The synthesis of spirophanes from a pentaerythrityl core

Article abstract of DOI:10.1016/j.tetlet.2005.01.085

Various thia- and oxa-spirobicyclic cyclophanes were synthesized from a pentaerythrityl building block and appropriate dithiols/bisphenols.

Full text of DOI:10.1016/j.tetlet.2005.01.085

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1905–1907
The synthesis of spirophanes from a pentaerythrityl core
Perumal Rajakumar,* Karuppannan Sekar and Kannupal Srinivasan
Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India
Received 4 November 2004; revised 13 January2005; accepted 18 January2005
Abstract—Various thia- and oxa-spirobicyclic cyclophanes were synthesized from a pentaerythrityl building block and appropriate
dithiols/bisphenols.
Ó 2005 Elsevier Ltd. All rights reserved.
The pentaerythrityl core acts as a versatile building
block in supramolecular chemistryand has been em-
ployed for the syntheses of various spiro crown ethers,1
spiro-macrocyclic ligands,2 spiro-bicyclic peptides,3
spiro-catenanes4 and dendrimers.5 However, to the best
of our knowledge, no pentaerythritol-based spirobicy-
clic cyclophanes incorporating rigid aromatic spacers
have been reported. These cyclophanes would function
as potential bi-site receptors and hence two guest mole-
cules could be accommodated in a single cyclophane
molecule despite the electrostatic repulsion between the
guest molecules.1b Since the two macrocyclic units in
these cyclophanes are oriented orthogonally to each
other, the resulting complexes are poised to be in differ-
ent planes and this phenomenon could be used for the
construction of novel magnetic6 and electronic
materials.7 Herein we report the synthesis of various
spiro-bicyclic cyclophanes viz., thiaspirophane 1, intra-
annularlyfunctionalized thiaspirophanes 2a–c, oxaspi-
rophane 3 and chiral oxaspirophane 4 from a pentae-
rythritol-derived aromatic tetrabromide 7.
This extended tetrabromide 7 has two advantages over
the starting pentaerythrityl tetrabromide: (i) it possesses
S
S
S
S
S
S
O
O
O
O
O
O
O
O
R
R
1
S
S
2a R = H
2b R = Br
2c R = CO Me
O
O
2
O
O
O
O
O
O
O
O
O
O
O
O
H C
CH
3
3
O
O
4
3
Keywords: Spirophanes; Pentaerythrityl; m-Terphenyl; Chiral cyclophane.
*
Corresponding author. Tel.: +91 44 22351269 213; fax: +91 44 22352494; e-mail: perumalrajkumar2003@yahoo.co.in
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.01.085

1906
P. Rajakumar et al. / Tetrahedron Letters 46 (2005) 1905–1907
R
R
R
2a-c
1
R
O
O
O
O
SH
SH
SH
SH
9a-c
8
i
i
R
5 R = CO2Me
6 R = CH2OH
7 R = CH2Br
7
i
ii
iii
ii
CH3
Scheme 1. Reagents and conditions: (i) LiAlH4, THF, reflux, 12 h,
72%; (ii) MsCl, Et3N, THF, 0 °C, 3 h; then LiBr, acetone, rt, 12 h,
69%.
OH
OH
3
HO
OH
4
10
11
R = H, Br, CO2Me
the more reactive benzylic bromide functionality and (ii)
the presence of aromatic spacers would avoid steric con-
gestion during cyclization. The tetrabromide 7 was syn-
thesized as outlined in Scheme 1. The tetraester 5,
obtained bythe fourfold O-alkylation of pentaerythrityl
tetrabromide with methyl-4-hydroxybenzoate,8 was
reduced with LiAlH4 in refluxing THF to afford the
tetra-alcohol 6 in a 72% yield. Conversion of the tetra-
alcohol 6 to the corresponding tetrabromide 7 was at-
tempted with various brominating agents such as PBr3
in CH2Cl2, CBr4/PPh3 in THF and Br2/PPh3 in CH3CN
but the results were not satisfactory. Thus, tetraalcohol
6 was treated with MsCl in the presence of Et3N in THF
to give a tetramesylated compound, which was then con-
verted into the tetrabromide 7 in 69% yield by an
exchange reaction with LiBr in acetone.
Scheme 2. Reagents and conditions: (i) KOH, C6H6/EtOH (1:9, v/v),
12 h; afforded 1 (40%) and 2a (25%) 2b (18%) and 2c (23%); (ii) K2CO3,
CH3CN, 60 °C, 16 h, 15%; (iii) K2CO3, acetone, rt, 10 d, 12%.
(Fig. 1) indicates that the two macrocyclic units are per-
pendicular to each other.
Incorporation of m-terphenyl building blocks into these
kinds of cyclophanes would make the cyclophanes have
large noncollapsible rigid cavities with intra-annular
functionality.11 With this idea in mind, the tetrabromide
7 was coupled with each of the m-terphenyl dithiols 9a–
c12 under high dilution conditions to afford the spirobi-
cyclic cyclophanes 2a,13 2b and 2c in 25%, 18% and 23%
yields, respectively (Scheme 2).
In order to test the utilityof the tetrabromide 7 for the
synthesis of spirobicyclic cyclophanes, 1 equiv of 7 was
reacted with 2 equiv of m-xylene dithiol (8) in the pres-
ence of KOH in a C6H6–EtOH (1:9, v/v) mixture under
high dilution conditions. The spirobicyclic cyclophane 1
was thus obtained in 40% yield after column chromato-
graphic purification (Scheme 2). The structure of the
cyclophane 1 was confirmed byspectroscopic and ana-
lytical data9 and XRD studies.10 It is interesting to note
that in the 1H NMR spectrum of 1, the intra-annular m-
xylenyl proton was highly shielded and appeared at d
6.09. The ORTEP plot of the crystal structure of 1
Having succeeded in establishing a method for the syn-
thesis of thia-spirobicyclic cyclophanes, we focussed our
attention on the synthesis of similar oxacyclophanes.
Thus stirring 1 equiv of 7 with 2 equiv of the bisphenol
10 (obtained bycleaving the corresponding dimethoxy
compound14 with HBr in AcOH) in the presence of
K2CO3 in CH3CN at 60 °C for 16 h afforded the spiro-
bicyclic oxacyclophane 315 in 15% yield (Scheme 2).
To extend the utilityof the tetrabromide 7 for the syn-
thesis of chiral spirophanes, 7 was stirred with 2 equiv
Figure 1. ORTEP plot of the crystal structure of 1.

P. Rajakumar et al. / Tetrahedron Letters 46 (2005) 1905–1907
1907
8. Oike, H.; Imamuva, H.; Imaizumi, H.; Tezuka, Y.
Macromolecules 1999, 32, 4819–4825.
of (S)-BINOL (11) in the presence of K2CO3 in acetone
at room temperature for 10 days to give cyclophane 416
in 12% yield (Scheme 2). This chiral cyclophane having a
spiro backbone maybe useful for chiral molecular rec-
9. Cyclophane 1: yield 40%; mp 208 °C; 1H NMR (500 MHz,
CDCl3): d 3.34 (s, 8H); 3.41 (s, 8H); 4.38 (s, 8H); 6.09 (s,
2H); 6.84 (d, 8H, J = 8.6 Hz); 7.10 (d, 8H, J = 8.6 Hz);
7.25–7.33 (m, 6H); 13C NMR (125 MHz, CDCl3); d 33.5,
33.8, 47.0, 66.2, 114.7, 127.6, 129.5, 130.0, 130.3, 131.3,
137.4, 158.0; m/z (FAB-MS) 828 (M+). Elemental anal.
calcd for C49H48O4S4: C, 70.98; H, 5.83. Found: C, 70.86;
H, 5.71.
1
ognition and asymmetric catalysis.17 In the H NMR
spectrum of cyclophane 4, the CH2 protons attached
to the BINOL unit as well as those attached to the spiro
carbon appear as two doublets due to the atropisomer-
ism of the (S)-BINOL unit.18
10. This work has been carried out as a collaborative work
with Prof. D. Velmurugan, Department of Crystallogra-
phyand Biophsyics, Universityof Madras, Guindy
Campus, Chennai 600 025 and will appear as a separate
communication.
In conclusion, we have synthesized various thia- and
oxa-spirobicyclic cyclophanes from a pentaerythritol-
derived aromatic tetrabromide. The utilityof this poten-
tial precursor for the synthesis of other similar
cyclophanes and detailed complexation studies with
these cyclophanes are under investigation.
11. Kannan, A.; Rajakumar, P.; Kabaleeswaran, V.; Rajan, S.
S. J. Org. Chem. 1996, 61, 5090–5102.
12. Hart, H.; Rajakumar, P. Tetrahedron 1995, 51, 1313–1336.
13. Cyclophane 2a: yield 25%; mp 185 °C; 1H NMR
(400 MHz, CDCl3): d 3.68 (s, 8H); 3.76 (s, 8H); 3.98 (s,
8H); 6.61 (d, 8H, J = 7.5 Hz); 6.88 (d, 8H, J = 7.2 Hz);
7.06 (d, 8H, J = 7.1 Hz); 7.24-7.67 (m, 16H); 13C NMR
(100 MHz, CDCl3); d 36.5, 36.8, 67.5, 114.6, 125.1, 125.7,
126.9, 129.4, 129.9, 131.4, 138.6, 138.7, 139.3, 141.5, 157.8;
m/z (FAB-MS) 1132 (M+). Elemental anal. calcd for
C73H64O4S4: C, 77.35; H, 5.69. Found: C, 77.27; H, 5.62.
14. Rajakumar, P.; Srinivasan, K. Tetrahedron 2004, 58,
10285–10291.
Acknowledgements
The authors thank CSIR, India for financial assistance;
SAIF, IIT Madras for NMR spectra and RSIC, Luc-
know for FAB-MS spectra.
15. Cyclophane 3: yield 15%; mp 155 °C; 1H NMR (400 MHz,
CDCl3): d 2.42 (s, 6H); 4.20 (s, 8H); 5.25 (s, 8H); 6.74–6.76
(m, 10H); 6.79 (d, 8H, J = 8.6 Hz); 7.15 (d, 8H,
J = 8.6 Hz); 7.19–7.20 (m, 12H); 13C NMR (100 MHz,
CDCl3); d 23.4, 46.5, 64.8, 69.6, 107.3, 114.4, 116.7, 124.9,
128.5, 129.6, 133.8, 134.5, 138.1, 157.8; m/z (FAB-MS)
1040 (M+). Elemental anal. calcd for C71H60O8: C, 81.90;
H, 5.81. Found: C, 81.79; H, 5.73.
16. Cyclophane 4: Yield 12%; ½aŠ ¼ ꢀ125:0; mp 139 °C; H
NMR (500 MHz, CDCl3): dD4.03 (d, 4H, J = 10.3 Hz);
4.26 (d, 4H, J = 10.3 Hz); 4.71 (d, 4H, J = 11.5 Hz); 4.95
(d, 4H, J = 11.5 Hz); 6.31 (d, 8H, J = 8.6 Hz); 6.61 (d, 8H,
J = 8.8 Hz); 7.12-7.32 (m, 12H); 7.53 (d, 4H, J = 9.2 Hz);
7.87 (d, 4H, J = 8.6 Hz); 7.96 (d, 4H, J = 9.2 Hz); 13C
NMR (125 MHz, CDCl3); d 47.9, 67.1, 70.9, 115.1, 116.8,
121.4, 123.8, 125.4, 126.4, 128.0, 128.1, 129.4, 129.7, 154.0,
159.2; m/z (FAB-MS) 1060 (M+). Elemental anal. calcd for
C73H56O8: C, 82.62; H, 5.32. Found: C, 82.52; H, 5.24.
17. Diederich, F. Cyclophanes. In Monographs in Supramo-
lecular Chemistry; Stoddart, J. F., Ed.; Royal Society of
Chemistry: Cambridge, 1991.
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