An enantiopure diselenide based on a chiral bicyclic backbone—synthesis and configuration assignment

Article abstract of DOI:10.1016/j.tetasy.2017.08.008

An enantiomerically pure diselenide containing two chiral bicyclic subunits was prepared from the respective halides. The stereochemical outcome of the reaction was established via NMR spectroscopy and X-ray diffraction measurements.

Full text of DOI:10.1016/j.tetasy.2017.08.008

Tetrahedron: Asymmetry xxx (2017) xxx–xxx
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
An enantiopure diselenide based on a chiral bicyclic backbone—
synthesis and configuration assignment
a
a,
b
b
⇑
_
´
´
Karolina Kaminska , Elzbieta Wojaczynska , Claudio Santi , Luca Sancineto ,
b
c
c
c
d
´
Marianna Francesca Pensa , Andrzej Kochel , Robert Wieczorek , Jacek Wojaczynski , Gauthier Slupski
a
_
´
Department of Organic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wrocław, Poland
b Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06134 Perugia, Italy
c Faculty of Chemistry, University of Wrocław, F. Joliot-Curie St., 50-383 Wrocław, Poland
d Univ. Lille, IUTA—Chemistry Department, UFR de Chimie, F-59000 Lille, France
a r t i c l e i n f o
a b s t r a c t
Article history:
An enantiomerically pure diselenide containing two chiral bicyclic subunits was prepared from the
respective halides. The stereochemical outcome of the reaction was established via NMR spectroscopy
and X-ray diffraction measurements.
Received 27 July 2017
Accepted 8 August 2017
Available online xxxx
Ó 2017 Elsevier Ltd. All rights reserved.
In memory of Professor Howard Flack
1. Introduction
and this determination was facilitated by the use of starting mate-
rials with multiple stereogenic centers with a defined geometry.
Selenium containing compounds are widely used as efficient
reagents in organic synthesis1–4 and more recently the scientific
interest in this field was directed to some derivatives exhibiting
various biological activities, such as antiviral, anticancer, anti-
inflammatory, antimicrobial agents and mimetics of glutathione
peroxidase.5–8 Among the various classes of organoselenium
derivatives, diselenides are considered as the most useful and ver-
satile, because of their stability in air, acid and basic conditions,
and the possibility to easily obtain their transformation into nucle-
ophilic, radical, and electrophilic reagents.1–4,9 Chiral diselenides
have been employed as effective reagents in many asymmetric
transformations, mainly involving electrophilic selenenylation or
cyclofunctionalization but also as ligands in metal-mediated reac-
tions such as the enantioselective diethylzinc addition to aldehy-
des.2,3 It was demonstrated that non-bonding interactions with
neighboring heteroatoms (e.g. Se-N, Se-O or Se-S) play an impor-
tant role both in enhancing the stereoselectivity in the selenium
promoted or catalyzed reactions, and modulating the antioxidant
activity of some diselenides.10–12
A
high-yielding, stereoselective aza-Diels–Alder reaction
between cyclopentadiene and chiral imines was used as a conve-
nient method for the preparation of enantiomerically pure 2-
azanorbornane (2-azabicyclo[2.2.1]heptane) derivatives.18–23 The
major exo-1 and endo-1 esters can be separated and converted into
respective epimeric alcohols, (1S,3R,4R)-3 and (1S,3S,4R)-4, versa-
tile precursors for the synthesis of a variety of chiral ligands that
were successfully applied in asymmetric catalysis (Scheme 1).24–26
Over the course of our investigations, we explored the possibility
of stereoselective incorporation of an additional carbon atom into
a bicyclic skeleton, which opens a route to bridged azepanes
(2-azabicyclo[3.2.1]octanes).27 Under the conditions of a Mit-
sunobu reaction as well as during mesylation, alcohols 3 and 4
formed aziridinium intermediates, which were specifically opened
by nucleophilic attack to yield the corresponding epimeric ring-
expanded compounds as exemplified by azide derivatives,
(1S,4S,5R)-5 and (1S,4R,5R)-6 in (Scheme 2). The identification of
products was based on the interpretation of correlation NMR spec-
tra, which allowed us to establish their structures and the config-
uration of 4-C. These assignments were further supported by X-
ray measurements for selected derivatives revealing their struc-
tures in the solid state.
Various chiral diselenides have been prepared and used in
asymmetric synthesis, although those containing a selenium atom
directly attached to a stereogenic center are relatively rare.13–17 In
these cases, the configuration of selenium-bearing carbon atoms
was determined by 1H NMR13 or X-ray diffraction analysis,14,16
This methodology developed in our laboratory enabled the
preparation of isomeric derivatives bearing desired (e.g. amine)
functionality and the chiral 2-azabicyclic skeleton of different
size.27,28 Herein we describe the synthesis of a novel enantiomeri-
cally pure diselenide based on a rigid 2-azabicyclo[3.2.1]octane
backbone.
⇑
Corresponding author.
E-mail address: elzbieta.wojaczynska@pwr.edu.pl (E. Wojaczyn´ ska).
http://dx.doi.org/10.1016/j.tetasy.2017.08.008
0957-4166/Ó 2017 Elsevier Ltd. All rights reserved.
´
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´
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K. Kaminska et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
1. H2, Pd(C)
N
Ph
OH
N
Ph
COOEt
2. LiAlH4
exo-1
3
(1S,3R,4R)-
major product
Ph
NH2
COOEt
O
1.
2.
+
H
1. H2, Pd(C)
2. LiAlH4
N
Ph
N
Ph
CO2Et
OH
endo-2
4
(1S,3S,4R)-
Scheme 1.
the presence of the 3-CH2 fragment in the ring is evidenced by
HMBC 1H–13C three-bond correlations with 1, 5 and 10 positions.27
The configuration of 4-C was established on the basis of contacts
observed in NOESY spectra as discussed below for the diselenide.
Crystals of (1S,4S,5R)-7 suitable for X-ray measurement were
grown and the solid state structure that is shown in Figure 1 was
solved revealing the formation of a bridged azepane and an (S)-
configuration for the substituted carbon atom.
N3
N
N3
DEAD
PPh3
Ph
Ph
N
N
Ph
N
Ph
OH
(1S,4S,5R)-5
3
(1S,3R,4R)-
N3
N
Ph
DEAD
PPh3
N
Ph
N3
OH
(1S,4R,5R)-6
(1S,3S,4R)-4
Scheme 2.
2. Results and discussion
We intended to use 2-azabicyclo[3.2.1]octane-based chlorides
and iodides, formed from alcohols 3 and 4, for the preparation of
chiral diselenides as new reagents for organic synthesis. In these
derivatives, selenium atoms would be directly attached to stere-
ogenic centers and it was expected to be an important factor of
the effective chirality induction in possible further stereoselective
reactions. We believed that the use of epimeric halides differing
by the configuration on 4-C atom should yield stereoisomeric
products in the substitution reaction. Together with derivatives
prepared from 2-azabicyclo[2.2.1]heptane-based halides, they
could form a family of diselenides with varied placement of dise-
lenide bridge with respect to a chiral bicyclic core of different size,
thus allowing for the adjustment of factors influencing the stereo-
chemical outcome. The presence of the appropriately located het-
Fig. 1. X-ray structure of (1S,4S,5R)-7. Thermal ellipsoids are drawn at 50%
probability level.
We believed that the corresponding bicyclic iodides should be
useful as substrates for the diselenide synthesis, and so we per-
formed reactions of alcohols 3 and 4 with molecular iodine in
the presence of imidazole and triphenylphosphine. In both prepa-
rations, we observed the formation of an identical ring-expanded
product, which on the basis of NMR spectroscopic data was identi-
fied as (1S,4S,5R)-9. This was in contrast to our previous findings
on the stereospecificity of ring expansion observed upon transfor-
mations of alcohols 3 and 4.27 This observation is presumably con-
nected with the nucleophile size: small ions (such as azide or
chloride anions) can attack the formed aziridinium cations via an
eroatom (2-N) should have
a beneficial influence on the
performance of these derivatives.
Epimeric chlorides 7 and 8 were prepared from the correspond-
ing alcohols, (1S,3R,4R)-3 and (1S,3S,4R)-4, respectively, by treat-
ment with thionyl chloride in pyridine (Scheme 3). Ring
expansion was confirmed by 2D NMR measurements. In particular,
Se, NaOH
Cl
N
N2H4.H2O
SOCl2, py
Ph
N
Ph
OH
3
83%
51%
7
9
(1S,4S,5R)-
(1S,3R,4R)-
Ph
Ph
N
Se
Se, NaOH
N2H4.H2O
I2, ImH, PPh3
26%
I2, ImH, PPh3
I
N
Ph
Ph
53%
Se
N
(1S,4S,5R)-
38%
Se, NaOH
N2H4.H2O
N
Ph
SOCl2, py
92%
N
10
[bis-(1S,4S,5R)]-
53%
Cl
OH
(1S,3S,4R)-4
8
(1S,4R,5R)-
ImH = imidazole
Scheme 3.
´
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K. Kaminska et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
SN2 mechanism, while for bigger nucleophiles, the approach from
the more hindered face can be limited. This indicates for the possi-
ble interconversion of aziridinium cations and formation of the
more stable isomer.
We tested various reaction conditions for the conversion of
chloride (1S,4S,5R)-7 into the desired diselenide derivatives. The
application of elemental selenium with lithium hydroxide or
sodium hydroxide and hydrazine hydrate was found to be effective
in the generation of Se22ꢀ dianion and the formation of diselenide 7
in ca. 40–50% yields. The identity of reaction product 10 was con-
firmed on the basis of mass spectrometry, 1H, 13C, and 77Se NMR
spectroscopy. The ESI mass spectrum shows peaks concentrated
remained unchanged upon the introduction of selenium into a
bicyclic substrate. Thus, the determination of relative configura-
tions by X-ray measurements gives directly information about
the absolute configuration of both carbon atoms linked by Se-Se
bridge; this is in agreement with the result of NMR analysis. The
value of the Flack parameter [-0.002(16)] confirms the stereo-
chemical assignment. The X-ray structure of diselenide 10 is
shown in Figure 3. The Se-Se bond length [2.3105(10) Å] and Se-
N distances [1.994(6) Å and 1.996(6) Å] are similar to those
observed in crystal structures of other diselenides.14,16 The dise-
lenide bridge torsion angle C–Se–Se–C equals 89.2(5)°, which
brings two bicyclic fragments close to each other.
around maximum at m/z = 589.1611 (value calculated for C30H41
-
Diselenide 10 was also prepared starting from iodide (1S,4S,5R)-
9 treated with elemental selenium, sodium hydroxide, and hydra-
zine hydrate under an inert atmosphere. The desired product was
obtained in a comparable yield as in case of chloride 7 (53%).
We then subjected chloride (1S,4R,5R)-8, the epimer of
(1S,4S,5R)-7, to the reaction with elemental selenium, sodium
hydroxide and hydrazine hydrate, which led to the diselenide
product in 53% yield. Both the 1H and 13C NMR spectra of this
Se2N+2 ([M+H]+) m/z = 589.1606) with an isotope pattern character-
istic for the presence of two selenium atoms. One set of signals was
observed in the 1H and 13C NMR spectra of the reaction product,
and a single resonance at 394 ppm was found in the 77Se NMR
spectrum. These observations are consistent with the selective for-
mation of only one of the three possible stereoisomeric products,
which could differ by the configurations on bridgehead carbon
atoms, and result from the effective symmetry of a dimeric mole-
cule. Two-dimensional NMR techniques (1H–1H COSY and NOESY,
1H–13C HMQC and HMBC) were applied to gain insight into the
molecular structure of compound 10. This led to the assignment
of 1H and 13C NMR signals. The unknown configuration on the
4-C atoms was established by NOESY measurements. Previously,
we used an observation of through-space magnetization transfer
resulting from the vicinity of particular hydrogen atoms to deduce
the structure of bicyclic and tetracyclic compounds.27,29,30 The
expected contacts for the two possible situations are shown in Fig-
ure 2. For the (4S)-configuration, the 4-H is located close to one of
6-H atoms, while in case of the (4R)-epimer, a correlation of 4-H
with one of 8-H nuclei is observed.
A fragment of the NOESY spectrum of 10 shown in Figure 2
clearly indicates that besides the obvious cross-peaks between
4-H and 3-H and 5-H signals, 4-H–6-H correlation is present and
no 4-H–8-H contacts can be seen. Therefore, both carbon atoms
attached to selenium atoms have an (S)-configuration, identical
to the starting chloride (1S,4S,5R)-7. This is in contrast to the
preparation of terpene–derived diselenides under SN2 reaction
conditions in which an inversion of configuration was found.16
Establishing the (S)-configuration of the 4-C atoms in a solid
state was straightforward, since the remaining stereogenic centers
Fig. 3. X-ray structure of diselenide 10. Thermal ellipsoids are drawn at 50%
probability level.
Fig. 2. Key contacts expected for two 4-substituted epimers of 2-azabicyclo[3.2.1]octane and a fragment of NOESY spectrum of compound 10 (CDCl3, 300 K).
´
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K. Kaminska et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
4
compound, the measured values of the specific rotation and melt-
ing point as well as and its TLC behavior showed that it is identical
with the already obtained isomer 10 (Scheme 3). Thus, the reaction
proceeded with inversion of configuration on both 4-C stereogenic
centers.
dinium cations. Studies on the use of the established protocol for
the synthesis of other enantiopure diselenides and their applica-
tions as chirality inducers in stereoselective reactions are currently
in progress in our laboratory.
These observations proved that substitution with diselenide
leads to the same product independent of which halide,
(1S,4S,5R)-7, (1S,4S,5R)-9 or (1S,4R,5R)-8, is used as the substrate.
To explain this selectivity, we performed DFT calculations, which
shed some light on the plausible mechanism of the reaction. In
our previous research, computational methods proved its utility
as a tool for the prediction of certain structural features and the
stability of prepared compounds.27–29 The optimized structures
of starting chlorides showed that epimer 7 is slightly more stable
than 8 (1.7 kcal/mol difference in energy). Removal of the chloride
anion from these two isomers leads to the respective cations; DFT
calculations indicated that their formation is associated with an
attack of a lone electron pair from 2-N on the electron deficient
4-C atom and the formation of a three-membered aziridine ring
(Scheme 4). An intermediate 11 derived from compound 7 is also
energetically favored, this time by 2.8 kcal/mol, over cation 12
formed from 8. A reaction of these intermediates with diselenide
dianion could lead to epimeric species 13 and 14; the energy of
the latter, resulting from the approach from the more hindered
face, is higher by 3.4 kcal/mol. The reaction of the more stable
intermediates 11 and 13 resulted in the formation of the only iso-
lated diselenide 10. We did not observe other isomers that could be
obtained, if anion 14 took part in the reaction. In our opinion, the
observed stereochemical outcome for chloride 8 is connected with
the isomerization of 12 to the more stable aziridinium cation 11
under reaction conditions.
4. Experimental
4.1. General
IR spectra were recorded on a 2000 FTIR spectrophotometer. 1H
NMR and 13C NMR spectra were measured on a 500 MHz spec-
trometer using solvent residual peak (chloroform-d, d(1H)
= 7.28 ppm, d(13C) = 77.0 ppm) as a reference. The reported J values
are those observed from the splitting patterns in the spectrum and
may not reflect the true coupling constant values. High resolution
mass spectra were recorded utilizing electrospray ionization mode.
Chromatographic separations were performed on silica gel 60 (70–
230 mesh). Thin layer chromatography was carried out using silica
gel 60 precoated plates.
4.2. X-ray crystallography
Data collection for single crystals of compounds 7 and 9 was
performed using XCalibur Ruby diffractometer at 100(2) K. The
graphite monochromatized MoK
a radiation (k = 0.71073 Å) were
used for data collection. Data collection and reduction, along with
absorption correction, were performed using CrysAlis software
package.31 The structure was solved by direct methods using
SHELXT2014 revealing the positions of almost all non-hydrogen
atoms. The remaining atoms were located from subsequent differ-
ence Fourier syntheses. The structure was refined using
SHELXL2014 with the anisotropic thermal displacement parame-
ters.32 Aromatic C-bonded H and CH2, CH atoms were generated
in their calculated positions and a riding model was used with
In the DFT optimized structure of compound 10, the relative
position of the two bicyclic subunits resembles the one observed
in a crystal structure, while the obtained value of torsion angle
characterizing the diselenide bridge (C-Se-Se-C, 91.7°) is also sim-
ilar. Another stable conformation was found to exhibit more open
structure (C-Se-Se-C torsion angle of 106.6°); its energy was found
significantly higher (10.5 kcal/mol) in comparison with the ‘‘com-
pact” conformer. All optimized structures are shown in Supple-
mentary Information.
Ueq = 1.2 or 1.5 Ueq(parent C atom). CCDC 1562828 and CCDC
61496 contain the supplementary crystallographic data. These
data can be obtained free of charge via www.ccdc.cam.ac.
uk/conts/retrieving.html (or from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Tel.: +44
1223 336408; fax:+44 1223 336033; E-mail: deposit@ccdc.cam.
ac.uk).
3. Conclusions
4.3. Calculations
Our investigations showed that the stereochemical outcome of
nucleophilic substitution of 2-azabicycloalkane derivatives, pro-
ceeding either with an expansion of the bicyclic system or without
its modification, is strongly dependent on the size of the nucle-
ophile. The formation of an identical iodide or diselenide from epi-
meric starting compounds can be accounted for by the reaction
mechanism involving the formation of interconvertible aziri-
The DFT calculations were carried out using the Gaussian 09
rev. C.01 package of computer codes.33 The structures of molecules
and ions were fully optimized by using the BLYP functional with
the 6-311G(d,p) basis set. The fully DFT optimized structures can
be found in supplementary data.
Ph
Ph
N
Se
Se2
N
Cl
N
2
Se2
11
-Cl
Ph
Ph
N
Ph
Se
N
H
H
H
7
11
13
10
H
H
H
N
Ph
N
Ph
N
-Cl
Ph
Se2
Cl
8
12
14
Scheme 4.
´
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K. Kaminska et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
4.4. Preparation of compounds
J = 4.9 Hz), 4.22–4.25 (m, 1H), 7.20–7.37 (m, 5H, ArH) ppm. 13C
NMR (chloroform-d, 125 MHz): d 21.6, 23.3, 29.1, 35.5, 37.6, 44.3,
53.6, 56.1, 61.8, 61.6, 126.7, 127.5, 128.3, 146.2 ppm. IR (film):
695, 1126, 1226, 1450, 1489, 2817, 2924, 2966, 3442 cmꢀ1. HRMS
(ESI-TOF): m/z [M+H]+ calcd for (C15H21NI)+ 342.0713; found
342.0710.
The bicyclic Diels–Alder adducts 1, 2 and the respective alcohols
3, 4 were prepared as described previously.22,24,27,34
4.4.1. The procedure for the preparation of chlorides
Alcohol exo-(1S,3R,4R)-4 (2.50 g, 9.2 mmol) and pyridine (0.74
mL, 9.2 mmol, 1.0 equiv) were dissolved in 20 mL of dry dichloro-
methane and cooled in an ice bath. Thionyl chloride (1.34 mL,
18.5 mmol, 2.0 equiv) was then slowly added. The reaction mixture
was stirred overnight at room temperature. The crude reaction
mixture was rendered alkaline with 20% aqueous NaOH and
extracted with CH2Cl2 (3 ꢁ 10 mL). The organic phases were col-
lected, dried over Na2SO4 and evaporated. After evaporation of sol-
vent, the residue was chromatographed on a silica column using n-
hexane/ethyl acetate (5:1 v/v), yielding a fraction containing chlo-
ride (1S,4S,5R)-7. Its spectral characteristics were identical with
the reported parameters.27 (1S,4R,5R)-8 isomer was prepared in a
similar manner starting from endo-(1S,3S,4R)-4.
4.4.4. Synthesis of diselenide 10
Compound 10 was prepared according to the adapted literature
procedure.36 Hydrazine monohydrate (0.11 ml, 2.2 mmol) was
slowly added to a suspension of selenium (0.17 g, 2.2 mmol) and
sodium hydroxide (0.12 g, 3.0 mmol) in DMF (10 ml). The mixture
was stirred at 100 °C under argon for 3 h. Next, chloride 7 or 8
(0.50 g, 2.0 mmol) or iodide 9 (0.68 g, 2.0 mmol) was added por-
tionwise and the mixture was stirred for 24 h. The resulting crude
reaction mixture was dissolved in petroleum ether and washed
several times with water and brine. The organic phase was dried
over sodium sulfate, filtered, and evaporated under a reduced pres-
sure. Reaction product was chromatographed on a silica column
using n-hexane/ethyl acetate (9:1 v/v), yielding a fraction contain-
ing pure diselenide 10.
4.4.1.1. (1S,4S,5R)-2-[(S)-1-Phenylethyl]-4-chloro-2-azabicyclo
[3.2.1]octane 7.
Colorless crystals. Mp 72–77 °C. Yield 1.90 g
The reaction of chloride 7 with selenium and hydrazine mono-
hydrate was also conducted in the presence of lithium hydroxide in
DMF at 120 °C under an inert atmosphere for 20 h,37 leading to dis-
elenide 10 in lower yield (40%).
(83%). [
a]
20 = ꢀ37.8 (c 1.64, CH2Cl2). 1H NMR (chloroform-d,
D
500 MHz): d 1.28–1.48 (m, 3H), 1.33 (d, 3H, J = 6.6 Hz), 1.68–1.82
(m, 2H), 2.39–2.55 (m, 3H), 2.75 (part of AB system, 1H,
J = 13.8 Hz), 3.43 (q, 1H, J = 6.6 Hz), 3.59 (t, 1H, J = 5.0 Hz), 3.87–
3.92 (m, 1H), 7.20–7.36 (m, 5H, ArH) ppm. 13C NMR (chloroform-
d, 125 MHz): d 21.7, 22.2, 28.4, 33.7, 42.4, 51.5, 56.1, 61.2, 62.0,
126.8, 127.3, 128.4, 145.4 ppm. IR (film): 546, 681, 702, 769, 957,
1137, 1261, 1452, 1491, 1686, 2098, 2795, 2806, 2952, 3025,
4.4.5. Bis{(1S,4S,5R)-2-[(S)-1-phenylethyl]-2-azabicyclo[3.2.1]
octan-4-yl} diselenide 10
Yellow solid. Mp 83–85 °C. Yield 0.60 g (51%, from 7) or 0.62 g
(53%, from 8 or 9). [
a
]
D
20 = ꢀ142.6 (c 0.7, CH2Cl2). 1H NMR (CDCl3,
3061, 3082 cmꢀ1. HRMS (ESI-TOF): m/z [M+H]+ calcd for (C15H21
-
500 MHz): d 1.21 (d, 6H, J = 6.6 Hz), 1.22–1.30 (m, 6H), 1.57–1.69
(m, 4H), 1.94 (d, 2H, J = 11.6 Hz), 2.24 (part of ABX system, 2H,
J1 = 13.5 Hz, J2 = 4.2 Hz), 2.43–2.48 (m, 2H), 2.51 (part of AB system,
2H, J = 13.5 Hz), 2.84–2.85 (m, 2H), 3.22 (q, 2H, J = 6.6 Hz), 3.46 (t,
2H, J = 4.8 Hz), 7.11–7.22 (m, 10H) ppm. 13C NMR (chloroform-d,
125 MHz): d 21.5, 22.3, 29.9, 36.1, 40.6, 51.0, 56.5, 62.3, 126.7,
127.4, 128.2, 145.7 ppm. 77Se NMR (95 MHz, chloroform-d) d
NCl)+ 250.1379; found 250.1357.
4.4.1.2. (1S,4R,5R)-2-[(S)-1-Phenylethyl]-4-chloro-2-azabicyclo
[3.2.1]octane 8. Orange oil. Yield 2.11 g (92%). [
20 = +19.8
a]
D
(c 1.00, CH2Cl2). 1H NMR (chloroform-d, 500 MHz): d 1.12–1.17
(m, 1H), 1.26 (d, 3H, J = 6.6 Hz), 1.28–1.39 (m, 2H), 1.71–1.81 (m,
2H), 2.28 (d, 1H, J = 11.6 Hz), 2.45–2.47 (m, 1H), 2.70 (part of
ABX system, 1H, J1 = 13.5 Hz, J2 = 3.4 Hz), 3.10 (bt, 1H, J = 4.9 Hz),
3.15 (part of AB system, 1H, J = 13.5 Hz), 3.46 (q, 1H, J = 6.6 Hz),
4.02–4.04 (m, 1H), 7.21–7.38 (m, 5H, ArH) ppm. 13C NMR (chloro-
form-d, 125 MHz): d 22.0, 22.1, 28.3, 33.4, 42.3, 50.7, 57.2, 61.3,
61.6, 126.7, 127.5, 128.3, 146.2 ppm. IR (film): 547, 701, 1261,
1451, 2793, 2952, 2972, 3469 cmꢀ1. HRMS (ESI-TOF): m/z [M+H]+
calcd for (C15H21NCl)+ 250.1379; found 250.1356.
394 ppm. IR (KBr): 543, 699, 772, 1313, 1451, 2924, 3022 cmꢀ1
.
HRMS (ESI-TOF): m/z [M+H]+ calcd for (C30H41N2Se2)+ 589.1606;
found 589.1611.
Acknowledgments
Financial support from a statutory activity subsidy from the
Polish Ministry of Science and Higher Education for the Faculty
of Chemistry of Wrocław University of Science and Technology is
gratefully acknowledged. M.F.P. and G.S. are thankful for Erasmus
+ grants.
4.4.2. Preparation of iodide 9
A modified literature procedure was used for this preparation.35
To a suspension of imidazole (0.3 g, 4.43 mmol) and triphenylphos-
phine (0.85 g, 3.26 mmol) in dry CH2Cl2 at 0 °C under an argon
atmosphere was added iodine (0.83 g, 3.26 mmol) in three portions
over 30 minutes. After stirring for an additional 10 minutes at
room temperature, a solution of alcohol 3 or 4 (0.50 g, 2.17 mmol)
in dry CH2Cl2 was added and the resulting mixture was stirred for
2.5 h at room temperature. The resulting reaction mixture was
concentrated and dried in vacuo and chromatographed on a silica
column using n-hexane/ethyl acetate (9:1 v/v), to yield a fraction
containing iodide 9.
A. Supplementary data
Supplementary data (copies of NMR spectra, X-ray data for 7
and 10, DFT optimized structures) associated with this article can
be found, in the online version, at http://dx.doi.org/10.1016/j.
tetasy.2017.08.008.
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