Electrochemical generation and catalytic use of selenium electrophiles

Article abstract of DOI:10.1055/s-2005-923585

The generation and use of selenium electrophiles in catalytic, electrochemically driven selenenylation-elimination sequences is described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-923585

LETTER
251
Electrochemical Generation and Catalytic Use of Selenium Electrophiles
Electrochemical
G
s
eneration
a
and
U
se of
m
Selenium
E
lectroph
u
iles Niyomura, Matthew Cox, Thomas Wirth*
Cardiff University, School of Chemistry, Park Place, Cardiff CF10 3AT, UK
Fax +44(29)20876968; E-mail: wirth@cf.ac.uk
Received 7 November 2005
featured prominently in the literature.7 Most notably, the
catalytic use of diphenyl diselenide in an oxyselenenyl-
ation–deselenenylation sequence for the conversion of
alkenes 1 into allylic compounds 3 has been reported.8
Herein we describe the application of catalytic amounts of
diphenyl diselenide in electrochemical alkoxyselenenyl-
ation–deselenenylation sequences.
Abstract: The generation and use of selenium electrophiles in
catalytic, electrochemically driven selenenylation–elimination se-
quences is described.
Key words: electrochemistry, electrophilic addition, elimination,
selenium, stereoselective synthesis
Conditions were established for the electrochemical con-
version of alkenes of type 1 with R2 being an acceptor sub-
stituent to the addition–elimination products 3 using 10
mol% diphenyl diselenide in methanol. Tetraethylammo-
nium bromide was employed to act both as a redox cata-
lyst and as an electrolyte. Dry methanol was used as the
solvent and the reaction was carried out using platinum
foil electrodes. Graphite electrodes can be used with
similar efficiency.
Organoselenium compounds are known to be very useful
reagents in organic synthesis.1 The reaction of carbon–
carbon double bonds with selenium electrophiles is per-
formed under mild reaction conditions and the reaction
products can be used in a variety of subsequent function-
alizations. A general protocol for selenenylations of al-
kenes 1 is shown in Scheme 1. Selenide 2 is then oxidized
and, after elimination, compounds 3 are obtained. The use
of enantiomerically pure selenium electrophiles can lead
to addition products in high diastereomeric ratios and to
highly enantiomerically enriched elimination products 3.2
ArSe+Br–
3
1
4
–Nu
ArSe+X–
NuH
Nu
H
Nu
Nu
Oxidation
R1
R2
R1
R2
R1
R2
R1
R2
R1
R2
Br–
SeAr
2
SeAr
Br SeAr
Br
1
3
6
5
Scheme 1 Functionalization of double bonds with selenium electro-
philes and subsequent oxidative elimination
Nu
Br2
R1
R2
SeAr
Due to the necessity to use these reagents in stoichio-
metric quantities in addition reactions to double bonds,
the development of alternative methods is becoming in-
creasingly important. We already developed a series of
polymer-supported selenium electrophiles which allow
easy purification of the addition products (filtration) and,
after cleavage of the reaction products from the solid
support, a recycling of the reagent for the next reaction.3
A superior solution is the development of a protocol using
only catalytic amounts of selenium electrophiles. We4 and
other research groups5 have already reported the use of
peroxodisulfates as oxidants in such reactions, but the
turnover numbers are still small and the amount of
selenium reagent as catalyst relatively high.
2
Scheme 2 Electrochemical oxyselenenylation–elimination of
alkenes
The reaction is initiated by anodic oxidation of bromide to
bromine and subsequent reaction with diaryl diselenide to
form arylselenenyl bromide 4 (Scheme 2). Reagent 4 re-
acts with alkene 1 to form the seleniranium cation 5,
which undergoes reaction with the nucleophile giving se-
lenide 2. The next equivalent of bromine is electrochemi-
cally generated and this reacts with 2 to give the unstable
tetravalent selenenylbromide 6. Elimination of the seleni-
um moiety produces the allylic ether 3 and arylselenenyl
bromide, thus completing the catalytic cycle. In an inde-
pendent reaction we showed that the reaction of 2 with
bromine generates the elimination product 3 and arylsele-
nenyl bromide, which was isolated as diaryl diselenide af-
ter the aqueous work up. The deselenenylation of 2 to 3 is
traditionally achieved by selenoxide elimination.5f Elec-
trochemical eliminations by oxidation of selenides via the
corresponding selenoxides have been described.8
Various transformations of organoselenium compounds
have been performed using electrochemical methods.6
The reaction of a electrochemically generated selenium
electrophile (Ar = Ph) with a variety of substrates has
SYNLETT 2006, No. 2, pp 0251–0254
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1.
0
2.
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Advanced online publication: 23.12.2005
DOI: 10.1055/s-2005-923585; Art ID: D33405ST
© Georg Thieme Verlag Stuttgart · New York

252
O. Niyomura et al.
LETTER
R2
The reaction conditions for the methoxyselenenylation of
1a9 (R1 = Ph, R2 = CO2Me) using 10 mol% diphenyl di-
selenide were optimized.10 At low currents the addition
product 2a was the main product (Table 1, entry 1) and at
very high currents the elimination product 3a11 was fur-
ther oxidized to 7a12 as shown in Scheme 3 and Table 1.
This was also confirmed by an independent experiment
where 3a as a starting material was converted to 7a under
similar high current reaction conditions.
8a: R1 = OMe, R2 = Bz
8b: R1 = OH, R2 = Et
8c: R1 = OEt, R2 = Me
8d: R1 = SEt, R2 = Me
R1
Se)2
Figure 2 Enantiomerically pure diselenides 8
Scheme 1). Diastereoselectivities of up to 96% have been
obtained in the addition products 2.
Catalytic quantities of several enantiomerically pure dise-
lenides 815 were then used in this reaction in place of
diphenyl diselenide. For each diselenide it was necessary
to adjust the conditions to achieve the highest yields. The
functionality present in the side chain R1 of the chiral se-
lenium reagent was the determining factor in optimizing
these conditions. For example, the use of sulfuric acid
proved unsurprisingly incompatible with diselenides con-
taining a methoxymethyl-protected alcohol in the chiral
side chain. Some selected results are shown in Table 2.
OMe
2a
Ph
CO2Me
10 mol% (PhSe)2
Et4NBr (1 equiv)
SeAr
OMe
Ph
CO2Me
3a
7a
MeOH, cat. H2SO4
r.t., electrolysis
Ph
CO2Me
CO2Me
1a
MeO OMe
Ph
Scheme 3 Addition–elimination sequence leading to various pro-
ducts depending on reaction conditions
Table 2 Electrochemical Selenenylation–Elimination Sequence to
Allylic Ether 3aa
Table 1 Addition–Elimination Reaction Using 1a
Entry
1c
8 (R1)
OMe
OH
8 (R2)
Bz
Yield (%) of 3a ee (%) of 3ab
Entry
Current (mA)
Product ratioa 2a:3a:7a:otherb
19:64:0:17
56
29
55
38
18 (S)
44 (S)
5 (S)
1
2
3
4
0.5
3
2c
Et
5:83c:0:12
3d
OEt
Me
Me
10
30
0:46:36:18
4e
SEt
66 (S)
0:10:85d:5
a Conditions: 10 mol% diselenide, cat. H2SO4.
a Determined by 1H NMR.
b Determined by HPLC: Chiracel OD-H, hexane–i-PrOH 98:2, 0.5
mL/min, 254 nm, Rf (R) = 18.3 min, Rf (S) = 20.2 min.
c 20 mol% Et4NBr.
b Other compounds identified as reaction products are methyl
4-phenyl-4-oxo-butanoate and methyl 4-hydroxy-4-phenyl-(E)-but-
2-enoate.
d 10 mol% Et4NBr.
c Isolated yield: 50%.
d Isolated yield: 42%.
e 50 mol% Et4NBr, 5 mol% diselenide.
Traces of sulfuric acid were found to be essential for the
success of this reaction. Previous workers have described
the use of sulfuric acid to prevent the elimination from 2
to 3 from occurring, enabling isolation of the selenide. We
found, however, that while sulfuric acid enhances the rate
and yield of the reaction, it does not prevent the elimina-
tion step proceeding. The increased rate and yield is
probably due to the free proton acting as an excellent
electrolyte.
The use of other nucleophiles in the addition–elimination
sequence led to compounds 3b–d13 in moderate yields. A
replacement of tetraethylammonium bromide with ammo-
nium peroxodisulfate was only advantageous when using
acetic acid as nucleophile in the synthesis of 3e
(Figure 1).14
3b (40% conversion)
3c (62% yield by NMR)
3d (48%)
R = H
R = Et
R = i-Pr
OR
Ph
CO2Me
R = Ac 3e (49%)
The effect of various electrolytes in place of sulfuric acid
on this reaction was studied in order to overcome the acid
dependence, but neither tetraethylammonium hexafluoro-
phosphate, tetraethylammonium tetrafluoroborate nor an
excess of tetraethylammonium bromide proved as effec-
tive as sulfuric acid using enantiomerically pure dise-
lenides 8. Previous workers have used a range of salts to
prevent disproportionation of phenylselenenic acid into
the inert phenylseleninic acid, leading to enhanced yields.
We have found that the use of these salts (MgSO4, CaSO4
and Na2SO4) has no effect on the above reactions other
than to increase the reaction times. The use of tetraethyl-
Figure 1 Addition–elimination products 3 using different nucleo-
philes
The development of organoselenium reagents for asym-
metric synthesis has produced a range of chiral reagents
such as diselenides, which are efficient in the transfer of
chiral information.2 Enantiomerically pure selenium elec-
trophiles, easily prepared from the corresponding dise-
lenides of type 8 (Figure 2), have proven themselves as
powerful reagents for the stereoselective functionalization
of non-activated carbon–carbon double bonds (1 → 2,
Synlett 2006, No. 2, 251–254 © Thieme Stuttgart · New York

LETTER
Electrochemical Generation and Use of Selenium Electrophiles
253
ammonium chloride and tetraethylammonium iodide has phenylpropane23 or, in the presence of a bromide source,
also been investigated in a variety of different conditions 2-bromo-1-methoxy-1-phenylpropane.24 We conclude
but yields were lower than with tetraethylammonium that the oxidation potential of b-methyl styrene is too low
bromide.
to enable the selective oxidation of either the diselenide or
a redox catalyst.
The restriction on temperature imposed by the electro-
chemical approach accounts for the low selectivities when Work is currently underway to broaden the scope of this
selenium reagents optimized for much lower temperatures reaction by the development of efficient chiral selenium
are employed. Varying the amount of tetraethylammoni- reagents optimized for room temperature reactions. We
um bromide had no effect on selectivity. In the absence of were able to demonstrate the catalytic use of chiral di-
any tetraethylammonium bromide, the increased cell po- selenides in an electrochemical selenenylation–deselene-
tential required for the direct oxidation of the diselenide nylation sequence.
resulted in a multitude of side reactions. Highest selectiv-
ities are obtained with a sulfur-containing diselenide
(Table 2, entry 4) leading to product 3a in 66% ee. This is
Acknowledgment
We thank Prof. R. Breinbauer, University of Leipzig, Germany, for
fruitful discussions and for graphite electrodes. We thank the Royal
Society for a fellowship (O.N.), EPSRC for support and the
National Mass Spectrometry Service Centre, Swansea, for mass
spectrometric data.
in agreement with the results using similar sulfur-contain-
ing selenium electrophiles reported recently by Tiecco et
al.5e These results are quite remarkable as the diselenides
investigated previously that have been designed for low-
temperature reactions but the electrochemical reactions
are performed at room temperature.
References and Notes
OMe
(1) Organoselenium Chemistry, In Top. Curr. Chem., Vol. 208;
Wirth, T., Ed.; Springer: Berlin, 2000.
3f
electrolysis
Ph
CN
Ph
CN
(2) (a) Wirth, T. Angew. Chem. Int. Ed. 2000, 39, 3742.
(b) Tiecco, M. Top. Curr. Chem. 2000, 208, 55.
(3) (a) Uehlin, L.; Wirth, T. Chimia 2001, 55, 65. (b) Uehlin,
L.; Wirth, T. Org. Lett. 2001, 3, 189.
(4) Wirth, T.; Häuptli, S.; Leuenberger, M. Tetrahedron:
Asymmetry 1998, 9, 547.
MeO OMe
1b
7b
Ph
CN
O
O
Ph
2b
electrolysis
(5) (a) Iwaoka, M.; Tomoda, S. J. Chem. Soc., Chem. Commun.
1992, 1165. (b) Fujita, K.; Iwaoka, M.; Tomoda, S. Chem.
Lett. 1994, 923. (c) Fukuzawa, S.; Takahashi, K.; Kato, H.;
Yamazaki, H. J. Org. Chem. 1997, 62, 7711. (d) Tiecco,
M.; Testaferri, L.; Santi, C.; Tomassini, C.; Marini, F.;
Bagnoli, L.; Temperini, A. Tetrahedron: Asymmetry 2000,
11, 4645. (e) Tiecco, M.; Testaferri, L.; Santi, C.;
Tomassini, C.; Marini, F.; Bagnoli, L.; Temperini, A.
Chem.–Eur. J. 2002, 8, 1118. (f) Nishibayashi, Y.; Uemura,
S. Top. Curr. Chem. 2000, 208, 201.
(6) (a) Inokuchi, T.; Kusomoto, M.; Torii, S. J. Org. Chem.
1990, 55, 1548. (b) Suriwiec, K.; Fuchigami, T. J. Org.
Chem. 1992, 57, 5781. (c) Smith, D. S.; Winnick, J.; Ding,
Y.; Bottomley, L. Electrochim. Acta 1998, 43, 335.
(7) (a) Torii, S.; Uneyama, K.; Ono, M. Tetrahedron Lett. 1980,
21, 2653. (b) Torii, S.; Uneyama, K.; Handa, K.
Tetrahedron Lett. 1980, 21, 1863. (c) Bewick, A.; Coe, D.
E.; Fuller, G. B.; Mellor, J. M. Tetrahedron Lett. 1980, 21,
3827. (d) Torii, S.; Uneyama, K.; Takano, K. Tetrahedron
Lett. 1982, 23, 1161. (e) Konstantinovic, S.; Vukicevic, R.;
Mihailovic, M. L. Tetrahedron Lett. 1987, 28, 6511.
(8) Torii, S.; Uneyama, K.; Ono, M. J. Am. Chem. Soc. 1981,
103, 4606.
PhSe
O
Ph
CO2H
O
Ph
O
Ph
O
1c
9
10
Scheme 4 Catalytic electrochemical reactions of other alkenes
Other alkenes have also been investigated in the addition–
elimination sequence. Compound 1b16 (R1 = Ph,
R2 = CN) and 1c5e (R1 = Ph, R2 = CO2H) were subjected
to similar reaction conditions and the formation of com-
pounds 3f/7b and 2b/9/10 was observed (Scheme 4).
The expected methoxyselenenylation–elimination com-
pound 3f17 was formed in 50% yield and at higher currents
(30 mA), the corresponding dimethoxylated product 7b18
was isolated in 43% yield. Cyclizations were studied us-
ing 1c as substrate. After initial formation of 2b,19 elimi-
nation to 5-phenylfuran-2(3H)-one (9)20 together with
small amounts of 5-phenylfuran-2(5H)-one (10,21 ratio
9:10 = 85:15) was observed by using tetraethylammoni-
um bromide in acetonitrile. The use of acetonitrile–meth-
anol (40:1) as solvent mixture and ammonium
peroxodisulfate instead of tetraethylammonium bromide
allowed a complete suppression of the formation of 9 and
only 10 was isolated in 32% yield.
b-Methyl styrene 1 (R1 = Ph, R2 = H) has also been used
in this reaction. The catalytic use of diphenyl diselenide
produces allylic ether 322 (R1 = Ph, R2 = H, Nu = OMe)
in low yields, with most of the b-methyl styrene under-
going direct transformation to 1,2-dimethoxy-1-
(9) Hoye, T. R.; Richardson, W. S. J. Org. Chem. 1989, 54, 668.
(10) Typical Experimental Procedure.
The alkene (0.1 mmol) was dissolved in MeOH (7 mL) and
tetraethylammonium bromide (0.1 mmol), diselenide (0.01
mmol) and H2SO4 (1 mL) were added. The electrodes were
inserted into the reaction mixture and constant current of 3
mA applied. After 6 h, electrolysis was stopped and the
MeOH removed in vacuo. The mixture was dissolved in
Et2O, washed with NaHCO3 solution and H2O before drying
over MgSO4. The products were purified by preparative
TLC or column chromatography.
Synlett 2006, No. 2, 251–254 © Thieme Stuttgart · New York

254
O. Niyomura et al.
LETTER
(15) Diselenides 8 were synthesized according to literature
(11) Pak, C. S.; Lee, E.; Lee, G. H. J. Org. Chem. 1993, 58, 1523.
(12) Spectroscopic data for 7a: 1H NMR (400 MHz, CDCl3):
d = 3.12 (s, 6 H), 3.65 (s, 3 H), 6.24 (d, J = 15.7 Hz, 1 H),
6.73 (d, J = 15.7 Hz, 1 H), 7.20–7.28 (m, 3 H), 7.38–7.40 (m,
2 H) ppm. 13C NMR (100 MHz, CDCl3): d = 49.7, 51.7,
100.9, 122.0, 126.9, 128.31, 128.33, 139.0, 147.8, 166.7
ppm. IR (NaCl): n = 2950, 2832, 1727, 1659, 1449, 1436,
1304, 1276, 1192, 1167, 1072, 1046, 988, 700 cm–1. HRMS:
m/z calcd for C13H16O4: 259.0941; found: 259.0941.
procedures: (a) Compounds 8a,c: Wirth, T.; Fragale, G.
Chem.–Eur. J. 1997, 3, 1894. (b) Compound 8b: Uehlin, L.;
Fragale, G.; Wirth, T. Chem.–Eur. J. 2002, 8, 1125. (c) For
compound 8d see ref. 5e.
(16) Prepared by reaction of phenyl acetaldehyde and
cyanoacetic acid. Spectroscopic data: Tsuji, Y.; Yamada, N.;
Tanaka, S. J. Org. Chem. 1993, 58, 16.
(17) Keinan, E.; Sahai, M.; Roth, Z.; Nudelman, A.; Herzig, J. J.
Org. Chem. 1985, 50, 3558.
(13) Spectroscopic data for 3d: 1H NMR (400 MHz, CDCl3):
d = 1.07 (d, J = 6.1 Hz, 3 H), 1.13 (d, J = 6.1 Hz, 3 H), 3.57
(sept, J = 6.1 Hz, 1 H), 3.64 (s, 3 H), 4.95 (dd, J = 5.4, 1.4
Hz, 1 H), 6.02 (dd, J = 15.6, 1.4 Hz, 1 H), 6.91 (dd, J = 15.6,
5.4 Hz, 1 H), 7.19–7.30 (m, 5 H) ppm. 13C NMR (100 MHz,
CDCl3): d = 21.8, 22.6, 51.6, 69.5, 77.8, 120.1, 127.3, 128.0,
128.7, 140.0, 148.8, 166.9 ppm. IR (NaCl): n = 2971, 1725,
1659, 1453, 1435, 1298, 1272, 1167, 1120, 978, 699 cm–1.
HRMS: m/z calcd for C14H18O3: 252.1594; found: 252.1593.
(14) Spectroscopic data for 3e: 1H NMR (400 MHz, CDCl3):
d = 2.06 (s, 3 H), 3.67 (s, 3 H), 5.97 (dd, J = 15.7, 1.5 Hz, 1
H), 6.32 (dd, J = 5.0, 1.5 Hz, 1 H), 6.95 (dd, J = 15.7, 5.0 Hz,
1 H), 7.27–7.31 (m, 5 H). 13C NMR (100 MHz, CDCl3): d =
21.1, 51.8, 74.2, 121.2, 127.4, 128.83, 128.86, 137.1, 144.9,
166.4, 169.7. IR (NaCl): n = 2952, 2918, 2849, 1738, 1727,
1662, 1436, 1372, 1310, 1279, 1228, 1197, 1171, 1069,
1022, 980, 699 cm–1. HRMS: m/z calcd for C13H14O4:
252.1230; found: 252.1229.
(18) Spectroscopic data for 7b: 1H NMR (400 MHz, CDCl3):
d = 3.11 (s, 6 H), 5.85 (d, J = 16.2 Hz, 1 H), 6.43 (d, J = 16.2
Hz, 1 H), 7.25–7.38 (m, 5 H) ppm. 13C NMR (100 MHz,
CDCl3): d = 49.8, 100.2, 101.4, 116.8, 126.9, 128.6, 128.8,
137.8, 154.0 ppm. IR (NaCl): n = 2916, 2848, 2228, 1732,
1450, 1261, 1226, 1191, 1159, 1071, 1047, 972, 774, 746,
702 cm–1. HRMS: m/z calcd for C12H13NO2: 221.1285;
found: 221.1283.
(19) Tiecco, M.; Testaferri, L.; Temperini, A.; Bagnoli, L.;
Marini, F.; Santi, C. Synlett 2001, 1767.
(20) Knochel, P.; Rao, C. J. Tetrahedron 1993, 49, 29.
(21) Renard, M.; Ghosez, L. A. Tetrahedron 2001, 57, 2597.
(22) Fukuzawa, S.; Takahashi, K.; Kato, H.; Yamazaki, H. J.
Org. Chem. 1997, 62, 7711.
(23) Hassner, A.; Reuss, R. H. J. Org. Chem. 1974, 39, 553.
(24) Ruasse, M. F.; Argile, A.; Dubois, J. E. J. Am. Chem. Soc.
1978, 100, 7645.
Synlett 2006, No. 2, 251–254 © Thieme Stuttgart · New York