Bull. Chem. Soc. Jpn. Vol. 79, No. 1 (2006)
Ó 2006 The Chemical Society of Japan
141
reaction progress was very slow (5–7% of yield) and in other
solvents such as THF, NMP with KOtBu, which did not fur-
nish the expected product under the above experimental condi-
tions, demonstrated the efficacy of our reagent in the arylsele-
nenylation.
aryl halides with Ph2Se2 to give the corresponding aryl sele-
nides can be promoted with CsOH H2O. The reaction condi-
ꢁ
tions are compatible with functional groups in the substrates as
well with some limitations. Since the seleno group could be
subjected to diverse transformations, there is a possibility that
this reaction may be developed into a synthetically useful
process, although further work is needed to expand the scope
of the reaction in large scale applications.
Encouraged by these results, we carried out the reaction un-
der different conditions and the results were quite satisfactory.
At ambient temperatures the cross coupling between bromo-
benzene and Ph2Se2 did not proceed, even after stirring the
reaction for several days. As a control experiment, the same re-
action mixture was heated in the absence of the base at 110 ꢂC.
No cross-coupled product was formed, even after heating the
coupling fragments for a longer period of time. Thus, base
plays a vital role in this reaction. The optimum yields of the
product were obtained with a ratio of aryl halide to Ph2Se2
of 1:1.5. Among the solvents used were DMSO–THF, NMP,
THF, and DMSO and all were found to be good media for this
transformation. It seems that DMSO is a much better solvent in
terms of yields than all of the other tested solvents. With the
absence of DMSO, no product could be isolated from the crude
reaction mixture.
V. R is thankful to CSIR, India for the award of fellowship.
References
#
1
IICT Communication No: 050813.
For selected examples of an aryl–heteroatom bond forma-
tion, see: a) B. H. Yang, S. L. Buchwald, J. Organomet. Chem.
1999, 576, 125. b) J.-F. Marcoux, S. Doye, S. L. Buchwald, J. Am.
Chem. Soc. 1997, 119, 10539. c) F. Hartwig, G. Mann, J. Org.
Chem. 1997, 62, 5413.
2
a) E. Block, S. Bird, J. F. Tyson, P. C. Uden, X. Zhang,
E. Denoyer, Phosphorus, Sulfur, Silicon Relat. Elem. 1998, 136, 1.
b) K. El-Bayoumy, Nutr. Cancer 2001, 40, 4. c) C. Ip, H. E.
Ganther, Carcinogenesis 1992, 13, 1167. d) C. Ip, D. J. Lisk, H. E.
Ganther, H. Thompson, J. Anticancer Res. 1997, 17, 3195.
Having found the optimum reaction conditions, we carried
out the reactions of Ph2Se2 with bromobenzene. We then inves-
tigated the direct cross-coupling reactions of a wide range of
substituted aryl halides, having both electron withdrawing
and electron donating substituents Ph2Se2. The results from this
study are shown in Table 1. It is clear from Table 1 that most
substrates underwent direct cross-coupling reactions to afford
the corresponding selenides in moderate to good yields. Reac-
tion times are also very short (5–20 min) for most of the sub-
strates. However, the areneselenenylation of aryl halides con-
taining electron-donating substituents required a longer reac-
tion time. The electron-withdrawing group containing (–NO2)
aryl halides reacted faster when compared to electron-donating
groups like the –CH3 counter part (see Entries 3–6, Table 1).
For Entries 3 and 4, the product is formed in a 1:1 ratio of re-
gioisomers (meta:para). The iodo aryl analogues when com-
pared to bromo aryl analogues gave good yields on reacting
with diphenyl diselenides (see Table 1). Heterocyclic aryl hal-
ide, like 2-bromopyridine (Entry 8), reacted slowly to form the
corresponding product exclusively in ortho-position with a low
yield of 47% on reacting with Ph2Se2. However, aryl halides
that contain p-hydroxy, p-amino, and p-methoxy substituents
do not undergo adduct formation at all under our experimental
conditions (Entries 9–11).9 We evaluated the feasibility of the
direct cross coupling of bromo/iodobenzenes with diphenyl
disulfide (Ph2S2) also as described in the general procedure,
(see Entries 12 and 13, Table 1) and the results are satisfacto-
ry. However, this type of coupling reaction does not seem to
work well with aryl chlorides and fluorides. We have also eval-
uated the feasibility of this reaction with chlorobenzene and
Ph2Se2, which did not furnish the desired product even after
1 h. Also, with o-bromotoluene as an example, m-substituted
product is exclusively formed with Ph2Se2. In the case of alkyl-
halide such as benzyl bromide, the corresponding coupled
product is formed in 5 min at 70 ꢂC with a yield of 82%. The
mechanism of this facile arylselenenylation is not clear at pres-
ent and investigation is under way.
3
a) Comprehensive Organic Chemistry, ed. by A. Krief,
Pergamon, Oxford, 1991; Organoselenium Chemistry, ed. by A.
Krief, Springer-Verlag, Berlin, 1988. b) D. J. Procter, J. Chem.
Soc., Perkin Trans. 1 1999, 641.
4
a) D. J. Procter, J. Chem. Soc., Perkin Trans. 1 2001, 335.
b) Organoselenium Chemistry, Topics in Current Chemistry, ed.
by T. Wirth, Springer-Verlag, Heidelberg, 2000, Vol. 208. c) N.
Taniguchi, T. Onami, J. Org. Chem. 2004, 69, 915. d) R. K.
Gujadhur, D. Venkataraman, Tetrahedron Lett. 2003, 44, 81.
e) Y. Nishiyama, K. Tokunaga, N. Sonada, Org. Lett. 1999, 1,
1725. f) P. I. Beletskaya, A. S. Sigeev, A. S. Peregudov, P. V.
Petrovskii, Tetrahedron Lett. 2003, 44, 7039. g) N. Taniguchi,
T. Onami, Synlett 2003, 829. h) M. Kosugi, T. Ogata, M. Terada,
H. Sano, T. Migita, Bull. Chem. Soc. Jpn. 1985, 58, 3657.
5
a) H. Suzuki, H. Abe, A. Osuka, Chem. Lett. 1981, 151.
b) A. Osuka, N. Ohmasa, H. Suzuki, Synth. Commun. 1982, 857.
N. E. Leadbeater, M. Marco, Angew. Chem., Int. Ed. 2003,
42, 1407.
6
7
a) D. Tzalis, P. Knochel, Angew. Chem., Int. Ed. Engl.
1999, 38, 1463. b) R. N. Salvatore, A. S. Nagle, K. W. Jung,
J. Org. Chem. 2002, 67, 674. c) E. J. Corey, Y. Bo, J. B. Petersen,
J. Am. Chem. Soc. 1998, 120, 13000. d) R. Varala, E. Ramu,
M. M. Alam, S. R. Adapa, Synlett 2004, 1747. e) R. Varala, E.
Ramu, M. M. Alam, S. R. Adapa, Chem. Lett. 2004, 33, 1614.
8
mmol), and CsOH H2O (2 mmol) in DMSO (3 mL) was taken
A mixture of aryl halide (1 mmol), Ph2Se2/Ph2S2 (1.5
ꢁ
in a sealed tube placed in preheated oil bath at the given temper-
ature (Table 1) and then held at that temperature for the given
time. Then, the reaction mixture was cooled to rt, poured into
water containing crushed ice, and stirred for 5 min. Saturated
aqueous NH4Cl solution was added to this mixture, and the organ-
ic portion was extracted with Et2O (3 ꢃ 20 mL). The combined
organic extracts were washed with a saturated NH4Cl solution
and brine, and dried over anhydrous Na2SO4. After removal of
the solvent, the residue was purified by column chromatography
on silica gel to furnish the product. All isolated compounds were
fully characterized by comparing their spectral data (1H NMR and
mass spectra) to authentic compounds.4c
In conclusion, we have demonstrated that the coupling of