Study toward the synthesis of selenofurans via seleno-Claisen rearrangement of allyl arylselenides

Article abstract of DOI:10.1081/SCC-120021044

Selenofuran derivatives were prepared using several phenyl alkenyl selenides via seleno-Claisen rearrangement.

Full text of DOI:10.1081/SCC-120021044

This article was downloaded by: [York University Libraries]
On: 27 December 2014, At: 03:25
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Study Toward the Synthesis of Selenofurans via Seleno-
Claisen Rearrangement of Allyl Arylselenides
a
b
a
c
Hélio A. Stefani , Nicola Petragnani , Maria F. C. Ascenso & Gilson Zeni
a
Faculdade de Ciências Farmacêuticas , Departamento de Farmácia , Universidade de São
Paulo , São Paulo, Brazil
b
Instituto de Química , Universidade de São Paulo , São Paulo, Brazil
c
Departamento de Química , Universidade Federal de Santa Maria , Santa Maria, Brazil
Published online: 17 Aug 2006.
To cite this article: Hélio A. Stefani , Nicola Petragnani , Maria F. C. Ascenso & Gilson Zeni (2003) Study Toward the Synthesis
of Selenofurans via Seleno-Claisen Rearrangement of Allyl Arylselenides, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 33:12, 2161-2166, DOI: 10.1081/SCC-120021044
To link to this article: http://dx.doi.org/10.1081/SCC-120021044
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 12, pp. 2161–2166, 2003
Study Toward the Synthesis of Selenofurans
via Seleno-Claisen Rearrangement of
Allyl Arylselenides
1
,
2
1
He
´
lio A. Stefani, * Nicola Petragnani, Maria F. C. Ascenso,
3
and Gilson Zeni
1
Faculdade de Cie
ˆ
ncias Farmace
ˆ
uticas, Departamento
cia, and Instituto de Quımica, Universidade
de Sao Paulo, Sao Paulo, Brazil
Departamento de Quımica, Universidade Federal de
2
de Farma
´
´
˜
˜
3
´
Santa Maria, Santa Maria, Brazil
ABSTRACT
Selenofuran derivatives were prepared using several phenyl alkenyl
selenides via seleno-Claisen rearrangement.
Key Words: Selenofuran; Seleno-Claisen rearrangement; Allyl aryl-
selenides.
*
Correspondence: He
Departamento de Farma
Universidade de Sao Paulo, Sa
´
lio A. Stefani, Faculdade de Cie
cia, Av. Prof. Lineu Prestes, 580-Bloco 13 Sup. 05508,
o Paulo, Brazil; E-mail: hstefani@usp.br.
ˆ ncias Farmac eˆ uticas,
´
˜
˜
2
161
DOI: 10.1081/SCC-120021044
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2
162
Stefani et al.
Furocoumarins, represented by the parent compound Psoralen 1
and its angular isomer Angelicin 2 are a group of natural and synthetic
compounds that find application in the photochemotherapy of some skin
diseases.
[1a]
Some new isoesters of furocoumarins, i.e., derivatives with an hetero-
atom such N, S, Se substituting the oxygen in the furan or coumarin ring,
[1a–c]
have been synthesized.
With the objective of minimizing the side
effects of furocoumarin photochemotherapy, and possibly for increasing
the therapeutic effects of these drugs, we are directing our efforts toward
O
O
O
O
O
O
1
2
the synthesis of several new types of selenopsoralenes and angelicins.
Considering that the selenofuran moiety of some selenoangelicins
could be constructed via a seleno-Claisen rearrangement and that this
[
2]
reaction, unlike to the well-known thio-Claisen rearrangement, has
[3]
been poorly investigated, we were stimulated to devote further studies
to the former rearrangement employing model substrates. This report
describes our present results.
Phenyl allyl, methallyl, crotyl, cyclohexenyl selenides 3a–d and the
phenyl propargyl selenide 3e, prepared by treatment of PhSeNa (from
PhSeSePh and NaBH ) with the corresponding bromides, when heated
4
ꢀ
in quinoline at 210 C (thio-Claisen conditions) furnished respectively
2,3-dihydrobenzoselenophenes 5a–d and the benzoselenophene 7 deriva-
R
1
Se
R
2
SeH R
Se
R
, 210 o
C
R
R1
N
R
1
R
2
R
2
3a-d
4
5a-d
a: R, R , R = H; 3b:R = H, R1 = Me, R2 = H; 3c:R = H, R1 = H, R2 = Me; 3d:R = H; R, R2 = -CH
1
2
1
CH CH -
2 2 2
3
Se
SeH
Se
,
210 o
C
N
3
e
6
7

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Seleno-Claisen Rearrangement of Allyl Arylselenides
Table 1. Products of seleno-Claisen rearrangement.
2163
Item
Structure
Reaction time (h)
2
Yield (%)
42
Se
5
a
Se
5
5
5
b
c
d
2
3
3
36
32
29
Se
Se
Se
7
3
22
tives, in moderate nonoptimized yields. These results are in agreement
with the cyclization of the intermediate ‘‘Claisen product,’’ the
o-allyl and o-propargylbenzene selenols 4 and 6 (Table 1).
It was also observed that phenyl cinnamylselenide (R ¼ H, R ¼ H,
1
R ¼ C H –) does not undergo the described Claisen rearrangement,
2
6
5
probably due to the decreased reactivity of the carbon-carbon double
bond conjugated with the phenyl ring.
In all cases diphenyldiselenide was detected as a by-product that is
very likely formed via a radical pathway promoted by the low termal
[
3]
stability of the allylic bond.
Se
Se
+
Se Se
With the aim of improving the yields of the reactions, some runs were
carried out in the presence of several Pd(II) Lewis acid catalysts that are
[
4]
known to promote the Claisen rearrangement under mild conditions.
Unfortunately, no better results were observed (see Table 2).

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2
164
Stefani et al.
Table 2. Catalyzed seleno-Claisen rearrangement of aryl
allylselenide.
Se
Se
Catalyst
o
,
210 C
N
3
a
5a
Catalyst (5 mol%)
Reaction time (h)
Yield (%)
No catalyst
Pd(Ph P)
2
2
3
2
2
3
42
40
39
32
37
36
3
4
Pd(OAc)2
Pd(C
NiBr
PdCl2
H
5 7
O
2
)
2
2
In summary, we have developed an experimentally simple method to
prepare selenofuran derivatives using a seleno-Claisen rearrangement.
Future work will focus on gaining better understanding of the reaction
mechanism in addition to expanding the substrates scope.
EXPERIMENTAL
General
1
13
H NMR and C NMR spectra were recorded on a Bruker DPX
00 MHz spectrometer with tetramethylsilane as the internal standard.
3
IR spectra were recorded on a Bhomen FT-IR spectrometer. Low
resolution mass spectra were obtained on a Shimadzu QP5050 spectrom-
eter operating at 70 eV. High resolution mass spectra were obtained on a
VG Autospec-Micromass-EBE spectrometer. Purification and separa-
tions by column chromatography were performed on silica gel, using
flash chromatography.
Typical Procedure for Selenofuran Derivatives Preparation
Phenyl alkenyl selenides 3a–d and phenyl propargyl selenide 3e were
refluxed (1 mmol) with quinoline (3 mmol, 0.38 g, 0.35 mL), previously
ꢀ
distilled, for 2–3 h at 210 C (silicon oil bath). The reaction was followed

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Seleno-Claisen Rearrangement of Allyl Arylselenides
2165
by TLC and GC. The products were purified by column chromatography
using hexane as an eluent.
1
-Methyl-2,3-dihydrobenzo[b] selenophene (5a). H NMR (300 MHz,
2
CDCl ): ꢀ 1.55–1.57 (s, 3H), 3.28–3.42 (m, 2H), 4.06–4.16 (m, 1H),
3
1
3
7
(
.08–7.10 (d, 1H), 7.25–7.28 (m, 1H), 7.51–7.54 (m, 1H). C NMR
75.1 MHz, CDCl ): ꢀ 34.40, 43.66, 45.75, 125.46, 127.93, 129.73,
3
1
1
3
33.82, 136.63, 141.76. LRMS (70 eV, m/z): 63.05 (8.28), 77.10 (11.55),
02.15 (7.28), 116.10 (100), 195.15 (35.15), 197.15 (55.96). IR (neat, ꢁmax):
058.09, 2923.16, 2856.17, 1439.28, 1196.43, 1023.56, 738.44, 690.37. MS
þ
(
high resolution): m/e 197.9887 (M calculated for C H Se 197.9947).
9
10
1
2
,2-Dimethyl-2,3-dihydrobenzo selenophene (5b). H NMR (300 MHz,
CDCl ): ꢀ 1.75 (s, 3H), 3.56 (s, 2H), 6.96–7.02 (m, 1H), 7.22–7.24 (m, 1H),
3
1
.48–7.51 (m, 1H). C NMR (75.1 MHz, CDCl ): ꢀ 27.69, 42.59, 50.88,
3
7
6
5
2
1
2
3
0.00, 125.25, 127.70, 129.12, 132.97, 137.43, 141.85. LRMS (70 eV, m/z):
1.05 (12.95), 77.10 (15.58), 115.05 (36.63), 130.10 (100), 183.10 (13.70),
09.15 (35.43), 211.15 (69.73). IR (neat, ꢁmax): 3059.24, 2921.78, 1577.74,
447.11, 1373.99, 1025.87, 737.20, 690.40. MS (high resolution): m/e
þ
12.0104 (M calculated for C H Se 212.0104)
1
0
12
1
-Ethyl-2,3-dihydrobenzo[b] selenophene (5c). H NMR (300 MHz,
2
CDCl ): ꢀ 1.25–1 (s, 1, 25), 1.50 (d, J ¼ 6.0 Hz, 2H), 3.40–3.52 (m, 2H),
3
4
1
1
5
1
.19–4.22 (m, 1H), 7.05–7.09 (m, 1H), 7.24–7.30 (m, 1H), 7.56–7.59 (m,
1
H). C NMR (75.1 MHz, CDCl ): ꢀ 19.32, 41.75, 44.57, 54.73, 127.08,
3
3
27.45, 129.27, 135.52, 135.69, 142.30. LRMS (70 eV, m/z): 39.10 (11.24),
1.10 (14.18), 77.10 (19.94), 91.15 (21.55), 102.20 (14.82), 115.20 (33.76),
30.25 (100), 183.00 (26.70), 209.00 (49.44), 211.00 (95.56), 213.00 (17.29).
IR (neat, ꢁmax): 3057.56, 2960.11, 2920.18, 1578.45, 1441.36, 1374.95,
1
2
241.91, 1153.39, 1022.40, 740.64, 692.33. MS (high resolution): m/e
þ
12.0103 (M calculated for C H Se 212.0104).
12
1
0
1
1,2,3,4,4a,9b-Hexahydrobenzo[b,d] selenophene (5d).
H NMR
300 MHz, CDCl ): ꢀ 1.50–1.58 (m, 2H), 2.16 (s, 2H), 3.50 (d,
(
3
J ¼ 6.0 Hz, 1H), 4.06 (t, J ¼ 14.4 Hz, 1H), 7.09–7.12 (m, 1H), 7.26–7.29
1
3
(
d, 1H), 7.55–7.57 (m, 1H). C NMR (75.1 MHz, CDCl ): ꢀ 23.10, 28.24,
3
3
(
9
(
2.95, 47.20, 49.84, 124.93, 127.76, 129.41, 136.24, 137.97, 143.90. LRMS
70 eV, m/z): 28.15 (21.78), 39.10 (21.58), 51.10 (33.74), 77.10 (51.45),
1.10 (33.61), 115.15 (63.15), 128.20 (40.22), 157.05 (29.48), 194.95
100), 237.05 (81.84). IR (neat, ꢁmax): 3056.43, 2928.05, 2854.07,
1
2
578.01, 1444.02, 1022.53, 740.51, 692.29. MS (high resolution): m/e
þ
38.0298 (M calculated for C H Se 238.0260).
14
1
2
1
-Methylbenzo[b] selenophene (7). H NMR (300 MHz, CDCl ): ꢀ 2.14
2
s, 3H), 6.74 (s, 1H), 7.25–7.30 (m, 1H), 7.42–7.43 (m, 1H), 7.50–7.53 (m,
3
(
1
H). C NMR (75.1 MHz, CDCl ): ꢀ 23.71, 122.48, 125.02, 127.52,
3
1
1
3
27.70, 129.72, 132.06, 133.97, 134.46. LRMS (70 eV, m/z): 51.05

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2
166
Stefani et al.
(
(
49.46), 77.10 (100), 115.10 (69.49), 116.10 (92.61), 157.00 (69.97), 182.05
22.80), 195.10 (27.34). IR (neat, ꢁmax): 3058.56, 2926.82, 1577.11,
1
1
475.11, 1066.34, 1022.06, 734.99, 690.18. MS (high resolution): m/e
þ
95.9807 (M calculated for C H Se 195.9791).
9
8
ACKNOWLEDGMENTS
Financial support was provided by the FAPESP (00/08629-5,
8/10821-0, 99/12182) and CNPq.
9
1
REFERENCES
. (a) Guiotto, A.; Chilin, A.; Manzini, P.; Dall’Acqua, F.; Bordin, F.;
Rodighiero, P. II Farmaco 1995, 50, 479; (b) Jakobs, A.E.;
Christiaens, L.E.; Renson, M.J. Tetrahedron 1994, 50, 9315; (c)
Wellman, G.R. J. Heteroc. Chem. 1980, 17, 911.
2. Rhoads, S.J.; Raulins, N.R. Org. React. XXII 1975, 47.
3
. (a) Kataev, E.G.; Chmutova, G.A.; Musina, A.A.; Anastas’eva, A.P.
J. Org. Chem. USSR 1967, 3, 573; (b) Kataev, E.G.; Chmutova,
G.A.; Musina, A.A.; Anastas’eva, A.P. J. Org. Chem. USSR 1972,
7
, 1560; (c) Bellinger, N.; Cagniant, O.; Cagniant, P. Tetrahedron
Lett. 1971, 49; (d) Vallee, Y.; Worrell, M. J. Chem. Soc., Chem.
Commun. 1992, 1680.
. Watson, D.J.; Devine, P.N.; Meyers, A.I. Tetrahedron Lett. 2000, 41,
4
1363 and references therein.
Received in the USA October 28, 2002