Synthesis and reactions of conformational isomers of a stable selenenic acid bearing a bridged calix[6]arene framework

Article abstract of DOI:10.1002/hc.1031

A stable selenenic acid bearing a bridged calix[6]arene framework fixed in the 1,2,3-alternate conformation was synthesized. Its properties were compared with those of its conformational isomer fixed in the cone conformation, indicating that the reactivity of the endohedral SeOH group can be regulated by the conformation of the calix[6]arene framework.

Full text of DOI:10.1002/hc.1031

Heteroatom Chemistry
Volume 12, Number 4, 2001
Rapid Communication
Synthesis and Reactions of Conformational
Isomers of a Stable Selenenic Acid Bearing a
Bridged Calix[6]arene Framework
Kei Goto, Toshiyuki Saiki, Shigehisa Akine, Takayuki Kawashima,
and Renji Okazaki
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan; Fax: ם81-3-5800-6899; E-mail: goto@chem.s.u-tokyo.ac.jp
Received 4 January 2001; revised 8 February 2001
INTRODUCTION
ABSTRACT: A stable selenenic acid bearing a bridged
calix[6]arene framework fixed in the 1,2,3-alternate
conformation was synthesized. Its properties were
compared with those of its conformational isomer
fixed in the cone conformation, indicating that the
reactivity of the endohedral SeOH group can be regu-
lated by the conformation of the calix[6]arene frame-
work. ᭧ 2001 John Wiley & Sons, Inc. Heteroatom
Chem 12:195–197, 2001
Although selenenic acids (RSeOH) have been well
recognized as important intermediates in organic
and biochemical reactions of selenium compounds,
the elucidation of their chemistry has been ham-
pered by the absence of a methodology to get a stable
compound of this species [1]. We investigated the
development of the bridged calixarenes represented
by the general formula 1 [2] and successfully applied
it to the synthesis of the first isolable selenenic acid
2a [3]. A stable selenenic acid bearing a 9-triptycyl
group was also recently reported [4]. When ca-
lix[6]arenes are used as a molecular platform, it is
often problematic that their conformational flexibil-
ity is very large [5]. We have found, however, that in
the case of the bridged calix[6]arenes 1, two confor-
mationally frozen isomers, that is, the cone isomer
and the 1,2,3-alternate isomer, can be easily obtained
by arylmethylation of the four hydroxy groups at the
lower rim [6]. Selenenic acid 2a, bearing four ben-
zyloxy groups at the lower-rim, is fixed in the cone
conformation. It is very intriguing how the proper-
ties of the functional group embedded in the cavity
are regulated by the conformation of the ca-
lix[6]arene framework. Here we report the synthesis
of a selenenic acid 2c bearing the 1,2,3-alternate con-
formation and the relationship between the proper-
Dedicated to Professor Naoki Inamoto on the occasion of his
72nd birthday.
Correspondence to: Kei Goto and Renji Okazaki. Present address
(R.O.): Department of Chemical and Biological Sciences, Faculty
of Science, Japan Women’s University, 2-8-1 Mejirodai, Bunkyo-
ku, Tokyo 112-8681.
Contract Grant Sponsor: Ministry of Education, Science, Sports
and Culture.
Contract Grant Number: Grant-in-Aid for Scientific Research
08304037.
Contract Grant Number: Grant-in-Aid for Scientific Research
08740487.
Contract Grant Number: Grant-in-Aid for Scientific Research
12440204.
᭧ 2001 John Wiley & Sons, Inc.
195

196 Goto et al.
TABLE 1 Spectral Data of Selenenic Acids 2a and 2c
ties of the SeOH functionality and the conformation
of the molecule.
a
מ1b
dH (OH)a
dSe
m(OH)/cm
2ac
2c
מ0.05
4.34
1133.8
1097.5
3523
3392
aIn CDCl3.
bIn CH2Cl2.
cRef. [3].
SCHEME 2
RESULTS AND DISCUSSION
The butyl selenide 4c bearing the 1,2,3-alternate con-
formation was prepared by the reaction of the tet-
rahydroxy compound 3 with benzyl bromide in the
presence of NaH followed by chromatographic sep-
aration from the cone isomer 4b (Scheme 1), al-
though the isolated yield of 4c (4%) was much lower
than that of 4b (59%) [7]. Oxidation of selenide 4c
with m-chloroperbenzoic acid (mCPBA) followed by
thermolysis in toluene at 80ЊC afforded selenenic
acid 2c with the 1,2,3-alternate conformation, which
was isolated by silica gel chromatography as color-
less crystals in 44% yield [8]. Selenenic acid 2c
showed high stability both in the crystalline state
and in solution, similarly to the cone isomer 2a.
Even after heating at 120ЊC for 5 hours in
CDCl2CDCl2, 2c underwent only slight decomposi-
tion. Some spectral data of 2c are shown in Table 1
together with those of 2a. The OH absorption bands
of 2a and 2c in the IR spectra suggest that there are
SCHEME 3
intramolecular hydrogen bonding interactions in the
latter while no significant interaction of such kind
exists in the former. This interpretation is supported
1
by observation of the H NMR signal due to the hy-
droxy proton of 2c appearing at a much lower field
than that of 2a, even if it is taken into account that
the OH group of 2a is likely to be more highly
shielded by the calix[6]arene macroring. Apparently,
in these two kinds of isomers, the calix[6]arene
macroring of each conformation provides a consid-
erably different environment for the SeOH function-
ality, although both of them stabilize this otherwise
unstable species effectively (See Table 1).
Both conformational isomers 2a and 2c reacted
with mCPBA to afford the corresponding seleninic
acids 5a and 5c, respectively (Scheme 2). On the
other hand, they showed different reactivities to-
ward a thiol. While the cone isomer 2a reacted with
an excess amount of 1-butanethiol at room tempera-
ture to give selenenyl sulfide 6a, the 1,2,3-alternate
isomer 2c underwent no reaction even at 50ЊC
(Scheme 3). This result can be explained by assum-
ing that the intramolecular hydrogen bonding of the
OH group of 2c reduces the electrophilicity of the Se
atom of the SeOH group, although the steric con-
gestion around the SeOH group may also be respon-
sible. These results clearly demonstrate that the
SCHEME 1

Synthesis and Reactions of Conformational Isomers of a Stable Selenenic Acid Bearing a Bridged Calix[6]arene Framework 197
Stoddart, J. F., Ed.; The Royal Society of Chemistry:
reactivity of the endohedral functionality can be reg-
Cambridge, U.K., 1989; (c) In Calixarenes: A Versatile
Class of Macrocyclic Compounds; Vicens, J., Bo¨hmer,
V., Eds.; Kluwer Academic Publishers: Dordrecht,
ulated by the conformation of the calix[6]arene
framework.
1991; (d) Gutsche, C. D. In Calixarenes Revisited in
Monographs in Supramolecular Chemistry;Stoddart,
J. F., Ed.; The Royal Society of Chemistry: Cam-
ACKNOWLEDGMENTS
bridge, U.K., 1998.
[6] (a) Saiki, T.; Goto, K.; Okazaki, R. Chem Lett 1996,
We thank Tosoh Akzo Co., Ltd., for a generous
993–994; (b) Akine, S.; Goto, K.; Kawashima, T.; Oka-
gift of alkyllithiums.
zaki, R. Bull Chem Soc Jpn 1999, 72, 2781–2783; (c)
Akine, S.; Goto, K.; Kawashima, T. J Inclusion Phe-
nomena and Macrocyclic Chem 2000, 36, 119–124.
[7] The structure of 4b was determined by X-ray crystal-
lographic analysis, the details of which will be re-
ported elsewhere.
REFERENCES
[8] 2c: colorless crystals; m.p. 103–110ЊC (dec); 1H NMR
(500 MHz, CDCl3, TMS, 57ЊC) d 0.98 (s, 18H, t-Bu),
1.00 (s, 18H, t-Bu), 0.98 (s ם s, 9 ם 9H, t-Bu), 3.26
(d, 2J ס 15.9 Hz, 2H, ArCH2Ar), 3.34 (d, 2J ס 15.6 Hz,
[1] (a) For reviews, see: In The Chemistry of Organic Se-
lenium and Tellurium Compounds; Patai, S., Rappo-
port, Z., Eds.; John Wiley & Sons: New York,
1986, 1987; Vols. 1, 2; (b) Flohe´, L. In Free Radicals
in Biology; Pryor, W. A., Ed.; Academic Press: New
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H. E.; Kraus, R. J. In Methods in Enzymology; Colo
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[2] (a) Tokitoh, N.; Saiki, T.; Okazaki, R. J Chem Soc
Chem Commun 1995, 1899–1900; (b) Saiki, T.; Goto,
K.; Tokitoh, N.; Okazaki, R. J Org Chem 1996, 61,
2924–2925; (c) Saiki, T.; Goto, K.; Tokitoh, N.; Goto,
M.; Okazaki, R. Tetrahedron Lett 1996, 37, 4039–
4042; (d) Saiki, T.; Saiki, T.; Akine, S.; Goto, K.; To-
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[3] Saiki, T.; Goto, K.; Okazaki, R. Angew Chem Int Ed
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[4] Ishii, A.; Matsubayashi, S.; Takahashi, T.; Nakayama,
J. J Org Chem 1999, 64, 1084–1085.
[5] For reviews of the chemistry of calixarenes, see: (a)
Pochini, A.; Ungaro, R. Comprehensive Supramolec-
ular Chemistry; Vo¨gtle, F., Ed.; Pergamon: Oxford,
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2
2H, ArCH2Ar), 3.72 (d, J ס 13.0 Hz, 2H, ArCH2Ar),
2
2
3.74 (d, J ס 13.0 Hz, 2H, ArCH2Ar), 3.99 (d, J ס
15.9 Hz, 2H, ArCH2Ar), 4.05 (s, 1H, SeOH), 4.06 (dd,
4
3J ס 7.6 Hz, J ס 1.5 Hz, 1H, arom), 4.22 (s, 2H,
ArOCH2Ar), 4.35 (s, 2H, ArCH2OAr), 4.61 (d, 2J ס 15.6
Hz, 2H, ArCH2Ar), 4.65 (d, 2J ס 11.0 Hz, 2H,
2
PhCH2O), 4.72 (d, J ס 10.4 Hz, 2H, PhCH2O), 4.78
(d, 2J ס 11.0 Hz, 2H, PhCH2O), 5.00 (d, 2J ס 10.4 Hz,
3
2H, PhCH2O), 6.18 (dd, J ס 7.6, 7.5 Hz, 1H, arom),
3
4
6.69 (br d, 2H), 6.80 (dd, J ס 7.5 Hz, J ס 1.5 Hz,
1H), 6.83 (br d, 2H, arom), 6.94 (d, 4J ס 2.5 Hz, 2H),
7.07 (d, J ס 2.4 Hz, 2H), 7.13 (s, 2H), 7.14 (s, 2H),
4
7.31–7.60 (m, 20H). 13C NMR (125 MHz, CDCl3) d
28.6 (t), 28.9 (t), 31.2 (q), 31.3 (q), 31.58 (q), 31.62 (q),
34.03 (s), 34.05 (s), 34.14 (s ן 2), 35.1 (t), 72.4 (t),
74.1 (t), 74.7 (t), 75.8 (t), 123.9 (d), 125.5 (d), 127.3
(d), 127.4 (d), 127.5 (d), 127.7 (d), 127.86 (s), 127.86
(d), 127.93 (d), 128.0 (d), 128.4 (d), 128.5 (s), 128.5
(d), 128.8 (d), 129.3 (d), 130.6 (d), 131.5 (s), 131.8 (d),
132.0 (s), 132.7 (s), 132.9 (s), 135.7 (s), 137.1 (s), 137.2
(s), 138.1 (s), 139.1 (s), 144.3 (s), 144.6 (s), 144.9 (s),
145.6 (s), 150.6 (s), 152.6 (s), 152.9 (s), 153.1 (s); 77Se
NMR (95 MHz, CDCl3) d 1097.5; IR (CH2Cl2) 3392
ם
cmמ1 (mOH). HRMS (FAB) found m/z 1530.7771 (M ),
calcd for C102H114O780Se 1530.7730.