Synthesis of macrocyclic inclusion complexes using olefin metathesis

Article abstract of DOI:10.1055/s-1999-2923

The ruthenium-catalysed synthesis of a macrocyclic chelate is described. The reaction proceeds at room temperature using 5% catalyst to afford 4 in 80% isolated yield.

Full text of DOI:10.1055/s-1999-2923

LETTER
1749
Synthesis of Macrocyclic Inclusion Complexes Using Olefin Metathesis
Po Ling Ng, John N. Lambert*
School of Chemistry, The University of Melbourne, Grattan Street, Parkville, Victoria 3052, Australia
Fax +613-9347-5180; e-mail j.lambert@chemistry.unimelb.edu.au
Received 1 July 1999
2,6-dibutenylpyridine (DBP) 2 which was reacted with
trans-bis(benzonitrile)dichloropalladium(II) to give the
complex trans-[PdCl2(DBP)2] 3 (Scheme 1).
Abstract: The ruthenium-catalysed synthesis of a macrocyclic che-
late is described. The reaction proceeds at room temperature using
5% catalyst to afford 4 in 80% isolated yield.
Key words: metathesis, macrocycles, ruthenium, ring closure, mo-
lecular recognition
The ability of macrocyclic compounds to sequester vari-
ous metal atoms and form useful inclusion complexes has
seen their widespread application in molecular recogni-
tion and metal ion transport.1 Many macrocyclic synthe-
ses overcome the entropic barrier to closure of medium to
large rings by the exploitation of a template effect where
the termini of linear precursors are favorably disposed to-
wards intramolecular reaction. In this regard, templated
macrocyclic syntheses have previously been performed
using either kinetically inert or kinetically labile complex-
es. In general, where the ligand itself is the synthetic tar-
get, labile templates are preferred while in cases where the
macrocyclic complex is the target, inert complexes are
usually employed. Recent reports of templated ring-clos-
ing metathesis (RCM)2 promoted by the Grubbs rutheni-
um catalyst 1 have detailed the synthesis of macrocycles
using kinetically labile metal ion coordination.3,4 In these
Scheme 1
and other cases where RCM has been used to form mac- The x-ray crystal structure of complex 3 showed a high
rocyclic closures, a mixture of geometric isomers is gen- degree of similarity to that reported for its DAP analogue.7
erally obtained. Here we report the synthesis of a The most notable feature was the orthogonal orientation
macrocyclic (18-membered) inclusion complex in high of the pyridine rings relative to the square planar coordi-
yield as a single geometric isomer using olefin metathesis nation environment and the nearly coplanar arrangement
of a kinetically inert precursor.5
of the pyridine rings with respect to the first three carbon
atoms of their olefinic side chains.
We chose to study the reactions of 2,6-disubstituted pyri-
dine diene ligands that had been preorganised around a
central palladium (II) centre. It was envisaged that RCM
of templated olefins would be largely dependent on the
ability of the olefinic arms to span the rift between the
trans-disposed coordination sites of the central palladium
(II) complex with minimal distortion of the square planar
coordination environment. Furthermore, our choice of
complex was partly based upon assurances that the reac-
tive olefins would not themselves be coordinated to the
central metal atom as we expected that this would impede
their metathesis. Initially, we prepared the previously re-
ported 2,6-diallylpyridine (DAP) complex trans-
[PdCl2(DAP)2] which has been found not to engage in ole-
fin-metal coordination.6 When exposed to catalyst 1 in
dichloromethane for three days, we observed no evidence
for any degree of olefinic metathesis. Failure of trans-
[PdCl2(DAP)2] to engage in metathesis is attributed to the
development of excessive ring strain. We then prepared
X-ray analysis of complex 3
Figure 1
Synlett 1999, No. 11, 1749–1750 ISSN 0936-5214 © Thieme Stuttgart · New York

1750
P. L. Ng, J. N. Lambert
LETTER
When exposed to Grubbs catalyst (5 mol%) at ambient the double bond geometry that will facilitate further con-
temperatures for 30 hours, complex 3 underwent metathe- trolled modifications as these sites. Given the general in-
sis to form the macrocyclic chelate 4 in 80% isolated yield terest in these macrocyclic complexes and the tolerant
(Scheme 2).8
nature of catalyst 1, we anticipate that many related com-
plexes would also be available using this methodology.
Acknowledgement
We thank Drs Robert Gable and Jonathan White for x-ray crystallo-
graphic analyses.
References and Notes
(1) Dietrich, B.; Viout, P.; Lehn, J.-M. Macrocyclic Chemistry;
VCH: Weinheim, 1993.
(2) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
(3) Marsella, M. J.; Maynard, H. D.; Grubbs, R. H. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1101.
Scheme 2
(4) Mohr, B.; Weck, M.; Sauvage, J.-P.; Grubbs, R. H. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1308.
(5) Martin-Alvarez, J. M.; Hampel, F.; Arif, A. M.; Gladysz, J. A.
Organometallics 1999, 18, 955.
(6) Vasapollo, G.; Nobile, F. C.; Latronico, M.; Lanfranchi, M.;
Pellinghelli, M. A. J. Organomet. Chem. 1987, 336, 429.
(7) Gable, R. W.; Lambert, J. N.; Ng, P.-L.; White, J. M. Acta
Cryst. C. 1999, Submitted.
The structure of 4 was initially supported by mass spectro-
metric and NMR analysis. The 1H NMR of 4 showed the
complete degeneracy of the olefinic protons into a multip-
let but it was not possible to unambiguously assign the ge-
ometry of the new olefins as either E or Z except to say
that the product had been formed as a single geometric
isomer. In a control experiments, attempted metathesis of
both the free ligand 2 and its acetate salt failed to deliver
the products of any metathesis-type processes. The struc-
ture of the product was confirmed by x-ray crystallogra-
phy and revealed that the geometry of the newly formed
olefin was Z .7 The x-ray analysis also confirmed the for-
mation of the 18-membered macrocycle and showed that
the pyridine rings were now tilted away from their initial-
ly orthogonal orientation, presumably to accommodate
the strain of the new macrocyclic ligand. In a previous re-
port, Grubbs and coworkers established that related reac-
tions are under thermodynamic control and the present
example is presumably also under such control.3 The ex-
clusive formation of the Z-isomer here is probably a re-
flection on the higher strain energy of the geometric
alternative: an outcome that is consistent with molecular
modeling studies where we compared the relative ener-
gies of the E- and Z-isomers using PCMODEL and found
the Z-isomer to be of significantly (ca 30kcal mol-1) lower
energy than the E-isomer.
(8) A solution of ruthenium catalyst 1 (8mg, 0.01mmole, 5mol%)
in dry CH2Cl2 (1mL) was added to a stirred solution of
complex 3 (108mg, 0.196mmol) in dry CH2Cl2 (5mL). The
resulting mixture was left to stir at room temperature for 6h
under nitrogen. Another batch of catalyst (5mol%) was then
added and the reaction mixture was left to stir for 18h and then
a further batch of catalyst (5mol%) was added and the reaction
stirred for 6h. Water (20mL) and CH2Cl2 (15mL) were added
to the reaction mixture and left to stir for 30min. The organic
phase was then collected and the aqueous phase was extracted
with CH2Cl2 (3x20mL). The combined organic phases were
dried over Na2SO4, filtered and concentrated. The crude solid
was purified by TLC chromatography (Rf 0.11; 3:7 ethyl
acetate:light petroleum) to yield a light yellow solid (82mg,
80%). Crystals for the X-ray study were obtained by slow
diffusion of hexane into saturated chloroform solution. Mp
159-166 oC. 1HNMR (CDCl3, 300MHz): d 7.61(t, J=7.5Hz,
1H), 7.16(d, J=7.5Hz, 2H), 6.03-5.95(m, 2H), 3.99 (t,
J=7.2Hz, 4H), 3.21(m, 4H); 13CNMR (CDCl3, 75MHz):
d171.12, 147.81, 139.64, 132.24, 50.25, 36.81; MS: (FAB, m/
z) 496(M+. (108Pd, 35Cl) 1%), 495(M+.(106Pd, 5%),
494(M+.(106Pd, 35Cl), 8%), 319(M+. – PdCl2 + H, 21%),
215(100%).
In summary, we have shown that RCM represents a viable
approach to the synthesis of macrocyclic chelates. An ad-
ditional feature is the complete geometrical control over
Article Identifier:
1437-2096,E;1999,0,11,1749,1750,ftx,en;G17499ST.pdf
Synlett 1999, No. 11, 1749–1750 ISSN 0936-5214 © Thieme Stuttgart · New York