1,3-calix[4]arene crown ether conformers with a 3-thienyl pendant functionality at the lower rim

Article abstract of DOI:10.1021/jo990336v

Synthetic protocols to novel thienyl-calix[4]crown building blocks are reported. The selective distal introduction of a 2-(3-thienyl)ethoxy functionality into mono-O-alkylated calix[4]arenes 1 (R = Me, Bn), followed by cyclization of the mixed di-O-alkylated intermediates 2 with tetra- and pentaethylene glycol ditosylate and base, produced mixtures of 1,3-alternate and cone 1,3-calix[4]arene crown ether conformers 3 and 4, respectively. On the other hand, the selective debenzylation (Me₃-SiCl) of 1-benzyloxy-3- propoxycalix[4]arene crown-5 (cone conformer 4c) led to cone monohydroxy- derivative 5, which upon alkylation with 2-(3-thienyl)ethanol tosylate and Cs₂CO₃ afforded the rigid partial cone calix[4]arene crown-5 6, having the heterocyclic pendant functionality anti to the polyether ring. The ¹H NMR resonances of (t)Bu substituents at the upper rim of conformationally rigid mixed 1,3-dialkoxycalix[4]arene crown ethers provide a diagnostic tool for establishing the mutual inclinations of the opposing pairs of aromatic rings. The structures of 5,11,17,23-tetrakis(1,1-dimethylethyl)-25-methoxy-27-{[2- (3-thienyl)ethoxy]}(β)-26,28-(crown-6)(α)-calix[4]arene (anti-3aa) and 5,11,17,23-tetrakis(1,1-dimethylethyl)-25-methoxy-27-{[2-(3- thienyl)ethoxy]}(a)-26,28-(crown-6)(α)-calix[4]arene (syn-4aa) conformers were determined by single-crystal X-ray analyses. Methoxy-containing calix[4]arene crown ethers possess fluxional properties, and the conformational equilibria in solution are strongly affected by alkali-metal complexation.

Full text of DOI:10.1021/jo990336v

5876
J . Org. Chem. 1999, 64, 5876-5885
1,3-Ca lix[4]a r en e Cr ow n Eth er Con for m er s w ith a 3-Th ien yl
P en d a n t F u n ction a lity a t th e Low er Rim
George Ferguson,† J ohn F. Gallagher,† Alan J . Lough,‡ Anna Notti,§
Sebastiano Pappalardo,*,| and Melchiorre F. Parisi§
Department of Chemistry and Biochemistry, University of Guelph, Guelph, Ontario, Canada N1G 2W1,
Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6, Dipartimento di
Chimica Organica e Biologica, Universita` di Messina, Salita Sperone 31, I-98166 Vill. S. Agata,
Messina, Italy, and Dipartimento di Scienze Chimiche, Universita` di Catania, Viale A. Doria 6,
I-95125 Catania, Italy
Received February 23, 1999
Synthetic protocols to novel thienyl-calix[4]crown building blocks are reported. The selective distal
introduction of a 2-(3-thienyl)ethoxy functionality into mono-O-alkylated calix[4]arenes 1 (R ) Me,
Bn), followed by cyclization of the mixed di-O-alkylated intermediates 2 with tetra- and penta-
ethylene glycol ditosylate and base, produced mixtures of 1,3-alternate and cone 1,3-calix[4]arene
crown ether conformers 3 and 4, respectively. On the other hand, the selective debenzylation (Me3-
SiCl) of 1-benzyloxy-3-propoxycalix[4]arene crown-5 (cone conformer 4c) led to cone monohydroxy-
derivative 5, which upon alkylation with 2-(3-thienyl)ethanol tosylate and Cs2CO3 afforded the
rigid partial cone calix[4]arene crown-5 6, having the heterocyclic pendant functionality anti to
the polyether ring. The 1H NMR resonances of tBu substituents at the upper rim of conformationally
rigid mixed 1,3-dialkoxycalix[4]arene crown ethers provide a diagnostic tool for establishing the
mutual inclinations of the opposing pairs of aromatic rings. The structures of 5,11,17,23-tetrakis-
(1,1-dimethylethyl)-25-methoxy-27-{[2-(3-thienyl)ethoxy]}â-26,28-(crown-6)R-calix[4]arene (anti-3a a )
and 5,11,17,23-tetrakis(1,1-dimethylethyl)-25-methoxy-27-{[2-(3-thienyl)ethoxy]}R-26,28-(crown-6)R-
calix[4]arene (syn-4a a ) conformers were determined by single-crystal X-ray analyses. Methoxy-
containing calix[4]arene crown ethers possess fluxional properties, and the conformational equilibria
in solution are strongly affected by alkali-metal complexation.
In tr od u ction
and selectivities in some instances even higher than the
naturally occurring ionophore valinomycin.4 Calixarene-
based receptors are now being used as selective sensing
agents in the microconstruction of ion sensory devices.5
Recently, we became involved in a long-term project
aimed at grafting 1,3-bridged calix[4]arene crown ether
units to the â-position of polythiophenes, in order to
create new classes of molecular sensors able to recognize
and electrochemically respond to alkali-metal ions.6 The
electro-oxidative polymerization of appropriately substi-
tuted (oligo)thiophene monomers was shown to provide
a useful strategy for the preparation of functionalized
polythiophenes.7 A similar strategy could be applied to
the synthesis of calix[4]arene-crown-ether/polythiophene
conjugates, by exploiting suitably designed calixarene
crown ether building blocks, bearing an electropolymer-
izable (oligo)thiophene pendant functionality at the lower
Conducting polythiophenes with ion receptor sites (e.g.,
crown ethers) covalently anchored to the polymer back-
bone constitute a class of hybrid materials that are
receiving considerable attention for the development of
advanced sensing devices.1 Calixarene-based ion recep-
tors are far more size-selective than crown ethers,
because the calixarene platform provides a highly pre-
organized architecture for the assembling of converging
binding sites.2 To date, 1,3-bridged calix[4]arene crown
ethers probably represent the most potent synthetic
complexing agents for alkali-metal ions,3 with efficiencies
† University of Guelph.
‡ University of Toronto.
§ Universita` di Messina.
| Universita` di Catania.
(1) For leading reviews on these topics see (a) Roncali, J . Chem. Rev.
1992, 92, 711. (b) Higgins, S. J . Chem. Soc. Rev. 1997, 26, 247.
(2) For full reviews on calixarene chemistry, cf. (a) Gutsche, C. D.
Calixarenes. In Monographs in Supramolecular Chemistry; Stoddart,
J . F., Ed.; Royal Society of Chemistry: London, U.K. 1989. (b)
Calixarenes, A Versatile Class of Macrocyclic Compounds; Vicens, J .,
Bo¨hmer, V., Eds.; Kluwer: Dordrecht, The Netherlands, 1991. (c)
Bo¨hmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713. (d) Ikeda, A.;
Shinkai, S. Chem. Rev. 1997, 97, 1713. (e) Gutsche, C. D. Calixarenes
Revisited. In Monographs in Supramolecular Chemistry; Stoddart, J .
F., Ed.; Royal Society of Chemistry: London, U.K., 1998.
(3) (a) Yamamoto, H.; Shinkai, S. Chem. Lett. 1994, 1115. (b)
Ghidini, E.; Ugozzoli, F.; Ungaro, R.; Harkema, S.; Abu El-Fadl, A.;
Reinhoudt, D. N. J . Am. Chem. Soc. 1990, 112, 6979. (c) Brzozka, Z.;
Lammerink, B.; Reinhoudt, D. N.; Ghidini, E.; Ungaro, R. J . Chem.
Soc., Perkin Trans. 2 1993, 1037. (d) Ungaro, R.; Casnati, A.; Ugozzoli,
F.; Pochini, A.; Dozol, J .-F.; Hill, C.; Rouquette, H. Angew. Chem., Int.
Ed. Engl. 1994, 33, 1506. (e) Casnati, A.; Pochini, A.; Ungaro, R.;
Ugozzoli, F.; Arnaud, F.; Fanni, S.; Schwing, M.-J .; Egberink, R. J .
M.; de J ong, F.; Reinhoudt, D. N. J . Am. Chem. Soc. 1995, 117, 2767.
(4) (a) Casnati, A.; Pochini, A.; Ungaro, R.; Bocchi, C.; Ugozzoli, F.;
Egberink, R. J . M.; Struijk, H.; Lugtenberg, R.; de J ong, F.; Reinhoudt,
D. N. Chem. Eur. J . 1996, 2, 436. (b) Arnaud-Neu, F.; Deutsch, N.;
Fanni, S.; Schwing-Weill, M.-J .; Casnati, A.; Ungaro, R. Gazz. Chim.
Ital. 1997, 127, 693. (c) Arnaud-Neu F.; Ferguson, G.; Fuangswasdi,
S.; Notti, A.; Pappalardo, S.; Parisi, M. F.; Petringa, A. J . Org. Chem.
1998, 63, 7770.
(5) Lugtenberg, R. J . W.; Brzozka, Z.; Casnati, A.; Ungaro, R.;
Engbersen, J . F. J .; Reinhoudt, D. N. Anal. Chim. Acta 1995, 310, 263.
Bocchi, C.; Careri, M.; Casnati, A.; Mori, G. Anal. Chem. 1995, 67,
4234. Diamond, D.; McKervey, M. A. Chem. Soc. Rev. 1996, 25, 15.
(6) For the first example of incorporation of a calix[4]crown into the
polymeric backbone of conducting poly(thiophenes), see Marsella, M.
J .; Newland, R. J .; Carroll, P. J .; Swager, T. M. J . Am. Chem. Soc.
1995, 117, 9842.
(7) Ba¨uerle, P.; Scheib, S. Adv. Mater. 1993, 5, 848. Passos, M. S.;
Queiros, M. A.; Le Gall, T.; Ibrahim, S. K.; Pickett, C. J . J . Electroanal.
Chem. 1997, 435, 189.
10.1021/jo990336v CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/16/1999

1,3-Calix[4]arene Crown Ether Conformers
J . Org. Chem., Vol. 64, No. 16, 1999 5877
Sch em e 1. Rea gen ts a n d Con d ition s: i,
2-(3-Th ien yl)eth a n ol Tosyla te, K2CO3, MeCN,
Reflu x; ii, n -P r I, KHCO3, MeCN, Reflu x; iii,
TsOCH2YCH2OTs, Cs2CO3, MeCN, Reflu x.
F igu r e 1. Structures of target conducting polymers derivable
from the four possible atropisomeric calix[4]crown monomers.
The sensing agents ((A) cone; (B) syn-partial cone; (C) 1,3-
alternate; (D) anti-partial cone) are covalently linked to the
â-position of the polythiophene backbone through a connecting
spacer at the lower rim.
rim. Because calix[4]crowns with mixed functionalities
at the lower rim may give rise to four atropisomers (cone,
syn-partial cone, 1,3-alternate, and anti-partial cone),
conducting polymers A-D with a different topology of
the ionophoric moiety (see Figure 1) can be derived. It
follows that the ion sensing properties of such polymers
could be modulated, at least in principle, by varying the
conformation of the calixarene platform, the size of the
crown ether ring, and the length of the connecting spacer.
To this end, the first mandatory steps are the search for
efficient synthetic protocols for the stereocontrolled in-
troduction of a 3-(oligo)thienyl pendant functionality onto
the calixcrown framework, and the investigation of the
ionophoric properties of the resulting calixarene building
blocks. In this paper we report our initial studies on the
synthesis, structural characterization, and coordinating
behavior of the first 1,3-calix[4]arene crown ether con-
formers endowed with 2-(3-thienyl)ethoxy pendant func-
tionality at the lower rim.8
with 2-(3-thienyl)ethanol tosylate, followed by intrabridg-
ing of the mixed dialkylated intermediates 2 with oligo-
ethylene glycol ditosylate and base, gave 1,3-alternate
and/or cone calixcrown monomers 3 and 4 (Scheme 1);
(ii) the selective debenzylation10,11 of 1-benzyloxy-3-
alkoxycalix[4]arene crown ethers (e.g., 4c), followed by
stereo-controlled introduction of the thienyl functionality
afforded conformationally locked partial cone conformers
(e.g., 6, Scheme 2).
Following the first strategy, treatment of mono-O-
alkylated calix[4]arenes 1a ,b with 2-(3-thienyl)ethanol
tosylate or 1-iodopropane and K2CO3 (molar ratio 1:1:1)
in anhydrous MeCN at reflux afforded the pivotal syn-
distal mixed di-O-alkylated derivatives 2a -c in good
1
yield (Scheme 1). The H and 13C NMR spectra of 2a -c
are consistent with a cone conformation, which is cor-
roborated by the two AX systems of equal intensity for
ArCH2Ar protons and the two resonances for the relevant
carbons around 31 ppm.2a,12 Subsequent reaction of
intermediates 2a ,b with the appropriate oligoethylene
glycol ditosylate and base produced a mixture of the
Resu lts a n d Discu ssion
Syn th esis. For the synthesis of thienyl-containing
p-tert-butylcalix[4]arene crown ether conformers we used
two synthetic approaches: (i) the selective distal alky-
lation9 of mono-O-alkylated p-tert-butylcalix[4]arenes 1
(9) (a) Dijkstra, P. J .; Brunink, J . A.; Bugge, K. E.; Reinhoudt, D.
N.; Harkema, S.; Ungaro, R.; Ugozzoli, F.; Ghidini, E. J . Am. Chem.
Soc. 1989, 111, 7567. (b) van Loon, J . D.; Verboom, W.; Reinhoudt, D.
N. Org. Prep. Proced. Int. 1992, 24, 437.
(10) Iwamoto, K.; Yanagi, A.; Araki, K.; Shinkai, S. Chem. Lett. 1991,
473.
(8) Very recently, calix[4]arenes bearing two or four 2-methyl-
thiophene functionalities at the lower rim were reported: Danil de
Namor, A. F.; Hutcherson, R. G.; Sueros Velarde, F. J .; Alvarez-Larena,
A.; Brianso´, J . L. J . Chem. Soc., Perkin Trans. 1 1998, 2933.
(11) Iwamoto, K.; Araki, K.; Shinkai, S. Tetrahedron 1991, 47, 4325.

5878 J . Org. Chem., Vol. 64, No. 16, 1999
Ferguson et al.
Sch em e 2
Sch em e 3
The intrabridging of distal hydroxyl groups in 2b,c
with a polyether chain affords atropisomeric 1,3-alternate
and/or cone crown ether derivatives. Because conforma-
tionally rigid partial cone calix[4]arene crown ethers are
precluded by this procedure, a sequence involving the
debenzylation of the 1,3-alternate conformer 3b with Me3-
SiBr in CHCl3 followed by the stereocontrolled alkylation
of the resulting mono-hydroxy intermediate was envi-
sioned. Unfortunately, the reaction was rather unselec-
tive and produced intractable mixtures, from which no
pure components could be isolated. Thus, to circumvent
this problem, we applied the debenzylation procedure to
the mixed benzyloxy-propoxy derivative 4c, postponing
the introduction of the thienyl functionality to the last
step. Indeed, treatment of 4c with Me3SiCl (20 equiv) in
anhydrous CHCl3 at room temperature smoothly afforded
mono-hydroxy calixcrown 5 (75%), which was converted
into anti-partial cone 6 (54%) by alkylation with 2-(3-
thienyl)ethanol tosylate and Cs2CO3 in refluxing MeCN
(Scheme 2). This second route paves the way to the
synthesis of thieno-calix[4]arene crown ethers in a fixed
anti-partial cone conformation.
Ta ble 1. P r od u ct Com p osition in th e Rea ction of 2a ,b
w ith Oligoeth ylen e Glycol Ditosyla te a n d Cs2CO3 in
Reflu xin g MeCNa
substrate
ditosylate
3 (anti) %
4 (syn) %
2a
2a
2b
2b
TGD
PGD
TGD
PGD
3a 55 (47)
3a a 57 (41)
3b 79 (53)
3bb 65 (55)
4a 45 (31)
4a a 43 (24)
4b 21 (18)
4bb 35 (25)
a
Determined by 1H NMR analysis of the crude product.
Numbers in parentheses refer to isolated yields.
desired 1,3-calix[4]arene crown ether conformers 3 and
4 endowed with a 3-thienyl pendant functionality at the
lower rim (Scheme 1), which were easily separated by
column chromatography.
The stereochemical outcome of these reactions can be
driven by the template effect of the cation present in the
base used.3d,e,4c Accordingly, a preliminary reaction of 2b
with tetraethylene glycol ditosylate (TGD) and NaH in
anhydrous tetrahydrofuran (THF) afforded cone crown-5
derivative 4b as the sole product, whereas with Cs2CO3/
MeCN a mixture of 1,3-alternate and cone conformers
3b and 4b (ratio 4:1, respectively) was produced. Because
1,3-alternate calix[4]arene crown ethers were shown to
be more efficient and selective ionophores than their cone
analogues,4 the Cs2CO3/MeCN system was chosen for
further reactions.
The conformer distribution in the reaction of 2a ,b with
oligoethylene glycol ditosylates and Cs2CO3 in anhydrous
MeCN is shown in Table 1. The reactions of 2a with TGD
and pentaethylene glycol ditosylate (PGD) surprisingly
afford almost comparable yields of the two conformers.
These results can be explained by taking into account
the fluxional properties of methoxy derivatives, owing to
the easy passage of the methoxy substituent through the
annulus (vide infra).13 Given that the p-tert-butylanisyl
moiety can assume two extreme “up” or “down” orienta-
tions, henceforth the structure of each pair of isolated
conformational isomers of calix[4]arene crown ethers with
methoxy substituents will be designated as syn and anti,
according to whether the heterocyclic pendant group is
on the same side or the opposite side with respect to the
polyether chain. Obviously, these notations are indepen-
dent of the overall conformation(s) adopted by the
molecule.
Attempts to extend the debenzylation procedure to the
1,3-alternate isomer 3c were unsuccessful. The reaction
with Me3SiCl gave unreacted 3c, while the more reactive
Me3SiBr produced a mixture of 7 (75% yield, product of
further opening of the polyether ring) and 8 (8% yield,
product of further cleavage of the propoxy group) (see
Scheme 3). Structures 7 and 8 were assigned by NMR
1
spectroscopy. The H NMR spectrum of the inherently
chiral 7 is very complex, and was analyzed with the aid
of a 2D correlation spectroscopy (COSY) experiment. The
diagnostically important ArCH2Ar protons of 7 give rise
to two AX systems, a pseudo singlet and an AB system
of relative intensity 1:1:1:1, and the relevant carbons
show four resonances at δ 32.5, 32.9, 37.2, and 39.2 ppm.
Although these patterns are compatible with a partial
cone or 1,2-alternate structure, the former was ruled out
on the basis of the remarkable upfield shifts experienced
by both propoxy and oxyethylene protons, which only in
the 1,2-alternate conformation are respectively exposed
to the diamagnetic shielding effect from two pairs of
adjoining aryl rings (one hemicavity above the main
plane containing the four methylene groups and one
below). On the other hand, the NMR spectral character-
istics of 8 support a cone conformation.
The different behavior of 3c compared to 4c upon
exposure to trimethylsilyl halides is likely ascribed to
steric factors which are due to the inaccessibility in the
former of the nucleophilic center (O-Bn oxygen, see
Figure 2), which is shielded by the adjoining aryl rings.
In agreement with this interpretation, the crystal struc-
(12) (a) Gutsche, C. D.; Dhawan, B.; Levine, J . A.; No, K. H.; Bauer,
L. J . Tetrahedron 1983, 39, 409. (b) J aime, C.; de Mendoza, J .; Prados,
P.; Nieto, P. M.; Sa´nchez, C. J . Org. Chem. 1991, 56, 3372.
(13) Groenen, L. C.; van Loon, J .-D.; Verboom, W.; Harkema, S.;
Casnati, A.; Ungaro, R.; Pochini, A.; Ugozzoli, F.; Reinhoudt, D. N. J .
Am. Chem. Soc. 1991, 113, 2385.

1,3-Calix[4]arene Crown Ether Conformers
J . Org. Chem., Vol. 64, No. 16, 1999 5879
t
Ta ble 2. Ch em ica l Sh ifts (300 MHz, CDCl3) of Bu
Gr ou p s in Con for m a tion a lly Rigid 1,3-Ca lix[4]a r en e
Cr ow n Eth er s 3 a n d 4, bis-Cr ow n Eth er s 10 a n d 11, a n d
p-ter t-bu tyl-ca lix[4]a r en e (9)
compound
δtBu, ppm
3b
3bb
3c
4b
4bb
4c
9
10
11
0.94 (18 H)
0.95 (18 H)
1.01 (18 H)
0.80 (9 H)
0.82 (9 H)
0.80 (9 H)
1.40 (9 H)
1.38 (9 H)
1.38 (9 H)
0.82 (9 H)
0.83 (9 H)
0.82 (9 H)
1.15 (36 H)
1.15 (36 H)
1.36 (36 H)
1.41 (9 H)
1.40 (9 H)
1.40 (9 H)
1.34 (18 H)
1.33 (18 H)
1.34 (18 H)
F igu r e 2. A representation of the different orientation of the
benzylic oxygen lone pair in the two conformers 3c and 4c.
The nucleophilic attack on the bulky trimethylsilyl halide is
prevented in 3c by the steric encumbrance of the two rotated
aryl rings.
Sch em e 4
ture of the diethoxy analogue of 3c (1,3-alternate 1,3-
diethoxy-p-tert-butylcalix[4]arene crown-5) showed that
the oxygen lone pairs of the appended substituents point
inside the cavity.3d Therefore, the isolation of 7 and 8
from the reaction of 3c and Me3SiBr implies that the less
reactive but more accessible CR-O bond of the polyether
ring is cleaved first (relieving the steric overcrowding by
conformational reorganization of the molecule), followed
then by the scission of the O-Bn and eventually O-nPr
linkages in that order.
NMR Ch ar acter ization of Con for m ation ally Fixed
Ca lix[4]a r en e Cr ow n Eth er s. Structural assignments
of rigid calix[4]arene crown ethers 3, 4, and 6 were firmly
established by 1H and 13C NMR spectroscopy, on the basis
of distinctive spectral patterns of the bridging methylene
protons and the position of the resonances of pertinent
carbons.12
undergo a downfield shift. The extent of these upfield and
downfield shifts reaches a maximum (∆δ ca. 0.30-0.35
ppm) when two opposing aryl rings lie in parallel planes
and the other two are essentially normal to one another.
The low symmetry of our mixed di-O-alkylated crown
The spectra of each set of conformers are uniform, and
as an example we here discuss the spectral characteris-
tics of crown-6 conformers 3bb and 4bb. Both compounds
show a Cs symmetry (plane passing through the two
distal substituents as the only symmetry element), which
is reflected in the NMR patterns of the calixarene
skeleton. Accordingly, 3bb and 4bb show three singlets
t
ethers allows us to distinguish and easily assign the Bu
resonances of the aryl rings holding the polyether chain
by integration of the signals. The chemical shifts of the
tBu groups of conformationally fixed calix[4]arene crown
ethers 3 and 4 are gathered in Table 2. For comparison
purposes, the tBu resonances of 9, 1,3-2,4-p-tert-butylcalix-
[4]arene bis-crown-5 (10)3b and 1,3-2,4-p-tert-butylcalix-
[4]arene bis-crown-6 (11), the latter obtained in 32% yield
t
for Bu groups, and an AB system and two singlets for
the aromatic protons (relative intensity 2:1:1). However,
they can be easily differentiated by the diagnostic
spectral patterns of ArCH2Ar protons: the cone con-
former 4bb shows two AX systems (ratio 1:1), with a ∆δ
separation > 1 ppm between geminal protons, whereas
the 1,3-alternate conformer 3bb exhibits an AB system
and a pseudo-singlet (ratio 1:1) in the region 3.75-3.95
ppm. The cone and 1,3-alternate structures are further
corroborated by their 13C NMR spectra, which show two
resonances for the ArCH2Ar groups close to 31 or 39 ppm,
respectively, in agreement with the de Mendoza rule for
the determination of calix[4]arene conformations.12b
t
The chemical shifts of the Bu groups in these mol-
ecules deserve further comment. In the parent p-tert-
butylcalix[4]arene (9), which adopts a regular C4v cone
conformation by virtue of a cyclic array of H bonds,14 the
tBu groups resonate at δ 1.15 ppm. On the other hand,
in the usual C2v cone conformation of 1,3-dialkoxy-p-tert-
butylcalix[4]arene crown ethers, the tBu groups of the two
converging aryl rings experience an upfield shift, while
concomitantly those of the two diverging aryl rings
by reaction of 9 with PGD and Cs2CO3 in refluxing MeCN
(Scheme 4), are also reported. It is easily deduced that
the aryl rings supporting the polyether chain are con-
verging (δt < 1.15 ppm) in 1,3-alternate conformers 3
Bu
and diverging (δt > 1.15 ppm) in the cone conformers
Bu
4. The isocrony of tBu resonances in 9 and 10 (δt ) 1.15
Bu
ppm) suggests the same inclination of aryl residues with
respect to the reference plane, whereas those in 11 (δt
Bu
) 1.36 ppm) assume a more flattened shape.15 Therefore,
(14) Andreetti, G. D.; Ungaro, R.; Pochini, A. J . Chem. Soc. Chem.
Commun. 1979, 1005.
t
the Bu resonances of mixed 1,3-dialkoxycalix[4]arene

5880 J . Org. Chem., Vol. 64, No. 16, 1999
Ferguson et al.
crown ether conformers provide a diagnostic tool for
establishing the mutual inclination of opposing pairs of
aryl rings with respect to the methylene carbon plane.
The NMR spectra of conformer 6, synthesized via the
protection-deprotection method, are consistent with a
partial cone conformation, because its methylene protons
show up as an AX system and a pseudo-singlet (relative
intensity 1:1) with resonances for the respective carbons
close to 31 and 39 ppm. The protons of the pendant
heterocyclic moiety attached to the inverted phenol ring
are particularly shielded, because of their tendency to
fill the hydrophobic cavity generated by the three re-
maining phenol rings.16
F lu xion a l P r op er t ies of Ca lix[4]a r en e Cr ow n
Eth er s w ith a Meth oxy Su bstitu en t a t th e Low er
Rim . Structural assignments of methoxy-containing
calix[4]arene crown ethers (3a , 4a , 3a a , and 4a a ) were
complicated by their fluxional behavior, so that dynamic
NMR studies (from -50 to +120 °C) were deemed
essential to establish their conformation in solution. The
1
room temperature H NMR spectrum (CDCl3, 300 MHz)
of anti-3a shows broad signals, especially for the diag-
nostically important bridging methylene protons, com-
patible with a slow interconversion between conformers
on the NMR time scale (Figure 3, trace c). The presence
of a triplet in the high field region (ca. 2 ppm), assigned
to the â-oxymethylene protons of the ethylene spacer
connecting the 3-thienyl ring to the calixarene, is sug-
gestive of an anti orientation of the heterocyclic ring
relative to the polyether chain. Upon heating, a simpli-
fication of the various spectral regions is observed. At
100 °C in deuterated 1,1,2,2-tetrachloroethane (TCE), the
spectrum shows an AX system (δ 3.47 and 4.22 ppm, J AX
) 13.9 Hz) and a pseudo-singlet at δ 3.89 ppm of equal
intensity for the ArCH2Ar groups, indicative of a pref-
erential partial cone conformation (Figure 3, trace e). The
aromatic region shows, as expected, an AB system and
two singlets for the aromatic protons of the calixarene
skeleton, and a well-resolved 12-line pattern (AMX
system) for the 3-thienyl residue. On the other hand,
upon lowering the temperature to 0 °C, broadening of
every region is observed (Tc) (Figure 3, trace b). Below
-20 °C doubling of most signals occurs, indicating a slow
equilibrium between partial cone and 1,3-alternate con-
formers. At -50 °C the tBu region shows two distinct sets
of signals (δ 0.84, 1.36, and 1.46 ppm; δ 1.20, 1.37, and
1.38 ppm; relative intensities 2:1:1) in the ratio 3:2, which
were assigned to partial cone and 1,3-alternate conform-
ers, respectively, by correlation of their relative intensi-
ties with those of the AX system (ArCH2Ar, δ 3.18 and
4.29, J AX ) 12.4 Hz) diagnostic for the partial cone
conformer, and of the multiplet centered at δ 2.99 ppm
(R-oxymethylenes of the polyether bridge), peculiar to the
1,3-alternate conformer (Figure 3, trace a). The latter
protons are typically shifted upfield by the ring current
diamagnetic shielding effect of the two rotated aryl rings.
1
F igu r e 3. Variable-temperature H NMR spectra (300 MHz)
of anti-3a . Traces (a)-(d) in CDCl3 and trace (e) in TCE.
Spectral regions are plotted on different horizontal and vertical
scales.
Hz; δ 3.38 and 4.26, J AX ) 12.2 Hz). The former remains
sharp in the temperature range investigated (-50 to
+120 °C), while the latter is broad and disappears below
+70 °C to reappear again at temperatures below 0 °C.
However, even at -50 °C the up-down interconversion
of the p-tert-butylanisyl moiety is fast enough to prevent
the freezing of cone and partial cone conformers.
From a comparison of the fluxional properties of anti-
3a and syn-4a , it emerges that the flipping motion of the
p-tert-butylanisyl group is considerably slowed in anti-
3a by the self-inclusion of the heterocyclic functionality
attached to the inverted phenol ring inside the cavity,16
which makes the up-down movement of the methoxy
substituent more difficult. This conclusion is supported
by the fact that at -50 °C in anti-3a the partial cone
conformer prevails over cone.
1
The H NMR spectrum (TCE) of conformer syn-4a at
Not unexpectedly, anti-3a a and syn-4a a are more
mobile than their crown-5 counterparts, because of the
increased size of the polyether chain. Their 1H NMR
spectra show sharp resonances in a wide temperature
range (-30 to +120 °C), suggestive of a conformational
preference for partial cone (anti-3a a ) or cone (syn-4a a ).
Broadening of signals occurs at temperatures below -50
°C (CD2Cl2), but even at -90 °C it was not possible to
freeze the two extreme conformations and establish their
+100 °C is consistent with an “up” orientation of the
p-tert-butylanisyl residue (cone conformation), as evi-
denced by the presence of two AX systems of equal
intensity for ArCH2Ar groups (δ 3.19 and 4.45, J AX ) 12.6
(15) Single-crystal X-ray analysis of 10 has shown an unusually
regular 1,3-alternate conformation: Asfari, Z.; Harrowfield, J . M.;
Sobolev, A. N.; Vicens, J . Aust. J . Chem. 1994, 47, 757.
(16) Pappalardo, S. New J . Chem. 1996, 20, 465.

1,3-Calix[4]arene Crown Ether Conformers
J . Org. Chem., Vol. 64, No. 16, 1999 5881
F igu r e 4. 1H NMR spectrum (300 MHz, CDCl3-CD3OD, 1:1, v/v, 22 °C) of syn-4a (slow cone h partial cone equilibrium) (a), and
spectral changes upon addition of 0.5 (b) and 1.0 equiv. (c) of KSCN. Spectral regions are plotted on different horizontal and
vertical scales and asterisk indicates residual solvent peak.
relative populations. Structure assignments for anti-3a a
and syn-4a a , deduced by dynamic NMR studies, were
further proven by single-crystal X-ray analyses (see
below).
The conformational equilibria of methoxy-containing
calix[4]arene crown ethers are strongly affected by the
presence of alkali-metal ions.3d,4a Previous studies in this
laboratory showed that the various conformers (cone,
partial cone, and 1,3-alternate) of 1,3-p-tert-butylcalix-
[4]arene crown-5 with picolyl pendant groups at the lower
rim display a remarkable affinity for K+.4c The sequence
of the stability constants of K+ complexes follows the
order partial cone > 1,3-alternate > cone. This trend is
qualitatively confirmed by preliminary 1H NMR titration
experiments (CDCl3-CD3OD 1:1, v/v) of syn-4a with
KSCN (up to 2 equiv.), shown in Figure 4. A sharpening
of the signals is observed from the addition of the first
aliquot of salt, and after 1 equiv of KSCN has been added
a single complexed species is present, which is not further
F igu r e 5. A view of anti-3a a with our numbering scheme
modified by the addition of an excess of salt. A close
made with PLATON.18 Displacement ellipsoids are drawn at
scrutiny of the spectrum of the complex indicates that
the 30% probability level, H atoms are omitted and only one
the K+ ion is best accommodated by the partial cone
orientation of the methyl groups at C38 is shown.
conformer. This is supported by a distinctive pattern for
the ArCH2Ar groups (one AX and one AB system of equal
intensity), and by the high field resonance of the methoxy
group (ca. 3.0 ppm), shielded by the two flanking aryl
rings (Figure 4, trace c).
On the other hand, the titration experiments of anti-
3a with KSCN (not shown) indicate the formation of both
partial cone and 1,3-alternate K+ complexes in the ratio
5:1, respectively. These results parallel the stability order
previously observed for the K+ complexes of the various
conformers of calix[4]arene crown-5 with picolyl pendant
groups.4c
Titration experiments of crown-6 derivatives anti-3a a
and syn-4a a with cesium picrate evidenced a higher
affinity of the former for Cs+, because it is the only isomer
able to assume the 1,3-alternate conformation, which
better stabilizes the Cs+ complex through additional
cation/π-electron interactions.3d,17
X-r a y An a lysis of a n ti-3a a a n d syn -4a a Con for m -
er s. Suitable crystals of the two conformers were ob-
tained by slow evaporation of MeCN solutions. Views of
the solid state conformation of anti-3a a and syn-4a a are
shown in Figures 5 and 6, respectively. Molecular dimen-
sions for both compounds are normal. In anti-3a a the
aromatic ring C11-C16, bearing the thienyl pendant
group, is on the opposite side of the plane of the bridging
methylene groups (C17, C27, C37, C47) from the remain-
ing three aromatic rings, with its ring plane essentially
normal to the methylene carbon plane (dihedral angle
89.8(1)°). The two aromatic rings linked by the polyether
chain (C21-C26, C41-C46) are almost parallel to one
another (interplanar angles of 85.6(1) and 86.8(1)° with
the reference plane), whereas ring C31-C36 containing
the methoxy substituent is tilted back and makes a
dihedral angle of 39.3(1)° with the methylene carbon
plane. Molecule syn-4a a adopts a conformation commonly
found in calix[4]arenes in the cone conformation, with
(17) Lamare, V.; Dozol, J . F.; Ugozzoli, F.; Casnati, A.; Ungaro, R.
Eur. J . Org. Chem. 1998, 1559, 9.

5882 J . Org. Chem., Vol. 64, No. 16, 1999
Ferguson et al.
conformers endowed with a 3-thienyl pendant functional-
ity at the lower rim. 1H NMR complexation studies,
presently confined to mobile methoxy derivatives, clearly
demonstrated that the presence of the heterocyclic moiety
in these systems is not prejudicial to their recognition
properties for alkali-metal ions, the trend observed being
consistent with previous findings on related ionophores
devoid of this group.4 The search for alternative synthetic
routes leading to rigid syn-partial cone congeners, the
extension of these protocols to the synthesis of analogous
systems bearing an (oligo)thiophene functionality at the
lower rim, and the use of these preorganized building
blocks for the electrochemical synthesis of target calix-
[4]arene-crown-ether/poly(thiophene) conjugates are un-
der current investigation.
Exp er im en ta l Section
Gen er a l. All chemicals were reagent grade and were used
without further purification. Anhydrous solvents and 2-(3-
thienyl)ethanol were obtained commercially. Melting points
were determined on an electrothermal melting point apparatus
and are uncorrected. Unless otherwise stated, 1H and 13C NMR
spectra were recorded in CDCl3 at 300 and 75 MHz, respec-
tively, with tetramethylsilane (TMS) as the internal standard.
The multiplicity of the 13C signals was determined with the
attached proton test (APT) technique. For fast atom bombard-
ment (FAB) (+) mass spectra, 3-nitrobenzyl alcohol was used
as the matrix. p-tert-Butylcalix[4]arene (9),19 monoalkylated
calix[4]arenes 1a ,20 1b,11b tetra- and pentaethylene glycol
ditosylates,21 and 2-(3-thienyl)ethanol tosylate22 were prepared
according to reported procedures or slight modifications thereof.
All reactions were carried out under nitrogen atmosphere.
Mixed Syn -d ista l Di-O-a lk yla ted Ca lix[4]a r en es 2.
Gen er a l P r oced u r e. A stirred mixture of 1 (0.4 mmol), the
appropriate electrophile (0.42 mmol), and K2CO3 (0.055 g, 0.4
mmol) in anhydrous MeCN (20 mL) was refluxed for 36-48
h. The reaction was monitored by thin-layer chromatography
(TLC) (petroleum ether-Et2O, 11:1). After the mixture was
cooled, the solvent was evaporated, and the residue was
partitioned between 1 N HCl and CH2Cl2. The organic extract
was washed with water, dried over MgSO4, and concentrated.
The crude product was purified by column chromatography
(SiO2, petroleum ether-Et2O 20:1 to 9:1), followed by recrys-
tallization from an appropriate solvent.
F igu r e 6. A view of syn-4a a with our numbering scheme.
For clarity, displacement ellipsoids are drawn at the 30%
probability level, H atoms are omitted and only one orientation
of the disordered moieties (methyl groups at C28, polyether
chain, and thienyl ring) is shown.
two opposite aromatic rings almost parallel and the
remaining two almost normal to each other. Thus, the
two rings C21-C26 and C41-C46 linked by the polyether
chain are almost parallel to one another (interplanar
angles of 89.5(1) and 86.5(1)°, respectively, with the
reference plane, C17, C27, C37, C47). Ring C11-C16
with the thienyl substituent is inclined at 45.0(1)° to the
reference plane, whereas the corresponding angle for ring
C31-C36 is 38.2°.
Not surprisingly, the polyether chains in the partial
cone and cone stereoisomers adopt significantly different
conformations. In partial cone anti-3a a the unsigned
values of 8 of the 10 C-O-C-C angles are in the range
169.3(2) to 179.4(2)° with the two values (C5-O6-C4-
C3 86.4(2) and C8-O8-C9-C10 -89.4(2)°) being sig-
nificantly different; the unsigned values of 4 of the 5
O-C-C-O angles are in the range 73.3(2) to 78.8(2)°
with one value (O7-C7-C8-O8, -177.6(2)°) signifi-
cantly different. By contrast, in the cone syn-4a a struc-
ture (in which the polyether chain is disordered over two
unequal conformations) in the major (90%) conformation
the unsigned values of the O-C-C-O torsion angles are
all in the range 62.8(3) to 77.3(3)° and in the C-O-C-C
torsion angles, only 1 of the 10 angles (C5-O6-C4-C3
-90.6(4)°) is markedly different from the others (un-
signed values of remaining C-O-C-C angles in the
range 166.9(2) to 179.9(2)°). In the minor conformation
two O-C-C-O conformations are gauche (-65(2) and
71(3)°) with the third value -119(2)°; four C-O-C-C
torsion angles are close to a fully trans conformation with
one value close to gauche (-73°). Inter-calixarene con-
tacts in both compounds are of the van der Waals variety
and there are no solvent accessible voids in the crystal
lattice.18
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25-m eth oxy-27-
[2-(3-th ien yl)eth oxy]-26,28-d ih yd r oxy-ca lix[4]a r en e (2a ):
obtained in 67% yield from 1a and 2-(3-thienyl)ethanol tosy-
1
late; mp 133-135 °C (MeOH); H NMR δ 0.93, 0.95, 1.29 (s,
ratio 1:1:2, 36 H), 3.29 (d, J ) 13.0 Hz, 4 H), 3.35 (t, J ) 7.4
Hz, 2 H), 3.96 (s, 3 H), 4.19 (t, J ) 7.4 Hz, 2 H), 4.25, 4.28 (d,
J ) 13.0 Hz, 2H each), 6.76, 6.79 (s, 2 H each), 7.06 (pseudo-s,
4 H), 7.11 (dd, J ) 4.8, 1.4 Hz, 1 H), 7.13 (br s, 1 H), 7.25 (br
s, 3 H), and 7.28 (dd, J ) 4.8, 2.9 Hz, 1 H); 13C NMR δ 30.9,
31.4, 31.66 (t, ArCH2Ar and OCH2CH2Th), 30.98, 31.00, 31.7
(q, C(CH3)3), 33.82, 33.87, 33.90 (s, C(CH3)3), 63.4 (q, OCH3),
76.4 (t, OCH2CH2Th), 121.9 (d, Th), 125.02, 125.04, 125.41,
125.46, 125.52 (d, Ar and Th), 127.8, 128.0 (s, bridgehead-C),
128.5 (d, Th), 132.3, 132.4 (s, bridgehead-C), 138.1 (s, 3-Th)
141.4, 146.7, 146.9 (s, Csp2-tBu), 150.1, 150.5, and 151.0 (s,
Csp2-O); FAB (+) MS, m/z 773 (MH+). Anal. Calcd for
C51H64O4S: C, 79.23; H, 8.35; S, 4.14. Found: C, 79.45; H, 8.52;
S, 4.08.
5,11,17,23-Tet r a k is(1,1-d im et h ylet h yl)-25-b en zyloxy-
27-[2-(3-t h ien yl)et h oxy]-26,28-d ih yd r oxy-ca lix[4]a r en e
(2b): obtained in 72% yield from 1b and 2-(3-thienyl)ethanol
Con clu sion s
We developed straightforward synthetic procedures for
the attainment of the first 1,3-calix[4]arene crown ether
(19) Gutsche, C. D.; Iqbal, M. Org. Synth. 1989, 68, 234.
(20) Groenen, L. C.; Rue¨l, B. H. M.; Casnati, A.; Verboom, W.;
Pochini, A.; Ungaro, R.; Reinhoudt, D. N. Tetrahedron 1991, 47, 8379.
(21) Ouchi, M.; Inoue, Y.; Kanzaki, T.; Hakushi T. J . Org. Chem.
1984, 49, 1408.
(18) Spek, A. L. PLATON Molecular Geometry and Graphics
Program, November, 1998 version. University of Utrecht, Utrecht,
Holland.
(22) Noyce, D. S.; Castenson, R. L. J . Am. Chem. Soc. 1973, 95, 1247.

1,3-Calix[4]arene Crown Ether Conformers
J . Org. Chem., Vol. 64, No. 16, 1999 5883
1
tosylate; mp 116-117 °C (MeCN); H NMR δ 0.97, 0.99, 1.27
(s, 2 H each), 6.93 and 7.01 (ABq, J ) 2.5 Hz, 4 H), 7.05 (dd,
J ) 4.9, 1.2 Hz, 1 H), 7.10 (dd, J ) 3.0, 1.2 Hz, 1 H), and 7.28
(dd, J ) 4.9, 3.0 Hz, 1 H); 13C NMR (TCE, +85 °C) δ 30.6,
30.9 (t, OCH2CH2Th and ArCH2Ar), 31.1, 31.2, 31.3 (×2) (q,
C(CH3)3), 33.4, 33.5, 33.6 (×2) (s, C(CH3)3), 60.7 (q, OCH3), 70.4,
70.9, 71.9, 72.3, 74.4 (t, OCH2CH2O and OCH2CH2Th), 120.8,
124.8 124.85, 124.91, 125.0, 125.1, 128.4 (d, Ar and Th), 132.7,
133.2, 133.7, 134.3 (s, bridgehead-C), 139.1 (s, 3-Th), 144.1,
144.8 (s, Csp2-tBu), 152.2, 153.9, and 154.6 (s, Csp2-O); FAB
(+) MS, m/z 931 (MH+). Anal. Calcd for C59H78O7S: C, 76.09;
H, 8.44; S, 3.44. Found: C, 75.82; H, 8.55; S, 3.51.
(s, ratio 1:1:2, 36 H), 3.26 and 4.34 (AX, J ) 12.8 Hz, 4 H),
3.29 (t, J ) 7.0 Hz, 2 H), 3.31 and 4.19 (AX, J ) 13.1 Hz, 4 H),
4.13 (t, J ) 7.0 Hz, 2 H), 5.04 (s, 2 H), 6.80, 6.85 (s, 2 H each),
7.03 (ABq, J ) 2.4 Hz, 4 H), 7.12 (dd, J ) 4.6, 1.5 Hz, 1 H),
7.19-7.22 (m, 2 H), 7.32-7.43 (m, 3 H), 7.46 (s, 2 H), 7.72 (d,
J ) 7.2 Hz, 2 H); 13C NMR δ 30.8, 31.7, and 31.8 (t, ArCH2Ar
and OCH2CH2Th), 31.03, 31.05, 31.6 (q, C(CH3)3), 33.8, 33.96,
34.0 (s, C(CH3)3), 76.4 (t, OCH2CH2Th), 78.3 (t, OCH2Ph),
122.0, 125.00, 125.04, 125.5, 125.6 (d, Ar and Ph), 127.7 (s,
bridgehead-C), 128.0, 128.1, 128.52, 128.56 (d, Ar, Ph, and Th),
132.7, 132.9 (s, bridgehead-C), 136.8 (s, Ph), 138.2 (s, 3-Th),
141.5, 147.1, 147.3 (s, Csp2-tBu), 149.7, 149.8, and 150.5 (s,
Csp2-O); FAB (+) MS, m/z 849 (MH+). Anal. Calcd for
C57H68O4S: C, 80.61; H, 8.08; S, 3.77. Found: C, 80.46; H, 8.17;
S, 3.82.
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25-p r op oxy-27-
ben zyloxy-26,28-d ih yd r oxy-ca lix[4]a r en e (2c): obtained in
68% yield from 1b and propyl iodide; mp 237-238 °C (MeOH);
1H NMR δ 1.00, (s, 18 H), 1.20 (t, J ) 7.4 Hz, 3 H), 1.27 (s, 18
H), 1.99 (m, 2 H), 3.29 (d, J ) 13.0 Hz, 4 H), 3. 92 (t, J ) 6.3
Hz, 2 H), 4.26, 4.32 (d, J ) 13.0 Hz, 2 H each), 5.05 (s, 2 H),
6.84, 6.85 (s, 2 H each), 7.03 (pseudo-s, 4 H), 7.36-7.45 (m, 3
H), and 7.71-7.74 (m, 4 H); 13C NMR δ 10.9 (q, OCH2CH2CH3),
23.4 (t, OCH2CH2CH3), 31.05, 31.06, 31.7 (q, C(CH3)3), 31.8 (t,
ArCH2Ar), 33.8, 33.9, 34.0 (s, C(CH3)3), 77.9, 78.0 (t, OCH2-
CH2CH3 and OCH2Ph), 125.0, 125.4, 125.6, 127.5, 127.8, 128.4
(d, Ar and Ph), 127.6, 127.7, 132.7, 132.8 (s, bridgehead-C),
137.1 (s, Ph), 141.2, 146.7, 146.9 (s, Csp2-tBu), 149.77, 149.81,
and 150.8 (s, Csp2-O); FAB (+) MS, m/z 781 (MH+). Anal. Calcd
for C54H68O4: C, 83.02; H, 8.78. Found: C, 82.75; H, 8.64.
Syn th esis of 1,3-Br id ged Ca lix[4]a r en e Cr ow n Eth er s
3 a n d 4. Gen er a l P r oced u r e. A mixture of 2 (1.0 mmol) and
Cs2CO3 (3.26 g, 10 mmol) in anhydrous MeCN (80 mL) was
refluxed for 1 h. Then a solution of the appropriate oligoeth-
ylene glycol ditosylate (1.1 equiv.) in anhydrous MeCN (20 mL)
was added dropwise over 2 h under rapid stirring. The mixture
was refluxed for an additional 36-48 h. Progress of the
reaction was monitored by TLC, following the disappearance
of the ditosylate. After evaporation of the solvent, the residue
was partitioned between 1 N HCl and CH2Cl2. The organic
extract was washed with water, dried over MgSO4, and
concentrated. The crude product was separated into the pure
components by column chromatography (SiO2, CH2Cl2-AcOEt
7:1; petroleum ether-AcOEt 10:1 for 3c and 4c) to afford
conformers 3 (fastest moving products) and 4. For 3a and 4a ,
the elution order was inverted.
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25-m eth oxy-27-
[2-(3-th ien yl)eth oxy]â-26,28-cr own -5r-calix[4]ar en e,23 an ti
Con for m er (3a ): 47% yield, mp 261-263 °C (MeCN); 1H NMR
(TCE, +100 °C) δ 1.22, 1.28, 1.46 (s, ratio 2:1:1, 36 H), 2.00,
2.96 (t, J ) 7.2 Hz, 2 H each), 3.33 (s, 3 H), 3.44-3.68 (m, 18
H), 3.89 (pseudo-s, 4 H), 4.22 (d, J ) 13.9 Hz, 2 H), 6.57 (dd,
J ) 3.0, 1.2 Hz, 1 H), 6.68 (dd, J ) 4.9, 1.2 Hz, 1 H), 6.98 and
7.05 (ABq, J ) 2.5 Hz, 4 H), 7.03 (s, 2 H), 7.14 (dd, J ) 4.9,
3.0 Hz, 1 H), and 7.16 (s, 2 H); 13C NMR (TCE, +85 °C) δ 30.0
(t, OCH2CH2Th), 31.2 (×2), 31.4, 31.6 (q, C(CH3)3), 33.5, 33.6,
33.7 (s, C(CH3)3), 33.8 (t, ArCH2Ar), 60.8 (q, OCH3), 69.4 (t,
OCH2CH2Th), 70.4, 70.5, 70.6, 72.2 (t, OCH2CH2O), 119.7,
124.2, 125.0, 125.5, 125.8, 126.4, 128.1 (d, Ar and Th), 132.7,
133.2, 133.6, 134.1 (s, bridgehead-C), 139.1 (s, 3-Th), 144.0,
144.3, 144.4 (s, Csp2-tBu), 154.1, 154.2, and 154.8 (s, Csp2-O);
FAB (+) MS, m/z 931 (MH+). Anal. Calcd for C59H78O7S: C,
76.09; H, 8.44; S, 3.44. Found: C, 76.27; H, 8.58; S, 3.35.
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25-m eth oxy-27-
[2-(3-th ien yl)eth oxy]r-26,28-cr ow n -5r-ca lix[4]a r en e,23 syn
Con for m er (4a ): 31% yield; mp 168-169 °C (MeCN); 1H NMR
(TCE, +100 °C) 1.03, 1.18, 1.24 (s, ratio 1:1:2, 36 H), 3.17 (br
s, 3 H), 3.19 and 4.45 (AX, J ) 12.6 Hz, 4 H), 3.30 (t, J ) 7.9
Hz, 2 H), 3.38 and 4.25 (AX, J ) 12.2 Hz, 4 H), 3.67-3.81 (m,
8 H), 4.00-4.13 (m, 8 H), 4.26 (t, J ) 7.9 Hz, 2 H), 6.72, 6.86
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25-m eth oxy-27-
[2-(3-th ien yl)eth oxy]â-26,28-cr own -6r-calix[4]ar en e,23 an ti
Con for m er (3a a ): 41% yield; mp 311-312 °C (MeCN-CH2-
1
Cl2); H NMR (CDCl3, +22 °C) δ 1.04, 1.35, 1.46 (s, ratio 2:1:
1, 36 H), 3.05 and 4.29 (AX, J ) 12.8 Hz, 4 H), 3.10 (br t, J )
9.0 Hz, 2 H), 3.33 (s, 3 H), 3.44-3.68 (m, 14 H), 3.70 (br s, 4
H), 3.80 (br t, J ) 8.6 Hz, 4 H), 3.95 (br d, J ) 9.3 Hz, 2 H),
3.94 (br t, J ) 9.0 Hz, 2 H), 6.57 and 6.90 (ABq, J ) 2.5 Hz,
4 H), 6.83 (dd, J ) 2.9, 1.2 Hz, 1 H), 6.94 (dd, J ) 4.9, 1.2 Hz,
1 H), 7.06 (s, 2 H), 7.26 (dd, J ) 4.9, 2.9 Hz, 1 H), and 7.27 (s,
1
2 H); H NMR (TCE, +120 °C) δ 1.12, 1.40, 1.52 (s, ratio 2:1:
1, 36 H), 3.04 (br t, J ) 8.3 Hz, 2 H), 3.12 and 4.35 (AX, J )
13.1 Hz, 4 H), 3.41 (s, 3 H), 3.53 (s, 4 H), 3.60-3.82 (m, 16 H),
3.86 (br t, J ) 8.3 Hz, 2 H), 3.96-4.08 (m, 4 H), 6.68 and 6.94
(ABq, J ) 2.5 Hz, 4 H), 6.92-6.96 (m, 2 H), 7.09, (s, 2 H), and
7.26-7.28 (m, 3 H); 13C NMR (CDCl3, +22 °C) δ 31.3 (t,
OCH2CH2Th), 31.4, 31.7 (q, C(CH3)3), 31.8 (t, ArCH2Ar), 32.0
(q, C(CH3)3), 33.7, 34.1 (s, C(CH3)3), 39.1 (t, ArCH2Ar), 61.1
(q, OCH3), 70.6, 70.7, 71.2, 71.5, 71.7, 73.1 (t, OCH2CH2O and
OCH2CH2Th), 120.8, 125.0, 125.4, 125.45, 125.47, 125.50, 128.2
(d, Th and Ar), 131.4, 132.8, 133.1, 135.9 (s, bridgehead-C),
138.3 (s, Th), 143.1, 143.8, 144.6 (s, Csp2-tBu), 154.2, 154.8,
and 156.0 (s, Csp2-O); FAB (+) MS, m/z 975 (MH+). Anal. Calcd
for C61H82O8S: C, 75.11; H, 8.48; S, 3.28. Found: C, 75.44; H,
8.31; S, 3.15.
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25-m eth oxy-27-
[2-(3-th ien yl)eth oxy]r-26,28-cr ow n -6r-ca lix[4]a r en e,23 syn
Con for m er (4a a ): 24% yield; mp 256-257 °C (MeOH-CH2-
1
Cl2); H NMR (CDCl3, -30 °C) δ 0.82, 1.35, 1.37 (s, ratio 2:1:
1, 36 H), 3.16, 3.18 (d, J ) 12.2 Hz, 2 H each), 3.51-3.78 (m,
18 H), 4.00 (t, J ) 9.1 Hz, 4 H), 4.18 (s, 3 H), 4.38-4.42 (m, 2
H), 4.41, 4.49 (d, J ) 12.2 Hz, 2 H each), 6.46 and 6.50 (ABq,
J ) 2.4 Hz, 4 H), 7.15, 7.19 (s, 2 H each), 7.27 (dd, J ) 4.9, 1.2
Hz, 1 H), 7.31 (dd, J ) 4.9, 2.8 Hz, 1 H), and 7.38 (dd, J ) 2.8,
1.2 Hz, 1 H); 1H NMR (TCE, +120 °C) 1.04, 1.26, 1.30 (s, ratio
2:1:1, 36 H), 3.20 and 4.49 (AX, J ) 12.4 Hz, 4 H), 3.22 and
4.48 (AX, J ) 13.1 Hz, 4 H), 3.50 (t, J ) 8.2 Hz, 2 H), 3.65 (s,
4 H), 3.68-3.78 (m, 8 H), 3.84-4.06 (m, 11 H), 4.39 (t, J ) 8.2
Hz, 2 H), 6.68 and 6.73 (ABq, J ) 2.5 Hz, 4 H), 6.98, 7.01 (s,
2 H each), 7.14 (dd, J ) 5.0, 1.2 Hz, 1 H), 7.21 (dd, J ) 3.0,
1.2 Hz, 1 H), and 7.29 (dd, J ) 5.0, 3.0 Hz, 1 H); 13C NMR
(CDCl3, +22 °C) δ 31.2 (q, C(CH3)3), 31.46, 31.50 (t, OCH2CH2-
Th and ArCH2Ar), 31.7 (q, C(CH3)3), 33.6, 34.07, 34.08 (s,
C(CH3)3), 61.9 (q, OCH3), 70.9, 71.0, 71.4, 74.4, 74.7 (t,
OCH2CH2O and OCH2CH2Th), 121.6, 124.3, 124.6, 124.7,
125.0, 125.4, 129.3 (d, Th and Ar), 131.8, 132.9, 135.5, 135.9
(s, bridgehead-C), 139.3 (s, Th), 144.3, 144.6, 144.8 (s, Csp2
-
tBu), 153.0, 154.6, and 156.5 (s, Csp2-O); FAB (+) MS, m/z 975
(MH+). Anal. Calcd for C61H82O8S: C, 75.11; H, 8.48; S, 3.28.
Found: C, 75.27; H, 8.32; S, 3.23.
5,11,17,23-Tet r a k is(1,1-d im et h ylet h yl)-25-b en zyloxy-
27-[2-(3-th ien yl)eth oxy]-26,28-cr ow n -5-ca lix[4]a r en e, 1,3-
Alter n a te Con for m er (3b): 53% yield; mp 252-254 °C
(MeCN); 1H NMR δ 0.94, 1.40, 1.41 (s, ratio 2:1:1, 36 H), 2.44
(dd, J ) 9.3, 7.8 Hz, 2 H), 2.96-3.04 (m, 4 H), 3.37-3.69 (m,
14 H), 3.80 and 3.87 (ABq, J ) 16.7 Hz, 4 H), 3.91 (pseudo-s,
4 H), 4.59 (s, 2 H), 6.68-6.71 (m, 4 H), 6.84 (m, 1 H), 6.86 (dd,
J ) 4.9, 1.3 Hz, 1 H), 6.94 (d, J ) 2.6 Hz, 2 H), 7.03-7.05 (m,
3 H), 7.06, 7.10 (s, 2 H each), and 7.24 (dd, J ) 4.9, 2.9 Hz, 1
H); 13C NMR δ 30.3 (t, OCH2CH2Th), 31.3, 31.9 (q, C(CH3)3),
33.6, 34.04, 34.06 (s, C(CH3)3), 39.2, 39.5 (t, ArCH2Ar), 67.1,
70.3, 70.5, 70.9, 71.1, 73.5 (t, OCH2CH2O, OCH2CH2Th, and
OCH2Ph), 120.1, 125.1, 125.2, 125.4, 125.5, 125.6, 126.0, 126.2,
127.7, 128.1 (d, Th, Ar, and Ph), 132.97, 132.99 133.05, 133.4
(23) Notations R and â were introduced by Shinkai11 to define the
stereochemistry of calix[4]arene atropisomers having mixed substit-
uents at the lower rim.

5884 J . Org. Chem., Vol. 64, No. 16, 1999
Ferguson et al.
(s, bridgehead-C), 138.4, 138.6 (s, 3-Th and Ph), 144.4, 144.5,
144.8 (s, Csp2-tBu), 153.8, 154.4, and 154.8 (s, Csp2-O); FAB
(+) MS, m/z 1007 (MH+). Anal. Calcd for C65H82O7S: C, 77.50;
H, 8.20; S, 3.18. Found: C, 77.18; H, 8.31; S, 3.15.
144.2 (×3), 144.7 (s, Csp2-tBu), 153.9, 154.5, and 154.8 (s, Csp2
-
O); FAB (+) MS, m/z 939 (MH+). Anal. Calcd for C62H82O7: C,
79.28; H, 8.80. Found: C, 79.05; H, 8.66.
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25-p r op oxy-27-
ben zyloxy-26,28-cr ow n -5-ca lix[4]a r en e, Con e Con for m er
(4c): 24% yield; mp 252-253 °C (MeCN-CH2Cl2); 1H NMR δ
0.80, 0.82, 1.34 (s, ratio 1:1:2, 36 H), 1.01 (t, J ) 7.4 Hz, 3 H),
1.82-1.96 (m, 2 H), 3.07 and 4.35 (AX, J ) 12.5 Hz, 4 H), 3.12
and 4.33 (AX, J ) 12.8 Hz, 4 H), 3.50-3.72 (m, 10 H), 4.02-
4.22 (m, 8 H), 4.73 (s, 2 H), 6.41, 6.44 (s, 2 H each), 7.10
(pseudo-s, 4 H), and 7.32-7.51 (m, 5 H); 13C NMR δ 10.7 (q,
OCH2CH2CH3), 23.4 (t, OCH2CH2CH3), 31.0 (t, ArCH2Ar), 31.1,
31.7 (q, C(CH3)3), 33.5, 33.6, 34.1 (s, C(CH3)3), 69.9, 71.1, 71.7,
72.5 (t, OCH2CH2O), 77.7 (t, OCH2CH2CH3), 78.2 (t, OCH2-
Ph), 124.4, 124.5, 125.4, 125.6, 127.9, 128.5, 128.8 (d, Ar and
Ph), 131.7, 131.8, 135.3, 135.4 (s, bridgehead-C), 137.7 (s, Ph),
143.9, 144.3, 144.9 (s, Csp2-tBu), 152.0, 152.4, and 155.0 (s,
Csp2-O); FAB (+) MS, m/z 939 (MH+). Anal. Calcd for
C62H82O7: C, 79.28; H, 8.80. Found: C, 79.35; H, 8.71.
5,11,17,23-Tet r a k is(1,1-d im et h ylet h yl)-25-b en zyloxy-
27-[2-(3-th ien yl)eth oxy]-26,28-cr own -5-calix[4]ar en e, Con e
Con for m er (4b): 12% yield; mp 254-255 °C (MeOH-CH2-
Cl2); 1H NMR δ 0.80, 0.82, 1.34 (s, ratio 1:1:2, 36 H), 3.08 and
4.36 (AX, J ) 12.4 Hz, 4 H), 3.11 and 4.31 (AX, J ) 12.5 Hz,
4 H), 3.26 (t, J ) 7.9 Hz, 2 H), 3.53-3.74 (m, 8 H), 3.99 (t, J
) 7.9 Hz, 2 H), 4.04-4.20 (m, 8 H), 4.74 (s, 2 H), 6.43, 6.44 (s,
2 H each), 6.98 (dd, J ) 4.9, 1.3 Hz, 1 H), 7.06 (dd, J ) 2.9,
1.3 Hz, 1 H), 7.10 (pseudo-s, 4 H), 7.25 (dd, J ) 4.9, 2.9 Hz, 1
H), and 7.35-7.53 (m, 5 H); 13C NMR δ 31.0 (×2) (t, OCH2CH2-
Th and ArCH2Ar), 31.1, 31.7 (q, C(CH3)3), 33.56, 33.59, 34.1
(s, C(CH3)3), 70.0, 71.0, 71.9, 72.5 (t, OCH2CH2O), 75.4 (t,
OCH2CH2Th), 78.2 (t, OCH2Ph), 121.2, 124.46, 124.52, 125.4,
125.49, 125.52 127.9, 128.3, 128.5, 129.8 (d, Ph, Th, and Ar),
131.7, 131.8, 135.3 (×2) (s, bridgehead-C), 137.7, 138.6 (s, 3-Th
and Ph), 144.2, 144.4, 145.0 (s, Csp2-tBu), 151.9, 152.0, and
154.9 (s, Csp2-O); FAB (+) MS, m/z 1007 (MH+). Anal. Calcd
for C65H82O7S: C, 77.50; H, 8.20; S, 3.18. Found: C, 77.40; H,
8.11; S, 3.12.
5,11,17,23-Tet r a k is(1,1-d im et h ylet h yl)-25-b en zyloxy-
27-[2-(3-th ien yl)eth oxy]-26,28-cr ow n -6-ca lix[4]a r en e, 1,3-
Alter n a te Con for m er (3bb): 59% yield; mp 247-249 °C
(MeCN); 1H NMR δ 0.95, 1.37, 1.38 (s, ratio 2:1:1, 36 H), 2.52
(dd, J ) 9.7, 7.7 Hz, 2 H), 2.92-2.99 (m, 4 H), 3.26 (t, J ) 7.5
Hz, 4 H), 3.51-3.59 (m, 12 H), 3.70 (dd, J ) 9.7, 7.7 Hz, 2 H),
3.78 and 3.86 (ABq, J ) 16.3 Hz, 4 H), 3.90 (pseudo-s, 4 H),
4.61 (s, OCH2Ph, 2 H), 6.69-6.72 (m, 4 H), 6.86-6.89 (m, 2
H), 6.97 (d, J ) 2.4 Hz, 2 H), 7.05-7.10 (m, 7 H), and 7.25
(dd, J ) 4.9, 2.9 Hz, 1 H); 13C NMR δ 30.3 (t, OCH2CH2Th),
31.2, 31.8 (q, C(CH3)3), 33.6, 34.05, 34.07 (s, C(CH3)3), 39.1,
39.4 (t, ArCH2Ar), 68.0, 70.2, 70.4, 71.0, 71.1, 71.3, 71.4 (t,
OCH2CH2O, OCH2CH2Th, and OCH2Ph), 120.2, 125.2, 125.8,
125.9, 126.09, 126.11, 126.3, 127.8, 128.1 (d, Ar, Th and Ph),
133.0, 133.1, 133.3, 133.7 (s, bridgehead-C), 138.4, 138.6 (s,
3-Th and Ph), 144.3, 144.6, 144.9 (s, Csp2-tBu), 153.9, 154.6,
and 155.0 (s, Csp2-O); FAB (+) MS, m/z 1051 (MH+). Anal.
Calcd for C67H86O8S: C, 76.53; H, 8.25; S, 3.04. Found: C,
76.30; H, 8.37; S, 3.15.
5,11,17,23-Tet r a k is(1,1-d im et h ylet h yl)-25-b en zyloxy-
27-[2-(3-th ien yl)eth oxy]-26,28-cr own -6-calix[4]ar en e, Con e
Con for m er (4bb): 26% yield; mp 207-208 °C (MeOH-CH2-
Cl2); 1H NMR δ 0.82, 0.83, 1.33 (s, 1:1:2, 36 H), 3.07 and 4.36
(AX, J ) 12.4 Hz, 4 H), 3.10 and 4.31 (AX, J ) 12.5 Hz, 4 H),
3.25 (t, J ) 7.9 Hz, 2 H), 3.56-3.70 (m, 12 H), 4.01 (t, J ) 7.9
Hz, 2 H), 3.94-4.19 (m, 8 H), 4.77 (s, 2 H), 6.45, 6.46 (s, 2 H
each), 6.99 (dd, J ) 4.9, 1.3 Hz, 1 H), 7.07 (dd, J ) 2.9, 1.3 Hz,
1 H), 7.08 (pseudo-s, 4 H), 7.25 (dd, J ) 4.9, 2.9 Hz, 1 H), and
7.35-7.52 (m, 5 H); 13C NMR δ 30.99, 31.02, 31.05 (t,
OCH2CH2Th and ArCH2Ar), 31.1, 31.7 (q, C(CH3)3), 33.58,
33.61, 34.1 (s, C(CH3)3), 69.7, 70.5, 70.8, 71.1, 72.2 (t,
OCH2CH2O), 75.4 (t, OCH2CH2Th), 78.0 (t, OCH2Ph), 121.3,
124.5, 125.36, 125.43, 125.5, 128.0, 128.3, 128.4, 129.8 (d, Ar,
Th and Ph), 131.9, 132.0, 135.33, 135.35 (s, bridgehead-C),
137.7, 138.6 (s, 3-Th and Ph), 144.2, 144.4, 145.1 (s, Csp2-tBu),
151.9, 152.1, and 154.5 (s, Csp2-O); FAB (+) MS, m/z 1051
(MH+). Anal. Calcd for C67H86O8S: C, 76.53; H, 8.25; S, 3.04.
Found: C, 76.33; H, 8.46; S, 3.14.
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25-p r op oxy-27-
ben zyloxy-26,28-cr own -5-calix[4]ar en e, 1,3-Alter n ate Con -
for m er (3c): 58% yield; mp 234-235 °C (MeCN-CH2Cl2); 1H
NMR δ 0.62 (t, J ) 7.6 Hz, 3 H), 0.84-0.96 (m, 2 H), 1.01,
1.38, 1.40 (s, ratio 2:1:1, 36 H), 2.90-3.07 (m, 4 H), 3.21-3.27
(m, 2 H), 3.31-3.48 (m, 8 H), 3.60-3.65 (m, 4 H), 3.77 and
3.85 (ABq, J ) 16.4 Hz, 4 H), 3.88 (pseudo-s, 4 H), 4.57 (s, 2
H), 6.69 and 6.91 (ABq, J ) 2.5 Hz, 4 H), 6.75 (m, 2 H), 7.02,
7.09 (s, 2 H each), and 7.03-7.10 (m, 3 H); 13C NMR δ 9.7 (q,
OCH2CH2CH3), 22.1 (t, OCH2CH2CH3), 31.3, 31.9 (q, C(CH3)3),
33.6, 34.00, 34.04 (s, C(CH3)3), 39.2, 39.4 (t, ArCH2Ar), 67.1,
70.5, 70.9, 71.6, 72.2, 73.4 (t, OCH2CH2CH3, OCH2CH2O, and
OCH2Ph), 125.0, 125.5, 125.6, 126.4, 126.5, 127.7 (d, Ar and
Ph), 132.89 (×2), 132.93, 133.4 (s, bridgehead-C), 138.4 (s, Ph),
Compound 4c was prepared more conveniently by treatment
of 2c with tetraethylene glycol ditosylate and NaH in anhy-
drous THF at reflux for 24 h. The reaction produced exclusively
the cone conformer 4c, which was isolated in 70% yield by
direct crystallization of the crude product.
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25,27-cr ow n -5-
26-p r op oxy-28-h yd r oxy-ca lix[4]a r en e, Con e Con for m er
(5): A solution of Me3SiCl (0.65 g, 6 mmol) in anhydrous CHCl3
(2 mL) was added dropwise to a stirred solution of 4c (0.28 g,
0.3 mmol) in anhydrous CHCl3 (8 mL) at room temperature.
After 5 h, the reaction was quenched with water (3 mL). The
organic layer was separated, and dried over MgSO4. After
evaporation of the solvent, the residue was purified by column
chromatography (SiO2, petroleum ether-AcOEt 4:1) to give 5
1
in 75% yield; mp 221-222 °C (MeOH); H NMR δ 0.91, 1.22,
1.26 (s, ratio 2:1:1, 36 H), 0.97 (t, J ) 7.5 Hz, 3 H), 2.06-2.09
(m, 2 H), 3.18 and 4.43 (AX, J ) 12.5 Hz, 4 H), 3.20 and 4.54
(AX, J ) 13.0 Hz, 4 H), 3.70-4.17 (m, 18 H), 6.67 and 6.68
(ABq, J ) 2.5 Hz, 4 H), 6.89 (br s, 1 H), 6.98 and 7.00 (s, 2 H
each); 13C NMR δ 10.1 (q, OCH2CH2CH3), 22.9 (t, OCH2CH2-
CH3), 31.1 (×2) (q, C(CH3)3), 31.3 (t, ArCH2Ar), 31.6, 31.7 (q,
C(CH3)3), 33.7 (×3), 34.0 (s, C(CH3)3), 70.7, 70.87, 70.95, 75.6
(t, OCH2CH2O), 76.0 (t, OCH2CH2CH3), 124.6, 124.8, 125.2,
125.3 (d, Ar), 128.4, 132.7, 133.1, 135.1 (s, bridgehead-C), 140.6
(s, Csp2-tBu, unalkylated ring), 145.0, 145.5 (×2) (s, Csp2-tBu,
alkylated rings), 150.6, 151.4 (×2), and 153.4 (s, Csp2-O); FAB
(+) MS, m/z 849 (MH+). Anal. Calcd for C55H76O7: C, 77.79;
H, 9.02. Found: C, 77.47; H, 8.95.
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25,27-cr ow n -5r-
26-pr opoxyr-28-[2-(3-th ien yl)eth oxy]â-calix[4]ar en e,23 P ar -
tia l Con e Con for m er (6): A stirred mixture of 5 (0.17 g, 0.2
mmol), 2-(3-thienyl)ethanol tosylate (0.12 g, 0.4 mmol), and
Cs2CO3 (0.32 g, 1 mmol) in anhydrous MeCN was refluxed for
40 h. Usual workup followed by chromatography (SiO2 column,
CH2Cl2-AcOEt 10:1) gave 6 in 54% yield; mp 265-267 °C
1
(MeOH-CH2Cl2); H NMR δ 0.96 (t, J ) 7.5 Hz, 3 H), 1.00,
1.28, 1.42 (s, ratio 1:2:1, 36 H), 1.03, 1.81 (t, J ) 5.5 Hz, 2 H
each), 1.85-1.95 (m, 2 H), 3.24 and 4.38 (AX, J ) 12.0 Hz, 4
H), 3.52-3.95 (m, 22 H), 6.42 (dd, J ) 4.9, 1.2 Hz, 1 H), 6.47
(dd, J ) 2.9, 1.2 Hz, 1 H), 6.85 (s, 2 H), 6.97 and 7.23 (ABq, J
) 2.5 Hz, 4 H), 7.00 (dd, J ) 4.9, 2.9 Hz, 1 H), and 7.17 (s, 2
H); 13C NMR δ 10.2 (q, OCH2CH2CH3), 23.2 (t, OCH2CH2CH3),
30.2, 30.5 (t, OCH2CH2Th and ArCH2Ar), 31.3, 31.6, 31.9 (q,
C(CH3)3), 33.9, 34.05, 34.09 (s, C(CH3)3), 38.6 (t, ArCH2Ar),
69.1 (t, OCH2CH2Th), 70.3, 71.2, 71.6, 73.7 (t, OCH2CH2O),
77.8 (t, OCH2CH2CH3), 119.8, 123.8, 124.9, 125.6, 125.9, 126.2,
128.5 (d, Ar and Th), 132.5, 133.42, 133.45, 136.4 (s, bridgehead-
C), 140.6 (s, Th), 144.0, 144.2, 145.4 (s, Csp2-tBu), 152.5,
154.27, and 154.30 (s, Csp2-O); FAB (+) MS, m/z 959 (MH+).
Anal. Calcd for C61H82O7S: C, 76.36; H, 8.62; S, 3.34. Found:
C, 76.54; H, 8.77; S, 3.31.
Deben zyla tion of 3c w ith Me3SiBr . Reaction of 3c with
Me3SiBr (20 equiv.) in CHCl3 was conducted as described
above for the debenzylation of 4c. TLC analysis of the crude
product showed the presence of two components (7 and 8),

1,3-Calix[4]arene Crown Ether Conformers
J . Org. Chem., Vol. 64, No. 16, 1999 5885
which were separated in a pure form by column chromatog-
raphy (SiO2, petroleum ether-AcOEt 4:1).
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25,27;26,28-bis-
cr ow n -6-ca lix[4]a r en e (11). A slurry of 9 (toluene 1:1
complex, 0.37 g, 0.5 mmol) PGD (0.60 g, 1.1 mmol) and Cs2-
CO3 (0.65 g, 2 mmol) in anhydrous MeCN (25 mL) was refluxed
for 24 h. A second portion of Cs2CO3 (0.65 g, 2 mmol) was then
added, and heating was continued for an additional 48 h. After
the mixture was cooled, the solvent was evaporated and the
residue was partitioned between CH2Cl2 and 1 N HCl. The
organic layer was dried over anhydrous Na2SO4 and concen-
trated. The crude product was purified by column chromatog-
raphy (SiO2, 1% MeOH in CH2Cl2) to afford bis-crown 11 (32%)
as white crystals; mp > 280 °C (dec) (MeOH-CH2Cl2); 1H NMR
δ 1.36 (s, 36 H), 2.84, 3.39 (t, J ) 7.6 Hz, 8 H each), 3.51, 3.58,
3.91 (s, ratio 2:1:1, 32 H), and 7.04 (s, 8 H); 13C NMR δ 31.7
(q, C(CH3)3), 34.0 (s, C(CH3)3), 39.2 (t, ArCH2Ar), 68.0, 69.5,
70.4, 71.0, 71.4 (t, OCH2), 125.6 (d, Ar), 132.8 (s, bridgehead-
C), 144.7 (s, Csp2-tBu), and 154.5 (s, Csp2-O); FAB (+) MS,
m/z 1053 (MH+). Anal. Calcd for C64H92O12: C, 72.96; H, 8.81.
Found: C, 72.81; H, 8.97.
An ti-pr oxim a l 5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-
25-p r op oxy-26-(11-b r om o-3,6,9-t r ioxa -1-u n d ecen yloxy)-
27,28-d ih yd r oxy-ca lix[4]a r en e (7) (fr a ction A): 75% yield;
mp 142-143 °C; 1H NMR δ -0.34 (t, J ) 7.4 Hz, OCH2-
CH2CH3, 3 H), 0.53-0.65 (m, OCH2CH2CH3, 2 H), 1.219, 1.222,
1.26, 1.35 (s, tBu, 9 H each), 2.38 (dt, J ) 8.8, 6.0 Hz, OCHaHb-
CH2CH3, 1 H), 2.50 (dt, J ) 8.8, 6.0 Hz, OCHaHbCH2CH3, 1
H), 2.92 (ddd, J ) 10.5, 9.0, 3.0 Hz, OCH2CH2O, 1 H), 3.25-
3.36 (m, OCH2CH2O, 3 H), 3.40 (t, J ) 6.3 Hz, OCH2CH2Br, 2
H), 3.46-3.63 (m, OCH2CH2O, 6 H), 3.49 and 4.12 (AX, J )
13.8 Hz, ArCH2Ar, 2 H), 3.54 and 4.00 (AX, J ) 13.8 Hz,
ArCH2Ar, 2 H), 3.72 (t, J ) 6.3 Hz, OCH2CH2Br, 2 H), 3.71-
3.77 (m, OCH2CH2O, 1 H), 3.85-3.91 (m, OCH2CH2O, 1 H),
3.88 (pseudo-s, ArCH2Ar, 2 H), 3.90 and 4.03 (ABq, J ) 17.3
Hz, ArCH2Ar, 2 H), 6.97, 7.01, 7.02, 7.03, 7.04, 7.05, 7.19, 7.27
(d, J ) 2.4 Hz, ArH, 1 H each), 7.66 and 8.02 (s, OH, 1 H each);
13C NMR δ 8.6 (q, OCH2CH2CH3), 21.7 (t, OCH2CH2CH3), 31.3,
31.5 (×2), 31.6 (q, C(CH3)3), 32.5, 32.9 (t, ArCH2Ar), 33.80,
33.82, 34.07, 34.12 (s, C(CH3)3), 37.2, 39.2 (t, ArCH2Ar), 60.4
(t, OCH2CH2Br), 69.5, 70.32, 70.35, 70.5, 70.7, 71.1, 71.8, 72.5
(t, OCH2CH2O and OCH2CH2CH3), 124.6, 124.8 (×2), 125.1,
125.4, 125.8, 126.2, 127.6 (d, Ar), 126.6, 128.7, 128.8, 129.0,
132.1, 132.8, 134.1, 134.9 (s, bridgehead-C), 142.4, 142.9 (s,
Csp2-tBu, unalkylated ring), 145.2, 147.1 (s, Csp2-tBu, alky-
lated rings), 148.1, 150.0 (s, Csp2-O, unalkylated rings), 151.0,
and 153.1 (s, Csp2-O, alkylated rings); FAB (+) MS, m/z 929/
931 (MH+). Anal. Calcd for C55H77BrO7: C, 71.02; H, 8.34.
Found: C, 70.77; H, 8.55.
Str u ctu r e An a lysis of a n ti-3a a a n d syn -4a a . Details of
the X-ray analysis in Crystallographic Information File (CIF)
format are available in the Supporting Information. Data
collection was performed at 150 K. The structures were solved
using SHELXS-97.24 In anti-3a a there is disorder (0.53:0.47)
t
of the Bu methyl carbons at C38 over two sites. In syn-4a a
t
there is much more disorder; the Bu methyl carbons at C28
are disordered over two sites (0.55:0.45), the polyether chain
has two conformations (0.81:0.19) and the thienyl ring is
disordered over two orientations (0.90:0.10). Refinement was
done by full-matrix least-squares calculations using SHELXL-
9725 using 11262 measured data for anti-3a a and 11687
measured data for syn-4a a . Final Robs values are 0.0476 (for
8299 reflections with I > 2σI) and 0.0591 (for 6969 reflections
with I > 2σI) for anti-3a a and syn-4a a , respectively.
5,11,17,23-Tetr a k is(1,1-d im eth yleth yl)-25-[(11-br om o-
3,6,9-tr ioxa -1-u n d ecen yl)oxy]-26,27,28-tr ih yd r oxy-ca lix-
[4]a r en e (8) (fr a ction B): 8% yield; 1H NMR δ 1.19, 1.20,
1.22 (s, ratio 1:2:1, 36 H), 3.39 and 4.46 (AX, J ) 12.9 Hz, 4
H), 3.42 (t, J ) 6.4 Hz, 2 H), 3.43 and 4.26 (AX, J ) 13.0 Hz,
4 H), 3.60-3.71 (m, 4 H), 3.76 (t, J ) 6.4 Hz, 2 H), 3.79-3.88
(m, 4 H), 4.08-4.16 (m, 2 H), 4.31-4.33 (m, 2 H), 6.97 and
7.06 (ABq, J ) 2.4 Hz, 4 H), 7.05, 7.08 (s, 2 H each), 9.41 and
10.29 (s, ratio 2:1, 3 H); 13C NMR δ 30.3 (t, ArCH2Ar), 31.2,
31.5 (×3) (q, C(CH3)3), 32.1 (t, ArCH2Ar), 33.9, 34.0, 34.2 (s,
C(CH3)3), 60.4 (t, OCH2CH2Br), 70.0, 70.5, 70.7, 70.8, 70.9,
71.2, 75.1 (t, OCH2), 125.62, 125.66, 125.73, 126.4 (d, Ar),
127.6, 128.2, 128.3, 133.7 (s, bridgehead-C), 143.0, 143.5,
147.96 (s, Csp2-tBu), 148.05, 148.3, 149.3 (s, Csp2-O); FAB (+)
MS, m/z 887/889 (MH+). Anal. Calcd for C52H71BrO7: C, 70.33;
H, 8.06. Found: C, 70.56; H, 8.17.
Su p p or tin g In for m a tion Ava ila ble: Details of the X-ray
analysis in Crystallographic Information File (CIF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O990336V
(24) Sheldrick, G. M. SHELXS97. Program for the solution of crystal
structures. University of Go¨ttingen, Germany.
(25) Sheldrick, G. M. SHELXL97. Program for the refinement of
crystal structures. University of Go¨ttingen, Germany.