Syntheses and reactions of terpene β-hydroxyselenides and β-hydroxydiselenides

Article abstract of DOI:10.1016/j.tetasy.2009.12.001

A convenient method for the synthesis of optically active trans-hydroxyselenides and trans-hydroxydiselenides from the bicyclic terpene group based on the reactions of sodium selenide or sodium diselenide with cis- and trans-(+)-3-carane, trans-(+)-2-carane and (-)-β-pinane epoxides is described. The corresponding cis-hydroxy and cis-methoxydiselenides were obtained in the reaction of sodium diselenide with β-hydroxy- and β-methoxytosylates. The influence of a hydroxy group at the β-position on the diastereomeric ratio of the products of the asymmetric methoxyselenenylation of styrene has been established by composition of the products, crystal structure analyses, and theoretical calculations using a DFT method on the B3LYP level (6-311G(d)).

Full text of DOI:10.1016/j.tetasy.2009.12.001

Tetrahedron: Asymmetry 20 (2009) 2871–2879
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
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Syntheses and reactions of terpene b-hydroxyselenides
and b-hydroxydiselenides
a,
a
b
a
*
´
´
´
Jacek Scianowski , Zbigniew Rafinski , Andrzej Wojtczak , Krzysztof Burczynski
a Department of Organic Chemistry, Nicolaus Copernicus University, 7 Gagarin Street, 87-100 Torun, Poland
b Department of Crystallochemistry and Biocrystallography, Nicolaus Copernicus University, Gagarina 7, 87-100 Torun, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient method for the synthesis of optically active trans-hydroxyselenides and trans-hydroxydisel-
enides from the bicyclic terpene group based on the reactions of sodium selenide or sodium diselenide
with cis- and trans-(+)-3-carane, trans-(+)-2-carane and (ꢀ)-b-pinane epoxides is described. The corre-
sponding cis-hydroxy and cis-methoxydiselenides were obtained in the reaction of sodium diselenide
with b-hydroxy- and b-methoxytosylates. The influence of a hydroxy group at the b-position on the dia-
stereomeric ratio of the products of the asymmetric methoxyselenenylation of styrene has been estab-
lished by composition of the products, crystal structure analyses, and theoretical calculations using a
DFT method on the B3LYP level (6-311G(d)).
Received 12 November 2009
Accepted 1 December 2009
Available online 6 January 2010
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
During our earlier investigations, we had established that b-pi-
nane and (+)-2- and (+)-3-carane epoxides react easily with a
Optically active diselenides are a very important class of organic
compounds. They were frequently used as chiral auxiliaries and li-
gands in asymmetric syntheses.1,2 For example, the optically active
electrophilic reagents obtained from diselenides have been used for
the formation of new asymmetric carbon–oxygen, carbon–nitro-
gen, and carbon–carbon bonds in addition reactions to the double
bonds or in cyclization reactions.3–6 Another important example
is the use of chiral diselenides as the precursors of nucleophilic re-
agents for epoxide ring openings.7 An essential advantage of the use
of organoselenium reagents in synthesis is the fact that the prod-
ucts might easily be transformed by elimination or substitution of
a selenide group.4,8–10
selenium anion. For example, in the reactions of the (+)-3-carene
cis-epoxide 1 and trans-epoxide 2 with sodium benzenoselenolate,
we obtained the corresponding hydroxyphenylselenides 3 and 417
(Scheme 1).
OH
O
SePh
Ph2Se2, NaBH4
MeOH, 3h, reflux
56%
3
1
Recently we have reported a convenient method for the synthe-
sis of optically active non-functionalized and functionalized disel-
enides from mono- and bicyclic terpene group, based on the
reaction of alkyl tosylates and chlorides with sodium disele-
nide.11,12 We have demonstrated that the terpene diselenides can
be used successfully for asymmetric methoxyselenenylation and
selenocyclization reactions.12–16
OH
O
SePh
Ph2Se2, NaBH4
MeOH, 3h, reflux
84%
2
4
The main goal of the currently presented investigations was to
develop a new convenient methodology for the synthesis of trans-
hydroxydiselenides based on the reaction of sodium diselenide
with the epoxides derived from the carane and pinane groups. An-
other aim was to establish the regio- and stereoselectivity of the
epoxide ring opening in the reaction with sodium diselenide.
Scheme 1. Synthesis of hydroxyphenylselenides.
There are only two literature reports on the synthesis of
hydroxydiselenides from epoxides. One paper reported the reac-
tion of selenium hydride with ethylene oxide18,19 and the second
one described the reaction of propylene oxide with lithium
diselenide.20
To explore other possibilities, we decided to obtain the corre-
sponding cis-hydroxy- and cis-methoxydiselenides in the reaction
* Corresponding author. Tel.: +48 56 611 4532; fax: +48 56 654 2477.
E-mail address: jsch@chem.uni.torun.pl (J. Scianowski).
´
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.12.001

´
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J. Scianowski et al. / Tetrahedron: Asymmetry 20 (2009) 2871–2879
Table 1
of trans-hydroxy- and trans-methoxytosylates with sodium disel-
enide.
Yields and the products of the reaction of the epoxide ring opening with sodium
diselenide—method 1
The final goal was to use the hydroxy- and methoxydiselenides
for the methoxyselenenylation reaction of styrene to establish the
influence of hydroxy and methoxy groups at the b-position relative
to the diselenide group on the diastereomeric ratio of the reaction
products and to compare them with the results obtained for other
alkyl diselenides.
Temp (°C)
Time (h)
Yield (%)
Composition of productsa (%)
6
7
8
100
50
20
2
3
24
66
73
99
67
49
49
26
35
51
7
16
—
a
Established on the basis of 77Se NMR of the crude products.
2. Results and discussion
to those reported for other terpene diselenides.12,13 The Se–Se dis-
tances of 2.2995(7) and 2.2979(7) Å for Se1–Se2 and Se3–Se4,
respectively, are slightly shorter than that of 2.3182(11) Å reported
for dineomenthyl diselenide.12 The conformation of the diselenide
bridges in two molecules is almost identical with the C–Se–Se–C
torsion angles being 80.25(18)° and 80.19(19)° for C3–Se1–Se2–
C13 and C23–Se3–Se4–C33, respectively, with the absolute values
significantly lower than that of ꢀ112.1(4)°, reported for dineomen-
thyl diselenide.12
In compound 18, the hydroxy groups bound to C4 or its equiv-
alents occupy the positions resulting in the (4S)-configuration in all
carane moieties. The (3S,4S)-configuration observed for all carane
moieties results in the Se–C3–C4–O torsion angles being slightly
different for the two halves of each molecule. These values are
Se1–C3–C4–O1 99.5(4)° and Se2–C13–C14–O2 80.4(4)° in mole-
cule 1, while the corresponding values in molecule 2 are Se4–
The initial investigations on epoxide ring opening with sodium
diselenide were conducted with the use of cyclohexane epoxide 5.
Using the methodology of sodium diselenide generation (Se, NaOH,
N2H4ꢁH2O, DMF 15 min 100 °C—method 1) described by us earlier,12
we obtained a mixture of three products. The 77Se NMR analysis
revealed their identity as selenide 6, diselenide 7, and triselenide
8 (Scheme 2). The composition of the products depended on the
temperature and time of the reaction. The best yield was obtained
for the reaction conducted at room temperature for 24 h (Table 1).
Using a two-step methodology for the synthesis of sodium
diselenide described by Krief,21 we obtained a mixture of the two
products, selenide 6 and diselenide 7 in a 22:88 ratio (20 °C,
24 h—method 2). The problems caused by the separation of the
reaction mixture led us to further modify sodium diselenide syn-
thesis. The best result for the synthesis was observed using a
two-step method. In the first step, we obtained sodium selenide
(Se, NaBH4, DMF/EtOH 1:1, 65 °C, 15 min.), then a further equiva-
lent of selenium was added (1 h, rt)—method 3. From the reaction
with oxide 5, we obtained a mixture of diselenide 7 and triselenide
8 in a ratio 72:28. We did not observe the formation of selenide 6.
Purification of the crude reaction mixture, based on a reduction
with NaBH4 and subsequent air oxidation, selectively gave disele-
nide 7 (Scheme 3). The purification procedure of diselenides via
reduction and subsequent air oxidation has also been described
by Wirth et al.22,23
C33–C34–O4 95.7(4)° and Se3–C23–C24–O3 85.6(4)°. Such
a
geometry results in the intramolecular Seꢁ ꢁ ꢁO contacts varying be-
tween 3.459(3) Å for Se2–O2 to 3.690(3) Å for Se1–O1, the dis-
tances almost equal to the sum of the van der Waals radii of
these atoms. This indicates the intramolecular interactions be-
tween these heteroatoms. On the other hand, the positions of the
H atoms on the hydroxy groups do not suggest any OHꢁ ꢁ ꢁSe hydro-
gen bond.
The asymmetric part of compound 19 contains a single disele-
nide molecule. The hydroxy group and selenide atom are bound
to the ring system to give a (3R,4R)-absolute configuration, which
is opposite to that found for 18. The selenium atoms are bound to
C3, while the C–Se distances of 2.001(5) and 1.996(6) Å are slightly
longer that those reported for 18. The spatial arrangement of Se
and hydroxy group in 19 results in the torsion angles Se1–C3–
C4–O1 ꢀ55.4(6) and Se2–C13–C14–O2 ꢀ55.1(5)°, with their abso-
lute values being much smaller than those of 80.4(4)° to 99.5(4)°
found for 18. This indicates an increased steric hindrance in 19
when compared to its (3S,4S)-counterpart and explains the larger
C–Se distances observed in 19. Such a position of both the substit-
uents in 19 results in the Se–O distances being 3.141(4) and 3.145
(4) Å for Se1ꢁ ꢁ ꢁO1 and Se2ꢁ ꢁ ꢁO2, respectively. These distances are
more that 0.4 Å shorter than those calculated for 18, and this con-
firms that intramolecular interactions between the heteroatoms,
are much stronger for the (3R,4R)-diastereoisomer. On the other
As a result of the sodium selenide reaction with cyclohexane
oxide we obtained selenide 6 (Scheme 4).
The above methodology for the preparation of sodium selenide
and sodium diselenide was used for the synthesis of selenides 14–
17 and diselenides 18–21 derived from (+)-3-carene, (+)-2-carene,
and (ꢀ)-b-pinene (Scheme 5). These reactions were conducted at
75 °C for 9 h. The synthesis of selenide 16 from epoxide 12 was
unsuccessful, probably because of steric effects. The epoxides 10,
12, and 13 were prepared in the reaction of (+)-3-carene, (+)-2-car-
ene, and (ꢀ)-b-pinene with peracetic acid.24 cis-(+)-3-Carene epox-
25
´
ide 11 was obtained by the Chabudzynski method.
The structures of diselenides 18 and 19 were confirmed by
X-ray structural analysis (Figs. 1 and 2).26–28
Structure 18 contains two diselenide molecules in the asym-
metric unit. The selenium atoms are bound to C3, while the C–Se
distances vary between 1.968(5) and 1.985(5) Å and are similar
DMF, 100oC, 15 min.
4Se
+
4NaOH
+
N2H4xH2O
2Na2Se2 + 4H2O + N2
OH
OH
OH
OH
O
)2Se
Se)2
(Se)3
Na2Se2
DMF
+
+
6
7
8
5
Scheme 2. The epoxide ring opening with sodium diselenide—method 1.

´
J. Scianowski et al. / Tetrahedron: Asymmetry 20 (2009) 2871–2879
2873
DMF/EtOH 1:1
65oC, 15min.
Se
20oC, 1h
Na2Se2
Na2Se
2NaBH4
+ Se
1. NaBH4, MeOH
2. air
OH
OH
OH
O
Se)2
(Se)3
Na2Se2
DMF, 20oC, 24h
+
72 : 28
99%
7
8
5
Scheme 3. The epoxide ring opening with sodium diselenide—method 3.
The conformation of the diselenide bridge in 19 as described
with the torsion angle C3–Se1–Se2–C13 of ꢀ107.9(2)° is opposite
to that found for 18, but is similar to that of ꢀ112.1(4)°, found
for dineomenthyl diselenide.12 The Se–Se distance Se1–Se2 of
2.3136(9) Å is significantly longer than that found in both mole-
cules of the (3S,4S)-diastereoisomer 18, but is almost identical to
that found for dineomenthyl diselenide.12
OH
O
)2Se
Na2Se
DMF, 20 oC, 24h
99%
6
5
Scheme 4. Synthesis of trans-hydroxyselenide 6.
The syntheses of cis-hydoxydiselenide 24 and cis-methoxydi-
selenide 27 were conducted by the reaction of trans-hydroxytosy-
late 23 and trans-methoxytosylate 26 with sodium diselenide
(Scheme 6). Tosylates 23 and 26 were obtained from oxide 10 and
a 1% aqueous or methanolic solution of sulfuric acid. Then the reac-
tion was carried with tosyl chloride in pyridine.
hand, the Se1ꢁ ꢁ ꢁC10 and Se2ꢁ ꢁ ꢁC20 distances of 3.401(7) and
3.442(7) Å, are similar to those reported for 18.
OH
OH
O
1. Na2Se2
DMF/EtOH, 75oC, 9h
)2Se
Se)2
Na2Se
DMF/EtOH, 75oC, 9h
2. NaBH4, MeOH; air
10
14 68%
18 78%
OH
OH
O
1. Na2Se2
DMF/EtOH, 75oC, 9h
)2Se
Se)2
Na2Se
DMF/EtOH, 75oC, 9h
2. NaBH4, MeOH; air
15 57%
19 55%
11
HO
O
HO
1. Na2Se2
DMF/EtOH, 75oC, 9h
2(Se
Se2(
Na2Se
DMF/EtOH, 75oC, 9h
2. NaBH4, MeOH; air
12
20 15%
16
)2Se
OH
Se)2
O
OH
1. Na2Se2
DMF/EtOH, 75oC, 9h
Na2Se
DMF/EtOH, 75oC, 9h
2. NaBH4, MeOH; air
13
21 74%
17 65%
Scheme 5. Synthesis of trans-hydroxyselenides 14–17 and trans-hydroxydiselenides 18–21.

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J. Scianowski et al. / Tetrahedron: Asymmetry 20 (2009) 2871–2879
2874
1. 1M Br2, CCl4
2. AgOTf, MeOH
CH2Cl2 -78oC
Ter*Se)2
Ter*Se OTf
18a-21a, 24a, 27a
OMe
Ter*Se
*
, MeOH
CH2Cl2 -78oC
The highest diastereoselectivity of a methoxyselenenylation
reaction was obtained for electrophile 19a (dr 90:10). We assume,
that the significant increase in diastereoselectivity for electrophile
19a is the result of an equatorial–equatorial arrangement of a hy-
droxy and selenide group in the carane system, for which the effec-
tive interaction between the oxygen and selenium atom is possible
Figure 1. Asymmetric unit of the structure of diselenide 18.
(n ꢀ
r*). The possibility of heteroatom–selenium interactions and
their influence on the reactivity has been discussed earlier.29,30
On the basis of molecular modeling by a DFT method (B3LYP 6-
311G(d))31–33 we have optimized a geometry for selenium electro-
philes 32–34 derived from hydroxydiselenides 18, 19, and 24
(Fig. 3). To simplify the calculations, triflate anions have been re-
placed with bromine anions.
The DFT calculations for electrophile 32 proved that the axial–
axial arrangement of the hydroxy and selenide groups made the
interaction of oxygen with an antibonding orbital of a selenium–
bromine bond impossible. Also, the axial Se–Br group and the
equatorial OH group for an electrophile 34 did not permit the
Seꢁ ꢁ ꢁO interaction. Despite the fact that the sum of the van der
Walls radii (vdw(Se) + vdw(O) = 1.90 + 1.52 = 3.42 Å)34 is greater
than the calculated distance between selenium and oxygen
(rSeꢁ ꢁ ꢁO = 3.09 Å), an efficient overlap of orbitals was not possible
because of the 76.5° angle value (hOꢁ ꢁ ꢁSe–Br). For electrophile 33 in
which the hydroxy and selenium groups occupy an equatorial–
equatorial position, the interatomic distance Seꢁ ꢁ ꢁO (rSeꢁ ꢁ ꢁO
=
Figure 2. Asymmetric part of the structure of diselenide 19.
2.84 Å) and nearly linear arrangement of the OꢁꢁꢁSe–Br atoms
(hXꢁ ꢁ ꢁSe–Br = 155.8°) created a possibility of interactions between
oxygen and selenium atoms. It seems that the observed increase
of diastereoselection of a methoxyselenenylation reaction for an
electrophile 19a results from the possibility of such interaction.
Hydroxydiselenides 18–21, and 24 and methoxydiselenide 27
were used for the asymmetric methoxyselenenylation of styrene.
The first step of the methoxyselenenylation reaction involved the
generation of triflate salts 18a–21a, 24a, and 27a as a result of a
reaction of diselenides with bromine and silver triflate, then the
reaction with styrene was carried out(Table 2). The isolation of
the methoxyselenenylation products from diselenides 20 and 21
was unsuccessful.
3. Conclusions
A convenient method for the trans-hydroxyselenides and trans-
hydroxydiselenides synthesis from the pinane and carane groups
OH
OH
OH
O
OTs
Se)2
OH
Na2Se2
1% H2SO4
H2O
TsCl
DMF, 20oC, 24h
Py, 0oC, 24h
10
24 28%
22 79%
23 68%
OMe
OTs
OMe
Se)2
OMe
OH
Na2Se2
1% H2SO4
MeOH
TsCl
DMF, 20oC, 24h
Py, 0oC, 24h
27 28%
25 66%
26 68%
Scheme 6. Synthesis of cis-hydroxydiselenide 24 and cis-methoxydiselenide 27.

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J. Scianowski et al. / Tetrahedron: Asymmetry 20 (2009) 2871–2879
2875
Table 2
Methoxyselenenylation of styrene with triflate salts obtained from hydroxydiselenides
OH
OH
OH
OMe
Se OTf
Se OTf
Se OTf
Se OTf
24a
18a
19a
27a
Alcene
Electophile
Product
dra
Yield (%)
18a
19a
24a
27a
28
29
30
31
74:26
90:10
61:39
64:36
58
54
60
69
OMe
Ter *Se
*
a
dr established on the basis of 1H and 77Se NMR.
Figure 3. The DFT-optimized structures of selenium electrophiles 32–34.
based on the reaction of epoxides with sodium selenide and so-
dium diselenide has been described. It has been shown that the
method used for the synthesis of sodium diselenide influences
the composition of the products of the epoxide ring opening. Con-
venient conditions have also been established for the sodium disel-
enide synthesis leading to the epoxide ring opening products,
which do not contain selenides. It has been shown that the respec-
tive cis-hydroxy and cis-methoxydiselenides can be obtained as a
result of a reaction of sodium diselenide with trans-hydroxy and
trans-methoxytosylates.
The hydroxy- and methoxydiselenides have been used for the
asymmetric methoxyselenenylation of styrene. Analysis of the
reaction products, crystal structures, and DFT calculations showed
that the structure of the electrophile and the intramolecular oxy-
gen–selenium interactions seem to be an important factor result-
ing in a high diastereomeric ratio of the products. Diselenide 19
revealed the best diastereomeric ratio for the products of methox-
yselenenylation reactions of styrene among different alkyl disele-
nides derived from the p-menthane, pinane, and carane systems.
No significant increase in the diastereoselectivity after the change
of a hydroxy for a methoxy group was observed.
4. Experimental
Melting points were measured with a Büchi Tottoli SPM-20
heating unit and are uncorrected. NMR spectra were recorded on
Bruker AM-300 at 300 MHz or Varian 200 at 200 MHz for 1H and
75.5 MHz or 50.3 MHz for 13C. Chemical shifts are expressed in
parts per million (ppm) relative to TMS. 77Se NMR spectra were re-
corded on Varian 200 with diphenyl diselenide as an external stan-
dard. Elemental analyses were performed on a Vario MACRO CHN
analyzer. TLC was conducted on precoated silica gel plates (Merck
60F254) and the spots were visualized under UV light. Column chro-
matography was carried out on column using Silica Gel 60 Merck
(70–230 mesh). Methanol was distilled from magnesium turning.
Dichloromethane was distilled from calcium hydride and restored
under molecular sieves 4 Å. All reactions requiring anhydrous con-
ditions were conducted in flame-dried apparatus.

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J. Scianowski et al. / Tetrahedron: Asymmetry 20 (2009) 2871–2879
2876
4.1. General procedure for the preparation of dialkyl selenides
(Se) ppm. Elemental Anal. Calcd for C20H34O2Se (385.44): C,
62.32; H, 8.89. Found: C, 62.40; H, 8.96.
To a mixture of sodium tetrahydroborate (0.38 g, 10.0 mmol)
and selenium (0.40 g, 5.0 mmol), anhydrous ethanol (10 mL) was
carefully added at ambient temperature under an argon atmo-
sphere. Dry DMF (10 mL) was added and the mixture was warmed
up to 60 °C for 10 min. The dark brownish solution was decolor-
ized. The reaction mixture was then allowed to cool to ca. 20 °C
and epoxide (10 mmol) was added all at once. The reaction mixture
was stirred and kept at constant temperature (for terpene oxides,
75 °C) for 9–20 h. The solution was poured into water (50 mL)
and extracted with diethyl ether (3 ꢂ 50 mL). The combined ethe-
real layers were washed with water (50 mL), brine (50 mL), dried
with anhydrous MgSO4, and the solvent was evaporated. A crude
product was purified by column chromatography, eluting with
CH2Cl2/EtOAc, 95:5?90:10 to give the pure dialkyl selenide.
4.2. General procedure for the preparation of dialkyl diselenides
To a mixture of sodium tetrahydroborate (0.38 g, 10.0 mmol) and
selenium (0.40 g, 5.0 mmol), anhydrous ethanol (10 mL) was care-
fully added at ambient temperature under an argon atmosphere.
Then dry DMF (10 mL) was added and the mixture was warmed up
to 60 °C for 10 min. The dark brownish solution was decolorized.
The reaction mixture was then allowed to cool to ca. 20 °C and an-
other portion of selenium (0.40 g, 5.0 mmol) was added. The reac-
tion mixture was stirred at this temperature for an additional 1 h,
and the respective epoxide (10.0 mmol) was added with vigorous
stirring. Temperature was kept constant (for terpene oxides, 75 °C)
for 9–20 h. The solution was poured into water (50 mL), and ex-
tractedwith diethylether (3 ꢂ 50 mL). The combinedethereallayers
were washed with water (50 mL), brine (50 mL), dried with anhy-
drous MgSO4, and the solvent was evaporated. A crude product
was purified by column chromatography, eluting with CH2Cl2/
EtOAc, 95:5?90:10 to give the pure dialkyl diselenide.
4.1.1. rac-Bis(trans-2-hydroxycyclohexyl) selenide 6
Purification by column chromatography on silica gel with meth-
ylene chloride/ethyl acetate, 95:5. Yield 99%; colorless solid; mp
73–75 °C; 1H NMR (200 MHz, CDCl3): d = 1.15–1.39 (m, 6H),
1.40–1.97 (m, 6H), 2.02–2.30 (m, 4H), 2.60–3.08 (m, 4H), 3.30–
3.61 (m, 2H) ppm; 13C NMR (50.3 MHz, CDCl3): d = 24.3 (4 ꢂ
CH2), 26.6 (2 ꢂ CH2), 26.7 (2 ꢂ CH2), 34.3 (2 ꢂ CH2), 33.5 (2 ꢂ
CH2), 34.6 (2 ꢂ CH2), 34.7 (2 ꢂ CH2), 47.4 (2 ꢂ CH), 49.3 (2 ꢂ CH),
72.8 (2 ꢂ CH), 74.8 (2 ꢂ CH) ppm; 77Se NMR (38.1 MHz, CDCl3):
d = 272.6 (Se), 294.3 (Se) ppm. Elemental Anal. Calcd for
C12H22O2Se (277.26): C, 51.98; H, 8.00. Found: C, 52.07; H, 8.09.
4.2.1. rac-Bis(trans-2-hydroxycyclohexyl) diselenide 7
Purification by column chromatography on silica gel with meth-
ylene chloride/ethyl acetate, 95:5. Yield 91%; yellow crystalline so-
lid; mp 76–78 °C; 1H NMR (200 MHz, CDCl3): d = 1.28–1.48 (m,
6H), 1.50–1.85 (m, 6H), 2.05–2.25 (m, 2H), 2.64 (br s, 2H, OH),
2.71 (br s, 2H, OH), 2.80–2.95 (m, 2H), 3.40–3.55 (m, 2H) ppm;
13C NMR (50.3 MHz, CDCl3): d = 24.1 (2 ꢂ CH2), 24.2 (2 ꢂ CH2),
26.3 (4 ꢂ CH2), 33.3 (2 ꢂ CH2), 33.4 (2 ꢂ CH2), 34.3 (4 ꢂ CH2),
51.2 (2 ꢂ CH), 51.6 (2 ꢂ CH), 73.0 (2 ꢂ CH), 73.1 (2 ꢂ CH) ppm;
77Se NMR (38.1 MHz, CDCl3): d = 304.9 (Se2), 309.0 (Se2) ppm. Ele-
mental Anal. Calcd for C12H22O2Se2 (356.22): C, 40.46; H, 6.22.
Found: C, 40.49; H, 6.20.
4.1.2. (1S,3S,10S,30S)-(+)-Bis(3-hydroxy-4-caranyl) selenide 14
Purification by column chromatography on silica gel with meth-
ylene chloride/ethyl acetate, 90:10. Yield 68%; yellow solid; mp
97–98 °C; ½a 2D0
ꢃ
¼ þ117:3 (c 5.00, CHCl3); 1H NMR (300 MHz,
CDCl3): d = 0.68–0.88 (m, 4H), 0.96 (s, 6H, CH3), 0.99 (s, 6H, CH3),
1.23 (s, 6H, CH3), 1.25–1.35 (m, 4H), 2.02 (dd, J = 15.6, 9.0 Hz,
2H), 2.29–2.45 (m, 4H), 2.91 (dd, J = 10.8, 4.8 Hz, 2H) ppm; 13C
NMR (50.3 MHz, CDCl3): d = 15.4 (2 ꢂ CH3), 18.4 (2 ꢂ CH), 18.8
(2 ꢂ C), 23.7 (2 ꢂ CH), 27.6 (2 ꢂ CH2), 28.3 (2 ꢂ CH3), 28.6 (2 ꢂ
CH3), 33.2 (2 ꢂ CH2), 55.0 (2 ꢂ CH), 72.4 (2 ꢂ C) ppm; 77Se NMR
(38.1 MHz, CDCl3): d = 247.7 (Se) ppm. Elemental Anal. Calcd for
C20H34O2Se (385.44): C, 62.32; H, 8.89. Found: C, 62.41; H 8.96.
4.2.2. (1S,3S,10S,30S)-(+)-Bis(3-hydroxy-4-caranyl) diselenide 18
Purification by column chromatography on silica gel with
methylene chloride/ethyl acetate, 90:10. Yield 78%; yellow crystal-
line solid; mp 63–65 °C; ½a D20
ꢃ
¼ þ230:7 (c 5.50, CHCl3); 1H NMR
(200 MHz, CDCl3): d = 0.69–0.92 (m, 4H), 0.98 (s, 6H, CH3), 1.00
(s, 6H, CH3), 1.30 (s, 6H, CH3), 1.33 (m, 4H), 1.97 (dd, J = 15.3,
8.4 Hz, 2H), 2.31 (s, 2H, OH), 2.93 (ddd, J = 14.7, 7.8, 5.7 Hz, 2H),
3.37 (dd, J = 10.5, 5.7 Hz, 2H, CH) ppm; 13C NMR (50.3 MHz, CDCl3):
d = 15.3 (2 ꢂ CH3), 18.0 (2 ꢂ C), 18.7 (2 ꢂ CH), 22.8 (2 ꢂ CH), 26.9
(2 ꢂ CH2), 28.1 (2 ꢂ CH3), 28.3 (2 ꢂ CH3), 33.4 (2 ꢂ CH2), 55.3
(2 ꢂ CH), 73.0 (2 ꢂ C) ppm; 77Se NMR (38.1 MHz, CDCl3):
d = 360.8 (Se2) ppm. Elemental Anal. Calcd for C20H34O2Se2
(464.40): C, 51.73; H 7.38. Found: C, 51.65; H, 7.36.
4.1.3. (1S,3R,10S,30R)-(ꢀ)-Bis(3-hydroxy-4-isocaranyl) selenide 15
Purification by column chromatography on silica gel with meth-
ylene chloride/ethyl acetate, 90:10. Yield 57%; yellow solid; mp
99–101 °C; ½a 2D0
ꢃ
¼ ꢀ129:4 (c 4.80, CHCl3); 1H NMR (200 MHz,
CDCl3): d = 0.48–0.81 (m, 4H), 0.95 (s, 6H, CH3), 0.97 (s, 6H, CH3),
1.21 (s, 6H, CH3), 1.24–1.32 (m, 2H), 1.95–2.13 (m, 4H), 2.32 (dd,
J = 15.0, 7.2 Hz, 2H), 2.46 (s, 2H, OH), 2.71 (dd, J = 12.9, 7.2 Hz,
2H, CH) ppm; 13C NMR (50.3 MHz, CDCl3): d = 15.3 (2 ꢂ CH3),
17.7 (2 ꢂ C), 20.4 (2 ꢂ CH), 20.5 (2 ꢂ CH), 23.1 (2 ꢂ CH3), 28.7
(2 ꢂ CH3), 30.3 (2 ꢂ CH2), 33.4 (2 ꢂ CH2), 55.2 (2 ꢂ CH), 71.4
(2 ꢂ C) ppm; 77Se NMR (38.1 MHz, CDCl3): d = 206.8 (Se) ppm. Ele-
mental Anal. Calcd for C20H34O2Se (385.44): C, 62.32; H, 8.89.
Found: C, 62.44; H, 8.79.
4.2.3. (1S,3R,10S,30R)-(ꢀ)-Bis(3-hydroxy-4-isocaranyl) 19
Purification by column chromatography on silica gel with meth-
ylene chloride/ethyl acetate, 90:10. Yield 55%; yellow crystalline
solid; mp 102–104 °C; ½a D20
ꢃ
¼ ꢀ219:5 (c 5.10, CHCl3); 1H NMR
(200 MHz, CDCl3): d = 0.61 (t, J = 8.4 Hz, 2H), 0.78 (dt, J = 9.4,
5.0 Hz, 2H) 0.99 (s, 6H, CH3), 1.03 (s, 6H, CH3), 1.22 (s, 6H, CH3),
1.23–1.37 (m, 2H), 1.97–2.16 (m, 4H), 2.30 (dd, J = 15.0, 8.4 Hz,
2H), 2.39 (s, 2H, OH), 3.07 (dd, J = 12.6, 7.4 Hz, 2H, CH) ppm; 13C
NMR (50.3 MHz, CDCl3): d = 15.2 (2 ꢂ CH3), 17.8 (2 ꢂ C), 20.4
(2 ꢂ CH), 20.6 (2 ꢂ CH), 22.4 (2 ꢂ CH3), 28.6 (2 ꢂ CH3), 29.3
(2 ꢂ CH2), 34.7 (2 ꢂ CH2), 58.5 (2 ꢂ CH), 72.4 (2 ꢂ C) ppm; 77Se
NMR (38.1 MHz, CDCl3): d = 352.1 (Se2) ppm. Elemental Anal. Calcd
for C20H34O2Se2 (464.40): C, 51.73; H, 7.38. Found: C, 51.70; H, 7.40.
4.1.4. (1R,2S,10R,20S)-(ꢀ)-Bis(2-hydroxymyrtanyl) selenide 17
Purification by column chromatography on silica gel with meth-
ylene chloride/ethyl acetate, 95:5. Yield 65%; yellow solid; mp 71–
73 °C; ½a 2D0
ꢃ
¼ ꢀ70:0 (c 5.20, CHCl3); 1H NMR (200 MHz, CDCl3):
d = 0.92 (s, 6H, CH3), 1.22 (s, 6H, CH3), 1.49 (d, J = 10.0 Hz, 2H),
1.75–1.95 (m, 10H), 1.97–2.05 (m, 2H), 2.12–2.25 (m, 2H), 2.85
(br s, 2H, OH), 2.95 (s, 4H, CH2) ppm; 13C NMR (50.3 MHz, CDCl3):
d = 23.5 (2 ꢂ CH3), 24.8 (2 ꢂ CH2), 27.4 (2 ꢂ CH2), 27.5 (2 ꢂ CH3),
30.9 (2 ꢂ CH2), 38.1 (2 ꢂ C), 40.8 (2 ꢂ CH), 42.3 (2 ꢂ CH2), 52.1
(2 ꢂ CH), 75.8 (2 ꢂ C) ppm; 77Se NMR (38.1 MHz, CDCl3): d = 21.1
4.2.4. (1S,3R,10S,30R)-(ꢀ)-Bis(3-hydroxy-2-caranyl) 20
Purification by column chromatography on silica gel with
methylene chloride/ethyl acetate, 90:10. Yield 15%; yellow oil;

´
J. Scianowski et al. / Tetrahedron: Asymmetry 20 (2009) 2871–2879
2877
½
a 2D0
ꢃ
¼ ꢀ174:9 (c 4.86, CHCl3); 1H NMR (200 MHz, CDCl3): d = 0.81–
4.5. (1S,3R,10S,30R)-(+)-Bis(3-hydroxy-4-caranyl) diselenide 24
1.00 (m, 2H), 1.06 (s, 6H, CH3), 1.17 (s, 6H, CH3), 1.19–1.45 (m, 4H),
1.45 (s, 6H, CH3), 1.50–1.68 (m, 4H), 1.84–2.08 (m, 2H), 2.33 (s, 2H,
OH), 4.25 (d, J = 10.6 Hz, 2H) ppm; 13C NMR (50.3 MHz, CDCl3):
d = 16.1 (2 ꢂ CH2), 17.4 (2 ꢂ CH3), 22.2 (2 ꢂ C), 22.3 (2 ꢂ CH),
26.6 (2 ꢂ CH), 28.3 (2 ꢂ CH3), 30.1 (2 ꢂ CH3), 33.1 (2 ꢂ CH2), 55.6
(2 ꢂ CH), 72.6 (2 ꢂ C) ppm; 77Se NMR (38.1 MHz, CDCl3): d =
431.1 (Se2) ppm. Elemental Anal. Calcd for C20H34O2Se2 (464.40):
C, 51.73; H, 7.38. Found: C, 51.92; H, 7.57.
The compound was prepared according to the literature.12 The
crude product was purified on silica gel column chromatography
using chloroform. Yield 28%, yellow oil; ½a D22
¼ þ190:0 (c 10.70,
ꢃ
CHCl3); 1H NMR (200 MHz, CDCl3): d = 0.55–0.85 (m, 4H), 0.98 (s,
6H, CH3), 1.02 (s, 6H, CH3), 1.20 (s, 6H, CH3), 1.25–1.35 (m, 2H),
2.00–2.10 (m, 4H), 2.29 (dd, J = 15.0, 7.5 Hz, 2H), 2.55 (s, 2H, OH),
3.08 (dd, J = 12.3, 7.2 Hz, 2H) ppm; 13C NMR (50.3 MHz, CDCl3):
d = 15.3 (2 ꢂ CH3), 17.9 (2 ꢂ C), 20.5 (2 ꢂ CH), 20.7 (2 ꢂ CH), 22.4
(2 ꢂ CH3), 28.6 (2 ꢂ CH3), 29.4 (2 ꢂ CH2), 34.7 (C2 ꢂ H2), 58.7
(2 ꢂ CH), 72.5 (2 ꢂ C) ppm; 77Se NMR (38.1 MHz, CDCl3): d =
343.4 (Se2) ppm. Elemental Anal. Calcd for C20H34O2Se2 (464.40):
C, 51.73; H, 7.38. Found: C, 51.84; H, 7.52.
4.2.5. (1R,3S,10R,30S)-(ꢀ)-Bis(2-hydroxymyrtanyl) diselenide 21
Purification by column chromatography on silica gel with meth-
ylene chloride/ethyl acetate, 95:5. Yield 74%; yellow solid; mp 87–
90 °C; ½a 2D0
ꢃ
¼ ꢀ99:7 (c 5.40, CHCl3); 1H NMR (200 MHz, CDCl3):
d = 0.95 (s, 6H, CH3), 1.24 (s, 6H, CH3), 1.51 (d, J = 10.2 Hz, 2H),
1.75–2.10 (m, 8H), 2.12–2.32 (m, 2H), 2.35 (br s, 2H, OH), 3.44 (s,
4H, CH2), 2.55 (s, 2H), 3.08 (dd, J = 12.3, 7.2 Hz, 2H) ppm; 13C
NMR (50.3 MHz, CDCl3): d = 23.5 (2 ꢂ CH3), 24.8 (2 ꢂ CH2), 27.2
(2 ꢂ CH2), 27.4 (2 ꢂ CH3), 30.8 (2 ꢂ CH2), 38.2 (2 ꢂ C), 40.8
(2 ꢂ CH), 47.7 (2 ꢂ CH2), 51.8 (2 ꢂ CH), 76.4 (2 ꢂ C) ppm; 77Se
NMR (38.1 MHz, CDCl3): d = 278.0 (Se2) ppm. Elemental Anal. Calcd
for C20H34O2Se2 (464.40): C, 51.73; H, 7.38. Found: C, 51.89; H,
7.55.
4.6. (1S,3R)-(ꢀ)-3-Methoxy-4-isocaranol 25
(1S,3S)-3,4-Epoxycarane 10 (80.0 g, 0.53 mol) was shaken with
1% methanolic solution of H2SO4 (480 mL) at ambient temperature
for 20 h. The residue was quenched with 5% aqueous solution of so-
dium hydroxide and the solvent was removed in vacuo. The oily
residue was extracted with diethyl ether, washed with water and
with brine, dried over anhydrous magnesium sulfate, and concen-
trated. The crude product was purified by the distillation under re-
duced pressure 65–67 °C/0.5 mmHg. Yield 66%; colorless oil;
4.3. (1S,3R)-(ꢀ)-3-Hydroxy-4-isocaranol 22
½
a 2D0
ꢃ
¼ ꢀ9:5 (c 4.44, CHCl3); 1H NMR (200 MHz, CDCl3): d = 0.63–
(1S,3S)-3,4-Epoxycarane 10 (80.0 g, 0.53 mol) was shaken with
1% aqueous solution of H2SO4 (480 mL) and crumbled ice (160 g)
for 5 h for a decline of the smell of the oxide. Acid was neutralized
with 5% aqueous solution of sodium hydroxide, and the precipi-
tate formed was filtered off and dried under vacuum. The resulting
(1S,3R)-(ꢀ)-3-hydroxy-4-isocaranol hydrate (89.5 g) was crystal-
lized from hexane to afford the desired anhydrous diol 67.2 g,
0.69 (m, 2H), 0.95 (s, 3H, CH3), 0.98 (s, 3H, CH3), 1.11 (m, 1H),
1.15 (s, 3H, CH3), 2.03–2.16 (m, 2H), 2.27 (br s, 1H, OH), 3.20 (s,
3H, OCH3), 3.39 (dd, J = 10.2, 7.4 Hz, 1H, CH) ppm; 13C NMR
(50.3 MHz, CDCl3): d = 13.6 (CH3), 15.8 (CH3), 17.6 (C), 19.5 (CH),
20.4 (CH), 26.5 (CH2), 28.1 (CH2), 28.7 (CH3), 48.6 (OCH3), 72.9
(CH), 77.4 (C) ppm. Elemental Anal. Calcd for C11H20O2 (184.28):
C, 71.70; H, 10.94. Found: C, 71.76; H, 10.83.
79%; mp 84–86 °C;
½
a 2D3
ꢃ
¼ ꢀ0:6 (c 8.12, CHCl3); 1H NMR
(200 MHz, CDCl3): d = 0.68–0.75 (m, 2H), 0.97 (s, 3H, CH3), 0.98
(s, 3H, CH3), 1.22 (d, J = 1.0 Hz, 3H, CH3), 1.24 (m, 1H), 1.57–1.74
(m, 1H), 1.81 (br s, 1H, OH), 1.82–2.18 (m, 3H), 3.38 (dd,
J = 10.0, 7.1 Hz, 1H, CH) ppm; 13C NMR (75.5 MHz, CDCl3): d =
15.7 (CH3), 17.6 (C), 19.0 (CH), 20.0 (CH3), 21.0 (CH), 27.8 (CH2),
28.6 (CH3), 33.7 (CH2), 73.3 (C), 74.4 (CH) ppm. Elemental Anal.
Calcd for C10H18O2 (170.25): C, 70.55; H, 10.66. Found: C, 70.61;
H, 10.68.
4.7. (1S,3R)-(ꢀ)-3-Methoxy-4-isocaranyl tosylate 26
To a stirred solution of (1S,3R)-(ꢀ)-3-methoxy-4-isocaranol 25
(5.0 g, 27.13 mmol) in dry pyridine (27 mL) chilled below 5 °C
(ice bath), tosyl chloride (5.7 g, 30.0 mmol) was added in one por-
tion. The reaction mixture was stirred at this temperature for an
additional 1 h, after which the cooling bath was removed and stir-
ring was continued at ambient temperature for 20 h. It was then
poured into water and extracted with chloroform. The combined
organic phases were washed with water and brine and dried over
anhydrous MgSO4. A crude product left after solvent removal was
purified on silica gel column chromatography using chloroform.
4.4. (1S,3R)-(+)-3-Hydroxy-4-isocaranyl tosylate 23
To a stirred solution of a (1S,3R)-(ꢀ)-3-hydroxy-4-isocaranol
22 (2.0 g, 11.75 mmol) in dry pyridine (12 mL) chilled below
5 °C (ice bath) tosyl chloride (2.5 g, 13.0 mmol) was added in
one portion. The reaction mixture was stirred at this temperature
for an additional 1 h, the cooling bath was removed and stirring
was continued at ambient temperature for 20 h. It was then
poured into water and extracted with chloroform. The combined
organic phases were washed with water and brine and dried over
anhydrous MgSO4. A crude product left after solvent removal was
purified on silica gel column chromatography using chloroform/
Yield 68%, colorless oil; ½a D21
ꢃ
¼ ꢀ21:6 (c 7.63, CHCl3); 1H NMR
(200 MHz, CDCl3): d = 0.63–0.73 (m, 2H), 0.93 (s, 3H, CH3), 0.96
(s, 3H, CH3), 1.18 (s, 3H, CH3), 1.88–2.07 (m, 4H), 2.43 (s, 3H,
CH3), 3.00 (s, 3H, OCH3), 4.36 (dd, J = 8.8, 7.4 Hz, 1H, CH), 7.28 (d,
J = 8.4 Hz, 2H, 2 ꢂ CH), 7.78 (d, J = 8.4 Hz, 2H, 2 ꢂ CH) ppm; 13C
NMR (50.3 MHz, CDCl3): d = 15.6 (CH3), 16.1 (CH3), 17.9 (C), 18.8
(CH), 20.3 (CH), 21.5 (CH3), 26.3 (CH2), 28.2 (CH3), 29.6 (CH2),
48.9 (OCH3), 74.8 (C), 84.7 (CH), 127.7 (2 ꢂ CH), 129.3 (2 ꢂ CH),
135.0 (C), 144.0 (C) ppm. Elemental Anal. Calcd for C18H26O4S
(338.46): C, 63.88; H, 7.74. Found: C, 63.92; H, 7.79.
ethyl acetate, 50:50. Yield 68%, colorless oil; ½a D19
¼ þ12:5 (c
ꢃ
3.28, CHCl3); 1H NMR (200 MHz, CDCl3): d = 0.66–0.75 (m, 2H),
0.91 (s, 3H, CH3), 0.96 (s, 3H, CH3), 1.24 (s, 3H, CH3), 1.31 (m,
1H), 1.77–2.11 (m, 4H), 2.45 (s, 3H, CH3), 4.26 (dd, J = 10.0,
8.0 Hz, 1H, CH), 7.38 (d, J = 8.4 Hz, 2H, 2 ꢂ CH), 7.80 (d, J =
8.4 Hz, 2H, 2 ꢂ CH) ppm; 13C NMR (50.3 MHz, CDCl3): d = 15.7
(CH3), 17.8 (C), 19.2 (CH), 20.4 (CH3), 21.0 (CH), 21.6 (CH3),
26.5 (CH2), 28.2 (CH3), 33.5 (CH2), 70.9 (C), 87.2 (CH), 127.7
(2 ꢂ CH), 129.8 (2 ꢂ CH), 134.0 (C), 144.8 (C) ppm. Elemental
Anal. Calcd for C17H24O4S (324.44): C, 62.93; H, 7.46. Found: C,
63.92; H, 7.79.
4.8. (1S,3R,10S,30R)-(+)-Bis(3-methoxy-4-caranyl) diselenide 27
The compound was prepared according to the literature.12 The
crude product was purified on silica gel column chromatography
using petroleum ether/ethyl acetate, 95:5. Yield 28%, yellow solid;
mp 91–94 °C, ½a 2D2
ꢃ
¼ þ257:9 (c 4.28, CHCl3); 1H NMR (300 MHz,
CDCl3): d = 0.49 (dt, J = 8.4, 6.0 Hz, 2H), 0.70 (dt, J = 8.4, 7.5 Hz,
2H), 1.00 (s, 6H, CH3), 1.04 (s, 6H, CH3), 1.38 (s, 6H, CH3), 1.48–
1.60 (m, 4H), 1.82 (dd, J = 15.0, 8.4 Hz, 2H), 2.42 (ddd, J = 14.4,

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J. Scianowski et al. / Tetrahedron: Asymmetry 20 (2009) 2871–2879
2878
13.5, 4.8 Hz, 2H), 2.93 (dd, J = 12.6, 4.8 Hz, 2H), 3.15 (s, 6H, OCH3)
ppm; 13C NMR (50.3 MHz, CDCl3): d = 15.0 (2 ꢂ CH3), 18.7 (2 ꢂ C),
18.8 (2 ꢂ CH), 24.0 (2 ꢂ CH), 25.7 (2 ꢂ CH3), 26.2 (2 ꢂ CH2), 28.5
(2 ꢂ CH3), 28.6 (2 ꢂ CH2), 49.2 (2 ꢂ OCH3), 56.5 (2 ꢂ CH), 75.3
(2 ꢂ C) ppm; 77Se NMR (38.1 MHz, CDCl3): d = 341.2 (Se2) ppm.
Elemental Anal. Calcd for C22H38O2Se2 (492.46): C, 53.66; H, 7.78.
Found: C, 53.65; H, 7.80.
2.70 (dd, J = 12.6, 5.4 Hz, 1H, CHH), 2.91 (dd, J = 12.6, 8.0 Hz, 1H,
CHH), 3.24 (s, 3H, CH3), 4.29 (dd, J = 8.0, 5.4 Hz, 1H, CH) ppm; 13C
NMR (50.3 MHz, CDCl3): major diastereomer d = 15.3 (CH3), 17.9
(C), 20.5 (CH), 20.3 (CH), 20.8 (CH2), 22.5 (CH3), 28.5 (CH3), 29.3
(CH2), 31.2 (CH2), 53.9 (CH), 56.9 (OCH3), 71.6 (C), 84.5 (CH),
126.4 (2 ꢂ CH), 128.1 (CH), 128.5 (2 ꢂ CH), 140.9 (C) ppm; minor
diastereomer—only separated signals: 28.3 (CH3), 32.0 (CH2), 56.7
(OCH3), 71.5 (C), 84.3 (CH), 126.6 (2 ꢂ CH), 140.8 (C) ppm; 77Se
NMR (38.1 MHz, CDCl3): major diastereomer d = 146.7 (Se) ppm;
minor diastereomer: 147.2 (Se) ppm. Elemental Anal. Calcd for
C19H28O2Se (367.38): C, 62.12; H, 7.68. Found: C, 62.18; H, 7.75.
4.9. [(1S,3S)-3-Hydroxy-4-caranyl]-(2-methoxy-2-phenylethyl)
selenide 28
Purification by column chromatography on silica gel with chlo-
roform. Yield 58%; colorless oil; dr 74:26; 1H NMR (300 MHz,
CDCl3): major diastereomer d = 0.62–0.93 (m, 2H), 0.97 (s, 3H,
CH3), 1.02 (s, 3H, CH3), 1.06–1.22 (m, 2H), 1.25 (s, 3H, CH3), 2.03
(dd, J = 15.2, 8.4 Hz, 1H), 2.19–2.34 (m, 1H), 2.82–3.07 (m, 4H),
3.24 (s, 3H, OCH3), 4.36 (dd, J = 8.4, 5.6 Hz, 1H, CH), 7.26–7.41
(m, 5H, 5 ꢂ CH) ppm; minor diastereomer—only separated signals:
1.23 (s, 3H, CH3), 4.38 (dd, J = 8.4, 5.6 Hz, 1H, CH) ppm; 13C NMR
(50.3 MHz, CDCl3): major diastereomer d = 15.3 (CH3), 18.4 (CH),
18.7 (C), 24.0 (CH), 27.6 (CH2), 28.3 (CH3), 28.5 (CH3), 33.0 (CH2),
33.2 (CH2), 52.6 (CH), 56.8 (OCH3), 72.7 (C), 84.9 (CH), 126.5
(2 ꢂ CH), 128.1 (CH), 128.6 (2 ꢂ CH), 141.1 (C) ppm; minor diaste-
reomer—only separated signals: 23.6 (CH), 27.3 (CH2), 32.3 (CH2),
51.2 (CH), 72.6 (C), 84.1 (CH), 126.7 (2 ꢂ CH), 128.5 (2 ꢂ CH)
ppm; 77Se NMR (38.1 MHz, CDCl3): major diastereomer d = 195.7
(Se) ppm; minor diastereomer: 191.1 (Se) ppm. Elemental Anal.
Calcd for C19H28O2Se (367.38): C, 62.12; H, 7.68. Found: C, 62.05;
H, 7.63.
4.12. [(1S,3R)-3-Methoxy-4-caranyl]-(2-methoxy-2-phenyl-
ethyl) selenide 31
Purification by column chromatography on silica gel with
petroleum ether/ethyl acetate, 90:10. Yield 69%; light yellow oil;
dr 64:36; 1H NMR (300 MHz, CDCl3): major diastereomer
d = 0.38–0.50 (m, 1H), 0.59 (dt, J = 8.4, 7.5 Hz, 1H), 0.96 (s, 3H,
CH3), 1.02 (s, 3H, CH3), 1.24 (s, 3H, CH3), 1.42–1.61 (m, 2H), 1.71
(dd, J = 15.0, 8.1 Hz, 1H), 2.01–2.12 (m, 1H), 2.47 (dd, J = 12.3,
4.2 Hz, 1H), 2.71 (dd, J = 12.3, 6.3 Hz, 1H, CHH), 2.90 (dd, J = 12.3,
7.5 Hz, 1H, CHH), 3.10 (s, 3H, OCH3), 3.24 (s, 3H, OCH3), 4.32 (dd,
J = 7.5, 6.3 Hz, 1H, CHSe), 7.34 (m, 5H, 5 ꢂ CH) ppm; minor diaste-
reomer—only separated signals: 0.67 (dt, J = 8.4, 7.5 Hz, 1H), 0.98
(s, 3H, CH3), 1.03 (s, 3H, CH3), 1.36 (s, 3H, CH3), 1.78 (dd, J = 15.0,
8.1 Hz, 1H), 2.69 (dd, J = 12.3, 6.3 Hz, 1H, CHH), 2.94 (dd, J = 12.3,
7.5 Hz, 1H, CHH), 3.11 (s, 3H, OCH3), 3.24 (s, 3H, OCH3), 4.32 (dd,
J = 7.5, 6.3 Hz, 1H, CHSe) ppm; 13C NMR (50.3 MHz, CDCl3): major
diastereomer d = 14.8 (CH3), 18.4 (C), 18.5 (CH), 23.5 (CH), 25.7
(CH3), 25.8 (CH2), 28.1 (CH2), 28.4 (CH3), 29.7 (CH2), 48.8 (OCH3),
50.1 (CH), 56.6 (OCH3), 74.5 (C), 84.6 (CH), 126.7 (2 ꢂ CH), 127.6
(CH), 128.2 (2 ꢂ CH), 141.4 (C) ppm; minor diastereomer—only
separated signals: 25.9 (CH3), 29.9 (CH2), 50.2 (CH), 56.7 (OCH3),
74.6 (C), 85.0 (CH), 126.4 (2 ꢂ CH), 141.6 (C). 77Se NMR
(38.1 MHz, CDCl3): major diastereomer d = 205.3 (Se) ppm; minor
diastereomer: 212.2 (Se) ppm. Elemental Anal. Calcd for
C20H30O2Se (381.41): C, 62.98; H, 7.93. Found: C, 62.90; H, 8.01.
4.10. [(1S,3R)-3-Hydroxy-4-isocaranyl]-(2-methoxy-2-
phenylethyl) selenide 29
Purification by column chromatography on silica gel with chlo-
roform. Yield 54%; colorless oil; dr 90:10; 1H NMR (300 MHz,
CDCl3): major diastereomer d = 0.53 (t, J = 8.1 Hz, 1H), 0.79 (dt,
J = 9.9, 5.1 Hz, 1H), 0.97 (s, 3H, CH3), 0.99 (s, 3H, CH3), 1.27 (m,
1H), 1.28 (s, 3H, CH3), 1.88 (ddd, J = 15.0, 12.9, 8.1 Hz, 1H), 2.10
(dd, J = 14.7, 10.2 Hz, 1H), 2.25 (dd, J = 15.0, 7.5 Hz, 1H), 2.69 (dd,
J = 13.2, 6.0 Hz, 1H), 2.93 (d, J = 6.9 Hz, 2H, CH2), 3.27 (s, 3H,
OCH3), 3.80 (s, 1H), 4.24 (t, J = 6.9 Hz, 1H, CH), 7.26–7.39 (m, 5H,
5 ꢂ CH) ppm; minor diastereomer—only separated signals: 1.00
(s, 3H, CH3), 3.25 (s, 3H, OCH3) ppm; 13C NMR (50.3 MHz, CDCl3):
major diastereomer d = 15.3 (CH3), 17.6 (C), 20.2 (CH), 20.3 (CH),
22.7 (CH3), 28.6 (CH3), 28.9 (CH2), 33.0 (CH2), 33.4 (CH2), 53.9
(CH), 56.9 (OCH3), 71.6 (C), 84.6 (CH), 126.4 (2 ꢂ CH), 128.0 (CH),
128.5 (2 ꢂ CH), 140.7 (C) ppm; minor diastereomer—only sepa-
rated signals: 15.2 (CH3), 20.4 (CH), 22.8 (CH3), 28.7 (CH3), 32.8
(CH2), 56.7 (OCH3), 71.5 (C), 84.1 (CH), 126.6 (2 ꢂ CH), 140.8 (C)
ppm; 77Se NMR (38.1 MHz, CDCl3): major diastereomer d = 171.9
(Se) ppm; minor diastereomer: 165.0 (Se) ppm. Elemental Anal.
Calcd for C19H28O2Se (367.38): C, 62.12; H, 7.68. Found: C, 62.18;
H, 7.75.
4.13. Computational methods
All theoretical calculations were carried out by using the
GAUSSIAN03 program.31 The hybrid Berke 3-Lee-Yang-Parr (B3LYP) ex-
change—correlation functional32,33 was applied for DFT calculations.
Geometries were fully optimized at the B3LYP/6-311G(d) level of
theory. For all stable conformers a minimum of potential energy
was established at the B3LYP/6-311G(d) level by verifying that all
vibration frequencies were real.
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Purification by column chromatography on silica gel with chlo-
roform. Yield 60%; colorless oil; dr 61:39; 1H NMR (200 MHz,
CDCl3): major diastereomer d = 0.59 (t, J = 8.4 Hz, 1H), 0.73–0.86
(m, 1H), 0.99 (s, 3H, CH3), 1.04 (s, 3H, CH3), 1.22 (s, 3H, CH3),
1.25–1.35 (m, 1H), 1.91–2.05 (m, 2H), 2.16 (dd, J = 15.0, 7.5 Hz,
1H), 2.36 (s, 1H, OH), 2.61 (dd, J = 12.3, 7.2 Hz, 1H), 2.68 (dd,
J = 12.6, 5.4 Hz, 1H, CHH), 2.93 (dd, J = 12.6, 8.0 Hz, 1H, CHH),
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5H, 5 ꢂ CH) ppm; minor diastereomer—only separated signals:
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0.3599, structure solved in the monoclinic P2(1) space group, Flack
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absorption correction applied
K
a
radiation k = 0.71073 Å by
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(CRYSALIS171 package of programs, Oxford
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constrained during refinement. The absolute structure was determined with
the Flack method.25 For compound 18, the crystals obtained from the diethyl
ether/methanol, diffraction experiment for 0.44 ꢂ 0.42 ꢂ 0.22 mm yellow
crystal at 291(2) K, maximum and minimum transmissions of 0.5371 and
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