Reaction of lithium aluminum hydride with elemental selenium: Its application as a selenating reagent into organic molecules [1]

Full text of DOI:10.1021/ja005800o

8408
J. Am. Chem. Soc. 2001, 123, 8408-8409
Scheme 1
Scheme 2a
Reaction of Lithium Aluminum Hydride with
Elemental Selenium: Its Application as a Selenating
Reagent into Organic Molecules
Hideharu Ishihara,* Mamoru Koketsu,* Yoshihisa Fukuta, and
Futoshi Nada
Department of Chemistry
Faculty of Engineering, Gifu UniVersity
1-1 Yanagido, Gifu, 501-1193, Japan
ReceiVed NoVember 17, 2000
ReVised Manuscript ReceiVed April 13, 2001
Recently many syntheses of compounds containing selenium
have been studied and reported because of the interesting
reactivities1 and their potential pharmaceutical significance.2
Several methods for the synthesis of selenium-containing com-
pounds using various types of selenating reagents have been
developed. The alkali metal salts of hydrogen selenide, which
can be readily prepared in situ by the reaction of elemental
selenium and a reducing reagent such as Li, LiBEt3H, Na, NaBH4,
NaBEt3H, and i-Bu2AlH, have often been utilized as selenating
reagents for the introduction into organic molecules.3 However,
the utilization of these salts as selenating reagents has been limited
to the synthesis of either dialkyl diselenides,3a-c dialkyl selenides,3b,c
selenothiocarbamates,3d selenoamides,3e as well as certain other
applications.4 A selenating reagent, capable of preparing a wide
range of selenium-containing compounds, has not been reported
yet. Here, we describe the reaction of lithium aluminum hydride
with elemental selenium and a wide range of the applications
using this reagent.
a a: RCOCl (2.0 equiv)/THF, 0 °C, 2 h; b: (1) RCOCl (1.0 equiv)/
THF, 0 °C, 2 h; (2) I2/KI (1.0 equiv/0.2 equiv), 0 °C, 1.5 h; c:
ClCO(CH2)3COCl (1.0 equiv)/THF, rt, 2.0 h; d: ClCO(CH2)3Cl (1.0
equiv), 0 °C, 2 h; e: C6H5C(dO)N(C2H5)2 (1.0 equiv)/(COCl)2 (1.0
equiv)/diethyl ether, 0 °C, 1 h, and then rt, 3 h; f: (CH3)2CHNdCdNCH-
(CH3)2 (1.0 equiv), 0 °C, 1 h; g: (1) C6H5-NdCdO (1.0 equiv), rt, 1 h;
(2) CH3I (1.0 equiv), rt, 2 h; h: (1) [Cl2CdN(CH3)2]Cl (1.0 equiv), 0
°C, 1.5 h; (2) amine (2.0 equiv), rt, 2 h; i; (1) [Cl2CdN(CH3)2]Cl; (2)
lithium alkylthiolate (1.0 equiv)/THF, 0 °C, 2 h; j: (1) [Cl2CdN(CH3)2]Cl;
(2) lithium alkylselenolate (1.0 equiv)/THF, 0 °C, 2 h.
was recovered in the present reaction.5 (2) In the 1H NMR
spectrum of the product 2, two proton peaks of different chemical
shift, 1.86 and 3.75 ppm, were observed. These chemical shifts
are close to those of similar compounds in the literatures.3e,6 From
these facts, we inferred that the product generated in the present
reaction was LiAlHSeH 2 (Scheme 1). The product 2 formed in
situ was ready for further reaction without concentration. We
investigated various kinds of solvents and found that THF or
diethyl ether could be used in this reaction.
The product 2 in THF, prepared as described above, was
applied to the syntheses of many kinds of selenium-containing
molecules as a selenating reagent. The compounds prepared in
this study are shown in Scheme 2. Reaction of 2 with 2 equiv of
acyl chloride gave diacyl selenide 3 in excellent yields. The
synthesis of diacyl selenides has been infrequently reported.7
Jensen et al.7a observed the existence of unstable benzoyl selenide,
which was obtained by the elimination of hydrogen selenide from
selenobenzoic acid at room temperature. The benzoyl selenide
was in turn transformed into dibenzoyl diselenide and bis-
(selenobenzoate). Kato et al. reported the preparation of diacyl
selenides by the reaction of O-silyl selenocarboxylates with acyl
chorides.7b We described the preparation of diacyl selenides;8
however, these methods all required many steps, while the present
method is a one-pot reaction from which could be easily isolated
Lithium aluminum hydride 1 (1 equiv) was added with stirring
to black selenium powder (1 equiv) suspended in THF under an
argon atmosphere at 0 °C for 30 min. Considerable hydrogen gas
was immediately evolved, and the black selenium powder was
consumed in less than 10 min. The reaction mixture became a
heterogeneous grayish suspension. (1) Hydrogen gas (1 equiv)
(1) (a) Ogawa, A.; Sonoda, N. In ComprehensiVe Organic Synthesis; Trost,
B. M.; Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 6, p 461. (b)
Ogawa, A.; Sonoda, N. ReV. Heteroat. Chem. 1994, 10, 43. (c) Guziec, F. S.,
Jr.; Guziec, L. J. In ComprehensiVe Organic Functional Group Transforma-
tions; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.; Pergamon: Oxford,
1995; Vol. 6, p 587. (d) Dell, C. P. In ComprehensiVe Organic Functional
Group Transformations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.;
Pergamon: Oxford, 1995; Vol. 5, p 565. (e) Krief, A. In ComprehensiVe
Organometallic Chemistry; Abel, W. W., Stone, F. G. A.;,Wilkinson, G., Eds.;
Pergamon: Oxford, 1995; Vol. 11, p 515. (f) Organoselenium Chemistry: A
Practical Approach; Back, T. G., Ed.; Oxford University Press: U.K., 1999.
(2) (a) Kumar Y.; Green R.; Borysko K. Z.; Wise, D. S.; Wotring, L. L.;
Townsend, L. B. J. Med. Chem. 1993, 36, 3843. (b) Kumar, Y.; Green, R.;
Wise, D. S.; Wotring, L. L.; Townsend, L. B. J. Med. Chem. 1993, 36, 3849.
(c) Koketsu, M,; Ishihara, H.; Hatsu, M. Res. Commun. Mol. Pathol.
Pharmacol. 1998, 101, 179. (d) Koketsu, M.; Ishihara, H.; Wu, W.; Murakami,
K.; Saiki, I. Eur. J. Pharm. Sci. 1999, 9, 157. (e) Wu, W.; Murakami, K.;
Koketsu, M.; Yamada, Y.; Saiki, I. Anticancer Res. 1999, 19, 5375. (f) Cho,
S. I.; Koketsu, M.; Ishihara, H.; Matsushita, M.; Nairn, A. C.; Fukazawa, H.;
Uehara, Y. Biochim. Biophys. Acta 2000, 1475, 207.
(3) (a) Klayman, D. L.; Griffin, T. S. J. Am. Chem. Soc. 1973, 95, 197. (b)
Gladysz, J. A.; Hornby, J. L.; Garbe, J. E. J. Org. Chem. 1978, 43, 1204. (c)
Thompson, D. P.; Boudjouk, P. J. Org. Chem. 1988, 53, 2109. (d) Copeland,
C. M.; Ghosh, J.; McAdam, D. P.; Skelton, B. W.; Stick, R. V.; White, A. H.
Aust. J. Chem. 1988, 41, 549. (e) Li, G. M.; Zingaro, R. A. J. Chem. Soc.,
Perkin Trans. 1 1998, 647.
(4) As other applications of sodium hydrogen selenide: (a) Yoshida, Z.;
Konishi, H.; Ogushi, H. J. Chem. Soc., Chem. Commun., 1975, 359. (b)
Sandman, D. J.; Epstein, A. J.; Holmes, T. J.; Fisher, A. P. J. Chem. Soc.,
Chem. Commun. 1977, 177. (c) Barton, D. H. R.; Hansen, P.-E.; Picker, K. J.
Chem. Soc., Perkin Trans. 1 1977, 1723. (d) Reid, D. H.; Webster, R. G.;
McKnzie, S. J. Chem. Soc., Perkin Trans. 1 1979, 2334. (e) Guziec, F. S.,
Jr.; Russo, J. M.; Torres, F. F.; Long, G. C.; Tellez, M. R. J. Chem. Soc.,
Perkin Trans. 1 1989, 1068. (f) Nishiyama, Y,; Yoshida, M,; Ohkawa, S.;
Hamanaka, S. J. Org. Chem., 1991, 56, 6720. (g) Farooqui, F.; Sabahi, M.;
Schroeder, T. B.; Glass, R. S. Scientia Iranica 1997, 4, 121.
(5) The amount of hydrogen gas evolving in the present reaction was
quantitatively measured in accordance with the previously described method.
(a) Lalancette, J. M.; Monteux, R. Can. J. Chem. 1968, 46, 2754. (b)
Lalancette, J. M.; Arnac, M. Can. J. Chem. 1969, 47, 3695.
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51, 2421. (b) Guillemin, J. C.; Bellec, N.; Sze´tsi, S. K.; Nyula´szi, L.;
Veszpre´mi, T. Inorg. Chem. 1996, 35, 6586. (c) Guillemin, J. C.; Bouayad,
A.; Vijakumar, D. Chem. Commun. 2000, 1163.
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10.1021/ja005800o CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/03/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 34, 2001 8409
diacyl selenides 3 in very high yields using silica gel flash column
chromatography. Until now it has been relatively difficult to be
obtain aliphatic diacyl selenides 3 because of their instability.8
Both aromatic and aliphatic diacyl selenides 3 were obtained in
excellent yields by using 2. Acyl chloride (1 equiv) and I2/KI
(1.0 equiv/0.2 equiv) yielded diacyl diselenide9 4 in 75-86%
yields, respectively. Reaction of 2 with glutaryl chloride formed
glutaric selenoanhydride 5 in 66%. This method gave 5 in better
yield than the first reported synthesis of 5.10 γ-Selenobutyrolactone
6 was obtained by adding 4-chlorobutyryl chloride into com-
pounds 2 in 71%. There is only one additional example of the
synthesis of a γ-selenobutyrolactone 6 in the literature.11 The
present method requires fewer steps than the previously reported
method. Reaction of N,N-diethyl amide and oxalyl chloride with
2 gave N,N-diethyl selenoamide 7 in 68% yield. Reaction of 2
with carbodiimide afforded selenourea 8 in 62%. The carbodi-
imide was previously obtained via oxidation of selenourea using
NaIO4 in quantitative yield.12 This method involves the reverse
reaction. The Se-methyl N-phenylcarbamate 9 was obtained by
the reaction of 2 with phenyl isocyanate and methyl iodide. In
contrast, 9 could not be prepared using lithium selenide3b obtained
by lithium triethylborohydride reduction of selenium because of
being unable to supply the hydrogen. N,N-Dimethyl selenocar-
bamoyl chloride (CH3)2NC(dSe)Cl is easily prepared in situ from
reaction of 2 with dichloromethylenedimethyliminium chloride
[Cl2CdN(CH3)2]Cl and can be trapped with various nucleophiles
such as amines, lithium alkylthiolates, and lithium alkylseleno-
lates, to give the corresponding selenoureas 10, S-alkyl sele-
nothiocarbamates 11, and Se-alkyl diselenocarbamates 12 in good
to high yields. This is the first reported synthesis of N,N-dialkyl
diselenocarbamates 12.13 Previously, selenoureas and selenothio-
carbamates bearing limited types of functional groups have been
synthesized by using sodium hydrogen selenide.3d,14 Because the
present study can use various carbodiimides, isocyanates, amines,
lithium alkylthiolates, or lithium alkylselenolates as nucleophiles,
the compounds 8, 9, 10, 11, and 12 bearing various kinds of alkyl
groups are readily prepared.15
We have developed a novel and very useful selenating reagent.
This communication demonstrates the potential wide-ranging
utility of this reagent by the preparation of various organic
selenium compounds. Elucidation of the details of the precise
reaction mechanism and combined state of 2 requires further
study.
Acknowledgment. We thank Professor Robert J. Linhardt for critical
reading of our manuscript. This work was supported in part by Nihon
Nohyaku Co., Ltd.
Supporting Information Available: Synthetic procedures for the
compounds 2-12 prepared in this communication, including spectral
characterization (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
(9) As synthesis examples of diacyl diselenides: (a) Ishihara, H.; Hiraba-
yashi, Y. Chem. Lett. 1976, 203. (b) Wang, J.-X.; Cui, W.-F.; Hu, Y.-L.; Zang,
S.-S. J. Chem. Res. (S) 1990, 230. (c) Nishiyama, Y.; Katsuura, A.; Negoro,
A.; Hamanaka, S.; Miyoshi, N.; Yamana, Y.; Ogawa, A.; Sonoda, N. J. Org.
Chem. 1991, 56, 3776. (d) Niyomura, O.; Tani, K.; Kato, S. Heteroat. Chem.
1999, 10, 373 (f) Niyomura, O.; Kato, S.; Inagaki, S. J. Am. Chem. Soc. 2000,
122, 2132.
(10) Koketsu, M.; Hiramatsu, S.; Ishihara, H. Chem. Lett. 1999, 485.
(11) Gu¨nther, W. H. H. J. Org. Chem. 1966, 31, 1202.
(12) Koketsu, M.; Suzuki, N.; Ishihara, H. J. Org. Chem. 1999, 64, 6473.
JA005800O
(13) As an example of N-alkyl diselenocarbamate synthesis; Henriksen,
L. Int. J. Sulfur Chem. 1973, 8, 389.
(14) Klayman, D. L.; Shine, R. J. J. Org. Chem. 1969, 34, 3549.
(15) The use of NaHSe prepared in alcohol gave only O-alkyl selenocar-
bamate from N,N-dimethyl selenoamide chloride by the nucleophilic attack
of alcohol to selenocarbonyl carbon.