Efficient atom economic approaches towards macrocyclic crownamides via ring closure metathesis

Article abstract of DOI:10.1016/S0040-4039(02)00751-7

RCM of suitable 1,ω-dienes led to efficient atom economic synthetic approaches towards azacrown ether derivatives with eight- to twenty four-membered ring sizes.

Full text of DOI:10.1016/S0040-4039(02)00751-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4207–4210
Efficient atom economic approaches towards macrocyclic
crownamides via ring closure metathesis
Yehia A. Ibrahim,* Haider Behbehani and Maher R. Ibrahim
Chemistry Department, Faculty of Science, Kuwait University, PO Box 5969, Safat 13060, Kuwait
Received 30 January 2002; revised 27 March 2002; accepted 17 April 2002
Abstract—RCM of suitable 1,v-dienes led to efficient atom economic synthetic approaches towards azacrown ether derivatives
with eight- to twenty four-membered ring sizes. © 2002 Elsevier Science Ltd. All rights reserved.
Crown compounds and azacrown compounds consti-
tute important macrocyclic groups in supramolecular
chemistry. They have been shown to exhibit important
applications including selective ion separation and
detection, molecular recognition, catalysis, biological
applications as well as many other interesting applica-
tions in diverse fields of supramolecular chemistry.1,2
Synthetic approaches towards such macrocycles usually
suffer from low yields, losses of considerable amounts
of the starting precursors during the macrocyclization
step due to polymer formation in addition to the need
for high dilution conditions and template effect.1 We
have been investigating several synthetic approaches
towards macrocyclic azacrown compounds; some of
them showed useful applications in ion selective elec-
trodes and as spectrophotometric reagents.2 In the
present investigation we wish to report an interesting
efficient synthetic approach towards azacrown com-
pounds using ring closure metathesis as the key macro-
cyclization step.
been published.17 Molybdenum alkylidene (Schrock
catalysts)18 and ruthenium alkylidene (Grubbs’ cata-
lysts)16,19 have shown the best catalytic activity in the
area of RCM. The commercial availability and ease of
handling of some of the Grubbs’ catalysts (e.g. I) in
addition to their good tolerance of normal reaction
conditions and to a wide range of functional groups
attracted our attention for possible utility in the synthe-
sis of crown and azacrown macrocycles.
In the present work we report our initial investigations
on the application of RCM with catalyst I as the key
macrocyclization step in the synthesis of some diaza
and azacrown macrocyclic ethers. We have also investi-
gated the photo RCM technique recently reported by
Fu¨rstner and Ackermann20 using [(p-cymene)RuCl2]2
and PCy3 in the presence of normal laboratory neon
tubes for initiating this photo RCM. Table 1 illustrates
our results of the RCM reactions using these two
catalytic RCM techniques. Our results indicated that
whereas all attempts to conduct the catalytic RCM with
catalyst I were successful, the photo catalysis gave only
moderate yields of RCM products in two cases (runs 1
and 4, conditions b). Moreover, attempts to convert 3
into 15 (run 3) using photo RCM conditions20 gave less
than 10% conversion, yielding a mixture of products
including 15. Therefore, we applied in all other cases
catalyst I which showed excellent conversion yields
(Table 1).
Ring closure metathesis (RCM), a versatile technique
used for the formation of cyclic olefins has witnessed an
explosive growth in applications over the last decade. It
has been mainly applied for the formation of five- to
seven-membered carbocycles and heterocycles.3–7 Some
examples of macrocycle synthesis via RCM have been
reported.7–16 Several reviews dealing with RCM and
illustrating its wide range of applications have recently
Keywords: ring closure metathesis; 1,v-dienes; diazacycloalkenes;
diazadioxacycloalkenes; benzoazaoxacycloalkenes; dibenzoazadioxa-
cycloalkenes; dibenzodiazadioxacycloalkenes; tribenzoazatrioxacy-
cloalkenes; tetrabenzodiazatetraoxacycloalkenes.
* Corresponding author. Fax: (++965) 4816482; e-mail: yehiaai@
kuc01.kuniv.edu.kw
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00751-7

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Y. A. Ibrahim et al. / Tetrahedron Letters 43 (2002) 4207–4210
Table 1.
Scheme 1 illustrates our synthetic routes starting from
the appropriate readily available bistosylamides A and
C or tosylamide B, which were converted via their
potassium salts into the corresponding 1,v-dienes.
RCM of these dienes proceeded under mild conditions
using 2.5 mol% of I in CH2Cl2 to give excellent yields of
the corresponding macrocyclic products (Table 1).
In summary, the present work demonstrates the
efficient application of RCM techniques for the atom
economic synthesis of macrocyclic crown compounds
with potentially diverse applications in supramolecular
chemistry. Examples of RCM presented here offer one
of the best known macrocyclization reaction techniques
known for the synthesis of crown compounds. Applica-

Y. A. Ibrahim et al. / Tetrahedron Letters 43 (2002) 4207–4210
4209
Scheme 1.
tions of this method to the synthesis of other functional
derivatives of crown compounds are currently under
active investigation in our laboratory. Also, the macro-
cylic products of these RCM reactions are good start-
ing materials for other functional derivatives of
macrocycles through further transformation of the
newly formed double bond. We believe that removal of
the tosyl group will be possible using one of several
reported methods including LiAlH4 (under mild condi-
tions in THF, at 50°C) or by heating in KOH (in
DMSO at 80°C).1e,21
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Tetrahedron Lett. 1988, 29, 1709–1712; (f) Lehn, J. M.
Angew. Chem., Int. Ed. Engl. 1988, 27, 89–112; (g) Hamil-
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Acknowledgements
The support of the University of Kuwait received
through research grant no. SC01/00 and the facilities of
ANALAB and SAF are gratefully acknowledged.
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