Regioselective monoalkylation of calixarenes. Synthesis of homodimer calixarenes

Article abstract of DOI:10.1021/jo0003495

The selective monoalkylation at the smaller (lower) rim of the p-tert- butylcalix[4]- and -[6]arenes using bis(butyltin)oxide and different alkylating agents is described. The procedure is remarkable for the mild conditions used allowing an efficiently access to monoalkylated calixarene derivatives in moderate to good yields. Monoalkynylcalix[4]arene and monoalkynylcalix[6]arene have been synthetically exploited for the synthesis of bis-calix[n]arenes (n = 4, 6) with a diyne bridge by oxidative coupling of alkynes. In addition, intermolecular methathesis of the obtained monoalkenylcalix[4]arene allowed the preparation of bis-calix[4]arene that are single bridged at the smaller (lower) rim with a 2-butenyl moiety.

Full text of DOI:10.1021/jo0003495

J . Org. Chem. 2000, 65, 4409-4414
4409
Regioselective Mon oa lk yla tion of Ca lixa r en es. Syn th esis of
Hom od im er Ca lixa r en es
Francisco Santoyo-Gonza´lez,* Antonio Torres-Pinedo, and Adolfo Sanche´z-Ortega
Instituto de Biotecnologı´a, Departamento de Quı´mica Orga´nica, Facultad de Ciencias,
Campus Fuentenueva s/ n, Universidad de Granada, Granada. E-18071, Spain
fsantoyo@ugr.es
Received March 13, 2000
The selective monoalkylation at the smaller (lower) rim of the p-tert-butylcalix[4]- and -[6]arenes
using bis(butyltin)oxide and different alkylating agents is described. The procedure is remarkable
for the mild conditions used allowing an efficiently access to monoalkylated calixarene derivatives
in moderate to good yields. Monoalkynylcalix[4]arene and monoalkynylcalix[6]arene have been
synthetically exploited for the synthesis of bis-calix[n]arenes (n ) 4, 6) with a diyne bridge by
oxidative coupling of alkynes. In addition, intermolecular methathesis of the obtained monoalkenyl-
calix[4]arene allowed the preparation of bis-calix[4]arene that are single bridged at the smaller
(lower) rim with a 2-butenyl moiety.
In tr od u ction
alization from unsubstituted calix[4]arene was the syn-
thesis of a tribenzoate derivative from which monoethers
were prepared after hydrolysis of the ester groups.4
Another indirect procedure for the preparation of mono-
alkoxycalix[4]arenes has been devised that uses the
controlled cleavage of 1,3-dialkoxy- or tetraalkoxycalix-
[4]arenes with either 1 or 3 equiv of trimethylsilyl iodide.5
Complementary to those indirect monoalkylation proce-
dures, regioselective monoalkylation has been carried out
using an excess of the alkylating agent and K2CO3 or CsF
as a weak base,6 NaH,7 or Ba(OH)2.7a Compared with
calix[4]arenes, the regiochemical control of calix[6]arene
funtionalization is more difficult because of the presence
of a larger number of reactive centers and a higher
conformational mobility. However, high selectivity has
been obtained in the synthesis of monobenzyl ethers of
calix[6]arene and p-tert-calix[6]arene, using a weak base
(K2CO3) and stoichiometric amount of benzyl bromide in
dry acetone.8
The development of supramolecular chemistry has led
to a growing interest in the design and synthesis of
macrocyclic molecules containing intramolecular cavi-
ties.1 In this regard, calixarenes2 have been used as
building blocks for the synthesis of a large host molecules
with different supramolecular functions because they are
readily accessible for chemical modification on both
smaller (lower) and larger (upper) rims by attachment
of a wide range of potential ligating groups.
General and efficient procedures for the selective
alkylation of calix[4]arenes at the smaller (lower) rim
have been reported allowing the synthesis of monoalkoxy-
calixarenes and 1,2- and 1,3-dialkoxycalixarenes. The
reason of the observed selectivity is mainly due to the
different acidities of the phenolic OH groups which can
be selectively ionized by using an appropriate base. The
regioselective reaction of a single hydroxy group in
calixarenes is in particular important for the construction
of larger molecules using calixarenes as building units.3
One of the first examples described of selective function-
(3) van Loon, J . D.; Verboom, W.; Reinhoudt, D. N. Org. Prep.
Proced. Int. 1992, 24, 437.
(4) (a) Gutsche, C. D.; Lin, L.-G. Tetrahedron 1986, 42, 1633. (b)
Shang, S.; Khasnis, D. V.; Burton, J . M.; Santini, C. J .; Fan, M. M.;
Small, A. C.; Lattman, M. Organometallics 1994, 13, 5157. (c) King,
A. M.; Moore, C. P.; Samankumara Sandanayake, K. R. A.; Sutherland,
I. O. J . Chem. Soc., Chem. Commun. 1992, 582. (d) Berthalon, S.;
Motta-Viola, L.; Regnouf-de-Vains, J .-B.; Lamartine, B.; Lecocq, S.;
Perrin, M. Eur. J . Org. Chem. 1999, 2269, 9. (e) Gutsche, C. D.; Levine,
J . A. J . Am. Chem. Soc. 1982, 104, 2652. (f) Gutsche, C. D.; Dhawan,
B.; Levine, J . A.; No, K. H. Tetrahedron 1983, 39, 409.
* Phone and fax: +34-958243187.
(1) Comprehensive Supramolecular Chemistry; Lehn, J . M., Atwood,
J . L., Davies, J . E. D., McNicol, D. D., Vogtle, F., Eds.; Pergamon,
Elsevier Science: Oxford, 1996.
(2) (a) Gutsche, C. D. In Calixarenes; Stoddart, J . F., Eds.; Royal
Society of Chemistry: London, 1989. (b) Calixarenes. A versatile Class
of Macrocylcic Compounds; Vicens, J ., Bo¨hmer, V., Eds.; Kluwer
Academic Publishers: Dordrecht, The Netherlands, 1991. (c) Shinkai,
S. Biorg. Chem. Front. 1990, 1, 161. (d) Shinkai, S. Tetrahedron 1993,
49, 8933. (e) Ohtsuka, H.; Shinkai, S. Supramolecular Sci. 1996, 3,
189. (f) Atwood, J . L.; Orr, G. W.; Robinson, K. D.; Hamada, F.
Supramol. Chem. 1993, 2, 309. (g) Bo¨hmer, V. Angew. Chem., Int. Ed.
Engl. 1995, 34, 713. (h) Ikeda, A.; Shinkai, S. Chem. Rev. 1997, 97, 7,
1713. (i) Casnati, A. Gazz. Chim. Ital. 1997, 127, 637. (j) Danil de
Namor, A. F.; Cleverley, R. M.; Zapata-Ormachea, M. L. Chem. Rev.
1998, 98, 2495. (k) Pochini, A.; Ungaro, R. In Comprehensive Supramo-
lecular Chemistry; Vogtle, F., Ed.; Pergamon Press: Oxford, 1996; pp
103-142. (i) Gutsche, C. D. Aldrichim. Acta 1995, 28, 3. (l) Gutsche,
C. D.; Iqbal, M. Organic Syntheses; Wiley: New York, 1993; Collect.
Vol. VIII, p 75. (m) Gutsche, C. D.; Dhawan, B.; Leonis, M.; Stewart,
D. Organic Syntheses; Wiley: New York, 1993; Collect. Vol. VIII, p
77. (n) Munch, S. H.; Gutsche, C. D. Organic Syntheses; Wiley: New
York, 1993; Collect. Vol. VIII, p 80. (o) Arduini, A.; Casnati, A. In
Calixarenes in Macrocyclic Synthesis: A Practical Approach; Parker,
D., Ed.; Oxford University Press: Oxford, 1996; pp 145-173.
(5) Casnati, A.; Arduini, A.; Ghidini, E.; Pochini, A.; Ungaro, R.
Tetrahedron 1991, 47, 2221.
(6) Groenen, L. C.; Rue¨l, B. H. M.; Casnati, A.; Verboom, W.; Pochini,
A.; Ungaro, R.; Reinhoudt, D. N. Tetrahedron 1991, 47, 8379.
(7) (a) Iwamoto, K.; Araki, K.; Shinkai, S. Tetrahedron 1991, 47,
4325. (b) Iwamoto, K.; Yanagi, A.; Arimura, T.; Matsuda, T.; Shinkai,
S. Chem. Lett. 1990, 1901. (c) Iwamoto, K.; Yanagi, A.; Araki, K.;
Shinkai, S. Chem. Lett. 1991, 473. (d) Shu, C.-M.; Chung, W.-S.; Wu,
S.-H.; Ho, Z.-C.; Lin, L.-G. J . Org. Chem. 1999, 64, 2673.
(8) (a) Kanamathareddy, S.; Gutsche, C. D. J . Org. Chem. 1992, 57,
3160. (b) J anssen, R. G.; Verboom, W.; Reinhoudt, D. N.; Casnati, A.;
Freriks, M.; Pochini, A.; Ugozzoli, F.; Ungaro, R.; Nieto, P. M.;
Carramolino, M.; Cuevas, F.; Prados, P.; de Mendoza, J . Synthesis
1993, 380. (c) Casnati, A.; Domiano, L.; Pochini, A.; Ungaro, R.;
Carramolino, M.; Magrans, J . O.; Nieto, P. M.; Lopez-Prados, J .;
Prados, P.; de Mendoza, J .; J anssen, R. G.; Verboom, W.; Reinhoudt,
D. N. Tetrahedron 1995, 51, 12699.
10.1021/jo0003495 CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/13/2000

4410 J . Org. Chem., Vol. 65, No. 14, 2000
Santoyo-Gonza´lez et al.
The versatility of calix[4]arenes as host molecules has
suggested that they can serve as potential building blocks
for designing more elaborate structures consisting of
double calix[4]arenes.9 Three possibilities have been
envisaged: connection via both larger (upper) rims, head-
to-head, via both smaller (lower) rims, tail-to-tail, or via
the larger rim of one with the smaller rim of another,
head-to-tail. Shinkai et al.10 have reported the synthesis
of a series of bis-calix[4]arenes possessing two metal
binding sites, each of which contains four ester or four
ether groups. Double and triple calix[4]arenes connected
via the oxygen atoms have been described11 by reactions
between calix[4]arenes 1,3-difunctionalized at the smaller
(lower) rim and difunctional reagents such as diacid
dichlorides or diamines.11,12 Also, double-calixarenes
linked through one bridge at the smaller (lower) rim and
bearing urea groups on the larger (upper) rims have also
been reported.13 Recently, Rebek et al. have described14
the synthesis and the encapsulation behavior of bis-calix-
[4]arenes linked via one bridge at the larger (upper) rims
and bearing urea groups in the same rims. Bis-calix[n]-
arenes that are singly and doubly bridged at the larger
(upper) rims with 2-butenyl or 2-methylenepropyl moi-
eties have been prepared by tandem Claisen rearrange-
ment of bis-calix[n]arenes that are singly and doubly
bridged via ether linkages at the smaller (lower) rims
with the same spanners.15 A series of bis-calix[4]arenes
derivatives linked through the phenolic oxygens with the
help of single aliphatic or aromatic chain (tail-to-tail)
were obtained by alkylation of 25,26,27-tripropoxy-28-
hydroxycalix[4]arenes with R,ω-dibromoalkanes in the
presence of NaH,16 by condensation of p-tert-butylcalix-
[4]arene with methyl 2,6-bis(bromomethyl)benzoate,17
2,6-bis(bromomethyl)-4-methylanisole,18 or 5,5′-bis(bro-
momethyl)-2,2′-bipyridine N,N′-dioxide.19 Bis- and oligo-
calix[4]arenes have been obtained by intermolecular
methathesis of dialkenylcalix[4]arene derivatives.20
Trialkylstannyl ethers and dialkylstannylene acetals
have become widely used intermediates in synthesis
mainly of carbohydrate derivatives.21 The transformation
of hydroxy groups into organotin alkoxides strongly
increases the nucleophilic character of the oxygen atoms,
allowing easy alkylation and providing reliable, high-
yielding methods for obtaining monosubstituted deriva-
tives of diols or polyols often with high regioselectivity.
Application of these reagents in the phenol chemistry is
rare, and to the best of our knowledge, only Woodward
et al.22 have applied this approach for the selective
monoacylation of 2,2′-binaphthol.
We report in this paper the results of a systematic
study on the selective monoalkylation of the smaller
(lower) rim of the p-tert-butylcalix[4]- and -[6]arenes
using bis(butyltin)oxide and the synthetic applications
of the obtained monoalkynyl- and monoallylcalix[n]arene
(n ) 4, 6) derivatives for the synthesis of bis-calix[4]-
arenes by oxidative coupling of alkynes and intermolecu-
lar methathesis, respectively.
Resu lts a n d Discu ssion
In a project directed to the synthesis of modified
calixarenes, an efficient and general methodology was
needed for access to monoalkylated calixarenes. Consid-
ering the demonstrated utility of stannylene acetals for
the regioselective alkylation and acylation in the sugar
chemistry, it was thought that formation of these inter-
mediates in the case of calixarenes could be also an
adequate way for the synthesis of the desired targets.
To find the optimal conditions for those transformations,
p-tert-butyl calixarene (1) was chosen as the starting
material and propargyl bromide as the electrophile
reagent. The reaction was initially performed using Bu2-
SnO (0.5 equiv) in refluxing toluene with azeotropic
removal of water for 8 h. After this time, Bu4NBr and
propargyl bromide were added keeping the reflux for
additional 2 h. Compound 3 was thus isolated in 33%
yield (see Scheme 1). It was found that the use of Bu4NI
instead of Bu4NBr increased the yield up to 43% or up
to 52% when the initial treatment with Bu2SnO was
prolonged for 24 h. After several experiments, it was
finally found that the use of (Bu3Sn)2O (0.5 equiv) allowed
better results by extending the treatment of 1 with this
reagent for 4 days and subsequent treatment with the
alkylating reagent in the presence of Bu4NI. Thus, the
monoalkylated derivative 3 was obtained in 76% (see
Scheme 1), and these conditions were adopted for the
present study. Also, it should be mentioned that com-
pound 3 was prepared following the conditions described
by Reinhoudt et al.6 for the synthesis of several monoalky-
lated calix[4]arenes by using CsF. However, in our hands
this procedure led to compound 3 in low yield (31%).
(9) (a) Higler, I.; Timmerman, P.; Verboom, W.; Reinhoudt, D. N.
Eur. J . Org. Chem. 1998, 2689, 9. (b) Ikeda, A.; Shinkai, S. Chem. Rev.
1997, 97, 1713. (c) Asfari, Z.; Weiss, J .; Vicens, J . Synlett 1993, 719.
(d) Bo¨hmer, V. Liebigs Ann. Rcl. 1997, 2019.
(10) (a) Ohseto, F.; Shinkai, S. Chem. Lett. 1993, 2045. (b) Ohseto,
F.; Sakaki, T.; Araki, K.; Shinkai, S. Tetrahedron Lett. 1993, 32, 2149.
(c) Ohseto, F.; Shinkai, S. J . Chem. Soc., Perkin Trans. 2 1993, 2045.
(11) Kraft, D.; van Loon, J . D.; Owens, M.; Verboom, W.; Vogt, W.;
McKervey, M. A.; Bo¨hmer, V.; Reinhoudt, D. N. Tetrahedron Lett. 1990,
31, 4941.
(12) McKervey, M. A.; Owens, M.; Schulten, H.-R.; Vogt, W.;
Bo¨hmer, V. Angew. Chem., Int. Ed. Engl. 1990, 29, 280.
(13) (a) Schalley, C. A.; Castellano, R. K.; Brody, M. S.; Rudkevich,
D. M.; Siuzdak, G.; Rebek, J . J . Am. Chem. Soc. 1999, 121, 4568. (b)
Castellano, R. K.; Rebek, J . J . Am. Chem. Soc. 1998, 120, 3657.
(14) Brody, M. S.; Schalley, C. A.; Schalley, D. M.; Rudkevich, D.
M.; Rebek, J . Angew. Chem., Int. Ed. Engl. 1999, 38, 1640.
(15) Wang, J .; Gutsche, C. D. J . Am. Chem. Soc. 1998, 120, 12226.
(16) Lhotak, P.; Shinkai, S. Tetrahedron 1995, 51, 7681.
(17) Schmitt, P. D.; Beer, P. D.; Drew, M. G. B.; Sheen, P. D.
Tetrahedron Lett. 1998, 39, 6383.
(18) Zhong, Z. L.; Chen, Y.-Y.; Lu, X.-R. Tetrahedron Lett. 1995, 36,
6735.
(19) Prodi, L.; Pivari, S.; Bolleta, F.; Hissler, M.; Ziessel, R. Eur. J .
Inorg. Chem. 1998, 1958.
(20) Pitarch, M.; Mckee, V.; Nieuwenhuyzen, M.; McKervey, M. A.
J . Org. Chem. 1998, 63, 946.
(21) (a) David, S.; Hanessian, S. Tetrahedron 1985, 41, 643. (b)
Pereyre, M.; Quintard, J . P.; Rahm, A. Tin in Organic Synthesis;
Butterworth: London, 1987. (c) Blunden, S. J .; Cusack, P. A.; Smith,
P. J . J . Organomet. Chem. 1987, 325, 141. (d) Grindley, T. B. Adv.
Carbohydr. Chem. Biochem. 1998, 53, 17.
Compound 1 was then subsequently treated with (Bu3-
Sn)2O (0.5 equiv) and bromoacetonitrile, allyl bromide,
ethyl bromoacetate, 4-iodobenzyl iodide, benzyl bromide,
and 5-iodo-1-pentyne, respectively. In all of those reac-
tions the corresponding monoalkylated derivatives 4-9
were easily obtained in 34-84% yield (see Scheme 1). The
study was then extended to p-tert-butylcalix[6]arene 2
using the same alkylating reagents. In this case, the
reaction with propargyl bromide led to a complex mixture
from which compound 10 could not be isolated. In the
rest of the cases, the corresponding monoalkylated
derivatives 11-16 were obtained but with yields (23-
(22) (a) Green, J .; Woodward, S. Synlett 1995, 155. (b) Azad, S. M.;
Bennett, S. M.; Brown, S. M.; Green, J .; Sinn, E.; Topping, C. M.;
Woodward, S. J . Chem. Soc., Perkin Trans. 1 1997, 687.

Regioselective Monoalkylation of Calixarenes
J . Org. Chem., Vol. 65, No. 14, 2000 4411
Sch em e 1. Syn th esis of Mon oa lk yla ted
Sch em e 2a
Ca lix[n ]a r en es (n ) 4, 6)a ,b
a
Reagents and conditions: (i) Pd(PPh3)2Cl2, CuI, Et3N-DMF,
rt.
Sch em e 3a
a
A complex mixture was obtained from which compound 10
b
could not be isolated. Reagents and conditions: (i) (Bu3Sn)2O,
toluene, reflux; (ii) RX, Bu4NI, toluene, reflux.
52%) lower than those obtained when 1 was the starting
material (see Scheme 1).
Once the monoalkylated calixarenes were synthesized,
we thought that the alkynyl 3, 9, 16 and allyl 5, 12
derivatives could be adequate precursors for the synthesis
of homodimer calixarenes using carbon-carbon bond-
forming reactions such as oxidative dimerization under
Glasser’s conditions or olefin methathesis. Both types of
reactions were successfully carried out. Thus, treatment
of 3, 9, and 16 with cuprous iodide and a catalytic amount
of bis(triphenylphosphine) palladium dichloride in DMF/
Et3N23 gave the corresponding diynes 17-19 in moderate
to high yields (37-95%) (see Scheme 2). On the other
hand, homodimerization of compound 5 in refluxing
dichlomethane in the presence of the Grubb’s catalyst24
[bis(tricyclohexylphosphine)benzylidene ruthenium(IV)
dichloride] allowed the preparation of a Z/E mixture of
dimers 20 + 21 in a 3:1 proportion. Pure Z-isomer 20
could be obtained when calix[4]arene 1 was reacted with
(Z)-1,4-dichlorobutene following the procedure described
by Gutsche et al.15 in good yield (69%). Olefin hydrogena-
tion of the Z/E mixture of isomers 20 + 21 or pure
Z-isomer 20 was effected using Pd/C, and compound 22
was obtained (40%) (see Scheme 3).
In conclusion, use of bis(butyltin) oxide is first de-
scribed in the calixarene chemistry allowing the regiose-
lective synthesis of monoalkylated calix[4]arenes and
calix[6]arenes. The procedure is remarkable for its ef-
ficiency and mild conditions. This last characteristic
allowed the use of alkylating agents having different
functionalities (nitrile, esters, alkynes). Finally, we used
the monoalkynyl and monoalkenyl calixarenes for the
a
Reagents and conditions: (i) Grubb’s catalyst, CH2Cl2, reflux;
(ii) NaH, (Z)-1,4-dichlorobutene, CH2Cl2, rt; (iii) H2, Pd-C,
methanol-THF.
synthesis of homodimer calixarenes connected by the
smaller (lower) rims.
Exp er im en ta l Section
Gen er a l Exp er im en ta l Deta ils. TLC was performed on
Merck silica gel 60F245 aluminum sheets with detection using
the Mostain reagent [ceric sulfate (1%w/v and ammonium
(23) Liu, Q. B.; Burton, D. J . Tetrahedron Lett. 1997, 38, 4371.
(24) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997,
36, 2037.

4412 J . Org. Chem., Vol. 65, No. 14, 2000
Santoyo-Gonza´lez et al.
molybdate (2.5% w/v) in 10% (v/v) aqueous sulfuric acid] and
by UV light when applicable. Flash column chromatography
on silica gel Merck or Scharlau (230-400 mesh ASTM). All
the concentrations were carried out under diminished pressure
at 40 °C. Melting points were determinated with a Gallenkamp
apparatus and are uncorrected. NMR spectra were recorded
at room temperature on a Bruker AM-300 spectrometer. 1H
NMR chemical shifts are given in ppm and referenced to
internal CHCl3 (δ ) 7.26) for CDCl3 solutions. 13C NMR
chemical shifts are given in ppm and referenced to CDCl3 (δ
) 77.0). FAB mass spectra were obtained on a Fissons VG
Autospec-Q spectrometer using m-nitrobenzyl alcohol or
thioglicerol as matrix. Anhydrous solvents were prepared
according to standard procedures and were freshly distilled
prior to use. For reasons of clarity and to reduce space the
names calix[4]arene and calix[6]arene were used instead of
the original IUPAC names: pentacyclo[19.3.1.1.3,71.9,13115,19]-
octacosa-1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-dodeca-
ene and heptacyclo[31.3.1.1.3,71.9,131.15,191.21,25127,31]dotetra-
conta-1(37),3,5,7(42),9,11,13(41),15,17,19(40),21,23,25(39),-
27,29,31(38),33,35-octadecaene.
the crude (dichloromethane-hexane 1:4) gave 5 (80.5%) as a
solid: mp 167-168 °C (lit.6 mp 273-275 °C); 1H and 13C NMR
are identical as those reported;6 HRMS FAB+ m/z calcd for
C
47H60O4Na [M + Na]+ 711.4379, found 711.4389.
5,11,17,23-Tetr a -ter t-bu tyl-25-eth oxyca r bon ylm eth yl-
oxy-26,27,28-tr ih yd r oxyca lix[4]a r en e (6). Column chro-
matography of the crude (dichloromethane-hexane 2:1) gave
6 (34%) as a solid: mp 269-271 °C (lit.6 mp 264-266 °C); 1H
NMR identical as those reported in ref 6; HRMS (FAB) m/z
757.4444 for [M + Na]+, calcd for C48H62O6Na M 757.4428.
5,11,17,23-Tetr a -ter t-bu tyl-25-(4-iod oben zyloxy)-26,27,-
28-tr ih yd r oxyca lix[4]a r en e (7). Column chromatography of
the crude (dichloromethane/hexane 1:3) gave 7 (56%) as a
solid: mp 122-124 °C; IR (KBr) ν 3318, 1487, 1364, 1206, 1008
cm-1; 1H NMR (300 MHz, CDCl3) δ 9.96 (s, 1 H), 9.32 (s, 2 H),
7.66 (4 H, AB system, J ) 8.2 Hz, ∆ν ) 59.0 Hz), 7.11 (s, 2 H),
7.04 (d, 2 H, J ) 2.3 Hz), 7.03 (s, 2 H), 6.97 (d, 2 H, J ) 2.3
Hz), 5.09 (s, 2 H), 4.29 (d, 2 H, J ) 13.0 Hz), 4.22 (d, 2 H, J )
13.6 Hz), 3.41 (d, 4 H, J ) 13.4 Hz), 1.21 (s, 9 H), 1.21 (s, 18
H), 1.20 (s, 9 H); 13C NMR (75 MHz, CDCl3) δ 149.2, 148.6,
148.5, 147.7, 143.7, 143.2, 138.2, 135.4, 133.6, 130.9, 128.3,
127.9, 127.6, 126.7, 125.8, 125.7, 95.0, 78.4, 34.4, 34.1, 34.0,
33.0, 32.5; HRMS (FAB) m/z 887.3511 for [M + Na]+, calcd
for C51H61IO4Na M 887.3555.
5-Iodo-1-pentyne was obtained from 4-pentyn-1-ol in two
steps.25 4-Iodo-benzyl iodide was obtained from 4-nitrobenzyl
alcohol in two steps: reduction to 4-amino-benzyl alcohol and
reaction with NaNO2 and NaI.26
25-Ben zyloxy-5,11,17,23-t et r a -ter t-b u t yl-26,27,28-t r i-
h yd r oxyca lix[4]a r en e (8). Column chromatography of the
crude (dichloromethane/hexane 1:3) gave 8 (47%) as a solid:
Gen er a l P r oced u r e for th e Mon oa lk yla tion of 1 a n d
2. Syn th esis of 3-16. A suspension of the correponding
calixarene (1 mmol) in dry toluene (25 mL) was refluxed for 4
days in the presence of bis(tributyltin)oxide (0.5 mmol) in a
flask equipped with a Dean-Stark separator. The correspond-
ing alkylating agent (1.1 mmol) and tetrabutylammonium
iodide (1.1 mmol) were added, and the solution was refluxed
for 1-5 h. Toluene (50 mL) was added, and the organic phase
was treated with NaHCO3 saturated solution (2 × 50 mL) and
water (25 mL). The organic phase was dried and concentrated
yielding a crude product that was purified by column chro-
matography.
5,11,17,23-Tetr a -ter t-bu tyl-26,27,28-tr ih yd r oxy-25-p r o-
p a r gyloxyca lix[4]a r en e (3). Column chromatography of the
crude (dichloromethane/hexane 1.1) gave 3 (76%) as a solid:
mp 177-179 °C; IR (KBr) ν 3314, 3237, 2135, 1483, 1460, 1364,
1298, 1202, 1213 cm-1; 1H NMR (300 MHz, CDCl3) δ 10.03 (s,
1 H), 9.20 (s, 2 H), 7.09 (s, 2 H), 7.04 (d, 2 H, J ) 2.3 Hz), 7.03
(s, 2 H), 6.98 (d, 2 H, J ) 2.3 Hz), 4.91 (d, 2 H, J ) 2.4 Hz),
4.46 (d, 2 H, J ) 13.1 Hz), 4.27 (d, 2 H, J ) 13.6 Hz), 3.43 (d,
4 H, J ) 13.4 Hz), 2.72 (t, 1 H, J ) 2.0 Hz), 1.22 (s, 9 H), 1.20
(s, 18 H), 1.19 (s, 9 H); 13C NMR (75 MHz, CDCl3) δ 149.2,
148.8, 148.4, 147.8, 143.7, 143.3, 133.8, 128.2, 128.1, 127.8,
126.6, 125.9, 125.8, 125.6, 78.0, 77.4, 63.5, 34.3, 34.1, 34.0, 33.0,
32.7, 31.6, 31.3; HRMS (FAB) m/z 709.4221 for [M + Na]+,
calcd for C47H58O4Na M 709.4232.
5,11,17,23-Tetr a -ter t-bu tyl-25-cya n om eth yloxy-26,27,-
28-tr ih yd r oxyca lix[4]a r en e (4). Column chromatography of
the crude (dichloromethane/hexane 1:3) gave 4 (50.0%) as a
solid: mp 252-254 °C dec; IR (KBr) ν 3416, 3167, 1483, 1362,
1202 cm-1; 1H NMR (300 MHz, CDCl3) δ 9.78 (s, 1 H), 8.70 (s,
2 H), 7.14 (s, 2 H), 7.10 (d, 2 H, J ) 2.3 Hz), 7.07 (s, 2 H), 7.04
(d, 2 H, J ) 2.3 Hz), 5.02 (s, 2 H), 4.35 (d, 2 H, J ) 13.2 Hz),
4.26 (d, 2 H, J ) 13.8 Hz), 3.55 (d, 2 H, J ) 13.3 Hz), 3.48 (d,
2 H, J ) 13.8 Hz), 1.24 (s, 9 H), 1.24 (s, 18 H), 1.20 (s, 9 H);
13C NMR (75 MHz, CDCl3) δ 149.8, 148.4, 147.5, 144.0, 146.6,
133.0, 128.1, 127.5, 123.3, 126.2, 126.1, 125.8, 127.7, 115.0,
60.4, 34.4, 34.1, 32.7, 32.5; HRMS (FAB) m/z 710.4187 for [M
+ Na]+, calcd for C46H57NO4Na M 710.4158.
1
mp 198-200 °C (lit.5 mp 202-203 °C); H and 13C NMR are
identical to those described in ref 5.
5,11,17,23-Tet r a -ter t-b u t yl-26,27,28-t r ih yd r oxy-25-(4-
p en tyn -1-yloxy)ca lix[4]a r en e (9). Column chromatography
of the crude (dichloromethane/hexane 1:2) gave 9 (66%) as a
solid: mp 165-167 °C; IR (KBr) ν 3314, 1485, 1362, 1203 cm-1
;
1H NMR (300 MHz, CDCl3) δ 10.15 (s, 1 H), 9.52 (s, 2 H), 7.11
(s, 2 H), 7.08 (d, 2 H, J ) 2.4 Hz), 7.05 (s, 2 H), 7.01 (d, 2 H,
J ) 2.4 Hz), 4.38 (d, 2 H, J ) 12.9 Hz), 4.28 (d, 2 H, J ) 13.7
Hz), 4.26 (t, 2 H, J ) 6.4 Hz), 3.45 (d, 2 H, J ) 13.7 Hz), 3.45
(d, 2 H, J ) 13.0 Hz), 2.75 (dt, 2 H, J ) 6.9 and 2.7 Hz), 2.35
(m, 2 H), 2.06 (t, 1 H, J ) 2.6 Hz), 1.24 (s, 9 H), 1.23 (s, 18 H),
1.21 (s, 9 H); 13C NMR (75 MHz, CDCl3) δ 149.2, 148.5, 148.3,
147.7, 143.7, 143.2, 133.5, 128.4, 128.1, 127.5, 126.5, 125.8,
125.7, 125.7, 125.2, 83.3, 75.4, 69.5, 34.3, 34.1, 33.9, 33.1, 32.0,
31.9, 28.6, 15.4; HRMS (FAB) m/z 737.4553 for [M + Na]+,
calcd for C49H62O4Na M 737.4546.
5,11,17,23,29,35-Hexa -ter t-bu tyl-38,39,40,41,42-p en ta h y-
d r oxy-37-cya n om eth yloxyca lix[6]a r en e (11). Column chro-
matography of the crude (dichloromethane/hexane 1:1) gave
11 (23%) as a solid: mp 274-276 °C dec; IR (KBr) ν 3295,
1
2361, 2343, 1485,1364,1292, 1204 cm-1; H NMR (300 MHz,
CDCl3) δ 7.75 (s, 2 H), 7.72 (s, 2 H), 7.17 (s, 2 H), 7.13 (d, 6 H),
7.09 (s, 2 H), 6.96 (d, 2 H), 4.87 (s, 2 H), 4.03 (br s, 4 H), 3.89
(br s, 2 H), 3.70 (br s, 4 H), 1.29 (s, 18 H), 1.27 (s, 18 H), 1.21
(s, 9 H), 1.10 (s, 9 H); 13C NMR (75 MHz, CDCl3) δ 149.1, 148.8,
148.0, 146.5, 143.9, 143.9, 132.2, 128.5, 127.6, 127.3, 126.8,
126.5, 126.3, 126.1, 126.0, 125.9, 115.5, 60.1, 34.4, 34.1, 33.1,
32.6, 32.3; HRMS (FAB) m/z 1034.6288 for [M + Na]+, calcd
for C68H85NO6Na M 1034.6274.
5,11,17,23,29,35-Hexa -ter t-bu tyl-38,39,40,41,42-p en ta h y-
d r oxy-37-(2-p r op en -1-yloxy)ca lix[6]a r en e (12). Column
chromatography of the crude (dichloromethane/hexane 1:2)
gave 12 (51%) as a solid: mp 150-152 °C; IR (KBr) ν 3231,
1487, 1362, 1206 cm-1; 1H NMR (300 MHz, CDCl3) δ 9.84 (br
s, 2 H), 9.50 (br s, 1 H), 9.00 (s, 2 H), 7.13, 7.10, 7.08, 7.02 (4
s, 12 H), 6.24 (m, 1 H), 5.92 (d, 1 H, J ) 16.9 Hz), 5.56 (d, 1 H,
J ) 10.9 Hz), 4.66 (d, 2 H, J ) 4.5 Hz), 4.00-3.50 (m, 12 H),
1.28 (s, 18 H), 1.26 (s, 18 H), 1.21 (s, 9 H), 1.15 (s, 9 H); 13C
NMR (75 MHz, CDCl3) δ 149.5, 148.3, 148.1, 146.9, 144.4,
143.7, 143.1, 132.6, 128.2, 127.8, 126.3, 126.2, 126.1, 125.9,
125.5, 132.6, 117.8, 75.8, 34.1, 33.3, 32.6, 31.7, 31.7, 31.6, 31.5;
HRMS (FAB) m/z 1035.6472 for [M + Na]+, calcd for C69H88O6-
Na M 1035.6503.
5,11,17,23-Tet r a -ter t-b u t yl-26,27,28-t r ih yd r oxy-25-(2-
p r op en yloxy)ca lix[4]a r en e (5). Column chromatography of
(25) Conventional mesylation of 4-pentyn-1-ol in dry dichloromethane
at 0 °C with methanesulfonyl chloride gave the corresponding mesyl
derivative that was reacted with KI in dry butanone under reflux for
24 h to give 5-iodo-1-pentyne (65% overall yield) as a yellow liquid:
1H NMR (300 MHz, CDCl3): 3.30 (t, 2 H, J ) 6.7 Hz), 2.33 (dt, 2 H, J
) 6.7, 2.6 Hz), 1.99 (q, 2 H, J ) 2.73 Hz), 1.98 (m, 1 H); 13C NMR (75
MHz, CDCl3) 82.3, 69.5, 31.9, 19.5, 5.1.
5,11,17,23,29,35-Hexa -ter t-bu tyl-38,39,40,41,42-p en ta h y-
dr oxy-37-eth oxycar bon ylm eth yloxycalix[6]ar en e (13). Col-
umn chromatography of the crude (dichloromethane/hexane
1:1) gave 13 (47%) as a solid: mp 273-275 °C; IR (KBr) ν 3302,
(26) Santoyo-Gonza´lez, F.; Pe´rez-Balderas, F. M. Unpublished
results.

Regioselective Monoalkylation of Calixarenes
J . Org. Chem., Vol. 65, No. 14, 2000 4413
3200, 1749, 1489, 1464, 1207, 1067 cm-1; 1H NMR (300 MHz,
CDCl3) δ 9.70 (s, 2 H), 8.70 (s, 2 H), 7.13, 7.06, 7.00 (s, 12 H),
4.71 (s, 2 H), 4.41 (q, 2 H, J ) 7.2 Hz), 4.36 (d, 2 H, J ) 14.0
Hz), 4.16 (d, 2 H, J ) 14.4 Hz), 3.95 (d, 2 H, J ) 13.5 Hz), 3.55
(d, 2 H, J ) 14.4 Hz), 3.61 (d, 2 H, J ) 14.0 Hz), 3.52 (d, 2 H,
J ) 13.9 Hz), 1.41 (t, 3 H, J ) 7.2 Hz), 1.28 (s, 18 H), 1.25 (s,
18 H), 1.23 (s, 9 H), 1.14 (s, 9 H); 13C NMR (75 MHz, CDCl3)
δ 169.5, 149.4, 148.4, 147.1, 143.6, 143.0, 132.3, 127.3, 127.0,
126.9, 126.2, 126.1, 126.0, 125.5, 71.9, 61.7, 34.0, 33.1, 32.6,
32.5, 31.7, 31.6, 31.5, 31.3, 14.4; HRMS (FAB) m/z 1081.6538
for [M + Na]+, calcd for C70H90O8Na M 1081.6557.
H, J ) 2.4 Hz), 7.04 (s, 4 H), 6.98 (d, 4 H, J ) 2.4 Hz), 4.34 (d,
4 H, J ) 13.0 Hz), 4.26 (d, 4 H, J ) 13.9 Hz), 4.21 (t, 4 H, J )
6.3 Hz), 3.44 (d, 4 H, J ) 12.0 Hz), 3.43 (d, 4 H, J ) 13.8 Hz),
2.83 (t, 4 H, J ) 6.6 Hz), 2.33 (m, 4 H), 1.22 (s, 18 H), 1.21 (s,
36 H), 1.19 (s, 18 H); 13C NMR (75 MHz, CDCl3) δ 149.1, 148.6,
148.3, 147.7, 143.8, 143.2, 133.6, 128.5, 128.1, 127.6, 126.6,
125.9, 125.8, 76.5, 75.4, 66.5, 34.3, 34.1, 34.0, 33.1, 32.2, 28.6,
16.4.; HRMS (FAB) m/z 1449.9027 for [M + Na]+, calcd for
C
98H122O8Na M 1449.9096.
1,10-Bis[5,11,17,23,29,35-h exa -ter t-bu tyl-37,38,39,40,41-
p en ta h yd r oxy-42-oxyca lix[6]a r en e]-4,6-d eca d iyn e (19).
To a degassed solution of 16 (0.230 g, 0.22 mmol) in dry Et3N
(15 mL) were added Pd(PPh3)2Cl2 (0.016 g) and CuI (0.043 g).
The reaction mixture was stirred at room temperature for 1
h. Filtration over Celite was followed by concentration. Column
chromatography (dichloromethane/hexane 1:2) of the crude
gave 19 (0.086 g, 81%) as a solid: mp 216 °C dec; IR (KBr) ν
3320, 1485, 1203 cm-1; 1H NMR (300 MHz, CDCl3) δ 9.81 (br
s, 4 H), 8.98 (br s, 4 H), 7.45 (br s, 2 H), 7.19 (d, 4 H, J ) 2.4
Hz), 7.18, 7.17, 7.10, 7.07 (4s, 16 H), 7.13 (d, 4 H, J ) 2.4 Hz),
4.30 (d, 4 H, J ) 12.6 Hz), 4.22 (d, 4 H, J ) 14.4 Hz), 4.18 (t,
4 H, J ) 5.6 Hz), 3.97 (d, 4 H; J ) 13.9 Hz), 3.54 (d, 4 H, J )
14.6 Hz), 3.52 (d, 4 H, J ) 14.3 Hz), 3.44 (d, 4 H, J ) 14.1 Hz),
2.87 (t, 4 H, J ) 6.5 Hz), 2.20 (m, 4 H), 1.32 (s, 36 H), 1.30 (s,
36 H), 1.26 (s, 18 H), 1.21 (s, 18 H); 13C NMR (75 MHz, CDCl3)
δ 149.4, 148.3, 148.0, 146.9, 144.3, 143.6, 143.1, 132.5, 127.4,
127.3, 127.1, 126.8, 126.8, 126.2, 126.1, 125.9, 125.5, 76.3, 73.8,
66.8, 34.3, 34.0, 33.3, 32.7, 29.0, 16.0; HRMS (FAB) m/z
2076.3350 for [M + H]+, calcd for C142H179O12 M 2076.3396;
2099.3250 for [M + Na]+, calcd for C142H178O12Na M 2099.3250.
(Z)-1,4-Bis[5,11,17,23-t et r a -ter t-b u t yl-25,26,27-t r ih y-
d r oxy-28-oxyca lix[4]a r en e]-2-bu ten e (20). To a solution of
1 (1 g, 1.54 mmol) in dry dichloromethane (50 mL) was added
NaH (0.07 g, 3.08 mmol). The mixture was stirred for 30 min
under an inert atmosphere, treated with (Z)-1,4-dichloro-2-
butene (0.57 g, 1,54 mmol) and tetrabutylammonium iodide
(0.57 g), and stirred at room temperature for 24 h. The reaction
mixture was washed with 1 N HCl (25 mL) and water (25 mL)
and then dried (Na2SO4) to yield after concentration a crude
product that was purified by column chromatography (dichlo-
romethane/hexane 1:1) giving 20 (0.714 g, 69%) as a solid: mp
5,11,17,23,29,35-Hexa -ter t-bu tyl-37-(4-iod oben zyloxy)-
38,39,40,41,42-p en ta h yd r oxyca lix[6]a r en e (14). Column
chromatography of the crude (dichloromethane/hexane 1:4)
gave 14 (38%) as a solid: mp 178-180 °C; IR (KBr) ν 3422,
3225, 1485, 1364, 1204 cm-1 1H NMR (300 MHz, CDCl3) δ
;
9.92-9.80 (br s, 3 H), 8.88 (br s, 2 H), 7.96 (d, 2 H, J ) 8.2
Hz), 7.47 (d, 2 H, J ) 8.2 Hz), 7.12 (m, 12 H), 5.12 (s, 2 H),
4.37 (d, 4 H, J ) 13.4 Hz), 4.28 (d, 2 H, J ) 14.1 Hz), 3.99 (d,
2 H, J ) 13.9 Hz), 3.59 (d, 2 H, J ) 14.2 Hz), 3.52 (d, 2 H, J
) 13.6 Hz), 3.39 (d, 2 H, J ) 13.9 Hz), 1.27 (s, 18 H), 1.26 (s,
18 H), 1.22 (s, 9 H), 1.17 (s, 9 H); 13C NMR (75 MHz, CDCl3)
δ 149.5, 149.3, 148.4, 148.2, 146.7, 144.5, 143.7, 143.1, 138.3,
136.1, 132.6, 129.3, 127.6, 125.9, 127.5, 127.2. 126.8, 126.3,
126.2, 126.1, 125.8, 125.6, 94.4, 77.2, 34.4, 34.1, 35.1, 32.0, 33.4,
32.8; HRMS (FAB) m/z 1211.8653 for [M + Na]+, calcd for
C
73H89IO6Na M 1211.8645.
37-Ben zyloxy-5,11,17,23,29,35-h exa -ter t-bu tyl-38,39,40,-
41,42-p en ta h yd r oxyca lix[6]a r en e (15). Column chroma-
tography of the crude (dichloromethane/hexane 1:3) gave 15
1
(52%) as a solid: mp 225-227 °C (lit.32 mp 228-231 °C); H
and 13C NMR spectra are identical to those reported.8b
5,11,17,23,29,35-Hexa -ter t-bu tyl-38,39,40,41,42-pen ta h y-
d r oxy-37-(4-p en tyn -1-yloxy)ca lix[6]a r en e (16). Column
chromatography of the crude (dichloromethane-hexane 1:1)
gave 16 (27%) as a solid: mp 157-159 °C; IR (KBr) ν 3310,
2360, 1485, 1362, 1292, 1201 cm-1; 1H NMR (300 MHz, CDCl3)
δ 9.77, 9.00 (2 br s, 5 H), 7.12-7.01 (m, 12 H), 4.36 (d, 2 H, J
) 14.8 Hz), 4.28 (t, 2 H, J ) 5.7 Hz), 4.22 (d, 2 H, J ) 13.6
Hz), 4.00 (d, 2 H, J ) 13.6 Hz), 3.60-3.40 (m, 6 H), 2.81 (dt,
2 H, J ) 6.7 and 2.5 Hz), 2.27 (m, 2 H), 2.02 (t, 1 H, J ) 2.5
Hz), 1.28 (s, 18 H), 1.26 (s, 18 H), 1.21 (s, 9 H), 1.15 (s, 9 H);
13C NMR (75 MHz, CDCl3) δ 149.5, 148.3, 148.0, 146.7, 143.7,
143.1, 132.5, 127.4, 127.3, 127.1, 126.8, 126.3, 126.1, 126.0,
125.9, 125.5, 83.3, 73.9, 69.6, 36.5, 34.3, 32.6, 33.3, 32.7, 31.7,
29.1, 15.2; HRMS (FAB) m/z 1061.6653 for [M + Na]+, calcd
for C71H90O6Na M 1061.6635.
115-117 °C; IR (KBr) ν 3374, 1485, 1462, 1362, 1205 cm-1
;
1H NMR (300 MHz, CDCl3) δ 10.11 (s, 2 H), 9.44 (s, 4 H), 7.09
(s, 4 H), 7.02 (s, 8 H), 6.97 (d, 4 H, J ) 2.1 Hz), 6.63 (t, 2 H, J
) 4.0 Hz), 4.89 (d, 4 H, J ) 4.9 Hz), 4.39 (d, 4 H, J ) 13.1 Hz),
4.20 (d, 4 H, J ) 13.6 Hz), 3.43 (d, 4 H, J ) 13.0 Hz), 3.38 (d,
4 H, J ) 13.8 Hz), 1.26 (s, 18 H), 1.21 (s, 36 H), 1.18 (s, 18 H);
13C NMR (75 MHz, CDCl3) δ 149.5, 147.9, 143.6, 143.2, 133.7,
128.3, 128.1, 127.9, 126.6, 126.0, 125.9, 125.8, 125.7, 129.4,
71.3, 34.0, 33.0, 32.6; HRMS (FAB) m/z 1371.8562 for [M +
Na]+, calcd for C92H116O8Na M 1371.8626.
1,6-Bis(5,11,17,23-tetr a -ter t-bu tyl-25,26,27-tr ih yd r oxy-
28-oxyca lix[4]a r en e)-2,4-h exa d iyn e (17). To a degassed
solution of 3 (0.425 g, 0.61 mmol) in dry Et3N/DMF (30:3 mL)
were added Pd(PPh3)2Cl2 (0.04 g) and CuI (0.230 g). The
reaction mixture was stirred at room temperature for 1 h.
Filtration over Celite was followed by concentration. Column
chromatography (dichloromethane/hexane 1:2) of the crude
gave 17 (0.156 g, 37%) as a solid: mp 85-87 °C; IR (KBr) ν
3406, 3258, 2361, 2342, 1485, 1362, 1204 cm-1; 1H NMR (300
MHz, CDCl3) δ 10.01 (s, 2 H), 9.12 (s, 4 H), 7.09 (s, 4H), 7.04
(d, 4 H, J ) 2.3 Hz), 7.03 (s, 4 H), 6.97 (d, 4 H, J ) 2.3 Hz),
5.03 (s, 4 H), 4.43 (d, 4 H, J ) 13.1 Hz), 4.26 (d, 4 H, J ) 13.6
Hz), 3.46 (d, 4 H, J ) 13.1 Hz), 3.42 (d, 4 H, J ) 13.6 Hz),
1.21, 1.20, 1.20, 1.18 (3 s, 72 H); 13C NMR (75 MHz, CDCl3) δ
148.9, 148.4, 147.8, 143.7, 143.3, 133.6, 128.2, 128.0, 127.7,
126.7, 125.9, 125.8, 125.6, 74.8, 72.8, 64.0, 34.3, 34.0, 33.0, 32.7,
31.5, 31.3; HRMS (FAB) m/z 1393.8435 for [M + Na]+, calcd
for C94H114O8Na M 1393.8411.
(Z,E)-1,4-Bis(5,11,17,23-tetr a -ter t-bu tyl-25,26,27-tr ih y-
d r oxy-28-oxyca lix[4]a r en e)-2-bu ten e (20 + 21). To a solu-
tion of 5 (0.200 g, 0.029 mmol) in dry dichloromethane (2 mL)
was added Grubbs’ catalyst [bis(tricyclohexylphosphine)ben-
zylidene ruthenium(IV) dichloride] (0.012 g, 0.003 mmol). The
resulting solution was allowed to reflux under a nitrogen
atmosphere for 7 h. Concentration yielded a crude produt that
was purified by column chromatography (dichloromethane/
hexane 1:1) giving 20 + 21 (0.140 g, 72%) as a solid: 1H NMR
(300 MHz, CDCl3) selected signals δ 10.15 (s, 1.3 H, compound
20), 10.11 (s, 0.7 H, compound 21), 9.46 (s, 2.7 H compound
20), 9.44 (s, 1.3 H, compound 21), 7.10-6.90 (m, 16 H,
compounds 20 and 21), 6.69 (m, 1.3 H, compound 20), 6.63
(m, 0.7 H, compound 21), 4.89-4.80 (m, 4 H, compounds 20
and 21), 4.44 (d, J ) 13.0 Hz, compound 20), 4.14 (d, J ) 13.7
Hz, compound 20), 3.46 (d, J ) 13.0 Hz, compound 20), 3.29
1,10-Bis[5,11,17,23-tetr a -ter t-bu tyl-25,26,27-tr ih yd r oxy-
28-oxyca lix[4]a r en e]-4,6-d eca d iyn e (18). To a degassed
solution of 9 (0.250 g, 0.35 mmol) in dry Et3N/DMF (15:1 mL)
were added Pd(PPh3)2Cl2 (0.026 g) and CuI (0.075 g). The
reaction mixture was stirred at room temperature for 1 h.
Filtration over Celite was followed by concentration. Column
chromatography (dichloromethane/hexane 1:1) of the crude
gave 18 (0.237 g, 95%) as a solid: mp 210-212 °C; IR (KBr) ν
(d, J ) 13.8 Hz, compound 20), 1.26-1.1 (several s, 72 H); 13
C
NMR (75 MHz, CDCl3): δ 148.5, 147.9, 143.5, 413.1, 133.7,
128.3, 128.1, 128.0, 127.8, 126.6, 125.7, 130.2, 77.5, 34.0, 33.3,
32.5, 32.2, 31.8, 31.0; HRMS (FAB) m/z 1371.8562 [M + Na]+,
calcd for C92H116O8Na M 1371.8626.
1,4-Bis(5,11,17,23-tetr a -ter t-bu tyl-25,26,27-tr ih yd r oxy-
28-oxyca lix[4]a r en e)bu ta n e (22). A solution of 20 + 21
(0.150 g, 0.110 mmol) in methanol/THF (1:1, 20 mL) was
1
3329, 1485, 1460, 1362, 1298 1204 cm-1; H NMR (300 MHz,
CDCl3) δ 10.11 (s, 2 H), 9.48 (s, 4 H), 7.09 (s, 4 H), 7.06 (d, 4

4414 J . Org. Chem., Vol. 65, No. 14, 2000
Santoyo-Gonza´lez et al.
hydrogenated (3 atm) in the presence of Pd-C (50 mg). The
reaction was monitored by TLC (dichloromethane/hexane 1:2).
Filtration over Celite was followed by concentration and
purification of the resulting crude product by column chroma-
tography (dichloromethane/hexane 1:2) giving 22 (0.090 g,
40%) as a solid: mp 258-259 °C; IR (KBr) ν 3358, 3230, 1492,
1205, 1064 cm-1; 1H NMR (300 MHz, CDCl3) δ 10.18 (s, 2 H),
9.61 (s, 4 H), 7.10 (s, 4 H), 7.06 (d, 4 H, J ) 2.4 Hz), 7.03 (s, 4
H), 6.96 (d, 4 H, J ) 2.4 Hz), 4.43 (d, 4 H, J ) 12.9 Hz), 4.38
(br s, 4 H), 4.21 (d, 4 H, J ) 13.6 Hz), 3.46 (d, 4 H, J ) 13.0
Hz), 3.38 (d, 4 H, J ) 13.8 Hz), 2.62 (br s, 4 H), 1.21 (s, 18 H),
1.20 (s, 36 H), 1.19 (s, 18 H); 13C NMR (75 MHz, CDCl3) δ
149.4, 148.6, 143.6, 148.3, 147.8, 143.6, 143.1, 133.6, 128.4,
128.2, 127.6, 126.6, 125.8, 125.9, 76.5, 34.3, 34.1, 34.0, 33.0,
32.4, 29.8, 26.6; HRMS (FAB) m/z 1373.8712 for [M + Na]+,
calcd for C92H118O8Na M 1373.8724.
Ack n ow led gm en t. We thank Direccio´n General de
Investigacio´n Cient´ıfica y Te´cnica for financial support
(PB95-1207).
J O0003495