Photoluminescent selenospirocyclic and selenotetracyclic derivatives by domino reactions of amines and imines

Article abstract of DOI:10.1039/c1cc12152a

Novel photoluminescent selenospirocyclic and selenotetracyclic compounds, stabilized by intramolecular secondary Se...O interactions with an ortho-nitro group, have been accessed successfully through domino reactions of amines and imines, respectively.

Full text of DOI:10.1039/c1cc12152a

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COMMUNICATION
Photoluminescent selenospirocyclic and selenotetracyclic derivatives by
domino reactions of amines and iminesw
Vijay P. Singh,a Harkesh B. Singh*a and Ray J. Butcherb
Received 14th April 2011, Accepted 9th May 2011
DOI: 10.1039/c1cc12152a
Novel photoluminescent selenospirocyclic and selenotetracyclic
compounds, stabilized by intramolecular secondary Seꢀ ꢀ ꢀO
interactions with an ortho-nitro group, have been accessed
successfully through domino reactions of amines and imines,
respectively.
Spirocyclic systems, which are part of a large number of natural
products,1 have attracted immense interest and are challenging
targets in organic synthesis.2–4 Among the spirocyclic ring systems,
much attention has been focused on the efficient synthesis of
heterocyclic spiro compounds such as spiroisoxazolines,5
spirooxindoles,6 spirooxazines7 and spiro-b-lactams.8 The
synthetic approaches towards spirocyclic compounds involve
cycloaddition,9 radical cyclization,10 alkylation methods,11
metathesis-mediated,12 rearrangement-based,13 ring closure,14
ring expansion,15 domino reactions16 and metal-catalyzed17
cyclizations.
Fig. 1 Selenium containing spirocycles 1–3 and bicycles 4–5.
active bicyclic compound such as selenapenem 5 with potential
b-lactamase inhibitory properties has been obtained by intra-
molecular homolytic substitution at selenium by a radical
approach.22 Herein, we report new and unusual approaches
to the formation of selenospirocyclic and selenotetracyclic
derivatives.
Spirocyclic heterocycles containing selenium are rare. The
notable examples include the optically active selenium containing
spirocyclic compound 1, which was obtained by halogen mediated
intraselenyl cyclization of a cis-3-(prop-2-ynloxy)-3-benzylseleno-
b-lactam.18 Recently, Back and co-workers have shown that the
spirodioxyselenurane 2 and its homologues act as efficient mimics
of glutathione peroxidase (GPx).19 Another, selenospirocyclic
compound 3 was derived from rhodamine B by treating
rhodamine B acid chloride with selenium powder in the presence
of LiAlH4 (Fig. 1).20 Compound 3 exhibits good fluorescence
properties and has found application in imaging both Hg2+ and
Ag+ in the cell.
Recently, we achieved the syntheses of the novel ebselen
analogues (10–12) by the bromination of selenides 6–7
(Scheme 1).23 When the cyclization reactions of 6–7 were
carried out using Br2/Et3N, the reactions afforded ebselen
derivatives 10–12. However, selenide 8 on bromination
afforded selenospirocycle 15 (13%) in addition to the ebselen
analogues 13–14. The yield of 15 could be improved to 17% by
isolating the brominated yellow intermediate (see ESIw,
Scheme S2) followed by its treatment with Et3N. The
spirocyclization of 8, probably, occurs due to the electron-rich
sec-amine, which in turn activates the benzylic protons. To
establish the role of the electron donating group on the
spirocyclization reaction, when selenide 9, having a stronger
electron-donating methoxy group at the para-position of the
Similarly, there are very few effective methods for the synthesis
of selenium containing bicyclic compounds. To our knowledge,
the first optically active bicyclic compound, such as selenapenam 4
having a C–N bridge, was reported by Perrone and co-workers
from the reaction of 3,4-cis azetidione with Na2Se and followed by
quenching with AgNO3.21 In another approach, novel optically
a Department of Chemistry, Indian Institute of Technology Bombay,
Powai, Mumbai-400076, India. E-mail: chhbsia@chem.iitb.ac.in;
Fax: +91 22 2572 3480; Tel: +91 22 2576 7190
b Department of Chemistry, Howard University,
Washington DC 20059, USA
w Electronic supplementary information (ESI) available: Experimental
details of the synthesis, spectroscopic data, NMR, HRMS, FT-IR
UV-Vis, emission spectra and X-ray crystallographic data for 19.
CCDC 816431 and 816430. See DOI: 10.1039/c1cc12152a
Scheme 1 (i) Br2, CHCl3, 0 1C; (ii) Et3N.
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Fig. 2 Molecular structure of 15. Hydrogen atoms and solvate
Fig. 3 Molecular structure of 20. Hydrogen atoms and solvate
chloroform omitted for clarity.
chloroform omitted for clarity.
In the 77Se NMR spectrum of 20, a single peak at d 706 ppm
was observed. The two five-membered rings in 20 at the C–C
bridge make a dihedral angle of 81.92(11)1 and are stabilized
by intramolecular secondary Seꢀ ꢀ ꢀO (Se1ꢀ ꢀ ꢀO1A 2.721(5) A,
Se2ꢀ ꢀ ꢀO1B 2.719(5) A) interactions (Fig. 3).
N-phenyl ring, was treated with Br2/Et3N, afforded only
the selenospirocycle 16 (26%) as the major product along
with some intractable residue.
Selenospirocyclic compounds 15 and 16 were characterized by
spectroscopic methods. The 77Se NMR spectra show two peaks
each at d 667, 971 ppm (15) and 665, 971 ppm (16), respectively.
The 77Se NMR chemical shifts at d 971, 971 ppm are assigned to
the selenium bonded to a nitrogen atom and at d 665, 667 ppm
to the selenium bonded to a carbon atom, respectively. The
molecular structure of 15 was unambiguously established by single
crystal diffraction studies (Fig. 2).z Though the molecule had
crystallized as a racemate, the asymmetric unit is optically pure
and configuration of C7A is R. The two rings connected by C7A
make a dihedral angle of 89.72(12)1 and are stabilized by intra-
molecular secondary SeꢀꢀꢀO (Se1ꢀꢀꢀO1A 2.601(16) A, Se2ꢀꢀꢀO1B
2.751(9) A) interactions.
The formation of 20 is in contrast to our earlier observation,
where a N-bridged bicyclic compound was obtained from the
reaction of a selenium cation with tribromide as a counter-
anion with benzenethiol (PhSH).25 This is not surprising in
view of the pKa values of PhSH (6.5)26 and reduced
glutathione (GSH, 9.2),27 respectively. The results suggest that
the higher basicity of the thiolate (GSꢁ) anion favors attack at
the imine carbon instead of the selenium centre. A plausible
mechanism for the formation of 20 is proposed (see ESIw,
Scheme S4).
UV-Vis and photoluminescence spectra of 15, 16 (Fig. 4)
and 20 were recorded in CHCl3 at 10ꢁ5 M concentration at
25 1C. The absorption spectra of compounds 15 and 16
showed three well separated absorption bands at 270, 360
and 427 nm whereas compound 20 showed only two bands at
257 and 400 nm. The most prominent band of 15 and 16 is the
strong absorption band at 270 nm with high molar extinction
coefficient (see ESIw, Fig. S53–S54 and Table S2). The photo-
luminescence spectra of 15, 16 and 20 were recorded using an
excitation wavelength of 270 nm. Compounds 15 and 16
exhibited two bands in photoluminescence spectra at 400 nm
and 500 nm whereas compound 20 exhibited a single band at
360 nm with a shoulder in the red region. Quantum yields (F)
for compounds 15 (F = 0.006), 16 (F = 0.02) and 20
(F = 0.002) were estimated by using 9-hydroxymethylanthracene
(9-HMAn, F = 0.32) as a standard.28 The quantum yield
The additional –NO2 substituent at the ortho-position to the
selenium also plays a crucial role in the cyclization reactions
due to aromatic ring strain.24 Based on these observations
a plausible mechanism for the formation of 15 is proposed
(see ESIw, Scheme S2).
Interestingly, when the cyclization of 6 and 8 was attempted
by adding first Et3N followed by bromine/SO2Cl2 into the
reaction mixture, the reaction afforded selenium cations 17,25
18 and 19, respectively (Scheme 2). Cations 17–19 result
due to benzylic deprotonation of selenides 6 and 8 (see ESIw,
Scheme S3). Attempted reaction of 18 with reduced
glutathione (GSH) afforded an unexpected selenotetracyclic
compound; 4b,9b-di(phenylamino)-1,6-dinitro-4b,9b-dihydro-
[b]benzo[4,5]selenopheno[2,3-d]selenophene (20, 34%), instead
of the expected selenenyl sulfide 21.
Scheme 2 (i) Et3N/CHCl3, Br2, 0 1C; (ii) Et3N/CHCl3, SO2Cl2, 0 1C;
(iii) GSH, MeOH, H2O, rt.
Fig. 4 Normalized absorption and photoluminescence spectra of 16
in dilute CHCl3 solution (10ꢁ5 M).
c
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(0.02) of 16 is higher than that reported for related compound
3 (F = 0.01).20
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In summary, an unprecedented formation of novel seleno-
spirocycle 15 and 16 has been achieved by the reaction of
simple selenides 8 and 9 with Br2/Et3N in one-pot synthesis.
The presence of electron-donating para-substituents, such
as –OMe and –Me, at the N-phenyl ring and an additional
ortho-coordinating nitro group at the 6-position plays a crucial
role in the spirocyclization. Selenospirocycles 15 and 16
exhibit significant photoluminescence. The unique synthesis
and structural characterization of a new selenotetracycle 20
has also been demonstrated by interesting C–C bond formation
using a thiol group. Further studies on the scope of this new
reaction are underway in our laboratory.
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HBS is grateful to the Department of Science and Technology
(DST), New Delhi-110016 (India), for the Ramanna
Fellowship. We thank Prof. V. K. Singh and Prof. I. N. N.
Namboothiri (Department of Chemistry, Indian Institute of
Technology Bombay) for helpful discussions, Sophisticated
Analytical Instrumental Facility (SAIF), Indian Institute of
Technology Bombay (IITB), for recording 77Se NMR spectra.
VPS wishes to thank IIT Bombay for a teaching assistantship.
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Notes and references
z The data for 15: C29H21Cl3N4O4Se2, Mr = 753.77, triclinic, space
ꢀ
group P1, a = 10.5321(8) A, b = 10.6562(7) A, c = 14.6081(11) A,
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l = 1.541841, Z = 2, T = 295(2) K, rcalcd = 1.677 Mg mꢁ3, GOF =
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c
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Chem. Commun., 2011, 47, 7221–7223 7223