Design and formation of a large tetrahedral cluster using 1,1′-binaphthyl ligands

Article abstract of DOI:10.1002/anie.200801226

(Chemical Presented) Greater than 700 A³ is the calculated interior volume of a novel [Ga₄L₆] cluster constructed with a derivatized 1,1′-binaphthyl ligand. Due to the size of the cavity, a guest molecule of suitable size

Full text of DOI:10.1002/anie.200801226

Communications
DOI: 10.1002/anie.200801226
Supramolecular Chemistry
Design and Formation of a Large Tetrahedral Cluster Using
1,1’-Binaphthyl Ligands**
Shannon M. Biros, Robert M. Yeh, and Kenneth N. Raymond*
Many chemists have been fascinated with the development of
discrete supramolecular structures that encapsulate guest
molecules. These structures can be assembled through
covalent[1,2] or hydrogen bonds,[3] electrostatic[4] or metal–
ligand interactions.[5,6] These host structures have provided
valuable insight into the forces involved in small-molecule
recognition. Our work has focused on the design and study of
metal–ligand clusters of varying sizes.[7,8] The [M4L6]12À cluster
1 with a naphthalene derivative as the ligand[9] (Scheme 1a)
has demonstrated diastereoselective guest binding[10] and
chiral-induction properties[11] as well as the ability to catalyze
reactions carried out inside the cavity in an enzymelike
manner.[12] However, the size of the cavity (ca. 300 to 500 Š3)
has often limited the scope of substrates for these trans-
formations.[13]
In searching for new ligands for the construction of larger
M4L6 tetrahedra, we explored the derivatization of the 1,1’-
binaphthalene (binaph) core (Scheme 1a). When substituted
in the 5,5’ positions with catecholamides (8), the 1,1’-
binaphthalene unit, in the pseudo-C2h conformation, achieves
optimal relative positioning of the chelating groups for
formation of an M4L6 tetrahedron. This bis-catecholate
ligand is approximately 6.7 Š longer than the original
Scheme 1. a) Schematic diagrams of [M4L6]12À clusters: 1 with a
naphthalene ligand used to form cluster 1, resulting in a
naphthalene derivative as ligand[9] and 2 with a larger binaphthyl
calculated cavity size of at least 700 Š3.[14]
derivative as ligand; b) synthesis of binaph ligand 8.
The synthesis of bis-catecholate ligand 8 was accom-
plished in the modular manner shown in Scheme 1b. Selective
bromination of nitronaphthalene 3 followed by reduction
with iron in acetic acid gives mono-amine 4[17]. Acylation with
the acid chloride of 2,3-dimethoxybenzoic acid (5) provides
the aryl bromide 6 in good yield. This aryl bromide can be
dimerized efficiently under modified Suzuki conditions and
globally deprotected by using BBr3 to give final product 8.
In the case of the naphthalene-based cluster 1, the
assembly can be prepared at room temperature and in the
absence of guest molecules due to the rigid nature of the host
ligands. The cavity of this “empty” cluster is likely filled with
solvent molecules. Not surprisingly, with binaph ligand 8,
cluster formation requires both heating (due to the additional
six freely rotatable bonds) and the presence of a suitable guest
to thermodynamically template the assembly. As guests for
this system tetraalkylammonium salts were chosen due to a
readily available range of sizes and their compatibility with
supramolecular assemblies.[3,7,8] The thin outer layer of
positive charge on these salts is highly complementary to
the electron-rich interior surface of the clusterꢀs aromatic
walls. Dissolution of ligand 8 (6 equiv) in methanol with an
excess of R4NBr, base (KOH), and [Ga(acac)3] (4 equiv)
followed by heating provides the desired Ga–binaph host–
guest complexes. The 1H NMR spectra of these complexes are
shown in Figure 1.
[*]S. M. Biros, R. M. Yeh, K. N. Raymond
Department of Chemistry
University of California
Berkeley, CA 94720-1460 (USA)
Fax: (+1)510-486-5283
E-mail: raymond@socrates.berkeley.edu
Homepage: http://www.cchem.berkeley.edu/knrgrp/home.html
[**]We gratefully acknowledge financial support from the Director,
Office of Science, Office of Basic Energy Sciences, and the Division
of Chemical Sciences, Geosciences, and Biosciences of the US
Department of Energy at LBNL under Contract No. DE-AC02-
05CH11231. We thank Prof. R. G. Bergman, M. D. Pluth, C. J.
Hastings, and B. E. Tiedemann for helpful discussions and Dr. Ulla
Anderson for assistance with mass spectrometry experiments.
Supporting information for this article (detailed procedures for the
preparation of compounds 4, 6, 7, 8, and all Ga4L6–guest complexes
as well as the characterization data) is available on the WWW under
http://dx.doi.org/10.1002/anie.200801226.
The host–guest assemblies formed from the binaph
ligands and the tetraalkylammonium salts Pr4N+, Bu4N+,
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same configuration, much like their naphthalene predecessor.
The complex with Pr4N+ as the guest molecule shows nine
groups of aromatic resonance signals in this region, although
in this case there is some degree of asymmetry between the
ligands. This is likely a factor resulting from the ligands
“puckering” in toward the cavity to maximize contact with the
smaller guest molecules. This host also demonstrates size
selectivity: Et4N+ is too small to efficiently template the
Ga4L6 assembly, while (n-hexyl)4N+ is too large.
1
Further analysis of the H NMR spectra of these com-
plexes reveals information about the conformation of bound
guest molecules. As the alkyl chain length of the guest
molecule increases from propyl to pentyl, the resonance
signal corresponding to the methyl group progressively shifts
downfield (see Figure 1). This indicates a coiling of the alkyl
chains toward the center of the cavity as the size of the guest
increases.[16] Diastereotopic splitting of the geminal methyl-
ene proton resonance signals of the bound guest molecule is
also observed (see Figure 1), indicating that the host cavity is
chiral in nature.
1
Figure 1. Upfield and host-ligand portions of the H NMR spectra
(500 MHz, CD3OD) of Ga–binaph complexes with a series of tetraalkyl-
ammonium salts as guests: Pr4N+, Bu4N+,and (n-pentyl)4N+; peaks
&
*
marked with represent CH3 groups and peaks marked with
represent the CH2 groups of bound guest molecules.
Further evidence for host–guest complex formation is
provided by 2D NOESY experiments (Figure 2). For
{Bu4N+ꢁ[Ga4(binaph)6]}11À (where ꢁ denotes encapsulation),
strong NOE cross peaks are observed between the proton
resonance signals of the guest molecule and those of the
aromatic protons of the host ligands. This indicates close
through-space contacts between host and guest, concurrent
with a stable host–guest complex.
and (n-pentyl)4N+ are readily soluble in methanol and, to a
lesser extent, water. As expected, the resonance signals
corresponding to bound guest molecules are shifted upfield
(Dd ꢀ 3 ppm) in response to the shielding effect of the
aromatic host ligands. Integration of the 1H NMR spectra
indicates that the host–guest complexes have a stoichiometry
of six binaph ligands to one interior (bound) R4N+ to six
exterior (free) R4N+ cations. These exterior ions are likely
involved in cation–p interactions with the aromatic faces of
each ligand.[9] The presence of peaks for both free and bound
guest molecules in the 1H NMR spectra show that these
complexes are kinetically stable on the NMR time scale.
Cation–p[15] and CH–p interactions between host and guest as
well as desolvation effects likely contribute favorably to host–
guest complex formation.
Quaternary phosphonium salts bearing aromatic substitu-
ents are also suitable guests for this host. Triphenylpropyl-,
triphenylbutyl- and tetraphenylphosphonium efficiently tem-
plate the assembly of [Ga4(binaph)6]12À. The {Ph4P+ꢁ[Ga4-
(binaph)6]}11À complex retains overall T symmetry (Figure 3).
1
However, the aromatic regions of the H NMR spectra of
{[Ph3PrP+ꢁ[Ga4(binaph)6]}11À
and
[Ph3BuP+ꢁ[Ga4-
(binaph)6]}11À show 36 sets of resonance signals corresponding
to the aromatic hydrogen atoms of the host ligands. This
indicates a decrease in the overall symmetry of the host–guest
complex, likely resulting from a hindered rotation of the C3-
symmetric guest inside the hostꢀs cavity. A second possible
explanation for these complex 1H NMR spectra is that a
different host–guest assembly is
[Ga4(binaph)6]12À complexes containing Bu4N+ or (n-
pentyl)4N+ show nine resonance signals in the aromatic
1
region of the H NMR spectrum corresponding to the host
hydrogen atoms (Figure 2). This indicates that the complexes
have overall T symmetry with each gallium center having the
formed in the presence of a non-
ideal guest for the Ga4L6 struc-
ture. These theories are difficult
to prove without X-ray structural
data, however high-resolution
mass spectra of these complexes
(see below) support the forma-
tion of a complex with [Ga4L6-
(R4P+)] stoichiometry.
The host–guest complexes
were further analyzed using
high-resolution ESI-QTOF mass
spectrometry. The identity of the
complexes can be readily con-
firmed by their complex isotopic
pattern at various charge states.
For instance, the predicted
Figure 2. Left: Minimized structure (host: CPK colors, guest: orange CPK spheres; CAChe, version 6.1,
MM3); right: 2D NOESY spectrum (500 MHz, CD3OD) of {Bu4N+ꢁ[Ga4(binaph)6]}11À
.
Angew. Chem. Int. Ed. 2008, 47, 6062 –6064
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Communications
Keywords: chiral recognition · metal–ligand assembly ·
.
self-assembly · supramolecular chemistry
[1] F. Diederich, Cyclophanes: Monographs in Supramolecular
Chemistry, Royal Society of Chemistry, Cambridge, 1991.
[2] D. J. Cram, Container Molecules and Their Guests, Vol. 4, Royal
Society of Chemistry, Cambridge, 1994.
[3] F. Hof, S. L. Craig, C. Nuckolls, J. Rebek, Jr., Angew. Chem.
2002, 114, 1556; Angew. Chem. Int. Ed. 2002, 41, 1488.
[4] F. Corbellini, R. M. A. Knegtel, P. D. J. Grootenhuis, M. Crego-
Calama, D. N. Reinhoudt, Chem. Eur. J. 2005, 11, 298.
[5] M. A. Pitt, D. W. Johnson, Chem. Soc. Rev. 2007, 36, 1441.
[6] M. Fujita, M. Tominaga, A. Hori, B. Therrien, Acc. Chem. Res.
2005, 38, 371.
[7] D. L. Caulder, K. N. Raymond, Acc. Chem. Res. 1999, 32, 975.
[8] D. W. Johnson, K. N. Raymond, Inorg. Chem. 2001, 40, 5157.
[9] D. L. Caulder, R. E. Powers, T. N. Parac, K. N. Raymond,
Angew. Chem. 1998, 110, 1940; Angew. Chem. Int. Ed. 1998,
37, 1840.
1
Figure 3. Aromatic and upfield regions of the H NMR spectra
(500 MHz, CD3OD) of [Ga4(binaph)6]12À complexes with quaternary
+
+
+
*
phosphonium guests: Ph4P , Ph3PrP , Ph3BuP ; : resonance signals
&
of free guest molecules; : resonance signals of bound guest
molecules (one signal for each complex is beneath the solvent peak at
d=4.8); : resonance signals of the host [Ga4(binaph)6]
[10] D. Fiedler, D. H. Leung, R. G. Bergman, K. N. Raymond, J. Am.
Chem. Soc. 2004, 126, 3674.
12À
~
.
[11] D. H. Leung, D. Fiedler, R. G. Bergman, K. N. Raymond,
Angew. Chem. 2004, 116, 981; Angew. Chem. Int. Ed. 2004, 43,
963.
[12] M. D. Pluth, R. G. Bergman, K. N. Raymond, Science 2007, 316,
85.
m/z peak for [Bu4N+K5{Bu4N+ꢁ[Ga4(binaph)6]}]5À is 854.778,
and the observed value is 854.779. The predicted isotopic
splitting pattern of this peak is also in excellent agreement
with the experimental data (see the Supporting Information).
We have described herein the use of a bis-catecholate-1,1’-
binaphthalene ligand to form a novel self-assembled Ga4L6
cluster. This host binds larger guest molecules than previous
assemblies we have reported. Future work will explore guest
scope, the compatibility of host formation with varying metal
centers, and the dynamics of guest exchange. In addition, the
larger cavity will be exploited to facilitate reactivity.
[13] D. H. Leung, R. G. Bergman, K. N. Raymond, J. Am. Chem. Soc.
2007, 129, 2746.
[14] Cavity-volume calculations were carried out using Voidoo with a
1.4 Š diameter rolling ball on a minimized calculated structure
(CAChe) of the Ga4(binaph)6 assembly: a) G. J. Kleywegt, J. Y.
Zou, M. Kjeldgaard, T. A. Jones, International Tables for
Crystallography, Vol. F, Springer, Heidelberg, 2001; b) G. J.
Kleywegt, T. A. Jones, Acta Crystallogr. Sect. D 1994, 50, 178 –
185.
[15] J. C. Ma, D. A. Dougherty, Chem. Rev. 1997, 97, 1303.
[16] L. C. Palmer, J. Rebek, Jr., Org. Lett. 2005, 7, 787.
[17] L. H. Klemm, J. W. Sprague, E. Y. K. Mak, J. Org. Chem. 1957,
22, 161.
Received: March 13, 2008
Published online: June 20, 2008
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Angew. Chem. Int. Ed. 2008, 47, 6062 –6064