A C2-symmetric, basic Fe(iii) carboxylate complex derived from a novel triptycene-based chelating carboxylate ligand

Article abstract of DOI:10.1039/c2dt31260c

A triptycene-based bis(benzoxazole) diacid ligand H₂L2 ^Ph4 bearing sterically encumbering groups was synthesized. Treatment of H₂L2^Ph4 with Fe(OTf)₃ afforded a C ₂-symmetric trinuclear iron

Full text of DOI:10.1039/c2dt31260c

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A C2-symmetric, basic Fe(III) carboxylate complex derived from a novel
triptycene-based chelating carboxylate ligand†
Yang Li, Justin J. Wilson, Loi H. Do, Ulf-Peter Apfel and Stephen J. Lippard*
Received 16th May 2012, Accepted 14th June 2012
DOI: 10.1039/c2dt31260c
A triptycene-based bis(benzoxazole) diacid ligand H2L2Ph4
In line with the long-term goal of our laboratory to prepare
biomimetic models of the diiron active site of soluble methane
monooxygenase hydroxylase (sMMOH) and related bacterial
monooxygenases (BMMs),9–12 we previously synthesized a
triptycene-based diester ligand L1 and studied its iron complexes
(Fig. 2).13 To better match the active sites of the BMMs, it is
desirable to replace the ester ligands of L1 with more biologi-
cally relevant carboxylate groups, such as those present in the
related ligand H2L2. Although H2L2 can be prepared by
hydrolysis of L1, subsequent attempts to access iron complexes
of this ligand afforded only intractable materials. We hypothesize
that the bridging coordination mode of carboxylate ligands14
may facilitate the formation of insoluble coordination polymers
in the case of H2L2. Inspired by the success imparted by
sterically encumbering carboxylate ligands to prevent such
polymerization reactions and produce the desired diiron
cores,10,15 we designed a modified version of the ligand,
H2L2Ph4, with bulky phenyl groups incorporated at the ortho
positions of each carboxylic acid in H2L2. For synthetic con-
venience, the para positions of the carboxylate arenes were also
similarly functionalized.
bearing sterically encumbering groups was synthesized.
Treatment of H2L2Ph4 with Fe(OTf)3 afforded
a C2-
symmetric trinuclear iron(III) complex, [NaFe3(L2Ph4)2(μ3-O)-
(μ-O2CCPh3)2(H2O)3](OTf)2 (8). The triiron core of this
complex adopts the well known “basic iron acetate” structure
where the heteroleptic carboxylates, comprising two
Ph3CCO2− and two (L2Ph4 2−
late bridges. The (L2
)
ligands, donate the six carboxy-
)
Ph4 2− ligand undergoes only minor con-
formational changes upon formation of the complex.
The chemical and physical properties of oxo-bridged triiron car-
boxylates, also known as “basic iron acetates” (Fig. 1), were
studied decades ago, and the trinuclear μ3-oxo structural motif is
recognized as a ubiquitous feature of iron carboxylate chemi-
stry.1 The widespread occurrence of the {Fe3O(O2CR)6}+ motif
is most likely a consequence of its thermodynamic stability, and
the unit has been employed as a useful building block of metal–
organic frameworks (MOFs) and other solid state materials.2–5 In
addition, this family of complexes displays interesting catalytic
properties in olefin epoxidation6 and the oxidation of C–H
bonds.7,8 Aside from its distinctive {Fe3O(O2CR)6}+/0 core,
several other features are characteristic of basic iron carboxy-
lates. Most such complexes are bridged by ligands derived from
six monocarboxylate ligands (Fig. 1). The use of chelating
diacetate ligands in the core has only recently been reported.8
Moreover, to our knowledge, basic iron acetates are all derived
from a homoleptic set of carboxylate bridges. No {Fe3O-
(O2CR)6}+ cores bearing a mixture of different carboxylate
bridges are known. Here, we describe a novel chiral C2-
symmetric complex having a triiron(III) basic carboxylate struc-
ture that extends the type of known compounds in this class.
This cluster contains a chelating dicarboxylate ligand with a trip-
tycene backbone. We report the synthesis, structure, and charac-
terization of the ligand, as well as the triiron(III) complex.
Fig. 1 Basic iron acetate.
Department of Chemistry, Massachusetts Institute of Technology,
Cambridge, MA 02139, USA. E-mail: lippard@mit.edu;
Fax: +1-617-258-8150; Tel: +1-617-253-1892
†Electronic supplementary information (ESI) available: Detailed exper-
imental procedures, compound characterization, and the results of 1H
and 13C NMR spectroscopic and single crystal X-ray diffraction studies.
CCDC 881380, 881378, and 881379 for compounds 2, H2L2Ph4 and
complex 8. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c2dt31260c
Fig. 2 Ligand L1 and proposed diacid ligands.
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Scheme 1 Synthesis of methyl anthranilate analog 6.
Scheme 2 Synthesis of H2L2Ph4
.
Our proposed synthetic pathway to H2L2Ph4 used the
diphenyl substituted methyl (3-hydroxy)anthranilate analog 6 as
the starting material. The synthesis of 6 commenced with
3-chloro-2-nitrobenzolic acid (Scheme 1). Hydroxylation of this
electron deficient chlorobenzene gave 3-hydroxy-2-nitrobenzoic
acid (1) in quantitative yield. Although dibromination of 1 using
Br2–HOAc has been reported,16 we found the conditions to be
too harsh, for they produced many side products. An improved
reaction condition (Br2–NaOAc in EtOH) was devised that
was sufficiently mild, affording 4,6-dibromo-3-hydroxy-2-
nitrobenzoic acid (2) in 71% yield. An X-ray crystal structure of
2 confirmed the desired positions of the two bromine atoms
(Fig. S2†). A two-step, one-pot protection reaction of both the
carboxylic acid and the phenol of 2 using diazomethane and
dimethylsulfate–K2CO3, respectively, gave methyl 4,6-dibromo-
3-methoxy-2-nitrobenzoate (3) in 92% overall yield. Suzuki
coupling reaction of 3 with phenyl boronic acid successfully
introduced two phenyl groups on both the ortho and para pos-
itions of the arene in 3, giving 4 in 89% yield. The selective
deprotection of the methyl phenyl ether in the presence of the
methyl ester in 4 proved challenging. Ester groups are more vul-
nerable than ethers to deprotection under most commonly used
conditions. A literature search revealed that deprotection of nitro-
substituted methyl phenol ethers can be accomplished using
LiCl as a mild reagent in refluxing DMF.17 Using this condition,
however, resulted in demethylation of the ester moiety. We
hypothesized that the high temperature (160 °C) employed might
lead to the undesired hydrolysis of the ester group. Therefore, we
carried out the reaction with 4 using a lower temperature
(90 °C), and only the methyl phenyl ether moiety of 4 was
deprotected by LiCl, leaving the ester group unmodified. After
purification, phenol 5 was obtained in 86% yield. Finally, methyl
anthranilate 6 was achieved in 96% yield after hydrogenation
of 5.
Fig. 3 Thermal ellipsoid plot (50% probability) of X-ray structure of
ligand H2L2Ph4. Hydrogens on carbon are omitted for clarity. Carbon,
gray; oxygen, red; nitrogen, blue; hydrogen, white.
of H2L2Ph4 are oriented toward one another. The distances
between two pairs of oxygen atoms are 2.676(3) Å and 2.734(3)
Å, which are within hydrogen bonding distance. Furthermore,
the two hydrogen atoms could be located on the difference
Fourier map. The hydrogen bonds orient all of the potential
donor atoms toward the center of the ligand. The distance
between two nitrogen atoms is 6.013 Å and that between two
furan oxygen atoms on the triptycene backbone is 4.780 Å, indi-
cating that the ligand framework will provide a suitable binding
pocket for two metal atoms. In addition, the phenyl groups of
H2L2Ph4 significantly enhance the solubility of this diacid rela-
tive to the underivatized analog H2L2 in various non-polar
organic solvents; the additional phenyl groups efficiently
increase the hydrophobicity of the ligand.
Treatment of H2L2Ph4 with Fe(OTf)3 and triethylamine in the
presence of sodium 2,2,2-triphenylacetate (Ph3CCO2Na)
afforded red crystalline blocks after vapor diffusion of pentane
into a benzene solution of the reaction mixture. Although these
crystals diffracted only to 1 Å resolution, the structure solution
and refinement determined unambiguously the geometry of the
complex. The complex is best formulated as [NaFe3(L2Ph4)2-
(μ3-O)(μ-O2CPh3)2(H2O)3](OTf)2 (8) (Fig. 4), and the core is
depicted in Fig. 5. The latter features a triiron center, bridged
internally by a μ3-oxo atom and externally by the carboxylates
With our desired methyl anthranilate 6 in hand, we moved
forward with the assembly of the triptycene backbone. As shown
in Scheme 2, amide coupling of 6 with in situ generated benzoyl
chloride i gave diamide 7 in 70% yield.13 Next, compound
7 was cyclized using p-TsOH·H2O in HOAc to give L1Ph4 in
98% yield. Finally, the methyl esters in L1Ph4 were successfully
hydrolyzed by BBr3, giving H2L2Ph4 in 98% yield. The overall
yield of this 9-step synthesis is 32%.
X-ray diffraction quality crystals of H2L2Ph4 were obtained by
slow evaporation of a CD2Cl2 solution in an NMR tube. As
shown in Fig. 3, the two carboxylic acids in the crystal structure
of (L2Ph4 2− and by Ph3CCO2−. Complex 8 has a crystallo-
)
graphically required C2-axis passing through the μ3-oxo ion
(O12), Fe2 atom, and a coordinated water molecule (O13)
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Table 1 Mössbauer fits of two sites in complex 8
δ [mm s−1
]
ΔEq [mm s−1
]
Γ
Area [%]
Site 1
Site 2
0.472 0.02
0.684 0.02
0.604 0.02
0.600 0.02
0.384
0.252
71
29
complex crystallized in a centrosymmetric space group, both
enantiomers are present. Another noteworthy feature of this
structure is the apparent lack of coordination of the benzoxazole
nitrogen atoms. We hypothesize that the low basicity of benz-
oxazole renders such coordination unfavorable.
Mössbauer spectroscopy was performed to verify the
oxidation state assignment of the Fe atoms. The zero-field 57Fe
Mössbauer spectrum at 77 K, together with the fit, are shown in
Fig. S1† and Table 1, respectively. The data were best fit with a
two-site model. The approximate ratio of the two iron sites was
2 : 1, consistent with the presence of two chemically inequivalent
Fe sites observed in the X-ray structure. The major site has an
isomer shift of (δ) 0.472 mm s−1 and quadrupole splitting of
(ΔEq) 0.604 mm s−1. The minor site has an isomer shift
of (δ) 0.684 mm s−1 and quadrupole splitting of (ΔEq)
0.600 mm s−1. These values are consistent with those of other
triiron(III) centers having a basic carboxylate structural motif.8,18
Fig. 4 Ball-and-stick representation of the X-ray crystal structure of
[NaFe3(L2Ph4)2(μ3-O)(μ-O2CPh3)2(H2O)3](OTf)2 (8). Hydrogen atoms,
solvent molecules, and counter anions are omitted for clarity. The
carbons of two (L2Ph4 2−
are colored pink and bright green. Iron, dark
)
green; oxygen, red; nitrogen, blue; sodium, yellow. The depicted Na+
ion occurs at half-occupancy; the other ion, generated by a C2 axis, is
not shown.
Conclusions
In summary, we describe the synthesis of a preorganized tripty-
cene-based bis(benzoxazole) ligand, H2L2Ph4. To prevent unde-
sired formation of high nuclearity clusters and polymers,
sterically protecting phenyl groups were installed ortho to the
carboxylic acid units in the H2L2Ph4 ligand. A triiron(III)
complex [NaFe3(L2Ph4)2(μ3-O)(μ-O2CCPh3)2(H2O)3](OTf)2 (8),
was obtained having a “basic iron acetate” core in the structure.
Among this class of compounds, the structure of 8 is novel
because it utilizes a chelating dicarboxylate ligand, is constructed
from two different types of carboxylate bridges, and is chiral.
The observation that the benzoxazole nitrogen fails to coordinate
to iron suggests that a more basic N-donor is needed to success-
fully model the diiron site of sMMOH. The design and synthesis
of more basic analogs of H2L2Ph4 is the focus of our ongoing
work.
Fig. 5 Core structure of complex 8.
(Fig. 5). A sodium ion (yellow, Fig. 4) forms an intimate ion-
pair complex through coordination to carboxylate, water, and
benzofuran oxygen atoms of the core structure. The sodium ion
is spatially disordered, with 50% occupancy, between the site in
the asymmetric unit (Fig. 4) and its symmetry generated crystal-
lographic partner (not shown).
This work was supported by a grant from the National Insti-
tute of General Medical Sciences (GM-032134). Dr Apfel
thanks the Alexander von Humboldt Foundation for a Feodor
Lynen research fellowship.
The core structure of 8 is shown in Fig. 5 (see Fig. S5† for
detailed information). Among the six carboxylate bridges, four
are derived from two (L2Ph4 2−
anions and the other two are
)
Notes and references
Ph3CCO2−. Although a number of triiron basic carboxylate
structures are known, the structure of 8 is unique for several
reasons. The use of chelating dicarboxylate ligands for the
assembly of this {Fe3O}7+ core is rare. Furthermore, to the best
of our knowledge, all currently known complexes with such a
{Fe3O}7+ core are bridged by a homoleptic set of carboxylate
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