New nitrogen containing chiral diselenides: Synthesis and asymmetric addition reactions to olefins

Article abstract of DOI:10.1016/S0957-4166(00)00469-9

A simple synthesis of two new nitrogen containing diselenides, 7 and 8, is described. These compounds were employed as starting materials to effect the asymmetric methoxyselenenylation, the hydroxyselenenylation as well as the cyclofunctionalization of ol

Full text of DOI:10.1016/S0957-4166(00)00469-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 4645–4650
New nitrogen containing chiral diselenides: synthesis and
asymmetric addition reactions to olefins
Marcello Tiecco,* Lorenzo Testaferri, Claudio Santi, Cristina Tomassini, Francesca Marini,
Luana Bagnoli and Andrea Temperini
Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica, Universita` di Perugia,
I-06123 Perugia, Italy
Received 6 November 2000; accepted 20 November 2000
Abstract
A simple synthesis of two new nitrogen containing diselenides, 7 and 8, is described. These compounds
were employed as starting materials to effect the asymmetric methoxyselenenylation, the hydroxyselenenyl-
ation as well as the cyclofunctionalization of olefins. Starting from 7 all these addition processes occurred
with good facial selectivity. Poor results were however obtained with 8. One-pot selenenylation–elimina-
tion sequences using catalytic amounts of the diselenide 7 have also been investigated. © 2001 Published
by Elsevier Science Ltd.
Organoselenium reagents are widely used in organic synthesis to introduce new functional
groups into organic substrates under very mild experimental conditions.1 In recent years, several
research groups have described the synthesis of a number of chiral non-racemic diselenides
which can be transformed in situ into electrophilic selenenylating agents to effect efficient
asymmetric syntheses.2–7 Diselenides containing a nitrogen atom in the chiral moiety have also
been employed as useful ligands in various transformations such as diethylzinc additions to
aldehydes,8 asymmetric hydrosilylation9 and transfer hydrogenation reactions.10 Moreover, these
diselenides can also be employed in the sequential catalytic stereoselective oxyselenenylation–
elimination reactions using ammonium persulfate to generate the electrophilic selenenylating
species and to promote the elimination process.4c
Herein we report the synthesis of two new chiral nitrogen containing diselenides and the use
of these compounds as precursors of electrophilic species in asymmetric additions of organo-
selenium reagents to olefins.
The condensation of the commercially available compounds 1 and 2 (Scheme 1) readily
afforded the intermediate 3 which was reduced with sodium triacetoxyborohydride in acetic acid
* Corresponding author. Tel: +39 075 5855100; fax: +39 075 5855116; e-mail: tiecco@unipg.it
0957-4166/00/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0957-4166(00)00469-9

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M. Tiecco et al. / Tetrahedron: Asymmetry 11 (2000) 4645–4650
Scheme 1.
at −78°C to give a 9:1 mixture of the diastereomeric chiral secondary amines 4. The mixture of
4 was refluxed with formic acid and formaldehyde and was thus quantitatively converted into
the amines 5 and 6. The two compounds were separated by flash chromatography and
independently transformed into the corresponding diselenides 711 and 812 by treatment with
t-BuLi and elemental selenium. The absolute configuration of the stereogenic carbon atom
generated during the reduction was assigned on the basis of the observation that the debromina-
tion of 6 (t-BuLi, water) afforded the corresponding meso derivative.
Diselenides 7 and 8 were employed to effect asymmetric addition reactions to olefins.
Preliminary experiments were carried out in the methoxyselenenylation and hydroxyselenenyla-
tion of styrene. As indicated in Scheme 2, the two sets of experiments gave the addition products
9a–10a and 11a–12a, respectively. From the data collected in Table 1 it can be seen that, using
ammonium persulfate as the oxidizing agent and working at room temperature, the diselenide 7
(entries 1 and 4) gave higher diastereomeric ratios than 8 (entries 2 and 5). No substantial
differences were observed when the reactions were run at −78°C using the triflate as the counter
ion (entries 3 and 6).
Scheme 2.

M. Tiecco et al. / Tetrahedron: Asymmetry 11 (2000) 4645–4650
4647
Table 1
Methoxyselenenylation and hydroxyselenenylation of styrene promoted by the diselenides 7 and 8
Entry
Diselenide
ROH
X
T (°C)
Products
Yield (%)
d.r.
Abs. conf.
1
2
3
4
5
6
7
8
7
7
8
7
CH3OH
CH3OH
CH3OH
H2O
H2O
H2O
OSO3H
OSO3H
OTf
OSO3H
OSO3H
OTf
25
25
−78
25
25
−78
9a
11a
9a
10a
12a
10a
70
72
40
70
72
40
95:5
81:19
97:3
95:5
80:20
98:2
R
S
R
R
S
R
The absolute configuration of compounds 9a and 11a was established by reductive deselenenyla-
tion with triphenyltin hydride and AIBN in refluxing benzene. As indicated in Scheme 3,
compound 9a gave the chiral ether (+)-(R)-methoxyphenylethane 13 and compound 11a gave
(−)-(S)-methoxyphenylethane 14. As expected, the enantiomeric excesses of 13 and 14 corre-
sponded to the diastereomeric ratios in 9a and 11a, respectively.
Scheme 3.
On the basis of the results of the preliminary experiments described above, the selenomethoxyl-
ation and selenohydroxylation reactions of several alkenes were carried out using the diselenide
7 under the experimental conditions described in Table 1 (entries 1 and 4). The results obtained
from these experiments are collected in Table 2. In a typical experiment ammonium persulfate
and trifluoromethanesulfonic acid were added to a stirred solution of the diselenide 7 in diethyl
ether. The mixture was stirred at room temperature for 15 minutes and then a solution of the
Table 2
Selenoaddition reactions using the diselenide 7
Entry
Substrate
ROH
X
T (°C)
Products
Yield (%)
d.r.
1
2
3
4
5
b-Methyl-styrene
b-Methyl-styrene
2%,4%,6%-Trimethyl-styrene
E-5-Decene
CH3OH OSO3H
H2O OSO3H
CH3OH OSO3H
CH3OH OSO3H
CH3OH OSO3H
25
25
25
25
25
9b
10b
9c
9d
9e
80
82
60
79
55
95:5
81:19
95:5
92:8
75:25
Cyclohexene

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M. Tiecco et al. / Tetrahedron: Asymmetry 11 (2000) 4645–4650
alkene in methanol (entries 1, 3, 4, 5) or in a 1:1 mixture of acetonitrile and water (entry 2)
was added. Stirring was continued for 60 h. The results reported in Table 2 indicate that
satisfactory to good chemical yields were obtained in every case. Good facial selectivities
were observed in the case of the methoxyselenenylation reactions with the exception of the
reaction carried out with cyclohexene. As observed in previous cases13 the hydroxyselenenyla-
tion reactions gave poorer results.
The efficiency of diselenide 7 was also tested in the case of cyclofunctionalization pro-
cesses. For this purpose the E-3-alkenols 15 and 16 (Scheme 4) were treated with a stoichio-
metric amount of selenenylating agent prepared from 7 as described above in a 3:1 mixture
of diethyl ether and methanol. The nucleophilic solvent did not compete with the intramolec-
ular process and only the tetrahydrofurans 17 and 18 were isolated as the reaction products.
Good chemical yields and facial selectivities were observed.
Scheme 4.
Finally, further use of the diselenide 7 is illustrated in Scheme 5. Ammonium persulfate
and the diselenide 7 were employed to effect the catalytic one-pot conversion of the b,g-
unsaturated ester 19 into the allylic ether 20 according to our recently described selenenyla-
tion–elimination procedure.14 The results of these experiments are reported in Table 3. The
reaction was first carried out in diethyl ether and methanol (2:1) in the presence of tri-
fluoromethanesulfonic acid using stoichiometric (entry 1) and catalytic (entry 2) amounts of 7
and an excess of ammonium persulfate. Under these conditions conversion rates were very
low. However, in both cases excellent facial selectivities were observed (94% ee). The reaction
was repeated using a stoichiometric amount of nickel(II) nitrate as additive (entry 3). In this
case the conversion rate was considerably increased but the enantioselectivity was very poor
(45% ee). The facial selectivity observed in the present case is considerably higher than that
obtained with the use of camphor selenenyl sulfate.15 Reaction times, however, were much
longer. Further investigations are presently under way to improve the results of this one-pot
selenenylation–elimination sequence.

M. Tiecco et al. / Tetrahedron: Asymmetry 11 (2000) 4645–4650
4649
Scheme 5.
Table 3
One-pot conversion of the b,g-unsaturated ester 19 into the allylic ether 20
Entry
% of 7
Additive
T (°C)
Reaction time (days)
Yield (%)
Ee (%)
1
2
100
10
None
None
25
25
26
42
110
4
50
12
50
50
94
94
94
45
3
10
Ni(NO3)2
25
Acknowledgements
Financial support from MURST, National Project ‘Stereoselezione in Sintesi Organica.
Metodologie e Applicazioni’, the University of Perugia, Progetti di Ateneo, and CNR, Rome is
gratefully acknowledged.
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11. Selected physical and spectroscopic data of diselenide 7: oil, [h]2D4 −7.54 (c 1.5, CHCl3); H NMR l 7.85 (dd, 1H,
J=1.9 and 8.0 Hz), 7.4–7.9 (m, 9H), 4.21 (q, 1H, J=6.6 Hz), 3.8 (q, 1H, J=7.1 Hz), 2.0 (s, 3H), 1.58 (d, 3H,
J=7.1 Hz), 1.35 (d, 3H, J=6.6 Hz); 13C NMR l 144.2, 142.7, 133.1, 131.7, 128.1, 128.0, 127.6, 126.9, 126.8,
125.9, 60.2, 59.7, 31.9, 18.6, 13.7; 77Se NMR l 623.7. GC–MS m/z (relative intensity): 634 (1), 428 (49), 270 (45),
197 (82), 171 (100), 155 (47), 117 (49), 83 (25), 77 (46), 55 (16). Anal. calcd for C34H40N2Se: C, 64.36; H, 6.35;
N, 4.42. Found: C, 64.83; H, 6.50; N, 4.35.
1
12. Selected physical and spectroscopic data of diselenide 8: oil, [h]2D9 +1.53 (c 2.5, CHCl3); H NMR l 7.8 (dd, 1H,
J=1.2 and 7.8 Hz), 7.4–7.9 (m, 5H), 7.1 (dt, 1H, J=1.2 and 7.8 Hz), 7.15 (dt, 1H, J=1.3 and 7.8 Hz), 4.1 (q,
1H, J=6.6 Hz), 3.9 (q, 1H, J=6.7 Hz), 2.3 (s, 3H), 1.42 (d, 3H, J=6.7 Hz), 1.39 (d, 3H, J=6.6 Hz); 13C NMR
l 145.5, 143.7, 132.4, 131.9, 129.0, 128.8, 128.4, 128.0, 127.2, 126.8, 61.7, 58.6, 33.9, 17.1, 16.5; 77Se NMR l
626.1. Anal. calcd for C34H40N2Se: C, 64.36; H, 6.35; N, 4.42. Found: C, 64.48; H, 6.22; N, 4.55.
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