Novel reactivity of SeO2 with 1,3-dienes: Selenophene formation

Article abstract of DOI:10.1021/jo025630t

A novel and efficient method for the synthesis of selenophenes is disclosed. Selenophenes were synthesized in high yields in a single operation from 1,3-dienes containing a carbonyl group at the C-1 position and selenium dioxide. The bidirectional synthesis of selenophenes can also be demonstrated using this method. The selenophene is believed to form via a [4 + 2] cycloaddition between diene and selenium dioxide.

Full text of DOI:10.1021/jo025630t

we have shown that selenino lactone 2 derived from the
reaction of 1,3-diene 1 with SeO2 spontaneously trans-
formed to cyclic selenites 3 and 4 (Scheme 1).5 As opposed
to these examples, the 1,3-dienes with an electron-
withdrawing group at the C-1 position have been shown
to react with SeO2 to form furans and selenophenes.
Takeda and co-workers disclosed that the reaction of 2,4-
alkadienoic esters with SeO2 at elevated temperatures
produced a mixture of furan (major) and selenophene
(minor).6 Wender and co-workers reported that sele-
nophenes could be generated from reaction of SeO2 with
â,γ-unsaturated ketones.7 In the latter case the â,γ-
unsaturated carbonyl compounds were oxidized by SeO2
to the corresponding 1,3-diene, which reacted further
with SeO2. On the basis of these observations, we
anticipated that 1,3-dienes with a carbonyl substituent
at the C-1 position should be general substrates for the
SeO2-mediated selenophene synthesis.
Our investigation into this novel selenophene forming
reaction began with an efficient preparation of 1,3-diene
dienes 5 from (1S)-verbenone 10 and a variety of aromatic
aldehydes under thermodynamic aldol condensation con-
ditions (KOH, MeOH, 60 °C) (Table 1).8 With these dienes
on hand, we started to study the selenophene formation
with the simplest diene 5a (Scheme 2). When the reaction
was performed in dioxane at 60 °C, three main products
were obtained: selenophene 6a , furan 7, and the in-
tensely red-colored diselenide 8. Compounds 6a , 7, and
8 were fully characterized by 1H, 13C, 77Se (6a and 8 only)
NMR, and X-ray crystallography, respectively. Although
not directly observed, the selenino lactone 9 seems to be
a common intermediate to 6a , 7, and 8. Reaction of a
variety of verbenone-derived dienes (5b-k ) under similar
conditions consistently gave the corresponding seleno-
phene, furan, and diselenide derivatives.
Optimization experiments have identified that the
addition of pyridine (1,4-dioxane/pyridine, 5:1) to the
reaction minimizes or, in most cases, suppresses the
formation of the furan and diselenide. Under these
conditions, selenophene 6a was obtained in 86% yield.
Other amine bases, such as diisopropylamine, triethyl-
amine, and diisopropylethylamine, are not as effective
as pyridine. Alkoxide base, such as potassium tert-
butoxide, prevents the formation of selenophene.
Typically, the reactions of dienes 5 with SeO2 (20 equiv)
in 1,4-dioxane/pyridine (5:1) at 80 °C lead to high yields
of selenophenes 6 (Table 1).8 This protocol appears to be
general for dienes we examined. Both the dienes with
electron-withdrawing and electron-donating substituents
on the aromatic ring give selenophenes in high yields.
Longer reaction times are required for dienes with more
Novel Rea ctivity of SeO2 w ith 1,3-Dien es:
Selen op h en e F or m a tion
Truc M. Nguyen, Ilia A. Guzei, and Daesung Lee*
Department of Chemistry, University of
WisconsinsMadison, Madison, Wisconsin 53706
dlee@chem.wisc.edu
Received February 19, 2002
Abstr a ct: A novel and efficient method for the synthesis
of selenophenes is disclosed. Selenophenes were synthesized
in high yields in a single operation from 1,3-dienes contain-
ing a carbonyl group at the C-1 position and selenium
dioxide. The bidirectional synthesis of selenophenes can also
be demonstrated using this method. The selenophene is
believed to form via a [4 + 2] cycloaddition between diene
and selenium dioxide.
Five-membered ring heteroaromatic compounds, such
as furan, thiophene, oxazole, imidazole, and thiazole, con-
tinue to attract significant synthetic efforts due to their
important performance in a variety of disciplines.1 Re-
cently, the synthesis of oligomers and polymers of these
heterocycles has drawn much attention because of their
promising optical and electronic properties.2 Compared
to other congeners, however, selenophenes and their der-
ivatives have drawn less attention.3 In this report we
wish to disclose a novel synthesis of selenophenes from
the reaction of conjugated 1,3-dienes with selenium diox-
ide (SeO2).
The reaction between SeO2 and 1,3-dienes is known
to form selenino lactone via a [4 + 2] cycloaddition, but
little is known about the subsequent chemistry of this
adduct. Mock has shown that the reaction of SeO2 with
2,3-dimethylbutadiene produces a selenino lactone at
room temperature, the structure of which was confirmed
by the reduction of the Se-O bond followed by the
formation of the corresponding benzyl selenide.4 Recently
(1) (a) Belen’kii, L. I.; Kruchkovskaya, N. D.; Gramenitskaya, V. N.
Adv. Heterocycl. Chem. 1999, 73, 296-395. (b) For a comprehensive
listing of reviews of five-membered ring heterocycles from 1982 to 1995,
see J . Heterocycl. Chem. 1999, 36, 559-561. (c) Progress in Heterocyclic
Chemistry; Gribble, G. W.; Gilchrist, T. L., Eds; Elsevier: Amsterdam,
1999; Vol. 11.
(2) (a) Tovar, J .; Swager, T. M. Adv. Mater. 2001, 13, 1775-1780.
(b) Zhu, S. S.; Kingsborough, R. P.; Swager, T. M. J . Mater. Chem.
1999, 9, 2123-2131. (c) Ng, S. C.; Chan, H. S. O.; Ong, T. T.; Kumura,
K.; Mazaki, Y.; Kobayashi, K. Macromolecules 1998, 31, 1221-1228
and references therein. (d) Mahatsekake, C.; Catel, J . M.; Andrieu, C.
G.; Ebel, M.; Mollier, Y.; Tourillon, G. Phosphorus, Sulfur, Silicon 1990,
47, 35-41. (e) Vogel, E.; Frode, C.; Breihan, A.; Schmickler, H.; Lex,
J . Angew. Chem., Int. Ed. Engl. 1997, 36, 2609-2612.
(3) (a) Gronowitz, S. Phosphorus, Sulfur Silicon Relat. Elem. 1998,
136, 137, 138, 59-90 and references therein. (b) Aqad, E.; Lakshmi-
kantham, M. V.; Cava, M. P. Org. Lett. 2001, 3, 4283-4285. (c) Welch,
M.; Phillips, R. S. Bioorg. Med. Chem. Lett. 1999, 9, 637-640. (d)
Shilkina, T. A.; Papernaya, L. K.; Deryagina, E. N. Russ. J . Gen. Chem.
1998, 68, 831. (e) Koketsu, M.; Miyajima, Y.; Ishihara, H. Chem. Lett.
1998, 645-646. (f) Sashida, H.; Sadamori, K.; Tshuchiya, T. Synth.
Commun. 1998, 28, 713-727. (g) Deryagina, E. N.; Kochervin, N. A.
Russ. J . Gen. Chem. 1997, 67, 1582. (h) Lyons, J . E.; Schiesser, C. H.;
Sutej, K. J . Org. Chem. 1993, 58, 5632-5638. (i) Nakayama, J .; Murai,
F.; Hoshino, M.; Ishii, A. Tetrahedron Lett. 1988, 29, 1399-1400. (j)
Fagan, P. J .; Nugent, W. A. J . Am. Chem. Soc. 1988, 110, 2310-2312.
(k) Kulik, W.; Verkruijsse, H. D.; de J ong, R. L. P.; Hommes, H.;
Brandsma, L. Tetrahedron Lett. 1983, 24, 2203-2204. (l) See also The
Chemistry of Organic Selenium and Tellurium Compounds; Patai, S.;
Rappoport, Z., Eds.; Wiley: New York, 1986.
(5) Nguyen, T. M.; Lee, D. Org. Lett. 2001, 3, 3161-3163.
(6) Tsuboi, S.; Mimura, S.; Ono, S.; Watanabe, K.; Takeda, A. Bull.
Chem. Soc. J pn. 1987, 60, 1807-1812.
(7) Wender, P. A.; Lee, D.; Lal, T. K.; Horwitz, S. B.; Rao, S. Bioorg.
Med. Chem. Lett. 1997, 7, 1941-1944. An intriguing selenophene
synthesis from carvone, an γ,δ-unsaturated ketone, was reported. See
Schmitt, J .; Seilert, J . Ann. Chem. 1949, 562, 15-23.
(8) Please see Experimental Section for details. We chose these
dienes on the basis of their prompt and efficient synthesis. Another
reason for choosing these dienes is that they do not have any oxidizable
allylic protons or enolizable protons.
(4) Mock, W. L.; McCausland, J . H. Tetrahedron Lett. 1968, 3, 91-
392.
10.1021/jo025630t CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/03/2002
J . Org. Chem. 2002, 67, 6553-6556
6553

SCHEME 1
SCHEME 3
TABLE 1. F or m a tion of Selen op h en es 6
5k yielded only 5% of selenophene 6k , with the corre-
sponding furan as the major product (41%) within very
short reaction time. This reversal of the trend, so as to
generate more furan is not currently understood.
Our protocol would be flexible in that various aromatic
and heteroaromatic spacers could potentially be used in
the synthesis of oligoselenophenes. To demonstrate the
effectiveness of this approach, the bis-aldol products 11
and 13 were prepared from 2,5-thiophenedicarboxalde-
hyde and terephthaldicarboxaldehyde with verbenone,
respectively. Treatment of these tetraenes with SeO2
produced the bis-selenophenes 12 and 14 in 23% and 38%
yield, respectively (Scheme 3). In these reactions, the
monoselenophenes were initially observed, which in turn
were eventually converted to the bis-selenophenes.
To the best of our knowledge, this is the first efficient
synthesis of selenophenes from dienes with SeO2 under
mild neutral or slightly basic reaction conditions. Without
much precedent, it is not possible to propose a detailed
mechanism for the formation of selenophenes 6, furan
7, and diselenide 8. Our working hypothesis is that 6, 7,
and 8 are formed from the common selenino lactone
intermediate 9, the [4 + 2] cycloaddition product of SeO2
with diene 5a (Scheme 2). In contrast to the Mock
precedent in which the Diels-Alder type reaction oc-
curred at room temperature,4 the reaction of dienes 5
with SeO2 occurs only at higher temperature (>50 °C),
probably due to the deactivating nature of the carbonyl
substituent at the C-1 position. The intermediate 9 then
undergoes a series of transformations via yet unknown
mechanisms leading to selenophenes 6, furan 7, and
diselenide 8, respectively. The formation of diselenide 8
strongly suggests the intermediacy of the selenino lactone
9 together with the involvement of complicated redox
processes, involving a disproportionation mechanism of
selenium species of different oxidation states. It is also
intriguing how pyridine is involved in the reaction to
promote the formation of selenophene and suppress the
formation of furan and diselenide.
a
b
RCHO, KOH, MeOH, 60 °C. SeO2, dioxane:pyridine (5:1), 80
°C. c The corresponding furan derivative was obtained in 41%
yield.
SCHEME 2
electron-withdrawing aromatic substituents. This obser-
vation is consistent with our hypothesis of the initial [4
+ 2] cycloaddition between diene and SeO2. Electron-
donating substituents on the aromatic ring should in-
crease the reactivity of the diene, whereas electron-
withdrawing substituents should decrease it. Triene 5j,
derived from cinnamaldehyde, produces selenophene 6j
in moderate yield (48%), without any signs of the other
selenophene regioisomer. The pivaldehyde-derived diene
Interestingly, the carbonyl group at the C-1 position,
although detrimental for the initial [4 + 2] cycloaddition
reaction, is absolutely essential for the formation of
selenophenes and furans. It is assumed that the in-
6554 J . Org. Chem., Vol. 67, No. 18, 2002

58.2, 52.9, 43.6, 40.0, 26.7, 22.1; HRMS (EI) calcd for C17H17
OCl (M+) 272.0968, found 272.0956.
-
creased acidity of the R-proton to the carbonyl group is
crucial to initiate the decomposition of the selenino
lactone intermediate to the final products. This rationale
is supported by the experiments in Scheme 1 where the
reaction of TBS-ether 1 with SeO2 at room temperature
under otherwise identical reaction conditions afforded
only cyclic selenites 3 and 4 without yielding any of the
corresponding selenophene, furan, or diselenide.5 This
result clearly indicates that the reduction of the C-1
carbonyl group led to the increased reactivity of diene 1
for the initial [4 + 2] reaction with SeO2, but the
corresponding selenino lactone 2, without the carbonyl
group, took a different reaction pathway.
Dien e 5e (98%, solid, mp 104-106 °C): 1H NMR (CDCl3, 300
MHz) δ 7.48-7.43 (m, 2H), 6.92-6.89 (m, 2H), 6.90 (d, J ) 16.2
Hz, 1H), 6.83 (d, J ) 16.2 Hz, 1H), 5.89 (t, J ) 1.7 Hz, 1H), 3.84
(s, 3H), 3.12 (td, J ) 5.9, 1.3 Hz, 1H), 2.91 (dt, J ) 9.2, 5.7 Hz,
1H), 2.72 (td, J ) 5.7, 1.7 Hz, 1H), 2.12 (d, J ) 9.2 Hz, 1H), 1.58
(s, 3H), 1.02 (s, 3H); 13C NMR (CDCl3, 75.4 MHz) δ 204.2, 164.7,
142.6, 134.6, 130.0, 128.8, 125.1, 121.7, 114.3, 58.0, 55.3, 52.7,
43.6, 39.9, 26.7, 22.1; HRMS (EI) calcd for C18H20O2 (M+)
268.1463, found 268.1470.
1
Dien e 5f (94%, oil): H NMR (CDCl3, 300 MHz) δ 7.51 (d, J
) 8.7 Hz, 1H), 7.25 (d, J ) 16.4 Hz, 1H), 6.89 (d, J ) 16.4 Hz,
1H), 6.51 (dd, J ) 8.6, 2.4 Hz, 1H), 6.45 (d, J ) 2.4 Hz, 1H),
5.87 (s, 1H), 3.87 (s, 3H), 3.84 (s, 3H), 3.16 (td, J ) 5.7, 1.0 Hz,
1H), 2.90 (dt, J ) 9.2, 5.7 Hz, 1H), 2.71 (td, J ) 5.7, 1.7 Hz,
1H), 2.10 (d, J ) 9.2 Hz, 1H), 1.57 (s, 3H), 1.02 (s, 3H); 13C NMR
(CDCl3, 75.4 MHz) δ 204.3, 165.5, 161.8, 158.7, 129.6, 128.1,
125.1, 121.1, 117.9, 105.3, 98.2, 58.0, 55.4, 55.3, 52.6, 43.5, 39.9,
26.7, 22.0; HRMS (EI) calcd for C19H22O3 (M+) 298.1569, found
298.1561.
In summary, we have demonstrated that an efficient
one-step synthesis of selenophenes can be realized from
the reaction of SeO2 with 1,3-dienes containing a carbonyl
group at the C-1 position. The generality and mechanistic
study of these reactions will be explored in due course.
Dien e 5g (91%, solid, mp 124-126 °C): 1H NMR (CDCl3, 300
MHz) δ 7.29 (d, J ) 16.3 Hz, 1H), 7.09 (s, 1H), 6.84 (d, J ) 16.3
Hz, 1H), 6.51 (s, 1H), 5.90 (s, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 3.89
(s, 3H), 3.18 (t, J ) 5.3 Hz, 1H), 2.91 (dt, J ) 9.2, 5.5 Hz, 1H),
2.72 (t, J ) 4.9 Hz, 1H), 2.11 (d, J ) 9.2 Hz, 1H), 1.59 (s, 3H),
1.03 (s, 3H); 13C NMR (CDCl3, 75.4 MHz) δ 204.4, 165.8, 151.2,
143.4, 129.3, 125.0, 121.2, 116.5, 109.3, 96.8, 58.1, 56.5, 56.3,
56.0, 52.7, 43.6, 40.0, 26.7, 22.1; HRMS (EI) calcd for C20H24O4
(M+) 328.1675, found 328.1684.
Dien e 5h (94%, solid, mp 107-110 °C): 1H NMR (CDCl3, 300
MHz) δ 7.38 (d, J ) 16.6 Hz, 1H), 7.30 (d, J ) 16.6 Hz, 1H),
6.14_(s, 2H), 5.85 (t, J ) 1.5 Hz, 1H), 3.89 (s, 6H), 3.85 (s, 3H),
3.18 (td, J ) 5.9, 1.1 Hz, 1H), 2.90 (dt, J ) 9.2, 5.7 Hz, 1H), 2.70
(td, J ) 5.9, 1.7 Hz, 1H), 2.11 (d, J ) 9.2 Hz, 1H), 1.58 (s, 3H),
1.03 (s, 3H); 13C NMR (CDCl3, 75.4 MHz) δ 204.6, 167.3, 161.7,
160.3, 127.7, 126.5, 120.4, 106.9, 90.5, 58.1, 55.7, 55.2, 52.5, 43.1,
40.0, 26.7, 22.1; HRMS (EI) calcd for C20H24O4 (M+) 328.1675,
found 328.1681.
Exp er im en ta l Section
Ma ter ia ls a n d Meth od s. All reactions were monitored by
thin-layer chromatography (TLC) using 0.25 mm E. Merck
precoated silica gel 60 (particle size 0.040-0.063 mm). Yields
refer to chromatographically and spectroscopically pure com-
pounds, except as noted. Proton and carbon-13 NMR spectra
were recorded on Bruker AC-300 and Varian Unity-500 spec-
trometers. Proton and carbon-13 chemical shifts are reported
in δ values relative to the internal standard, tetramethylsilane
(TMS). High-resolution mass spectra were obtained with J EOL
AX-505 and J EOL SX-102 spectrometers.
A Typ ica l P r oced u r e for th e Syn th esis of Dien e 5. To a
stirred solution of (1S)-(-)-verbenone 10 (3.52 g, 23.4 mmol) and
2,4,6-trimethoxybenzaldehyde (5.52 g, 28.1 mmol) in 50 mL of
MeOH was added KOH (pellet, 2.6 g, 46.0 mmol). The mixture
was stirred at 60 °C for 6 h and then cooled to room temperature.
A few drops of H2O were added, and the mixture was allowed
to stand at room temperature for 24 h. Yellow solid 5h was
obtained by filtration and drying under vacuum (6.8 g, 94%).
Dien e 5i (48%, solid, mp 125-128 °C): 1H NMR (CDCl3, 300
MHz) δ 7.43-7.38 (m, 2H), 6.88 (d, J ) 16.0 Hz, 1H), 6.77 (d, J
) 16.0 Hz, 1H), 6.70-6.65 (m, 2H), 5.84 (s, 1H), 3.13 (td, J )
5.9, 1.1 Hz, 1H), 2.89 (dt, J ) 9.4, 5.5 Hz, 1H), 2.70 (td, J ) 5.9,
1.7 Hz, 1H), 2.11 (d, J ) 9.2 Hz, 1H), 1.57 (s, 3H), 1.02 (s, 3H);
13C NMR (CDCl3, 75.4 MHz) δ 204.4, 165.4, 151.0, 135.6, 128.9,
124.0, 122.6, 120.3, 112.0, 58.1, 52.6, 43.8, 40.2, 40.0, 26.8, 22.2;
HRMS (EI) calcd for C19H23ON (M+) 281.1780, found 281.1768.
Dien e 5a (92%, oil): 1H NMR (CDCl3, 300 MHz) δ 7.51-7.49
(m, 2H), 7.39-7.32 (m, 3H), 6.97 (d, J ) 16.2 Hz, 1H), 6.92 (d,
J ) 16.2 Hz, 1H), 5.93 (s, 1H), 3.12 (t, J ) 5.8 Hz, 1H), 2.92 (dt,
J ) 9.3, 5.6 Hz, 1H), 2.73 (td, J ) 5.6, 1.6 Hz, 1H), 2.12 (d, J )
9.4 Hz, 1H), 1.58 (s, 3H), 1.02 (s, 3H); 13C NMR (CDCl3, 75.4
MHz) δ 203.9, 164.1, 135.8, 134.9, 129.0, 128.7, 127.2, 122.5,
1
Dien e 5j (86%, oil): H NMR (CDCl3, 300 MHz) δ 7.47 (d, J
) 7.3 Hz, 2H), 7.38 (t, J ) 7.3 Hz, 2H), 7.32-7.29 (m, 1H), 6.96
(dd, J ) 16.1, 11.2 Hz, 1H), 6.83-6.78 (m, 2H), 6.55 (d, J ) 15.6
Hz, 1H), 5.89 (s, 1H), 3.06 (td, J ) 5.8, 1.0 Hz, 1H), 2.92 (dt, J
) 9.3, 5.9 Hz, 1H), 2.74 (td, J ) 5.9, 1.9 Hz, 1H), 2.12 (d, J )
9.3 Hz, 1H), 1.60 (s, 3H), 1.03 (s, 3H); 13C NMR (CDCl3, 75.4
MHz) δ 203.8, 164.0, 136.9, 136.4, 135.5, 131.2, 12.6, 128.3,
128.1, 126.7, 121.9, 57.9, 52.5, 43.6, 39.7, 26.6, 22.0; HRMS (EI)
calcd for C19H20O (M+) 264.1514, found 264.1512.
58.0, 52.7, 43.6, 39.9, 26.6, 22.0; HRMS (EI) calcd for C17H18
O
(M+) 238.1358, found 238.1353.
Dien e 5b (95%, solid, mp 72-74 °C): 1H NMR (CDCl3, 300
MHz) δ 7.37-7.34 (m, 2H), 7.18-7.12 (m, 1H), 7.04 (d, J ) 16.5
Hz, 1H), 6.95 (d, J ) 16.5 Hz, 1H), 5.95 (s, 1H), 3.13 (td, J )
5.7, 1.0 Hz, 1H), 2.96 (dt, J ) 9.3, 5.7 Hz, 1H), 2.76 (td, J ) 5.6,
1.7 Hz, 1H), 2.18 (d, J ) 9.3 Hz, 1H), 1.60 (s, 3H), 1.05 (s, 3H);
13C NMR (CDCl3, 75.4 MHz) δ 204.0, 163.5, 135.6, 134.5, 133.3,
129.0, 128.7, 128.5, 123.9, 58.2, 53.1, 43.3, 39.9, 26.7, 22.0;
HRMS (EI) calcd for C17H16OCl2 (M+) 306.0578, found 306.0588.
Dien e 5k (71%, solid, mp 60-62 °C): 1H NMR (CDCl3, 300
MHz) δ 6.19 (d, J ) 16.0 Hz, 1H), 6.13 (d, J ) 16.0 Hz, 1H),
5.75 (s, J ) 1.7 Hz, 1H), 2.96 (td, J ) 5.7, 1.3 Hz, 1H), 2.87 (dt,
J ) 9.0, 5.7 Hz, 1H), 2.68 (td, J ) 5.7, 1.8 Hz, 1H), 2.06 (d, J )
9.2 Hz, 1H), 1.55 (s, 3H), 1.09 (s, 9H), 0.98 (s, 3H); 13C NMR
(CDCl3, 75.4 MHz) δ 204.2, 165.1, 149.0, 124.4, 120.8, 57.9, 52.6,
43.6, 40.0, 33.8, 29.3, 29.1, 26.6, 21.9; HRMS (EI) calcd for
C15H22O (M+) 218.1671, found 218.1665.
Dien e 5c (95%, solid, mp 100-102 °C): 1H NMR (CDCl3, 300
MHz) δ 7.61 (d, J ) 8.4 Hz, 1H), 7.42 (d, J ) 2.0 Hz, 1H), 7.28-
7.24 (m, 1H), 7.25 (d, J ) 15.7 Hz, 1H), 6.92 (d, J ) 16.2 Hz,
1H), 5.98 (s, 1H), 3.13 (td, J ) 5.7, 1.1 Hz, 1H), 2.95 (dt, J )
9.3, 5.6 Hz, 1H), 2.76 (td, J ) 5.5, 1.1 Hz, 1H), 2.14 (d, J ) 9.5
Hz, 1H), 1.60 (s, 3H), 1.03 (s, 3H); 13C NMR (CDCl3, 75.4 MHz)
δ 203.9, 163.6, 130.1, 129.8, 129.3, 127.6, 127.5, 123.9, 58.2, 52.9,
43.7, 40.0, 26.7, 22.1; HRMS (EI) calcd for C17H16OCl2 (M+)
306.0578, found 306.0564.
Dien e 5d (77%, oil): 1H NMR (CDCl3, 300 MHz) δ 7.46-7.41
(m, 2H), 7.36-7.32 (m, 2H), 6.94 (d, J ) 16.2 Hz, 1H), 6.86 (d,
J ) 16.2 Hz, 1H), 5.94 (s, 1H), 3.10 (td, J ) 5.7, 1.3 Hz, 1H),
2.93 (dt, J ) 9.6, 5.7 Hz, 1H), 2.74 (td, J ) 5.7, 1.7 Hz, 1H), 2.12
(d, J ) 9.4 Hz, 1H), 1.59 (s, 3H), 1.02 (s, 3H); 13C NMR (CDCl3,
75.4 MHz) δ 204.0, 163.8, 134.8, 134.5, 129.1, 128.5, 127.9, 123.0,
Tetr a en e 11 (75%): 1H NMR (CDCl3, 300 MHz) δ 7.08 (s, 2H),
7.02 (d, J ) 15.8 Hz, 2H), 6.77 (d, J ) 15.8 Hz, 2H), 5.92 (s,
2H), 3.06 (t, J ) 5.7 Hz, 2H), 2.92 (dt, J ) 9.4, 5.7 Hz, 2H), 2.72
(td, J ) 5.9, 1.7 Hz, 2H), 2.10 (d, J ) 9.4 Hz, 2H), 1.58 (s, 6H),
1.01 (s, 6H); 13C NMR (CDCl3, 75.4 MHz) δ 203.5, 163.2, 142.8,
129.8, 127.8, 127.7, 122.5, 57.9, 52.5, 43.4, 39.7, 26.5, 21.9;
HRMS (ESI) calcd for C26H28O2S + Na+ (M+ + Na+) 427.1708,
found 427.1710.
Tetr a en e 13 (90%): 1H NMR (CDCl3, 300 MHz) δ 7.53 (s, 4H),
7.02 (d, J ) 16.2 Hz, 2H), 6.93 (d, J ) 16.0 Hz, 2H), 5.96 (s,
J . Org. Chem, Vol. 67, No. 18, 2002 6555

2H), 3.14 (t, J ) 5.0 Hz, 2H), 2.94 (dt, J ) 9.4, 5.5 Hz, 2H), 2.74
(td, J ) 5.7, 1.7 Hz, 2H), 2.12 (d, J ) 9.4 Hz, 2H), 1.59 (s, 6H),
1.02 (s, 6H); 13C NMR (CDCl3, 75.4 MHz) δ 203.8, 163.8, 136.5,
134.0, 127.8, 127.7, 122.8, 58.0, 52.6, 43.4, 39.8, 26.6, 22.0;
HRMS (ESI) calcd for C28H30O2 + Na+ (M+ + Na+) 421.2144,
found 421.2155.
A Typ ica l P r oced u r e for th e Syn th esis of Selen op h en e
6. To a stirred solution (open to air) of diene 5h (100 mg, 0.32
mmol) in 6 mL of 1,4-dioxane/pyridine (5:1) was added selenium
dioxide (390 mg, 3.5 mmol). The mixture was vigorously stirred
at 80 °C for 10 h and then cooled to room temperature. The
reaction was quenched with water, washed with aqueous CuSO4,
extracted (4×) with ether, and dried over MgSO4. Evaporation
of solvent, followed by flash column chromatography (hexanes-
ether, 4:1), provided selenophene 6h (130 mg, 90%).
Selen op h en e 6a (86%, solid, mp 102-104 °C): 1H NMR
(CDCl3, 300 MHz) δ 7.59 (dd, J ) 6.5, 1.2 Hz, 1H), 7.40-7.33
(m, 4H), 3.13 (t, J ) 5.6 Hz, 1H), 3.04 (dt, J ) 9.5, 5.7 Hz, 1H),
2.81 (t, J ) 5.8 Hz, 1H), 2.33 (d, J ) 9.5 Hz, 1H), 1.57 (s, 3H),
0.88 (s, 3H); 13C NMR (CDCl3, 125.7 MHz) δ 196.3, 163.8, 158.8,
135.5, 134.9, 129.0, 128.9, 126.4, 124.9, 57.9, 57.1, 46.7, 42.5,
26.7, 22.9; 77Se NMR (CDCl3, external Me2Se) δ 569.4; HRMS
(EI) calcd for C17H16OSe (M+) 316.0366, found 316.0351.
Selen op h en e 6b (67%, solid, mp 127-130 °C): 1H NMR
(CDCl3, 300 MHz) δ 7.43-7.40 (m, 2H), 7.30-7.24 (m, 1H), 7.07
(s, 1H), 3.17 (t, J ) 5.6 Hz, 1H), 3.09 (dt, J ) 9.5, 5.6 Hz, 1H),
2.85 (t, J ) 5.7 Hz, 1H), 2.45 (d, J ) 9.5 Hz, 1H), 1.61 (s, 3H),
0.92 (s, 3H); 13C NMR (CDCl3, 125.7 MHz) δ 197.4, 163.3, 151.5,
139.1, 136.0, 134.9, 131.7, 131.0, 128.9, 58.7, 58.6, 47.4, 43.5,
27.5, 23.6; 77Se NMR (CDCl3, external Me2Se) δ 618.5; HRMS
(EI) calcd for C17H14OCl2Se (M+) 383.9583, found 383.9601.
Selen op h en e 6c (79%, solid, mp 100-102 °C): 1H NMR
(CDCl3, 300 MHz) δ 7.51 (d, J ) 2.8 Hz, 1H), 7.50 (d, J ) 7.5
Hz, 1H), 7.42 (s, 1H), 7.29 (dd, J ) 8.5, 2.2 Hz, 1H), 3.17 (t, J )
5.7 Hz, 1H), 3.08 (dt, J ) 9.4, 5.7 Hz, 1H), 2.84 (t, J ) 5.7 Hz,
1H), 2.38 (d, J ) 9.4 Hz, 1H), 1.60 (s, 3H), 0.90 (s, 3H); 13C NMR
(CDCl3, 125.7 MHz) δ 197.2, 163.0, 153.0, 138.4, 135.5, 133.8,
133.3, 132.4, 131.2, 130.5, 128.1, 58.8, 58.1, 47.4, 43.5, 27.5, 23.7;
77Se NMR (CDCl3, external Me2Se) δ 615.0; HRMS (EI) calcd
for C17H14OCl2Se (M+) 383.9583, found 383.9576.
Selen op h en e 6h (90%, solid, mp 167-170 °C): 1H NMR
(CDCl3, 300 MHz) δ 7.91 (s, 1H), 6.23 (s, 2H), 3.92 (s, 6H), 3.87
(s, 3H), 3.15 (t, J ) 5.8 Hz, 1H), 3.04 (dt, J ) 9.2, 5.8 Hz, 1H),
2.78 (t, J ) 5.8 Hz, 1H), 2.37 (d, J ) 9.5 Hz, 1H), 1.58 (s, 3H),
0.87 (s, 3H); 13C NMR (CDCl3, 125.7 MHz) δ 198.3, 162.9, 161.6,
158.9, 148.7, 134.0, 129.4, 108.0, 91.8, 58.8, 58.1, 56.4, 56.1, 47.6,
43.6, 27.6, 23.7; 77Se NMR (CDCl3, external Me2Se) δ 632.7;
HRMS (EI) calcd for C20H22O4Se (M+) 406.0683, found 406.0667.
Selen op h en e 6i (48%, solid, mp >180 °C): 1H NMR (CDCl3,
300 MHz) δ 7.52-7.47 (m, 2H), 7.22 (s, 1H), 6.71-6.67 (m, 2H),
3.11 (t, J ) 5.5 Hz, 1H), 3.03 (dt, J ) 9.2, 5.5 Hz, 1H), 3.02 (s,
6H), 2.79 (t, J ) 5.5 Hz, 1H), 2.35 (d, J ) 9.2 Hz, 1H), 1.57 (s,
3H), 0.89 (s, 3H); 13C NMR (CDCl3, 125.7 MHz) δ 197.0, 165.2,
161.3, 151.7, 132.7, 128.3, 124.4, 122.9, 112.9, 58.7, 57.9, 47.6,
43.2, 40.9, 27.5, 23.7; 77Se NMR (CDCl3, external Me2Se) δ 554.5;
HRMS (EI) calcd for C19H21ONSe (M+) 359.0788, found 359.0780.
Selen op h en e 6j (48%, solid, mp 145-147 °C): 1H NMR
(CDCl3, 300 MHz) δ 7.48 (d, J ) 7.1 Hz, 2H), 7.39-7.27 (m, 3H),
7.20 (d, J ) 15.8 Hz, 1H), 7.11 (s, 1H), 7.00 (d, J ) 15.8 Hz,
1H), 3.08 (t, J ) 5.5 Hz, 1H), 3.01 (dt, J ) 9.3, 5.7 Hz, 1H), 2.80
(t, J ) 5.8 Hz, 1H), 2.30 (d, J ) 9.3 Hz, 1H), 1.56 (s, 3H), 0.87
(s, 3H); 13C NMR (CDCl3, 125.7 MHz) δ 196.2, 163.3, 156.5,
136.1, 133.6, 132.6, 128.7, 128.4, 128.0, 126.7, 123.7, 57.9, 57.0,
46.5, 42.3, 26.7, 22.8; 77Se NMR (CDCl3, external Me2Se) δ 555.2;
HRMS (EI) calcd for C19H18OSe (M+) 342.0523, found 342.0511.
Selen op h en e 6k (5%, oil): 1H NMR (CDCl3, 300 MHz) δ 6.93
(s, 1H), 3.08-2.97 (m, 2H), 2.76 (t, J ) 5.8 Hz, 1H), 2.32 (d, J )
9.0 Hz, 1H), 1.56 (s, 3H), 1.41 (s, 9H), 0.83 (s, 3H); 13C NMR
(CDCl3, 125.7 MHz) δ 197.3, 176.5, 164.0, 133.7, 124.8, 58.7, 58.3,
47.6, 43.6, 38.0, 33.6, 27.6, 23.6; 77Se NMR (CDCl3, external Me2-
Se) δ 568.2; HRMS (EI) calcd for C15H20OSe (M+) 296.0679,
found 296.0671.
F u r a n 7: 1H NMR (CDCl3, 500 MHz) δ 7.79 (dd, J ) 8.4, 1.6
Hz, 2H), 7.43-7.30 (m, 3H), 6.72_(s, 1H), 3.07 (dt, J ) 9.6, 5.5
Hz, 1H), 2.99 (t, J ) 5.5 Hz, 1H), 2.76 (t, J ) 5.8 Hz, 1H), 2.33
(d, J ) 9.5 Hz, 1H), 1.58 (s, 3H), 0.88 (s, 3H); 13C NMR (CDCl3,
125.7 MHz) δ 188.9, 157.9, 149.9, 145.9, 129.3, 129.2, 128.9,
125.1, 105.5, 59.4, 58.0, 44.2, 42.5, 27.2, 22.4; HRMS (EI) calcd
for C17H16O2 (M+) 252.1150, found 252.1160.
Diselen id e 8: 1H NMR (CDCl3, 500 MHz) δ 7.93 (d, J ) 8.2
Hz, 2H), 7.65 (t, J ) 7.6 Hz, 1H), 7.50 (t, J ) 7.6 Hz, 2H), 3.01
(t, J ) 6.1 Hz, 1H), 2.91 (q, J ) 5.8 Hz, 1H), 2.28 (t, J ) 7.3 Hz,
1H), 2.28 (d, J ) 9.5 Hz, 1H), 1.51 (s, 3H), 1.01 (s, 3H); 13C NMR
(CDCl3, 125.7 MHz) δ 198.0, 192.4, 191.5, 157.6, 141.1, 134.8,
132.6, 130.1, 128.9, 58.2, 55.0, 46.6, 39.7, 26.3, 22.3; 77Se NMR
(CDCl3, external Me2Se) δ 487.6; LRMS (EI) calcd for (C17H15O2-
Selen op h en e 6d (45%, solid, mp 124-127 °C): 1H NMR
(CDCl3, 300 MHz) δ 7.55-7.50 (m, 2H), 7.38-7.33 (m, 3H), 3.14
(t, J ) 5.8 Hz, 1H), 3.06 (dt, J ) 9.5, 5.5 Hz, 1H), 2.83 (t, J )
5.8 Hz, 1H), 2.35 (d, J ) 9.5 Hz, 1H), 1.59 (s, 3H), 0.89 (s, 3H);
13C NMR (CDCl3, 125.7 MHz) δ 196.3, 163.8, 157.2, 135.6, 134.9,
134.2, 129.3, 127.6, 125.4, 57.9, 57.2, 46.8, 42.6, 26.8, 23.0; 77Se
NMR (CDCl3, external Me2Se) δ 572.4; HRMS (EI) calcd for
Se) (M+) 694.0, found 694.0.
2
Bis-selen op h en e 12 (27%): 1H NMR (CDCl3, 300 MHz) δ 7.27
(s, 2H), δ 7.20 (s, 2H), 3.13 (t, J ) 5.5 Hz, 2H), 3.06 (dt, J ) 9.6,
5.5 Hz, 2H), 2.83 (t, J ) 5.9 Hz, 2H), 2.34 (d, J ) 9.6 Hz, 2H),
1.59 (s, 6H), 0.90 (s, 6H); 13C NMR (CDCl3, 125.7 MHz) 196.8,
164.2, 149.7, 140.5, 135.8, 127.7, 126.2, 58.7, 57.8, 47.5, 43.1,
27.5, 23.7; 77Se NMR (CDCl3, external Me2Se) δ 583.6; HRMS
(FAB) calcd for C26H24O2SSe2 + Na+ 582.9729, found 582.9720.
Bis-selen op h en e 14 (16%): 1H NMR (CDCl3, 300 MHz) δ
7.637 (s, 4H), δ 7.45 (s, 2H), 3.17 (t, J ) 5.5 Hz, 2H), 3.08 (dt, J
) 9.6, 5.5 Hz, 2H), 2.84 (t, J ) 5.7 Hz, 2H), 2.36 (d, J ) 9.6 Hz,
2H), 1.60 (s, 6H), 0.91 (s, 6H); 13C NMR (CDCl3, 125.7 MHz)
197.1, 164.6, 158.2, 136.9, 136.4, 127.8, 126.1, 58.7, 57.9, 47.5,
43.3, 27.5, 23.7; 77Se NMR (CDCl3, external Me2Se) δ 571.5;
LRMS (EI) calcd for (C28H26O2Se2) (M+) 554.0, found 554.0.
C
17H15OClSe (M+) 349.9977, found 349.9988.
Selen op h en e 6e (63%, solid, mp 136-139 °C): 1H NMR (CD-
Cl3, 300 MHz) δ 7.56-7.51 (m, 2H), 7.27 (s, 1H), 6.94-6.87 (m,
2H), 3.84 (s, 3H), 3.12 (t, J ) 5.9 Hz, 1H), 3.04 (dt, J ) 9.2, 5.9
Hz, 1H), 2.80 (t, J ) 5.5 Hz, 1H), 2.34 (d, J ) 9.2 Hz, 1H), 1.58
(s, 3H), 0.89 (s, 3H); 13C NMR (CDCl3, 125.7 MHz) δ 196.3, 164.1,
160.4, 159.0, 133.7, 128.4, 127.8, 123.8, 114.4, 57.9, 57.2, 55.3,
46.8, 42.5, 26.7, 22.9; 77Se NMR (CDCl3, external Me2Se) δ 563.7;
HRMS (EI) calcd for C18H18O2Se (M+) 346.0472, found 346.0461.
Selen op h en e 6f (55%, solid, mp 127-129 °C): 1H NMR
(CDCl3, 300 MHz) δ 7.69 (d, J ) 8.5 Hz, 1H), 7.49 (s, 1H), 7.27
(s, 1H), 6.61-6.52 (m, 2H), 3.97 (s, 3H), 3.86 (s, 3H), 3.14 (t, J
) 5.5 Hz, 1H), 3.05 (dt, J ) 9.6, 5.5 Hz, 1H), 2.79 (t, J ) 5.9 Hz,
1H), 2.34 (d, J ) 9.2 Hz, 1H), 1.58 (s, 3H), 0.86 (s, 3H); 13C NMR
(CDCl3, 125.7 MHz) δ 197.3, 162.3, 161.2, 156.9, 151.9, 135.0,
128.0, 123.7, 117.5, 105.7, 98.7, 58.0, 57.3, 55.5, 55.4, 46.8, 42.7,
26.9, 23.0; 77Se NMR (CDCl3, external Me2Se) δ 610.8; HRMS
(EI) calcd for C19H20O3Se (M+) 376.0578, found 376.0589.
Selen op h en e 6g (65%, solid, mp 113-115 °C): 1H NMR
(CDCl3, 300 MHz) δ 7.48 (s, 1H), 7.26 (s, 1H), 6.60 (s, 1H), 3.99
(s, 3H), 3.95 (s, 3H), 3.92 (s, 3H), 3.15 (t, J ) 5.5 Hz, 1H), 3.06
(dt, J ) 9.6, 5.5 Hz, 1H), 2.79 (t, J ) 5.9 Hz, 1H), 2.35 (d, J )
9.6 Hz, 1H), 1.59 (s, 3H), 0.87 (s, 3H); 13C NMR (CDCl3, 125.7
MHz) δ 198.0, 162.8, 152.1, 151.6, 144.2, 135.2, 124.2, 116.8,
110.7, 98.2, 58.7, 58.0, 57.4, 57.0, 56.8, 47.5, 43.4, 27.6, 23.7;
77Se NMR (CDCl3, external Me2Se) δ 615.16; HRMS (EI) calcd
for C20H22O4Se (M+) 406.0683, found 406.0686.
Ack n ow led gm en t. We thank Dr. Martha Vestling
for mass spectral analyses. NMR support through
grants NSF CHE-8813550, NIH 1 S10 RR04981-01, and
NSF CHE-9629688 are greatly appreciated. We also
thank Prof. Hans Reich for helpful discussions.
Su p p or t in g In for m a t ion Ava ila b le: Spectral data for
5a -k , 6a -k , 7, 8, and 11-14. X-ray structure for 6a , 6j, 7,
and 8. This material is available free of charge via the Internet
at http://pubs.acs.org.
J O025630T
6556 J . Org. Chem., Vol. 67, No. 18, 2002