A novel template method for preparing unidirectional kinetically inert metal complexes [9]

Full text of DOI:10.1021/ja973605c

2188
J. Am. Chem. Soc. 1998, 120, 2188-2189
A Novel Template Method for Preparing
Unidirectional Kinetically Inert Metal Complexes
Haim Weizman, Jacqueline Libman,† and Abraham Shanzer*
Department of Organic Chemistry
The Weizmann Institute of Science
RehoVot, 76100, Israel
Figure 1. Schematic representation of the synthetic strategy for preparing
unidirectional metal complexes. (a) Synthesis of a bifunctional binding
strands. (b) Attachment to a template. (c) Binding of kinetically inert
metal ion. (d) Template removal.
ReceiVed October 16, 1997
Metal complexes may serve as important building blocks for
molecular structures because of their unique structural and
physiochemical properties.1 So far, the design of most metal
containing structures has relied on symmetric ligands thus
preventing applications that rely on vectorial processes. The
limited availability of nonsymmetric, unidirectional metal com-
plexes is due to the fact that most of the preparation procedures
rely on spontaneous complexations. This results in a random
mutual orientation of nonsymmetric ligands leading to formation
of mixtures. For example, the complexation of nonsymmetric
ligands to octahedral complexes should theoretically result in a
1:3 ratio between the symmetric fac and nonsymmetric mer
isomers, but this ratio may shift dramatically toward the mer
isomer as a result of the ligand’s structure.2 Since the fac isomer
is the desired product, a better control over the ligand’s orientation
should be developed.
Scheme 1. Synthetic Scheme for Preparing Unidirectional
Chromium Tris Hydroxamate Complex
Examples for controlling the ligand’s direction by hydrophobic
interactions,3 by the trans effect,4 and by using two binding sites
with different binding affinities5 have been described. All of these
examples rely on the ligand’s structure and therefore cannot give
a general solution for controlling the ligand’s mutual orientation.
Since covalent templating has been successfully used for resolving
alignment problems and inducing chirality,6 it may be used for
preparing unidirectional metal complexes.
Here we introduce a general approach for preparing inert metal
complexes based on the use of a cyclic template for orienting
ligand strands (Figure 1). Complexation with a kinetically inert
metal ion followed by the template removal affords unidirectional
metal complexes. This method is suitable for preparing metal-
containing building blocks with complementary functional groups.
The feasibility of this method is demonstrated by preparing
octahedral Cr(III) and Ru(II) complexes with nonsymmetric chiral
binding units carrying amino and carboxylic acid groups on their
termini. For octahedral complexes where a second chiral center
is formed upon complexation (∆ or Λ), the chirality of the ligand
induces preferential formation of a given isomer in the diaster-
eomeric mixture. This enables monitoring of the orientation of
the ligand strands by circular dichroism (CD) and allows
separation between diastereoisomers. 1,3,5-Tris(hydroxymethyl)-
benzene was selected as a template, since it is suitable for
condensation with both carboxylic acids and amino groups (after
converting to isocyanates) to yield tris benzyl esters and tris benzyl
carbamates, respectively. Hydrogenolysis of the latter cleaves
the template and regenerates the original functional groups
(analogous to the benzyl and benzyloxycarbonyl protecting groups
in peptide synthesis).
The ligand for chromium was based on L-alanine-derived
hydroxamic acid (1, Scheme 1). Complexation of ligand 1 with
Cr(lll)7 produces the 1-Cr-T complex in which the UV/vis and
CD spectra (Table 1) are in agreement with Raymond’s published
spectra of tris hydroxamate chromium complexes.8 According
to the ∆ꢀ values, this is a diastreomeric mixture dominated by
the ∆ isomer. Hydrogenolysis of the complex removed the
template to form (1-Cr-D) as reflected by the disappearance of
the ester IR peak and by the appropriate FAB-MS. The CD
spectrum was identical to that of the templated complex. No
further separation between the diastroisomers was attempted.
The ligand for Ru(II) is based on 2,2′-bipyridine (bipy) which
was modified nonsymmetrically to contain carboxylic acid and a
protected amine groups on its 5 and 5′ positions9 (Scheme 2). A
chiral spacer (L-alanine) was introduced between the ligating
elements and the template to allow for the flexibility required
† Deceased, March 1997.
(1) Lehn, J. M. Supramolecular Chemistry: Concepts and PerspectiVes;
VCH: Weinheim, 1995; p 271. Philp, D.; Stoddart, J. F. Angew. Chem., Int.
Ed. Engl. 1996, 35, 1154-1196. Balzani, V.; Scandola, F. Supramolecular
Photochemistry; Ellis Horwood: New York, 1991; p 427. Beissel, T.; Powers,
R. E.; Raymond, K. N. Angew. Chem., Int. Ed. Engl. 1996, 35, 1084-1086.
Desmartin, P. G.; Williams, A. F. New. J. Chem. 1995, 19, 1109-1112.
Hasenknopf, B.; Lehn, J. M.; Baum, G.; Fenske, D. Proc. Natl. Acad. Sci.
U.S.A. 1996, 93, 1397-1400.
(2) Predieri, G.; Vignali, C.; Denti, G.; Serroni, S. Inorg. Chim. Acta 1993,
205, 145-148.
(3) Lieberman, M.; Sasaki, T. J. Am. Chem. Soc. 1991, 113, 1470-1471.
Ghadiri, M. R.; Case, M. A. Angew. Chem., Int. Ed. Engl. 1993, 32, 1594-
1597.
(4) Enemark, E. J.; Stack, T. D. P. Angew. Chem., Int. Ed. Engl. 1995, 34,
996-998.
(5) Piguet, C.; Hopfgartner, G.; Bocquet, B.; Schaad, O.; Williams, A. F.
J. Am. Chem. Soc. 1994, 116, 9092-9102. Albrecht, M.; Frochlich, R. J.
Am. Chem. Soc. 1997, 119, 1656-1661.
(7) The ligand and equivalent amounts of NaOAc and CrCl3‚3THF were
refluxed in dry CH3CN for 1 h. The complex was purified by preparative
TLC (CHCl3/6% MeOH), 30% yield.
(8) Leong, J.; Raymond, K. N. J. Am. Chem. Soc. 1975, 97, 293-296.
Detection, Determination, Isolation, Characterization and Regulation of
Microbial Iron Chelates; Matzanke, B. F., Ed.; CRC Press: Boston, 1991;
pp 15-64.
(6) Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of Organic
Compounds; Wiley: New York, 1994; pp 868-870. Guilhem, J.; Pascard,
C.; Sauvage, J. P.; Weiss, J. J. Am. Chem. Soc. 1988, 110, 8711-8713. Murner,
H.; von Zelewsky, A. Inorg. Chem. 1996, 35, 3931-3935. Woods, C. R.;
Benaglia, M.; Cozzi, F.; Siegel, J. S. Angew. Chem., Int. Ed. Engl. 1996, 35,
1830-1833.
(9) The synthesis was based on 5-ethyl ester 5′-carboxylic acid 2,2′-
bipyridine which was converted to carboazide and subsequently rearranged
and reacted with EtOH to give the 5-ethyl ester 5′-ethylcarbamate bipyridine.
The synthesis of the tripod was found to be more efficient if the triol was
first reacted with the amino acid to give the trisamine and then reacted with
the bipy unit.
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Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 9, 1998 2189
Table 1. Spectroscopic Data for Tripodal Ligands and Their Chromium and Ruthenium Complexes
cmpd
IR (cm-1)
UV λmax (ꢀ)
CD λext (∆ꢀ)
MS (m/e)
1
1736, 1707, 1657
1734, 1715, 1596
943.55
992.52
1-Cr-T
424 (61)
595 (58)
425 (60)
593 (60)
410 (-0.8), 465 (0), 542 (+1.52), 600 (0), 638 (-0.55)
410 (-0.75), 465 (0), 540 (+1.50), 600 (0), 642 (-0.4)
1-Cr-D
1700, 1650, 1597
877.26
2
1734, 1701, 1640
1733, 1701, 1651
1189.24
1290.50
2-Ru-T Λ
314 (67800)
460 (7600)
314 (67800)
460 (7600)
314 (67800)
460 (7600)
227 (-58), 290 (-48), 305 (0.0), 320 (+73), 350 (+92), 370 (0.0),
415 (-12.0), 451 (0.0), 468 (+6.0)
2-Ru-T ∆
2-Ru-D ∆
1733, 1701, 1651
1700, 1701, 1650
227 (0.0) 286 (+72), 302 (0.0), 319 (-68), 346 (-100), 366 (0.0),
412 (+12.7), 450 (0.0), 462 (-4.5)
1290.80
1176.40
227 (0.0), 286 (+68), 300 (0.0), 319 (-84), 346 (-100), 366 (0.0),
412 (+12.7), 450 (0.0), 462 (-7.5)
Scheme 2. Synthetic Scheme for Preparing Unidirectional
Ruthenium Tris Bipyridine Complex
Figure 2. CD spectra of 2-Ru-T ∆ before (s) and after template removal
(- - -) in MeOH.
NMR spectrum. The ꢀ/∆ꢀ ratio had the same value as prior to
the template removal, affirming no isomerization occurred (Figure
2). The complex was stable, and no isomerization was observed
even after heating it to 50 °C for several minutes. Because
racemization was not observed (Ray-Dutt or Bailar twists did not
occur14), it can be concluded that the directionality of the complex
was preserved.
The template method15 is the preferred choice for aligning
nonsymmetric ligands about inert metal ions, with the advantage
of exclusively generating the symmetric isomers, including
systems with orthogonal or complemental functional groups. In
addition, incorporating chiral centers into the ligating chains,16
optically pure complexes are easily obtained. Integration of these
are best demonstrated with chiral ligands possessing carboxylic
acids on one end and amino groups on the other, leading to the
formation of the first example of chiral “amino acids” metal-
containing building blocks. These building blocks are readily
available for stepwise oligomerization and multilayer formation
of anisotropic materials with electron and energy transfer proper-
ties. Efforts in these directions are currently in progress.
for Ru(II)-bipy tripod complexes10 and to permit separation
between the Λ and ∆ isomers. Separation of the complex to its
∆ and Λ components provides the shape and values for the fac
orientation. The retention of these values after removal of the
template will determine the extent to which the orientation of
the complexes has been preserved.
Ligand 2 was complexed with Ru(II)11 and gave two main
products which were separated by preparative TLC to give two
diasteriomers (2-Ru-T ∆ and 2-Ru-T Λ) as shown by their
identical MS, different NMR spectra,12 and CD Cotton effects
(Table 1). The unidirectionality of the strands was reflected by
a single set of peaks in the NMR spectrum. Hydrogenolysis of
the major product, 2-Ru-T ∆, resulted in the removal of the
template (2-Ru-D ∆) as reflected by the disappearance of the
aryl and benzyl peaks in the NMR spectrum (s, 7.32 ppm and
ABq, 5.08 ppm)13 and the appropriate MS. The fac symmetry
of the complex was conserved as indicated by the symmetric
Acknowledgment. This paper is dedicated to the memory of Dr.
Jacqueline Libman, whose untimely death was a great loss to her family,
to her colleagues, and to science. The authors thank Mr. Peter Oosting
for his technical assistance. Support of this work from the US-Israel
Binational Science Foundation, Israel Ministry of Science-Tashtyot
program and the Minerva Foundation, Munich, Germany is gratefully
acknowledged.
(10) Barigelletti, F.; De Cola, L.; Balzani, V.; Belser, P.; von Zelewsky,
A.; Vo¨gtle, F.; Ebmeyer, F.; Grammenudi, S. J. Am. Chem. Soc. 1989, 111,
4662-4668.
(11) Ethanolic solution of RuCl3 hydrate was added dropwise to a refluxed
solution of ligand 2 in EtOH and then refluxed for 18 h. The complexes were
purified over preparative TLC (8:1:0.35:0.1 CH3CN/BuOH/H2O/saturated
KNO3) 20% yield.
Supporting Information Available: NMR spectra (2 pages). See any
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JA973605C
(12) 2-Ru-T ∆ (CD3OD): δ 8.57 (m, 6H, Py), 8.29 (dd, J1 ) 1.9 Hz, J2
) 8.5 Hz, 3H, Py), 8.13 (d, J ) 2.3 Hz, 3H, Py), 8.06 (m, 3H, py), 8.01 (d,
J ) 1.5 Hz, 3H, Py), 7.32 (s, 3H, ArH), 5.08 (ABq, J ) 11.3 Hz, δ∆ ) 0.38,
6H, ArCH2), 4.67 (q, J ) 7.2 Hz, 3H, CRH), 4.08 (q, J ) 7.1 Hz, 6H,
CH2{Et}), 1.26 (d, J ) 7.2 Hz, 9H, CRHCH3), 1.20 (t, J ) 7.1 Hz, 9H,
CH3{Et}. 2-Ru-T Λ (CD3OD): δ 8.57 (m, 6H, Py), 8.36 (dd, J1 ) 1.9 Hz,
J2 ) 8.5 Hz 3H, Py), 8.28 (d, J ) 2.4 Hz, 3H, Py), 8.08 (dd, J1 ) 2.4 Hz, J2
) 8.6 Hz, 3H, Py), 7.87 (d, J ) 1.8 Hz, 3H, Py), 7.42 (s, 3H, ArH), 5.10
(ABq, J ) 11.8 Hz, δ∆ ) 0.15, 6H, ArCH2), 4.67 (q, J ) 7.2 Hz, 3H, CRH),
4.10 (q, J ) 7.1 Hz, 6H, CH2{Et}), 1.48 (d, J ) 7.3 Hz, 9H, CRHCH3), 1.21
(t, J ) 7.1 Hz, 9H, CH3{Et}).
(13) 2-Ru-D ∆ (CD3OD): δ 8.63 (d, J ) 8.6 Hz, 6H, Py), 8.44 (d, J )
8.6 Hz, 3H, Py), 8.24 (d, J ) 2.1 Hz, 3H, Py), 8.10 (m, 6H, Py), 5.00 (m, 3H,
CRH), 4.11 (q, J ) 7.1 Hz, 6H, CH2{Et}), 1.37 (b, 9H, CRHCH3), 1.22 (t, J
) 7.1 Hz, 9H, CH3{Et}).
(14) von Zelewsky A. Stereochemistry of Coordination Compounds
Concepts; John Wiley & Sons: Chichester, 1996; p 254.
(15) Complexes with different symmetries can be prepared by changing
the template symmetry [such as C2, C3, C4]
(16) Libman, J.; Tor, Y.; Shanzer, A. J. Am. Chem. Soc. 1987, 109, 5880-
5881. Shanzer, A.; Libman, J.; Lifson, S. Pure Appl. Chem. 1992, 64, 1421-
1435.