Convenient route to dialkyl diselenides from alkyl tosylates. Synthesis of di(cis-myrtanyl) diselenide

Article abstract of DOI:10.1016/j.tetlet.2005.03.073

A one-step method for the synthesis of dialkyl diselenides, by reaction of alkyl tosylates with sodium diselenide is described. Three variants of the synthesis, using as an example the preparation of optically active di(cis-myrtanyl) diselenide, are compared.

Full text of DOI:10.1016/j.tetlet.2005.03.073

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3331–3334
Convenient route to dialkyl diselenides from alkyl
tosylates. Synthesis of di(cis-myrtanyl) diselenide
´
Jacek Scianowski
*
Department of Chemistry, Nicolaus Copernicus University, 7 Gagarin Street, 87-100 Toru n´ , Poland
Received 16 February 2005; revised 11 March 2005; accepted 15 March 2005
Available online 2 April 2005
Abstract—Aone-step method for the synthesis of dialkyl diselenides, by reaction of alkyl tosylates with sodium diselenide is
described. Three variants of the synthesis, using as an example the preparation of optically active di(cis-myrtanyl) diselenide, are
compared.
ꢀ
2005 Elsevier Ltd. All rights reserved.
1
1
12
Recently the chemistry of organoselenium compounds
has played an important role in organic synthesis. The
use of reagents containing the selenium function makes
it possible to introduce new functional groups into
halides, (e) reduction of selenocyanates, or (f) the
1
reaction of selenocyanates with samarium iodide.
3
Efficient methods are available for the syntheses of
diaryl diselenides, but convenient routes to dialkyl
diselenides are still under investigation. Recently the
methods currently known were modified and new re-
agents to introduce a diselenide function, for example,
1
molecules. The oxidation of phenyl selenides, widely
employed in the formation of carbon–carbon double
1
14
bonds, serves as a classical example. The biological
and medicinal role of selenium and organoselenium
compounds is also increasingly appreciated, mainly
due to their antioxidant, antitumour, antimicrobial,
1
5
[Et N] WSe were described.
4
2
4
2
and antiviral properties.
Here we present a new and convenient method to make
dialkyl diselenides 1 based on the reaction of alkyl tosyl-
ates 2 with sodium diselenide 3. Sodium diselenide was
obtained according to the modified method described
Diselenides are of especial significance in organic syn-
thesis. These compounds can act as electrophilic re-
3
16
agents, for example, in additions to double bonds, as
well as nucleophilic reagents for the syntheses of allylic
earlier (Scheme 1).
4
alcohols and amines. Since the early nineties, diselen-
ides have been employed in asymmetric syntheses, for
The dialkyl diselenides were prepared in a one-step
reaction from tosylates, obtained using the pyridine
5
17
example, in the asymmetric opening of epoxides, in
7
method. As a result of the reactions of methyl 4, iso-
6
hydroxy and methoxyselenylation, azidoselenylation,
1
and others.
propyl 5, n-butyl 6, 2-pentyl 7, isoamyl 8, 2-octyl 9
and cyclohexyl 10 tosylates with sodium diselenide 3,
the corresponding dialkyl diselenides 11–17 were
obtained (Table 1).
Diselenides have been synthesised by (a) oxidation of
the products of reacting Grignard or organolithium
8
9
reagents with selenium, (b) oxidation of selenols, (c)
the reaction of sodium or lithium diselenide with alkyl
The reactions were conducted under argon, dropping
hydrazine monohydrate (0.3 mL) into a mixture of
1
0
halides, (d) the reaction of selenourea with alkyl
4
Se + 4NaOH + N H
2 4
2Na Se + 4 H O +
2
2
2
N2
3
Keywords: Dialkyl diselenides; Sodium diselenide; Di(cis-myrtanyl)
diselenide.
2 ROTs + Na2Se2
R2Se2 + 2 NaOTs
2
3
1
*
Tel.: +48 56 6114532; fax: +48 56 6542477; e-mail: jsch@chem.
uni.torun.pl
Scheme 1. Synthesis of dialkyl diselenides.
0
040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.073

´
J. Scianowski / Tetrahedron Letters 46 (2005) 3331–3334
3332
Table 1. Synthesis of dialkyl diselenides 11–17 from alkyl tosylates 4–10
7
7
Entry
1
Tosylate
Diselenide
Yield (%)
3
Se NMR d (CDCl )
OTs
Se
11
a,b
87
2
269.0
402.5
4
OTs
Se
b,c
90
2
3
4
5
2
5
12
OTs
Se
c
98
2
308.3
13
6
g
96
373.6, 373.9
Se ) 14
OTs
7
2
OTs
Se )
2
d
86
311.8
8
15
OTs
Se )
2
e
90
g
6
374.7, 375.1
5
5
9
16
Se )
c,f
69
OTs
0
7
2
364.2
1
17
a–f
g
18
Literature data.
Signals for diastereomers.
selenium (22 mmol) and sodium hydroxide (33 mmol) in
DMF (20 mL). After 15 min the respective tosylate
The methodology was employed for the synthesis of
optically active di(cis-myrtanyl) diselenide 18. Previ-
ously, only camphor derived dialkyl diselenides had
been investigated. In order to compare our method
with other routes to dialkyl diselenides, three other
syntheses of diselenide 18 from (ꢀ)-b-pinene 19 were
examined (Scheme 2).
(
22 mmol) dissolved in DMF (20 mL) was added and
2
0
the reaction mixture was heated for 1 h at 100 ꢁC. The
mixture was cooled, poured into water (100 mL) and
extracted with petroleum ether (3 · 100 mL). The
combined ethereal solutions were washed with water
(
100 mL) and dried over anhydrous MgSO . The ex-
4
2
1
tracts were evaporated and the crude product was
purified by column chromatography (petroleum ether,
silica gel 70–230 mesh).
Myrtanyl bromide 20 or myrtanyl tosylate 21 were
alternatively employed for the synthesis of 18. Reaction
of bromide 20 with magnesium and selenium then air,
gave di(cis-myrtanyl) diselenide 18 (32%), myrtanyl sel-
enide 22 (4%) and dimyrtanyl 23 (15%). Using sodium
diselenide prepared under the reaction conditions previ-
The structures of the obtained diselenides 11–17 were
confirmed on the basis of the H, C and Se NMR
spectra and by comparison to the literature data.
1
13
77
1
9
18
16
ously described by Syper and Młochowski, myrtanyl
Br
Se )
Se
2
)
)
2
+
2
a
b
+
1
9
20
1
1
8
8
22
23
c
Se )
d
2
OH
OTs
f
e
24
21
Scheme 2. Synthesis of di(cis-myrtanyl) diselenide. Reagents and conditions: (a) BH
xH O, 6 h, rt, 78%; (d) BH /THF, H
3
/THF, Br
/NaOH, 86%; (e) TsCl, pyridine, 87%; (f) Se NaOH, N
2
/CH
3
ONa, 60%; (b) Mg/Et
2 2
O, Se/O ; (c) Se, NaOH,
N
2
H
4
2
3
O
2 2
2
H
4
xH
2
O, 1 h, 100 ꢁC, 91%.

´
J. Scianowski / Tetrahedron Letters 46 (2005) 3331–3334
3333
bromide 20 gave diselenide 18 in 78% yield. Conducting
the same reaction in our one-step version from tosylate
3245; (c) Uehlin, L.; Fragale, G.; Wirth, T. Chem. Eur. J.
002, 8, 1125–1133; (d) Tiecco, M.; Testaferri, L.; Santi,
C.; Tomassini, C.; Marini, F.; Bagnoli, L.; Temperini, A.
Chem. Eur. J. 2002, 8, 1118–1124.
2
2
myrtanyl tosylate 21 was synthesised via hydrobora-
1, the diselenide 18 was formed in 91% yield. The
2
2
7. Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.;
Marini, F.; Bagnoli, L.; Temperini, A. Angew. Chem.,
Int. Ed. 2003, 42, 3131–3133.
tion–oxidation of (ꢀ)-b-pinene 19, and then further
reaction of the cis-myrtanol 24 obtained with tosyl chlo-
ride in pyridine. The structures of the resulting prod-
1
7
8
. (a) Nishibayashi, Y.; Singh, J. D.; Uemura, S. Tetrahedron
Lett. 1994, 35, 3115–3118; (b) Wirth, T. Tetrahedron Lett.
1995, 36, 7849–7852; (c) Deziel, R.; Goulet, S.; Grenier,
L.; Bordeleau, J.; Bernier, J. J. Org. Chem. 1993, 58, 3619–
3621; (d) Braga, A. L.; Silva, S. J. N.; Ludtke, D. S.;
Drekener, R. L.; Silveira, C. C.; Rocha, J. B. T.;
Wessjohann, L. A. Tetrahedron Lett. 2002, 43, 7329–7331.
. Krief, A.; DeMahieu, A. F.; Dumont, W.; Trabelsi, M.
Synthesis 1988, 131–133.
1
ucts 18, 22 and 23 were established from their H,
23
13
C
7
7
and Se NMR spectra.
In conclusion, a new rapid and efficient method for the
synthesis of other dialkyl diselenides from alkyl tosylates
has been established. This methodology was successfully
applied for the synthesis of optically active di(cis-myrt-
anyl) diselenide, not previously described in the litera-
ture. The applications of this method for the synthesis
of another dialkyl diselenides from the terpene group
are being investigated.
9
1
1
0. (a) Klayman, D. L.; Griffin, T. S. J. Am. Chem. Soc. 1973,
0, 197–199; (b) Thompson, D. P.; Boudiouk, P. J. Org.
1
Chem. 1988, 53, 2109–2112; (c) Syper, L.; Młochowski, J.
Tetrahedron 1988, 44, 6119–6130.
1. Ming-De, R.; Hua-Rong, Z.; Wei-Qiang, F.; Xun-Jun, Z.
J. Organomet. Chem. 1995, 485, 19–24.
References and notes
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13. Salama, P.; Bernard, Ch. Tetrahedron Lett. 1998, 39,
745–748.
14. (a) Krief, A.; Derock, M. Tetrahedron Lett. 2002, 43,
3083–3086; (b) Yang, X.; Wang, Q.; Tao, Y.; Xu, H.
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Tetrahedron Lett. 2005, 46, 755–758.
5
1
. (a) Paulmier, C. Selenium Reagents and Intermediates in
Organic Synthesis; Pergamon: Oxford, 1985; (b) Chemistry
of Organoselenium and Tellurium Compounds; Patai, S.,
Rappoport, Z., Eds.; John Wiley & Sons: New York,
1
987; (c) Organoselenium Chemistry:
A
Practical
Approach; Back, T. G., Ed.; Oxford University Press:
Oxford, 1999; (d) Topics in Current Chemistry; Wirth, T.,
Ed.; Springer: Heidelberg, 2000; Vol. 208.
2
. (a) Mugesh, G.; Singh, H. B. Chem. Soc. Rev. 2000, 29,
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Rev. 2001, 101, 2125–2179; (c) Malmstrom, J.; Jonsson,
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Schrauzer, G. N. U.S. Pat. Appl. Publ. US 2002197304,
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hedron Lett. 2003, 44, 2257–2260; (b) Bhat, R. G.; Porhiel,
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47–357; (b) Mugesh, G.; du Mont, W.-W.; Sies, H. Chem.
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17. Tipson, R. S. J. Org. Chem. 1944, 9, 235–241.
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X. Org. Prep. Proced. Int. 1995, 27, 492–494; (e) Thomp-
son, D. P.; Boudiouk, P. J. Org. Chem. 1988, 53, 2109–
2112; (f) Barton, D. H. R.; Fontana, G. Tetrahedron 1996,
52, 11163–11176.
2
002. Chem. Abstr. 2003, 138, 44741; (e) Back, T. G.;
Moussa, Z. J. Am. Chem. Soc. 2003, 125, 13455–13460; (f)
W o´ jtowicz, H.; Chojnacka, M.; Młochowski, J.; Palus, J.;
Syper, L.; Hudecowa, D.; Uher, M.; Piasecki, E.; Rybka,
M. Il Farmaco 2003, 58, 1235–1242; (g) Meotti, F. C.;
Stangherlin, G. Z.; Nogueira, C. W.; Rocha, J. B. T.
Environ. Res. 2004, 94, 276–282.
3
4
. (a) Liotta, D.; Zima, G. Tetrahedron Lett. 1978, 21, 4977–
4
980; (b) Diezel, R.; Goulet, S.; Grenier, L.; Bordeleau, J.;
Bernier, J. J. Org. Chem. 1993, 58, 3619–3621; (c) Santi,
C.; Fragale, G.; Wirth, T. Tetrahedron: Asymmetry 1998,
1
19. Spectral data; dimethyl diselenide 11: H NMR (200 MHz,
1
3
9
. (a) Sharpless, K. B.; Lauer, R. F. J. Am. Chem. Soc. 1972,
, 3625–3628.
CDCl
CDCl
3
): d 2.54 (s, 6H, 2 · CH
): d 10.5 (2 · CH ); diisopropyl diselenide 12: H
): d 1.39 (d, 12H, 4 · CH
3
); C NMR (200 MHz,
1
3
3
94, 7154–7155; (b) Reich, H. J. J. Org. Chem. 1975, 40,
2570–2572; (c) Hori, T.; Sharpless, K. B. J. Org. Chem.
1979, 44, 4208–4210; (d) Nishibayashi, Y.; Chiba, T.; Ohe,
NMR (200 MHz, CDCl
J = 7.0 Hz), 3.19 (m, 2H, 2 · CH); C NMR (200 MHz,
CDCl ), 33.5 (2 · CH); di(n-butyl)
): d 24.6 (4 · CH
diselenide 13: H NMR (200 MHz, CDCl ): d 0.92 (t,
6H, 2 · CH , J = 7.2 Hz), 1.45 (m, 4H, 2 · CH ), 1.74 (m,
4H, 2 · CH
(200 MHz, CDCl
(2 · CH ), 33.0 (2 · CH
NMR (200 MHz, CDCl
J = 6.4 Hz), 1.43 (d, 6H, 2 · CH
8H, 4 · CH ), 3.09 (m, 2H, 2 · CH); C NMR (200 MHz,
CDCl ): signals for diastereomers 13.80, 13.80
(2 · CH ), 21.14, 21.16 (2 · CH ), 22.62, 22.72 (2 · CH ),
39.47, 39.49 (2 · CH), 40.01, 40.06 (2 · CH ); diisoamyl
): d 0.91 (d,
, J = 6.2 Hz), 1.63 (m, 6H, 2 · CH, 2 · CH ),
): d
), 40.0
3
3
1
3
3
3
1
K.; Uemura, S. J. Chem. Soc., Chem. Commun. 1995,
´
243–1244; (e) Uzarewicz, A.; Scianowski, J.; B a˛ kowska-
3
1
Janiszewska, J. Pol. J. Chem. 1999, 74, 1791–1796; (f)
3
2
1
3
2
), 2.91 (t, 4H, 2 · CH
): d 13.5 (2 · CH
); di(2-pentyl) diselenide 14: H
): d 0.92 (t, 6H, 2 · CH
, J = 7.0 Hz), 1.57 (m,
2
, J = 7.4 Hz); C NMR
´
Uzarewicz, A.; Scianowski, J.; B a˛ kowska-Janiszewska, J.
Pol. J. Chem. 2000, 74, 1079–1084; (g) B a˛ kowska-Janis-
´
zewska, J.; Scianowski, J.; Uzarewicz, A. Pol. J. Chem.
), 22.5 (2 · CH ), 29.8
3
3
2
1
2
2
3
3
,
2
001, 75, 649–656.
3
1
3
5
6
. (a) Nishibayashi, Y.; Singh, J. D.; Fukazawa, S.; Uemura,
S. J. Chem. Soc., Perkin Trans. 1 1995, 2871–2876; (b)
Tomoda, S.; Iwaoka, M. J. Chem. Soc., Chem. Commun.
2
3
d
3
2
3
1
988, 1283–1284.
2
1
. (a) Fukazawa, S.; Takahashi, K.; Kato, H.; Yamazaki, H.
J. Org. Chem. 1997, 62, 7711–7716; (b) Tiecco, M.;
Testaferri, L.; Bagnoli, L.; Marini, F.; Temperini, A.;
Tomassini, C.; Santi, C. Tetrahedron Lett. 2000, 41, 3241–
diselenide 15: H NMR (200 MHz, CDCl
12H, 4 · CH
2.93 (m, 4H, 2 · CH
22.1 (4 · CH ), 28.0 (2 · CH), 28.1 (2 · CH
3
3
2
1
3
2
); C NMR (200 MHz, CDCl
3
3
2

´
J. Scianowski / Tetrahedron Letters 46 (2005) 3331–3334
3334
1
(
2 · CH
CDCl
): d 0.88, (t,6H, 2 · CH
· CH ), 1.41 (d, 6H, CH , J = 7.0 Hz), 3.05 (m, 2H,
2
); di(2-octyl) diselenide 16: H NMR (200 MHz,
22. Zweifel, G.; Brown, H. C. J. Am. Chem. Soc. 1964, 86,
393–397.
23. Spectral data; diselenide 18: H NMR (200 MHz, CDCl ):
3
3
, J = 6.8 Hz), 1.27 (m, 20H,
1
5
3
3
3
1
3
CH); C NMR (200 MHz, CDCl
2 · CH ), 22.6 (2 · CH ), 27.9 (2 · CH
1.7 (2 · CH ), 37.8 (2 · CH ), 39.8 (2 · CH); dicyclohexyl
diselenide 17: H NMR (200 MHz, CDCl ): d 1.55 (m,
3
): d 14.0 (2 · CH
3
), 22.5
0.92 (d, 2H, J = 8.4 Hz, 2 · CH), 0.99 (s, 6H, 2 · CH
1.19 (s, 6H, 2 · CH ), 1.51 (m, 2H, 2 · CH), 2.00 (m,
10H), 2.36 (m, 4H), 3.01 (m, 4H, 2 · CH
3
),
(
3
3
2
2
), 29.0 (2 · CH
2
),
3
1
3
2
2
2
); C NMR
1
(200 MHz, CDCl ): d 22.6 (2 · CH ), 23.2 (2 · CH ), 26.0
3
3
2
3
1
3
2
0H, 10 · CH
CDCl
): d 25.6 (2 · CH
3.3 (2 · CH).
0. (a) Back, T. G.; Dyck, P. B.; Parvez, M. J. Chem. Soc.,
2
), 3.05 (m, 2H, CH); C NMR (200 MHz,
(2 · CH
2
), 27.9 (2 · CH
3
), 33.2 (2 · CH
2
), 38.0 (2 · CH
2
),
3
2
), 26.9 (4 · CH ), 34.5 (4 · CH ),
2
2
38.6 (2 · C), 41.2 (2 · CH), 41.9 (2 · CH), 46.0 (2 · CH);
77
20
4
Se NMR (200 MHz, CDCl ): d 291.5; ½aꢁ ꢀ87.4 (c
3
D
: C, 55.55; H,
2
10.43, CHCl
7.93%. Found: C, 55.57; H, 8.06%; selenide 22: H NMR
3
); Anal. Calcd for C20
H34Se
2
1
Chem. Commun. 1994, 515–516; (b) Back, T. G.; Dyck, P.
B.; Parvez, M. J. Org. Chem. 1995, 60, 703–710; (c) Back,
T. G.; Dyck, P. B. Chem. Commun. 1996, 2567–2568; (d)
Tiecco, M.; Tastaferri, L.; Santi, C.; Marini, F.; Bagnoli,
L.; Temperini, A. Tetrahedron Lett. 1998, 39, 2809–2812;
(200 MHz, CDCl
3
): d 0.88 (d, 2H, J = 9.4 Hz, 2 · CH),
0.99 (s, 6H, 2 · CH ), 1.19 (s, 6H, 2 · CH ), 1.50 (m, 2H,
3
3
2 · CH), 1.98 (m, 10H), 2.66 (m, 4H), 2.62 (m, 2H,
1
3
2 · CH
23.3 (2 · CH
(2 · CH ), 33.4 (2 · CH ), 38.6 (2 · C), 41.3 (2 · CH),
2
); C NMR (200 MHz, CDCl
3
): d 23.0 (2 · CH
2
),
), 32.2
(
1
e) Back, T. G.; Nan, S. J. Chem. Soc., Perkin Trans. 1
998, 19, 3123–3124; (f) Tiecco, M.; Testaferri, L.; Marini,
3
), 26.2 (2 · CH ), 28.0 (2 · CH
2
3
2
2
7
7
F.; Santi, C.; Bagnoli, L.; Temperini, A. Tetrahedron:
Asymmetry 1999, 10, 747–757; (g) Tiecco, M.; Testaferri,
L.; Santi, C.; Tomassini, C.; Marini, F.; Bagnoli, L.;
Temperini, A. Eur. J. Org. Chem. 2000, 20, 3451–3458; (h)
Kurose, N.; Takahashi, T.; Koizumi, T. J. Org. Chem.
42.1 (2 · CH), 46.4 (2 · CH); Se NMR (200 MHz,
20
D
CDCl
for C H Se: C, 67.96; H, 9.70%. Found: C, 67.95; H,
3
): d 129.1; ½aꢁ ꢀ44.7 (c 9.84, CHCl
3
); Anal. Calcd
2
0
34
1
9.84%; dimyrtanyl 23: H NMR (200 MHz, CDCl ): d
3
0.85 (d, 2H, J = 9.3 Hz, 2 · CH), 0.99 (s, 6H, 2 · CH
3
),
1
996, 61, 2932–2933; (i) Kurose, N.; Takahashi, T.;
1.17 (s, 6H, 2 · CH ), 1.51 (m, 6H), 1.88 (m, 12H), 2.30
3
1
3
Koizumi, T. Tetrahedron 1997, 53, 12115–12130; (j)
Zhang, J.; Takahashi, S.; Saito, S.; Koizumi, T. Tetrahe-
dron: Asymmetry 1998, 18, 3303–3318; (k) Salama, P.;
Bernard, C. Tetrahedron Lett. 1998, 39, 745–748.
(m, 2H); C NMR (200 MHz, CDCl ): d 22.7(2 · CH ),
3
2
23.4 (2 · CH
3
), 26.6 (2 · CH
), 36.11 (2 · CH ), 38.7 (2 · C), 41.6 (2 · CH),
20
2
), 28.3 (2 · CH
3
), 33.8
(2 · CH
2
2
41.7 (2 · CH), 46.4 (2 · CH); ½aꢁ ꢀ45.3 (c 11.49, CHCl
3
);
D
2
1. Brown, H. C.; Lane, C. F. Tetrahedron 1988, 44, 2763–
Anal. Calcd for C H : C, 87.52; H, 12.48%. Found: C,
20 34
2772.
87.60; H, 12.56%.