Synthesis of functionalized diaryl selenides by the first [3+3] cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes with organoselenium compounds

Article abstract of DOI:10.1016/j.tetlet.2009.07.136

Functionalized diaryl selenides were prepared by the first [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with organoselenium compounds (i.e., 2-(phenylselanyl)-3-silyloxy-3-en-1-ones).

Full text of DOI:10.1016/j.tetlet.2009.07.136

Tetrahedron Letters 50 (2009) 5726–5728
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of functionalized diaryl selenides by the first [3+3]
cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes with
organoselenium compounds
Mohanad Shkoor a, Olumide Fatunsin a, Abdolmajid Riahi a,b, Alexander Villinger a, Peter Langer a,b,
*
a Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Functionalized diaryl selenides were prepared by the first [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-
1,3-butadienes with organoselenium compounds (i.e., 2-(phenylselanyl)-3-silyloxy-3-en-1-ones).
Ó 2009 Elsevier Ltd. All rights reserved.
Received 2 July 2009
Revised 19 July 2009
Accepted 27 July 2009
Available online 6 August 2009
Keywords:
Arenes
Cyclizations
Organoselenium compounds
Silyl enol ethers
Diaryl selenides are of considerable pharmacological relevance,
due to their antimicrobial, antitumor, and antioxidant properties.
They also play an important role as synthetic reagents (e.g., in
the context of elimination reactions based on selenoxide pyrolysis
or in the context of radical reactions) and in material sciences (e.g.,
conductive and supraconductive organic molecules).1 The synthe-
sis of organoselenium compounds is a demanding task, due to
the unstable nature of the products. In addition, most of the meth-
ods developed for the synthesis of organosulfur compounds are not
applicable to the synthesis of organoselenium compounds. A num-
ber of methods have been developed for the preparation of ali-
phatic organoselenium derivatives. This includes the reaction of a
metal selenolate with organic halides, acyl chlorides, epoxides,
and enones.2 However, the synthesis of diaryl selenides from sele-
nide anions with aryl halides is more difficult, due to the low reac-
tivity of the halides. The reaction of halogenated arenes with
phenylselenol or benzeneselenolate salts requires the use of a cat-
alyst, ligand and strong base, long reaction times, and harsh reac-
tion conditions.3 Other syntheses rely on the reaction of diaryl
diselenides with organometallic reagents (e.g., organolithiums,
Grignard reagents, or cuprates) or organoboronic acids.4 Unsym-
metrical diaryl selenides are also available from (toxic) arylselenyl
bromides with aryl lithium derivatives.5
tion conditions, and high temperatures. In addition, reduction and
formation of diselenides are often observed. Electron-rich arenes
and sterically encumbered substrates sometimes react sluggishly
or not at all. In addition, the synthesis of the required starting
materials, highly functionalized or sterically encumbered haloge-
nated arenes can be a difficult and tedious task.
Our concept to circumvent these problems is based on the
development of cyclization reactions of suitable selenium-contain-
ing molecules (‘building block strategy’). Examples for the applica-
tion of this strategy to the synthesis of phenylselanyl-substituted
carbacycles have only scarcely been reported to date. Stone and
co-workers reported the [4+2] cycloaddition of 2-(phenylsela-
nyl)-1,3-butadienes with alkenes and alkynes.6 Chan and Brown-
bridge were the first to report7 the synthesis of salicylates by
formal [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-butadienes8 with
3-silyloxy-2-en-1-ones.9 Herein, we report what is, to the best of
our knowledge, the first application of this methodology to the
synthesis of organoselenium compounds. The products reported
herein, 5-(phenylselanyl)salicylates, can be regarded as functional-
ized diaryl selenides and have, to the best of our knowledge, not
been previously prepared. Symmetrical salicylate-derived diaryl-
selenides are known and have been prepared by reaction of salic-
ylates with (toxic) SeOCl2 and subsequent reduction with zinc.10
Barton et al. have reported an isolated example of the formation
of an unsymmetrical derivative during their study of the oxidation
of phenols by benzeneselenic anhydride.11
The methods listed above, which all rely on the formation of a
C–Se bond, often suffer from their low regioselectivity, harsh reac-
Phenylselanyl-substituted 1,3-diketones 2a,b were prepared by
reaction of 1a,b with selenium dioxide and diphenyl diselenide in
* Corresponding author. Tel.: +49 381 4986410; fax: +49 381 4986412.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.136

M. Shkoor et al. / Tetrahedron Letters 50 (2009) 5726–5728
5727
Me3SiO
R2
OSiMe3
OR3
PhSeSePh
SeO2
O
O
O
OH
O
O
TiCl4
CH2Cl2
H2SO4 (cat.)
R2
R1
R1
R1
OR3
4a-i
R1
R1
CH2Cl2
10 to 20 °C
+
SePh
_
R1
SePh
1a,b
78 to 20 °C,
20 h
Me3SiO
R1
O
2a (R1 = Me): 52%
2b (R1 = Et): 47%
R1
5a-l
SePh
Me3SiCl
3a,b
Me3SiO
R1
O
C6H6, NEt3
Scheme 3. Synthesis of 5a–l.
R1
SePh
20 °C
3a (R1 = Me): 90%
3b (R1 = Et): 91%
The TiCl4-mediated cyclization of enones 3a,b with 1,3-bis(tri-
methylsilyloxy)-1,3-butadienes 4a–i afforded the highly function-
alized diaryl selenides 5a–l in 46–70% yield (Scheme 3, Table 1).
The structures of all compounds were established by spectroscopic
methods. The structure of 5b was independently confirmed
by X-ray crystal structure analysis (Fig. 1).16
In conclusion, we have reported a new and convenient synthe-
sis of various functionalized unsymmetrical diaryl selenides con-
taining a salicylate substructure.
Scheme 1. Synthesis of 3a,b.
the presence of catalytic amounts of sulfuric acid (Scheme 1). The
synthesis of 2a has been previously reported.12 The silylation of
2a,b with chlorotrimethylsilane afforded the novel 3-silyloxy-2-
en-1-ones 3a,b. 1,3-Bis(silyloxy)-1,3-butadienes 4a–i were pre-
pared as previously reported.7,13,14
The TiCl4-mediated cyclization of 3a with 4a afforded the diaryl
selenide 5a (Scheme 2). The best yield was obtained when the
reaction was carried out in a highly concentrated solution.15 The
formation of 5a can be explained by reaction of 3a with TiCl4 to
give allylic cation A. The attack of the terminal carbon atom of
4a onto A resulted in the formation of intermediate B. The elimina-
tion of hexamethyldisiloxane (intermediate C) and subsequent
cyclization gave intermediate D. The elimination of titanium
hydroxide and aromatization resulted in the formation of product
5a.
Table 1
Synthesis of 5a–l
3
4
5
R1
R2
R3
% (5)a
a
a
a
a
a
a
a
a
a
b
b
b
a
b
c
d
e
f
g
h
i
a
b
c
d
e
f
g
h
i
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
H
H
H
Me
Et
nBu
nHex
nHep
nOct
H
Me
59
57
46
68
70
69
62
62
59
56
55
61
(CH2)2OMe
CH2Ph
Me
Me
Me
Me
Me
Me
Me
a
b
d
j
k
l
Me3SiO OSiMe3
Et
Et
H
Me
(CH2)2OMe
Me
O
OH
TiCl4
OMe
CH2Cl2
a
4a
OMe
Me
Yields of isolated products.
Me3SiO
O
_
Me
78 to 20 °C
14 h
+
SePh
Me
Me
SePh
5a (59%)
3a
TiCl4
H2O
_
O
O
TiCl4
Me3SiO
Me
O
OMe
OTiCl3
Me
+
Me
Me
SePh
SePh
A
D
4a
Me3SiCl
Me3SiCl
O
O
Me3SiO
OMe
TiCl3
Me3SiO
Me
OMe
Me3SiCl
TiCl4
O
O
Me3SiO
Me
Me
Me
(Me3Si)2O
SePh
SePh
B
C
Scheme 2. Possible mechanism of the formation of 5a.
Figure 1. Crystal structure of 5b (50% probability level).

5728
M. Shkoor et al. / Tetrahedron Letters 50 (2009) 5726–5728
2007, 72, 7587; (i) Nakanishi, W.; Hayashi, S. J. Org. Chem. 2002, 67, 38; (j)
Acknowledgment
Arnauld, T.; Barton, D. H. R.; Normant, J.-F. J. Org. Chem. 1999, 64, 3722; (k)
Tiecco, M.; Testaferri, L.; Tingoli, M.; Marini, F.; Mariggio, S. Tetrahedron 1994,
50, 10549.
Financial support by the State of Mecklenburg-Vorpommern
(scholarship for M.S.) is gratefully acknowledged.
5. Hayashi, S.; Wada, H.; Ueno, T.; Nakanishi, W. J. Org. Chem. 2006, 71, 5574.
6. (a) Bates, G. S.; Fryzuk, M. D.; Stone, C. Can. J. Chem. 1987, 65, 2612; (b) Pearson,
W. H.; Bergmeier, S. C.; Degan, S.; Lin, K.-C.; Poon, Y.-F. J. Org. Chem. 1990, 55,
5719.
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10. Nelson, R. E.; Schroeder, R. A.; Bunting, W. R. J. Am. Chem. Soc. 1933, 55, 801.
11. Barton, D. H. R.; Ley, S. V.; Magnus, P. D.; Rosenfeld, M. N. J. Chem. Soc., Perkin
Trans. 1 1977, 567.
12. Miyoshi, N.; Yamamoto, T.; Kambe, N.; Murai, S.; Sonoda, N. Tetrahedron Lett.
1982, 46, 4813.
1. (a) The Chemistry of Organic Selenium and Tellurium Compounds; Patai, S.,
Rappoport, Z., Eds.; Wiley: Chichester, 1986; Vol. 1, (b) The Chemistry of Organic
Selenium and Tellurium Compounds; Patai, S., Rappoport, Z., Eds.; Wiley:
Chichester, 1987; Vol. 2, (c) Krief, A. In Comprehensive Organometallic
Chemistry; Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; pp 85–192; (d)
Krief, A.. In Comprehensive Organometallic Chemistry II; Abel, E. W., Stone, F. G.
A., Wilkinson, G., Eds.; Pergamon Press: New York, 1995; Vol. 11,. Chapter 13
(e) Organoselenium Chemistry: A Practical Approach; Back, T. G., Ed.; Oxford
University Press: New York, 1999; (f) Ip, C. J. Nutr. 1998, 128, 1845; (g) Ip, C.;
Lisk, D. J.; Ganther, H.; Thompson, H. J. Anticancer Res. 1997, 17, 3195; (h)
Organoselenium Chemistry; Wirth, T., Ed, Topics in Current Chemistry; Springer:
Heidelberg, 2000; Vol. 208, (i) Abdel-Hafez, Sh. H.; Anthonsen, H.; Sliwka, H.-R.;
Partali, V. Phosphorus, Sulfur Silicon Relat. Elem. 2005, 180, 2217; (j) Abbady, M.
A.; Abdel-Hafez, Sh. H. Phosphorus, Sulfur Silicon Relat. Elem. 2000, 160, 121.
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14. Nguyen, V. T. H.; Bellur, E.; Appel, B.; Langer, P. Synthesis 2006, 2865.
15. Typical procedure for the synthesis of diaryl selenides 5a–l. To a CH2Cl2 solution
(5 mL) of 3a (491 mg, 1.5 mmol) and 4a (429 mg, 1.65 mmol) was added
dropwise TiCl4 (0.18 mL, 1.6 mmol) at ꢀ78 °C. The reaction mixture was
allowed to warm to 20 °C for 6–12 h. After stirring for additional 2–6 h at 20 °C,
hydrochloric acid (10%, 20 mL) was added. The organic and the aqueous layers
were separated and the latter was extracted with dichloromethane
(3 ꢁ 25 mL). The combined organic layers were dried (Na2SO4), filtered, and
the filtrate was concentrated in vacuo. The residue was purified by
chromatography (silica gel, heptanes/ethyl acetate) to give 5a as a colorless
oil (297 mg, 59%). Methyl 6-hydroxy-2,4-dimethyl-3-(phenylselanyl)benzoate
(5a): 1H NMR (250 MHz, CDCl3): d = 2.34 (s, 3H, CH3), 2.66 (s, 3H, CH3), 3.83
(s, 3H, OCH3), 6.75 (s, 1H, CHAr), 6.94–6.98 (m, 2H, 2CHAr), 7.05–7.14 (m, 3H,
3CHAr), 10.91 (s, 1H, OH). 13C NMR (75 MHz, CDCl3): d = 24.4, 25.7 (CH3), 52.3
(OCH3), 112.2 (CCO2CH3), 117.3 (CHAr), 123.1 (CAr), 125.5 (CHAr), 128.18, 129.2
(2CHAr), 133.4, 146.6, 151.2 (CAr), 162.4 (COH), 171.7 (CO). IR (neat, cmꢀ1):
~
m
¼ 3054 (w), 2950 (w), 2922 (w), 2852 (w), 1730 (w), 1689 (w), 1656 (s), 1631
(m), 1593 (m), 1475 (m), 1375 (w), 1348 (s), 1298 (s), 1223 (s), 1186 (s), 1125
(s), 1101 (s), 1064 (s), 1020 (m), 997 (m), 947 (w), 858 (w), 801 (m), 731 (s),
688 (m), 664 (m), 589 (m). MS (GC-MS, 70 eV): m/z (%): 338 (16), 337 (15), 336
(M+, 79), 334 (40), 333 (15), 332 (15), 306 (21), 305 (23), 304 (100), 303 (17),
302 (52), 301 (23), 300 (20), 224 (25), 196 (15), 195 (12), 168 (13), 167 (21),
165 (10), 152 (11), 119 (12), 91 (25), 77 (12), 65 (13), 51 (10). HRMS (EI): Calcd
for C16H16O3Se: 336.02592; found: 336.025935.
16. CCDC-743731 contains all crystallographic details of this publication and is
available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be
ordered from the following address: Cambridge Crystallographic Data Centre,
12 Union Road, GB-Cambridge CB21EZ; Fax: (+44)1223-336-033; or
deposit@ccdc.cam.ac.uk.