Tris-(2-pyridylmethyl)amine-ligated Cu(II) 1,3-diketonate complexes: Anaerobic retro-Claisen and dehalogenation reactivity of 2-chloro-1,3-diketonate derivatives

Article abstract of DOI:10.1039/d0dt04074f

We report synthetic, structural and reactivity investigations of tris-(2-pyridylmethyl)amine (TPA)-ligated Cu(ii) 1,3-diketonate complexes. These complexes exhibit anaerobic retro-Claisen type C-C bond cleavage reactivity which exceeds that found in analo

Full text of DOI:10.1039/d0dt04074f

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PAPER
Tris-(2-pyridylmethyl)amine-ligated Cu(II) 1,3-
diketonate complexes: anaerobic retro-Claisen
and dehalogenation reactivity of 2-chloro-1,3-
diketonate derivatives†
Cite this: Dalton Trans., 2021, 50,
1712
b
Josiah G. D. Elsberg, a Stephen N. Anderson, a David L. Tierney,
a
Eric W. Reinheimer c and Lisa M. Berreau
*
Received 28th November 2020,
Accepted 5th January 2021
We report synthetic, structural and reactivity investigations of tris-(2-pyridylmethyl)amine (TPA)-ligated Cu
(II) 1,3-diketonate complexes. These complexes exhibit anaerobic retro-Claisen type C–C bond cleavage
reactivity which exceeds that found in analogs supported by chelate ligands with fewer and/or weaker
pyridyl interactions.
DOI: 10.1039/d0dt04074f
rsc.li/dalton
studies of the oxidative aliphatic C–C bond cleavage reactivity
of a Cu(II) chlorodiketonate complex (1, Scheme 2) supported
Introduction
Aliphatic carbon–carbon (C–C) bond cleavage reactions of 1,3- by the 6-Ph2TPA ligand.8,9 Notably, chloride anion binding to
diketones mediated by copper salts are of current interest.1,2 the Cu(II) center in this complex lowers the barrier for O2 acti-
In applications for organic synthesis, reports have appeared of vation, providing evidence for the importance of the primary
oxidative cleavage of dibenzoylmethane and other 1,3-dike- coordination sphere in influencing oxidative diketonate clea-
tones using CuBr or CuBr2 under air with excess pyridine (5 vage reactivity. In the solid state, the Cu(II) center of 1 exhibits
eq.) present as a supporting ligand (Scheme 1(a)) and with pro- coordination to the tertiary amine nitrogen (Cu(II)–Nam 2.0333
longed heating.3,4 For the most part, the mechanistic pathways (17) Å) and the unsubstituted pyridyl donor (Cu(II)–Npy 1.992
of these reactions remain undefined, as does the influence (18) Å) of the chelate ligand, with one phenyl-appended pyridyl
that pyridine ligation has on possible intermediates. Non- donor interacting more weakly (Cu(II)–NPhPy 2.3394(18) Å). The
redox reactions involving retro-Claisen-type aliphatic C–C remaining aryl-appended pyridine appendage of the chelate
bond cleavage reactivity of 1,3-diketones mediated by Cu(II)
salts have also been reported.5–7 Similar to Cu(II)-mediated oxi-
dative diketone cleavage (Scheme 1(a)), these reactions typi-
cally involve undefined Cu(II) diketone/diketonate species
under prolonged high temperature conditions (>80 °C)
(Scheme 1(b) and (c)) in the presence of water or alcohol.
We hypothesize that insight into the chemical factors that
influence copper-mediated oxidative and non-redox 1,3-di-
ketone cleavage can be gained through studies involving
copper complexes supported by pyridyl-containing chelate
ligands. In this regard, our laboratory has previously reported
aDepartment of Chemistry & Biochemistry, Utah State University, 0300 Old Main
Hill, Logan, UT 84322-0300, USA. E-mail: lisa.berreau@usu.edu
bDepartment of Chemistry & Biochemistry, Miami University, Oxford, OH 45056,
USA
cRigaku Americas Corporation, 9009 New Trails Drive, The Woodlands, TX 77381,
USA
†Electronic supplementary information (ESI) available: Experimental details and
spectral data. CCDC 2010712, 2010713, 2010714, 2010715, 2010716 and
2038517. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/d0dt04074f
Scheme 1 Aliphatic C–C bond cleavage reactions mediated by copper
salts.
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Experimental
General methods
All solvents and reagents were purchased from commercial
sources and used without prior purification unless otherwise
stated. Solvents were dried following a previously published
procedure and distilled under N2 prior to use.10 Tris(2-pyridyl-
methyl)amine (TPA),11 N,N-bis((6-phenyl-2-pyridyl)methyl)-N-
((2-pyridyl)methyl)amine (6-Ph2TPA),12 1,3-bis(4′-R-phenyl)-1,3-
propanediones,13
diones,14 2-chloro-1-(4′-R-phenyl)ethanones,14
2-chloro-1,3-bis(4′-R-phenyl)-1,3-propane-
[(TPA)Cu
15
11
(CH3CN)](ClO4)2 and [(TPA)Cu(CH3CN)]PF6 were prepared
according to literature procedures. All manipulations involving
the preparation of Cu(II) complexes were performed in an
MBraun Unilab glovebox under a N2 atmosphere unless other-
wise noted.
Scheme 2 (Top) Oxidative aliphatic C–C bond cleavage reactivity of 1.
(Bottom) Structures of 1-Cl and 2.
Physical methods
1H and 13C NMR spectra of diamagnetic compounds were col-
ligand is dissociated from the Cu(II) center. The EPR spectral lected using a Brüker Advance III HD Ascend-500 spectro-
features of 1 provide evidence for the retention of this five- meter. Chemical shifts (ppm) are reported relative to the
coordinate structure in frozen acetonitrile.8 DFT modelling of residual solvent peak in CD2HCN (1H NMR: 1.94 ppm, quintet)
the chloride-activated 1-Cl (Scheme 2) suggests formation of a or CHCl3 (1H NMR: 7.26 ppm, singlet). FTIR spectra were col-
square-pyramidal structure with chloride binding in the axial lected as KBr pellets using a Shimadzu FTIR-8400 spectro-
position and loss of the Cu(II)–NPhPy interaction. Consistent meter. UV-vis data was collected on a Hewlett-Packard 8453A
with the proposed structure of 1-Cl, a bipyridine-coordinated diode array spectrometer at ambient temperature. ESI mass
analog 2 also exhibits chloride-activated oxidative C–C bond spectral data were collected using a Shimadzu LCMS-2020.
cleavage reactivity.9
Elemental analyses were performed by Robertson Microlit
Based on the chloride- and O2-dependent C–C bond clea- Laboratories (Ledgewood, N.J.) or Atlantic Microlab (Norcross,
vage reactivity exhibited by 1 and 2, we hypothesized that GA).
increasing the donor properties of the pyridyl-containing
Caution! Perchlorate compounds containing organic ligands
chelate ligand would potentially limit anion binding to the are potentially explosive. These materials should be handled with
Cu(II) center and O2 activity. To probe this idea, we targeted care and in small quantities.16
for synthesis and reactivity studies two series of tris(2-pyri-
Synthesis of 2-chloro-1,3-bis(4′-chlorophenyl)-1,3-
propanedione
dylmethyl)amine (TPA)-ligated Cu(II) 1,3-diketonate com-
plexes. The first set of complexes, formulated as [(TPA)Cu(4′-
R-PhC(O)CHC(O)4′-R-Ph)]ClO4 (3–6, R = –H, –CH3, –OCH3, 1,3-Bis(4′-chlorophenyl)-1,3-propanedione (2.04 mmol) was
–Cl) contain a diketonate that is unsubstituted at the central dissolved in MeOH (80 mL) and ammonium chloride
position. Our hypothesis was that these complexes would be (4.08 mmol) and OXONE® (3.07 mmol) were added. The solu-
air stable and provide benchmark examples of rare pseudo- tion was refluxed for 5 h and then stirred for an additional
octahedral Cu(II) diketonate complexes. The second set of 12 h at ambient temperature. Following addition of H2O
complexes targeted for synthesis were TPA-ligated Cu(II) (30 mL) the volume of the solution was reduced using rotary
chlorodiketonate derivatives, [(TPA)Cu(4′-R-PhC(O)CClC(O)4′- evaporation. Water (20 mL) and EtOAc (20 mL) were added
R-Ph)]ClO4 (7–10, R = –H, –CH3, –OCH3, –Cl). Notably, we and the solution transferred to a separatory funnel. The
have found that using the synthetic conditions employed to organic layer was collected, and the aqueous phase was
generate 1 and 2 under N2 in attempts to make 7–10 leads extracted with two additional aliquots of EtOAc (2 × 20 mL).
to both retro-Claisen type aliphatic C–C bond cleavage reac- The combined organic fractions were dried over Na2SO4, the
tivity and dehalogenation of the chlorodiketonate ligand. We solution filtered, and the solvent from the filtrate was then
report herein comprehensive characterization details for 3–6 removed by rotary evaporation. The resulting solid was dis-
as well as a series of experiments to probe the retro-Claisen solved in a minimal amount of hot EtOH and then placed in
and dehalogenation reactivity identified in the anaerobic the freezer (−12° C) for 16 h which resulted in the deposition
reactions directed at the preparation of 7–10. Overall, the of a white solid. (0.26 g, 40%). Mp 124–125 °C, 1H NMR
results presented herein demonstrate that the pyridyl (CDCl3) δ (ppm): 7.94 (m, J = 8.7 Hz, 4H), 7.45 (m, J = 8.7 Hz,
donor characteristics of a supporting ligand significantly 4H), 6.25 (s, 1H). 13C NMR (CDCl3) δ (ppm): 188.4 (CvO),
influence the structure and reactivity of Cu(II) chlorodiketo- 141.4, 132.2, 131.0, 129.6, 63.5 (6 signals expected and
nate species.
observed). FTIR (KBr, cm−1): 1702(νCvO), 1680, 1587.
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General synthesis of [(TPA)Cu(4′-R-PhC(O)CHC(O)4′-R-Ph)]
ClO4 (3–6)
tion containing an insoluble precipitate for all derivatives. The
solutions were then combined and stirred overnight (16 h),
resulting in the formation of a clear green solution. Difficulties
in producing analytically pure crystalline products led us to
collect ESI-MS data for each final reaction mixture. This data
indicated the presence of the following ions: [(TPA)Cu(4′-
Under an inert atmosphere at ∼30 °C, Cu(ClO4)2·6H2O
(0.135 mmol) was dissolved in CH3CN (∼3 mL) and added to
solid TPA (0.135 mmol). The resulting deep blue solution was
stirred for 30 min. In a separate container, 1,3-bis(4′-R-
R-PhC(O)CClC(O)4′-R-Ph)]+,
[(TPA)Cu(4′-R-PhC(O)CHC(O)4′-
phenyl)-1,3-propanedione (R
= –H, –CH3, –OCH3, –Cl)
R-Ph)]+, [(TPA)Cu(O2C-4′-R-Ph)]+ and [(TPA)CuCl]+. These ions
suggested aliphatic C–C bond cleavage reactivity and dehalo-
genation within the diketonate moiety under anaerobic con-
ditions. Notably, attempted crystallization of 9 resulted in the
deposition of crystals of the dehalogenated product 5 and
[(TPA)Cu–Cl]2[Li(ClO4)3] (11).
(0.135 mmol) was combined with lithium bis(trimethylsilyl)
amide (0.135 mmol) dissolved in Et2O (∼3 mL) and stirred for
5 min. In all cases, this produced a murky solution containing
an insoluble white precipitate. The two solutions were then
combined and stirred for an hour, resulting in the formation
of a green reaction mixture. The solvent was then removed
under reduced pressure and the residual solid was dissolved in
CH2Cl2. This solution was passed through a Celite plug and
the eluent was brought to dryness under vacuum. Crystals suit-
able for X-ray diffraction were grown by vapor diffusion of Et2O
into a CH2Cl2 solution of 3–6. Yields and characterization data
are stated below:
Independent synthesis of [(TPA)Cu(O2CPh)]ClO4 (12)
Under an inert atmosphere at ∼30 °C, Cu(ClO4)2·6H2O
(0.0675 mmol) dissolved in CH3CN (∼3 mL) and added to
solid TPA (0.0675 mmol). The resulting deep blue solution was
stirred for 30 min. This solution was then added to a vial con-
taining solid sodium benzoate (0.0675 mmol). Following
addition of methanol sufficient to produce a homogenous
mixture, the solution was stirred overnight (16 h). After
removal of the solvent under reduced pressure, the remaining
solid was dissolved in CH2Cl2 (∼3 mL), and the solution
passed through a Celite plug. The filtrate was collected and
brought to dryness under reduced pressure. Crystals suitable
for X-ray diffraction were grown by vapor diffusion of Et2O into
a solution of 12 dissolved in 1 : 1 CH3CN : CH2Cl2. Yield:
18.1 mg (47%). Anal. calc. C25H23ClCuN4O6·0.6CH2Cl2: C,
49.16; H, 3.90; N, 8.96. Found: C, 49.08; H, 3.70; N, 8.95.
ESI-MS: m/z calc. for C25H23CuN4O2, 474.1 [M − ClO4]+; found
474.2 [M − ClO4]+.
[(TPA)Cu(PhC(O)CHC(O)Ph)]ClO4 (3). (22 mg, 22%). Anal.
calc. for C33H29ClCuN4O6: C, 58.58; H, 4.32; N, 8.28. Found: C,
58.52; H, 4.17; N, 7.85. ESI-MS: m/z calc. for C33H29CuN4O2,
576.2 [M − ClO4]+; found 576.3 [M − ClO4]+. UV–vis (CH3CN)
λmax, nm (ε, M−1 cm−1): 356 (16 270). FT-IR (KBr, cm−1): 1600,
1550, 1520, 1380, 1090(νClO ), 630(νClO ).
4
4
[(TPA)Cu(4′-CH3-PhC(O)CHC(O)4′-CH3-Ph)]ClO4 (4). (27 mg,
29%). Anal. calc. for C35H33ClCuN4O6·0.1CH2Cl2: C, 59.11; H,
4.69; N, 7.86. Found: C, 58.89; H, 4.51; N, 7.85. ESI-MS: m/z
calc. for C35H33CuN4O2, 604.2 [M − ClO4]+; found 604.3 [M −
ClO4]+. UV–vis (CH3CN) λmax, nm (ε, M−1 cm−1): 360 (18 230).
FT-IR (KBr, cm−1): 1590, 1530, 1370, 1090(νClO ), 620(νClO ).
4
4
[(TPA)Cu(4′-OCH3-PhC(O)CHC(O)4′-OCH3-Ph)]ClO4
(5).
(34 mg, 35%). Anal calc. for C35H33ClCuN4O8·0.2CH2Cl2: C,
56.10; H, 4.47; N, 7.43. Found: C, 55.76; H, 4.19; N, 7.43.
ESI-MS: m/z calc. for C35H33CuN4O4, 636.2 [M − ClO4]+; found
636.3 [M − ClO4]+. UV–vis (CH3CN) λmax, nm (ε, M−1 cm−1):
367 (22 030). FT-IR (KBr, cm−1): 1600, 1530, 1370, 1260, 1180,
1090(νClO ), 620(νClO ).
Organic product isolation from reaction mixtures of 7–10
To gain insight into the anaerobic diketonate cleavage and
dehalogenation reactivity occurring in the reaction mixtures of
7–10 the organic products of each reaction were isolated and
characterized. Under an inert atmosphere in a N2-filled glove-
box at ∼30 °C, Cu(ClO4)2·6H2O (0.0675 mmol) was dissolved in
CH3CN (∼2 mL) and added to solid TPA (0.0675 mmol). The
deep blue solution was stirred for approximately 30 min. In a
separate vial, 2-chloro-1,3-bis(4′-R-phenyl)-1,3-propanedione (R
= –H, –CH3, –OCH3, –Cl) (0.0675 mmol) was combined with
lithium bis(trimethylsilyl)amide (0.0675 mmol) in Et2O
(∼2 mL). This solution was stirred for 5 min, producing a
yellow mixture with insoluble precipitate for all derivatives.
The solutions were then combined and stirred for 48 h. One
equivalent of triphenylmethane (Ph3CH) was then added as an
4
4
[(TPA)Cu(4′-Cl-PhC(O)CHC(O)4′-Cl-Ph)]ClO4 (6). (12 mg,
12%). Anal calc. for C33H27Cl3CuN4O6: C, 53.17; H, 3.65; N,
7.52. Found: C, 53.48; H, 3.61; N, 7.50. ESI-MS: m/z calc. for
C33H27Cl2CuN4O2, 644.1 [M − ClO4]+; found 644.1 [M − ClO4]+.
UV–vis (CH3CN) λmax, nm (ε, M−1 cm−1): 363 (19 650). FT-IR
(KBr, cm−1): 1589, 1530, 1365, 1093(νClO ), 626(νClO ).
4
4
Attempted syntheses of [(TPA)Cu(4′-R-PhC(O)CClC(O)4′-R-Ph)]
ClO4 (7–10)
Under an inert atmosphere at ∼30 °C, Cu(ClO4)2·6H2O internal standard and the solvent removed under reduced
(0.135 mmol) was dissolved in CH3CN (∼3 mL) and added to pressure. The solid residue was removed from the glovebox,
solid TPA (0.135 mmol). The resulting deep blue solution was dissolved in ethyl acetate and passed through a silica plug.
stirred for 30 min. In a separate vial, 2-chloro-1,3-bis(4′-R- The eluent was dried over anhydrous sodium sulfate and the
phenyl)-1,3-propanedione (R
= –H, –CH3, –OCH3, –Cl) solvent removed by rotary evaporation. The remaining solid
1
(0.135 mmol) was combined with lithium bis(trimethylsilyl) was dissolved in CDCl3 and the H NMR spectrum obtained.
amide (0.135 mmol) dissolved in Et2O (∼3 mL) and the result- The retro-Claisen 2-chloro-1-(4′-R-phenyl)ethanone products
ing mixture was stirred for 5 min. This produced a yellow solu- were identified by comparison of spectral features to analyti-
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cally pure samples that had been independently prepared.14 lated using EasySpin run within MatLab. All of the simulations
Quantification of each 2-chloro-1-(4′-R-phenyl)ethanone deriva- presented used a 25 G Gaussian line shape with other para-
tive was achieved via integration of its methylene resonance meters as noted in the text. Low temperature X-band EPR
versus the methine proton resonance at 5.55 ppm (relative to spectra of 6 and reactions mixtures for 7–10 were acquired on
CDCl3) of the Ph3CH internal standard. Control experiments a Bruker EMX EPR spectrometer with an OxfordITC503 liquid
and examples involving excess H2O (200 eq.) were performed helium cryostat. The spectra were collected at 12 K on samples
in a similar manner.
that were ∼3 mM in 1 : 1 acetonitrile/toluene. Other spectro-
meter settings: νMW = 9.38 GHz (20 μW); time constant/conver-
sion time = 21 ms; modulation amplitude 8 G (100 kHz); recei-
ver gain = 104; 10 scans.
Organic product recovery from the attempted synthesis of 7
under conditions wherein the amount of water is varied
To probe the role of water in the retro-Claisen reactivity identi-
fied in the attempted preparation of 7, under an inert atmo-
X-Ray crystallography
sphere, [(TPA)Cu(CH3CN)](ClO4)2 (0.0675 mmol) was dissolved Single crystals of 3–6, 11 and 12 were used for X-ray crystallo-
in dry CH3CN (∼2 mL) and the solution was stirred for graphy studies. Structures for 3, 4, 11 and 12 were determined
∼5 min. In a separate vial, 2-chloro-1,3-diphenyl-1,3-propane- at the University of Montana (UM) wherein a crystal of each
dione (0.0675 mmol) was combined with lithium bis(tri- was mounted on a glass fiber loop using viscous oil and trans-
methylsilyl)amide (0.0675 mmol) in Et2O (∼2 mL) and stirred ferred to a Bruker D8 Venture using MoKα (λ = 0.71073 Å) radi-
for 5 min, producing a yellow solution with an insoluble pre- ation for data collection at 100 K. The structure of 5 was deter-
cipitate. These solutions were then combined resulting in the mined by Rigaku, wherein a single crystal was mounted on a
formation of a green solution that was stirred for 48 h. The glass fiber using viscous oil and transferred to a XtaLAB
internal standard Ph3CH (1 eq.) was added and the solvent Synergy-S using MoKα (λ = 0.71073 Å) radiation for data collec-
removed under reduced pressure. The organic extraction pro- tion at 100 K. The structure of 6 was determined at Utah State
cedure involving ethyl acetate described above was then used University, wherein a single crystal of 6 was mounted on a
to isolate the organic products. Controls involving excess (200 glass fiber loop using viscous oil and transferred to a Rigaku
eq.) H2O, D2O and MeOH were performed the same way, XtaLAB Mini II Diffractometer using MoKα (λ = 0.71073 Å) radi-
except each was added 30 minutes after the reaction had ation for data collection at 100 K.
started.
Data were corrected for absorption using SADABS17 (3, 4, 11
and 12) or Gaussian grid (numerical integration) (5 and 6 with
6 having a 0.5 mm 1D horizontal Gaussian beam correction
for the graphite monochromator). Using Olex2,18 the structure
Dehalogenation reactivity of 2-chloro-1,3-bis(4′-phenyl)-1,3-
propanedione mediated by [(TPA)Cu(CH3CN)]PF6
Under an inert atmosphere, [(TPA)Cu(CH3CN)]PF6 (0.02 mmol) of each complex was solved with the SHELXT19 structure solu-
was dissolved in a mixture of CH3CN/Et2O (1 : 1; 3 mL). The tion program using direct methods and refined with the
resulting yellow solution was added to solid 2-chloro-1,3-diphe- SHELXL20 refinement package using least square minimiz-
nyl-1,3-propanedione (0.02 mmol) which resulted in the for- ation. All non-hydrogen atoms were refined with anisotropic
mation of a green solution. After stirring for 1 h, the solvent thermal parameters. Hydrogen atoms in each structure (except
was removed under reduced pressure. The remaining solid was for the acetonitrile in 11) were placed in geometrically calcu-
removed from the glovebox, dissolved in HCl (8 mL, 1 M) and lated positions and refined using a riding model. Isotropic
CH2Cl2 (8 mL), and stirred for 1 h. The organic layer was separ- thermal parameters of all hydrogen atoms were fixed to 1.2
ated, dried over sodium sulfate and subsequently filtered. The times the U value of the atoms they are linked to (1.5 times for
filtrate was collected and brought to dryness under reduced methyl groups). Calculations and refinement of structures
pressure using a rotary evaporator. 1H NMR analysis of the were carried out using APEX221 for 3 and 12 (APEX322 for 4
yellow solid showed a 1 : 1 mixture of 1,3-diphenyl-1,3-propane- and 11), SHELXTL,19 and Olex218 software. For 5 and 6, calcu-
dione and unreacted 2-chloro-1,3-bisphenyl-1,3-propanedione. lations and refinement of structures were carried out using
Repeating the reaction with two equivalents of [(TPA)Cu CrysAlisPro,23 SHELXL,20 and Olex218 software.
(CH3CN)]PF6 revealed the formation of 1,3-diphenyl-1,3-propa-
nedione as the primary product (89%).
3. The perchlorate anion in 3 was modelled over two posi-
tions using a PART instruction and tied to a single free vari-
able. Refinement of the free variable shows an approximate
67 : 33 disorder. Thermal ellipsoid constraints and similarity
EPR spectroscopy
Low-temperature X-band EPR of 3–5 were acquired on a Bruker restraints (EADP and SADI) were used to model the disorder.
EMX EPR spectrometer equipped with a DM-4116 dual mode The structure presented some difficulties in space group deter-
resonator and an Oxford instruments ESR-900 cryostat and mination. Violations of systematic absences lead to a discre-
temperature controller. Spectra were collected at 4.5 K on pancy between two monoclinic space groups P21 or P21/c. The
samples that were ∼3 mM in 50/50 dichloromethane/toluene. reflections violating the symmetry element conditions for the
Other spectrometer settings: νMW = 9.62 GHz (2 μW); time con- P21/c are weak, suggesting that possible disorder, a satellite
stant/conversion time = 42 ms; modulation amplitude 2 G (100 crystal, or a small contributing twin could be causing this
kHz); receiver gain = 105; 4 scans. The EPR spectra were simu- observation. Multiple data sets were collected although the
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weak reflections violating systematic absences persisted. with a highly axial Cu(II) center (Fig. 2). Attempts to simulate
Therefore, the data were solved (and refined) in both space the spectral features required the inclusion of both the 63,65Cu
group settings and compared. The centrosymmetric P21/c hyperfine couplings and the hyperfine couplings of all four
resulted in a higher R1 statistic than the P21 model however, TPA-derived 14N donors. 63,65Cu couplings of [A||, A⊥] = [510,
this is not a valid reason to pick one model over the other. 60] MHz with [g||, g⊥] = [2.27, 2.06] reproduce nearly all of the
Geometrical parameters for the P21/c model produced better salient features of this spectrum, with the exception of the
statistics than the P21 model when compared to structures in signal at ∼3180 G (marked with an asterisk in Fig. 2). The
Cambridge Structural Database using the Cambridge pattern of 14N hyperfine couplings suggests that two of the pyr-
Crystallographic Data Centre program Mogul24 and Mercury.25 idine nitrogen atoms define g|| ([A||, A⊥] = [40, 20]), with the
Considering the better geometrical model and the relatively other pyridine nitrogen ([A||, A⊥] = [20, 40]) and the tertiary
weak reflections violating the systematic absences the centro- amine ([A||, A⊥] = [40, 40]) lying in the xy-plane (Fig. S1†). The
symmetric P21/c model was chosen. EPR spectrum of 6 collected at 12 K in frozen CH3CN : toluene
6. After anisotropic refinement of non-hydrogen atoms and (1 : 1) contains similar features (Fig. S2†).
H placement, the flack parameter was calculated at 0.517. A
The absorption spectra of 3–6 dissolved in CH3CN contain
twin law of (−1, 0, 0, 0, −1, 0, 0, 0, −1) was introduced for the a π–π* band at ∼355–370 nm (Fig. S3–S7†). Exposure of solu-
subsequent refinements along with the calculation of a batch tions of 3–6 to air over 12 h produced no change in the absorp-
scale factor (BASF). Additionally, a solvent mask was calcu- tion features, consistent with the complexes being air stable.
lated, and 6 electrons were found in a volume of 32 A3 in 1 ESI-MS spectra show the expected molecular ion cluster for
void per unit cell. This is consistent with the presence of one [(TPA)Cu(4′-R-PhC(O)CHC(O)Ph-4′-R)]+ for 3–6 (Fig. S8–S11†)
CH3CH2OCH2CH3 per asymmetric unit which accounts for 84 as well as a cluster for the [(TPA)Cu–Cl]+ ion may be appearing
electrons per unit cell.
as a result of perchlorate reduction in the mass spectrometer.
FTIR spectra of 3–6 collected as KBr pellets are provided in
Fig. S12–S15.†
Overall, 3–6 represent rare examples of structurally charac-
terized six coordinate Cu(II) diketonate complexes. TPA-ligation
differentiates 3–6 from 1 which exhibits a five-coordinate Cu(II)
center due to the weaker donation of a phenyl-appended
pyridyl donor.
Results and discussion
Synthesis and characterization of TPA-ligated Cu(II) diketonate
complexes 3–6
The series of complexes [(TPA)Cu(4′-R-PhC(O)CHC(O)4′-R-Ph)]
ClO4 (R = –H (3), –CH3 (4), –OCH3 (5), –Cl (6)) was synthesized
(Scheme 3) and isolated in crystalline form. Each complex was
characterized by elemental analysis, X-ray crystallography, EPR,
UV-Vis, ESI-MS and FT-IR (Fig. S1–S15†). The cation of 3
(Fig. 1(a)) exhibits a six-coordinate Cu(II) center with two
axially coordinated NPy donors with Cu–N distances of ∼2.3 Å
and equatorial Nam and Npy donors at 2.10 and 2.01 Å, respect-
ively. The cationic portions of 4–6 (Fig. 1(b)–(d)†) which have
electron donating (4, 5) or withdrawing (6) substituents on the
diketonate ligand, exhibit a more distorted geometry with one
weak axial Cu–NPy interaction (>2.75 Å). While variation is
found in the axial Cu–Npy interactions, 3–6 exhibit similar
equatorial Cu(II)–Nam and Cu–Npy distances (2.043–2.062 Å and
1.982–1.994 Å, respectively) to those found in 3. Both oxygen
donors of the diketonate ligand lie in the equatorial plane in
3–6, with Cu(II)–O distances in the range of 1.923–1.947 Å.
Frozen CH2Cl2 : toluene (1 : 1) solutions of 3–5 examined at
4.5 K exhibit similar EPR spectral features that are consistent
Anaerobic reactivity of TPA-ligated Cu(II) chlorodiketonate
complexes
We next targeted for synthesis a series of Cu(II) chlorodiketo-
nate complexes with the eventual goal of examining their reac-
tivity with O2 for comparison to the reactivity of 1 (Scheme 2).
Following the synthetic procedure outlined in Scheme 3 for
the preparation of 7–10 under N2 we found that a mixture of
products was generated. This initially became evident when we
attempted to crystallize the R = –OCH3 derivative 9 and
obtained X-ray quality crystals of [(TPA)Cu(4′-OCH3-PhC(O)
CHC(O)4′-OCH3-Ph)]ClO4 (5) and [(TPA)Cu–Cl]2[Li(ClO4)3] (11)
(Fig. S16†). The isolation of these complexes provides evidence
for dehalogenation reactivity. We subsequently investigated
each reaction mixture using ESI-MS. In the attempted syn-
thesis of the parent complex, [(TPA)Cu(PhC(O)C(Cl)C(O)Ph)]
ClO4 (7), isotope clusters were identified for the desired
product [(TPA)Cu(PhC(O)CClC(O)Ph)]+ (m/z 610.2) along with
clusters for [(TPA)Cu(PhC(O)CHC(O)Ph)]+ (m/z 576.3), [(TPA)
CuCl]+ (m/z 388.1) and [(TPA)Cu(O2CPh)]+ (m/z 474.2)
(Fig. S17†). Thus, in addition to the dehalogenation reactivity
noted above, the formation of the benzoate cluster also pro-
vided evidence for aliphatic C–C bond cleavage reactivity.
[(TPA)Cu(O2CPh)]ClO4 (12) was independently synthesized and
characterized by X-ray crystallography (Fig. S18†) and ESI-MS
(Fig. S19†) to support the formulation of this carboxylate
product. Similar ESI-MS reaction mixtures were found for the
Scheme 3 Synthesis of 3–6.
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Fig. 1 Representations of the cationic portions of the X-ray structures of 3 (a), 4 (b), 5 (c), and 6 (d). Ellipsoids are plotted at the 50% probability
level. Only one of two similar cations found in the asymmetric units of 3 and 6 are shown. Hydrogen atoms have been omitted for clarity.
(CHPh3) (Scheme 4). 1H NMR analysis of the organics revealed
the presence of
a 4′-R-chloroacetophenone derivative in
17–31% yield depending on the chlorodiketonate substituent
(Table 1, entries 1–4; Fig. S23–S26†). Addition of excess water
(200 eq.) more than doubled the yield of chloroacetophenone
for R = H, Cl (entries 5 and 8) but produced a lesser effect for
R = –CH3, –OCH3 (entries 6 and 7; Fig. S27–S30†). Eliminating
water from the reaction mixture by treating [(TPA)Cu(CH3CN)]
(ClO4)2 with 2-chloro-1,3-diphenyl-1,3-propanedione and
LiHMDS in dry CH3CN/Et2O produced no chloroacetophenone
(entry 9; Fig. S31†). However, addition of 200 eq. of water to
the mixture produced 34% yield of chloroacetophenone (entry
10; Fig. S32†) providing evidence for the necessity of water for
C–C cleavage. Using D2O (entry 11; Fig. S33†), d2-2-chloro-1-
(phenyl)ethanone was formed, indicating the methylene
protons in the product are derived from water. Use of excess
MeOH (200 eq.; entry 12; Fig. S34†) instead of water produces
2-chloro-1-(phenyl)ethanone (24%) as well as methyl benzoate
(16% yield). This ester represents the cleavage product that is
Fig. 2 EPR spectra of 3–5 in CH2CH2 : toluene (1 : 1) at 4.5 K and a
simulated spectrum. For 3–5, g|| = 2.27, g⊥ = 2.06, and 63,65Cu couplings
of [A||, A⊥] = [510, 60] MHz.
methyl-, methoxy- and chloro-substituted chlorodiketonate
derivatives (Fig. S20–S22†).
To gain further insight into the reaction mixtures of 7–10,
the free organic products in each were isolated via drying of
the mixture under reduced pressure followed by extraction
using ethyl acetate in the presence of an internal standard
Table 1 Yield of 2-chloro-1-(4’-R-phenyl)ethanone produced via retro-
Claisen reactivity
Entry
Ligand
R
% yield
1
2
3
4
5
6
7
8
TPA
TPA
TPA
TPA
H
22(3)
31(3)
28(1)
17(2)
49(1)
38(2)
28(2)
56(4)
0
CH3
OCH3
Cl
TPAa
TPAa
TPAa
TPAa
TPAb
TPAa,b
TPAb,c
H
CH3
OCH3
Cl
H
H
H
H
H
H
9
10
11
12
13
14
15
16
34
40
TPAb,d
24e
f
0
8
g
6-Ph2TPA
BPY
H
H
8(2)
13(2)
a 200 eq. of H2O added. b The reaction was performed using [(TPA)
CuII(CH3CN)](ClO4)2. c 200 eq. D2O added. d 200 eq. MeOH added.
e Methyl benzoate observed (16%). f Cu(ClO4)2·6H2O with no support-
ing chelate ligand. This reaction was worked up using HCl (4 mL, 1 M)
and CH2Cl2 (4 mL) instead of ethyl acetate. g 2-Chloro-1,3-diphenyl-1,3-
propanedione in the presence of LiHMDS and water (6 eq.) in CH3CN/
Et2O (1 : 1).
Scheme 4 Aliphatic C–X and C–C bond cleavage reactivity identified
in anaerobic reaction mixtures directed at the synthesis of TPA-ligated
Cu(II) chlorodiketonate complexes.
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benzoate in the H2O-mediated retro-Claisen reaction. The dis-
crepancy of the percentage yield between 2-chloro-1-(phenyl)
ethanone (bp 244–245 °C) and methyl benzoate (bp
198–200 °C) is related to the higher volatility of the latter.
A control reaction involving no TPA ligand provided evi-
dence that the supporting ligand is required for retro-Claisen
reactivity (entry 13; Fig. S35†). However, treatment of 2-chloro-
1,3-diphenyl-1,3-propanedione with LiHMDS and H2O in
absence of Cu(II) and TPA did produce a small amount of
2-chloro-1-(phenyl)ethanone (entry 14). Use of 6-Ph2TPA or
BPY as the supporting chelate ligand produced lower amounts
of the retro-Claisen product (entries 15 and 16; Fig. S36 and
S37†) than those found for the TPA-containing systems. Unlike
7–10, the Cu(II) chlorodiketonate complexes [(6-Ph2TPA)Cu
(PhC(O)CClC(O)Ph)]ClO4 (1) and [(bpy) Cu(PhC(O)CClC(O)Ph)]
ClO4 (2) can be isolated in reasonable yields as analytically
pure crystalline solids.8,9 This is consistent with the lower level
of retro-Claisen reactivity in these systems. The chloro substi-
tuent on the central carbon is required for the retro-Claisen
reactivity, as evidenced by no observed acetophenone pro-
duction for 3 (Fig. S38†). Notably, performing the product iso-
lation studies for 7 under O2 produced only a trace amount of
the retro-Claisen product and no oxidative cleavage products
(Fig. S39†). This lack of reactivity necessitates further investi-
gation, but initially indicates that the TPA-ligated complex
exhibits notably different reactivity than 1 and 2 in terms of
the cleavage of the chlorodiketonate ligand.
Fig. 3 EPR spectra of aliquots from the reaction mixture of 7 after stir-
ring for 1 h (black) and 48 h (red) at 30 °C. The samples were collected
in CH3CN : toluene (1 : 1) at 12 K. For the first product, g|| = 2.27, g⊥
=
2.08.
dehalogenation product [(TPA)Cu(PhC(O)CHC(O)Ph)]ClO4 (3).
The cations of both species were detected by ESI-MS.
Additional species that may be present based on ESI-MS could
be [(TPA)CuCl]+ or [(TPA)Cu(O2CPh)]+. An independently pre-
pared sample of [(TPA)Cu(O2CPh)]ClO4 (12) (Fig. S42†) exhibi-
ted EPR features consistent with a trigonal bipyramidal Cu(II)
center with g⊥ > g∥ and an unpaired electron in the dz2 orbital.
Contributions from such a species are suggested by the EPR
spectral features observed after 48 h for reaction mixtures
involving 8 and 9 (Fig. S43 and S44†). The EPR features for 10
(Fig. S45†) are similar to those of 7.
Absorption spectra of the reaction mixture involving 7 were
collected at 1, 24 and 48 h. These features were compared to
those of analytically pure 3 dissolved in CH3CN. A π–π* band is
present at 351 nm for the reaction mixture for 7 (Fig. S46†),
after 1 h which is slightly blue-shifted compared to the π–π*
band of 3 (356 nm). This feature indicates the formation of
diketonate complexes in the solution of 7 and changes mini-
mally over time. The d–d region for 7 after 1, 24 and 48 h was
also examined and compared to that of 3 (Fig. 4) and the ben-
Mechanistic investigations and in situ spectroscopic studies
To gain further insight into the dehalogenation and retro-
Claisen reactions identified in the reaction mixtures directed at
the formation of the TPA-ligated Cu(II) chlorodiketonate com-
plexes, additional mechanistic and spectroscopic investigations
were performed. While the dehalogenation product in the reac-
tions of 7–10 was not quantified, it appears in higher amounts in
the organic recovery of reaction mixtures containing excess water.
Organic dehalogenation reactivity is known for TPA-ligated Cu(I)
complexes to give [(TPA)Cu(II)-Cl]+ salts.26–28 We found that
mixing [(TPA)Cu(CH3CN)]PF6 with 2-chloro-1,3-diphenyl-1,3-pro-
panedione in CH3CN results in dehalogenation (Scheme S1 and
Fig. S40, S41†). Maximum yield is obtained using two equivalents
of [(TPA)Cu(CH3CN)]PF6 consistent with the two-electron
reduction of 2-chloro-1,3-diphenyl-1,3-propanedione to 1,3-diphe-
nyl-1,3-propanedione. Based on these studies, dehalogenation
reactivity could result from reduction of in situ generated [(TPA)
Cu(CH3CN)](ClO4)2 in CH3CN to give [(TPA)Cu(CH3CN)]+ which
mediates the dehalogenation. However, at this time, we cannot
identify the reducing agent for Cu(II) in the system.
We next investigated the reaction mixture of 7 as a function
of time using EPR. Aliquots for EPR studies were removed after
1 and 48 h of stirring at ∼30 °C, respectively. Each sample was
brought to dryness under reduced pressure, dissolved in
CH3CN/toluene (1 : 1) and subsequently frozen in liquid N2.
Spectra collected at 12 K are shown in Fig. 3. At least two
species are present, with one having g values (g|| > g⊥) similar
Fig. 4 Absorption spectral features of 3, in situ 7 at 1, 24 and 48 h, and
to 3–6. This may be [(TPA)Cu(PhC(O)CClC(O)Ph)]ClO4 (7) or its [(TPA)Cu(O2CPh)]ClO4 (12) in CH3CN.
1718 | Dalton Trans., 2021, 50, 1712–1720
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which exceeds that of analogs supported by chelate ligands
with fewer and/or weaker pyridyl interactions. These studies
demonstrate that the number of pyridyl donors surrounding a
Cu(II) center influences diketonate reactivity and therefore
should be a factor considered in reactions involving Cu(II) salt-
mediated diketonate cleavage reactivity.
Conflicts of interest
The authors declare no conflict of interest.
Acknowledgements
Scheme 5 Proposed mechanism of retro-Claisen reactivity in 7–10.
We thank the National Science Foundation (CHE-1664977 to
LMB; CHE-1429195 for Brüker Avance III HD 500 MHz NMR;
CHE-1828764 for Rigaku Benchtop XtaLAB Mini II X-ray diffr-
actometer). X-ray crystallographic studies of 3, 4, 11 and 12
were performed at the University of Montana (NIH, COBRE
NIGMS P20GM103546). Single crystal X-ray diffraction data
zoate complex 12. An enhanced d–d absorbance at ∼850 nm in
the reaction mixture of 7 at 1 h suggests the possible formation
of a mixture that includes trigonal bipyramidal Cu(II) species
in solution. This assessment is based on spectral comparison
to the features for [(TPA)CuCl]Cl (d–d absorption ∼855 nm)
and [(TPA)Cu(O2CPh)]+ (d–d absorption ∼876 nm).29,30
Notably, organic product recovery at 1 h (Fig. S47†) indicates
minimal dehalogenation or retro-Claisen reactivity has
occurred to that point. This suggests changes in the geometry
of the Cu(II) center prior to anaerobic C–C and C–X bond clea-
vage. After 48 h, when organic dehalogenation and retro-
Claisen products have been formed, the presence of the
∼850 nm absorption feature is consistent with the formation
of [(TPA)CuCl]+ and [(TPA)Cu(O2CPh)]+ (12), which is sup-
ported by the ESI-MS and EPR data.
were collected using
a Bruker D8 Venture (NSF MRI
CHE-1337908). We would also like to thank Dr. Zhiyong Yang
for his assistance with the collection of EPR data.
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