New chiral selenium electrophiles derived from functionalized terpenes

Article abstract of DOI:10.1016/j.tet.2009.10.005

A convenient method for the synthesis of optically active dialkyl diselenides derived from bicyclic terpenes functionalized with hydroxy, etheral, sulfide, and selenide groups is described. The diselenides were used for a synthesis of chiral electrophilic

Full text of DOI:10.1016/j.tet.2009.10.005

Tetrahedron 65 (2009) 10162–10174
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
New chiral selenium electrophiles derived from functionalized terpenes
a,
a
a
b
´
*
´
Jacek Scianowski , Zbigniew Rafinski , Aleksandra Szuniewicz , Andrzej Wojtczak
a Department of Organic Chemistry, Nicolaus Copernicus University, Gagarina 7, 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 dialkyl diselenides derived from bicyclic
terpenes functionalized with hydroxy, etheral, sulfide, and selenide groups is described. The di-
selenides were used for a synthesis of chiral electrophilic selenium reagents, then in the asymmetric
selenenylation of styrene and selenocyclization with o-allylphenol. The influence of nonbonding
selenium-heteroatom interactions in the generated organoselenium electrophiles on the stereo-
selectivity of an addition reaction has been investigated. Calculations by a DFT method on a B3LYP (6–
311G (d)) level, confirmed the existence of nonbonded selenium–heteroatom interactions in the
investigated systems.
Received 30 June 2009
Received in revised form
16 September 2009
Accepted 2 October 2009
Available online 7 October 2009
Dedicated to Professor Marek Zaidlewicz on
the occasion of his 70th birthday
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Terpenoids
Diselenides
Asymmetric synthesis
Selenenylation reaction
1. Introduction
selenocyclization of unsaturated alcohols and carboxylic acids.8 Until
now, the best stereoselectivity in the methoxyselenenylation of
Diselenides are important reagents in modern organic synthesis
and have been very often used as the key substrates in multistep
syntheses. The major advantage of diselenides is the ease of their
transformation into nucleophilic, radical, and electrophilic reagents,
as well as their air, acid, base, and temperature stability.1 Diselenides
are also used in asymmetric synthesis, for example, as ligands in the
addition of diethylzinc to aldehydes.2
styrene with the electrophile 1a containing a isopinocampheyl
group in its molecule (dr 82:18) has been observed.5 On the other
hand the best results for the selenocyclization of o-allylphenol have
been achieved with the triflate salt 3a generated from (þ)-neo-
menthyl diselenide 3 (dr 70:30) (Scheme 1). The diastereomeric
mixture of dihydrobenzofuran derivatives 4 was separated by
crystallization from n-pentane and the structure of the major ste-
reoisomer confirmed by X-ray crystal structure determination.8
Stereoselective selenenylation is a matter of permanent interest
for numerous scientific groups, and highly selective electrophilic
reagents are known. Inspite of numerous papers describing an
influence of a heteroatom on the asymmetric induction in addition,9
the lack of experimental examples showing a difference in stereo-
selection between unsubstituted alkyl electrophiles and their analogs
containing functional groups with different heteroatoms is evident.
Among the functionalized terpene diselenides used so far in the
asymmetric synthesis, a bornane system and its derivatives were
the only chiral source.10
The search for a useful method of a diselenide synthesis has also
great importance because of their physiological and pharmacological
role, in particular their antioxidant, antiviral, and antitumor activity.3
Our previous research has focused on the synthesis of nonracemic
monoterpene dialkyl diselenides, the precursors for a synthesis of
chiral electrophilic selenium reagents. Recently, we have described
a convenient methodology for epimeric dialkyl diselenides synthe-
sis, based on the reaction of alkyl tosylates or chlorides with
disodium diselenide generated in situ (Se, NaOH, N2H4ꢀH2O). The
obtained nonracemic diselenides derived from p-menthane, pinane,
carane or bornane groups4–7 have been converted to triflate salts and
5–7
used for a stereoselective selenenylation of olefins,
as well as
Furthermore, to date, no comparative analysis of the influence of
the structure, or the range of functional group or heteroatom, on
the stereoselectivity of selenenylation has been reported for
unfunctionalized and functionalized alkyl electrophiles. Therefore
the aim of the reported research was to investigate the syntheses
and reactions of functionalized dialkyl diselenides containing
* Corresponding author. Department of Chemistry, Nicolaus Copernicus Univer-
sity, 7 Gagarin street, 87-100 Torun, Poland. Tel.: þ48 56 611 4532; fax: þ48 56 654
2477.
´
E-mail address: jsch@chem.uni.torun.pl (J. Scianowski).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.005

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10163
OMe
1. Br2
2. AgOTf
CH2Cl2, −78 ο
Se OTf
Se
Se)2
styrene, MeOH
CH2Cl2, −78 ο
C
C
2
1
1a
1. Br2
2. AgOTf
CH2Cl2, −78 ο
o-allylphenol, MeOH
CH2Cl2, −78 ο
C
C
Se OTf
Se
Se)2
O
4
3
3a
Scheme 1. Asymmetric selenenylation of olefins.
hydroxy, etheral, sulfide, and selenide groups. The other goal was to
conduct the methoxyselenenylation of styrene and selenocycliza-
tion of o-allylphenol with the use of the respective triflate salts
generated from diselenides. The final goal was to explain the
influence of selenium–heteroatom interaction on the stereo-
selectivity of addition and to compare the results with those
obtained for electrophiles generated from diselenides not having
any functional groups.
OR
OH
OR
b)
a)
R = THP (74%)
R = Me (76%)
R = THP (75%)
R = Me (86%)
6
7
8
9
Cl
OAr
OAr
OH
OH
b)
c)
d)
2. Results and discussion
(74%)
Ar = Ph (53%)
12 Ar = C6F5 (71%) 14 Ar = C6F5 (57%)
Ar = Ph (74%)
5
10
b)
11
13
The first step of our investigation was the synthesis of terpene
alcohols containing functional groups at the C-10-position, to ob-
tain precursors for a synthesis of functionalized nonracemic
diselenides. The commercially available (1R)-(-)-myrtenol 5 was
used as a substrate for most of the obtained alcohols. Alcohols 8 and
9, with hydroxy groups protected with tetrahydropyranyl and
methoxy groups, were obtained directly from myrtenol 5 in a re-
action with dihydropyran in the presence of catalytic amounts of
p-toluenesulfonic acid or sodium hydride and methyl iodide, fol-
lowed by hydroboration-oxidation.7 Aryl ethers 11 and 12 were
obtained by chlorination of myrtenol 5 by means of carbon
tetrachloride in the presence of triphenylphosphine7 and sub-
sequent substitution with sodium phenolate or sodium penta-
fluorophenolate. Hydroboration of the resulting ethers gave chiral
alcohols 13 and 14 (Scheme 2).
Cl
OAr
OH
OH
e)
d)
Ar = C6H4(p-NO2) (28%)
(65%)
16
15
17 Ar = C6H4(p-OMe) (21%)
Br
Br
SPh
OH
OH
b)
d)
(59%)
(46%)
(45%)
18
19
20
Alcohol 16 was synthesized by inserting a p-nitrophenoxy group
to a pinane system after hydroboration-oxidation of myrtanyl
chloride 10. Alcohol 17 was obtained analogously. Because of the
higher reactivity of allylic bromides, myrtanyl bromide 18 was used
for the reaction with sodium benzenethiolate. 1H NMR spectro-
scopic analysis showed the presence of two products 21 and 22,
indicating that under the reaction conditions the product of rear-
rangement is also formed (Scheme 3).
Scheme 2. Synthesis of functionalized alcohols from the pinane system. Reagents and
conditions: (a) dihydropyrane, TsOH/CH2Cl2, RT, 18 h; or NaH, MeI, RT, 20 h; (b) (i)
BH3$SMe2, THF, 0 ꢁC/RT, 18 h; (ii) NaOH, 30% H2O2, RT/60 ꢁC, 5.5 h (two steps); (c)
CCl4, PPh3, reflux, 20 h; (d) NaXAr (X¼O, S), DMF, 100 ꢁC, 20 h; (e) PBr3, hexane,
ꢂ20 ꢁC/RT, 18.5 h.
Br
SPh
S
Na
SPh
The hydroboration-oxidation of myrtanyl bromide 18 and sub-
stitution of bromoalcohol 19 by means of sodium benzenethiolate
gave the isopinocampheyl derivative 20 with a sulfide substituent
(Scheme 2).
+
DMF, 100 οC, 20 h
18
21
22
We also tried to synthesis a ethers containing the bulky tert-
butyl groups in the ortho-position of a phenyl ring. Instead, the
reaction of myrtanyl chloride 10 with 2,6-di-tert-butyl phenolate
gave 23, a product of substitution in para-position relative to
hydroxyl. The similar substitution in the para-position in relation
to the hydroxyl group was observed, for example, by Hayakawa
and co-workers.11 Hydroboration-oxidation gave alcohol 24
(Scheme 4).
Scheme 3. Reaction of (ꢂ)-myrtenyl bromide with sodium benzenethiolate.
It is generally known that under oxidation conditions the SePh
group can easily undergo the syn-elimination to olefins. Hydrogen
peroxide usually used in hydroboration–oxidation is also com-
monly employed for elimination of a phenylselanyl group (SePh).1
The use of the standard conditions (30% hydrogen peroxide) in the
oxidation step gave allylic alcohol 28. An alternative oxidation with
sodium perborate (NaBO3) under alkaline conditions gave selec-
tively 10-phenylselanylisopinocampheol 29 without elimination of
the SePh group. To the best of our knowledge this is the first
10-Phenylselanylisopinocampheol 29, was obtained from 10-
phenylselanyl-2-pinene 27 via chlorination of
b-pinene 25 with
N-chlorosuccinimide12 and substitution by means of sodium ben-
zeneselenolate13 (Scheme 5).

´
10164
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
t
XR
Se)2
XR
OTs
Bu
OH
t
Bu
Na2Se2
DMF
TsCl, py
0 οC-20 ο
C
Cl
t
Bu
XR
OH
HO
24-72 h
t
32-38
NaH,
DMF, 100 οC, 20 h
45-51
Bu
XR
Se)2
XR
Cl
(73%)
10
23
Na2Se2
DMF
PPh3, CCl4
reflux, 20 h
1. BH3 SMe2
2. NaOH, H2O2
THF
X = O, S, Se
R = alkyl, aryl
52-57
39-44
Scheme 7. Syntheses of functionalized diselenides.
t
Bu
OH
t
Bu
OH
A route through tosylates 32–38 led via a single inversion of con-
figuration and gave diselenides 45–51. Alternatively, when chlo-
rides 39–44 were employed, double inversion was observed during
transformation of alcohols to the corresponding chlorides. Reaction
of these chlorides with disodium diselenide gave epimeric
diselenides 52–57. The yields of the syntheses of tosylates, chlo-
rides, and diselenides are presented in Table 1.
The reaction of alcohol 8 with tosyl chloride in pyridine or car-
bon tetrachloride in the presence of triphenylphosphine gave the
respective tosylate 58 and chloride 59 (Scheme 8). An attempt at
deprotection of the tosylate 58 THP group to a hydroxyl group
failed. As a result of the reaction of chloride 59 with catalytic
amounts of p-toluenesulphonic acid in methanol, the respective
hydroxychloride 39 was obtained, which was used for the synthesis
of diselenide 52 (Table 1).
Tosylate 60 with pentafluorinated phenoxy group at the C-10-
position proved to be unreactive in a reaction with disodium
diselenide at room temperature, as well as when heated to 50 ꢁC for
24 h. When this reaction was conducted at 100 ꢁC a reaction
product was obtained, being a result of intramolecular substitution
of the pentafluorophenoxyl group to give unsymmetric cyclic di-
selenide 61 in 11% yield (Scheme 9). The same product was also
obtained conducting a reaction of tosylate 38 with a disodium
diselenide at 100 ꢁC.
When analogous conditions were employed for chloride 44,
only a mixture of undefined products was observed. The lowering
of the reaction temperature to 20 ꢁC allowed us to obtain dis-
elenides bis(10-phenylselanylpinocampheyl) 51 and bis(10-phe-
nylselanylisopinocampheyl) 57 in good yields. There is only one
literature example of the synthesis of a chiral aryl diselenide with
a selenide substituent (SeMe).15 The structure of diselenide 51 was
confirmed by X-ray analysis (Fig. 1).
(59%)
24
Scheme 4. Synthesis of alcohol 24.
SePh
Se Na
NCS, py
cat. Ph2Se2
Cl
CH2Cl2
EtOH, 0 οC, 1 h,
50 οC, 1 h
0 οC, 5 h,
RT, 24 h
(87%)
(63%)
25
27
26
1. BH3 SMe2
2. NaOH, 30% H2O2
OH
THF
(70%)
28
SePh
OH
1. BH3 SMe2
2. NaOH, NaBO3
THF
(63%)
29
Scheme 5. Synthesis of 10-phenylselanylisopinocampheol 29.
example of hydroboration–oxidation in the presence of SePh
leading to formation of hydroxyphenylselenides. To confirm the
universal character of the described oxidation methodology we
also obtained the respective 10-phenylselanyl-4-isocaranol 31,
which was formed from 10-phenylselanyl-3-carene 3014 by
hydroboration with the adduct of borane-dimethyl sulfide and
subsequent oxidation with sodium perborate (Scheme 6).
We used the obtained diselenides for asymmetric methoxy-
selenenylation of styrene. The diselenides 45–51 and 52–57 were
treated with a 1 M solution of bromine and then with silver triflate
to obtain the corresponding triflate salts 46a–57a, which in turn
were used for the addition to styrene in the presence of methanol
SePh
SePh
OH
1. BH3 SMe2
2. NaOH, NaBO3
as
a nucleophile. Stereoselectivities and yields of methoxy-
selenenylation of styrene for products 63–75 are presented in
Table 2.
THF
Attempts to isolate the methoxyselenenylation derivatives of
diselenides 45 and 49 failed. For electrophiles 46a–51a having
a selenenyl group (SeOTf) in the cis position relative to the group
bound to C-2, we observed the stereoselection to be higher than
that found with the use of electrophile 62, which has no functional
group (dr 52:48). That might be caused by a selenium–heteroatom
interaction in the transition state of the methoxyselenenylation
reaction. It has been found that for electrophiles 46a–51a the best
stereoselectivity can be obtained for electrophile 46a with a phe-
noxy group (dr 70:30). Introduction of an electron-acceptor (–NO2)
(33%)
30
31
Scheme 6. Synthesis of 10-phenylselanyl-4-isocaranol 31.
The terpene alcohols obtained using the previously developed
methodology based on a reaction of alkyl tosylates and halides with
generated in situ disodium diselenide5 (Scheme 7), were used in
the synthesis of chiral tosylates and chlorides leading to the re-
spective diselenides.

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10165
Table 1
Syntheses of functionalized tosylates, chlorides and diselenides
Tosylate
OMe
OTs
Yield [%]
Diselenide
Yield [%]
81
Chloride
Yield [%]
62
Diselenide
Yield [%]
OH
OH
OMe
Cl
Se)2
Se)2
67
55
45
45
32
39
52
OPh
OMe
Cl
OMe
Se)2
OPh
Se)2
OTs
69
91
30
27
69
43
46
40
33
53
OC6H4(p-NO2)
OC6H4(p-NO2)
OPh
Cl
OPh
Se)2
OTs
Se)2
19
33
41
54
47
34
OC6H4(p-OMe)
OC6H4(p-OMe)
OC6F5
Cl
OC6F5
Se)2
OTs
Se)2
83
25
72
41
73
55
35
48
42
t
t
Bu
Bu
OH
OH
SPh
Cl
SPh
Se)2
t
t
Bu
Bu
OTs
Se)2
70
8
23
56
43
49
36
SPh
OTs
SPh
Se)2
SePh
Cl
SePh
Se)2
79
88
15
68
47
37
50
44
57
SePh
OTs
SePh
Se)2
38
51
Na
OC6F5
C6F5O
OC6F5
OH
Se
OTHP
OTs
OTs
Se
Na2Se2
DMF
100 οC, 24 h
TsCl, py
20 οC, 20 h
TsCl, py
mixture of products
0 οC-20 ο
C
OTHP
OH
24-72 h
14
60 (69%)
(68%)
58
(11%)
OH
Cl
SePh
OTs
OTHP
Cl
Se
Se
8
Na2Se2
PPh3, CCl4
reflux, 20 h
cat. TsOH
DMF, 100 οC, 24 h
MeOH
50 oC, 4 h
(22%)
(86%)
(62%)
39
59
38
61
Scheme 8. Synthesis of 10-hydroxyisopinocampheyl chloride 39.
Scheme 9. Formation of cyclic diselenide 61.

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10166
a stereoselection correlated with ability of heteroatoms to donate
electrons into the sigma-* orbital of the selenium atom in the
N<O<S series.16 In the reported research we have observed the
opposite tendency for electrophiles 46a, 50a or 51a with OPh, SPh,
and SePh groups (O>SzSe).
Among the selenium electrophiles 52a–57a with the selenenyl
group (SeOTf) positioned trans relative to the group bound to C-2,
the best results have been obtained for triflate 55a with a penta-
fluorophenoxy group (OC6F5, dr 84:16) and 57a with a selenide
group (SePh, dr 72:28). Comparison with electrophiles 46a and 54a
with the opposite configuration at C-3, showed a decrease in
stereoselection for electrophile 54a, which seems to be caused by
a lack of Se/O interaction. Our results revealed that in methoxy-
selenenylation with electrophiles 54a, 56a, and 57a containing the
OPh, SPh or SePh groups, the stereoselectivity increases with the
atomic mass and the size of a heteroatom in the Se>S>O series.
Such a dependence of stereoselection on the size of a heteroatom
suggests that in these cases the effects connected with a steric
hindrance of the functional group has a predominant influence on
the asymmetric induction. The role of the substituents in the
pinane ring can be determined by comparison of a stereoselection
of nonfunctionalized electrophilic reagents 62 and 1a with func-
tionalized compounds 46a, and 52a–57a. Data for the pair of
electrophiles 62 and 46a suggest, that the increased selectivity
found for electrophile 46a when compared to unsubstituted 62, can
be caused by the Se/O interaction between the phenoxy group
oxygen and selenium atom. For triflates 52a–54a the presence of
a hydroxy, methoxy or phenoxy group in the C-10-position of
pinane reduces the stereoselectivity with respect to electrophile 1a.
On the other hand, an increase in asymmetric induction has been
Figure 1. Crystal structure of 51 with the thermal ellipsoids plotted at 30% probability.
or electron-donor (–OMe) substituents reduced the stereo-
selectivity of the reaction. Replacement of the etheral group of
electrophile 46a with a sulfide or a selenide group (electrophiles
50a and 51a) resulted in a considerable drop in the stereo-
selectivity. So far, the literature reports for chiral aryl electrophilic
reagents demonstrated a dependence in which the increase of
Table 2
Methoxyselenenylation of the styrene with the use of functionalized selenium electrophiles
OMe
1. 1M Br2, CCl4
2. AgOTf, MeOH
Ter*Se
*
, MeOH
CH2Cl2 −78 ο
C
Ter*Se OTf
Ter*Se)2
CH2Cl2 −78 ο
C
63-75
Entry
Alkene
Electrophile
Product
Dr
Yield [%]
1
2
3
4
62
63
64
65
66
67
68
69
70
71
72
73
74
75
52:48
70:30
65:35
61:39
52:48
56:44
82:18
52:48
52:48
52:48
86:14
56:44
72:28
48
70
40
65
82
14
57
61
80
73
56
63
28
46a
47a
48a
50a
51a
1a
52a
53a
54a
55a
56a
57a
5
OMe
6
7a
8
Ter*Se
*
9
10
11
12
13
a
See ref 5.
OPh
Se OTf
OC6H4NO2
Se OTf
SePh
Se OTf
OC6H4OMe
Se OTf
SPh
Se OTf
Se OTf
62
48a
47a
51a
46a
50a
OH
Se OTf
OPh
Se OTf
OC6F5
Se OTf
SePh
Se OTf
OMe
SPh
Se OTf
Se OTf
Se OTf
1a
52a
53a
55a
57a
54a
56a

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10167
Table 3
observed for the bulky aryl group –OC6F5 of electrophile 55a and
Selected structural parameters for bromides 76–80
phenylselanyl group –SePh in 57a, suggesting a dependence of the
stereoselection on steric effects.
Entry
Electrophile
rSe/Xa, [Å]
qX/Se-Brb, [deg]
To confirm the hypothesis concerning the role of the selenium–
heteroatom interactions in the cis-pinane system, the molecular
modeling was performed with density functional theory (DFT)
using the B3LYP method17 and a 6–311G(d) functional base, as
implemented in GAUSSIAN 03.18 The aim was an optimization of
geometric parameters for the selected selenium electrophiles and
to check if a linear arrangement of heteroatom with a selenenyl
group is possible. Calculations have been conducted for selenenyl
bromides containing phenoxy 76, p-nitrophenoxy 77, p-methoxy-
phenoxy 78, phenylsulphanyl 79, and phenylselanyl 80 groups.
The optimized structures are presented in Figure 2.
On the basis of the calcd structural parameters (Table 3) it can be
established that atomic distances (rSe/X) between the selenium
atom (SeBr) and heteroatoms (O, S, Se) are significantly smaller
then the sum of the van der Waals radii (Se/O, 3.40 Å Se/S, 3.68 Å
Se/Se, 3.76 Å).19
1
2
3
4
5
76
77
78
79
80
2.66
2.67
2.56
2.88
2.90
172.0
169.6
170.6
173.9
176.0
a
Distance between selenium atom of SeBr and heteroatom.
Angle between bromine atom and heteroatom in X/Se–Br.
b
o-allylphenol led to dihydrobenzofuran derivatives 95 and 99. The
diastereomeric ratio was estimated on the basis of the 1H NMR and
77Se NMR spectroscopic analyses. A small increase in diaster-
eoselection was observed for methoxyselenenylation with
diselenide 93, in which the groups in positions 3 and 4 are in a cis-
relationship, compared to diselenide 97 in which these groups are
positioned trans. No differences were observed in the diaster-
eoselection for the selenocyclization reaction.
Furthermore, a near linear arrangement of X/Se–Br with angles
close to 180ꢁ (OX/Se–Br) revealed the presence of selenium-het-
eroatom interactions for the model compounds.
3. Conclusion
The selenocyclization of o-allylphenol with electrophiles gen-
erated from functionalized diselenides 46–57 was also investigated.
The resulting diselenides were transformed to the respective tri-
flate salts 46a–57a and converted to the dihydrobenzofuran de-
rivatives 81–91 in the reaction with o-allylphenol. The highest
stereoselectivity of selenocyclization was obtained for electrophile
55a with a OC6F5 group (dr 77:23) and for electrophile 57a with a –
SePh (Table 4).
The developed methodology was used to synthesize a series of
optically active dialkyl diselenides, derivatives of monoterpenes
from the pinane and carane systems and functionalized with hy-
droxy, methoxy, phenoxy, phenylsulfanyl and phenylselanyl
groups. We have developed a convenient method of oxidation of
products of the hydroboration reaction in the presence of a phe-
nylselanyl group with the use of NaBO3. It has been demonstrated
that when in the pinane system the functional group bound to C-2
is in a cis-relationship to the selenide group at the C-3-position,
the stereoselectivity of methoxyselenenylation of styrene is
increased relative to the nonfunctionalized pinocampheyl elec-
trophile. DFT calculations on model selenenyl bromides have
confirmed that the stereoselectivity may be coupled to the
interaction between a heteroatom and selenium atom in the
transition state of the addition reaction. For compounds having
substituents in the C-2 and C-3 positions in the cis stereochem-
istry, it is evident that the highest stereoselectivity of methoxy-
selenenylation can be achieved for a substituent with an oxygen
atom and it decreases with a size of the heteroatom (S and Se). For
We also conducted the syntheses of diselenides from the carane
system starting from alcohol 31 and used them in methoxy-
selenenylation and selenocyclization (Scheme 10).
The reaction of alcohol 31 with tosyl chloride in pyridine or with
carbon tetrachloride in the presence of triphenylphosphine gave
tosylate 92 and chloride 96, respectively, that were further trans-
formed to diselenides 93 and 97 with the use of disodium di-
selenide. During the reaction of diselenides with bromine and silver
triflate in situ, the triflate salts 93a and 97a were obtained. These
salts reacted with styrene and methanol giving the methoxy-
selenenylation products 94 and 98, whereas reaction with
Figure 2. Structures of 76–80 optimized with the DFT method. Heteroatoms are color-coded: nitrogen blue, oxygen red, sulfur yellow, selenium orange, bromine brown.

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10168
Table 4
Asymmetric selenocyclization of o-allylphenol
1. 1M Br2, CCl4
2. AgOTf, MeOH
*
HO
, MeOH
Ter*Se OTf
Ter*Se)2
CH2Cl2 −78 ο
C
CH2Cl2 −78 ο
C
O
Ter*Se
81-91
Entry
Alkene
Electrophile
Product
Dra
Yield
[%]
1
2
3
4
46a
47a
48a
50a
51a
52a
53a
54a
55a
56a
57a
81
82
83
84
85
86
87
88
89
90
91
63:37
63:37
61:39
61:39
56:44
d
23
28
34
60
57
d
5
*
6
7a
8
57:43
52:48
77:23
52:48
72:28
60
57
49
62
23
O
Ter*Se
HO
9
10
13
a
Dr estimated on the basis of 1H NMR and 77Se NMR.
compounds with these substituents at the C-2 positioned trans
relative to the selenide group at position C-3, the presence of
substituents with heteroatoms decreased the diastereomeric ex-
cesses in selenenylation when compared to a non-substituted
system. In these cases the increase in size of the heteroatoms or
the introduction of bulky groups improves the stereoselection of
addition and the effects connected with a steric hindrance of the
functional group have a dominating influence on the asymmetric
induction. The best results have been observed for –OC6F5 and
–SePh substituents. We demonstrated that the stereoselection of
selenocyclization is lower than the stereoselection of methoxy-
selenenylation in the investigated systems. The use of electro-
philes from the carane system in methoxyselenenylation of
styrene and selenocyclization of o-allylphenol has not revealed
any significant improvement in the stereoselection. Until now the
results of addition and cyclization reactions with the use of ter-
pene selenium electrophiles are lower than presented for aryl
selenium electrophiles, inspite searching for new electrophiles
derived from natural products seems to be interesting course of
research.
4. Experimental section
4.1. General
Unless otherwise stated, all manipulations were performed in
dried glassware under argon atmosphere using dried solvents.
The 1H, 13C, and 77Se NMR spectra were measured in CDCl3 with
SePh
OMe
Se
e)
SePh
Se)2
SePh
SePh
OTs
Se OTf
(82%, dr 60:40)
94
a)
c)
d)
SePh
Se
O
f)
(40%)
(42%)
92
93
93a
SePh
OH
(64%, dr 54:46)
95
98
99
SePh
OMe
Se
e)
31
SePh
Se)2
SePh
Cl
SePh
Se OTf
(59%, dr 53:47)
c)
d)
b)
SePh
Se
O
f)
(76%)
96
(47%)
97
97a
(51%, dr 54:46)
Scheme 10. Synthesis of the functionalized diselenides from carane systems and selenenylation reaction. Reagents and conditions: (a) TsCl, py, 0 ꢁC/RT, 20 h; (b) CCl4, PPh3, reflux,
20 h; (c) (i) Se, NaOH, N2H4ꢀH2O, 100 ꢁC, 15 min; (ii) terpene chloride or tosylate, RT, 20 h (two steps); (d) (i) 1 M Br2/CCl4, ꢂ78 ꢁC, 15 min; (ii) AgOTf/MeOH, ꢂ78 ꢁC, 15 min (two
steps); e) styrene, ꢂ78 ꢁC, 5 h; f) o-allylphenol, ꢂ78 ꢁC, 5 h.

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10169
TMS as an internal standard. All melting points are uncorrected.
Elemental analyses were carried out by the Instrumental Analy-
ses Laboratory. All alcohols, chlorides, tosylates and diselenides
were obtained according to procedures described in the litera-
ture.5,6 The methoxyselenenylation and selenocyclization re-
actions were carried out according to the protocols described in
the literature.5,8
ppm; elemental analysis calcd (%) for C15H26O3 (254.37): C 70.83, H
10.30; found: C 70.98, H 10.44.
4.2.4. (1S)-(þ)-10-Methoxyisopinocampheol (9). Yield: 11.5 g (86%),
19
colorless oil; bp 72–74 ꢁC/0.6 Torr; [
a]
¼þ4.8 (c 5.4, CHCl3); 1H
D
NMR (200 MHz, CDCl3):
d
¼0.90 (s, 3H, CH3), 1.12 (d, 1H, J¼9.9 Hz,
CHH), 1.20 (s, 3H, CH3), 1.68–2.04 (m, 3H), 2.12–2.25 (m, 1H) 2.31
(bs, 1H, OH), 2.35–2.58 (m, 2H), 3.36 (s, 3H, OCH3), 3.38–3.43 (m,
2H), 4.23–4.34 (m, 1H); 13C NMR (50.3 MHz, CDCl3):
d
¼23.8 (CH3),
4.2. Synthesis of ethers and alcohols
27.5 (CH3), 34.3 (CH2), 36.9 (CH2), 38.0 (C), 41.8 (CH), 43.4 (CH), 53.1
(CH), 55.5 (OCH3), 68.3 (CH), 77.5 (CH2) ppm; elemental analysis
calcd (%) for C11H20O2 (184.28): C 71.70, H 10.94; found: C 71.62, H
10.73.
4.2.1. (1R)-Myrtenyl tetrahydro-2H-pyrane ether (6). A solution of
myrtenol (10.0 g, 65.7 mmol), dihydropyran (9.5 g, 112.7 mmol)
and p-TSA (130 mg) in CH2Cl2 (130 mL) was stirred at room
temperature for 18 h. The reaction mixture was washed with the
saturated Na2CO3 solution, water, brine and dried over anhydrous
MgSO4. The solvent was evaporated, and the residue was purified
by distillation to afford the desired ether 6 (11.5 g, 74%) as a col-
orless oil; bp 84–86 ꢁC/0.15 Torr; 1H NMR (300 MHz, CDCl3):
4.2.5. (1S)-(þ)-10-Phenoxyisopinocampheol (13). Yield: 3.2 g (74%),
17
colorless oil; [
a
]
¼þ0.7 (c 4.12, CHCl3); 1H NMR (200 MHz, CDCl3):
D
d
¼0.94 (s, 3H, CH3),1.19 (d,1H, J¼9.6 Hz, CHH),1.25 (s, 3H, CH3),1.82
(dd,1H, J¼13.5 Hz, J¼4.5 Hz), 2.01 (d, 2H, J¼6.1 Hz, CH2), 2.28 (d,1H,
J¼2.7 Hz), 2.41–2.59 (m, 3H), 3.94–4.05 (m, 2H), 4.33–4.44 (m, 1H),
6.90–6.99 (m, 3H, arom. H), 7.27–7.33 (m, 2H, arom. H); 13C NMR
mixture of diastereomers
d
¼0.84 (s, 3H; CH3), 1.18 (d, J¼8.7 Hz,
1H, CHH), 1.28 (s, 3H, CH3), 1.46–1.90 (m, 6H), 2.06–2.20 (m, 2H),
2.23–2.33 (m, 2H), 2.35–2.44 (m, 1H), 3.46–3.55 (m, 1H), 3.84–
3.93 (m, 2H), 3.99–4.09 (m, 1H), 4.62 (m, 1H), 5.45–5.52 (m, 1H);
(50.3 MHz, CDCl3):
d
¼23.9 (CH3), 27.3 (CH3), 34.0 (CH2), 37.1 (CH2),
38.0 (C), 41.7 (CH), 43.3 (CH), 52.7 (CH), 67.8 (CH), 71.8 (CH2), 114.4
(2ꢀCH), 120.8 (CH), 129.4 (2ꢀCH), 158.7 (C) ppm; elemental anal-
ysis calcd (%) for C16H22O2 (246.34): C 78.01, H 9.00; found: C 77.95,
H 8.91.
13C NMR (50.3 MHz, CDCl3): mixture of diastereomers
d
¼19.3
(CH2), 19.4 (CH2), 20.9 (CH3), 21.0 (CH3), 25.4 (CH2), 25.5 (CH2),
26.0 (CH3), 26.1 (CH3), 30.5 (CH2), 30.6 (CH2), 31.0 (CH2), 31.2
(CH2), 31.3 (CH2), 31.5 (CH2), 37.9 (C), 38.0 (C), 40.8 (CH), 40.9
(CH), 43.3 (CH), 43.6 (CH), 61.9 (CH2), 62.0 (CH2), 69.4 (CH2), 69.5
(CH2), 97.1 (CH), 97.4 (CH), 118.9 (CH), 119.4 (CH) ppm; elemental
analysis calcd (%) for C15H24O2 (236.35): C 76.23, H 10.24; found:
C 76.02, H 10.17.
4.2.6. (1S)-(-)-10-Pentafluorophenoxyisopinocampheol (14). Yield:
20
1.8 g, (57%); colorless oil; [
(200 MHz, CDCl3):
a
]
D
¼ꢂ0.2 (c 2.09, CHCl3); 1H NMR
d
¼0.88 (s, 3H, CH3), 1.20 (d, 1H, J¼9.6 Hz, CHH),
1.23 (s, 3H, CH3), 1.76–1.88 (m, 1H), 1.97–2.06 (m, 2H), 2.18 (m, 1H),
2.21–2.63 (m, 3H), 4.19 (d, 2H, J¼7.8 Hz, CH2), 4.34–4.46 (m, 1H);
13C NMR (50.3 MHz, CDCl3):
37.2 (CH2), 37.8 (C), 41.4 (CH), 42.8 (CH), 53.2 (CH), 67.4 (CH), 79.6 (t,
J¼3.4 Hz, CH2) ppm; elemental analysis calcd (%) for C16H17F5O2
(336.30): C 57.14, H 5.10; found: C 57.10, H 5.08.
d
¼23.7 (CH3), 27.1 (CH3), 33.4 (CH2),
4.2.2. (R)-(-)-Methyl myrtenyl ether (7). To a solution of sodium
hydride (4.7 g, 197.1 mmol) in dry THF (110 mL), the THF (100 mL)
solution of myrtenol (15.0 g, 98.5 mmol) was slowly added at room
temperature. After stirring for 20 min, methyl iodide (12.3 mL,
197.1 mmol) was added dropwise. The resulting solution was stir-
red at 20 ꢁC for 24 h. The reaction was quenched by addition of
water, then the volatiles were removed under reduced pressure.
Subsequently ethyl acetate (100 mL) was added and the mixture
was washed sequentially with water, saturated aq Na2S2O3 and
brine. The organic phase was dried over magnesium sulfate, fil-
tered, and the solvent was removed under vacuum. The crude
product was purified by the distillation under reduced pressure to
4.2.7. (1S)-(-)-10-(3,5-Di-tert-butyl-4-hydroxyphenyl)isopinocampheol
20
(24). Yield: 1.6 g (59%), colorless oil; [
a
]
D
¼ꢂ15.3 (c 3.59, CHCl3);
1H NMR (200 MHz, CDCl3):
d
¼1.04 (s, 3H, CH3), 1.19 (d,1H, J¼9.9 Hz,
CHH), 1.24 (s, 3H, CH3), 1.44 (s, 18H, 6ꢀCH3), 1.67 (ddd, 1H,
J¼14.0 Hz, J¼4.6 Hz, 2.0 Hz), 1.90–1.99 (m, 3H), 2.03–2.17 (m, 1H),
2.30–2.58 (m, 2H), 2.64–2.70 (m, 2H), 4.16–4.27 (m, 1H), 5.07 (s, 1H,
OH), 7.00 (s, 2H, arom. H); 13C NMR (50.3 MHz, CDCl3):
d
¼24.0
(CH3), 27.6 (CH3), 30.3 (6ꢀCH3), 34.0 (2ꢀC), 34.2 (CH2), 37.9 (C),
38.0 (CH2), 41.4 (CH), 41.6 (CH2), 45.1 (CH), 55.3 (CH), 69.6 (CH),
125.3 (2ꢀCHar),131.4 (Car),136.0 (2ꢀCar), 151.9 (Car) ppm; elemental
analysis calcd (%) for C24H38O2 (358.56): C 80.39, H 10.68; found: C
80.37, H 10.64.
afford ether 7 (12.5 g, 76%) as a colorless liquid; bp 36–38 ꢁC/
20
0.6 Torr; [
d
a]
¼ꢂ32.6 (c 8.0, CHCl3); 1H NMR (300 MHz, CDCl3):
D
¼0.84 (s, 3H, CH3), 1.17 (d, 1H, J¼9.9 Hz, CHH), 1.29 (s, 3H, CH3),
2.08–2.14 (m, 1H), 2.16 (dt, 1H, J¼5.7 Hz, J¼1.5 Hz), 2.25–2.30 (m,
2H), 2.40 (dt, 1H, J¼8.7 Hz, J¼5.7 Hz), 3.29 (s, 3H, OCH3), 3.76–3.79
(m, 2H), 5.48–5.51 (m, 1H); 13C NMR (75.5 MHz, CDCl3):
d
¼21.0
4.2.8. General procedure for a preparation of aryl ethers 11, 12, 16, 17,
20, and 23. To a stirred solution of sodium hydride (33.0 mmol) in
DMF (20 mL) under Argon, a DMF (10 mL) solution of phenol
(33.0 mmol) was slowly added at room temperature. The reaction
mixture was stirred for 20 min, then a solution of terpene chloride
(30.0 mmol) in DMF (10 mL) was added and the mixture was stirred
at 100 ꢁC for 20 h. After quenching with water, the mixture was
extracted with Et2O (3ꢀ40 mL), and the combined organic phases
were washed with a 1.5 M solution of NaOH, water, brine, and dried
over anhydrous MgSO4. The solvent was removed under vacuum,
and the crude product was purified by silica gel column
chromatography.
(CH3), 26.1 (CH3), 31.2 (CH2), 31.5 (CH2), 37.9 (C), 40.9 (CH), 43.3
(CH), 57.7 (OCH3), 75.5 (CH2), 119.9 (CH]), 145.3 (C]) ppm; ele-
mental analysis calcd (%) for C11H18O (166.26): C 79.46, H 10.91;
found: C 79.40, H 10.88.
4.2.3. (1S)-10-(Tetrahydro-2H-pyran-2-yloxy)isopinocampheol
(8). Yield: 9.0 g, (75%), colorless oil; bp 120–122 ꢁC/0.2 Torr; 1H
NMR (200 MHz, CDCl3): mixture of diastereomers
d
¼0.90 (s, 3H,
CH3), 1.12 (d, J¼9.8 Hz, 1H CHH), 1.20 (s, 3H, CH3), 1.47–1.68 (m, 4H),
1.70–2.03 (m, 5H), 2.16–2.60 (m, 4H), 3.34–3.58 (m, 2H), 3.62–3.93
(m, 2H), 4.36–4.44 (m, 1H), 4.62 (m, 1H); 13C NMR (50.3 MHz,
CDCl3): mixture of diastereomers
d
¼19.3 (CH2), 19.5 (CH2), 23.6
(CH3), 23.7 (CH3), 25.0 (CH2), 25.1 (CH2), 27.2 (CH3), 27.3 (CH3), 30.4
(CH2), 30.5 (CH2), 33.9 (CH2), 34.1 (CH2), 36.5 (CH2), 36.6 (CH2), 37.8
(C), 41.6 (CH), 43.1 (CH), 43.4 (CH), 52.8 (CH), 61.9 (CH2), 62.4 (CH2),
67.5 (CH), 68.1 (CH), 71.7 (CH2), 72.0 (CH2), 98.6 (CH), 99.4 (CH)
4.2.8.1. (1R)-Myrtenyl phenyl ether (11). Yield: 3.6 g (53%), col-
20
orless oil; [
d
a
]
¼ꢂ12.6 (c 2.92, CHCl3); 1H NMR (300 MHz, CDCl3):
D
¼0.84 (s, 3H, CH3), 1.20 (d, 1H, J¼8.4 Hz, CHH), 1.30 (s, 3H, CH3),
2.09–2.15 (m, 1H), 2.20 (dt, 1H, J¼5.4 Hz, J¼1.2 Hz), 2.27–2.32 (m,

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10170
2H), 2.42 (dt, 1H, J¼8.7 Hz, J¼5.4 Hz), 4.34–4.44 (m, 2H, CH2), 5.58–
5.62 (m, 1H, CH]), 6.88–6.96 (m, 3H, arom. H), 7.25–7.38 (m, 2H,
4.2.9. General procedure for the preparation of alcohols 29 and
31. To a solution of olefin (15.0 g, 51.5 mmol) in dry THF (75 mL),
borane–dimethyl sulfide complex (5.2 mL, 10 M, 51.5 mmol) was
added dropwise at 0 ꢁC and stirred for 20 h at room temperature.
The reaction mixture was carefully quenched by addition of water
and stirred at room temperature until hydrogen was no longer
evolved. The volatiles were pumped off, then THF (75 mL) was
added. The reaction mixture was immersed in an ice-water bath,
then 3 M sodium hydroxide (8.6 mL, 25.8 mmol) and sodium per-
borate (7.9 g, 51.5 mmol) was added. The reaction mixture was
stirred at 0 ꢁC for 4 h, then at room temperature overnight. After
quenching with sodium chloride, the organic phase was separated
and dried over anhydrous MgSO4 in a presence of MnO2. The sol-
vent was removed under vacuum, and the crude product was
purified by column chromatography (silica gel, chloroform as an
eluent) to give the terpene alcohols with the phenylselenide group
as a yellow oils.
arom. H); 13C NMR (75.5 MHz, CDCl3):
d
¼21.0 (CH3), 26.2 (CH3), 31.2
(CH2), 31.5 (CH2), 38.1 (C), 40.8 (CH), 43.2 (CH), 70.5 (CH2), 114.8
(2ꢀCH), 120.1 (CH), 120.5 (CH), 129.2 (2ꢀCH), 144.0 (C]), 159.0
(CH) ppm; elemental analysis calcd (%) for C16H20O (228.33): C
84.16, H 8.83; found: C 84.06, H 8.76.
4.2.8.2. (1R)-(þ)-Myrtenyl pentafluorophenyl ether (12). Yield:
22
6.8 g (71%), colorless oil; [
a]
¼þ8.9 (c 3.33, CHCl3); 1H NMR
D
(200 MHz, CDCl3):
d
¼0.78 (s, 3H, CH3), 0.98 (d, 1H, J¼9.6 Hz, CHH),
1.31 (s, 3H, CH3), 2.04–2.13 (m, 1H), 2.24–2.45 (m, 4H), 4.51–4.63
(m, 2H), 5.60–5.68 (m, 1H, CH]); 13C NMR (50.3 MHz, CDCl3):
d
¼20.9 (CH3), 26.0 (CH3), 31.4 (CH2), 31.5 (CH2), 38.0 (C), 40.5 (CH),
43.3 (CH), 77.7 (t, J¼3.4 Hz, CH2), 124.4 (CH]), 143.5 (C]) ppm;
elemental analysis calcd (%) for C16H15F5O (318.28): C 60.38, H 4.75;
found: C 60.26, H 4.71.
4.2.8.3. (1S)-(þ)-10-(4-Nitrophenoxy)isopinocampheol
4.2.9.1. (1S)-(-)-10-Phenylselanylisopinocampheol (29). Yield:
24
17
(16). Yield: 2.4 g (28%), white solid; mp 95–98 ꢁC; [
a
]
¼þ5.6 (c
10.0 g (63%), yellow oil, [
(200 MHz, CDCl3):
CHH), 1.20 (s, 3H, CH3), 1.70–1.78 (m, 1H), 1.92–2.03 (m, 2H),
2.11–2.22 (m, 1H), 2.34–2.43 (m, 2H), 2.47–2.55 (m, 1H), 3.15 (d,
2H, J¼8.1 Hz, CH2), 4.20–4.28 (m, 1H), 7.24–7.31 (m, 3H, arom.
H), 7.48–7.53 (m, 2H, arom. H); 13C NMR (50.3 MHz, CDCl3):
a
]
¼ꢂ35.5 (c 5.18, CHCl3); 1H NMR
D
D
1.43, CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼0.94 (s, 3H, CH3), 1.19
d
¼0.90 (s, 3H, CH3), 1.06 (d, 1H, J¼9.0 Hz,
(d, 1H, J¼9.9 Hz, CHH), 1.26 (s, 3H, CH3), 1.82 (ddd, 1H, J¼14.1 Hz,
J¼4.8 Hz, 2.4 Hz), 1.97 (bs, 1H, OH), 2.00–2.09 (m, 2H), 2.43–2.62
(m, 3H), 4.05 (dd, 1H, J¼8.7 Hz, J¼6.6 Hz, CHH), 4.14 (dd, 1H,
J¼8.7 Hz, J¼8.7 Hz, CHH), 4.30–4.39 (m, 1H), 6.97 (d, 2H, J¼9.6 Hz,
arom. H), 8.20 (d, 2H, J¼9.6 Hz, arom. H); 13C NMR (50.3 MHz,
d
¼23.6 (CH3), 27.1 (CH3), 33.4 (CH2), 33.6 (CH2), 37.6 (CH2), 37.8
CDCl3):
d
¼24.0 (CH3), 27.3 (CH3), 33.8 (CH2), 37.7 (CH2), 38.0 (C),
(C), 41.3 (CH), 46.4 (CH), 52.8 (CH), 69.9 (CH), 126.7 (CH), 129.0
41.6 (CH), 43.1 (CH), 52.4 (CH), 67.4 (CH), 72.5 (CH2), 114.5
(2ꢀCH), 126.0 (2ꢀCH), 141.6 (C), 163.8 (C) ppm; elemental anal-
ysis calcd (%) for C16H21NO4 (291.34): C 65.96, H 7.27; found: C
65.87, H 7.20.
(2ꢀCH), 129.9 (C), 132.2 (2ꢀCH); 77Se NMR (38.1 MHz, CDCl3):
d
¼277.1 (Se) ppm; elemental analysis calcd (%) for C16H22OSe
(309.31): C 62.13, H 7.17; found: C 62.11, H 7.22.
4.2.9.2. (1S)-(-)-10-Phenylselanyl-4-isocaranol (31). Yield: 5.3 g
21
4.2.8.4. (1S)-(þ)-10-(4-Methoxyphenoxy)isopinocampheol
(33%), yellow oil; [
CDCl3):
a]
¼ꢂ63.4 (c 1.58, CHCl3); 1H NMR (300 MHz,
D
24
(17). Yield: 1.7 g (21%), colorless oil; [
a
]
¼þ1.9 (c 2.27, CHCl3); 1H
d
¼0.62 (m, 2H), 0.85–0.88 (m, 1H), 0.92 (s, 3H, CH3), 0.97 (s,
D
NMR (300 MHz, CDCl3):
d
¼0.93 (s, 3H, CH3), 1.18 (d, 1H, J¼9.9 Hz,
3H, CH3),1.45–1.67 (m, 3H), 2.06 (dd,1H, J¼14.4 Hz, J¼6.9 Hz), 2.13–
2.27 (m, 1H), 2.85 (dd, 1H, J¼12.0 Hz, J¼7.5 Hz, CHH), 3.25 (dd, 1H,
J¼12.0 Hz, 3.9 Hz, CHH), 3.32–3.42 (m, 1H, CH), 7.19–7.38 (m, 3H,
arom. H), 7.45–7.55 (m, 2H, arom. H); 13C NMR (50.3 MHz, CDCl3):
CHH), 1.24 (s, 3H, CH3), 1.80 (ddd, 1H, J¼13.8 Hz, 5.1 Hz, 1.8 Hz),
1.96–2.04 (m, 2H), 2.26 (bs, 1H, OH), 2.36–2.58 (m, 3H), 3.77 (s, 3H,
CH3), 3.89–3.99 (m, 2H, CH2), 4.36–4.42 (m, 1H, CH), 6.84 (s, 2H,
arom. H), 6.85 (s, 2H, arom. H); 13C NMR (75.5 MHz, CDCl3):
d¼23.8
d
¼15.8 (CH3), 17.8 (C), 20.0 (CH), 21.4 (CH), 26.1 (CH2), 28.7 (CH3),
(CH3), 27.3 (CH3), 33.9 (CH2), 37.1 (CH2), 38.4 (C), 41.6 (CH), 43.1
(CH), 52.7 (CH), 55.5 (CH3), 67.5 (CH), 72.5 (CH2), 114.4 (2ꢀCH),
115.3 (2ꢀCH), 152.8 (C), 153.8 (C) ppm; elemental analysis calcd (%)
for C17H24O3 (276.37): C 73.88, H 8.75; found: C 73.77, H 8.64.
30.7 (CH2), 32.0 (CH2), 42.3 (CH), 72.7 (CH), 126.6 (CH), 129.1
(2ꢀCH), 131.1 (C), 132.2 (2ꢀCH) ppm; elemental analysis calcd (%)
for C16H22OSe (309.31): C 62.13, H 7.17; found: C 62.32, H 7.45.
4.3. Synthesis of tosylates
4.2.8.5. (1S)-(-)-10-Phenylsulfanylisopinocampheol (20). Yield:
22
2.0 g (45%), yellow oil; [
a
]
¼ꢂ11.9 (c 6.15, CHCl3); 1H NMR
4.3.1. (1S)-(þ)-10-Methoxyisopinocampheyl tosylate (32). Yield:
D
24
(300 MHz, CDCl3):
d
¼0.92 (s, 3H, CH3), 1.18 (d, J¼9.9 Hz, 1H, CHH),
3.60 g (67%), colorless oil; [
a]
¼þ36.1 (c 7.4, CHCl3); 1H NMR
D
1.22 (s, 3H, CH3), 1.74 (ddd, 1H, J¼14.2 Hz, J¼4.6 Hz, J¼2.4 Hz), 1.90–
2.02 (m, 2H), 2.08–2.19 (m, 1H), 2.23 (bs, 1H, OH), 2.32–2.61 (m,
2H), 3.03 (d, J¼8.0 Hz, 2H, CH2), 4.28 (qui, 1H, J¼4.8 Hz, CH), 7.16–
(200 MHz, CDCl3):
d
¼0.83 (s, 3H, CH3), 1.14 (d, 1H, J¼9.6 Hz, CHH),
1.19 (s, 3H, CH3),1.85–1.99 (m, 2H), 2.03–2.14 (m, 2H), 2.32–2.42 (m,
2H), 2.44 (s, 3H, CH3), 3.14 (s, 3H, OCH3), 3.16–3.22 (m, 2H), 4.80
(ddd, 1H, J¼9.6 Hz, J¼5.4 Hz, J¼4.2 Hz, CH), 7.26–7.36 (m, 2H, arom.
7.38 (m, 5H, arom. H); 13C NMR (50.3 MHz, CDCl3):
d
¼23.8 (CH3),
27.4 (CH3), 33.6 (CH2), 37.8 (CH2), 38.0 (C), 39.1 (CH2), 41.5 (CH),
45.8 (CH), 52.2 (CH), 69.6 (CH), 126.1 (CH), 129.0 (2ꢀCH), 129.1
(2ꢀCH), 136.1 (C) ppm; elemental analysis calcd (%) for C16H22OS
(262.41): C 73.23, H 8.45; found: C 73.16, H 8.38.
H), 7.78–7.84 (m, 2H, arom. H); 13C NMR (50.3 MHz, CDCl3):
d¼21.5
(CH3), 24.0 (CH3), 27.0 (CH3), 32.9 (CH2), 36.1 (CH2), 38.0 (C), 41.3
(CH), 42.6 (CH), 49.1 (CH), 58.4 (OCH3), 74.1 (CH2), 77.9 (CH), 127.8
(2ꢀCH), 129.6 (2ꢀCH), 134.6 (C), 144.4 (C) ppm; elemental analysis
calcd (%) for C18H26O4S (338.46): C 63.88, H 7.74; found: C 63.97,
H 7.93.
4.2.8.6. (1R)-(-)-10-(3,5-Di-tert-butyl-4-hydroxyphenyl)-2-pinene
¼ꢂ4.5 (c 2.34, CHCl3); 1H
22
(23). Yield: 7.5 g (73%), colorless oil; [
NMR (200 MHz, CDCl3):
a
]
D
d
¼0.76 (s, 3H, CH3), 1.11 (s, 3H, CH3), 1.37
4.3.2. (1S)-(þ)-10-Phenoxyisopinocampheyl tosylate (33). Yield:
19
(d, 1H, J¼9.9 Hz, CH2), 1.43 (s, 18H, 6ꢀCH3), 1.97–2.42 (m, 5H),
2.08 g, (69%), white solid; mp 92–94 ꢁC; [
a
]
¼þ41.2 (c 2.32,
D
3.18–3.27 (m, 2H), 5.03 (s, 1H, OH), 5.25 (m, 1H), 6.98 (s, 2H, arom.
CHCl3); 1H NMR (200 MHz, CDCl3):
d
¼0.90 (s, 3H, CH3), 1.14 (d, 1H,
H); 13C NMR (50.3 MHz, CDCl3):
d¼21.0 (CH3), 26.2 (CH3), 30.3
J¼9.9 Hz, CHH), 1.21 (s, 3H, CH3), 1.91–2.15 (m, 2H), 2.18–2.26 (m,
1H), 2.36 (s, 3H, CH3), 2.37–2.62 (m, 3H), 3.69 (d, 2H, J¼7.0 Hz, CH2),
4.91–5.01 (m, 1H), 6.72 (d, 2H, J¼8.2 Hz, arom. H). 6.89–6.97 (m, 1H,
arom. H), 7.22–7.29 (m, 4H, arom. H), 7.82 (d, 2H, J¼8.2 Hz, arom.
(6ꢀCH3), 31.4 (CH2), 31.9 (CH2), 34.2 (2ꢀC), 37.8 (C), 40.6 (CH), 43.3
(CH2), 45.4 (CH), 117.3 (CH]), 125.4 (2ꢀCH), 129.9 (C), 135.4 (2ꢀC),
147.6 (C]), 151.8 (C) ppm; elemental analysis calcd (%) for C24H36
O
(340.54): C 84.65, H 10.66; found: C 84.71, H 10.74.
H); 13C NMR (75.5 MHz, CDCl3):
d
¼21.6 (CH3), 24.2 (CH3), 27.0

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10171
(CH3), 33.6 (CH2), 36.1 (CH2), 38.1 (C), 41.3 (CH), 42.9 (CH), 48.9
mixture of diastereomers
d
¼0.85 (s, 3H, CH3), 1.11–1.16 (m, 1H), 1.20
(CH), 68.5 (CH2), 77.2 (CH), 114.4 (2ꢀCH), 120.7 (CH), 127.8 (2ꢀCH),
129.3 (2ꢀCH), 129.8 (2ꢀCH), 134.2 (C), 144.6 (C), 158.5 (C) ppm;
elemental analysis calcd (%) for C23H28O4S (400.53): C 68.97, H 7.05;
found: C 68.85, H 7.01.
(s, 3H, CH3), 1.42–1.65 (m, 5H), 1.68–2.19 (m, 5H), 2.34 (m, 2H), 2.44
(s, 3H, CH3), 3.16–3.22 (m, 1H), 3.42–3.65 (m, 2H), 3.72–3.84 (m,
1H), 4.40–4.46 (m, 1H), 4.80–4.95 (m, 1H), 7.35 (m, 2H, arom. H),
7.81 (m, 2H, arom. H); 13C NMR (50.3 MHz, CDCl3): mixture of dia-
stereomers
d¼19.2 (CH2), 19.3 (CH2), 21.6 (2ꢀCH3), 24.0 (CH3), 24.2
4.3.3. (1S)-(þ)-10-(4-Nitrophenoxy)isopinocampheyl tosylate
(CH3), 25.3 (CH2), 25.4 (CH2), 27.0 (CH3), 27.1 (CH3), 30.3 (CH2), 30.4
(CH2), 32.9 (CH2), 33.4 (CH2), 36.0 (CH2), 36.1 (CH2), 38.0 (C), 38.1
(C), 41.3 (CH), 41.4 (CH), 42.8 (CH), 43.4 (CH), 49.4 (CH), 49.5 (CH),
61.8 (2ꢀCH2), 68.6 (CH2), 68.8 (CH2), 77.7 (CH), 77.9 (CH), 98.5 (CH),
98.9 (CH), 127.7 (2ꢀCH), 129.9 (2ꢀCH), 134.7 (C), 144.4 (C) ppm;
elemental analysis calcd (%) for C23H34O5S (422.58): C 65.37, H 8.11;
found: C 65.53, H 8.23.
23
(34). Yield: 1.80 g (91%), white solid; mp 98–99 ꢁC; [
a
]
¼þ23.8 (c
D
1.63, CHCl3); 1H NMR (200 MHz, CDCl3):
d¼0.92 (s, 3H, CH3), 1.18 (d,
1H, J¼9.9 Hz, CHH), 1.23 (s, 3H, CH3), 1.90–2.08 (m, 2H), 2.15–2.24
(m, 1H), 2.40 (s, 3H, CH3), 2.41–2.58 (m, 2H), 2.60–2.71 (m, 1H),
3.81–4.00 (m, 2H, CH2), 4.96–5.05 (m, 1H), 6.83 (d, 2H, J¼7.8 Hz,
arom. H), 7.28 (d, 2H, J¼7.8 Hz, arom. H), 7.82 (d, 2H, J¼7.8 Hz, arom.
H), 8.18 (d, 2H, J¼7.8 Hz, arom. H); 13C NMR (75.5 MHz, CDCl3):
d
¼21.6 (CH3), 24.2 (CH3), 27.0 (CH3), 33.3 (CH2), 35.8 (CH2), 38.1 (C),
4.3.8. (1S)-(þ)-10-Pentafluorophenoxyisopinocampheyl tosylate
19
41.3 (CH), 42.9 (CH), 48.9 (CH), 69.6 (CH2), 76.7 (CH), 114.4 (2ꢀCH),
125.8 (2ꢀCH),127.7 (2ꢀCH),129.8 (2ꢀCH),134.4 (C),141.6 (C),144.8
(C), 163.6 (C) ppm; elemental analysis calcd (%) for C23H27NO6S
(445.53): C 62.00, H 6.11; found: C 61.98, H 6.06.
(60). Yield: 1.80 g (69%), white solid; mp 90–92 ꢁC; [
a]
¼þ33.4 (c
D
1.64, CHCl3); 1H NMR (200 MHz, CDCl3):
d
¼0.83 (s, 3H, CH3), 1.17 (d,
1H, J¼9.9 Hz, CHH), 1.21 (s, 3H, CH3), 1.82–2.17 (m, 2H), 2.21–2.32
(m, 1H), 2.43 (s, 3H, CH3), 2.45–2.70 (m, 3H), 3.88 (d, 2H, J¼7.4 Hz,
CH2), 4.77–4.87 (m, 1H, CHSe), 7.28 (d, 2H, J¼7.8 Hz, arom. H), 7.78
4.3.4. (1S)-(þ)-10-(4-Methoxyphenoxy)isopinocampheyl tosylate
(d, 2H, J¼7.8 Hz, arom. H); 13C NMR (50.3 MHz, CDCl3):
¼21.4
d
21
(35). Yield: 1.32 g (83%), white solid; mp 73–76 ꢁC; [
a
]
¼þ39.6 (c
(CH3), 23.9 (CH3), 26.9 (CH3), 32.7 (CH2), 36.1 (CH2), 38.0 (C), 41.2
(CH), 42.3 (CH), 49.6 (CH), 76.1 (CH), 76.2 (CH2), 127.8 (2ꢀCH), 129.6
(2ꢀCH), 134.2 (C), 144.6 (C) ppm; elemental analysis calcd (%) for
C23H23F5O4S (490.48): C 56.32, H 4.73; found: C 56.23, H 4.70.
D
4.03, CHCl3); 1H NMR (200 MHz, CDCl3):
d
¼0.89 (s, 3H, CH3), 1.17 (d,
1H, J¼9.9 Hz, CHH), 1.21 (s, 3H, CH3), 1.84–2.12 (m, 3H), 2.18–2.24
(m, 1H), 2.38 (s, 3H, CH3), 2.40–2.62 (m, 2H), 3.65 (d, 2H, J¼7.2 Hz,
CH2), 3.77 (s, 3H, OCH3), 4.91–5.01 (m, 1H), 6.60–6.68 (m, 2H, arom.
H), 6.77–6.89 (m, 2H, arom. H), 7.26–7.36 (m, 2H, arom. H), 7.76–
4.3.9. (1S)-(-)-10-Phenylselanyl-4-isocaranyl tosylate (92). Yield:
20
7.84 (m, 2H, arom. H); 13C NMR (75.5 MHz, CDCl3):
d
¼21.5 (CH3),
2.42 g (40%), yellow oil; [
(200 MHz, CDCl3):
a
]
D
¼ꢂ36.6 (c 4.40, CHCl3); 1H NMR
24.1 (CH3), 27.0 (CH3), 33.2 (CH2), 36.0 (CH2), 38.0 (C), 41.3 (CH),
42.9 (CH), 49.0 (CH), 55.6 (OCH3), 69.3 (CH2), 77.2 (CH), 114.4
(2ꢀCH), 115.2 (2ꢀCH), 127.7 (2ꢀCH), 129.7 (2ꢀCH), 134.2 (C), 144.5
(C), 152.6 (C), 153.7 (C) ppm; elemental analysis calcd (%) for
C24H30O5S (430.56): C 66.95, H 7.02; found: C 66.92; H 6.93.
d
¼0.63–0.83 (m, 2H), 0.86 (s, 3H, CH3), 0.96 (s,
3H, CH3), 1.64–1.89 (m, 3H), 2.20–2.36 (m, 2H), 2.40 (dd, 1H,
J¼12.2 Hz, J¼9.8 Hz, CHH), 2.43 (s, 3H, CH3), 3.10 (dd, 1H, J¼12.2 Hz,
J¼3.4 Hz, CHH), 4.28 (dt, 1H, J¼9.8 Hz, J¼7.2 Hz, CH), 7.19–7.42 (m,
7H, arom. H), 7.77 (d, 2H, J¼8.4 Hz, arom. H); 13C NMR (50.3 MHz,
CDCl3):
d
¼15.6 (CH3), 17.9 (C), 19.7 (CH), 20.6 (CH), 21.6 (CH3), 25.4
4.3.5. (1S)-(þ)-10-Phenylsulphanylisopinocampheyl tosylate
(CH2), 27.7 (CH2), 28.2 (CH3), 30.6 (CH2), 39.9 (CH), 85.1 (CH), 126.5
(CH), 127.6 (2ꢀCH), 129.0 (2ꢀCH), 129.7 (2ꢀCH), 130.6 (C), 131.9
(2ꢀCH), 134.4 (C), 144.5 (C) ppm; elemental analysis calcd (%) for
C23H28O3SSe (463.49): C 59.60, H 6.09; found: C 59.52, H 6.01.
20
(37). Yield: 2.50 g (79%), yellow solid; mp 95–96 ꢁC; [
a
]
D
¼þ19.2 (c
1.88, CHCl3); 1H NMR (200 MHz, CDCl3):
d
¼0.87 (s, 3H, CH3), 1.03 (d,
1H, J¼9.9 Hz, CHH), 1.18 (s, 3H, CH3), 1.82–2.05 (m, 2H), 2.22–2.41
(m, 4H), 2.43 (s, 3H, CH3), 2.76 (dd, 1H, J¼10.5, J¼9.9 Hz, CHH), 2.98
(dd, 1H, J¼10.5 Hz, J¼3.8 Hz, CHH), 4.82–4.94 (m, 1H), 7.16–7.26 (m,
5H, arom. H), 7.34 (d, 2H, J¼7.8 Hz, arom. H), 7.80 (d, 2H, J¼7.8 Hz,
4.4. Synthesis of chlorides
arom. H); 13C NMR (50.3 MHz, CDCl3):
d
¼21.6 (CH3), 23.8 (CH3), 27.0
4.4.1. (1S)-(-)-10-Hydroxypinocampheyl chloride (39). A mixture of
(1S)-10-(tetrahydro-2H-pyran-2-yloxy)pinocampheyl chloride
(2.0 g, 7.3 mmol) and p-toluenesulfonic (100 mg) acid in methanol
(50 mL) was stirred at 50 ꢁC for 4 h. The resulting mixture was
allowed to stir at room temperature, then a saturated solution of
sodium hydrogen carbonate (10 mL) was added and stirring was
continued for another 30 min. The organic phase was separated,
and the aqueous layer was extracted with ethyl acetate (2ꢀ50 mL).
The combined organic phases were washed with water and brine,
dried over MgSO4, filtered and the solvent was removed under
vacuum. The crude product was purified by column chromatogra-
phy (silica gel, petroleum ether/chloroform/ethyl acetate¼15/7/1 as
(CH3), 33.0 (CH2), 36.2 (CH2), 36.6 (CH2), 38.1 (C), 41.2 (CH), 43.1
(CH), 48.8 (CH), 80.5 (CH), 125.9 (CH), 127.8 (2ꢀCH), 128.8 (4ꢀCH),
129.8 (2ꢀCH),134.3 (C),136.1 (C),144.7 (C) ppm; elemental analysis
calcd (%) for C23H28O3S2 (416.60): C 66.31, H 6.77; found: C 66.39,
H 6.70.
4.3.6. (1S)-(þ)-10-(Phenylselanyl)isopinocampheyl tosylate
22
(38). Yield: 4.61 g (88%), white solid; mp 67–69 ꢁC [
a
]
¼þ5.7 (c
D
7.60, CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼0.84 (s, 3H, CH3), 1.01 (d,
1H, J¼9.9 Hz, CHH), 1.14 (s, 3H, CH3), 1.86–2.00 (m, 2H), 2.24–2.42
(m, 4H), 2.43 (s, 3H, CH3), 2.77 (dd, 1H, J¼12.3 Hz, J¼12.3 Hz, CHH),
2.93 (dd, 1H, J¼12.3 Hz, J¼4.2 Hz, CHH), 4.75 (ddd, 1H, J¼9.6 Hz,
J¼5.4 Hz, J¼4.2 Hz, CH), 7.21–7.26 (m, 3H, arom. H), 7.31 (d, 2H,
J¼8.4 Hz, arom. H), 7.36–7.41 (m, 2H, arom. H), 7.79 (d, 2H, J¼8.4 Hz,
an eluent) to afford deprotected alcohol 39 (1.20 g, 86%) as a col-
21
orless oil. [
d
a
]
¼ꢂ18.0 (c 3.9, CHCl3); 1H NMR (200 MHz, CDCl3):
D
¼0.88 (s, 3H; CH3), 1.12 (d, J¼9.8 Hz, 1H, CHH), 1.22 (s, 3H, CH3),
2ꢀCH); 13C NMR (50.3 MHz, CDCl3):
d
¼21.6 (CH3), 23.7 (CH3), 26.9
1.75–1.84 (m, 1H), 1.93–2.02 (m, 2H), 2.08 (bs, 1H, OH), 2.20–2.35
(m, 1H), 2.38–2.62 (m, 2H), 3.54 (dd, J¼10.4, J¼6.2 Hz, 1H, CHH),
3.54 (dd, J¼10.4, J¼10.4 Hz, 1H, CHH), 4.28 (qui, J¼5.4, 1H, CHSe);
(CH3), 31.0 (CH2), 33.0 (CH2), 36.1 (CH2), 38.0 (C), 41.2 (CH), 43.7
(CH), 49.8 (CH), 81.1 (CH), 126.7 (CH), 127.7 (2ꢀCH), 129.0 (2ꢀCH),
129.7 (2ꢀCH), 130.2 (C), 132.2 (2ꢀCH), 134.2 (C), 144.6 (C); 77Se
13C NMR (50.3 MHz, CDCl3):
d¼23.6 (CH3), 27.0 (CH3), 33.0 (CH2),
NMR (38.1 MHz, CDCl3):
d
¼280.8 (Se) ppm; elemental analysis
37.3 (CH2), 37.6 (C), 41.3 (CH), 44.4 (CH), 48.5 (CH2), 55.5 (CH), 67.9
(CH) ppm; elemental analysis calcd (%) for C10H17ClO (188.69): C
63.35, H 9.08; found: C 66.31, H 9.04.
calcd (%) for C23H28O3SSe (463.49): C 59.60, H 6.09; found: C 59.64,
H 6.16.
4.3.7. (1S)-10-(Tetrahydro-2H-pyran-2-yloxy)isopinocampheyl tosy-
4.4.2. (1S)-(-)-10-Methoxypinocampheyl chloride (40). Yield: 4.60 g
24
late (58). Yield: 4.9 g (68), colorless oil; 1H NMR (300 MHz, CDCl3):
(69%), colorless oil; bp 54–56 ꢁC/0.3 Torr; [
a
]
¼ꢂ24.2 (c 5.9,
D

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10172
CHCl3); 1H NMR (200 MHz, CDCl3):
d
¼0.98 (s, 3H, CH3), 1.20 (s, 3H,
NMR (300 MHz, CDCl3): mixture of diastereomers
d
¼0.88 (s, 3H,
CH3), 1.24 (d, 1H, J¼9.8 Hz, CHH), 1.85–1.96 (m, 1H), 2.14–2.28 (m,
3H), 2.56–2.79 (m, 2H), 3.33 (s, 3H, OCH3), 3.44 (dd, 1H, J¼10.2 Hz,
J¼5.8, Hz, CHH), 3.86 (dd, 1H, J¼10.2 Hz, J¼8.6 Hz, CHH), 4.73 (dt,
CH3), 1.10 (d, J¼9.6 Hz,1H, CHH), 1.24 (s, 3H, CH3),1.50–1.60 (m, 2H),
1.68–2.03 (m, 5H), 2.16–2.54 (m, 4H), 3.47–3.54 (m, 2H), 3.64 (dd,
J¼10.5, J¼6.6 Hz,1H, CHH), 3.80 (dd, J¼10.5, J¼4.5 Hz,1H CHH), 3.86
(m, 2H), 4.68–4.78 (m, 1H); 13C NMR (50.3 MHz, CDCl3): mixture of
1H, J¼8.6 Hz, J¼6.0 Hz, CH); 13C NMR (50.3 MHz, CDCl3):
¼22.8
d
(CH3), 26.8 (CH3), 27.7 (CH2), 38.6 (CH2), 39.0 (C), 41.2 (CH), 45.3
(CH), 45.4 (CH), 53.5 (CH), 58.2 (OCH3), 74.3 (CH2) ppm; elemental
analysis calcd (%) for C11H19ClO (202.74): C 65.17, H 9.45; found: C
65.34, H 9.61.
diastereomers
d
¼19.4 (CH2), 20.0 (CH2), 23.4 (CH3), 23.6 (CH3), 25.5
(CH2), 25.6 (CH2), 27.1 (CH3), 27.2 (CH3), 31.2 (CH2), 32.2 (CH2), 32.5
(CH2), 35.1 (CH2), 36.9 (CH2), 38.0 (C), 38.3 (C), 41.3 (CH), 41.5 (CH),
41.9 (CH), 43.1 (CH), 47.4 (CH2), 48.0 (CH2), 52.7 (CH), 53.2 (CH), 62.5
(CH2), 63.1 (CH2), 70.5 (CH), 73.3 (CH), 96.0 (CH), 99.3 (CH) ppm;
elemental analysis calcd (%) for C15H25ClO2 (272.81): C 66.04, H
9.24; found: C 66.31, H 9.54.
4.4.3. (1S)-(-)-10-Phenoxypinocampheyl chloride (41). Yield: 1.71 g
20
(43%), colorless liquid; [
(300 MHz, CDCl3):
a
]
D
¼ꢂ23.3 (c 2.06, CHCl3). 1H NMR
d
¼1.06 (s, 3H, CH3), 1.23 (s, 3H, CH3), 1.25 (d, 1H,
J¼9.9 Hz, CHH), 1.93–1.99 (m, 1H), 2.24–2.39 (m, 3H), 2.69 (ddd, 1H,
J¼14.4 Hz, J¼9.9 Hz, J¼4.8 Hz), 3.02 (dddd, 1H, J¼10.2 Hz,
J¼10.2 Hz, J¼6.9 Hz, J¼3.3 Hz), 4.05 (dd, 1H, J¼9.9 Hz, J¼6.9 Hz,
CHH), 4.50 (dd, 1H, J¼9.9 Hz, J¼6.3 Hz, CHH), 4.82 (ddd, 1H,
J¼10.2 Hz, J¼10.2 Hz, J¼7.2 Hz, CH), 6.68–6.98 (m, 2H, arom. H),
4.4.8. (1S)-(þ)-10-Phenylselanyl-4-caranyl chloride (96). Yield:
20
2.80 g (76%), yellow oil; [
a
]
¼þ83.6 (c 4.26, CHCl3); 1H NMR
D
(300 MHz, CDCl3):
d
¼0.38 (dt, 1H, J¼9.3 Hz), 0.83–0.97 (m, 2H),
0.99 (s, 3H, CH3), 1.09 (s, 3H, CH3), 1.64–1.74 (m, 1H), 1.78–1.87 (m,
1H), 1.98 (dt, 1H, J¼17.1 Hz, J¼2.4 Hz), 2.59 (dt, 1H, J¼17.1 Hz,
J¼9.0 Hz), 2.87 (dd, 1H, J¼12.6 Hz, J¼6.6 Hz, CHH), 2.87 (dd, 1H,
J¼12.6 Hz, J¼8.1 Hz, CHH), 4.56–4.63 (m, 1H, CH), 7.21–7.31 (m, 3H,
arom. H), 7.45–7.53 (m, 2H, arom. H); 13C NMR (75.5 MHz, CDCl3):
7.23–7.37 (m, 3H, arom. H); 13C NMR (75.5 MHz, CDCl3):
d¼22.8
(CH3), 26.9 (CH3), 27.7 (CH2), 38.6 (CH2), 39.1 (C), 41.1 (CH), 44.5
(CH), 44.8 (CH), 53.1 (CH), 69.2 (CH2), 114.7 (2ꢀCH), 120.6 (CH),
129.4 (2ꢀCH), 158.8 (C) ppm; elemental analysis calcd (%) for
C16H21ClO (264.79): C 72.57, H 7.99; found: C 72.54, H 7.98.
d
¼15.9 (CH3), 17.4 (CH), 18.0 (C), 20.7 (CH2), 23.4 (CH), 28.6 (CH3),
29.2 (CH2), 32.0 (CH2), 40.0 (CH), 61.3 (CH), 126.8 (CH), 129.0
(2ꢀCH), 130.3 (C), 132.5 (2ꢀCH); 77Se NMR (38.1 MHz, CDCl3):
4.4.4. (1S)-(-)-10-Pentafluorophenoxypinocampheyl chloride
(42). Yield: 3.70 g (72%), colorless oil; [
d
¼266.7 (Se); elemental analysis calcd (%) for C16H21ClSe (327.75):
22
a
]
¼ꢂ35.6 (c 4.10, CHCl3);
C 58.63, H 6.46; found: C 58.76, H 6.57.
D
1H NMR (300 MHz, CDCl3):
d
¼1.01 (s, 3H, CH3),1.24 (s, 3H, CH3),1.28
(d, 1H, J¼9.9 Hz, CHH), 1.90–1.99 (m, 1H), 2.25 (ddt, 1H, J¼14.4 Hz,
J¼7.5 Hz, J¼1.5 Hz), 2.31–2.41 (m, 2H), 2.68 (ddd, 1H, J¼14.4 Hz,
J¼9.9 Hz, J¼4.8 Hz), 3.02 (dddd, 1H, J¼9.9 Hz, J¼9.9 Hz, J¼6.6 Hz,
J¼3.0 Hz), 4.28 (dd, 1H, J¼9.6 Hz, J¼7.2 Hz, CHH), 4.64 (dd, 1H,
J¼9.6 Hz, J¼6.6 Hz, CHH), 4.77 (ddd,1H, J¼9.9 Hz, J¼9.9 Hz, J¼7.2 Hz,
4.5. Synthesis of diselenides
4.5.1. (1S,10S)-(þ)-Bis(10-methoxypinocampheyl) diselenide
30
(45). Yield: 2.10 g (81%), yellow oil; [
a]
¼þ44.2 (c 3.6, CHCl3); 1H
D
NMR (200 MHz, CDCl3):
d
¼0.92 (s, 6H, CH3), 1.19 (s, 6H, CH3), 1.37
CHSe); 13C NMR (75.5 MHz, CDCl3):
d
¼22.7 (CH3), 26.7 (CH3), 27.6
(d, 2H, J¼9.3 Hz, CHH), 1.90–1.95 (m, 2H), 2.06 (dd, 2H, J¼14.1 Hz,
J¼9.3 Hz), 2.14–2.24 (m, 4H), 2.52 (ddd, 2H, J¼14.1 Hz, J¼9.3 Hz,
J¼4.8 Hz), 2.64–2.70 (m, 2H), 3.32 (s, 6H, OCH3), 3.43 (dd, 2H,
J¼9.3 Hz, J¼6.0 Hz, CHH), 3.79 (dd, 2H, J¼9.3 Hz, J¼7.2 Hz, CHH),
(CH2), 38.6 (CH2), 39.0 (C), 41.0 (CH), 44.6 (CH), 45.4 (CH), 52.3 (CH),
77.0 (t, J¼2.9 Hz, CH2) ppm; elemental analysis calcd (%) for
C16H16ClF5O (354.74): C 54.17, H 4.55; found: C 54.16, H 4.52.
4.11 (q, 2H, J¼9.6 Hz, CH); 13C NMR (50.3 MHz, CDCl3):
¼23.0
d
4.4.5. (1S)-(-)-10-Phenylsulfanylpinocampheyl chloride (43). Yield:
(2ꢀCH3), 27.1 (2ꢀCH3), 27.2 (2ꢀCH2), 36.4 (2ꢀCH2), 37.5 (2ꢀCH),
39.2 (2ꢀC), 41.8 (2ꢀCH), 44.4 (2ꢀCH), 45.6 (2ꢀCH), 58.2 (2ꢀOCH3),
20
1.30 g (41%), colorless liquid; [
(300 MHz, CDCl3):
a
]
D
¼ꢂ32.2 (c 4.90, CHCl3); 1H NMR
d
¼1.08 (s, 3H, CH3), 1.18 (d, 1H, J¼10.2 Hz, CHH),
76.2 (2ꢀCH2); 77Se NMR (38.1 MHz, CDCl3):
¼366.5 ppm; ele-
d
1.21 (s, 3H, CH3), 1.90–1.96 (m, 1H), 2.20–2.42 (m, 3H), 2.66 (ddd, 1H
J¼14.7 Hz, J¼9.9 Hz, J¼5.1 Hz), 2.70–2.79 (m, 1H), 3.12 (dd, 1H,
J¼13.5 Hz, J¼9.3 Hz, CHH), 3.58 (dd, 1H, J¼13.5 Hz, J¼6.0 Hz, CHH),
4.77 (ddd, 1H, J¼9.9 Hz, J¼9.9 Hz, J¼7.8 Hz, CH), 7.22–7.36 (m, 5H,
mental analysis calcd (%) for C22H38Se2 (492.46): C 53.66, H 7.78;
found: C 53.81, H 7.94.
4.5.2. (1S,10S)-(þ)-Bis(10-phenoxypinocampheyl) diselenide
18
arom. H); 13C NMR (75.5 MHz, CDCl3):
d
¼22.8 (CH3), 26.8 (CH3),
(46). Yield: 170 mg (30%), yellow oil; [
a
]
D
¼þ131.8 (c 6.23, CHCl3);
27.9 (CH2), 35.9 (CH2), 38.7 (CH2), 39.2 (C), 41.2 (CH), 44.4 (CH), 45.0
(CH), 54.7 (CH), 125.7 (CH), 128.8 (2ꢀCH), 128.9 (2ꢀCH), 136.9 (C)
ppm; elemental analysis calcd (%) for C16H21ClS (280.86): C 68.42; H
7.54%. found: C 68.65, H 7.83.
1H NMR (300 MHz, CDCl3):
d
¼1.00 (s, 6H, CH3), 1.23 (s, 6H, CH3),
1.42 (d, 2H, J¼10.2 Hz, CHH), 1.97 (q, 2H, J¼4.8 Hz,), 2.06 (dd, 2H,
J¼13.8 Hz, J¼9.3 Hz,), 2.23–2.38 (m, 4H), 2.56 (ddd, 2H, J¼13.8 Hz,
J¼9.6 Hz, J¼4.8 Hz), 2.95 (dddd, 2H, J¼10.5 Hz, J¼10.5 Hz, J¼6.9 Hz,
J¼3.6 Hz), 4.04 (dd, 2H, J¼9.6 Hz, J¼6.9 Hz, CHH), 4.20 (q, 2H,
J¼9.9 Hz, CHSe), 4.46 (dd, 2H, J¼9.6 Hz, J¼6.9 Hz, CHH), 6.90–6.97
(m, 6H, arom. H), 7.23–7.32 (m, 4H, arom. H); 13C NMR (50.3 MHz,
4.4.6. (1S)-(-)-10-Phenylselanylpinocampheyl chloride (44). Yield:
21
3.10 g (73%), yellow oil; [
a
]
¼ꢂ47.5 (c 10.54, CHCl3); 1H NMR
D
(300 MHz, CDCl3):
d
¼1.05 (s, 3H, CH3), 1.17 (s, 3H, CH3), 1.19 (d, 1H,
CDCl3):
d
¼23.0 (2ꢀCH3), 27.2 (2ꢀCH3), 27.3 (2ꢀCH2), 36.2 (2ꢀCH2),
J¼9.6 Hz, CHH), 1.89–1.95 (m, 1H), 2.17–2.40 (m, 3H), 2.65 (ddd, 1H,
J¼14.4 Hz, J¼9.6 Hz, J¼4.5 Hz), 2.83 (dddd, 1H, J¼9.6 Hz, J¼9.6 Hz,
J¼6.3 Hz, J¼3.3 Hz), 3.11 (dd, 1H, J¼12.3 Hz, J¼9.6 Hz, CHH), 3.57
(dd, 1H, J¼12.3 Hz, J¼6.3 Hz, CHH), 4.75 (dt, 1H, J¼9.9 Hz, J¼7.5 Hz,
CH), 7.20–7.31 (m, 3H, arom. H), 7.46–7.54 (m, 2H, arom. H); 13C
37.4 (2ꢀCH), 39.2 (2ꢀC), 41.7 (2ꢀCH), 43.4 (2ꢀCH), 45.1 (2ꢀCH),
71.0 (2ꢀCH2), 114.7 (4ꢀCH), 120.5 (2ꢀCH), 129.3 (4ꢀCH), 158.6
(2ꢀC); 77Se NMR (38.1 MHz, CDCl3):
¼364.7 (Se2) ppm; elemental
d
analysis calcd (%) for C32H42O2Se2 (616.59): C 62.33, H 6.8; found: C
62.21; H 6.84.
NMR (50.3 MHz, CDCl3):
d
¼22.7 (CH3), 26.8 (CH3), 28.0 (CH2), 31.0
(CH2), 38.6 (CH2), 39.0 (C), 41.2 (CH), 45.6 (CH), 45.8 (CH), 55.1 (CH),
4.5.3. (1S,10S)-(þ)-Bis[10-(4-nitrophenoxy)pinocampheyl] diselenide
126.5 (CH), 128.9 (2ꢀCH), 131.0 (C), 132.3 (2ꢀCH); 77Se NMR
(47). Yield: 320 mg (27%), yellow solid; mp 43–45 ꢁC;
21
(38.1 MHz, CDCl3):
for C16H21ClSe (327.75): C 58.63, H 6.46; found: C 58.77, H 6.59.
d
¼299.8 (Se) ppm; elemental analysis calcd (%)
[
a
]
¼þ170.1 (c 1.82, CHCl3); 1H NMR (200 MHz, CDCl3):
¼0.97
d
D
(s, 6H, CH3), 1.23 (s, 6H, CH3), 1.42 (d, 2H, J¼9.9 Hz, CHH), 1.94–
2.10 (m, 4H), 2.22–2.38 (m, 4H), 2.52 (ddd, 2H, J¼14.1 Hz,
J¼6.9 Hz, J¼4.2 Hz), 2.86–2.97 (m, 2H), 4.11 (dd, 2H, J¼9.6 Hz,
J¼6.6 Hz, CHH), 4.18 (q, 2H, J¼9.6 Hz, CHSe), 4.55 (dd, 2H,
4.4.7. (1S)-10-(Tetrahydro-2H-pyran-2-yloxy)pinocampheyl chloride
(59). Yield: 3.0 g (62%), colorless oil; bp 80–82 ꢁC/0.4 mmHg; 1H

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10173
J¼9.6 Hz, J¼6.9 Hz, CHH), 6.92 (d, 4H, J¼9.2 Hz, arom. H), 8.16 (d,
(2ꢀC), 132.4 (4ꢀCH); 77Se NMR (38.1 MHz, CDCl3):
d
¼295.0 (Se),
4H, J¼9.2 Hz, arom. H); 13C NMR (75.5 MHz, CDCl3):
d
¼23.0
360.2 (Se2) ppm; elemental analysis calcd (%) for C32H42Se4
(742.52): C 51.76, H 5.70; found: C 51.79, H 5.75.
(2ꢀCH3), 27.0 (2ꢀCH3), 27.1 (2ꢀCH2), 35.7 (2ꢀCH2), 37.5 (2ꢀCH),
39.0 (2ꢀC), 41.4 (2ꢀCH), 43.0 (2ꢀCH), 45.0 (2ꢀCH), 72.2 (2ꢀCH2),
114.5 (4ꢀCH), 125.8 (4ꢀCH), 141.3 (2ꢀC), 144.8 (2ꢀC), 163.6
4.5.8. (1S,10S)-(þ)-Bis(10-methoxyisopinocampheyl) diselenide
30
(2ꢀC); 77Se NMR (38.1 MHz, CDCl3):
d
¼361.4 (Se2) ppm; ele-
(53). Yield: 1.80 g (45%), yellow oil; [
a
]
D
¼þ166.2 (c 4.1, CHCl3); 1H
mental analysis calcd (%) for C32H40N2O6Se2 (706.59): C 54.39, H
5.71; found: C 54.29, H 5.70.
NMR (200 MHz, CDCl3):
d
¼0.99 (s, 6H, CH3), 1.19 (d, 2H, J¼9.6 Hz,
CHH), 1.21 (s, 6H, CH3), 1.90–2.01 (m, 2H), 2.10–2.27 (m, 4H), 2.33–
2.64 (m, 6H), 3.33 (s, 6H, CH3), 3.38–3.54 (m, 6H); 13C NMR
4.5.4. (1S,10S)-(þ)-Bis[10-(4-methoxyphenoxy)pinocampheyl] di-
(50.3 MHz, CDCl3):
d
¼23.2 (2ꢀCH3), 27.5 (2ꢀCH3), 32.5 (2ꢀCH2),
23
selenide (48). Yield: 250 mg (25%), yellow oil; [
a
]
¼þ135.3 (c 5.24,
35.8 (2ꢀCH), 38.2 (2ꢀCH2), 38.5 (2ꢀC), 42.3 (2ꢀCH), 43.3 (2ꢀCH),
D
CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼0.97 (s, 6H, CH3), 1.21 (s, 6H,
51.5 (2ꢀCH), 58.6 (2ꢀOCH3), 75.6 (2ꢀCH2); 77Se NMR (38.1 MHz,
CH3), 1.39 (d, 2H, J¼9.9 Hz, CHH), 1.93–1.98 (m, 2H), 2.07 (dd, 2H,
J¼14.1 Hz, J¼9.6 Hz), 2.12–2.34 (m, 4H), 2.54 (ddd, 2H, J¼14.1 Hz,
J¼9.9 Hz, J¼4.8 Hz), 2.90 (dddd, 2H, J¼10.2 Hz, J¼10.2 Hz, J¼6.6 Hz,
J¼3.6 Hz), 3.76 (s, 6H, OCH3), 3.97 (dd, 2H, J¼9.6 Hz, J¼6.6 Hz, CHH),
4.17 (q, 2H, J¼9.6 Hz, CHSe), 4.38 (dd, 2H, J¼9.6 Hz, J¼6.9 Hz, CHH),
CDCl3):
d
¼462.8 ppm; elemental analysis calcd (%) for C22H38Se2
(492.46): C 53.66, H 7.78; found: C 53.63, H 7.80.
4.5.9. (1S,10S)-(þ)-Bis(10-phenoxyisopinocampheyl) diselenide
20
(54). Yield: 308 mg (19%), yellow oil; [
a]
¼þ62.6 (c 1.27, CHCl3);
D
6.78–6.86 (m, 8H, arom. H); 13C NMR (75.5 MHz, CDCl3):
d¼23.0
1H NMR (200 MHz, CDCl3):
d
¼1.01 (s, 6H, CH3), 1.08 (d, 2H,
(2ꢀCH3), 27.2 (2ꢀCH3), 27.3 (2ꢀCH2), 36.2 (2ꢀCH2), 37.4 (2ꢀCH),
39.2 (2ꢀC), 41.8 (2ꢀCH), 43.6 (2ꢀCH), 45.2 (2ꢀCH), 55.7 (2ꢀOCH3),
71.9 (2ꢀCH2), 114.6 (4ꢀCH), 115.7 (4ꢀCH), 152.9 (2ꢀC), 153.8 (2ꢀC);
J¼9.6 Hz, CHH), 1.22 (s, 6H, CH3), 1.93–2.08 (m, 2H), 2.18–2.38 (m,
4H), 2.39–2.72 (m, 8H), 3.50–3.62 (m, 2H), 3.87–4.17 (m, 2H), 6.81–
7.00 (m, 6H, arom. H), 7.19–7.36 (m, 4H, arom. H); 13C NMR
77Se NMR (38.1 MHz, CDCl3):
d
¼364.9 (Se2) ppm; elemental anal-
(50.3 MHz, CDCl3):
d
¼23.3 (2ꢀCH3), 27.5 (2ꢀCH3), 32.7 (2ꢀCH2),
ysis calcd (%) for C34H46O4Se2 (676.65): C 60.35, H 6.85; found: C
60.30, H 6.81.
35.4 (2ꢀCH), 38.1 (2ꢀCH2), 38.5 (2ꢀC), 42.3 (2ꢀCH), 43.4 (2ꢀCH),
51.4 (2ꢀCH), 70.0 (2ꢀCH2), 114.4 (4ꢀCH), 120.5 (2ꢀCH), 129.4
(4ꢀCH), 158.8 (2ꢀC); 77Se NMR (38.1 MHz, CDCl3):
¼461.0 (Se2)
d
4.5.5. (1S,10S)-(-)-Bis[10-(3,5-di-tert-butyl-4
hydroxyphenyl)pino
ppm; elemental analysis calcd (%) for C32H42O2Se2 (616.59): C
62.33, H 6.87; found: C 62.45, H 6.98.
campheyl] diselenide (49). Yield: 59.0 mg, (8%), yellow solid; mp
22
173–175 ꢁC; [
d
a
]
¼ꢂ11.9 (c 1.08, CHCl3); 1H NMR (300 MHz, CDCl3):
D
¼1.20 (s, 6H, CH3), 1.24 (s, 6H, CH3), 1.29 (d, 2H, J¼10.2 Hz, CHH),
4.5.10. (1S,10S)-(-)-Bis(10-pentafluorophenoxyisopinocampheyl) di-
22
1.44 (s, 36H, CH3), 1.89–1.98 (m, 4H), 2.12–2.33 (m, 4H), 2.59–2.69
(m, 4H), 2.80 (dd, 2H, J¼12.9 Hz, J¼12.9 Hz), 3.15 (dd, 2H, J¼12.9 Hz,
J¼4.5 Hz), 4.33 (q, 2H, J¼9.9 Hz, CH), 5.02 (s, 2H, OH), 6.95 (s, 4H,
selenide (55). Yield: 1.10 g, (33%), yellow oil; [
a
]
¼ꢂ12.3 (c 13.36,
D
CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼1.03 (s, 6H, CH3), 1.24 (s, 6H,
CH3), 1.26 (d, 2H, J¼9.6 Hz, CHH), 1.94–2.05 (m, 2H), 2.17–2.48 (m,
6H), 2.67 (ddd, 2H, J¼14.4 Hz, J¼9.9 Hz, J¼4.8 Hz), 3.05 (dddd, 2H,
J¼9.9 Hz, J¼9.9 Hz, J¼6.1 Hz, J¼3.0 Hz,), 4.36–4.44 (m, 2H), 4.74–
arom. H); 13C NMR (50.3 MHz, CDCl3):
d
¼24.1 (2ꢀCH3), 27.5
(2ꢀCH3), 27.9 (2ꢀCH2), 30.4 (12ꢀCH3), 34.3 (4ꢀC), 37.3 (2ꢀC), 39.1
(2ꢀCH2), 39.3 (2ꢀCH), 40.4 (2ꢀCH2), 42.1 (2ꢀCH), 43.9 (2ꢀCH),
46.6 (2ꢀCH), 125.8 (4ꢀCHar), 132.5 (2ꢀCar), 135.5 (4ꢀCar), 151.6
4.84 (m, 4H); 13C NMR (75.5 MHz, CDCl3):
d
¼22.7 (2ꢀCH3), 26.7
(2ꢀCH3), 27.5 (2ꢀCH2), 38.5 (2ꢀCH2), 39.0 (2ꢀC), 41.0 (2ꢀCH), 44.6
(2ꢀCar); 77Se NMR (38.1 MHz, CDCl3):
¼362.0 (Se2) ppm; ele-
d
(2ꢀCH), 45.4 (2ꢀCH), 52.2 (2ꢀCH), 76.5 (t, J¼3.8 Hz, 2ꢀCH2); 77Se
mental analysis calcd (%) for C48H74O2Se2 (841.02): C 68.55, H 8.87;
found: C 68.49, H 8.95.
NMR (38.1 MHz, CDCl3):
d
¼383.5 (Se2) ppm; elemental analysis
calcd (%) for C32H32F10O2Se2 (796.50): C 48.25, H 4.05; found: C
48.44, H 4.21.
4.5.6. (1S,10S)-(þ)-Bis(10-phenylsulfanylpinocampheyl)
diselenide
¼þ121.6 (c 0.65, CHCl3);
22
(50). Yield: 120 mg, (15%), yellow oil; [
a
]
4.5.11. (1S,10S)-(þ)-Bis(10-phenylsulfanylisopinocampheyl) diselenide
D
20
1H NMR (200 MHz, CDCl3):
d
¼1.01 (s, 6H, CH3), 1.20 (s, 6H, CH3),
(56). Yield: 350 mg (23%), yellow oil;
[
a
]
¼þ108.7 (c 2.14,
D
1.33 (d, 2H, J¼9.9 Hz, CHH), 1.86–1.99 (m, 2H), 2.11 (dd, 2H,
J¼13.8 Hz, J¼9.3 Hz), 2.18–2.28 (m, 2H), 2.37–3.77 (m, 6H), 3.18 (dd,
2H, J¼10.2 Hz, J¼9.6 Hz, CHH), 3.56 (dd, 2H, J¼10.2 Hz, J¼4.2 Hz,
CHH), 4.19 (q, 2H, J¼10.2 Hz, CHSe), 7.10–7.37 (m, 10H, arom. H); 13C
CHCl3); 1H NMR (200 MHz, CDCl3):
d
¼1.01 (s, 6H, CH3), 1.14 (d,
2H, J¼9.6 Hz, CHH), 1.19 (s, 6H, CH3), 1.92–2.01 (m, 2H), 2.16–2.48
(m, 8H), 2.50–2.66 (m, 2H), 2.94 (dd, 2H, J¼12.8 Hz, J¼10.4 Hz,
CHH), 3.18 (dd, 2H, J¼12.8 Hz, J¼4.2 Hz, CHH), 3.44–3.62 (m, 2H,
CHSe), 7.11–7.37 (m, 10H, arom. H); 13C NMR (50.3 MHz, CDCl3):
NMR (50.3 MHz, CDCl3):
d
¼22.9 (2ꢀCH3), 27.2 (2ꢀCH3), 27.5
(2ꢀCH2), 36.4 (2ꢀCH2), 38.2 (2ꢀCH), 39.3 (2ꢀC), 40.1 (2ꢀCH), 41.8
d
¼23.2 (2ꢀCH3), 27.5 (2ꢀCH3), 32.8 (2ꢀCH2), 38.3 (2ꢀCH2), 38.5
(2ꢀCH), 43.0 (2ꢀCH), 45.0 (2ꢀCH), 125.6 (2ꢀCH), 128.8 (4ꢀCH),
(2ꢀCH), 38.6 (2ꢀC), 39.9 (2ꢀCH), 42.3 (2ꢀCH), 44.2 (2ꢀCH), 51.2
(2ꢀCH), 125.7 (2ꢀCH), 128.7 (4ꢀCH), 128.9 (4ꢀCH), 136.8 (2ꢀC);
128.9 (4ꢀCH), 137.0 (2ꢀC); 77Se NMR (38.1 MHz, CDCl3):
¼360.0
d
(Se2) ppm; elemental analysis calcd (%) for C32H42S2Se2 (648.73): C
59.25, H 6.53; found: C 59.20, H 6.39.
77Se NMR (38.1 MHz, CDCl3):
d
¼458.6 (Se2) ppm; elemental
analysis calcd (%) for C32H42S2Se2 (648.73): C 59.25, H 6.53;
found: C 59.24, H 6.50.
4.5.7. (1S,10S)-(þ)-Bis(10-Phenylselanylpinocampheyl) diselenide
(51). Yield: 1.09 g (68%), yellow solid; mp 90–92 ꢁC;
4.5.12. (1S,10S)-(þ)-Bis(10-phenylselanylisopinocampheyl) diselenide
20
20
[
a
]
¼þ115.5 (c 1.90, CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼1.00
(57). Yield: 311 mg (35%), yellow oil; [
a
]
¼þ64.0 (c 1.00, CHCl3);
D
D
(s, 6H, CH3), 1.17 (s, 6H, CH3), 1.31 (d, 2H, J¼9.9 Hz, CHH), 1.88–
1.98 (m, 2H), 2.03–2.11 (m, 2H), 2.18–2.29 (m, 2H), 2.35–2.43 (m,
2H), 2.54 (ddd, 2H, J¼14.1 Hz, J¼9.6 Hz, J¼4.1 Hz,), 2.72–2.85 (m,
2H), 3.21 (dd, 2H, J¼12.0 Hz, J¼10.5 Hz, CHH), 3.54 (dd, 2H,
J¼12.0 Hz, J¼6.0 Hz, CHH), 4.15 (q, 2H, J¼9.6 Hz, CH), 7.16–7.32
(m, 6H, arom. H), 7.41–7.53 (m, 4H, arom. H); 13C NMR (50.3 MHz,
1H NMR (300 MHz, CDCl3):
d
¼1.00 (s, 6H, CH3),1.15 (d, 2H, J¼9.9 Hz,
CHH), 1.16 (s, 6H, CH3), 1.93–1.98 (m, 2H), 2.18–2.47 (m, 8H), 2.50–
2.61 (m, 2H), 2.99 (dd, 2H, J¼12.0 Hz, J¼10.5 Hz, CHH), 3.54 (dd, 2H,
J¼12.0 Hz, J¼4.8 Hz, CHH), 4.15 (m, 2H, CH), 7.18–7.32 (m, 6H, arom.
H), 7.43–7.53 (m, 4H, arom. H); 13C NMR (50.3 MHz, CDCl3):
d
¼23.1
(2ꢀCH3), 27.4 (2ꢀCH3), 32.7 (2ꢀCH2), 33.3 (2ꢀCH2), 38.5 (2ꢀCH2),
38.6 (2ꢀC), 40.5 (2ꢀCH), 42.2 (2ꢀCH), 44.9 (2ꢀCH), 52.2 (2ꢀCH),
126.6 (2ꢀCH), 129.0 (4ꢀCH), 130.9 (2ꢀC), 132.2 (4ꢀCH); 77Se NMR
CDCl3):
d
¼22.8 (2ꢀCH3), 27.1 (2ꢀCH3), 27.7 (2ꢀCH2), 33.4
(2ꢀCH2), 36.4 (2ꢀCH2), 39.2 (2ꢀCH), 40.7 (2ꢀCH), 41.8 (2ꢀC),
44.2 (2ꢀCH), 45.6 (2ꢀCH), 126.6 (2ꢀCH), 128.9 (4ꢀCH), 131.1
(38.1 MHz, CDCl3):
d¼297.3 (Se), 461.2 (Se2) ppm; elemental

´
J. Scianowski et al. / Tetrahedron 65 (2009) 10162–10174
10174
analysis calcd (%) for C32H42Se4 (742.52): C 51.76, H 5.70; found: C
51.85, H 5.68.
included in Supplementary data. Supplementary data associated
with this article can be found in online version, at doi:10.1016/
j.tet.2009.10.005.
4.5.13. (1S,2R,3R,5S)-(-)-3,10-Pinane diselenide (61). Yield: 0.56 g
22
(22%), red oil; [
a
]
¼ꢂ258.1 (c 4.68, CHCl3); 1H NMR (300 MHz,
D
References and notes
CDCl3):
d
¼1.12 (s, 3H, CH3), 1.20 (d, 1H, J¼9.6 Hz, CHH), 1.22 (s, 3H,
CH3), 1.88–1.99 (m, 2H), 2.21–2.33 (m, 2H), 2.39–2.48 (m, 1H), 2.84
(dddd, 1H, J¼13.8 Hz, J¼11.1 Hz, J¼5.7 Hz, J¼3.0 Hz), 3.34 (dd, 1H,
J¼11.1 Hz, J¼5.7 Hz, CHH), 3.68 (dd, 1H, J¼12.9 Hz, J¼11.1 Hz, CHH),
4.49 (dt, 1H, J¼10.5 Hz, J¼6.6 Hz, CHSe); 13C NMR (75.5 MHz,
1. (a) Paulmier, C. Selenium Reagents and Intermediates in Organic Synthesis; Per-
gamon: Oxford, 1985; (b) Chemistry of Organoselenium and Tellurium Com-
pounds; Patai, S., Rappoport, Z., Eds.; John Wiley & Sons: New York, NY, 1987; (c)
Organoselenium Chemistry: A Practical Approach; Back, T. G., Ed.; Oxford Uni-
versity: Oxford, 1999; (d) Topics in Current Chemistry; Wirth, T., Ed.; Springer:
Heidelberg, 2000; Vol. 208.
2. (a) Wirth, T. Tetrahedron Lett. 1995, 36, 7849; (b) Wirth, T.; Kulicke, K. J.; Fragale,
G. Helv. Chim. Acta 1996, 79, 1957; (c) Braga, A. L.; Paixa˜o, M. W.; Lu¨dtke, D. S.;
Silveira, C. C.; Rodrigues, O. E. D. Org. Lett. 2003, 5, 2635.
CDCl3):
d
¼24.9 (CH3), 27.0 (CH3), 29.1 (CH2), 33.9 (CH2), 39.1 (C),
39.2 (CH2), 40.3 (CH), 41.1 (CH), 46.3 (CH), 56.9 (CH); 77Se NMR
(38.1 MHz, CDCl3):
d
¼342.3 (Se), 435.2 (Se) ppm; elemental anal-
3. (a) Mugesh, G.; Singh, H. B. Chem. Soc. Rev. 2000, 29, 347; (b) Mugesh, G.; du
Mont, W.-W.; Sies, H. Chem. Rev. 2001, 101, 2125; (c) Malmstrom, J.; Jonsson, M.;
Cotgreave, I. A.; Hammarstrom, L.; Sjodin, M.; Engman, L. J. Am. Chem. Soc. 2001,
123, 3434; (d) Back, T. G.; Moussa, Z. J. Am. Chem. Soc. 2003, 125, 13455; (e)
Wo´jtowicz, H.; Chojnacka, M.; M1ochowski, J.; Palus, J.; Syper, L.; Hudecowa, D.;
Uher, M.; Piasecki, E.; Rybka, M. Il Farmaco 2003, 58, 1235; (f) Meotti, F. C.;
Stangherlin, G. Z.; Nogueira, C. W.; Rocha, J. B. T. Environ. Res. 2004, 94, 276; (g)
Schrauzer, G.N. Patent US, 6,867,238, 2005.
ysis calcd (%) for C10H16Se2 (294.15): C 40.83, H 5.48; found C 40.87,
H 5.54.
4.5.14. (1S,10S)-(þ)-Bis(10-phenylselanyl-4-caranyl) diselenide
20
(93). Yield: 490 mg (42%), yellow oil; [
a
]
D
¼þ140.0 (c 0.50, CHCl3);
1H NMR (200 MHz, CDCl3):
d
¼0.53 (dt, 2H, J¼9.0 Hz, J¼4.6 Hz),
´
4. Scianowski, J. Tetrahedron Lett. 2005, 46, 3331.
0.72–0.95 (m, 4H), 0.98 (s, 6H, CH3), 1.03 (s, 6H, CH3), 1.77–2.03 (m,
6H), 2.50 (dt, 2H, J¼16.2 Hz, J¼8.6 Hz), 2.88 (dd, 2H, J¼12.2 Hz,
J¼7.6 Hz, CHH), 3.17 (dd, 2H, J¼12.2 Hz, J¼6.8 Hz, CHH), 3.75 (m, 2H,
CHSe), 7.19–7.30 (m, 6H, arom. H), 7.43–7.57 (m, 4H, arom. H); 13C
´
5. Scianowski, J.; Rafin´ ski, Z.; Wojtczak, A. Eur. J. Org. Chem. 2006, 14, 3216.
´
´
6. Rafinski, Z.; Scianowski, J. Tetrahedron: Asymmetry 2008, 19, 1
237.
´
7. Rafin´ ski, Z.; Scianowski, J.; Wojtczak, A. Lett. Org. Chem. 2009, 6, 321.
´
8. Rafin´ ski, Z.; Scianowski, J.; Wojtczak, A. Tetrahedron: Asymmetry 2008, 19, 223.
9. (a) Browne, D. M.; Wirth, T. Curr. Org. Chem. 2006, 10, 1893; (b) Tiecco, M.;
Testaferri, L.; Bagnoli, L.; Marini, F.; Santi, C.; Temperini, A.; Scarponi, C.;
Sternativo, S.; Terlizzi, R.; Tomassini, C. ARKIVOC 2006, 186; (c) Zhu, C.; Huang,
Y. Curr. Org. Chem. 2006, 10, 1905; (d) Coles, M. P. Curr. Org. Chem. 2006, 10,
1993.
10. (a) Back, T. G.; Dyck, B. P. Chem. Commun. 1996, 2567; (b) Back, T. G.; Nan, S.
J. Chem. Soc., Perkin Trans. 1 1998, 3123; (c) Back, T. G.; Dyck, B. P.; Nan, S.
Tetrahedron 1999, 55, 3191; (d) Back, T. G.; Moussa, Z. Org. Lett. 2000, 19,
3007.
NMR (50.3 MHz, CDCl3):
d
¼16.3 (2ꢀCH3), 18.2 (2ꢀC), 19.6 (2ꢀCH),
22.8 (2ꢀCH), 23.6 (2ꢀCH2), 27.7 (2ꢀCH2), 28.5 (2ꢀCH3), 34.4
(2ꢀCH2), 38.9 (2ꢀCH), 48.5 (2ꢀCH), 126.6 (2ꢀCH), 128.9 (4ꢀCH),
131.0 (2ꢀC), 132.3 (4ꢀCH); 77Se NMR (38.1 MHz, CDCl3):
¼275.4
d
(Se2), 368.6 (Se) ppm; elemental analysis calcd (%) for C32H42Se4
(742.52): C 51.76, H 5.70; found: C 51.74, H 5.66.
11. Le Noble, W. J.; Hayakawa, T.; Sen, A. K.; Tatsukami, Y. J. Org. Chem. 1971, 36, 193.
12. Hori, T.; Sharpless, K. B. J. Org. Chem. 1979, 44, 4204.
13. Uzarewicz, A.; Scianowski, J.; Ba˛kowska-Janiszewska, J. Pol. J. Chem. 1999, 73,
4.5.15. (1S,10S)-(-)-Bis(10-phenylselanyl-4-isocaranyl) diselenide
20
(97). Yield: 530 mg (47%), yellow oil; [
a
]
¼ꢂ108.0 (c 0.50, CHCl3);
´
D
1H NMR (300 MHz, CDCl3):
d
¼0.55–0.78 (m, 4H), 0.93 (m, 2H), 0.99
1791.
´
14. Uzarewicz, A.; Scianowski, J.; Ba˛kowska–Janiszewska, J. Pol. J. Chem. 2000, 74,
(s, 12H, CH3), 1.55–1.78 (m, 2H), 2.00 (ddd, 2H, J¼15.0 Hz, J¼6.3 Hz,
J¼3.3 Hz), 2.15–2.27 (m, 4H), 2.87 (m, 2H), 2.90 (dd, 2H, J¼12.0 Hz,
J¼7.8 Hz, CHH), 3.36 (dd, 2H, J¼12.0 Hz, J¼3.9 Hz, CHH), 7.18–7.30
(m, 6H, arom. H), 7.45–7.55 (m, 4H, arom. H); 13C NMR (50.3 MHz,
1079.
15. Cox, M.; Wirth, T. Phosphorus Sulfur 2005, 180, 659.
16. (a) Wirth, T. Angew. Chem., Int. Ed. Engl. 1995, 34, 1726; (b) Wirth, T.; Fragale, G.
Chem.dEur. J. 1997, 3, 1894; (c) Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini,
C.; Marini, F.; Bagnoli, L.; Temperini, A. Tetrahedron: Asymmetry 2000, 11,
4645; (d) Wirth, T. Liebigs Ann./Recueil 1997, 2189; (e) Wirth, T. Tetrahedron
1999, 55, 1; (f) Tiecco, M.; Testaferri, L.; Bagnoli, L.; Marini, F.; Temperini, A.;
Tomassini, C.; Santi, C. Tetrahedron Lett. 2000, 41, 3241; (g) Tiecco, M.; Testaferri, L.;
Santi, C.; Tomassini, C.; Marini, F.; Bagnoli, L.; Temperini, A. Chem.dEur. J.
2002, 8, 1118.
CDCl3):
d
¼15.6 (2ꢀCH3), 17.9 (2ꢀC), 20.5 (2ꢀCH), 20.6 (2ꢀCH), 26.6
(2ꢀCH2), 28.6 (2ꢀCH3), 28.9 (2ꢀCH2), 35.3 (2ꢀCH2), 40.2 (2ꢀCH),
47.2 (2ꢀCH), 126.5 (2ꢀCH), 129.0 (4ꢀCH), 131.1 (2ꢀC), 132.2
(4ꢀCH); 77Se NMR (38.1 MHz, CDCl3):
¼255.4 (Se2), 368.7 (Se)
d
ppm; elemental analysis calcd (%) for C32H42Se4 (742.52): C 51.76, H
5.70; found: C 51.71, H 5.65.
17. (a) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B. 1988, 37, 785; (b) Becke, A. D. J. Chem.
Phys. 1993, 98, 5648.
18. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J.
V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-
Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M. W.; Gill, P. M.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03,
Revision B.01; Gaussian: Pittsburgh PA, 2003.
Acknowledgements
This work was financially supported by the Nicolaus Copernicus
University under Grant 377-Ch and the European Social Fund and
state budget under the project of Self-government of the Voivo-
deship ‘Step in the future’ -scholarship for PhD students.
Supplementary data
Characterization data of all methoxyselenenylation and sele-
nocyclization products are provided. Crystallographic data of 51 is
19. Bondi, A. J. Phys. Chem. 1964, 68, 441.