One-pot synthetic method of unsymmetrical diorganyl selenides: Reaction of diphenyl diselenide with alkyl halides in the presence of lanthanum metal

Article abstract of DOI:10.1021/jo026032h

A convenient synthetic method of unsymmetrical selenides has been developed. When diphenyl diselenide was allowed to react with two equimolar amounts of primary alkyl iodides and bromides in the presence of an equimolar amount of lanthanum metal, alkyl ph

Full text of DOI:10.1021/jo026032h

SCHEME 1
On e-P ot Syn th etic Meth od of
Un sym m etr ica l Dior ga n yl Selen id es:
Rea ction of Dip h en yl Diselen id e w ith Alk yl
Ha lid es in th e P r esen ce of La n th a n u m
Meta l
TABLE 1. Syn th esis of Or ga n oselen iu m Com p ou n d sa
Toshiki Nishino, Mitsuo Okada, Takamasa Kuroki,
Toshihisa Watanabe, Yutaka Nishiyama,* and
Noboru Sonoda*
Department of Applied Chemistry, Faculty of Engineering,
Kansai University, Suita, Osaka 564-8680, J apan
nishiya@ipcku.kansai-u.ac.jp
Received J une 9, 2002
Abstr a ct: A convenient synthetic method of unsymmetrical
selenides has been developed. When diphenyl diselenide was
allowed to react with two equimolar amounts of primary
alkyl iodides and bromides in the presence of an equimolar
amount of lanthanum metal, alkyl phenyl selenides were
formed in moderate to good yields. For the reaction of
primary alkyl chlorides and secondary alkyl iodides, the
yields of the selenides were low; however, the yields were
dramatically improved by the addition of TMEDA or HMPA.
A reaction pathway involving the generation of a lanthanum
phenylselenolate intermediate was suggested.
Organic selenides are widely accepted as key interme-
diates in organic synthesis, and much effort is being
devoted to accomplishing the synthesis of these com-
pounds.1 Although numerous reports on the synthesis of
organoselenium compounds have already been published,
it usually requires the handling of unstable reagents,
strongly basic or acidic reaction conditions, and two-step
procedures. Therefore, the development of a one-step
synthetic method using stable reagents under neutral
conditions has attracted much attention. In this paper,
we show a novel one-step synthetic method of unsym-
metrical selenides by the reaction of diselenide with alkyl
halides in the presence of lanthanum metal (Scheme 1).2
When diphenyl diselenide (1) (1.0 mmol) was allowed
to react with two equimolar amounts of iodododecane (2.0
mmol) in the presence of an equimolar amount of lan-
thanum metal (1.0 mmol) and a catalytic amount of
iodine at 67 °C for 5 h, dodecyl phenyl selenide was
obtained in 1.56 mmol (156% yield based on lanthanum
a
Reaction conditions: RX (2.0 mmol), PhSeSePh (1.0 mmol),
La (1.0 mmol), I2 (0.2 mmol), and THF (5 mL) at 67 °C for 5 h.
GC yield based on RX. c GC yield based on lanthanum metal.
b
HMPA (1 mL) was added. e Yield of 3-phenylseleno-1-butene.
d
f TMEDA (1 mL) was added. At 110 °C for 13 h.
g
metal) (entry 1 in Table 1).5 Table 1 shows the results
on the synthesis of various alkyl phenyl selenides using
lanthanum metal-assisted reaction of 1 with alkyl ha-
lides. Dodecyl and benzyl phenyl selenides were also
formed by the reaction of dodecyl and benzyl bromides
in moderate yields (entries 2 and 5). In contrast, for the
alkyl chloride, the yield of alkyl phenyl selenide was low
under the same reaction conditions as that of the primary
alkyl iodides and bromides; however, the reaction of alkyl
chloride was accelerated by the addition of HMPA
(entries 3 and 4). The similar treatment of PhSeSePh
with 3-iodopropene produced 3-phenylselenopropene in
72% yield (entry 6). In the case of crotylbromide, allylic
phenyl selenides were formed in 73% yield with a mixture
of regioisomers (entry 7). Although the synthesis of
unsymmetrical selenide having a branched alkyl chain
and cyclic ring was successfully achieved by the elevation
(1) For recent reviews: (a) Krief, A.; Hevesi, L. In Organoselenium
Chemistry; Springer-Verlag: Berlin, 1988; Vol. 1. (b) Paulmier, C. In
Selenium Reagents and Intermediates in Organic Synthesis; Pergamon
Press: Oxford, 1986. (c) Patai, S.; Rappoport, Z. In The Chemistry of
Organic Selenium and Tellurium Compounds; Wiley & Sons: New
York, 1986 and 1987; Vols. 1 and 2. (d) Krief, A. In Comprehensive
Organometallic Chemistry; Trost, B. M., Eds.; Pergamon Press: Oxford,
1991; pp 85-192 and references therein.
(2) Recently, there have been some reports on methods for generat-
ing lanthanoid selenolate anion species via the reductive cleavage of
(3) Wang, L.; Zhang, Y. Heteroat. Chem. 1999, 10, 203.
(4) (a) Fukuzawa, S.; Niimoto, Y.; Fujinami, T.; Sakai, S. Heteroat.
Chem. 1990, 1, 491. (b) Sekiguchi, M.; Tanaka, H.; Takemi, N.; Ogawa,
A.; Ryu, I.; Sonoda, N. Heteroat. Chem. 1991, 2, 427. (c) Zhang, Y.;
Yu, Y.; Lin, R. Synth. Commun. 1993, 23, 189.
(5) We have already shown that the addition of a catalytic amount
of iodine dramatically enhanced the reductive dimerization of carbonyl
compounds,6 imines,7 and alkyl halides.8
3
the Se-Se bond with samarium compounds such as Sm/HgCl2 and
SmI2.4 However, these methods required the handling of reagents
unstable toward air and/or moisture and the poisonous reagents.
Furthermore, to the best of our knowledge, there are no examples of
methods for generating lanthanoid selenolate anion by use of other
lanthanoid metals.
10.1021/jo026032h CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/01/2002
8696
J . Org. Chem. 2002, 67, 8696-8698

SCHEME 2
SCHEME 4
SCHEME 5
SCHEME 3
ethyl acrylate in the presence of lanthanum metal gave
the Michael addition product, ethyl 3-phenylseleno pro-
pionate, in 32% yield (Scheme 5).10 In addition, even
when alkyl phenyl selenides were not obtained, reductive
dimerization, reduction, and/or dehydroiodination prod-
ucts of alkyl halide were not formed in the reaction of
PhSeSePh with alkyl halide. Furthermore, the addition
of TMEDA and HMPA to the reaction solution caused
an increase in the yield of the alkyl phenyl selenides.11,12
On the basis of these results, at the present time, while
the preparation pathway of alkyl phenyl selenides is not
clearly shown, the reaction pathway including the alky-
lation of lanthanum phenyl selenolate, generated by the
reduction of diphenyl diselenide with lanthanum metal,
with alkyl halides was strongly suggested.
In summary, a one-pot synthetic method of unsym-
metrical selenides by the treatment of diphenyl diselenide
with alkyl halides in the presence of lanthanum metal
has been developed. The present method has the follow-
ing noteworthy features: (1) the high and moderate yield
preparation method of alkyl phenyl selenides; (2) a simple
operation; (3) neutral reaction conditions; and (4) the
efficient transfer of electrons of the lanthanum metal. A
wide range of diorganyl selenides were synthesized
successfully by employing this reaction system.
of the reaction temperature and extension of the reaction
time, tertiary alkyl phenyl selenide was not formed even
under harsh reaction conditions (entries 8-10). The
treatment of diphenyl diselenide with benzoyl chloride
gave Se-phenyl selenobenzoate in 43% yield (entry 11).
This reaction can be applicable to the synthesis of alkyl
phenyl sulfide and telluride. When diphenyl disulfide or
ditelluride instead of the diselenide was used as diphenyl
dichalcogenide, alky phenyl sulfide and telluride were
formed in 23 and 87% yields, respectively (Scheme 2).
Nakamura and Mashima et al. have shown a direct
synthetic method toward lanthanoid thiolate complexes
(Ln ) Sm and Eu) via the reaction of diaryl disulfide with
samarium and europium metal in the presence of a
catalytic amount of iodine.9 We have recently found that
alkyl radicals were easily generated by the reduction of
alkyl halides with lanthanum metal and coupled to form
the corresponding dimerization products.8 On the basis
of both results, two reaction pathways for the formation
of alkyl phenyl selenides were shown in Scheme 3. One
was the alkylation pathway of lanthanum phenylseleno-
late prepared by the reduction of diphenyl diselenide with
lanthanum metal with alkyl halides to form alkyl phenyl
selenides (Path 1). Another pathway including the SH2
reaction of alkyl radicals, which was generated by the
reduction of alkyl halides with lanthanum metal, with
PhSeSePh was suggested (Path 2). To better understand
the reaction pathway, we carried out some experiments
and obtained the following results. When PhSeSePh was
treated with lanthanum metal at 67 °C for 5 h, lantha-
num metal was gradually dissolved to give a brown
solution. Subsequently, an addition of 1-iodododecane to
the solution provided dodecyl phenyl selenide in 72%
yield (Scheme 4). By quenching the brown solution with
aqueous HCl, the formation of benzeneselenol was certi-
fied by GC. The treatment of diphenyl diselenide with
Exp er im en ta l Section
In str u m en ts. 1H and 13C NMR spectra were recorded
on a 400 and 99.5 MHz spectrometer using CDCl3 as a
solvent with tetramethylsilane as the internal standard.
IR spectra were recorded on a FT-IR spectrophotometer.
Gas chromatography (GC) was carried out on a flame
ionizing detector-equipped instrument and using a capil-
lary column (0.25 mm × 25 m). HPLC separation was
(10) Fujiwara et al. reported that the reaction of diaryl and dialkyl
disulfide with ytterbium metal was activated by benzophenone to afford
ytterbium(III) thiolates. The thiolates thus formed in situ were reacted
with enones to give Michael adducts. See: Taniguchi, Y.; Maruo, M.;
Takaki, K.; Fujiwara, Y. Tetrahedron Lett. 1994, 35, 7789.
(11) It was known that the reduction of organic compounds with
samarium(II) iodide was promoted by the addition of HMPA.13
However, the reductive coupling of carbonyl compounds with lantha-
num metal was not accelerated by the addition of HMPA.6
(6) Nishino, T.; Nishiyama, Y.; Sonoda, N. Heteroat. Chem. 2000,
11, 81.
(7) Nishino, T.; Nishiyama, Y.; Sonoda, N. Heteroat. Chem. 2002,
13, 131.
(8) Nishino, T.; Watanabe, T.; Okada, M.; Nishiyama, Y.; Sonoda,
N. J . Org. Chem. 2002, 67, 966.
(9) Mashima, K.; Nakayama, Y.; Fukumoto, H.; Kanehisa, N.; Kai,
Y.; Nakamura, A. J . Chem. Soc., Chem. Commun. 1994, 2523.
(12) It is well-known that the nucleophilic addition of organometallic
compounds such as alkyllithium compounds is promoted by the
addition of HMPA and TMEDA due to the deaggregation of organo-
metallic compound by these reagents. From the background, we
suggested that the deaggregation of lanthanum selenolate with HMPA
or TMEDA raised the nucleophilicity of selenolate.
J . Org. Chem, Vol. 67, No. 24, 2002 8697

performed on recycling preparative HPLC equipped with
GPC columns (20 × 1200 mm).
Meta l in th e P r esen ce of TMEDA. Lanthanum powder
(1.0 mmol, 139 mg), iodine (0.2 mmol, 51 mg), diphenyl
diselenide (1.0 mmol, 312 mg), organic halide (2.0 mmol),
TMEDA (1 mL), and THF (5 mL) were added to the
autoclave, and the mixture was stirred at 110 °C for 13
h under a nitrogen atmosphere. After the reaction, the
same workup as described in the general procedure for
the reaction of organic halides with diphenyl diselenide
with lanthanum metal was carried out to give the
corresponding alkyl phenyl selenides. The product was
characterized by comparison of its spectra data with
those of authentic samples. The structures of the products
Rea gen ts. Organic halides and iodine were com-
mercially available high-grade products and used without
purification. Lanthanum metal was commercially avail-
able high-grade products and used after powderization.
Diphenyl diselenide was synthesized by the literature
method.14 The other reagents and solvents were purified
by the usual mehods before use.
Gen er a l P r oced u r e for th e Rea ction of Or ga n ic
Ha lid es a n d Dip h en yl Diselen id e w ith La n th a n u m
Meta l. Lanthanum powder (1.0 mmol, 139 mg), iodine
(0.2 mmol, 51 mg), and diphenyl diselenide (1.0 mmol,
312 mg) were placed in a two-necked flask. THF (5 mL)
and organic halide (2.0 mmol) were added to the flask,
and the mixture was stirred at 67 °C for 5 h under a
nitrogen atmosphere. The color of the solution gradually
changed to dark gray. After the reaction, aqueous HCl
(1 M) was added to the reaction mixture, and the mixture
was extracted with diisopropyl ether (three times). The
organic layer was dried over MgSO4. The resulting
mixture was filtered, and the organic solvent was re-
moved under the reduced pressure. Purification of the
residue by HPLC afforded the corresponding alkyl phenyl
selenide. Products were characterized by comparison of
their spectra data with those of authentic samples. The
1
were assigned by their H and 13C NMR and IR spectra.
Tw o Step P r oced u r e for Syn th esis of Alk yl P h en -
yl Selen id e. A THF (5 mL) solution of lanthanum
powder (1.0 mmol, 139 mg), iodine (0.2 mmol, 51 mg),
and diphenyl diselenide (1.0 mmol, 312 mg) were stirred
at 67 °C for 5 h under a nitrogen atmosphere. Iododode-
cane (2.0 mmol, 592 mg) was added to the resulting
solution, and the mixture was stirred at 67 °C for 3 h.
After the reaction, the same workup as described in the
general procedure for the reaction of organic halides with
diphenyl diselenide with lanthanum metal was carried
out to give the corresponding alkyl phenyl selenides. The
product was characterized by comparison of its spectra
data with those of authentic samples. The structures of
1
1
the products were assigned by their H and 13C NMR and
structures of the products were assigned by their H and
13C NMR and IR spectra.
IR spectra.
Gen er a l P r oced u r e for th e Rea ction of Or ga n ic
Ha lid es a n d Dip h en yl Diselen id e w ith La n th a n u m
Ack n ow led gm en t. We thank the Santoku Co. for
supplying the lanthanum metal.
(13) (a) Otsubo, K.; Inanaga, J .; Yamaguchi, M. Tetrahedron Lett.
1986, 27, 5763. (b) Otsubo, K.; Inanaga, J .; Yamaguchi, M. Tetrahedron
Lett. 1987, 28, 4437. (c) Inanaga, J .; Ishikawa, M.; Yamaguchi, M.
Chem. Lett. 1987, 1485. (d) Hou, Z.; Wakatuki, Y. J . Chem. Soc., Chem.
Commun. 1994, 1205. (e) Hou, Z.; Zhang, Y.; Wakatuki, Y. Bull. Chem.
Soc. J pn. 1997, 70, 149.
Su p p or t in g In for m a t ion Ava ila b le: Copies of spectra
(1H and 13C NMR and IR) for all coupling products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(14) Reich, H. J .; Renga, J . M.; Reich, I. L. J . Am. Chem. Soc. 1975,
97, 5434.
J O026032H
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