Novel synthesis of macrocycles with 1,1′-binaphthalene-2,2′-diol using intramolecular oxidative coupling

Article abstract of DOI:10.1016/j.tetlet.2006.09.161

A new series of BINOL-based macrocycles with two phenolic protons have been synthesized via oxidative coupling reaction using CuCl(OH)-TMEDA.

Full text of DOI:10.1016/j.tetlet.2006.09.161

Tetrahedron Letters 47 (2006) 8563–8566
Novel synthesis of macrocycles with
1,10-binaphthalene-2,20-diol using intramolecular oxidative coupling
Satoshi Ito,* Kazuya Koizumi, Katsuhiko Fukuda, Naohiro Kameta, Tsukasa Ikeda,
Toru Oba and Kazuhisa Hiratani
Department of Applied Chemistry, Faculty of Engineering, Utsunomiya University, Youtou 7-1-2, Utsunomiya,
Tochigi 321-8585, Japan
Received 28 July 2006; revised 14 September 2006; accepted 22 September 2006
Abstract—A new series of BINOL-based macrocycles with two phenolic protons have been synthesized via oxidative coupling reac-
tion using CuCl(OH)–TMEDA.
ꢀ 2006 Published by Elsevier Ltd.
Macrocycles containing hydrogen bonding sites have at-
tracted much attention due to their complexing ability
toward ions or molecules.1 1,10-Binaphthol (BINOL)-
based macrocycles possess an excellent ability of chiral
recognition, which has been applied to chiral stationary
phases for HPLC.2 It has been expected that macro-
cycles with a 1,10-binaphthalene-2,20-diol moiety have
superior chiral recognition ability compared with the
established BINOL-based chiral macrocycles, because
their two phenolic protons can interact with chiral
molecules by hydrogen bonding. Cram and co-workers
synthesized macrocycles having a 1,10-binaphthalene-
2,20-diol unit from 1,10-binaphthalene-2,20-diol deriva-
tive and oligothioethers.3 Kellogg and co-worker
synthesized their analogues of a,x-bis(hydroxynaph-
thyl)oligoethers by intramolecular oxidative coupling
using FeCl3, K3Fe(CN)6 and Cu(II)(RNH2)4 as oxi-
dants, although the starting materials were recovered.4
In our laboratory, various macrocyclic compounds with
plural phenolic protons have been synthesized via tan-
dem Claisen rearrangement. These macrocycles recog-
nized ions or molecules effectively.5 Macrocycles with
optimizing tandem Claisen rearrangement using precur-
sor macrocycles. We report here the novel synthesis of
macrocycles bearing the 1,10-binaphthalene-2,20-diol
unit, 1 and 2, by intramolecular oxidative coupling reac-
tion of a,x-bis(hydroxynaphthyl)oligoethers using
CuCl(OH)–TMEDA as oxidant.7
Schemes 1 and 2 show synthesis of the target 1,10-
binaphthalene-2,20-diol-based macrocycles bearing
phenolic protons 1a–c and 2a–c. Catechol was reacted
with 2-(2-chloroethoxy)ethanol, 2-(2-(2-chloroethoxy)-
ethoxy)ethanol, and 2-(2-(2-(2-ethoxy)ethoxy)ethoxy)-
ethanol monotosylate in the presence of NaOH to give
diols 3a–c in good yields (50–70%), respectively. Ditosyl-
ates 4a–c and 7a–c were obtained by reaction of p-tolu-
enesulfonylchloride with 3a–c and oligoethyleneglycols
(n = 1,2,3), respectively, in excellent yields (82–96%).
Ditosylates 4a–c and 7a–c were converted to the corre-
sponding diiodides 5a–c and 8a–c with excess NaI in
acetone, respectively (81–93%).8
Chain compounds 6a–c and 9a–c were obtained by
etherification between the polyether diiodides 5a–c,
8a–c and 2,3-dihydroxynaphthalene derivative 10 in
60–70% yield, followed by deprotection of THP.
Mono-THP-protected 2,3-dihydroxynaphthalene 10
was prepared from 2,3-dihydroxynaphthalene in two
steps as previously reported.9 The target macrocycles
1a–c and 2a–c were then obtained as racemic mixtures
by oxidative coupling reaction under high dilution
(1.0 mmol/100 ml) using CuCl(OH)–TMEDA in accept-
able yield (18–32%), and their cyclic oligomers (dimer,
a
chiral 1,10-bi-4,5,6,7-tetrahydroxynaphthalene-2,20-
diol have been synthesized from macrocyclic bis(allylic
ether)s by Lewis acid-mediated tandem Claisen rear-
rangement.6 However, the synthesis of macrocycles with
1,10-binaphthalene-2,20-diol-based macrocycles has been
limited in this synthetic strategy, because of difficulty in
*
Corresponding author. Fax: +81 28 689 6009; e-mail: s-ito@
cc.utsunomiya-u.ac.jp
0040-4039/$ - see front matter ꢀ 2006 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2006.09.161

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S. Ito et al. / Tetrahedron Letters 47 (2006) 8563–8566
O
O
O
O
X
X
OH
OH
n
n
3a-c: X = OH
4a-c: X = OTs
5a-c: X = I
i
ii
iii
+
2
X
O
OH
O
n
O
O
O
O
n
O
n
O
iv
1a: n = 1 (28%)
1b: n = 2 (29%)
1c: n = 3 (32%)
v
OH
OH
OH
OH
ONa
O
O
OTHP
O
O
O
10
6a-c
n
n
Scheme 1. Reagents and conditions: (i) NaOH, n-BuOH, reflux, 2 d; (ii) TsCl, NaOH, THF–H2O (1:1), 0 ꢁC, 4 h; (iii) NaI, acetone, reflux, 8 h;
(iv) n-BuOH, reflux, 12 h, then p-TsOH, MeOH, reflux, 8 h; (v) air, CuCl(OH)–TMEDA, rt.
O
O
O
O
O
O
iv
iii
OH
OH
OH
OH
2a: n = 1 (18%)
2b: n = 2 (26%)
2c: n = 3 (28%)
O
X
O
O
O
X
O
n
ONa
X = OH
i
ii
OTHP
7a-c: X = OTs
8a-c: X = I
O
O
10
n
n
9a-c
Scheme 2. Reagents and conditions: (i) TsCl, NaOH, THF–H2O (1:1), 0 ꢁC, 4 h; (ii) NaI, acetone, reflux, 8 h; (iii) n-BuOH, reflux, 12 h, then
p-TsOH, MeOH, reflux, 8 h; (iv) air, CuCl(OH)–TMEDA, rt.
trimer, and tetramer) were also detected by TOF-
MS.10,11 When FeCl3 was used as an oxidative coupling
reagent, the starting materials were recovered, which is
consistent with the report by Kellogg et al.4
cycles is drastically changed by introduction of the
benzene unit on the polyether ring. Interestingly, neither
macrocycles without the benzene unit 2 nor larger
macrocycles 1c (34-membered) have been separated
under any conditions due to flexibility of the ring
moiety. Macrocycles 1 and 2 could not exhibit chiral rec-
ognition ability for any amino acids, sugar derivatives,
and amino alcohols.
Figure 1 represents HPLC profiles of 22-membered mac-
rocycles 1a and 2b. Stereoisomers of 22-membered 1a
and 28-membered 1b macrocycles were separated com-
pletely using
a chiral HPLC column (DAICEL
CHIRALPAK IA); eluent, chloroform:n-hexane:etha-
nol = 55:45:1). The (S)-isomer eluted earlier than the
(R)-isomer in each case, assigned by using the exciton
chirality method (Fig. 2).12 In contrast, the enantiomer
of macrocycle 2b that has the same ring size as 1a could
not be separated by using the above chiral column, indi-
cating that the chiral recognition ability of the macro-
Single crystals of macrocycles 1a, 1b, and 2b were read-
ily obtained from several solvents such as acetonitrile,
ethyl acetate, and a mixture of ethyl acetate–toluene
(1:1), respectively. In each case, the single crystal con-
sisted of a racemic mixture. One water molecule was in-
cluded in the center position of the cyclic polyether
moiety, and was fixed triply by hydrogen bondings with
a
b
(S)
(R)
17.72 min
28.76 min
14.30 min
Figure 1. HPLC profiles of 25-membered macrocycles 1a (a) and 2b (b). HPLC conditions: column, DAICEL CHIRALPAK IA; eluent,
chloroform:n-hexane:ethanol = 55:45:1; flow rate, 0.3 ml/min.

S. Ito et al. / Tetrahedron Letters 47 (2006) 8563–8566
8565
Acknowledgments
(R): 28.76 min
We wish to thank Professor Dr. Hidemitsu Uno (Divi-
sion of Synthesis and Analysis, Department of Mole-
cular Science, Integrated Center for Sciences, Ehime
University) for carrying out the X-ray single crystal
analysis (for 2b), and Dr. Michinori Karikomi (Depart-
ment of Applied Chemistry, Faculty of Engineering,
Utsunomiya University) for carrying out the CD
measurement.
Δε
References and notes
(S): 17.72 min
1. In Host–Guest Complex Chemistry I, II, and III; Voegtle,
F., Ed.; Springer-Verlag-VCH: Berlin, 1981 (I), 1982 (II),
1984 (III); In Inclusion Compounds Vols. 1–5; Atwood, J.
L.; Davies, J. E. D.; MacNicol, D. D., Eds.; Academic
Press: London, 1984 (Vols. 1–3); 1991 (Vols. 4–5).
2. Pirkle, W. H.; Finn, J. M.; Schreiner, J. L.; Hamper, B. C.
J. Am. Chem. Soc. 1981, 103, 3964; Pirkle, W. H.;
Schreiner, J. L. J. Org. Chem. 1981, 46, 4988.
3. Koenig, K. E.; Helgeson, R. C.; Cram, D. J. J. Am. Chem.
Soc. 1976, 98, 4018; Helgeson, R. C.; Tarnowski, T. L.;
Cram, D. J. J. Org. Chem. 1979, 44, 2538.
4. Stock, H. T.; Kellogg, R. M. J. Org. Chem. 1996, 61, 3093.
5. Naher, S.; Hiratani, K.; Karikomi, M.; Haga, K. J.
Heterocycl. Chem. 2005, 42, 575; Hiratani, K.; Sakamoto,
N.; Kameta, N.; Karikomi, M.; Nagawa, Y. Chem.
Commun. 2004, 1474.
250
300
350
400 (nm)
Figure 2. CD spectra of (R)-1a and (S)-1a.
the macrocycles (O10–H–O16, O7–H–O16, and O11–
H–O16 in Fig. 3: dotted lines). The cavity of macro-
cycles 1 and 2 was reduced by intramolecular hydrogen
bonding (C65–H–O4 in Fig. 3: wavy line).13 These
resemble the crystal structures of macrocycles with a
1,10-binaphthalene-2,20-diol unit reported by Cram and
coworkers.3
In summary, we have developed a novel synthesis of
macrocycles with a 1,10-binaphthalene-2,20-diol unit by
using intramolecular oxidative coupling reaction. These
macrocycles will also be converted to novel asymmetric
catalysts or chiral supramolecules. We are now explor-
ing the chiral recognition ability of macrocycles 1 and
2 as well as the synthesis of novel chiral supramolecules
such as rotaxanes and catenanes.14
6. Yoshida, H.; Kobayashi, Y.; Hiratani, K.; Saigo, K.
Tetrahedron Lett. 2005, 46, 3901, and references are
herein.
7. Bhushan, S.; Vijayakumaran, K. Acros Org. Acta 2003,
10; Bringmann, G.; Mortimer, A. J. P.; Keller, P. A.;
Gresser, M. J.; Garner, J.; Breuning, M. Angew. Chem.,
Int. Ed. 2005, 44, 5384.
8. Macrocycle Synthesis, A Practical Approach; Parker, D.,
Ed.; Oxford University Press: Oxford, 1996.
9. Hiratani, K.; Kasuga, K.; Goto, M.; Uzawa, H. J. Am.
Chem. Soc. 1997, 119, 12677; Hiratani, K.; Uzawa, H.;
Kasuga, K.; Kambayashi, H. Tetrahedron Lett. 1997, 38,
8993.
10. Typical procedure of macrocycle 1a: A solution of 6a
(1.75 g, 3.07 mmol) and CuCl(OH)–TMEDA (68.5 mg,
0.30 mmol) in CHCl3 (500 ml) was stirred for one day at
room temperature under air. The reaction mixture was
washed with water (· 3) and brine (· 1). The organic phase
was dried with anhydrous Na2SO4 and evaporated to
dryness on a rotary evaporator. After evaporation, mac-
rocycle 1a was purified by column chromatography (silica
gel) using CHCl3/EtOH (93:7) as eluent. It was then
crystallized from acetonitrile (0.494 g, 28%) as white
plates.
11. Selected spectra data for 6a: colorless paste; 1H NMR
(CDCl3): d 8.51 (s, 2H), 7.60 (m, 4H), 7.28–7.20 (m, 6H),
7.04 (s, 2H), 6.91–6.64 (m, 4H), 4.30 (m, 4H), 4.18 (m,
4H), 4.11 (m, 4H), and 4.04 (m, 4H); 13C NMR (CDCl3): d
148.1, 147.2, 146.7, 130.0, 128.7, 126.4, 124.1, 123.4, 121.3,
112.8, 110.0, 107.0, 69.4, 69.3, 67.8, and 67.8; MS
(MALDI-TOF) m/z 571 (M+H+). Anal. Calcd for
C34H34O8: C, 71.56; H, 6.01. Found: C, 71.18; H, 6.23.
Compound 1a: white crystals: mp = 146–148 ꢁC; 1H
NMR (CDCl3): d 7.71 (d, 2H), 7.43 (br s, 2H, OH), 7.41
(s, 2H), 7.28 (m, 2H), 7.15 (m, 4H), 6.87 (m, 4H), 4.50–
4.37 (m, 4H), 4.20–4.10 (m, 4H), and 4.02–3.73 (m, 8H);
13C NMR (CDCl3) d 147.9, 146.1, 146.0, 130.4, 128.7,
Figure 3. ORTEP diagram of macrocycle 1a with crystallographic
numbering system.

8566
S. Ito et al. / Tetrahedron Letters 47 (2006) 8563–8566
126.9, 125.1, 124.8, 123.5, 121.3, 116.1, 113.0, 111.8, 70.2,
128.6, 126.8, 125.0, 124.6, 123.4, 116.2, 111.2, 70.4, 70.2,
69.9, 69.8, 68.8; MS (MALDI-TOF) 520 (M+). Anal.
Calcd for C30H32O8ÆH2O: C, 65.80; H, 6.44. Found: C,
66.04; H, 6.41.
68.9, 66.9, and 66.9; MS (MALDI-TOF) m/z 569
(M+H+). Anal. Calcd for C34H32O8ÆH2O: C, 69.61; H,
5.84. Found: C, 69.08; H, 5.75. Compound 9b: colorless
paste; 1H NMR (CDCl3) 7.63–7.58 (m, 4H), 7.30–7.23 (m,
4H), 7.22 (s, 2H), 7.08 (s, 2H), 6.65 (br s, 2H, OH), 4.29–
4.25 (m, 4H), 3.96–3.92 (m, 4H), 3.76–3.67 (m, 12H); 13C
NMR (CDCl3) d 146.9, 146.1, 130.1, 128.7, 126.4, 126.2,
124.2, 123.5, 110.7, 107.9, 70.5, 70.3, 69.3, 69.2, 68.2; MS
(MALDI-TOF) m/z 523 (M+H+). Anal. Calcd for
C30H34O8: C, 68.95; H, 6.56. Found: C, 69.19; H, 6.66.
Compound 2b: colorless crystals; mp = 198–199 ꢁC, 1H
NMR (CDCl3) d 7.73 (d, 2H), 7.39 (br s, 2H, OH), 7.38 (s,
2H), 7.30–7.25 (m, 2H), 7.12 (m, 4H), 4.43 (m, 4H), 3.92–
3.56 (m, 16H); 13C NMR (CDCl3) d 146.5, 145.6, 130.2,
12. Circular Dichroism; Berova, N., Nakanishi, K., Woody,
R. W., Eds.; Wiley-VCH: New York, 2000.
13. CCDC 607513 (1a), CCDC 609971 (1b), and CCDC
609972 (2b) contain the crystallographic data for this
paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
14. Hiratani, K.; Kaneyama, M.; Nagawa, Y.; Koyama, E.;
Kanesato, M. J. Am. Chem. Soc. 2004, 126, 13568;
Kameta, N.; Hiratani, K.; Nagawa, Y. Chem. Commun.
2004, 466.