Tetrahedron Letters
Synthesis of cryptands with di-yne units via acetylenic homocoupling
reactions of C3 tripodands
a
a
a,
Vlad Paßscanu a, , Monica Cîrcu a, , Crina Socaci a,b, , Anamaria Terec , Albert Soran , Ion Grosu
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a Babeßs-Bolyai University, Center of Supramolecular Organic and Organometallic Chemistry (CSOOMC), 11 Arany Janos Str., 400028 Cluj-Napoca, Romania
b National Institute of Research and Development for Isotopic and Molecular Technologies–INCDTIM, 65-103 Donath, 400293 Cluj-Napoca, Romania
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 July 2013
Revised 14 August 2013
Accepted 4 September 2013
Available online 11 September 2013
Cryptands with di-yne units were obtained in good yields by the acetylenic homocoupling reaction of
tripodands possesing terminal ethynyl units on the pendant arms. The coupling reactions also led to iso-
meric bismacrocylic compounds, and the shifting of the process toward the products of intramolecular or
intermolecular coupling reactions was influenced by the structure of tripodands and by the coupling
reaction conditions.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Cryptands
Bismacrocycles
Hay homocoupling reaction
Di-ynes
Tripodands
The synthesis of three-dimensional, cage-like molecules is of
interest in the field of supramolecular chemistry.1 A large amount
of work has been dedicated toward the investigation of molecules
with a well-defined cavity, especially for their potential binding
properties.1 Due to their relative rigidity, buta-1,3-diyne-diyl spac-
ers represent a secure building block for the construction of such
three-dimensional molecular frameworks. Cryptands bearing this
structural unit have already proved to be useful in the study of
host–guest complexes.2,3 Despite their obvious potential, access
to these cage architectures is somewhat limited due to the lack
of consistent information on oxidative homoacetylenic coupling
as a synthetic pathway for the one-pot macrocyclization reaction.
As part of our work in this direction, we decided to investigate
the macrocyclization reaction of tripodands with different C3 cen-
tral units and similar pendant arms exhibiting terminal triple
bonds (I) and to monitor the formation of the corresponding crypt-
and-like compounds (II, Fig. 1). Symmetric tris-heteroaromatics
are interesting skeletons4 for capping cage molecules. Trithienyl-
methanophanes were reported by Oda,5 the thiophene rings being
bridged by alkene groups. The triphenylamine capping unit is
known for its fluorescence properties and its tri-amino derivative
has been reported by Vögtle as a precursor for the synthesis of a
bismacrocycle.6 The third target external unit (Fig. 1) bears three
1,3-dioxane groups (the linkage points are situated in the ketal
part of the heterocycles), and was reported by our group7 as a pos-
sible pre-organized synthon due to the conformational equilibrium
being shifted toward the conformer with the phenyl ring in an ax-
ial position for all three 1,3-dioxane units.
The proposed podands (I) exhibit favorable structures for the
building of cryptand-like architectures (II) due to the C3 symmetry
of the aromatic platforms, the presence of three terminal attach-
ment points with high reactivity (triple bonds), and the flexibility
of the pendant arms. In addition, they possess other advantages
such as being readily available and the reduced costs of starting
materials.
The synthesis of podands 4–6 started from the corresponding
alcohols 1–38 via nucleophilic substitution reactions with propar-
gyl bromide in a heterogeneous mixture of dichloromethane and
sodium hydroxide solution with tetrabutylammonium bromide
as a phase-transfer catalyst (Scheme 1). Podands 4–6 were isolated
in fair to good yields, either as oils in the case of triaromatic exter-
nal units (4 and 5; 90% and 87%, respectively), or as a solid in the
case of podand 6 (52%). The compounds were characterized in
solution by 1H and 13C NMR spectroscopy and by MS. The proce-
dure and the physico-chemical description of compounds 4 and 5
are provided in the Supplementary data section, while the synthe-
sis of 6 has already been reported.9
For podand 6, the solid state molecular structure was obtained
by single crystal X-ray diffraction measurements and the results
are reported in the Supplementary data section.10
The three podands with terminal triple bonds were submitted
to Cu(I)-catalyzed acetylenic homocoupling reactions (Scheme 2).
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Corresponding authors. Tel.: +40 264593833; fax: +40 264590818.
These authors contributed equally to this work.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.