Selective O-alkylations with glycol chlorohydrins via the Mitsunobu reaction. A versatile route to calix[4]- and 1,1′-binaphthocrowns

Article abstract of DOI:10.1016/j.tet.2004.04.020

Selective monoalkylation of p-tert-butylcalix[4]arene and BINOL with oligoethylene glycol chlorohydrins was achieved under the Mitsunobu protocol using DEAD/TPP. The method provides a simple access to ether precursors capable of cyclising to various crowns.

Full text of DOI:10.1016/j.tet.2004.04.020

Tetrahedron 60 (2004) 5041–5048
Selective O-alkylations with glycol chlorohydrins via the
Mitsunobu reaction. A versatile route to
calix[4]- and 1,10-binaphthocrowns
´
Alajos Gru¨n, Eva Koszegi and Istvan Bitter
*
˝
´
Department of Organic Chemical Technology, Budapest University of Technology and Economics, Muegyetem rakpart 3, H-1521,
1111 Budapest, Hungary
Received 23 January 2004; revised 16 March 2004; accepted 8 April 2004
´
Dedicated to Professor Karoly Lempert on his 80th birthday
Abstract—Selective monoalkylation of p-tert-butylcalix[4]arene and BINOL with oligoethylene glycol chlorohydrins was achieved under
the Mitsunobu protocol using DEAD/TPP. The method provides a simple access to ether precursors capable of cyclising to various crowns.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
In the last decade a large number of supramolecular systems
combining the unique properties of calixarenes (CA) and
crowns have been described1,2 and applied in analytical and
separation chemistry.3,4 Recently, calix[4](aza)crowns have
attracted great interest due to the easy and versatile
derivatisation of the nitrogen atom in the crown ring.
N-Alkylation provides a convenient route to the introduc-
tion of various side-chains, most frequently additional
binding sites or sensing (chromo/fluorophore) units.5–12
Scheme 1. Synthetic routes to monoazacrowns.
Although the classical synthesis of azacrown ethers (route
A) has also been utilised in the access to calix(aza)crowns,7
bin0ding site.13 Apart from calix(aza)crowns, the respective
the cyclisation of v-chloro or tosyloxy-glycolethers with
1,1 -binaphthyl analogues have only been examplified by a
different amine derivatives is preferred (route B)5,6,8
few racemic derivatives,14 though these chiral molecules
(Scheme 1). The protecting groups (R¼Ts, Bn) can then
may have potential in designing chromoionophores for the
be removed by reductive methods to afford a free NH in the
optical recognition of ammonium salt enantiomers.15
symmetric position of the crown ring (n¼m), which can be
further derivatised.6,8 Although the complexation charac-
The synthesis of asymmetric CA- and BINOL-azacrown
teristics of calix(aza)crowns should be infuenced by the
hosts (m–n) require precursors with two different
position of the nitrogen atom in the ring, asymmetric
v-halogen/(tosyloxy)ether chains which cannot be intro-
analogues (where m–n), still have not been studied. This
duced either in the CA or in the BINOL molecule by simple
kind of structure was also found to be essential in chiral 1,10-
stepwise base-promoted alkylations. In both cases protec-
binaphtho(crowns), where the recognition of primary amine
tion/deprotection methods16–18 have to be used to obtain the
enantiomers was improved by an asymmetric crown ether
target compounds. To overcome the inconvenience and low
overall yields of the four-step procedures, a rapid alkylation
method is herein reported for the selective etherification of
Keywords: Calix[4]arene; BINOL; O-Alkylation; Mitsunobu reaction;
Crown ethers.
p-tert-butylcalix[4]arene and BINOL with oligoethylene
glycol chlorohydrins.
*
Corresponding author. Tel.: þ36-1-463-1379; fax: þ36-1-463-3648;
e-mail address: ibitter@mail.bme.hu
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.04.020

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A. Grun et al. / Tetrahedron 60 (2004) 5041–5048
5042
2. Results and discussion
2/3/(TPP/DEAD)¼1:3:3.5. On the use of 3b, however, 1 h
reflux was required to complete the reaction. As expected,
the long chain chlorohydrin 3c was not sufficiently reactive
to afford CA or BINOL diethers even under vigorous
conditions. Making use of the high reactivity of 3a,d, mixed
diethers 9a-c and 10c,d including (S)-10c could easily be
prepared by the treatment of monoethers 5b,c and 7b with
1.5 equiv. of 3a or 3d at room temperature. In contrast, the
reaction of 7c with 3a did not lead to complete conversion
even at elevated temperature, and pure asymmetric diether
could not be separated from the mixture.
Recently, we have described the convenient application of
the Mitsunobu reaction in the selective 1,3-dialkylation- and
cycloalkylation of p-tert-butylthiacalix[4]arene (TCA) with
alcohols and glycols.19,20 We have shown that quite
different results were achieved with the calix[4]arene
(CA) counterpart in the same reactions.20 The higher
reactivity and lower selectivity of TCA versus CA were
attributed to the more acidic (and less differences in pKa)
OHs and to the 15% larger cavity size. Actually, mono-
alkylation of TCA with any alcohols could not be attained,
and 1,3-diethers or tetraethers always being formed.19 These
observations prompted us to investigate the possibility of
selective alkylation of CA and BINOL21 with oligoethylene
glycol derivatives under the standard Mitsunobu
protocol using triphenylphosphine (TPP) and diethyl
azodicarboxylate (DEAD) coupling agents (Scheme 2).
From a synthetic point of view it was of interest to check the
reactivity of tosylates 4a and 4b under similar conditions.
Both analogues reacted more sluggishly with CA 1 as
compared with the respective chlorohydrins 3 requiring two
molar excess of reagents for the monoether derivatives 6a,b,
and four molar excess of reagents for the diethers 8c,d under
2 h reflux in both cases. Notably, these reactions took place
in the BINOL series, too, but we failed to obtain pure
tosylethers due to separation problems. The molecules
containing reactive tosylate end-groups in the chain are
regarded as valuable intermediates, albeit they are acces-
sible otherwise, but in significantly longer multi-step
reactions.
2.1. Synthesis of CA- and BINOL mono- and diethers
The reactions were performed at ambient temperature
treating CA 1 or (^)-BINOL 2 with glycol chlorohydrins
3a-c and TPP/DEAD (Caution! DEAD may explode if
exposed to shock, friction, or heating) in toluene using
different molar ratios: (1) 1/3/(TPP/DEAD)¼1:2:2.2, (2)
2/3/(TPP/DEAD)¼1:1.2–1.5:1.3–1.6, respectively. After
2 h reaction (0.5 h was sufficient for 2) the starting material
was consumed and exclusively monoethers 5b,c and 7b,c
were formed when 3b,c had been used. In this way, (S)-7b
was prepared in enantiomerically pure form from (S)-
BINOL. The more reactive 3a afforded a separable mixture
of monoethers 5a (with a small amount of diether 9a), and
7a with diether 10a in 2:1 ratio, respectively. The generally
moderate yields of monoethers (35–50%) refer to 1 mmol
scale and can be increased by scaling-up (in 5 mmol scale
5b and 7b were obtained in yields of 65–70%).
None of the mono and diethers prepared in this study have
been described until now, except for the debutylated
analogue of 8a, which was obtained in a slow, base-
promoted alkylation of the parent CA with diethylene glycol
monochlorohydrin tosylate.10
2.2. Cyclisations of mono- and diethers
The calixarene- and BINOL monoethers and diethers in
hand provided a simple access to crowns and azacrowns of
different type by self-condensation (monoethers) or by
cyclising with p-toluenesulfonamide (diethers). Although
these reactions were not optimised, they offer a useful
synthetic alternative for the preparation of certain crowns.
Symmetrical diethers 8a,b and 10a,b were cleanly obtained
under the same protocol by increasing the molar ratios to 1,
Scheme 2. Synthesis of CA and BINOL mono- and diethers via the Mitsunobu reaction.

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A. Grun et al. / Tetrahedron 60 (2004) 5041–5048
5043
2.3. Calix[4]- and 1,10-binaphthocrowns
crown-8) (^)-13b and (S)-13b, respectively, which were
also the major products in the direct ring closure of 1,10-bi-
2-naphthol with triethylene glycol ditosylate.26 Compound
7c, however, gave a 2:1 mixture of mono-(binaphtho-
crown-5) 13a and bis(binaphtho-crown-10) 13c indicating
that the longer tetraethyleneoxy chain of 7c allows
simultaneous intra- and intermolecular reaction pathways.
That is the reason why only a low yield of 13a was achieved
in the cyclisation of 2 with tetraethylene glycol ditosylate.14
Better results were reported for the Okahara cyclisation of
O,O-bis(2-hydroxyethoxyethoxy)-1,10-bi-2-naphthol.27
Monoethers 5a-c, and 7b,c exposed to basic conditions
underwent intra- and/or intermolecular cyclisations
depending on the chain length, affording calix- and
binaphthocrowns 11-13 (Fig. 1).
The reactions were conducted in MeCN (48 h reflux) using a
large excess of K2CO3 (equimolar KI was added).
Compound 5a possessing a short chain cyclised to 1,2-
calix[4](crown-3) 11a,22 while 5c with a long chain afforded
exlusively 1,3-calix[4](crown-5) 12b.23 Compound 5b,
which has a medium chain length, gave predominantly
also the 1,3-calix[4](crown-4) 12a24 with traces of the 1,2-
isomer 11b.25 Interestingly, we have obtained the same
results, when CA was treated with di-, tri- and tetraethylene
glycol under the Mitsunobu protocol.20 The structure of
regioisomers 11 and 12 has been determined earlier by
2.4. Calix[4]- and 1,10-binaphtho(aza)crowns
Di-chloroethers 8-10 were cyclised with p-tosylamide
(TsNH2) to 1,3-calix[4]- and 1,10-binaphtho(aza)crown-5,-
6, and 7 (14, 15), respectively. This base-promoted ring
closure has been used mainly in the case of 1,3-
calix[4]arene (bis)chloroethers not containing free phenolic
OH groups, probably to avoid a possible self-condensation.
Indeed, when the debutylated analogue of 14a was
synthesized by this method using Cs2CO3 in DMF solvent,
a low yield was reported.28 Since the N-alkylation of TsNH2
can effectively be performed in the presence of a weaker
base, we used a 5-fold excess of K2CO3 in DMF at 100 8C
(48 h) to effect the cyclisation. Under these conditions the
expected N-cyclised products were obtained in good yields.
Thus, compounds 8a,b gave the symmetric calix[4](aza)-
crowns 14a,b, while 9b resulted in the asymmetric analogue
14c. Analogously, BINOL diethers 10a-c cleanly furnished
the symmetric- and asymmetric binaphtho(azacrowns) (^)-
15a-c and (S)-15c. The latter molecule is an appropriate
candidate for the synthesis of chiral receptors. Notably, in
these experiments, self-cyclised side-products were not
formed due to the much higher acidity of the tosylamide
NH’s versus the remaining calixarene OH’s.
1
others with the aid of the H NMR spectra, which display
characteristic differences in the splitting pattern of the
bridging methylene protons for the proximally-coupled
1122,25 versus the distally-coupled 12.23,24
Notably, Shinkai et al.24 investigated the reaction of
calix[4]arene tetrols and triethylene glycol ditosylate in
the presence of various alkali carbonate bases to optimise
the yield of the 1,3-calix[4](crown-4) 12a. In these reactions
a complex mixture was obtained containing the target 12a
and several side-products, among others 1,2-calixcrown-4
11b, non-cyclised intermediate and dimers in comparable
amounts. In the light of these results, our indirect method,
after optimisation, may have advantages over the traditional
direct cyclisations.
Racemic BINOL monoether 7b and its enantiomer (S)-7b
were smoothly cyclised exclusively to bis(binaphtho-
Figure 1. Survey of cyclisation products obtained from monoethers 5, 7 and diethers 8-10.

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A. Grun et al. / Tetrahedron 60 (2004) 5041–5048
5044
With mixed diethers 9a, 9c and 10d an inseparable mixture
was obtained and we failed to recover the expected cyclised
products. These examples clearly show that the success of
ring closure is not dependent on the size of the crown ring
being formed, rather on the difference between the chain
lengths (n, m) of the precursors. In case of n2m.1, for
example, in 9c (2), 9a and 10d (3), the cyclisation is not
preferred.
4.2. Calix[4]- and BINOL monoethers
4.2.1. 25-(1-Chloro-3-oxapent-5-yl)oxy-26,27,28-tri-
hydroxy-5,11,17,23-tetra-tert-butyl-calix[4]arene (5a).
White solid, mp 162–166 8C, (triturated with MeOH); H
1
NMR: d 10.25 (s, 1H, OH), 9.38 (s, 2H, OH), 7.09 (s, 2H,
ArH), 7.05 (m, 4H, ArH), 6.98 (d, 2H, J¼2.5 Hz, ArH), 4.47
(d, 2H, J¼13 Hz, ArCH2Ar), 4.31 (m, 2H, CH2), 4.26 (d,
2H, J¼13.5 Hz, ArCH2Ar), 4.13 (m, 2H, CH2), 3.97 (t, 2H,
J¼6 Hz, CH2), 3.78 (t, 2H, J¼5.5 Hz, CH2), 3.43 (d, 2H,
J¼14 Hz, ArCH2Ar), 3.40 (d, 2H, J¼14 Hz, ArCH2Ar),
1.22 (s, 9H, C(CH3)3), 1.21 (s, 18H, C(CH3)3), 1.19 (s, 9H,
C(CH3)3); FAB-MS m/z (%): 754.4 (M(þ(24) (Calcd 754.4).
Anal. Calcd for C48H63O5Cl (755.47): C, 76.31; H, 8.41,
found: C, 76.05; H, 8.45%.
3. Conclusions
A series of calixarene- and BINOL mono- and diethers
comprised of oligoethylene glycol chains supplied with
reactive terminal groups have been synthesized via the
Mitsunobu reaction. This selective and rapid alkylation with
glycol derivatives provides an easy access to prec0ursors
capable of cyclising to various calix[4]- and 1,1 -bi-2-
naphthocrowns.
4.2.2. 25-(1-Chloro-3,6-dioxaoct-8-yl)oxy-26,27,28-tri-
hydroxy-5,11,17,23-tetra-tert-butyl-calix[4]arene (5b).
White solid, mp 162–165 8C (eluent: hexane/
1
EtOAc¼8:2); H NMR: d 10.27 (s, 1H, OH), 9.40 (s, 2H,
OH), 7.09 (s, 2H, ArH), 7.05 (m, 4H, ArH), 6.98 (d, 2H,
J¼2 Hz, ArH), 4.47 (d, 2H, J¼13 Hz, ArCH2Ar), 4.32 (m,
2H, CH2), 4.26 (d, 2H, J¼13.5 Hz, ArCH2Ar), 4.11 (m, 2H,
CH2), 3.87 (m, 2H, CH2), 3.82 (m, 2H, CH2), 3.76 (t, 2H,
J¼6 Hz, CH2), 3.54 (t, 2H, J¼5.5 Hz, CH2), 3.43 (d, 2H,
J¼14 Hz, ArCH2Ar), 3.39 (d, 2H, J¼13 Hz, ArCH2Ar),
1.22 (s, 9H, C(CH3)3), 1.21 (s, 18H, C(CH3)3), 1.19 (s, 9H,
C(CH3)3); 13C NMR: d 149.6, 148.5, 148.3, 148.2, 143.8,
143.3, 133.9, 128.5, 127.9, 126.6, 126.0, 125.9 (ArC), 75.3,
71.7, 71.1, 71.0, 70.3, 42.9 (CH2), 34.4, 34.2, 34,1 (CCH3),
33.3, 32.3 (ArCH2Ar), 31.7, 31.5 (CCH3); FAB-MS m/z
(%): 821.5 (MþNa)þ (100) (Calcd 821.5). Anal. Calcd for
C50H67O6Cl (799.53): C, 75.11; H, 8.45, found: C, 74.62; H,
8.38%.
4. Experimental
Melting points are uncorrected. NMR spectra were recorded
in CDCl3 at 500:125 MHz on a Bruker Avance DRX-500
spectrometer. Pre-coated silica gel plates (Merck 60 F254
were used for analytical TLC and Kieselgel 60 for column
chromatography. All chemicals were reagent grade and used
without further purification. TPP, 3a,d were purchased from
Merck. p-tert-Butylcalix[4]arene 1,29 BINOL 2,30 glycol
chlorohydrins 3b,c31 tosylates 432 and DEAD33 were
prepared as described in the literature.
)
4.1. General procedure for the synthesis of monoethers
5, 6, 7 and diethers 8, 9, 10
4.2.3. 25-(1-Chloro-3,6,9-trioxaundec-11-yl)oxy-
26,27,28-trihydroxy-5,11,17,23-tetra-tert-butyl-calix[4]-
arene (5c). White solid, mp 103–105 8C (eluent: hexane/
1
To the mixture of CA 1 (0.65 g, 1 mmol), glycol derivatives
3 or 4 (2 mmol) and TPP (0.6 g, 2.3 mmol) in toluene
(25 ml), a 40% toluene solution of DEAD (1.05 ml,
2.3 mmol) was added dropwise with stirring at room
temperature. After 2 h reaction the solution was evaporated
to dryness and the residue was separated by column
chromatography on silica. The same procedure was applied
for the monoalkylation of BINOL 2 (2 mmol) using 3
(1.2 mmol), TPP/DEAD (0.4 g/0.75 ml, 1.5 mmol each) in
0.5 h reactions.
EtOAc¼7:3); H NMR: d 10.28 (s, 1H, OH), 9.40 (s, 2H,
OH), 7.08 (s, 2H, ArH), 7.05 (m, 4H, ArH), 6.97 (d, 2H,
J¼2 Hz, ArH), 4.46 (d, 2H, J¼13 Hz, ArCH2Ar), 4.32 (m,
2H, CH2), 4.26 (d, 2H, J¼13.5 Hz, ArCH2Ar), 4.10 (m, 2H,
CH2), 3.86 (m, 2H, CH2), 3.81 (m, 2H, CH2), 3.72 (m, 4H,
CH2), 3.59 (m, 4H, CH2), 3.43 (d, 2H, J¼13.5 Hz,
ArCH2Ar), 3.39 (d, 2H, J¼13 Hz, ArCH2Ar), 1.22 (s, 9H,
C(CH3)3), 1.21 (s, 18H, C(CH3)3), 1.19 (s, 9H, C(CH3)3);
FAB-MS m/z (%): 865.5 (MþNa)þ (46) (Calcd 865.5),
842.5 (M)þ (49); (Calcd 842.5). Anal. Calcd for
C52H71O7Cl (843.58): C, 74.04; H, 8.48, found: C, 73.98;
H, 8.31%.
During the synthesis of symmetric diethers 8a,b and 10a,b
an enhanced reagent ratio of 1 or 2/3/(TPP/DEAD)¼1:3:3.5
was used. The less reactive 3b required 0.5 h reflux for
completion of the reaction. Mixed diethers 9a-c and 10c,d
were prepared by the treatment of monoethers 5b,c or 10b
(1 mmol) with 3a or 3d (0.19 g, 1.5 mmoI each) and TPP/
DEAD (045 g/0.85 ml, 1.7 mmol each) at ambient
temperature.
4.2.4. 25-(1-p-Toluenesulfonyloxy-3-oxapent-5-yl)oxy-
26,27,28-trihydroxy-5,11,17,23-tetra-tert-butyl-calix[4]-
arene (6a). White solid, mp 81–84 8C (eluent: hexane/
1
EtOAc¼8:2); H NMR: d 10.22 (s, 1H, OH), 9.37 (s, 2H,
OH), 7.80 (d, 2H, J¼8 Hz, ArH), 7.25 (d, 2H, J¼8 Hz,
ArH), 7.08 (s, 2H, ArH), 7.04 (m, 4H, ArH), 6.97 (d, 2H,
J¼1 Hz, ArH), 4.36 (d, 2H, J¼13 Hz, ArCH2Ar), 4.32 (t,
2H, J¼4.5 Hz, CH2), 4.24 (m, 2H, CH2), 4.18 (d, 2H,
J¼14 Hz, ArCH2Ar), 4.05 (m, 2H, CH2), 3.91 (t, 2H,
J¼4.5 Hz, CH2), 3.39 (d, 2H, J¼13.5 Hz, ArCH2Ar), 3.37
(d, 2H, J¼13 Hz, ArCH2Ar), 2.39 (s, 3H, CH3), 1.22 (s, 9H,
C(CH3)3), 1.21 (s, 18H, C(CH3)3), 1.19 (s, 9H, C(CH3)3);
Tosylethers 6a,b and 8c,d were prepared following the
procedures above but using reagent ratios of 1/4a,b/(TPP/
DEAD)¼1:3:3
(monoethers)
and
1/4a,b/(TPP/
DEAD)¼1:6:6 (diethers), respectively, under 2 h reflux in
both cases.

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5045
FAB-MS m/z (%): 890.5 (M(þ (71) (Calcd 890.5). Anal.
Calcd for C55H70O8S (891.21): C, 74.12; H, 7.94, found: C,
74.22; H, 7.86%.
NMR: d 7.14 (s, 2H, OH), 7.07 (s, 4H, ArH), 6.78 (s, 4H,
ArH), 4.34 and 3.31 (dþd, 4þ4H, J¼13 Hz, ArCH2Ar),
4.16 (t, 4H, J¼4 Hz, CH2), 4.01 (t, 4H, J¼4 Hz, CH2),
3.98 (t, 4H, J¼6 Hz, CH2), 3.74 (t, 4H, J¼6 Hz, CH2), 1.30
(s, 18H, C(CH3)3), 0.95 (s, 18H, C(CH3)3); 13C NMR: d
150.5, 149.7, 146.9, 141.4, 133.3, 132.5, 127.8, 126.4,
125.6, 125.1 (ArC), 75.5, 71.9, 70.3, 43.1 (CH2), 34.2, 34,1
(CCH3), 32,1, 31.3 (CCH3), 31.8 (ArCH2Ar); FAB-MS m/z
(%): 860.5 (M(þ (24) (Calcd 860.5). Anal. Calcd for
C52H70O6Cl2 (862.03): C, 72.45; H, 8.18, found: C, 72.96;
H, 8.10%.
4.2.5. 25-(1-1-p-Toluenesulfonyloxy-3,6-dioxaoct-8-
yl)oxy-26,27,28-trihydroxy-5,11,17,23-tetra-tert-butyl-
calix[4]arene (6b). White solid, mp 160–163 8C (eluent:
1
hexane/ EtOAc¼7:3); H NMR: d 10.24 (s, 1H, OH), 9.38
(s, 2H, OH), 7.78 (d, 2H, J¼8 Hz, ArH), 7.29 (d, 2H,
J¼8 Hz, ArH), 7.08 (s, 2H, ArH), 7.05 (m, 4H, ArH), 6.97
(d, 2H, J¼2 Hz, ArH), 4.43 (d, 2H, J¼13 Hz, ArCH2Ar),
4.28 (m, 2H, CH2), 4.23 (d, 2H, J¼13.5 Hz, ArCH2Ar), 4.08
(m, 4H, CH2), 3.79 (m, 2H, CH2), 3.72 (m, 4H, CH2), 3.41
(d, 2H, J¼14 Hz, ArCH2Ar), 3.38 (d, 2H, J¼13.5 Hz,
ArCH2Ar), 2.40 (s, 3H, CH3), 1.22 (s, 9H, C(CH3)3), 1.20 (s,
18H, C(CH3)3), 1.19 (s, 9H, C(CH3)3); FAB-MS m/z (%):
957.5 (MþNa)þ (65) (Calcd 957.5). Anal. Calcd for
C57H74O9S (935.26): C, 73.20; H, 7.97, found: C, 72.84;
H, 8.03%.
4.3.2. 25,27-Bis(1-chloro-3,6-dioxaoct-8-yl)oxy-26,28-
dihydroxy-5,11,17,23-tetra-tert-butyl-calix[4]arene (8b).
1
Yellow oil (eluent: hexane/EtOAc¼7:3); H NMR: d 7.09
(s, 2H, OH), 7.05 (s, 4H, ArH), 6.75 (s, 4H, ArH), 4.36 and
3.28 (dþd, 4þ4H, J¼13 Hz, ArCH2Ar), 4.23 (m, 4H, CH2),
4.15 (t, 4H, J¼4.5 Hz, CH2), 3.96 (t, 4H, J¼5 Hz, CH2),
3.83 (m, 4H, CH2), 3.76 (m, 4H, CH2), 3.53 (t, 4H, J¼6 Hz,
CH2), 1.31 (s, 18H, C(CH3)3), 0.93 (s, 18H, C(CH3)3). Anal.
Calcd for C56H78O8Cl2 (950.13): C, 70.79; H, 8.27, found:
C, 70.25; H, 8.36%.
4.2.6. (6)-O-(1-Chloro-3-oxapent-5-yl)-1,10-bi-2-
naphthol (7a). Yellow oil (eluent: toluene/MeOH¼95:5);
1H NMR: d 8.02 (d, 1H, J¼9 Hz, ArH), 7.88 (m, 3H, ArH),
7.45 (d, 1H, J¼9 Hz, ArH), 7.39–7.20 (m, 6H, ArH), 7.04
(d, 1H, J¼8.5 Hz, ArH), 5.08 (s, 1H, OH), 4.19 (m, 1H,
CH2), 4.10 (m, 1H, CH2), 3.55 (t, 2H, J¼4.5 Hz, CH2),
3.23–3.10 (m, 4H, CH2); FAB-MS m/z (%): 392.1 (M(þ
(30) (Calcd 392.1). Anal. Calcd for C24H21O3Cl (392.88):
C, 73.37; H, 5.39, found: C, 73.63; H, 5.44%.
4.3.3. 25,27-Bis(1-p-toluenesulfonyloxy-3-oxapent-5-
yl)oxy-26,28-dihydroxy-5,11,17,23-tetra-tert-butyl-
calix[4]arene (8c). White solid, mp 160–163 8C (triturated
with MeOH); 1H NMR: d 7.73 (d, 4H, J¼7 Hz, ArH), 7.20
(d, 4H, J¼7 Hz, ArH), 7.17 (s, 2H, OH), 7.05 (s, 4H, ArH),
6.77 (s, 4H, ArH), 4.25 (m, 4þ4H, ArCH2Ar, CH2), 4.05
(m, 4H, CH2), 3.89 (m, 8H, CH2), 3.26 (d, 4H, J¼13 Hz,
ArCH2Ar), 2.37 (s, 6H, CH2), 1.30 (s, 18H, C(CH3)3), 0.94
(s, 18H, C(CH3)3). Anal. Calcd for C66H84O12S2 (1133.50):
C, 69.94; H, 7.47, found: C, 69.44; H, 7.52%.
4.2.7. (6)-O-(1-Chloro-3,6-dioxaoct-8-yl)-1,10-bi-2-
naphthol (7b). Yellow oil (eluent: hexane/EtOAc¼6:4);
1H NMR: d 7.99 (d, 1H, J¼9 Hz, ArH), 7.86 (m, 3H, ArH),
7.45 (d, 1H, J¼9 Hz, ArH), 7.37–7.16 (m, 6H, ArH), 7.04
(d, 1H, J¼8 Hz, ArH), 5.32 (s, 1H, OH), 4.25 (m, 1H, CH2),
4.10 (m, 1H, CH2), 3.55 (t, 2H, J¼4.5 Hz, CH2), 3.50–3.34
(m, 4H, CH2), 3.30–3.19 (m, 4H, CH2); 13C NMR: d 155.5,
151.6, 134.2, 134.1, 130.9, 129.8, 129.7, 129.3, 128.3,
128.2, 127.4, 126.5, 125.3, 125.1, 124.5, 123.4, 118.1,
116.9, 115.7, 115.6 (ArC), 71.3, 70.6, 70.0, 69.6, 42.6
(CH2); FAB-MS m/z (%): 436.1 (M)þ (10) (Calcd 436.1).
Anal. Calcd for C26H25O4Cl (436.93): C, 71.47; H, 5.77,
found: C, 71.22; H, 5.82%.
4.3.4. 25,27-Bis(1-p-toluenesulfonyloxy-3,6-dioxaoct-8-
yl)oxy-26,28-dihydroxy-5,11,17,23-tetra-tert-butyl-
calix[4]arene (8d). Yellow oil (eluent: hexane/
EtOAc¼7:3); 1H NMR: d 7.79 (d, 4H, J¼7 Hz, ArH),
7.34 (d, 4H, J¼7 Hz, ArH), 7.16 (s, 2H, OH), 7.06 (s, 4H,
ArH), 6.77 (s, 4H, ArH), 4.35 and 3.29 (dþd, 4þ4H,
J¼13 Hz, ArCH2Ar), 4.12 (m, 8H, CH2), 3.92 (m, 4H,
CH2), 3.77 (m, 4H, CH2), 3.68 (m, 8H, CH2), 2.43 (s, 6H,
CH2), 1.31 (s, 18H, C(CH3)3), 0.95 (s, 18H, C(CH3)3). Anal.
Calcd for C70H92O14S2 (1221.61): C, 68.82; H, 7.59, found:
C, 69.19; H, 7.63%.
4.2.8. (S)-O-(1-Chloro-3,6-dioxaoct-8-yl)-1,10-bi-2-
naphthol ((S)-7b). Yellow oil (eluent: hexane/
EtOAc¼6:4), yield: 79%, [a]2D0¼þ21.7 (c¼1, CHCl3).
4.2.9. (6)-O-(1-Chloro-3,6,9-trioxaundec-11-yl)-1,10-bi-
2-naphthol (7c). Yellow oil (eluent: hexane/EtOAc¼7:3);
1H NMR: d 7.99 (d, 1H, J¼9 Hz, ArH), 7.85 (m, 3H, ArH),
7.46 (d, 1H, J¼9 Hz, ArH), 7.37–7.17 (m, 6H, ArH), 7.04
(d, 1H, J¼8.5 Hz, ArH), 5.50 (s, 1H, OH), 4.26 (m, 1H,
CH2), 4.10 (m, 1H, CH2), 3.64–3.22 (m, 14H, CH2); FAB-
MS m/z (%): 503.2 (MþNa)þ (16) (Calcd 503.2). Anal.
Calcd for C28H29O5Cl (480.98): C, 69.92; H, 6.08, found: C,
69.31; H, 6.11%.
4.3.5. (6)-O,O0-Bis(1-chloro-3-oxapent-5-yl)-1,10-bi-2-
naphthol (10a). Yellow oil (eluent: toluene/
1
MeOH¼97:3); H NMR: d 7.94 (d, 2H, J¼9 Hz, ArH),
7.85 (d, 2H, J¼8 Hz, ArH), 7.41 (d, 2H, J¼9.5 Hz, ArH),
7.33 (t, 2H, J¼7 Hz, ArH), 7.23 (t, 2H, J¼7 Hz, ArH), 7.17
(d, 2H, J¼8.5 Hz, ArH), 4.15–4.05 (m, 4H, CH2), 3.49 (t,
4H, J¼4.5 Hz, CH2), 3.15–3.06 (m, 8H, CH2). Anal. Calcd
for C28H28O4Cl2 (499.43): C, 67.34; H, 5.65, found: C,
67.86; H, 5.70%.
4.3.6. (6)-O,O0-Bis(1-chloro-3,6-dioxaoct-8-yl)-1,10-bi-2-
naphthol (10b). Yellow oil (eluent: toluene/MeOH¼95:5);
1H NMR: d 7.93 (d, 2H, J¼9 Hz, ArH), 7.85 (d, 2H,
J¼8 Hz, ArH), 7.41 (d, 2H, J¼9 Hz, ArH), 7.32 (td, 2H,
J¼7 Hz, 1 Hz, ArH), 7.21 (td, 2H, J¼8 Hz, 1 Hz, ArH),
7.15 (d, 2H, J¼8.5 Hz, ArH), 4.09 (m, 4H, CH2), 3.55–3.45
(m, 12H, CH2), 3.20 (t, 4H, J¼4 Hz, CH2), 3.15–3.05 (m,
4.3. Symmetrical calix[4]- and BINOL diethers
4.3.1. 25,27-Bis(1-chloro-3-oxapent-5-yl)oxy-26,28-di-
hydroxy-5,11,17,23-tetra-tert-butyl-calix[4]arene (8a).
1
White solid, mp 110–113 8C (triturated with MeOH); H

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A. Grun et al. / Tetrahedron 60 (2004) 5041–5048
5046
4H, CH2). Anal. Calcd for C32H36O6Cl2 (587.54): C, 65.42;
H, 6.18, found: C, 65.08; H, 6.22%.
(94%), eluent: toluene/MeOH¼95:5; [a]2D0¼245 (c¼1,
CHCl3).
4.4. Mixed calix[4]- and BINOL diethers
4.4.6. (6)-O-(1-Chloro-3-oxapent-5-yl)-O0-(2-bromo-
ethoxy)-1,10-bi-2-naphthol (10d). Yellow oil (53%),
eluent: toluene/MeOH¼95:5; 1H NMR: d 7.94 (t, 2H,
J¼9.5 Hz, ArH), 7.85 (d, 2H, J¼8 Hz, ArH), 7.41 (m, 2H,
ArH), 7.32 (m, 2H, ArH), 7.22 (m, 2H, ArH), 7.14 (m, 2H,
ArH), 3.57 (m, 4H, CH2), 3.48 (m, 4H, CH2), 3.24–3.09 (m,
6H, CH2). Anal. Calcd for C30H32O5BrCl (587.93): C,
61.29; H, 5.49, found: C, 61.11; H, 5.52%.
4.4.1. 25-(1-Chloro-3,6,9-trioxaundec-11-yl)oxy-27-(2-
bromoethoxy)-26,28-dihydroxy-5,11,17,23-tetra-tert-
butyl-calix[4]arene (9a). White solid, mp 57–59 8C
(eluent: hexane/EtOAc¼7:3); 1H NMR: d 7.06 (d, 4H,
J¼0.5 Hz, ArH), 7.01 (s, 2H, OH), 6.79 (s, 2H, ArH), 6.73
(s, 2H, ArH), 4.34 and 3.30 (dd, 4Hþ4H, J¼13.5, 3 Hz,
ArCH2Ar), 4.30 (t, 2H, J¼6.5 Hz, CH2), 4.16 (t, 2H,
J¼4 Hz, CH2), 4.00 (t, 2H, J¼4.5 Hz, CH2), 3.88 (t, 2H,
J¼4.5 Hz, CH2), 3.81 (t, 2H, J¼6.5 Hz, CH2), 3.75 (t, 2H,
J¼4.5 Hz, CH2), 3.68 (m, 4H, CH2), 3.59 (m, 4H, CH2),
1.30 (s, 18H, C(CH3)3), 0.96 (s, 9H, C(CH3)3), 0.90 (s, 9H,
C(CH3)3). Anal. Calcd for C54H74O7BrCl (950.53): C,
68.23; H, 7.85, found: C, 68.65; H, 7.94%.
4.5. General procedure for the self-condensation of
mono-chloroethers
The mixture of mono-chloroethers 5a,b,c or 7b,c
(0.5 mmol), K2CO3 (0.7 g, 5 mmol) and KI (0.17 g,
0.5 mmol) in MeCN (20 ml) was stirred for 48 h under
reflux. The solvent was then evaporated, the residue was
extracted with CH2Cl2 (30 ml), washed with dilute aq. HCl,
water and dried. The crude products were separated by
column chromatography on silica to afford white solids
(except for 13c).
4.4.2. 25-(1-Chloro-3-oxapent-5-yl)oxy-27-(1-chloro-3,6-
dioxaoct-8-yl)oxy-26,28-dihydroxy-5,11,17,23-tetra-tert-
butyl-calix[4]arene (9b). White solid, mp 80–82 8C
(eluent: hexane/EtOAc¼7:3); 1H NMR: d 7.11 (s, 2H,
OH), 7.05 (s, 4H, ArH), 6.76 (d, 4H, J¼4 Hz, ArH), 4.37
and 4.33 (dþd, 2Hþ2H, J¼13.5 Hz, ArCH2Ar), 4.15 (m,
4H, CH2), 3.98 (m, 6H, CH2), 3.87 (m, 2H, CH2), 3.75 (m,
6H, CH2), 3.52 (t, 2H, J¼5.5 Hz, CH2), 3.29 (d, 4H,
J¼13 Hz, ArCH2Ar), 1.30 (s, 18H, C(CH3)3), 0.94 (s, 9H,
C(CH3)3), 0.93 (s, 9H, C(CH3)3); 13C NMR: d 150.8, 150.0,
147.1, 141.6, 132.7, 128.0, 125.7, 125.3, (ArC), 75.6, 72.0,
71.7, 71.2, 71.0, 70.3, 43.1, 43.0 (CH2), 34.1, 34,0 (CCH3),
32,0, 31.2 (CCH3), 31.7 (ArCH2Ar). Anal. Calcd for
C54H74O7Cl2 (906.08): C, 71.58; H, 8.23, found: C, 71.11;
H, 8.28%.
4.6. Calix[4]crowns
4.6.1. 25,26-(3-Oxapenta-1,5-diyl)oxy-27,28-dihydroxy-
5,11,17,23-tetra-tert-butyl-calix[4]arene (11a). Yield:
69%, mp 152–155 8C (triturated with MeOH). The 1H
NMR data are identical to those reported in Ref. 22.
4.6.2. 25,27-(3,6-Dioxaocta-1,8-diyl)oxy-26,28-di-
hydroxy-5,11,17,23-tetra-tert-butyl-calix[4]arene (12a).
Yield: 55%, eluent: hexane/EtOAc¼8:2, mp 235–237 8C
1
(lit.24 mp 259–262 8C). The H NMR data are identical to
4.4.3. 25-(1-Chloro-3-oxapent-5-yl)oxy-27-(1-chloro-
3,6,9-trioxaundec-11-yl)oxy-26,28-dihydroxy-5,11,17,23-
tetra-tert-butyl-calix[4]arene (9c). Yellow oil (eluent:
those reported in Ref. 24.
4.6.3. 25,27-(3,6,9-Trioxaundeca-1,11-diyl)oxy-26,28-
dihydroxy-5,11,17,23-tetra-tert-butyl-calix[4]arene
(12b). Yield: 35%, eluent: hexane/EtOAc¼7:3, mp 224–
226 8C (lit.23 mp 246–248 8C). The 1H NMR data are
identical to those reported in Ref. 23.
1
hexane/EtOAc¼8:2); H NMR: d 7.12 (s, 2H, OH), 7.05
(s, 4H, ArH), 6.76 (s, 4H, ArH), 4.35 and 4.33 (dþd,
2Hþ2H, J¼13.5 Hz, ArCH2Ar), 4.14 (m, 4H, CH2), 3.99
(m, 4H, CH2), 3.95 (t, 2H, J¼5 Hz, CH2), 3.85 (t, 2H,
J¼4.5 Hz, CH2), 3.72 (m, 4H, CH2), 3.66 (m, 4H, CH2),
3.58 (m, 4H, CH2), 3.28 (dd, 4H, J¼13.5, 2.5 Hz, ArCH2-
Ar), 1.29 (s, 18H, C(CH3)3), 0.94 (s, 9H, C(CH3)3), 0.93 (s,
9H, C(CH3)3). Anal. Calcd for C56H78O8Cl2 (950.13): C,
70.79; H, 8.27, found: C, 70.23; H, 8.32%.
4.7. 1,10-Binaphthocrowns
4.7.1. (6)-1,10-Bi-2-naphtho(17-crown-5) (13a). Yield:
36%, eluent: hexane/EtOAc¼3:7, mp 103–105 8C (lit.24
1
mp 114–115 8C); H NMR: d 7.92 (d, 2H, J¼9 Hz, ArH),
4.4.4. (6)-O-(1-Chloro-3-oxapent-5-yl)-O0-(1-chloro-3,6-
dioxaoct-8-yl)-1,10-bi-2-naphthol (10c). Yellow oil
7.84 (d, 2H, J¼8 Hz, ArH), 7.47 (d, 2H, J¼8.5 Hz, ArH),
7.30 (t, 2H, J¼7 Hz, ArH), 7.19 (t, 2H, J¼8 Hz, ArH), 7.11
(d, 2H, J¼8.5 Hz, ArH), 4.25 (m, 2H, CH2), 3.99 (m, 2H,
CH2), 3.65 (m, 2H, CH2), 3.57–3.36 (m, 10H, CH2); FAB-
MS; m/z (%): 467.0 (MþNa)þ (82) (Calcd 467.2). Anal.
Calcd for C28H28O5 (444.52): C, 75.66; H, 6.35, found: C,
75.23; H, 6.40%.
1
(eluent: toluene/MeOH¼95:5); H NMR: d 7.93 (d, 2H,
J¼9 Hz, ArH), 7.85 (d, 2H, J¼8 Hz, ArH), 7.41 (t, 2H,
J¼8 Hz, ArH), 7.32 (t, 2H, J¼7 Hz, ArH), 7.24–7.14 (m,
4H, ArH), 4.09 (m, 4H, CH2), 3.56–3.48 (m, 8H, CH2), 3.21
(t, 2H, J¼4.5 Hz, CH2), 3.16–3.05 (m, 6H, CH2); 13C
NMR: d 154.5, 154.4, 134.3, 129.7, 129.6, 129.5, 128.0,
126.5, 125.7, 125.6, 124.0, 120.8, 120.7, 115.8, 115.7
(ArC), 71.4, 71.3, 70.7, 70.6, 70.2, 70.1, 69.9, 69.8, 43.0,
42.8 (CH2). Anal. Calcd for C30H32O5Cl2 (543.48): C,
66.30; H, 5.93, found: C, 66.02; H, 5.99%.
4.7.2. (6)-Bis(1,10-bi-2-naphtho-28-crown-8) (13b).
Yield: 21%, eluent: hexane/EtOAc¼1:1, mp 119–122 8C;
1H NMR: d 7.93 (d, 4H, J¼8.5 Hz, ArH), 7.85 (d, 4H,
J¼8 Hz, ArH), 7.49 (d, 4H, J¼8.5 Hz, ArH), 7.32–7.05 (m,
12H, ArH), 4.11 (m, 4H, CH2), 4.03 (m, 4H, CH2), 3.50–
3.34 (m, 8H, CH2), 3.16 (m, 8H, CH2); FAB-MS m/z (%):
822.9 (17) (MþNa)þ (Calcd 823.3). Anal. Calcd for
4.4.5. (S)-O-(1-Chloro-3-oxapent-5-yl)-O0-(1-chloro-3,6-
dioxaoct-8-yl)-1,10-bi-2-naphthol ((S)-10c). Yellow oil

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A. Grun et al. / Tetrahedron 60 (2004) 5041–5048
5047
C52H48O8 (800.94): C, 77.98; H, 6.04, found: C, 78.44; H,
6.00%.
2þ2H, J¼13 Hz, ArCH2Ar), 2.38 (s, 3H, CH3), 1.29 (s,
18H, C(CH3)3), 0.92 (s, 18H, C(CH3)3); 13C NMR: d 150.9,
150.1, 150.0, 147.1, 143.2, 141.5, 137.3, 132.8, 132.7,
129.7, 128.0, 127.9, 127.4, 127.3, 125.7, 125.2 (ArC), 76.2,
75.8, 71.3, 71.2, 70.9, 70.6, 70.0, 49.1, 49.0 (CH2), 34.1,
34,0 (CCH3), 31.9, 31.2 (CCH3), 31.7, 31.6 (ArCH2Ar),
21.6 (CH3); FAB-MS m/z (%): 1026.5 (MþNa)þ (100)
(Calcd 1026.5). Anal. Calcd for C61H81NO9S (1004.37): C,
72.95; H, 8.13, found: C, 73.24; H, 8.15%.
4.7.3. (S)-Bis(1,10-bi-2-naphtho-28-crown-8) ((S)-13b).
Yield: 56%; eluent: hexane/EtOAc¼1:1, [a]2D0¼2119
(c¼1, CHCl3).
4.7.4. (6)-Bis(1,10-bi-2-naphtho-34-crown-10) (13c).
1
Yellow oil (27%), eluent: hexane/EtOAc¼3:7; H NMR:
d 7.91 (d, 4H, J¼9 Hz, ArH), 7.83 (d, 4H, J¼8 Hz, ArH),
7.43 (d, 4H, J¼9 Hz, ArH), 7.30 (t, 4H, J¼7 Hz, ArH), 7.19
(t, 4H, J¼8 Hz, ArH), 7.13 (d, 4H, J¼8.5 Hz, ArH), 4.12
(m, 4H, CH2), 4.02 (m, 4H, CH2), 3.51 (m, 4H, CH2), 3.42
(m, 4H, CH2), 3.28–3.16 (m, 16H, CH2); FAB-MS m/z (%):
927.3 (MþK)þ (15)(Calcd 927.3). Anal. Calcd for C56H56O10
(889.05): C, 75.66; H, 6.35, found: C, 75.19; H, 6.40%.
4.10. 1,10-Binaphtho(aza)crowns
4.10.1. (6)-O,O0-(3,9-Dioxa-6-N-tosylazaundeca-1,11-
diyl)-1,10-bi-2-naphthol (15a). Yield: 70% (eluent:
1
toluene/MeOH¼97:3), mp 71–74 8C; H NMR: d 7.92 (d,
2H, J¼9 Hz, ArH), 7.84 (d, 2H, J¼8 Hz, ArH), 7.62 (d, 2H,
J¼8 Hz, ArH), 7.44 (d, 2H, J¼9 Hz, ArH), 7.30 (t, 2H,
J¼7.5 Hz, ArH), 7.24 (d, 2H, J¼8.5 Hz, ArH), 7.19 (t, 2H,
J¼7.5 Hz, ArH), 7.10 (d, 2H, J¼8.5 Hz, ArH), 4.22 (m, 2H,
CH2), 3.93 (m, 2H, CH2), 3.55 (m, 2H, CH2), 3.46–3.36 (m,
6H, CH2), 3.24–3.09 (m, 4H, CH2), 2.40 (s, 3H, CH3);
FAB-MS m/z (%): 597.3 (M(þ (9) (Calcd 597.2). Anal.
Calcd for C35H35NO6S (597.72): C, 70.33; H, 5.90, found:
C, 69.89; H, 5.94%.
4.8. General procedure for the synthesis of (aza)crowns
The mixture of di-chloroethers 8a,b, 9b or 10a-c
(0.5 mmol), TsNH2 (0.085 g, 0.5 mmol), K2CO3 (0.35 g,
2.5 mmol) in DMF (20 ml) was stirred at 100 8C for 48 h.
The solvent was then evaporated, the residue was extracted
with CH2Cl2 (30 ml), washed with dilute aq. HCl, water and
dried. The crude products were separated by column
chromatography on silica to afford white solids (except
for 15b,c).
4.10.2. (6)-O,O0-(3,6,12,15-Tetraoxa-9-N-tosylazahepta-
deca-1,17-diyl)-1,10-bi-2-naphthol (15b). Yellow oil
1
(51%), eluent: hexane/ EtOAc¼3:7); H NMR: d 7.92 (d,
4.9. Calix[4](aza)crowns
2H, J¼9 Hz, ArH), 7.84 (d, 2H, J¼8 Hz, ArH), 7.69 (d, 2H,
J¼8 Hz, ArH), 7.43 (d, 2H, J¼8.5 Hz, ArH), 7.32–7.26 (m,
4H, ArH), 7.18 (t, 2H, J¼7.5 Hz, ArH), 7.13 (d, 2H,
J¼8.5 Hz, ArH), 4.15 (m, 2H, CH2), 4.01 (m, 2H, CH2),
3.64–3.54 (m, 6H, CH2), 3.42–3.28 (m, 14H, CH2), 2.41 (s,
3H, CH3); FAB-MS m/z (%): 724.3 (MþK)þ (35) (Calcd
724.2). Anal. Calcd for C39H43NO8S (685.83): C, 68.30; H,
6.32, found: C, 68.42; H, 6.28%.
4.9.1. 25,27-(3,9-Dioxa-6-N-tosylazaundeca-1,11-diyl)-
oxy-26,28-dihydroxy-5,11,17,23-tetra-tert-butyl-calix[4]-
arene (14a). Yield: 31%, mp 127–129 8C (triturated with
1
MeOH); H NMR: d 7.70 (d, 2H, J¼13 Hz, ArH), 7.32 (s,
2H, OH), 7.25 (d, 2H, J¼13 Hz, ArH), 7.03 (s, 4H, ArH),
6.78 (s, 4H, ArH), 4.29 and 3.27 (dþd, 4þ4H, J¼21.5 Hz,
ArCH2Ar), 3.99 (m, 12H, CH2), 3.44 (t, 4H, J¼10.5 Hz,
CH2), 2.37 (s, 3H, CH3), 1.28 (s, 18H, C(CH3)3), 0.94 (s,
18H, C(CH3)3). Anal. Calcd for C59H77NO8S (960.32): C,
73.79; H, 8.08, found: C, 73.21; H, 8.0.2%.
4.11. (6)-O,O0-(3,9-Dioxa-6-N-tosylazaundeca-1,11-
diyl)-1,10-bi-2-naphthol (15c)
Yellow oil (37%), eluent: toluene/MeOH¼95:5; 1H NMR: d
7.91 (t, 2H, J¼8.5 Hz, ArH), 7.84 (t, 2H, J¼9 Hz, ArH),
7.64 (d, 2H, J¼8 Hz, ArH), 7.43 (d, 2H, J¼9 Hz, ArH),
7.33–7.12 (m, 8H, ArH), 4.16 (m, 2H, CH2), 3.95 (m, 2H,
CH2), 3.66–3.16 (m, 16H, CH2), 2.41 (s, 3H, CH3); 13C
NMR: d 154.6, 143.3, 136.8, 134.3, 129.8, 129.7, 129.6,
129.5, 129.4, 128.1, 128.0, 127.4, 126.4, 125.6, 125.5,
123.9, 123.8, 121.0, 116.6, 116.4, 116.2 (ArC), 71.0, 70.9,
70.8, 70.4, 70.3, 70.1, 69.8, 49.5, 49.4 (CH2), 21.7 (CH3);
FAB-MS m/z (%): 664.2 (MþNa)þ (59) (Calcd 664.2).
Anal. Calcd for C37H39NO7S (641.77): C, 69.25; H, 6.13,
found: C, 69.61; H, 6.07%.
4.9.2. 25,27-(3,6,12,15-Tetraoxa-9-N-tosylazaheptadeca-
1,17-diyl)oxy-26,28-dihydroxy-5,11,17,23-tetra-tert-
butyl-calix[4]arene (14b). Yield: 20% (eluent: hexane/
1
EtOAc¼6:4), mp 173–176 8C; H NMR: d 7.64 (d, 2H,
J¼7 Hz, ArH), 7.25 (d, 2H, J¼7 Hz, ArH), 7.14 (s, 2H,
OH), 7.02 (s, 4H, ArH), 6.74 (s, 4H, ArH), 4.36 and 3.26
(dþd, 4þ4H, J¼12.5 Hz, ArCH2Ar), 4.12 (m, 4H, CH2),
3.92 (m, 8H, CH2), 3.68 (m, 8H, CH2), 3.19 (m, 4H, CH2),
2.40 (s, 3H, CH3), 1.26 (s, 18H, C(CH3)3), 0.92 (s, 18H,
C(CH3)3). Anal. Calcd for C63H85NO10S (1048.42): C,
72.17; H, 8.17, found: C, 71.73; H, 8.11%.
4.9.3. 25,27-(3,9,12-Trioxa-6-N-tosylazatetradeca-1,14-
diyl)oxy-26,28-dihydroxy-5,11,17,23-tetra-tert-butyl-
calix[4]arene (14c). Yield: 36% (eluent: hexane/
EtOAc¼7:3), mp 76–79 8C; 1H NMR: d 7.70 (d, 2H,
J¼8 Hz, ArH), 7.24 (d, 2H, J¼6 Hz, ArH), 7.15 (s, 2H,
OH), 7.05 (s, 4H, ArH), 6.75 (d, 4H, J¼2 Hz, ArH), 4.32
(dd, 4H, J¼12.5, 5 Hz, ArCH2Ar), 4.06 (m, 4H, CH2), 4.01
(m, 2H, CH2), 3.88 (m, 6H, CH2), 3.72 (t, 2H, J¼5 Hz,
CH2), 3.68 (t, 2H, J¼4.5 Hz, CH2), 3.54 (t, 2H, J¼6 Hz,
CH2), 3.49 (t, 2H, J¼5 Hz, CH2), 3.27 and 3.25 (dþd,
4.12. (S)-O,O0-(3,9-Dioxa-6-N-tosylazaundeca-1,11-diyl)-
1,10-bi-2-naphthol (S)-15c
Yellow oil (44%), eluent: toluene/MeOH¼95:5;
[a]2D0¼294.7 (c¼1, CHCl3).
Acknowledgements
Financial support by the Hungarian Scientific Research

¨
A. Grun et al. / Tetrahedron 60 (2004) 5041–5048
5048
Future Applications; Cooper, S. R., Ed.; VCH: New York,
1992; Chapter 12.
Foundation (OTKA No. T 034347) is gratefully acknowl-
´
edged. The authors express their gratitude to Mr Janos
Kovacs for FAB-MS measurements. E. K. thanks the Varga
´
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16. Iwamoto, K.; Araki, K.; Shinkai, S. Tetrahedron 1991, 47,
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Jozsef Foundation for a fellowship.
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