A new intermolecular photochemical approach to calix[4]arene synthesis

Article abstract of DOI:10.1055/s-1998-1643

Calix[4]arene analogs 4a and b were obtained in 15 and 13% yields, respectively, by intermolecular [2 + 2] photocycloaddition. The conformations of 4a and b are assigned to be 1,2-alternate form and cone one, respectively. The calix[4] arenes 5a and b hav

Full text of DOI:10.1055/s-1998-1643

March 1998
SYNLETT
269
A New Intermolecular Photochemical Approach to Calix[4]arene Synthesis
Yukihiro Okada, Masatoshi Hagihara, Masatoshi Mineo, and Jun Nishimura*
Department of Chemistry, Gunma University, Tenjin-cho Kiryu 376, Japan
Received 28 November 1997
Abstract: Calix[4]arene analogs 4a and b were obtained in 15 and 13%
yields, respectively, by intermolecular [2 + 2] photocycloaddition. The
conformations of 4a and b are assigned to be 1,2-alternate form and
cone one, respectively. The calix[4]arenes 5a and b having hydroxy
groups were also obtained in 84 and 80% yields, respectively, by ether
cleavage of 4, whose conformations are maintained by this
transformation.
Pd(PPh ) Cl (5 mol%), LiCl (5 equiv.), and 4-tert-butylcatechol in
3 2 2
DMF at 80 - 90 °C for 3 h. Intermolecular [2 + 2] photocycloaddition
of 3 was carried out by the irradiation with a 400 W high-pressure Hg
5
lamp (Pyrex filter) in benzene for 18 - 47 h under N . The pertinent
2
concentration in this photoreaction was determined as summarized in
Table I. In a low and high concentration (run 1 and 3), 4a-b were
produced in moderate yields. On the other hand, in a medium
concentration (run 2, 31 mM), those yields were remarkably improved
in 15 and 13%, respectively. Therefore, the further [2
photocycloaddition of 3 was performed in 30 mM of benzene solution.
After irradiation and evaporation, 4a and b were isolated in 6.9 - 15 and
+ 2]
1
2
Calixarenes composed of tert-butylphenol or resorcinol are well-
known to act as useful receptors for metal ions and organic molecules.
The sophisticated modifications of their skeletons are widely carried out
7.6 - 13% yields, respectively, by column chromatography (SiO ,
3
2
to extract some new characteristics in host-guest chemistry.
Rigidification of calix[4]arenes was previously reported by using the
dimerization of a metacyclophane unit as a building block, which was
6
benzene/ethyl acetate = 9/1 as an eluent).
made from styrene derivatives by intramolecular [2
+
2]
4
photocycloaddition.
The cyclobutane rings formed by this
photocycloaddition greatly contribute to maintain the syn-conformation.
The rigidified calix[4]arenes have introduced some dramatic change of
binding property compared with parent calixarenes.
Recently, we have aimed to design a new calixarene-type molecule
having endo-hydroxy groups instead of exo-ones like the structural
alteration of calix[4]arene toward resorc[4]arene.
A
simple
intermolecular [2 + 2] photocycloaddition of styrene derivatives was
used for the design of new calixarenes. The transformation of functional
groups was also examined to clarify whether they would change their
molecular conformations. In this communication, we report the
synthesis and characterization of new calix[4]arene analogs by
intermolecular [2 + 2] photocycloaddition.
Structural determination of calix[4]arenes 4 was carried out by NMR
13
spectroscopy in CDCl , including COSY, NOESY, and C NMR
3
experiments. The cyclobutane ring of 4a-b was assigned to be of cis
1
configuration by H NMR chemical shifts at δ 4.32 of its methine
7
protons. The direction of the cyclobutane ring to the methoxy group of
The synthetic route of calix[4]arene analogs 4 is shown in Scheme 1. 4-
Methoxydiphenylmethane 1 was used as a starting material. Dibromide
2 was obtained in 85% yield by the treatment with bromine (1.2 equiv.)
4a - b was easily confirmed by NOESY experiments. That is, the
methylene protons of the cyclobutane ring clearly show an NOE
interaction with Hc aromatic protons. Accordingly, the cyclobutane ring
of 4 is concluded to face to the opposite direction (exo configuration) of
the methoxy groups as shown in Scheme 1.
in CCl at 0 °C for 12 h. Diolefin 3 was obtained in 50% yield by
4
Kosugi-Migita-Stille reaction with vinyltributyltin (1.5 equiv.),
Scheme 1

270
LETTERS
SYNLETT
were isolated in 84 and 80% yields, respectively, by column
chromatography (SiO , benzene/ethyl acetate = 9/1 as an eluent).
2
1
Structures of calix[4]arenes
5
were determined by
H NMR
spectroscopy in DMSO-d . The configuration of cyclobutane ring for
6
calix[4]arenes was assigned to be cis by chemical shift of its methine
7
protons at δ 4.16 (5a) and 4.11 (5b). The methylene bridges of 5b show
AB type coupling (δ 3.06 with J=14 Hz and δ 3.37 with J=14 Hz),
which means the same cone conformation of 4b. Furthermore, 5b held
the cone form from r.t. to 110 °C in same solvent. Accordingly, its
structure is fixed to take the cone conformation even after the
transformation to hydroxy groups from methoxy ones. On the other
hand, those of 5a show a sharp singlet at δ 3.16 to take an alternate
conformation and do not change from r.t. to 110 °C as the same results
for 4a. Based on these observations, calix[4]arenes 4 and 5 rigidified
and maintained their conformation even at a high temperature because
of cyclobutane rings.
In conclusion, we have successfully obtained new calix[4]arene analogs
4 and 5 by intermolecular [2 + 2] photocycloaddition. They were
isolated as both cone and 1,2-alternate isomers. Further investigation
including a synthesis of resorcinol-based calixarenes is now in progress
and will be reported elsewhere.
Acknowledgement. This work was supported in part by grants from the
Japan Society for the Promotion of Science.
References and Notes
1)
Gutsche, C. D. Acc. Chem. Res. 1983, 16, 161; Shinkai, S. J. Incl.
Phenom. 1989, 7, 193.
2)
Arnecke, R.; Böhmer, V.; Paulus, E. F.; Vogt, W. J. Am. Chem.
Soc. 1995, 117, 3286.
The methylene bridges of 4b show AB type coupling (δ 3.55 with J=15
Hz and δ 3.64 with J=15 Hz), which is the same as those ascribed to the
cone form of calixarenes. The same coupling constant is maintained
3)
4)
Böhmer,V. Angew. Chem. Int. Ed. Engl. 1995, 34, 713.
Okada, Y.; Ishii, F.; Kasai, Y.; Nishimura, J. Chem. Lett. 1992,
755; Okada, Y.; Ishii, F.; Kasai, Y.; Nishimura, J. Tetrahedron
Lett. 1993, 34, 1971.
8
from r.t. to 110 °C in CDCl -CDCl (δ 3.56 with J=15 Hz and δ 3.64
2
2
with J=15 Hz) by VT NMR experiments. Moreover, those protons
clearly show only an NOE interaction with Hc aromatic protons.
Accordingly, its aromatic rings are perfectly fixed to take the cone
conformation. On the other hand, those protons of 4a show a sharp
5)
6)
Okada, Y.; Ishii, F.; Akiyama, I.; Nishimura, J. Chem. Lett. 1992,
1579.
+
1
Compd.; Anal. Calcd (found); MS (M ); H NMR δ (intensity,
multiplicity, J in Hz). 4a C O 0.5H O, C, 80.11 (79.95), H,
8
singlet at δ 3.47, which takes an alternate conformation. Furthermore,
H
38 40 4•
2
they clearly show an NOE interaction with both Hb and Hc aromatic
protons. These results obviously suggest that the conformation of
aromatic ring connecting the methylene bridges is completely opposite
(1,2-alternate form). The singlet peak of methylene bridges do not
change at all from r.t. to 110 °C in CDCl -CDCl . Accordingly, VT
7.25 (7.42); 560; 2.26 (4H, m), 2.38 (4H, m), 3.47 (4H, s), 3.52
(12H, s), 4.32 (4H, m), 6.49 (4H, d, 8.3), 6.66 (4H, d, 2.2), 6.82
(4H, dd, 2.2 & 8.3) in CDCl . 4b C
H O 0.5H O, C, 80.11
3
38 40 4• 2
(80.19), H, 7.25 (7.28); 560; 2.36 (8H, m), 3.50 (12H, s), 3.55
(2H, d, 15), 3.64 (2H, d, 15), 4.32 (4H, m), 6.46 (4H, dd, 1.9 &
2
2
NMR experiments demonstrate that the interconversion between 4a and
b cannot take place in NMR time scale even at 110 °C after the
cyclobutane ring formation.
8.2), 6.48 (4H, d, 8.2), 6.76 (4H, d, 1.9) in CDCl . 5a
3
C
H O H O, C, 78.14 (78.41), H, 6.56 (6.62); 504; 2.12 (4H,
34 32 4• 2
m), 2.26 (4H, m), 3.00 (4H, m), 3.16 (4H, s), 4.16 (4H, m), 6.43
(4H, d, 8.0), 6.62 (4H, d, 2.0), 6.71 (4H, dd, 2.0 & 8.0) in DMSO-
The methoxy groups of 4a and b show the same syn conformation,
judging from their NOE interactions with Ha aromatic protons and their
chemical shift of singlet at δ 3.52 and 3.50, respectively. Based on these
observations, it is concluded that 4a takes 1,2-alternate form and 4b
takes cone form as shown in Scheme 1.
d . 5b C
H O H O, C, 78.14 (78.30), H, 6.56 (6.82); 504; 2.17
34 32 4• 2
6
(4H, m), 2.25 (4H, m), 3.00 (4H, m), 3.06 (2H, d, 14), 3.37 (2H, d,
14), 4.11 (4H, m), 6.39 (4H, d, 8.0), 6.66 (4H, dd, 2.0 & 8.0), 6.76
(4H, d, 2.0) in DMSO-d .
6
7)
Okada, Y.; Sugiyama, K.; Wada, Y.; Nishimura, J. Tetrahedron
Lett. 1990, 31, 107; Okada, Y.; Mabuchi, S.; Kurahayashi, M.;
Nishimura, J. Chem. Lett. 1991, 1345.
MM2 calculations showed that the steric energies (SE) for 4a-b were
nearly the same (SE=76.5 kcal/mol for 4a and 77.0 kcal/mol for 4b).
Accordingly, the product distribution by photocycloaddition is expected
ca.1:1 ratio. In fact, the product ratio of 4a-b was ca. 1:1 through all
experiments (see Table I).
9
8)
9)
Gustche, C. D.; Dhawan, B.; Levine, J. A.; No, K. H.; Bauer, L. J.
Tetrahedron 1983, 39, 409.
The synthetic route to hydroxycalix[4]arenes 5a-b is shown in Scheme
1. Thus, 4a and b were treated individually with excess of boron
These values are about 2 kcal/mol less than those of other possible
isomers.
tribromide in dry CH Cl at r.t. for 12 h. After evaporation, 5a and b
2
2