Entrapment of a dirhodium tetracarboxylate unit inside the aromatic bowl of a calix[4]arene: Unique catalysts for C-H amination

Article abstract of DOI:10.1039/b611280c

Unique calix[4]arene-derived, tetracarboxylate dirhodium(ii) inclusion complexes have been prepared and evaluated as catalysts for C-H amination. The Royal Society of Chemistry.

Full text of DOI:10.1039/b611280c

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Entrapment of a dirhodium tetracarboxylate unit inside the aromatic
bowl of a calix[4]arene: Unique catalysts for C–H amination{
Benjamin H. Brodsky and J. Du Bois*
Received (in Cambridge, UK) 4th August 2006, Accepted 30th August 2006
First published as an Advance Article on the web 26th September 2006
DOI: 10.1039/b611280c
platform upon which to base such a design.5–7 The availability of
Unique calix[4]arene-derived, tetracarboxylate dirhodium(II)
selective methods for the functionalization of calix[4]arenes further
enables this plan. Following this rationale, we have exploited the
chemistry of calix[4]arenes for the preparation of CLX-H4, a
unique tetracarboxylate ligand that we hoped would furnish the
desired C4-symmetric dirhodium complex.
inclusion complexes have been prepared and evaluated as
catalysts for C–H amination.
Rhodium-catalyzed oxidative amination of saturated C–H bonds
has advanced as a valuable method for the construction of
stereodefined carbamine centers.1 The continued evolution of this
and related processes, however, necessitates the development of
new, robust catalyst systems capable of enhancing reaction yields
and influencing product selectivities. Motivated by such pursuits,
our group has described the preparation and highlighted the
performance of a unique dinuclear Rh(II) catalyst, Rh2(esp)2. In
this complex, a pair of covalently linked carboxylate ligands span
cis-equatorial sites on the dirhodium center (Fig. 1).2 The marked
stability of Rh2(esp)2 under oxidizing reaction conditions enables
C–H amination with sulfamate and carbamate esters to be
conducted at low catalyst loadings (0.1–2 mol%) and significantly
broadens the scope of this chemistry to include urea, guanidine,
and sulfamide substrates.3,4 Based on these findings, we considered
next generation catalyst designs in which three or four carboxylate
groups would be affixed to a common frame. From an
architectural standpoint, devising a tethered tetracarboxylate
ligand for these types of lantern-like dimetallic structures offers
an enticing challenge. Herein, we present a strategy aimed at such a
goal using a 4-fold symmetric calixarene-based platform. Although
the assembled dirhodium complexes differ from the expected form,
they are novel structural entities and highly effective catalysts for
C–H amination. The modular nature of these complexes has
empowered investigations aimed at understanding the influence of
the equatorial bridging ligands on catalyst function.
Synthesis of the target ligand is readily accomplished in two
steps from a substituted calix[4]arene 1, and affords CLX-H4 in
high yield (Fig. 2).8 The four phenolic hydroxyl groups of the
lower rim of the calixarene were intentionally left unprotected, as
the intramolecular hydrogen bond network established between
these moieties sustains the requisite CLX-H4 ‘‘cone’’ conforma-
tion.5 We anticipated that the strong preorganizational influence of
these hydrogen bonds would be critical for achieving selective
chelation of the dinuclear Rh core in preference to competing
oligomerization processes.
Treatment of Rh2(OAc)4 with CLX-H4 afforded a single
tractable product as a dark green crystalline solid in 67% isolated
yield. The 1H NMR spectrum{ of this species, however, was
inconsistent with that expected for the product of complete acetate
exchange. Two singlets assigned as acetate –CH3 groups are
present in the spectrum (d = 1.88 and 22.30 ppm), accordant with
a complex having the general formula Rh2(CLX-H2)(OAc)2. The
extreme upfield shift of one of these signals (22.30 ppm) gave
strong evidence that one acetate ligand was entrapped in the
aromatic bowl of the calixarene. Subsequent X-ray crystal-
lographic analysis of Rh2(CLX-H2)(OAc)2 confirmed that two
carboxylate arms of CLX–H2 had bridged the dirhodium core in a
trans orientation (Fig. 3). The two carboxylic acid groups which
failed to adopt an equatorial mode of coordination instead occupy
both axial sites along the Rh–Rh vector. In all, Rh2(CLX-
H2)(OAc)2 2 possesses a most unusual mixed carboxylate ligand
set with a rare calixarene-encapsulated acetate unit.9–11 The
The strict geometrical constraints imposed by the paddlewheel
architecture of the Rh2(O2CR)4 unit limit the number of practical
scaffolds that may be employed to anchor four orthogonally
displayed carboxylate ligands. Calix[4]arenes, a readily accessed
class of macrocyclic, tetrameric phenols, represent one possible
Fig. 1 C–H amination mediated by Rh2(esp)2.
Department of Chemistry, Stanford University, Stanford, CA 94305-
5080, USA. E-mail: jdubois@stanford.edu; Fax: (+1)650-725-0259
{ Electronic supplementary information (ESI) available: experimental
procedures and characterization data. See DOI: 10.1039/b611280c
Fig. 2 Synthesis of a novel tetracarboxylate rhodium dimer.
Chem. Commun., 2006, 4715–4717 | 4715
This journal is ß The Royal Society of Chemistry 2006

View Article Online
Fig. 3 ORTEP representation (50% thermal ellipsoid probability) of
Rh2(CLX-H2)(OAc)2 2. Hydrogen atoms have been omitted for clarity.
Fig. 4 ORTEP representation (50% thermal ellipsoid probability) of
˚
Rh2(CLX-H2)(OAc)(O2CCF3) 3. Selected bond distances (A) and angles
˚
Selected bond distances (A) and angles (u): Rh1–Rh2 2.374(3), Rh1–O9
2.311(16), Rh1–O1 2.030(15), Rh2–O4 2.039(16), O7–Rh1–O3 89.5(7),
(u): Rh1–Rh2 2.3867(5), Rh1–O7 2.302(3), Rh2–O3 2.301(3), Rh1–O9
2.054(3), Rh1–O11 2.009(3), Rh1–O1 2.035(3), Rh1–O5 2.039(3), O1–O8
2.755(5), O4–O6 2.724(5), O1–H8–O8 164.72, O4–H4–O6 165.68.
O9–Rh1–Rh2 178.7(4), O2–Rh2–O4 176.5(7).
˚
measured Rh–Rh bond distance of 2.374 A is quite similar to those
Presumably, these H-bond contacts provide additional stabiliza-
tion to the complex.13 This image also captures what is possibly a
snap-shot of the mechanism by which carboxylic acids exchange
from axial to bridging equatorial coordination modes, and likely
explains why all four carboxylate arms of the calixarene do not
adopt a bridging coordination mode.14
of related dirhodium complexes bearing neutral axial O-atom
donor ligands.12
The ability to substitute one of the four bridging carboxylate
ligands selectively in Rh2(CLX-H2)(OAc)2 distinguishes this
complex from other dirhodium(II) lantern structures. We have
found that treating Rh2(CLX-H2)(OAc)2 with different carboxylic
acids results in the efficient displacement of only the solvent-
exposed acetate group (entries 1–6, Table 1). These new complexes
represent the first series of dinuclear Rh(II) adducts to bear three
disparate bridging carboxylate types. Single crystal X-ray analysis
of one of these, Rh2(CLX-H2)(OAc)(O2CCF3) 3 (entry 1), shows
the trifluoroacetate moiety positioned opposite the encapsulated
acetate (Fig. 4). Also apparent in this structure are intramolecular
H–bonds between the protons of the axial carboxylic acid ligands
and the bridging carboxylate groups (e.g., O8–H8–O1).
Importantly, the lability of the trifluoroacetate ligand in 3
facilitates selective metathesis reactions with hydroxypyridine and
carboxamide ligands (entries 7 and 8, Table 1), thus giving rise to
truly unique carboxylate–amidate hybrid structures. The ability to
vary a single carboxylate with other bridging groups should help
forward efforts to elucidate pathways for catalyst decomposition
vis-a´-vis ligand dissociation under the oxidizing conditions of our
C–H amination reaction.
A particularly striking and unanticipated feature of these
dirhodium complexes is the unprecedented trans relationship
between the two bridging carboxylate groups of CLX-H2. To the
best of our knowledge, all polycarboxylate ligands used to form
such lantern structures are linked to the metal centers in a cis-
orientation, as in the case of Rh2(esp)2 (Fig. 1).15 We suspected
that the mechanism for assembly of these unusual CLX-H2
complexes may initiate through non-covalent association between
a methyl group of the Rh2(OAc)4 starting material and the
calixarene pocket. As observed crystallographically in both 2 and
Table 1 Selective ligand metathesis reactionsa
˚
3, distances of 3.6–4.0 A from the a-carbon to the centroids of the
arene rings are indicative of strong C–H/p interactions.16 To
investigate the self-assembly process, metathesis reactions were
conducted using CLX-H4 and a series of Rh2(O2CR)4 adducts.
Due to the small volume of the calixarene cavity, CLX-H4 fails to
entrap larger carboxylate groups such as those in Rh2(O2CC2H5)4
and Rh2(O2CCF3)4. When using these starting materials, only
intractable polymeric materials are formed. Conversely, the
complex derived from Rh2(O2CH)4 can be generated, but in very
poor yield (18%). Such data intimate that cooperative non-
covalent interactions between the aromatic bowl of CLX-H4 and
guest ligands are critical for the efficient assembly of these
supramolecular systems.
Entry
R9C(O)XH
Starting Complex
Yield [%]
1
2
3
4
5
6
7
8
a
CF3CO2H
C6H5CO2H
Ph3CCO2H
o-PhC6H4CO2H
p-VinylC6H4CO2H
1-AdCO2Hb
2
2
2
2
2
2
3
3
85
84
80
81
91
79
67
47
2-Hydroxypyridine
C6H5C(O)NH2
A representative illustration of the dirhodium complex viewed
down the Rh–Rh axis. Typical reaction conditions employ 5 equiv
of R9C(O)XH, see supporting information for more details.
b
1-AdCO2H = 1-adamantylcarboxylic acid.
4716 | Chem. Commun., 2006, 4715–4717
This journal is ß The Royal Society of Chemistry 2006

View Article Online
Wiley-VCH, Weinheim, 2005, pp. 379; (c) P. Mu¨ller and C. Fruit, Chem.
Rev., 2003, 103, 2905; (d) P. Dauban and R. H. Dodd, Synlett, 2003,
1571.
Table 2 Comparative data for C–H amination mediated by CLX-
based Rh2 complexesa
2 C. G. Espino, K. W. Fiori, M. Kim and J. Du Bois, J. Am. Chem. Soc.,
2004, 126, 15378.
3 M. Kim, J. V. Mulcahy, C. G. Espino and J. Du Bois, Org. Lett., 2006,
8, 1073.
4 The enhanced stability exhibited by this catalyst is likely due to the
chelate effect provided by the tethered cis-dicarboxylate design, see: (a)
J. Bickley, R. Bonar-Law, T. McGrath, N. Singh and A. Steiner,
New J. Chem., 2004, 28, 425. See also: (b) H. M. L. Davies and
C. Venkataramani, Org. Lett., 2003, 5, 1403; (c) D. F. Taber,
R. P. Meagley, J. P. Louey and A. L. Rheingold, Inorg. Chim. Acta,
1995, 239, 25.
Conversion Yield
[%]
Entry Catalyst
Substrate [%]
1
2
3
Rh(CLX-H2)(OAc)2
Rh(CLX-H2)(OAc)(O2CCF3)
Rh(CLX-H2)(OAc)2
A
A
B
B
B
C
C
C
C
C
C
100
,10
90
,10
95
65
80
65
20
10
100
93
—
81
—
88
58
69
—
—
—
90
5 C. D. Gutsche, Calixarenes Revisited, The Royal Society of Chemistry,
Cambridge, 1998.
4
5
6
Rh(CLX-H2)(OAc)(O2CCF3)
Rh(CLX-H2)(OAc)(O2CCPh3)
Rh(CLX-H2)(OAc)2
6 S. Steyer, C. Jeunesse, D. Armspach, D. Matt and J. Harrowfield, in
Calixarenes 2001, ed. Z. Asfari, V. Bohmer, J. Harrowfield and J. Vicens,
Kluwer Academic Publishers, Dordrecht, 2001, pp. 513.
7 For examples of calix[4]arene-based ligands for dirhodium complexes,
see: (a) J. Seitz and G. Maas, Chem. Commun., 2002, 338; (b)
F. A. Cotton, P. Lei, C. Lin, C. A. Murillo, X. Wang, S.-Y. Yu and
Z.-X. Zhang, J. Am. Chem. Soc., 2004, 126, 1518.
7
8
Rh(CLX-H2)(OAc)(O2CCPh3)
Rh(CLX-H2)(OAc)(O2CAd)b
9
Rh2(O2CC7H15)4
Rh2(O2CCPh3)4
Rh2(esp)2
10
11
a
c
Reactions performed with 1.1 equiv of PhI(OAc)2 and 2.3 equiv of
MgO at 0.15 M [substrate] in CH2Cl2. Conversion percentages are
estimated based on integration of the 1H NMR of the unpurified
8 M. Almi, A. Arduini, A. Casnati, A. Pochini and R. Ungaro,
Tetrahedron, 1989, 45, 2177.
b
c
9 For previous examples of dimeric Rh compounds possessing mixed
carboxylate ligand sets, see 4c and (a) H. J. Callot, A.-M. Albrecht-
Gary, M. Al Joubbeh, B. Metz and F. Metz, Inorg. Chem., 1989, 28,
3633; (b) F. A. Cotton and J. L. Thompson, Inorg. Chim. Acta, 1984, 81,
193.
reaction
mixture.
Ad
=
1-adamantyl.
Rh2(esp)2
Rh2(a,a,a9,a9-tetramethyl-1,3-benzenedipropionate)2, see ref. 2.
=
The catalytic performance of the calixarene-based complexes for
the oxidative amination of C–H bonds is higher than almost all
other dinuclear Rh systems tested (Table 2). Of these, only
Rh2(esp)2 has proven more effective (entry 11). Interestingly,
catalyst turnover expresses a noted dependence on the steric and
electronic structure of the solvent-exposed mono-carboxylate
ligand. As an example, Rh2(CLX-H2)(OAc)(O2CCF3) 3, with its
highly labile trifluoroacetate goup, is entirely ineffective when
tested against two sulfamate esters (entries 2 and 4, Table 2). This
finding suggests that partial or complete dissociation of a single
bridging ligand may trigger catalyst decomposition. Conversely,
Rh2(CLX-H2)(OAc)(O2CCPh3) exhibits greater stability and
higher turnover numbers when compared to the parent diacetate
complex (entries 5 and 7). Studies to determine the precise
mechanistic reasons for these phenomena are currently in progress.
A unique family of dirhodium complexes supported by the
tetracarboxylate ligand CLX-H4 is described. Favorable non-
covalent interactions between the methyl group of an acetate
ligand and the aromatic walls of the calixarene frame make
possible the efficient assembly of these unprecedented lantern
structures. A second acetate bridge, which sits opposite the
calixarene, is readily exchanged with different carboxylate groups.
These mixed-carboxylate systems have been tested as catalysts for
C–H amination and display estimable performance when com-
pared to other known Rh dimers. Accordingly, access to disparate
dirhodium complexes based on the multidentate CLX-H4 ligand
will aid investigations to reveal the complex process(es) that lead to
catalyst inactivation and decomposition in these C–H oxidation
reactions. We anticipate that such insights will give way to
subsequent methodological advances for both intra- and inter-
molecular C–H functionalization chemistry.
10 For previous examples of ligand entrapment by calix[4]arenes, see ref. 6
and: (a) C. Jeunesse, D. Armspach and D. Matt, Chem. Commun., 2005,
5603; (b) C. Wieser-Jeunesse, D. Matt and A. De Cian, Angew. Chem.,
1998, 110, 3027, (Angew. Chem., Int. Ed., 1998, 37, 2861).
11 A) 2?EtOAc: C60H76O22Rh2: Mr = 1355.03, orthorhombic, space group
3
Pbca, a = 20.989(3), b = 19.577(3), c = 29.775(4) A, V = 12235(3) A , Z =
˚
˚
8, T = 170 K, 66 886 reflections measured, 12 453 unique (Rint
=
0.0490), m = 0.62 cm21, R1 = 0.0903, wR2 = 0.2045 for F0 . 4s(F0).
The hydroxyl groups of the axially disposed carboxylic acid ligands
display significant positional disorder, suggesting two H-bond interac-
tions with proximal carboxylate ligands. B) 3?Et2O: C60H75F3O21Rh2:
¯
Mr = 1395.02, triclinic, space group P1, a = 11.144(1), b = 15.847(2), c =
˚
17.717(2) A, a = 86.286(2), b = 88.553(2), c = 86.249(2)u, V =
3
˚
3115.0(5) A , Z = 2, T = 170 K, 20 750 reflections measured, 12 496
unique (Rint = 0.0397), m = 0.61 cm21, R1 = 0.0526, wR2 = 0.1370 for
F0 . 4s(F0). CCDC 606038 and CCDC 606037. For crystallographic
data in CIF or other electronic format see DOI: 10.1039/b611280c.
12 H. T. Chifotides and K. R. Dunbar, in Multiple Bonds Between Metal
Atoms, ed. F. A. Cotton, C. A. Murillo and R. A. Walton, Springer
Science and Business Media, Inc., New York, 3rd edn., 2005, pp. 465.
13 For examples of intramolecular hydrogen bonds between axial and
equatorial ligands of dinuclear Rh complexes, see: (a) K. Aoki and
M. A. Salam, Inorg. Chim. Acta, 2002, 339, 427; (b) K. Aoki, M. Inaba,
S. Teratani, H. Yamazaki and Y. Miyashita, Inorg. Chem., 1994, 33,
3018; (c) P. Lahuerta, J. Latorre, E. Peris, M. Sanau´ and S. Garc´ıa-
Granda, J. Organomet. Chem., 1993, 456, 279; (d) H. T. Chifotides,
K. R. Dunbar, J. H. Matonic and N. Katsaros, Inorg. Chem., 1992, 31,
4628; (e) P. Lahuerta, J. Paya´, E. Peris, M. A. Pellinghelli and
A. Tiripicchio, J. Organomet. Chem., 1989, 373, C5; (f) A. R.
Chakravarty, F. A. Cotton, D. A. Tocher and J. H. Tocher,
Organometallics, 1985, 4, 8.
14 P. Lahuerta and E. Peris, Inorg. Chem., 1992, 31, 4547.
15 See Ref. 4 and: (a) R. P. Bonar-Law, T. D. McGrath, N. Singh,
J. Bickley, C. Femoni and A. Steiner, J. Chem. Soc., Dalton Trans.,
2000, 4343; (b) J. F. Gallagher, G. Ferguson and A. J. McAlees, Acta
Crystallogr., Sect. C: Cryst. Struct. Commun., 1997, C53, 576.
16 (a) U. Darbost, M.-N. Rager, S. Petit, I. Jabin and O. Reinaud, J. Am.
Chem. Soc., 2005, 127, 8517; (b) O. Se´ne`que, M. Giorgi and O. Reinaud,
Chem. Commun., 2001, 984; (c) H. Takahashi, S. Tsuboyama,
Y. Umezawa, K. Honda and M. Nishio, Tetrahedron, 2000, 56, 6185;
(d) M. Nishio, Y. Umezawa, M. Hirota and Y. Takeuchi, Tetrahedron,
1995, 51, 8665; (e) G. D. Andreetti, R. Ungaro and A. Pochini, J. Chem.
Soc., Chem. Commun., 1979, 1005.
Notes and references
1 (a) J. Du Bois, Chemtracts, 2005, 18, 1; (b) C. G. Espino and J. Du Bois,
in Modern Rhodium-Catalyzed Organic Reactions, ed. P. A. Evans,
This journal is ß The Royal Society of Chemistry 2006
Chem. Commun., 2006, 4715–4717 | 4717