW, Yiannikouros G, Prasad CVC, Veale
CA, Hark RR (1990) J Am Chem Soc 112: 6263
[36] Carling RW, Clark JS, Holmes AB (1992) J Chem Soc
Perkin Trans 1: 83
[37] Carling RW, Clark JS, Holmes AB, Sartor D (1992) J
Chem Soc Perkin Trans 1: 95
[38] Fuhry MA, Holmes AB, Marshall DR (1993) J Chem
Soc Perkin Trans 1: 2743
´
[39] Alvarez E, Diaz MT, Perez R, Ravelo JL, Requeiro A,
Vera JA, Zurita D, Martin JD (1994) J Org Chem 59:
2848
[40] Bugarcic Z, Konstantinovic S, Mojsilovic B (1999) Ind
J Chem 38B: 728
[27] Aicher TD, Buszek KR, Fang FK, Forsyth CJ, Jung SH,
Kishi Y, Scola PM (1992) Tetrahedron Lett 33: 1549
[41] Petrovic Z, Mojsilovic B, Bugarcic Z (2001) J Mol Cat
A: Chem 170: 267
´
[28] Martin VS, Polazon JM (1992) Tetrahedron Lett 33:
2399
[42] Mojsilovic B, Bugarcic Z (2001) Heteroatom Chem 12:
475