Tris(pyrazolyl)borate Copper Hydroxide Complexes Featuring Tunable Intramolecular H-Bonding

Article abstract of DOI:10.1021/acs.inorgchem.9b01991

A modular synthesis provides access to a series of new tris(pyrazolyl)borate ligands ^XpyMeTpK that possess a single functionalized pendant pyridyl (py) or pyrimidyl (pyd) arm designed to engage in tunable intramolecular H-bonding to metal-bound functionalities. To illustrate such H-bonding interactions, a series of [^XpyMeTpCu]₂(μ-OH)₂ (6a-6e) complexes were synthesized from the corresponding ^XpyMeTpCu-OAc (5a-5e) complexes. Single crystal X-ray structures of three new dinuclear [^XpyMeTpCu]₂(μ-OH)₂ complexes reveal H-bonding between the pendant heterocycle and bridging hydroxide ligands while the donor arm engages the copper center in an unusual monomeric ^DMAPMeTpCu-OH complex. Vibrational studies (IR) of each bridging hydroxide complex reveal reduced ν_OH frequencies that tracks with the H-bond accepting ability of the pendant arm. Reversible protonation studies that interconvert [^XpyMeTpCu]₂(μ-OH)₂ and [^XpyMeTpCu(OH₂)]OTf species indicate that the acidity of the corresponding aquo ligand decreases with increasing H-bond accepting ability of the pendant arm.

Full text of DOI:10.1021/acs.inorgchem.9b01991

Article
pubs.acs.org/IC
Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
Tris(pyrazolyl)borate Copper Hydroxide Complexes Featuring
Tunable Intramolecular H‑Bonding
Evan J. Gardner, Caitlyn R. Cobb, Jeffery A. Bertke, and Timothy H. Warren*
Department of Chemistry, Georgetown University, Box 51277-1227, Washington, D.C. 20057, United States
S
* Supporting Information
ABSTRACT: A modular synthesis provides access to a series
of new tris(pyrazolyl)borate ligands XpyMeTpK that possess a
single functionalized pendant pyridyl (py) or pyrimidyl (pyd)
arm designed to engage in tunable intramolecular H-bonding
to metal-bound functionalities. To illustrate such H-bonding
interactions, a series of [XpyMeTpCu]2(μ-OH)2 (6a−6e)
complexes were synthesized from the corresponding XpyMeTp-
Cu−OAc (5a−5e) complexes. Single crystal X-ray structures
of three new dinuclear [XpyMeTpCu]2(μ-OH)2 complexes
reveal H-bonding between the pendant heterocycle and
bridging hydroxide ligands while the donor arm engages the
copper center in an unusual monomeric DMAPMeTpCu−OH
complex. Vibrational studies (IR) of each bridging hydroxide complex reveal reduced νOH frequencies that tracks with the H-
bond accepting ability of the pendant arm. Reversible protonation studies that interconvert [XpyMeTpCu]2(μ-OH)2 and
[
XpyMeTpCu(OH2)]OTf species indicate that the acidity of the corresponding aquo ligand decreases with increasing H-bond
accepting ability of the pendant arm.
INTRODUCTION
■
In metalloenzymes, hydrogen bonding (H-bonding) inter-
actions prevalent in the tightly regulated microenvironment of
metal ions are closely tied to functionality.1−3 When applied in
synthetic systems, arrays of rigid H-bonding frameworks have
had notable effects on chemical reactivity.4−8 The number and
diversity of new synthetic systems featuring secondary
coordination sphere H-bonding are expanding as efforts to
better understand these phenomena continue.
Secondary sphere H-bond donor and/or acceptor groups are
featured especially often in tripodal systems (Figure 1).9−15
For instance, several synthetic systems showcase the utility of
H-bonding interactions with oxygen-containing small mole-
cules. The stabilization of the peroxide anion (O22−) via
interactions with H-bond donors, first observed in Cummins’16
metal-free cryptand, is underscored by Szymczak’s17 tripodal
Zn(II) complex, where secondary coordination sphere H-
2−
Figure 1. Examples of systems incorporating second sphere H-bond
donor and/or acceptor groups.
bonding governs O2 binding at Zn (Figure 1a). Fewer
systems possessing H-bond acceptors have been re-
ported14,18,19 but include Fout’s10 tripodal scaffold with
pyrrole-imine H-bond acceptors that H-bond to coordinated
water (Figure 1b). In addition, this ligand can undergo redox
tautomerization to form a “hybrid” H-bond donor/acceptor
system as well as an all H-bond donor variant. Borovik’s20
recent example of this hybrid class is a tripodal scaffold
containing a mix of two amine H-bond donors and one
phosphinic amide H-bond acceptor (Figure 1c).
stable hydroxide complexes possessing secondary sphere H-
bonding serve useful roles to survey H-bond contribu-
tions.21−23 Such hydroxide species have been important for
revealing the influence of the number of H-bonding groups as
well as the type of H-bonding groups on the properties of the
complex.11,14,21,24
Since it can be difficult to directly examine the nature of the
hydrogen bonding with highly reactive intermediates, more
Received: July 5, 2019
© XXXX American Chemical Society
A
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Scheme 2. Synthesis of XpyMePzH (3a−3d)
In a landmark report, Kitajima and Fujisawa established
TpCu scaffolds (Tp = tris(pyrazolyl)borate) as important
biorelevant models for O2 reactivity at copper-based
hemocyanin with [iPr2TpCu]2(μ-O2) and the related
[
iPr2TpCu]2(μ-OH)2.25 Molecular copper−oxygen complexes
attract interest as intermediates in chemical transformations
mediated by hemocyanin,25−27 copper oxidases,28−30 and other
copper-based enzymes.31,32
We set out to construct a new family of Tp ligands with
tunable secondary sphere H-bonding through only a single
heterocyclic pyridyl (py) or pyrimidyl group (pyd). While
examples of Tp scaffolds bearing pendant H-bonding
groups33−37 or ancillary ligands capable of H-bonding have
been reported,38−40 particularly inspiring is a py3TpK
ligand35,37,41 that bears three pendant pyridyl groups that
engages in secondary sphere H-bonding with an aqua ligand at
CuII (Figure 2a).35,37 The targeted Tp ligand, however, bears
(DMAP) functionality. Instead, nucleophilic aromatic sub-
stitution of chloropyridine-pyrazole 3d with neat 40% aqueous
dimethyl amine under reflux gives 3e in 73% yield (Scheme
S4). Single crystal X-ray diffraction structures obtained for 3c
and 3e illustrate intermolecular Xpy···H−Pz H-bonding
interactions (Figures S10 and S11).
A pyrazole exchange reaction starting from the symmetric
iPr2TpK ligand42 conveniently leads to singly substituted
XpyMeTpK heteroscorpionates (4a−4e) (Scheme 3). Unlike
Scheme 3. Synthesis of XpyMeTpK Ligands (4a−4e)
Figure 2. Intramolecular H-bonding in TpCu complexes featuring
pendant H-bond acceptor groups.
only a single pendant base, since Tp systems with three pyridyl
groupsone pyridyl arm per pyrazolelead to an array of Cu
coordination motifs involving Cu−py interactions (Figure
2).35,37,41 We report herein a new, modular synthesis for singly
functionalized XpyMeTpK heteroscorpionates along with
crystallographic and spectroscopic characterization of corre-
sponding [XpyMeTpCu]2(μ-OH)2 complexes that demonstrate
tunable secondary coordination sphere H-bonding.
other heteroscorpionates that bear nonsymmetric function-
alities,43−46 parallel efforts to generate the monosubstituted
XpyMeTpK from a molten reaction of KBH4 2:1 ratio of the
corresponding pyrazoles or postmetalation modifications to
the ligand were unsuccessful. Instead, XpyMeTpK can be
synthesized by combining equimolar amounts of iPr2TpK and
XpyMePzH (3a−3e) at 160 °C under a dynamic vacuum. These
conditions facilitate both pyrazole exchange and removal of
iPr2PzH via sublimation onto a coldfinger, recycled for future
use (Figure S1). Crystallization from minimal dichloromethane
(DCM) with several drops of acetonitrile provide XpyMeTpK
ligands 4a−4e as acetonitrile adducts, which can be dried in
vacuo to provide solvent-free species in 46−60% yields. X-ray
crystallography of acetonitrile adducts reveals either mono- or
dinuclear structures (Figure 3). For instance, 4a crystallizes as
monomeric CF3pyMeTpK(NCMe)2 whereas 4c is isolated as a
dimer bridged by three MeCN molecules (Figure 3).
Transmetalation of ligands 4a−4e occurs smoothly with
anhydrous Cu(OAc)2 in DCM to afford XpyMeTpCu−OAc
complexes 5a−5e in 72−88% yield (Scheme 4). Single crystal
structures of 5b and 5c reveal coordination of the py and pyd
donor arms with the respective Cu centers. A τ5 analysis47 (τ5
= 0, square pyramidal; τ5 = 1, trigonal bipyramidal) reveals a
slight distortion toward trigonal bipyramidal geometries (τ5 =
0.56 and 0.62) for 5b and 5c respectively (Figure 4). Both
feature monodentate acetate coordination, unlike in a simple
TnTpCu−OAc48 complex that possesses a bidentate acetate
ligand. Related TpCu−OAc complexes with an extra copper
donor such as [PhMeTpCu(PhMePzH)]OAc49 and [PhTpCu-
(PhPzH)]OAc50 also feature monodentate acetate ligands,
RESULTS AND DISCUSSION
■
A series of substituted pyrazoles was prepared starting with the
Claisen condensation of a series of commercially available py
or pyd (pyrimidine) ester derivatives with acetone to give the
corresponding diketone (Scheme 1). This reaction most
reliably proceeds with a non-nucleophilic base such as KH in
Et2O. Condensation of respective diketones 2a−2d with
anhydrous hydrazine in methanol affords the py and pyd
functionalized pyrazoles (XpyMePzH) 3a−3d in high yields
(Scheme 2). This approach was not successful, however, in the
synthesis of 3e that possesses a dimethylamino-pyridine
Scheme 1. Synthesis of Diketones (2a−2d)
B
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Figure 3. X-ray structures of CF3pyMeTpK(NCMe)2 (4a) and [pyMeTpK]2(μ-NCMe)3 (4c). In structure 4a the CF3 group is disordered over two
positions and is represented by sites of highest occupancy. Isopropyl groups on the pyrazoles, MeCN solvate molecules, and most hydrogen atoms
are omitted for clarity.
Scheme 4. Synthesis of XpyMeTpCuOAc (5a−5e)
Scheme 5. Synthesis of [XpyMeTpCu]2(μ-OH)2 (6a−6e)
[
XpyMeTpCu]2(μ-OH)2 complexes (6) result from stirring
XpyMeTpCuOAc (5) in a biphasic DCM/aqueous NaOH
indicating that the presence of an additional ligand disfavors
bidentate acetate coordination. Coordination of the pendant
py and pyd groups in 5b and 5c leads to C1−C4−N3 bond
angles of 112.81(19)° and 113.22(15)° (Figure 4), respec-
tively. While these angles are below the idealized 120° for sp2
carbon centers, other Cu centers coordinated to bidentate pyPz
ligands similarly show modest strain.51,52 We hypothesized that
the presence of a H-bond donor at copper would turn on
intramolecular H-bonding that then would compete with the
py-Cu or pyd-Cu interaction.
mixture (Scheme 5), similar to that used to prepare
[
iPr2TpCu]2(μ-OH)2 (7).25 Crystallization from DCM sol-
utions layered with MeCN allows for isolation of
[
XpyMeTpCu]2(μ-OH)2 (6a−6e) in 75−95% yields. Single
crystal X-ray structures of [XpyMeTpCu]2(μ-OH)2 species 6a−
6c reveal intramolecular H-bonding between the respective
pendant py and pyd arms with the bridging hydroxo groups
(Figure 5). The CuII centers in 6a−6c adopt a more square
pyramidal geometry (τ5 = 0.22 (6a), 0.19 (6b), and 0.27 (6c)
similar to [iPr2TpCu]2(μ-OH)2 (τ5 = 0.31) that does not have
Figure 4. X-ray structures of pymMeTpCu−OAc (5b) and pyMeTpCu−OAc (5c), respectively. Isopropyl groups on the pyrazoles, solvate molecules,
and most hydrogen atoms are omitted for clarity.
C
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Figure 5. X-ray structures of [CF3pyMeTpCu]2(μ-OH)2 (6a), [pymMeTpCu]2(μ-OH)2 (6b), [pyMeTpCu]2(μ-OH)2 (6c), and DMAPMeTpCu−OH (6e),
respectively. In structure 6a, the CF3 groups are disordered and are represented by sites of highest occupancy. Isopropyl groups on the pyrazoles
and hydrogen atoms are omitted for clarity.
an additional donor arm.25 The distance between Cu centers
for 6a−6c (2.9384(7) to 2.9457(11) Å) are also nearly
identical to unmodified 7 (2.937(2) Å).25 As a measure of the
H-bonding interaction, the py−N···O(H) and pyd−N···O(H)
distance decreases with increasing basicity of the N-based H-
bond acceptor.53−55
Curiously, the crystal X-ray structure of the copper(II)
hydroxide with the most electron-rich donor arm corresponds
to a mononuclear DMAPMeTpCu−OH (6e) complex (Figure 5).
Instead of H-bonding with the hydroxide group, the pendant
DMAP binds the CuII center (Figure 5). Close inspection
reveals no H-bonding interactions with the terminal OH−
ligand. The five-coordinate environment is between square
Figure 6. H-bonding in dinuclear copper(II) hydroxides as revealed
through IR spectra. The νOH stretching region of IR spectra of 6a−6e
and 7.
pyramidal and trigonal bipyramidal (τ5 = 0.51). This
mononuclear copper hydroxide, however, is somewhat
surprising due to the enhanced H-bond accepting ability of
its DMAP arm as well as the scarcity of structurally
characterized mononuclear CuII−OH species.56−59
bond accepting ability of the donor arm increases (Table 1).
To probe the influence of H-bonding on the hydroxide
ligand, 6a−6e as well as 7 were characterized via IR
spectroscopy (Figure 6 and S10). Species 6a−6c and 7 were
analyzed as KBr pellets whereas 6e was analyzed as a thin film
evaporated from DCM on a KBr window. The variant lacking
any H-bonding, 7, features a high energy νOH stretch at 3660
cm−1. In contrast, dinuclear and H-bonded 6a−6c exhibit
broad νOH bands centered at ever decreasing energy as the H-
Interestingly, the IR spectrum of complex 6e features a broad
νOH band lower in energy than observed for 6a−6c consistent
with the greatest H-bond accepting ability of the DMAP arm
despite the mononuclear structure indicated in crystals from
DCM by X-ray crystallography (Figure 5). The IR spectra were
taken as films that result from solvent evaporation of DCM
solutions of 6, and therefore this suggests a dinuclear species
[
DMAPMeTpCu]2(μ-OH)2 that features intramolecular H-
D
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Table 1. H-Bonding: Comparison of 6a−6e and 7
complex
νO−H (cm−1
)
O(H)···N (Å)
[
[
[
[
[
iPr2TpCu]2(μ-OH)2 (7)
3660
3340
3331
3267
CF3pyMeTpCu]2(μ-OH)2 (6a)
pymMeTpCu]2(μ-OH)2 (6b)
pyMeTpCu]2(μ-OH)2 (6c)
DMAPMeTpCu]2(μ-OH)2 (6e)
2.901(4)
2.864(4)
2.849(3)
3223, 3647
bonding is accessible in solution. Nonetheless, the IR spectrum
of 6e also possesses a sharp νOH at 3647 cm−1 consistent with
the mononuclear DMAPMeTpCu−OH that lacks H-bonding.
We hypothesize that intramolecular H-bonding between the
pendant base and the bridging hydroxyl ligands in 6a−6e
influences the basicity of the Cu−OH moiety. As an indirect
measure, we sought to assess the relative acidity of the
corresponding aquo moiety [Cu−OH2]+ formed upon
protonation (Figure 7). Titrating dinuclear hydroxide com-
Figure 8. Stepwise protonation of [CF3pyMeTpCu]2(μ-OH)2 (6a) with
HOTf in DCM at −10 °C.
3262 and 3176 cm−1 respectively (Figures S31 and S32).
These new bands occur at similar energies as other reported
[Cu]−OH2 species.60,61 In contrast, protonation of
+
[
iPr2TpCu]2(μ-OH)2 (7) without the pendant arm reaches
completion after addition of 0.5 equiv HOTF/Cu. This result
reveals the decisive role played by the pendant arm in
modifying the basicity of the bridging hydroxide ligands in
[
XpyMeTpCu]2(μ-OH2)2 (6a−6d).
Backtitration of these cationic aquo species 8 to return the
dinuclear hydroxo species 6 exhibits a dependency on the
added base used. In this study, we examined three different
bases of increasing strength: 2,4,6-collidine (col) < triethyl-
amine (Et3N) < DBU. Aquo complex 9 that lacks any pendant
donor is most acidic, amenable to deprotonation back to 7
with the least basic collidine. Deprotonation of complexes 8
that possess pendant arms require stronger bases with the base
required correlating with the basicity of the pendant arm.
While CF3−pyridine 8a and pyrimidine 8b undergo deproto-
nation with Et3N, the more basic pyridine 8c and DMAP 8e
species require DBU to affect deprotonation.
CONCLUSIONS
■
The modular synthesis of a Tp scaffold possessing a single
pyridine or pyrimidine donor arm allows ready access to a new
class of heteroscorpionate ligands capable of H-bonding in the
second coordination sphere. While a series of XpyMeTpCu−
OAc complexes reveal that the respective py and pyd arms can
coordinate to the copper center, this coordination is absent
when intramolecular H-bonding occurs between the pendant
arm and the hydroxide O−H moiety in corresponding
Figure 7. Reversible protonation of 6a−6e and 7. The pendant
groups of each respective [XTpCu(OH2)]OTf species (8) is
illustrated next to the weakest base (collidine, Et3N, DBU) required
for deprotonation to the corresponding [XTpCu]2(OH)2 species in
DCM.
[
XpyMeTpCu]2(μ-OH)2 complexes. Single crystal X-ray struc-
plexes [XpyMeTpCu]2(μ-OH2)2 (6a−6d) with HOTf in CH2Cl2
at −10 °C results in the loss of the band near 600 nm
corresponding to 6 with concomitant growth of a lower energy
band near 800 nm (Figures 8, S19, and S23). Since titration
end points for 6a−6d occur with 2 equiv of HOTf, it suggests
the conversion of dinuclear [XpyMeTpCu]2(μ-OH)2 (6a−6d) to
2 equiv of mononuclear [XpyMeTpCu(OH2)]OTf (8a−8d).
Although DMAP substituted 6e may exist in both mono-
nuclear and dinuclear forms, titration with HOTf reaches an
end point at 1:1 ratio of Cu: HOTf suggesting similar
formation of [DMAPMeTpCu(OH2)]OTf (8e). While attempts
to structurally characterize 8a−8e via X-ray diffraction were
unsuccessful, characterization of 8a and 8e by IR show the
formation of two new broad νHO−H bands centered around
tures and IR spectroscopy of these copper−hydroxide species
reveal a direct correlation between the N···O(H) bond
distance and νOH stretching frequency with the electronic
nature of the H-bond acceptor arm. This family of Tp ligands
features highly tunable pendant arms that participate in H-
bonding interactions illustrated through copper(II) hydroxides
[
XpyMeTpCu]2(μ-OH)2. For instance, the corresponding
cationic aquo complexes {[XpyMeTpCu](OH2)}+ (8) formed
upon protonation of [XpyMeTpCu]2(μ-OH)2 (6) require added
bases that correlate with the basicity of the pendant arm. The
synthetic accessibility and tunability of these pyTp ligands
suggest that they may enable H-bonding interactions with
other functionalities bridged between two TpM centers. One
such target is diazene, an important intermediate in dinitrogen
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.9b01991.
■
S
Experimental and X-ray structure details (PDF)
Accession Codes
CCDC 1890609−1890618 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
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AUTHOR INFORMATION
Corresponding Author
*E-mail: thw@georgetown.edu.
ORCID
Jeffery A. Bertke: 0000-0002-3419-5163
Timothy H. Warren: 0000-0001-9217-8890
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
T.H.W. acknowledges support from the U.S. Department of
Energy, Office of Science, Basic Energy Sciences (DE-
SC001779). E.J.G. acknowledges support from the ARCS
foundation Gladi Mathews fellowship. T.H.W. thanks Prof.
Claire Besson for a stimulating conversation regarding ligand
synthesis.
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