Asymmetric selenocyclization with the use of dialkyl monoterpene diselenides

Article abstract of DOI:10.1016/j.tetasy.2007.11.032

Selenocyclization with the use of the monoterpene diselenides from menthane, carane and pinane groups has been studied. The conditions for asymmetric selenocyclization have been optimized. It has been established that the best enantiomeric excesses were o

Full text of DOI:10.1016/j.tetasy.2007.11.032

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 223–230
Asymmetric selenocyclization with the use of
dialkyl monoterpene diselenides
´
*
´
Zbigniew Rafinski, Jacek Scianowski and Andrzej Wojtczak
Department of Chemistry, Nicolaus Copernicus University, 7 Gagarin Street, 87-100 Torun, Poland
Received 21 November 2007; accepted 27 November 2007
Available online 21 December 2007
Abstract—Selenocyclization with the use of the monoterpene diselenides from menthane, carane and pinane groups has been studied.
The conditions for asymmetric selenocyclization have been optimized. It has been established that the best enantiomeric excesses were
obtained in the case of selenocyclization for the unsubstituted alkyl diselenides with (+)-dineomenthyl diselenide. The results of the seleno-
cyclization of the (+)-dineomenthyl diselenide with the unsaturated alcohols and acids are presented.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
double bond takes place. During the second step, the intra-
molecular addition of the nucleophile leading to the respec-
tive heterocyclic system is observed (Scheme 1).
There is increasing interest in the use of selenoorganic
reagents in organic synthesis, which is a consequence of
the fact that their reactions can be carried out under mild
experimental conditions. Another advantage of selenium-
containing groups is their compatibility with most func-
tional groups existing in organic molecules.1–4
In our previous papers we described a convenient method
for the synthesis of optically active monocyclic and bicyclic
terpene diselenides. Diselenide derivatives of menthanes 1
and 2, caranes 3 and 4 and pinane 5–7 groups were
obtained in a reaction of sododiselenide with alkyl tosy-
lates and chlorides (Fig. 1). These optically active disele-
nides have been used in asymmetric additions to a double
bond.10
In recent years the procedures for using selenoorganic com-
pounds in asymmetric syntheses have become of special
interest.5–8 Among them, optically active diselenides have
been especially studied. Hitherto, investigations in this
group of compounds have been focused on finding conve-
nient methods for the synthesis of optically active disele-
nides, as well as on their use in asymmetric synthesis.9–11
Optically active diselenides have been employed as electro-
philes in the asymmetric addition to a double bond with the
formation of new carbon–oxygen, carbon–nitrogen, or car-
bon–carbon bonds.5
Herein we report the influence of the structures of non-
substituted optically active monoterpene diselenides 1–7
on the diastereomeric excesses of the products of the
selenocyclization reactions. Until now, the influence of
the reagent structure on the diastereomeric excess of the
selenocyclization reaction products for the optically
active non-functionalized dialkyl diselenides has not been
studied.
Cyclization reactions with the use of selenoorganic com-
pounds have been widely employed. Many optically active
heterocyclic compounds have been obtained with the use
of chiral selenoorganic compounds.12 Selenocyclizations
using optically active diselenides proceed as a two-stage
process. In the first step of the reaction, addition of the
selenium electrophile obtained from the diselenide to a
2. Result and discussion
The first stage in our research of the selenocyclization reac-
tion of optically active dialkyl diselenides was the optimiza-
tion of the reaction conditions.
*
The optimisation was carried out using (+)-dineomenthyl
Corresponding author. Tel.: +48 56 6114532; fax: +48 56 6542477;
e-mail: jsch@chem.uni.torun.pl
diselenide 1 in the reaction with o-allylphenol 8 (Scheme 2).
0957-4166/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.11.032

224
Z. Rafin´ski et al. / Tetrahedron: Asymmetry 19 (2008) 223–230
AgX
1M Br2, CCl4
Ar*Se X
Ar*Se Br
Ar*SeSeAr*
X = OTf, PF6, SbF6, BF4
R1
R3
SeAr*
R2
Ar*
Se
Nu
endo
exo
R1
R3
R2
Ar*Se
_
R1
R3
R2
H
*ArSe
R2
Nu
HNu
R1
R3
Nu
R1,2,3 = alkyl, aryl
Scheme 1. The mechanism of the selenocyclization reaction.
bromide counterions and 7 h for the triflate or tetrafluo-
roborane counterions.
Se)
Se)
2
2
Modification of the counterions and the reaction time
indicated that the best diastereomeric ratio (70:30) for
dineomenthyl diselenide 1 was obtained with a triflate
counterion in the presence of the 2.5% addition of metha-
nol for 7 h (Table 1).
Se)
Se)
2
2
4
3
2
6
1
Se)
2
Table 1. Optimization of selenocyclization conditions with (+)-dineomen-
thyl diselenide 1
Se)
Se)
2
2
Entry Counterion Time [h] Additive
dra
Yield [%]
1
2
3
4
5
Brꢀ
2
2
7
7
7
—
—
60:40 89
60:40 73
7
5
Clꢀ
OTfꢀ
OTfꢀꢀ
BF4
2.5% MeOH 70:30 23
2.5% AcOH 70:30 19
2.5% MeOH 62:38 63
Figure 1. Optically active terpene diselenides.
a dr was estimated on the basis of 1H NMR spectra.
The respective selenium electrophiles were obtained by the
addition of bromine or sulfuryl chloride to a solution of
diselenide 1. We also investigated the possibility of using
the triflate and tetrafluoroborane counterions obtained in
the reaction of selenoneomenthyl bromide with the corre-
sponding silver salts. A 2.5% additive of methanol or acetic
acid was used to dissolve the silver salts. The selenocycliza-
tion reactions were conducted for 2 h for the chloride or
The main, enantiomerically pure product 9 was isolated
from a diastereomeric mixture (70:30) by crystallization
from n-pentane. The structure of 9 was confirmed on the
1
basis of the H and 13C NMR spectra and X-ray structure
analysis13 (Fig. 2).
Substrate
HO
CH2Cl2, -78 °C
8
*
Se)
CH2Cl2, -78 °C
2
SeX
Se
O
1
Substrates
Counterion
Br -
9
1. 1M Br2 in CCl
2. SO2Cl2
Cl -
3. 1M Br2 in CCl4, AgOTf in MeOH
4. 1M Br2 in CCl4, AgBF4 in MeOH
OTf -
-
BF4
Scheme 2. Selenocyclization reaction with the use of (+)-dineomenthyl diselenide 1.

Z. Rafin´ski et al. / Tetrahedron: Asymmetry 19 (2008) 223–230
225
Figure 2. The molecule of (R)-2-(((1S,2S,5R)-2-isopropyl-5-methylcyclohexylselanyl)methyl)-2,3-dihydrobenzofuran 9.
Table 2. Optimization of the selenocyclization conditions with the use of
(ꢀ)-dimenthyl diselenide 2
The absolute configuration, as determined by the Flack
method,14 the Flack x = 0.14(5), was (2R,10S,20S,50R). A
comparison to the known absolute configuration of C10,
C50 and C2010 confirmed the correct solution. Selected dis-
Entry Counterion Time [h] Additive
dra
Yield [%]
1
2
3
4
5
Brꢀ
2
2
2
7
7
—
—
55:45 86
54:46 97
0
˚
Clꢀ
tances are Se(1)–C(9) 1.957(15), Se(1)–C(1 ) 2.005(12) A
and C(9)–Se(1)–C(10) and the angle C(9)–Se(1)–C(10) is
95.8(6)°. Torsion angles describing the molecule conforma-
tion: C(3)–C(2)–C(9)–Se(1) 68.0(16)°, C(2)–C(9)–Se(1)–
C(10) 87.0(12)°, C(9)–Se(1)–C(10)–C(60) 79.0(11)°. The
cyclohexyl ring of the neomenthyl moiety has a chair con-
formation. The 2,3-dihydrobenzofurane ring is planar, the
OTfꢀ
OTfꢀꢀ
BF4
2.5% MeOH 63:37 32
2.5% MeOH 63:37 77
2.5% MeOH 60:40 62
a dr was estimated on the basis of 1H NMR spectra.
˚
rms deviation from the best plane being 0.021 A.
of o-allylphenol 8, the best diastereomeric excess dr 70:30
was obtained for (+)-dineomenthyl diselenide 1 (Table 3).
To confirm the choice of the selenocyclization conditions,
we carried out an analogous optimization using (ꢀ)-dimen-
thyl diselenide 2 (Scheme 3).
Table 3. Asymmetric selenocyclization with the use of alkyl terpene
diselenides
Alkene
Diselenide Product
dra
Yield
[%]
HO
1
2
3
9
70:30 57
8
10 63:37 92
11 52:48 55
12 52:48 64
13 52:48 87
14 65:35 59
15 52:48 83
*
CH2Cl2, -78 °C
SeX
Se
10
*
O
4
O
TerSe
HO
X
2
5
1. Br -
2. Cl -
3. OTf -
8
9-15
6
7
-
a dr was estimated on the basis of 1H NMR spectra; Ter—terpene moiety.
4. BF4
Scheme 3. Selenocyclization reaction with the use of (ꢀ)-dimenthyl
diselenide 2.
(+)-Dineomenthyl diselenide 1 has been used as a precur-
sor for further investigations upon selenocyclization reac-
tions with unsaturated acids 16–18 and alcohols 19–22
(Table 4). The transformations were carried out at
ꢀ78 °C using the triflate ion as a counterion. The respective
lactones 23–25 and cyclic ethers 26–29 were the products of
this selenocyclization. An increase in the reaction tempera-
ture to 30 °C and long time of the reaction (24 h) were nec-
essary for compound 20. It is known that Z-disubstituted
alkenes tend to react very slowly in selenocyclizations reac-
tions to compare with E-disubstituted alkenes.15
The best diastereomeric excesses for product 10 formed
from (ꢀ)-dimenthyl diselenide were also obtained for the
reaction carried out with the addition of triflate anion in
2.5% MeOH over 7 h (Table 2).
˚
The addition of molecular sieves 4 A increased the yield
of the selenocyclization reaction from 23% to 57% for
(+)-dineomenthyl diselenide 1 and from 77% to 92% for
(ꢀ)-dimenthyl diselenide 2. By employing the optimized
reactions conditions, we conducted the selenocyclization
reactions for optically active dialkyl diselenides 1–7, thus
obtaining the respective cyclic ethers 9–15. For the reaction
The cyclization products have been isolated by a column
chromatography and their structure was confirmed by

226
Z. Rafin´ski et al. / Tetrahedron: Asymmetry 19 (2008) 223–230
Table 4. The results of the selenocyclization reaction of unsaturated acid and alcohols with the use of (+)-dineomenthyl diselenide 1
Alkene
Producta
SeNm
Temp. [°C]
Time [h]
drb
Yield [%]
O
ꢀ78
ꢀ30
0
7
3
3
—
52:48
52:48
—
18
21
O
OH
O
16
23
NmSe
O
ꢀ78
7
63:37
17
OH
Et
O
O
24
17
OH
NmSe
*
ꢀ78
ꢀ78
7
7
65:35
68:32
87
72
O
O
O
18
O
25
NmSe
OH
OH
*
19
26
NmSe
Et
ꢀ78
0
30
30
7
3
3
—
—
—
56:44
—
—
—
12
20
O
24
27
NmSe
Et
OH
ꢀ78
7
77:23
56:44
29
50
21
O
28
NmSe
OH
ꢀ78
7
O
29
22
a Nm—neomenthyl moiety; the stereochemistry of the main diastereomers have not been determined.
b dr was estimated on the basis of 1H and 77Se NMR spectra.
means of the 1H, 13C and 77Se NMR spectra. The diastereo-
4. Experimental
meric excess of the product was estimated on the basis of
1
the H and 77Se NMR spectra analysis. The best result
4.1. General
77:23 was achieved for compound 28.
Melting points were measured with a Buchi Tottoli SPM-
¨
20 heating unit and are uncorrected. NMR spectra were
recorded on Bruker AM-300 at 300 MHz or Varian 200
1
at 200 MHz for H and 75.5 MHz or 50.3 MHz for 13C.
3. Conclusions
Chemical shifts are expressed in parts per million (ppm)
relative to TMS. 77Se NMR spectra were recorded on
Varian 200, with diphenyl diselenide as the external stan-
dard. Elemental analyses were performed on a Vario
MACRO CHN analyzer. TLC was conducted on pre-
coated silica gel plates (Merck 60F254) and the spots were
visualized under UV light. Column chromatography was
carried out on a column using Silica Gel 60 Merck (70–
230 mesh) with the indicated solvents (petroleum ether
(Pet ether): 40–60 °C). All reactions requiring anhydrous
conditions were conducted in a flame-dried apparatus.
As a result of the conducted investigations, we have esta-
blished, that terpene alkyl diselenides under the seleno-
cyclization conditions gave the respective heterocyclic
products. The best diastereomeric excesses were obtained
when using (+)-dineomenthyl diselenide 1 at ꢀ78 °C in
the presence of a triflate counterion. The use of molecular
sieves considerably increased the yield of the selenocycli-
zation reaction. The use of bicyclic systems at the seleno-
cyclization conditions decreased the diastereomeric excess
of the product of selenocyclization reaction. For the reac-
tion of the (+)-dineomenthyl diselenide 1 with o-allylphe-
nol the preferred diastereomer has an (R)-configuration
on the newly formed stereogenic centre. The results ob-
tained may be a convenient base for further investigations
on functionalized dialkyl diselenides from the terpene
group.
4.2. Asymmetric selenocyclization of olefins with the use of
chiral monoterpene diselenides
A typical experimental procedure for the asymmetric cycli-
zation of alkene is as follows. To a CH2Cl2 solution

Z. Rafin´ski et al. / Tetrahedron: Asymmetry 19 (2008) 223–230
227
(22.5 mL) of diselenide (250 mg, 0.58 mmol) and powdered
molecular sieves (4 A, 1.7 g) at ꢀ78 °C, a CCl4 (0.6 mL)
(CH), 124.7 (CH), 126.3 (C); 77Se (38.1 MHz, CDCl3): d
major diastereomer 204.7; minor diastereomer 201.6; Anal.
Calcd for C19H28OSe: C, 64.95; H, 8.03. Found: C, 64.96;
H, 7.91.
˚
solution of bromine (96 mg, 0.6 mmol) was slowly added
under an argon atmosphere. After 20 min, a solution of
silver triflate (320 mg, 1.24 mmol) in methanol (1.0 mL)
was added. The resulting heterogeneous mixture was
stirred at ꢀ78 °C for 20 min. Olefin (1.16 mmol) was then
added to the solution and stirred for 7 h at the same
temperature. The mixture was treated with an aqueous
solution of 10% NaHCO3, extracted with CH2Cl2
(3 ꢁ 20 mL). The combined organic phases were dried over
MgSO4, and the solvent was removed under reduced pres-
sure. The residue was purified by chromatography on silica
gel, yielding the addition products as yellow oils, and in
one case, as white crystals. The diastereomers could not
be separated by column chromatography, and diastereo-
meric ratios were determined after chromatography by
1H and 77Se NMR spectra analysis.
4.2.3. 2-(((1R,3S,4R,6S)-4,7,7-Trimethylbicyclo[4.1.0]hep-
tan-3-ylselanyl)methyl)-2,3-dihydrobenzofuran 11. The title
compound was obtained as a mixture of diastereomers.
Yield 55%; yellow oil; column chromatography (70–
230 mesh silica gel, 10% EtOAc/Pet ether); 1H NMR
(200 MHz, CDCl3): d major diastereomer 0.66–0.85 (m,
3H), 0.97–1.01 (m, 9H), 1.41–1.59 (m, 1H), 1.78–1.93 (m,
2H), 2.21–2.32 (m, 1H), 2.71–2.81 (m, 1H), 2.97 (dd,
J = 5.7, 12.4 Hz, 1H, CH2), 3.09 (dd, J = 7.2, 15.9 Hz,
1H, CH2), 3.19–3.33 (m, 1H), 3.38 (dd, J = 9.0, 15.9 Hz,
1H, CH2), 4.88–5.03 (m, 1H), 6.76 (m, 1H), 6.81–6.87 (m,
1H), 7.09–7.18 (m, 2H); minor diastereomer 0.98 (d,
J = 6.4 Hz, 3H, CH3), 2.93 (dd, J = 5.7, 12.4 Hz, 1H,
CH2); 13C NMR (50.3 MHz, CDCl3): d major diastereomer
15.9 (CH3), 17.6 (C), 20.2 (CH3), 21.2 (CH), 21.4 (CH), 25.6
(CH2), 26.5 (CH2), 28.5 (CH3), 28.8 (CH2), 31.1 (CH), 35.7
(CH2), 43.4 (CH), 82.7 (CH), 109.3 (CH), 120.4 (CH), 124.9
(CH), 126.3 (C), 127.9 (CH), 159.2 (C); minor diastereomer
25.5 (CH2), 26.2 (CH2), 29.2 (CH2), 43.9 (CH); 77Se
(38.1 MHz, CDCl3): d major diastereomer 180.2; minor
diastereomer 178.3; Anal. Calcd for C19H26OSe: C, 65.32;
H, 7.50. Found: C, 65.19; H, 7.26.
4.2.1. (R)-2-(((1S,2S,5R)-2-Isopropyl-5-methylcyclohexyl-
selanyl)methyl)-2,3-dihydrobenzofuran 9. The title com-
pound was obtained as a single diastereomer from the
diastereomeric mixture (70:30) by crystallization from n-
20
pentane. Yield 40%; white crystals; mp 85–86 °C; ½aꢂD
¼
1
þ80:8 (c 1.48, CHCl3); H NMR (300 MHz, CDCl3): d
0.89 (d, J = 6.3 Hz, 3H, CH3), 0.92 (d, J = 6.6 Hz, 3H,
CH3), 0.96 (d, J = 6.6 Hz, 3H, CH3), 0.96–1.15 (m, 4H),
1.29–1.38 (m, 1H), 1.57–1.65 (m, 1H), 1.70–1.78 (m, 2H),
1.86–2.03 (m, 2H), 2.76 (dd, J = 8.1, 12.3 Hz, 1H, CH2),
2.95 (dd, J = 5.7, 12.3 Hz, 1H, CH2), 3.04 (dd, J = 7.2,
15.9 Hz, 1H, CH2), 3.38 (dd, J = 9.0, 15.9 Hz, 1H, CH2),
3.49 (m, 1H, CHSe), 6.74 (m, 1H), 6.81–6.87 (m, 1H),
7.09–7.17 (m, 2H); 13C NMR (50.3 MHz, CDCl3): d 20.8
(CH3), 21.0 (CH3), 22.1 (CH3), 26.9 (CH2), 27.6 (CH),
28.2 (CH2), 31.2 (CH), 35.3 (CH2), 35.8 (CH2), 41.8
(CH2), 45.9 (CH), 49.4 (CH), 82.7 (CH), 109.4 (CH),
120.4 (CH), 125.0 (CH), 126.4 (C), 128.0 (CH), 159.3 (C);
77Se (38.1 MHz, CDCl3): d 119.6; Anal. Calcd for
C19H28OSe: C, 64.95; H, 8.03. Found: C, 64.92; H, 7.99.
4.2.4. 2-(((1R,3R,4R,6S)-4,7,7-Trimethylbicyclo[4.1.0]hep-
tan-3-ylselanyl)methyl)-2,3-dihydrobenzofuran 12. The title
compound was obtained as a mixture of diastereomers.
Yield 64%; yellow oil; column chromatography (70–
230 mesh silica gel, 10% EtOAc/Pet ether); 1H NMR
(200 MHz, CDCl3): d major diastereomer 0.66–0.74 (m,
1H), 0.76–0.94 (m, 2H), 0.96 (s, 3H, CH3), 0.97 (s, 3H,
CH3), 0.99 (d, J = 6.4 Hz, 3H, CH3), 1.12–1.43 (m, 1H),
1.92–2.25 (m, 3H), 2.40–2.59 (m, 1H), 2.80 (dd, J = 8.1,
12.3 Hz, 1H, CH2), 2.97 (dd, J = 5.4, 12.3 Hz, 1H, CH2),
3.09 (dd, J = 6.9, 15.6 Hz, 1H, CH2), 3.38 (dd, J = 9.0,
15.6 Hz, 1H, CH2), 4.88–5.03 (m, 1H), 6.74 (m, 1H),
6.81–6.87 (m, 1H), 7.09–7.17 (m, 2H); minor diastereomer
1.03 (d, J = 6.4 Hz, 3H, CH3), 2.99 (dd, J = 5.4, 12.3 Hz,
1H, CH2); 13C NMR (50.3 MHz, CDCl3): d major diaste-
reomer 15.5 (CH3), 17.4 (C), 20.5 (CH), 20.6 (CH), 21.6
(CH3), 27.2 (CH2), 28.8 (CH3), 29.4 (CH2), 29.8 (CH2),
35.1 (CH), 35.7 (CH2), 44.8 (CH), 82.8 (CH), 109.3 (CH),
120.3 (CH), 124.8 (CH), 126.3 (C), 127.9 (CH), 159.1 (C);
minor diastereomer 15.6 (CH3), 27.5 (CH2), 34.8 (CH),
45.2 (CH), 82.9 (CH), 109.4 (CH), 159.2 (C); 77Se
(38.1 MHz, CDCl3): d major diastereomer 229.0; minor
diastereomer 233.2; Anal. Calcd for C19H26OSe: C, 65.32;
H, 7.50. Found: C, 65.19; H, 7.28.
4.2.2. 2-(((1R,2S,5R)-2-Isopropyl-5-methylcyclohexylselan-
yl)methyl)-2,3-dihydrobenzofuran 10. The title compound
was obtained as a mixture of diastereomers. Yield 92%; yel-
low oil; column chromatography (70–230 mesh silica gel,
5% EtOAc/Pet ether); 1H NMR (300 MHz, CDCl3): d ma-
jor diastereomer 0.78 (d, J = 6.9 Hz, 3H, CH3), 0.87 (d,
J = 7.2 Hz, 3H, CH3), 0.91 (d, J = 7.2 Hz, 3H, CH3),
0.97–1.12 (m, 2H), 1.19–1.44 (m, 3H), 1.67–1.78 (m, 2H),
2.16–2.24 (m, 1H), 2.34 (dquin, J = 3.0, 6.9 Hz, 1H), 2.77
(dd, J = 8.1, 12.3 Hz, 1H, CH2), 2.82–2.89 (m, 1H), 2.97
(dd, J = 5.4, 12.3 Hz, 1H, CH2), 3.06 (dd, J = 6.9,
15.6 Hz, 1H, CH2), 3.37 (dd, J = 9.0, 15.6 Hz, 1H, CH2),
4.90–5.01 (m, 1H), 6.74 (m, 1H), 6.81–6.87 (m, 1H),
7.09–7.17 (m, 2H); minor diastereomer 0.71 (d,
J = 6.9 Hz, 3H, CH3), 2.94 (dd, J = 5.4, 12.3 Hz, 1H,
CH2), 3.36 (dd, J = 9.0, 15.6 Hz, 1H, CH2); 13C NMR
(50.3 MHz, CDCl3): d major diastereomer 15.1 (CH3),
21.4 (CH3), 22.1 (CH3), 24.8 (CH2), 26.2 (CH2), 28.9
(CH), 34.2 (CH), 34.7 (CH2), 35.7 (CH2), 43.6 (CH), 44.9
(CH2), 47.6 (CH), 82.7 (CH), 109.2 (CH), 120.3 (CH),
124.8 (CH), 126.2 (C), 127.8 (CH), 159.2 (C); minor diaste-
reomer 15.0 (CH3), 26.5 (CH2), 35.6 (CH2), 47.9 (CH), 82.6
4.2.5. 2-(((1R,2R,3S,5S)-2,6,6-Trimethylbicyclo[3.1.1]hep-
tan-3-ylselanyl)methyl)-2,3-dihydrobenzofuran 13. The title
compound was obtained as a mixture of diastereomers.
Yield 87%; yellow oil; column chromatography (70–
230 mesh silica gel, 5% EtOAc/Pet ether); 1H NMR
(300 MHz, CDCl3): d major diastereomer 1.01 (s, 3H,
CH3), 1.20 (s, 3H, CH3), 1.23 (d, J = 6.9 Hz, 3H, CH3),
1.33 (d, J = 9.9 Hz, 1H, CH2), 1.89–2.01 (m, 2H), 2.05–
2.25 (m, 2H), 2.38–2.50 (m, 1H), 2.52–2.62 (m, 1H), 2.85

228
Z. Rafin´ski et al. / Tetrahedron: Asymmetry 19 (2008) 223–230
(dd, J = 7.5, 12.3 Hz, 1H), 2.76–3.12 (m, 2H), 3.35–3.45 (m,
1H), 3.87–3.99 (m, 1H), 4.94–5.06 (m, 1H), 6.77 (m, 1H),
6.82–6.87 (m, 1H), 7.09–7.18 (m, 2H); minor diastereomer
1.03 (s, 3H, CH3), 2.80 (dd, J = 7.5, 12.3 Hz, 1H); 13C
NMR (50.3 MHz, CDCl3): d major diastereomer 19.4
(CH3), 23.4 (CH3), 27.4 (CH3), 27.8 (CH2), 27.9 (CH2),
34.3 (CH), 35.7 (CH2), 36.4 (CH2), 37.9 (CH), 39.4 (C),
41.8 (CH), 48.7 (CH), 82.6 (CH), 109.2 (CH), 120.3 (CH),
124.8 (CH), 126.2 (C), 127.8 (CH), 159.1 (C); minor diaste-
reomer 27.7 (CH2), 28.2 (CH2), 33.7 (CH), 35.8 (CH2), 36.5
(CH2), 37.8 (CH), 82.5 (CH), 109.3 (CH), 126.1 (C); 77Se
(38.1 MHz, CDCl3): d major diastereomer 185.4; minor
diastereomer 190.3; Anal. Calcd for C19H26OSe: C, 65.32;
H, 7.50. Found: C, 65.43; H, 7.44.
4.2.8. trans-3a-((1S,2S,5R)-2-Isopropyl-5-methylcyclohex-
ylselanyl)-hexahydrobenzofuran-2(3H)-one 23. The title
compound was obtained as a mixture of diastereomers.
Yield 21%; yellow oil; column chromatography (70–
230 mesh silica gel, 10% EtOAc/Pet ether); 1H NMR
(300 MHz, CDCl3):
d major diastereomer 0.90 (d,
J = 6.4 Hz, 3H, CH3), 0.92 (d, J = 6.4 Hz, 3H, CH3),
0.99 (d, J = 6.2 Hz, 3H, CH3), 1.10–1.46 (m, 3H), 1.49–
1.68 (m, 5H). 1.70–1.90 (m, 4H), 1.92–2.07 (m, 4H),
2.12–2.33 (m, 1H), 2.56 (d, J = 16.8 Hz, 1H), 2.92 (d,
J = 16.8 Hz, 1H), 3.67–3.71 (m, 1H), 4.49 (t, J = 3.9 Hz,
1H); minor diastereomer 0.91 (d, J = 6.4 Hz, 3H, CH3),
0.97 (d, J = 6.2 Hz, 3H, CH3), 2.47 (d, J = 16.8 Hz, 1H),
2.98 (d, J = 16.8 Hz, 1H), 4.52 (t, J = 3.9 Hz, 1H); 13C
NMR (50.3 MHz, CDCl3): d major diastereomer 19.6
(CH2), 20.8 (CH3), 21.1 (CH3), 21.8 (CH2), 21.9 (CH3),
25.2 (CH2), 26.2 (CH2), 27.4 (CH), 31.3 (CH), 33.2
(CH2), 35.2 (CH2), 41.8 (CH2), 45.2 (CH2), 45.3 (C), 49.6
(CH), 52.6 (CH), 82.8 (CH), 174.9 (C@O); minor diastereo-
mer 20.9 (CH3), 26.1 (CH2), 33.1 (CH2), 41.7 (CH2), 45.1
(CH2), 45.4 (C), 52.5 (CH); 77Se (38.1 MHz, CDCl3): d
major diastereomer 282.2; minor diastereomer 282.1; Anal.
Calcd for C18H30O2Se: C, 60.50; H, 8.46. Found: C, 60.87;
H, 8.62.
4.2.6. 2-(((1R,2R,3R,5S)-2,6,6-Trimethylbicyclo[3.1.1]hep-
tan-3-ylselanyl)methyl)-2,3-dihydrobenzofuran 14. The title
compound was obtained as a mixture of diastereomers.
Yield 59%; yellow oil; column chromatography (70–
230 mesh silica gel, 5% EtOAc/Pet ether); 1H NMR
(300 MHz, CDCl3): d major diastereomer 1.05 (s, 3H,
CH3), 1.07 (d, J = 9.9 Hz, 1H, CH2), 1.16 (d, J = 6.9 Hz,
3H, CH3), 1.21 (s, 3H, CH3), 1.81–1.90 (m, 1H), 1.93–
1.98 (m, 1H), (dquin, J = 1.8, 7.2 Hz, 1H), 2.20 (ddd,
J = 2.4, 6.6, 13.8 Hz, 1H), 2.35–2.44 (m, 1H), 2.52–2.65
(m, 1H), 2.83 (dd, J = 7.8, 12.3 Hz, 1H), 2.96–3.12 (m,
2H), 3.21–3.45 (m, 2H), 4.97–5.09 (m, 1H), 6.76 (m, 1H),
6.82–6.87 (m, 1H), 7.09–7.18 (m, 2H); minor diastereomer
1.03 (s, 3H, CH3), 1.09 (d, J = 6.9 Hz, 3H, CH3); 13C
NMR (50.3 MHz, CDCl3): d major diastereomer 21.4
(CH3), 23.2 (CH3), 27.8 (CH3), 28.0 (CH2), 34.0 (CH2),
35.9 (CH2), 37.1 (CH), 38.4 (C), 38.5 (CH2), 42.4 (CH),
45.4 (CH), 48.3 (CH), 82.8 (CH), 109.3 (CH), 120.3 (CH),
124.9 (CH), 126.2 (C), 127.9 (CH), 159.2 (C); minor diaste-
reomer 27.9 (CH3), 33.9 (CH2), 35.7 (CH2), 37.5 (CH), 38.6
(CH2), 45.6 (CH), 82.6 (CH), 109.2 (CH), 126.3 (C), 127.8
(CH); 77Se (38.1 MHz, CDCl3): d major diastereomer
292.4; minor diastereomer 287.0; Anal. Calcd for C19H26-
OSe: C, 65.32; H, 7.50. Found: C, 65.13; H, 7.57.
4.2.9.
trans-5-Ethyl-4-((1S,2S,5R)-2-isopropyl-5-methyl-
cyclohexylselanyl)-dihydrofuran-2(3H)-one 24. The title
compound was obtained as a mixture of diastereomers.
Yield 17%; yellow oil; column chromatography (70–
230 mesh silica gel, 10% EtOAc/Pet ether); 1H NMR
(200 MHz, CDCl3):
d 0.78–1.01 (m, 9H), 1.08 (t,
J = 7.5 Hz, 3H, CH3), 1.15–1.47 (m, 3H), 1.51–1.96 (m,
7H), 2.12–2.26 (m, 1H), 2.55–2.96 (m, 2H), 3.23–3.44 (m,
1H), 3.60–3.68 (m, 1H), 4.27–4.41 (m, 1H); 13C NMR
(75.5 MHz, CDCl3): d major diastereomer 9.8 (CH3), 20.9
(CH3), 21.0 (CH3), 22.0 (CH3), 26.4 (CH2), 26.8 (CH2),
27.5 (CH), 31.4 (CH), 35.2 (CH2), 36.9 (CH), 37.2 (CH2),
41.7 (CH2), 49.6 (CH), 53.1 (CH), 88.3 (CH), 174.7
(C@O); minor diastereomer 9.7 (CH3), 21.1 (CH3), 27.6
(CH), 36.8 (CH), 37.1 (CH2), 41.9 (CH2), 49.7 (CH), 53.3
(CH), 88.2 (CH); 77Se (38.1 MHz, CDCl3): d major diaste-
reomer 281.6; minor diastereomer 283.5; Anal. Calcd for
C16H28O2Se: C, 58.00; H, 8.52. Found: C, 58.23; H, 8.31.
4.2.7. 2-((((1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptan-2-
yl)methylselanyl)methyl)-2,3-dihydrobenzofuran 15. The
title compound was obtained as a mixture of diastereo-
mers. Yield 83%; yellow oil; column chromatography
4.2.10. 5-(((1S,2S,5R)-2-Isopropyl-5-methylcyclohexylselan-
yl)methyl)-dihydrofuran-2(3H)-one 25. The title com-
pound was obtained as a mixture of diastereomers. Yield
87%; yellow oil; column chromatography (70–230 mesh sil-
ica gel, 10% EtOAc/Pet ether); 1H NMR (200 MHz,
CDCl3): d major diastereomer 0.75 (d, J = 6.8 Hz, 3H,
CH3), 0.89 (d, J = 7.0 Hz, 3H, CH3), 0.92 (d, J = 7.0 Hz,
3H, CH3), 0.94–1.13 (m, 1H), 1.17–1.50 (m, 3H), 1.67–
1.82 (m, 2H), 1.90–2.08 (m, 2H), 2.10–2.32 (m, 2H),
2.33–3.55 (m, 1H), 2.57–2.98 (m, 5H), 4.11–4.74 (m, 1H);
minor diastereomer 0.73 (d, J = 6.8 Hz, 3H, CH3); 13C
NMR (50.3 MHz, CDCl3): d major diastereomer 15.1
(CH3), 21.4 (CH3), 22.1 (CH3), 24.8 (CH2), 25.4 (CH2),
27.8 (CH2), 28.7 (CH), 28.9 (CH2), 34.1 (CH), 34.6
(CH2), 44.1 (CH), 44.9 (CH2), 47.7 (CH), 80.0 (CH),
176.6 (C@O); minor diastereomer 25.6 (CH2), 27.6
(CH2), 44.5 (CH), 48.0 (CH), 80.1 (CH); 77Se (38.1 MHz,
CDCl3): d major diastereomer 200.1; minor diastereomer
1
(70–230 mesh silica gel, 5% EtOAc/Pet ether); H NMR
(200 MHz, CDCl3): d 0.89 (d, J = 9.6 Hz, 1H, CH2), 1.01
(s, 3H, CH3), 1.20 (s, 3H, CH3), 1.41–1.61 (m, 1H), 1.83–
2.17 (m, 5H), 2.20–2.42 (m, 2H), 2.74–2.84 (m, 3H), 2.95
(dd, J = 5.8, 12.4 Hz, 1H, CH2), 3.07 (dd, J = 6.9,
15.9 Hz, 1H, CH2), 3.40 (dd, J = 9.0, 15.9 Hz, 1H, CH2),
4.88–5.03 (m, 1H), 6.74 (m, 1H), 6.81–6.87 (m, 1H),
7.09–7.17 (m, 2H); 13C NMR (50.3 MHz, CDCl3): d major
diastereomer 22.8 (CH2), 23.1 (CH3), 27.9 (CH2), 27.9
(CH3), 28.5 (CH2), 32.7 (CH2), 33.3 (CH2), 35.8 (CH2),
38.5 (C), 41.1 (CH), 41.7 (CH), 46.1 (CH), 82.5 (CH),
109.2 (CH), 120.3 (CH), 124.8 (CH), 126.2 (C), 127.8
(CH), 159.1 (C); minor diastereomer 28.6 (CH2), 32.8
(CH2), 41.8 (CH), 46.2 (CH), 82.6 (CH), 126.1 (C); 77Se
(38.1 MHz, CDCl3): d major diastereomer 116.1; minor
diastereomer 114.9; Anal. Calcd for C19H26OSe: C, 65.32;
H, 7.50. Found: C, 65.33; H, 7.10.

Z. Rafin´ski et al. / Tetrahedron: Asymmetry 19 (2008) 223–230
229
196.5; Anal. Calcd for C15H26O2Se: C, 56.78; H, 8.26.
Found: C, 56.60; H, 8.20.
(CH), 36.2 (CH2), 40.3 (CH), 43.1 (CH2), 45.9 (CH), 49.7
(CH), 86.6 (CH); 77Se (38.1 MHz, CDCl3): d major diaste-
reomer 229.2; minor diastereomer 234.9; Anal. Calcd for
C16H30OSe: C, 60.55; H, 9.53. Found: C, 60.57; H, 9.08.
4.2.11. 2-(((1S,2S,5R)-2-Isopropyl-5-methylcyclohexylselan-
yl)methyl)-tetrahydrofuran 26. The title compound was
obtained as a mixture of diastereomers. Yield 72%; yellow
oil; column chromatography (70–230 mesh silica gel, 5%
4.2.14.
2-(1-((1S,2S,5R)-2-Isopropyl-5-methylcyclohexyl-
selanyl)ethyl)-tetrahydrofuran 29. The title compound
was obtained as a mixture of diastereomers. Yield 50%; yel-
low oil; column chromatography (70–230 mesh silica gel,
10% EtOAc/Pet ether); 1H NMR (200 MHz, CDCl3): d
0.79–1.01 (m, 12H), 1.03–1.21 (m, 1H), 1.28 (t,
J = 7.5 Hz, 3H, CH3), 1.35–1.48 (m, 2H), 1.62–1.78 (m,
3H), 1.84–2.16 (m, 4H), 2.81–2.93 (m, 1H), 3.23–3.36 (m,
1H), 3.40–3.62 (m, 2H), 3.86–4.04 (m, 1H); 13C NMR
(50.3 MHz, CDCl3): d major diastereomer 20.7 (CH3),
20.9 (CH3), 21.0 (CH3), 22.1 (CH3), 22.9 (CH2), 26.9
(CH2), 27.6 (CH), 31.0 (CH), 31.6 (CH2), 35.3 (CH2),
42.2 (CH2), 45.3 (CH), 45.5 (CH), 49.5 (CH), 67.6 (CH2),
76.1 (CH); minor diastereomer 26.8 (CH2), 27.4 (CH),
32.2 (CH2), 42.8 (CH2), 45.1 (CH), 45.8 (CH), 49.9 (CH),
67.9 (CH2), 76.2 (CH); 77Se (38.1 MHz, CDCl3): d major
diastereomer 158.1; minor diastereomer 156.3; Anal. Calcd
for C16H30OSe: C, 60.55; H, 9.53. Found: C, 60.57; H, 9.12.
1
EtOAc/Pet ether); H NMR (300 MHz, CDCl3): d major
diastereomer 0.86 (d, J = 6.6 Hz, 3H, CH3), 0.88 (d,
J = 6.6 Hz, 3H, CH3), 0.92 (d, J = 6.6 Hz, 3H, CH3),
1.00–1.13 (m, 1H), 1.26–1.43 (m, 3H), 1.53–1.74 (m, 4H),
1.79–2.09 (m, 5H), 2.63 (dd, J = 7.2, 9.6 Hz, 1H), 2.71
(dd, J = 5.7, 11.7 Hz, 1H), 3.39 (m, 1H), 3.70–3.78 (m,
1H), 3.85–3.92 (m, 1H), 3.99–4.08 (m, 1H); minor diaste-
reomer 2.58 (dd, J = 7.2, 9.6 Hz, 1H), 2.73 (dd, J = 5.7,
11.7 Hz, 1H); 13C NMR (50.3 MHz, CDCl3): d major dia-
stereomer 20.7 (CH3), 20.8 (CH3), 22.0 (CH3), 25.8 (CH2),
26.7 (CH2), 27.4 (CH), 28.5 (CH2), 31.0 (CH), 31.6 (CH2),
35.2 (CH2), 41.8 (CH2), 45.5 (CH), 49.3 (CH), 68.1 (CH2),
79.4 (CH); minor diastereomer 27.5 (CH), 29.0 (CH2), 42.2
(CH2), 46.0 (CH), 49.4 (CH), 67.9 (CH2); 77Se (38.1 MHz,
CDCl3): d 124.4; Anal. Calcd for C15H28OSe: C, 59.39; H,
9.30. Found: C, 59.47; H, 9.38.
4.2.12. cis-2-Ethyl-3-((1S,2S,5R)-2-isopropyl-5-methylcyclo-
hexylselanyl)-tetrahydrofuran 27. The title compound was
obtained as a mixture of diastereomers. Yield 12%; yellow
oil; column chromatography (70–230 mesh silica gel, 10%
References
1. Paulmier, C. Selenium Reagents and Intermediates in Organic
Synthesis; Pergamon: Oxford, 1985.
1
EtOAc/Pet ether); H NMR (200 MHz, CDCl3): d 0.88–
1.06 (m, 15H), 1.18–1.48 (m, 2H), 1.51–1.82 (m, 4H),
1.86–2.18 (m, 3H), 2.23–2.52 (m, 1H), 3.34–3.45 (m, 2H),
3.75–3.84 (m, 2H), 3.96–4.07 (m, 1H); 13C NMR
(50.3 MHz, CDCl3): d major diastereomer 10.9 (CH3),
20.8 (CH3), 21.1 (CH3), 22.1 (CH3), 25.8 (CH2), 26.9
(CH2), 27.8 (CH), 31.1 (CH), 35.3 (CH2), 35.4 (CH2),
41.9 (CH), 43.3 (CH2), 45.9 (CH), 49.8 (CH), 65.9 (CH2),
83.4 (CH); minor diastereomer 10.8 (CH3), 20.7 (CH3),
20.9 (CH3), 26.1 (CH2), 27.0 (CH2), 27.5 (CH), 31.0
(CH), 34.9 (CH2), 35.5 (CH2), 40.8 (CH), 41.7 (CH), 44.8
(CH), 49.4 (CH), 66.0 (CH2), 83.3 (CH); 77Se (38.1 MHz,
CDCl3): d major diastereomer 180.0; minor diastereomer
174.0; Anal. Calcd for C16H30OSe: C, 60.55; H, 9.53.
Found: C, 60.61; H, 9.22.
2. Chemistry of Organoselenium and Tellurium Compounds;
Patai, S., Rappoport, Z., Eds.; John Wiley & Sons: New
York, 1987.
3. Organoselenium Chemistry: A Practical Approach; Back, T.
G., Ed.; Oxford University Press: Oxford, 1999.
4. Topics in Current Chemistry; Wirth, T., Ed.; Springer:
Heidelberg, 2000; Vol. 208.
5. Brown, D. M.; Wirth, T. Curr. Org. Chem. 2006, 10, 1893–
1903.
6. Zhu, C.; Huang, Y. Curr. Org. Chem. 2006, 10, 1905–1920.
7. Braga, A. L.; Ludtke, D. S.; Vargas, F. Curr. Org. Chem.
¨
2006, 10, 1921–1938.
8. Cardinal-David, B.; Brazeau, J.-F.; Katsoulis, I. A.; Guin-
don, Y. Curr. Org. Chem. 2006, 10, 1939–1961.
´
9. Scianowski, J. Tetrahedron Lett. 2005, 46, 3331–3334.
´
´
10. Scianowski, J.; Rafinski, Z.; Wojtczak, A. Eur. J. Org. Chem.
2006, 14, 3216–3225, and references cited therein.
4.2.13. trans-2-Ethyl-3-((1S,2S,5R)-2-isopropyl-5-methylcy-
clohexylselanyl)-tetrahydrofuran 28. The title compound
was obtained as a mixture of diastereomers. Yield 29%; yel-
low oil; column chromatography (70–230 mesh silica gel,
´
´
11. Skowronek, P.; Gawronski, J.; Scianowski, J. Tetrahedron:
Asymmetry 2006, 17, 2408–2412.
12. For reviews, see: (a) Petragnani, N.; Stefani, H. A.; Valduga,
C. J. Tetrahedron 2001, 57, 1411–1448; (b) Tiecco, M.;
Testaferri, L.; Bagnoli, L.; Marini, F.; Santi, C.; Temperini,
A.; Scarponi, C.; Sternativo, S.; Terlizzi, R.; Tomassini, C.
ARKIVOC 2006, 20, 186–206.
1
10% EtOAc/Pet ether); H NMR (300 MHz, CDCl3): d
major diastereomer 0.74–0.84 (m, 2H), 0.87 (d,
J = 6.3 Hz, 3H, CH3), 0.89 (d, J = 6.6 Hz, 3H, CH3),
0.92 (d, J = 6.6 Hz, 3H, CH3), 0.98 (t, J = 7.5 Hz, 3H,
13. Colourless 0.25 ꢁ 0.13 ꢁ 0.06 mm crystals of (R)-2-
(((1S,2S,5R)-2-isopropyl-5-methylcyclohexylselanyl)methyl)-
2,3-dihydrobenzofuran 9 were obtained from the methanol
solution. The compound crystallized in the monoclinic space
group C2. The X-ray data were collected at 293(2) K with the
Oxford Sapphire CCD diffractometer, graphite monochro-
CH ), 0.99–1.12 (m, 1H), 1.29–1.40 (m, 1H), 1.48–1.64
3
(m, 2H), 1.70–1.76 (m, 3H), 1.84–2.05 (m, 3H), 2.31–2.44
(m, 1H), 2.84 (m, 1H), 3.42 (m, 1H), 3.59 (dt, J = 4.2,
7.5 Hz, 1H), 3.78–3.89 (m, 2H); minor diastereomer 0.91
(d, J = 6.6 Hz, 3H, CH3), 0.97 (t, J = 7.5 Hz, 3H, CH3);
13C NMR (50.3 MHz, CDCl3): d major diastereomer 10.4
(CH3), 20.8 (CH3), 20.9 (CH3), 22.1 (CH3), 26.9 (CH2),
27.0 (CH2), 27.6 (CH), 31.0 (CH), 35.3 (CH2), 35.8
(CH2), 39.6 (CH), 42.4 (CH2), 45.4 (CH), 49.4 (CH), 66.7
(CH2), 86.4 (CH); minor diastereomer 27.2 (CH2), 31.1
˚
mator, MoKa radiation (k = 0.71073 A), cell parameters a =
˚
20.017(4), b = 5.262(1), c = 19.194(4) A, b = 116.92(3)°, V =
1802.6(6) A , Dcalc 1.295 Mg/m3, Z = 4, F(000) = 736,
3
˚
l = 2.081 mmꢀ1. The absorption correction was applied
(CrysAlis RED 171 package, Oxford Diffraction, 2000), with
the maximum and minimum transmissions of 0.8871 and

230
Z. Rafin´ski et al. / Tetrahedron: Asymmetry 19 (2008) 223–230
0.6285. The structure was solved by direct methods and
was determined. The structural data for 9 have been
deposited at the Cambridge Crystallographic Data Centre:
(CCDC No. 623526).
refined with the full-matrix least-squares on F2 with the use of
SHELX-9716 to R1 = 0.1222, wR2 = 0.3021 for reflections
I > 2r(I). The extinction correction applied, extinction coef-
ficient 0.017(4). Absolute structure was determined by the
Flack method,14 x = 0.14(5). Non-hydrogen atoms were
refined anisotropically, hydrogen atoms were constrained as
riding atoms. The (R,S,S,R)—C2, C10, C20 and C50 chirality
14. Flack, H. D. Acta Crystallogr., Sect. A 1983, 39, 876–881.
15. Fragale, G.; Wirth, T. Eur. J. Org. Chem. 1998, 1361–
1369.
16. Sheldrick, G. M.; Schneider, T. M. Methods Enzymol. 1997,
277B, 319–343.