Novel chiral organoselenenyl halides stabilized by Se ··· N nonbonded interactions: Synthesis and structural characterization

Article abstract of DOI:10.1016/S0957-4166(98)00507-2

The first examples of structurally characterized chiral organoselenenyl halides stabilized by Se ··· N intramolecular interactions are described. The existence of strong nonbonded Se ··· N interactions in the solid state as well as in solution was unambiguously determined by single-crystal X-ray analysis and ⁷⁷Se NMR spectroscopy.

Full text of DOI:10.1016/S0957-4166(98)00507-2

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 10 (1999) 237–242
Novel chiral organoselenenyl halides stabilized by Se···N
nonbonded interactions: synthesis and structural characterization
G. Mugesh,a Harkesh B. Singh a,∗ and Ray J. Butcher b
aDepartment of Chemistry, Indian Institute of Technology, Powai, Bombay 400 076, India
bDepartment of Chemistry, Howard University, Washington D.C. 20059, USA
Received 29 October 1998; accepted 2 December 1998
Abstract
The first examples of structurally characterized chiral organoselenenyl halides stabilized by Se···N intramole-
cular interactions are described. The existence of strong nonbonded Se···N interactions in the solid state as well as
in solution was unambiguously determined by single-crystal X-ray analysis and 77Se NMR spectroscopy. © 1999
Elsevier Science Ltd. All rights reserved.
1. Introduction
Organoselenium compounds have become standard reagents for organic synthesis.1 Chiral organose-
lenenyl halides and related derivatives in particular have attracted much attention recently because of
their versatility as chiral electrophilic reagents in asymmetric reactions such as methoxyselenenylation,2
aminoselenenylation,3 and selenocyclization.4 The applications of organoselenenyl halides for the syn-
thesis of natural products such as (+)-samin5 and (+)-membrine6 have also been reported. Interestingly,
most of the selenium reagents used have an asymmetric moiety with a heteroatom in close proximity
to the selenium atom. It has been proposed that there should be a strong Se···N or Se···O interaction
which would allow chiral sources on the nitrogen or oxygen atom to come close to the reaction center
in the transition state of the reaction.2f,h,l The Se···N or Se···O interactions in such cases, therefore,
not only dictate the molecular structure of the active selenium reagent so that the reaction proceeds
through a relatively confined transition state but also increase the electrophilic reactivity of the selenium
compounds.
Although the chemistry of chiral organoselenenyl halides and related derivatives having basic amino
groups has led to very promising results, to the best of our knowledge, no chiral organoselenenyl
halide has been structurally characterized. In continuation of our work on intramolecularly coordinated
∗
Corresponding author. E-mail: chhbsia@chem.iitb.ernet.in
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00507-2

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organochalcogens,7 we report here the synthesis and the first structural characterization of two novel
chiral organoselenenyl halides derived from (R)-(4-ethyl)-2-phenyloxazoline.
2. Results and discussion
Synthesis of (R)-(4-ethyl)-2-phenyloxazoline (2) was accomplished by the reaction of benzoyl chloride
with (R)-(−)-2-amino-1-butanol. Although the oxazoline obtained by this method was pure enough
for further reaction, the yield was poor. Alternatively, when the reaction of ethylbenzimidate (1)
with (R)-(−)-2-amino-1-butanol under reflux conditions was carried out, the desired oxazoline was
obtained in 80% yield. The diselenide (4) was then synthesized by the organolithium route. The lithium
areneselenolate, OxSe−Li+ (3), was easily prepared by the direct low temperature metalation of (R)-
(4-ethyl)-2-phenyloxazoline (2) with n-BuLi in ether followed by the addition of selenium powder.
Oxidation of this lithium selenolate (3) then gave the desired diselenide (4)8 (Scheme 1).
Scheme 1. Reagents and conditions (i) HCl gas, EtOH; (ii) (R)–(−)-2-Amino-1-butanol, ClCH2CH2Cl, reflux, 24 h; (iii) n-BuLi,
ether, −5°C, 4 h; (iv) Se powder, −5°C, 2 h; (v) O2, aq. NaHCO3; (vi) Br2, CCl4, 0°C, 0.5 h; (vii) I2, CCl4, 0°C, 1 h
The stable bromo compound (5) was obtained as a crystalline solid in good yield by reacting the
diselenide (4) with a stoichiometric amount of bromine. It is known that diorgano diselenides (R2Se2)
react with iodine to give only charge-transfer adducts (R2Se2·I2) instead of the selenenyl iodides (RSeI).9
The isolation of the stable binary compounds between iodine and selenium has, however, been difficult
due to their similar electronegativities.10 Du Mont et al. have used a more hindered bis(2,4,6-tri-tert-
butylphenyl) diselenide to synthesize the stable selenenyl iodide.11 However, it was later reported by the
same authors that the slight reduction in the steric bulk (2,4,6-tri-iso-propylphenyl) again leads to the
formation of a charge-transfer complex.12 When the reaction of 4 was carried out with a stoichiometric
amount of iodine, the novel monoiodide 6 was obtained. In 6 the intramolecular stabilization leading to
the formation of 10-Se-3 selane (10 valence electrons, 3 bound ligands) seems to be responsible for the
formation of a covalent Se–I bond rather than a charge-transfer adduct.13

G. Mugesh et al. / Tetrahedron: Asymmetry 10 (1999) 237–242
239
The 77Se NMR chemical shifts are quite informative about the Se···N nonbonded interactions. The
77Se NMR chemical shift for 4 (456 ppm) is shifted more downfield than the systems having sp3 nitrogen
atoms such as bis[2-(dimethylaminomethyl)-phenyl]diselenide (430 ppm)7g and 2,20-diselenobis(N-
cyclohexyl-methylbenzylamine) (432 ppm).14 In the monohalides (5 and 6) a large deshielding is
observed with respect to the diselenide (4) and the magnitude of downfield shift is according to the
electronegativity of the atom attached to the selenium. The chemical shift value of 5 (877.7 ppm) is more
downfield shifted compared with the achiral analogue, [2-(4,4-dimethyl-2-oxazolinyl)phenyl]selenenyl
bromide (849.5 ppm).15 This is probably due to the stronger Se···N interaction (vide infra) in the former
case [2.050(9) Å] compared with the latter one [2.063(3) Å]. However, for 6 the 77Se chemical shift
value (769.3 ppm) is very close to the value observed for the achiral analogue, [2-(4,4-dimethyl-2-
oxazolinyl)phenyl]selenenyl iodide (762.2 ppm).15 It is worth noting that the halo derivatives are quite
stable in solution for a long time, and particularly in the case of 6, no peaks were detected for the
diselenide (4), indicating much higher stability as a result of the intramolecular Se···N coordination.
This is in contrast to a previous report where the authors had observed an equilibrating phenomenon
between the diselenide and its iodo derivative.11
Optical rotations are given with the analytical data. The enantiomeric purity of the compounds was
determined by recording the 1H NMR spectra in the presence of a chiral shift reagent in CDCl3. While
compound 2 was found to be 95% enantiomerically pure, the enantiomeric excess of compounds 4,
5 and 6 was found to be >99%. This suggests that the minor isomer has been removed during the
recrystallization process.
The molecular structures of compounds 5 and 6 with significant bond distances and angles are shown
in Figs. 1 and 2, respectively.
Figure 1. X-Ray structure of 5. Selected bond distances (Å) and angles (°): Se–N(1): 2.050(9); Se–Br: 2.661(2); Se–C(1):
1.933(9); C(1)–Se–N(1): 82.4(4); C(1)–Se–Br: 93.8(3); N(1)–Se–Br: 175.6(3); C(7)–N(1)–Se: 112.5(8); C(9)–N(1)–Se:
136.5(6); C(2)–C(1)–Se: 127.9(8)
The geometry around Se is T-shaped with strong nonbonded Se···N interactions. The Se···N sepa-
rations of 2.050(9) Å for 5 and 2.074(6) Å for 6 are much shorter than the sum of van der Waal’s radii
(3.5 Å).16 The Se–Br [2.661(2) Å] and Se–I [2.8616(10) Å] distances are significantly longer than the
sum of single-bond covalent radii of Se–Br [2.31 Å] and Se–I [2.50 Å], respectively. The intermolecular
distance between Se and Br(A) is 3.856(9) Å which is higher than the sum of single bond covalent radii
(2.310 Å), but considerably shorter than the sum of the van der Waal’s radii (3.95 Å) indicates weak
secondary interactions between the molecules. The iodo compound (6) does not show any intermolecular
interactions. The N···Se–X (X=Br, I) unit is nearly linear due to the Se···N interaction. It is observed
that the deviation of Se–X (X=Br or I) bond from the phenyl plane is significantly reduced by the Se···N
interaction, accompanied by an increase in the Se–X bond length. The interaction between the nitrogen

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G. Mugesh et al. / Tetrahedron: Asymmetry 10 (1999) 237–242
Figure 2. X-Ray structure of 6. Selected bond distances (Å) and angles (°): Se–N: 2.074(6); Se–I: 2.8616(10); Se–C(1): 1.927(6);
C(1)–Se–N: 82.0(3); C(1)–Se–I: 96.5(2); N–Se–I: 176.1(2); C(7)–N–Se: 111.6(6); C(9)–N–Se: 137.1(5); C(2)–C(1)–Se:
126.4(7)
lone pair and the Se–X bond causes a significant charge-transfer from the nitrogen to Se–X bond and
weakens the Se–X bond considerably. This elongation of the Se–X bond increases the possibility of
nucleophilic attack on the selenium. Refinement of the Flack enantiopole parameter17 led to a value of
approximately zero for 5 and 6, thus confirming that the crystals of 5 and 6 are enantiomerically very
pure.
3. Experimental
3.1. General procedures
All reactions were carried out under nitrogen or argon using standard vacuum-line techniques. Solvents
were purified by standard procedures18 and were freshly distilled prior to use. Melting points were
recorded in capillary tubes and are uncorrected. 1H and 13C NMR spectra were obtained at 300 and 75.42
MHz, respectively in CDCl3 on a Varian VXR 300S spectrometer. 77Se NMR spectra were obtained at
95.34 MHz on a Bruker 500 spectrometer. Chemical shifts are cited with respect to SiMe4 as internal
(1H and 13C) and Me2Se (77Se) as external standard. The enantiomeric purity of the compounds was
determined by the integration of signals in the 1H NMR spectrum using the chiral shift reagent Eu(tfc)3.
Elemental analyses were performed on a Carlo–Erba model 1106 elemental analyzer. IR spectra were
recorded as KBr pellets on a Nicolet Impact 400 FTIR spectrometer. Fast atom bombardment (FAB)
mass spectra were recorded at room temperature on a JEOL SX 102 DA-6000 mass spectrometer/data
system using xenon (6 kV, 10 mV) as the bombarding gas. Optical rotations were measured by a JASCO
Model DIP 370 digital polarimeter.
3.2. Synthesis of (R)-(−)-[2-(4-ethyl-2-oxazolinyl)phenyl]selenenyl bromide (5)
To a cold solution of diselenide 4 (0.5 g, 1 mmol) in CCl4 (25 ml) was added a solution of bromine
(0.16 g, 1 mmol) in CCl4. The addition was carried out dropwise over a period of 0.5 h and then allowed
to come to room temperature. The solution obtained was concentrated to give yellow crystalline product,
5. This was recrystallized from chloroform:hexane mixture to give yellow crystals. Yield: 0.61 g (75%),
mp 156–158°C. Anal. calcd for C11H12NOSeBr: C, 39.65; H, 3.60; N, 4.21. Found: C, 39.18; H, 3.91;
N, 3.79; 1H NMR (CDCl3, δ ppm) 1.11 (t, 3H, –CH3, J=7.4 Hz), 1.83–1.92 (m, 1H, –CH–Et), 4.86 (dd,

G. Mugesh et al. / Tetrahedron: Asymmetry 10 (1999) 237–242
241
2H, –CH2O–, J=8.5 Hz), 4.65–4.75 (m, 2H, –CH2–Me), 7.42–7.66 (m, 2H, Ar–H), 7.75–8.82 (m, 2H,
Ar–H); 77Se NMR (CDCl3, δ ppm): 877.7; IR (KBr, cm−1): 736, 927, 1025, 1420, 1493, 1585, 1618,
25
2927; m/z: 333 (M+)(80Se, 78Br)(78Se, 81Br), 252 (100%) (78Se), 199, 181, 155, 116, 54; [α]D −22.0
(c 0.5, CHCl3).
3.3. Synthesis of (R)-(−)-[2-(4-ethyl-2-oxazolinyl)phenyl]selenenyl iodide (6)
To a cold solution of diselenide 4 (0.5 g, 1 mmol) in CCl4 (25 ml) was added a solution of iodine
(0.25 g, 1 mmol) in CCl4. The addition was carried out dropwise over a period of 1 h and then allowed to
come to room temperature and the stirring was continued for additional 2 h. The solution obtained was
concentrated to give red crystalline product, 6. This was recrystallized from chloroform:hexane mixture
to give brick red crystals of 6. Yield: 0.64 g (87%), mp 118–120°C. Anal. calcd for C11H12NOSeI: C,
34.76; H, 3.16; N, 3.69. Found: C, 34.32; H, 3.08; N, 3.54. 1H NMR (CDCl3, δ ppm) 1.15 (t, 3H, –CH3,
J=7.4 Hz), 1.77–1.86 (m, 1H, –CH–Et), 4.66 (dd, 2H, –CH2O–, J=8.8 Hz), 4.51–4.61 (m, 2H, –CH2–Me),
7.39–7.53 (m, 2H, Ar–H), 7.69–8.54 (m, 2H, Ar–H); 77Se NMR (CDCl3, δ ppm): 769.3; IR (KBr, cm−1):
25
736, 933, 1163, 1420, 1499, 1585, 1618, 2927; m/z: 254 (I2), 253 (100%), 200, 147, 136, [α]D −28.0
(c 0.5, CHCl3).
3.4. Crystallography
(−)-(R)-5: Monoclinic, space group C2, a=16.245(3) Å, b=7.028(2) Å, c=11.393(3) Å,
β=113.508(13)°, Z=4, V=1192.9(5) Å3, D=1.855 Mg/m3. Of the 1099 reflections collected, 1009
reflections (F>2σ (Fo)) were used for refinement. The final residuals were R1=4.55%, wR2=9.52%,
and GOF=1.077. For (−)-(R)-6: Orthorhombic, space group P212121, a=6.9470(7) Å, b=11.8683(9) Å,
c=15.5507(13) Å, α, β, γ =90°, Z=4, V=1282.1(2) Å3, D=1.969 Mg/m3. All 1677 reflections collected
were used for refinement. The final residuals were R1=3.55%, wR2=8.60%, and GOF=1.040. The
diffraction measurements for 5 and 6 were performed at room temperature (293 K) on a Siemens
R3m/V diffractometer using graphite-monochromated Mo-Kα radiation (λ=0.7170Å). The unit cell was
determined from 25 randomly selected reflections using the automatic search index and least-squares
routine. The data were corrected for Lorentz, polarization and absorption effects. The data were
monitored by measuring two standard reflections every 60 min of X-ray exposure time. The structures
for 5 and 6 were solved by routine heavy-atom (using SHELXS 8619) and Fourier methods and refined
by full-matrix least squares with the non-hydrogen atoms anisotropic and hydrogens with fixed isotropic
thermal parameters of 0.07 Å2 using the SHELXL 93 program.19 The hydrogens were partially located
from difference electron-density maps and the rest were fixed at calculated positions. Scattering factors
were from common sources.20
Acknowledgements
We are grateful to the Department of Science and Technology (DST), New Delhi for funding this
work. Additional help from the Regional Sophisticated Instrumentation centre (RSIC), Indian Institute
of Technology (IIT), Bombay for 300 MHz NMR spectroscopy and Tata Institute of Fundamental
Research (TIFR), Bombay for 500 MHz NMR spectroscopy is gratefully acknowledged. RJB wishes
to acknowledge the DOD-ONR program for funds to upgrade the diffractometer.

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G. Mugesh et al. / Tetrahedron: Asymmetry 10 (1999) 237–242
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