New Copper Complexes with N,O-Donor Ligands Based on Pyrazole Moieties Supported by 3-Substituted Acetylacetone Scaffolds

The new 3-monosubstituted acetylacetone ligands, 3-(phenyl(1H-pyrazol-1-yl)methyl)pentane-2,4-dione (HLacPz) and 3-((3,5-dimethyl-1H-pyrazol-1-yl)(phenyl)methyl)pentane-2,4-dione (HLacPzMe), were synthesized and used as supporting ligands for new copper(II) and copper(I) phosphane complexes of the general formulae [Cu(HLacX)2(LacX)2] and [Cu(PPh3)2(HLacX)]PF6 (X = Pz (pyrazole) or PzMe (3,5-dimethylpyrazole)), respectively. In the syntheses of the Cu(I) complexes, the triphenylphosphine coligand (PPh3) was used to stabilize copper in the +1 oxidation state, avoiding oxidation to Cu(II). All compounds were characterized by CHN analysis, 1H-NMR, 13C-NMR, FT-IR spectroscopy, and electrospray ionization mass spectrometry (ESI-MS). The ligands HLacPz (1) and HLacPzMe (2) and the copper complex [Cu(PPh3)2(HLacPz)]PF6 (3) were also characterized by X-ray crystallography. The reactivity of these new compounds was investigated and the new compounds 4-phenyl-4-(1H-pyrazol-1-yl)butan-2-one (7) and 4-(3,5-dimethyl-1H-pyrazol-1-yl)-4-phenylbutan-2-one (8) were obtained in basic conditions via the retro-Claisen reaction of related 3-monosubstituted acetylacetone, providing efficient access to synthetically useful ketone compounds. Compound 8 was also characterized by X-ray crystallography.

β-diketones are known to form complexes with almost every metal [16] and despite the enormous amount of work devoted to the synthesis and characterization of copper(II) β-diketonate complexes [27], there are relatively few reports devoted to the corresponding Cu(I) complexes showing undergoing disproportionation to copper metal and copper(II) compounds in the absence of stabilizing ligands [28][29][30].In particular, very little attention has been paid to the study of triorganophosphane adducts of copper(I) β-diketonates of the general formula (β-diketonate)Cu(PR 3 ) n , although a rich structural diversity can also be expected there [31][32][33][34][35][36][37][38][39][40][41][42][43].On the other hand, very few studies on the biological activity of group 11 metal complexes of β-diketones have been reported in the literature to date [44] and copper(I)-based anticancer complexes supported by β-diketonate ligands remain an unexplored research field.Recently, as part of our continuous investigation on the chemical and biological properties of coinage metal complexes [45][46][47][48][49][50][51], we reported the first study on the syntheses, characterization and biological evaluation of new Cu(I) complexes containing triorganophosphanes and the anion of several sterically hindered the β-diketone ligands [52].
On the other hand, α-monosubstituted β-diketones exhibit a range of reactivities depending on the nature of the substituents attached to the α-carbon atom [53].The presence of the α-substituent significantly influences the behavior of these compounds, affecting their stability, reactivity, and reaction pathways [54].There are three possible tautomeric isomers for symmetric and α-monosubstituted β-diketones (Scheme 1).Many factors influence the keto-enol tautomeric equilibrium [53,55], and among them it was found that electronegative β-substituents (R groups in Scheme 1) sharply increase the degree of enolization, whereas α-substituents (Z group in Scheme 1) cause a marked decrease in the percentage of enol [56].However, the cause is mainly steric-repulsion between the α-moiety and the other β-substituents, which makes the chelate ring of the cis-enolic form unstable [55].On the other hand, for 3-substituted-2,4-pentanediones, the keto form is predominant in the presence of bulky substituents in the 3-position [56].
Therefore, as an extension of our studies on pyrazolyl derivatives and as part of our continuous investigation on the chemical and biological properties of copper-containing coordination compounds [46][47][48][49]52,86], we report here for the first-time a study on the syntheses, characterization and reactivity of new 3-monosubstituted acetylacetone ligands, HL acPz and HL acPzMe (Scheme 2), and related Cu(II) and Cu(I) complexes containing phosphane co-ligands, that could be evaluated for their biological effects and for their catalytic activity and selectivity.In particular, these species may be considered as versatile coordinating ligands having two different donor sites of different Pearson hardness [87] (a soft neutral nitrogen atom of the pyrazolyl moiety and a hard oxygen donor atoms of the acetylacetone moiety).In addition, in contrast to the aforementioned ditopic 3monosubstituted acetylacetone ligands, HL acPz and HL acPzMe may act also as bidentate ligands at either the N or the O donor sites.In an endeavor to extend the range of metal chelates in which the β-diketones attain a conformation other than the usually encountered [85], herein we report the crystal structure of compound Scheme 1. Keto-enol tautomeric equilibria.
Therefore, as an extension of our studies on pyrazolyl derivatives and as part of our continuous investigation on the chemical and biological properties of copper-containing coordination compounds [46][47][48][49]52,86], we report here for the first-time a study on the syntheses, characterization and reactivity of new 3-monosubstituted acetylacetone ligands, HL acPz and HL acPzMe (Scheme 2), and related Cu(II) and Cu(I) complexes containing phosphane co-ligands, that could be evaluated for their biological effects and for their catalytic activity and selectivity.In particular, these species may be considered as versatile coordinating ligands having two different donor sites of different Pearson hardness [87] (a soft neutral nitrogen atom of the pyrazolyl moiety and a hard oxygen donor atoms of the acetylacetone moiety).In addition, in contrast to the aforementioned ditopic 3-monosubstituted acetylacetone ligands, HL acPz and HL acPzMe may act also as bidentate ligands at either the N or the O donor sites.In an endeavor to extend the range of metal chelates in which the β-diketones attain a conformation other than the usually encountered [85], herein we report the crystal structure of compound [Cu(HL acPz )(PPh 3 ) 2 ]PF 6 that reveals the formation of a chelate complex, wherein the HL acPz ligand coordinates in bidentate κ 2 N,O fashion to the copper(I) ion.

Synthesis and Characterization
The ligands HL acPz (1) and HL acPzMe (2) were prepared, using a modified literature method [88], from the reaction of 3-benzylidenepentane-2,4-dione and pyrazole or 3,5dimethylpyrazole, respectively, in ethanol solution with triethylamine as basic catalyst, and isolated as white solids in very good yield and high purity (Scheme 2).The precursor 3-benzylidenepentane-2,4-dione can be synthetized by Knövenagel condensation of an equimolar amount of acetylacetone and benzaldehyde in the presence of piperidine as a catalyst [89,90].
Ligands 1 and 2 are soluble in methanol, diethyl ether, chloroform, acetonitrile, DMSO, THF, dichloromethane, ethyl acetate and acetone.They were fully characterized by multinuclear NMR spectroscopy, FT-IR, ESI-MS and elemental analysis.A batch of good quality crystals of 1 and 2, suitable for X-ray analysis, was obtained by slow evaporation of a n-hexane and diethyl ether/ n-hexane solution, respectively.
The IR spectra of 1 and 2 have been carried out on solid samples and show all the expected absorption bands.Weak bands in the region 2916-3108 cm −1 are assigned to C-H stretching vibrations.The ligands also show two sharp strong bands in the region 1699-1732 cm −1 attributable to the stretching vibrations of the two carbonyl groups.The bands at ca. 1500 cm −1 correspond to C=C/C=N rings stretching.The 1 H-NMR spectra of HL acPz and HL acPzMe in CDCl3 suggest the presence of the keto form in solution.In the 1 H-NMR spectrum of 1, the 3-CH and 4-CH protons of pyrazole ring are present at 7.50 and 6.22 ppm, respectively.The 5-CH of pyrazole and the CH aromatic protons of the phenyl ring are present in the range 7.32-7.41ppm.The α-CH and γ-CH protons are present at 5.32 (J = 11.28Hz) and 6.01 ppm (J = 11.28Hz).The singlets at 2.03 and 2.22 ppm are attributable to the methyl groups bonded to the β-dicarbonyl moieties.In the 13 C-NMR spectrum in CDCl3, the C=O signals are detectable at about 200.0 ppm, while the α-CH and γ-CH carbons are visible at 72.6 and 64.2 ppm; the 4-CH of the pyrazole ring and the CH3 carbons are present at 106.1 and 29.9-30.9ppm, respectively.In the 1 H-NMR spectrum of 2 recorded in CDCl3 solution, the CH aromatic protons are present in the range 7.28-7.37ppm and the α-CH and γ-CH proton are present at 5.82 ppm (J = 11.13Hz) and 5.41 ppm (J = 11.11Hz), respectively The singlets in the range 2.00-2.22ppm are attributable to the methyl groups bonded to the β-dicarbonyl moieties and to the 3-and 5-CH3 of pyrazole, while the 4-CH proton is present as a singlet at 5.75 ppm.In the 13 C-NMR spectrum, the C=O signals are detectable at 199.9 and 200.9 ppm, while the α-and γ-CH are at 72.4, and 60.6 ppm.The 4-CH carbon of the pyrazole ring is detectable at 105.6 ppm, while the 3and 5-CH3 of the pyrazole and the CH3 of the β-dicarbonyl moieties are present at 10.9-13.6 and 30.3-31.6, respectively.The ESI-MS study has been performed by dissolving 1 and 2 in CH3CN and recording the spectra in the positive-and negative-ion modes.The molecular structure of 1 has been confirmed by the presence of the molecular peaks at m/z Scheme 2. Synthesis of HL acPz (1) and HL acPzMe (2) ligands.

Synthesis and Characterization
The ligands HL acPz (1) and HL acPzMe (2) were prepared, using a modified literature method [88], from the reaction of 3-benzylidenepentane-2,4-dione and pyrazole or 3,5dimethylpyrazole, respectively, in ethanol solution with triethylamine as basic catalyst, and isolated as white solids in very good yield and high purity (Scheme 2).The precursor 3-benzylidenepentane-2,4-dione can be synthetized by Knövenagel condensation of an equimolar amount of acetylacetone and benzaldehyde in the presence of piperidine as a catalyst [89,90].
Ligands 1 and 2 are soluble in methanol, diethyl ether, chloroform, acetonitrile, DMSO, THF, dichloromethane, ethyl acetate and acetone.They were fully characterized by multinuclear NMR spectroscopy, FT-IR, ESI-MS and elemental analysis.A batch of good quality crystals of 1 and 2, suitable for X-ray analysis, was obtained by slow evaporation of a n-hexane and diethyl ether/n-hexane solution, respectively.
The IR spectra of 1 and 2 have been carried out on solid samples and show all the expected absorption bands.Weak bands in the region 2916-3108 cm −1 are assigned to C-H stretching vibrations.The ligands also show two sharp strong bands in the region 1699-1732 cm −1 attributable to the stretching vibrations of the two carbonyl groups.The bands at ca. 1500 cm −1 correspond to C=C/C=N rings stretching.The 1 H-NMR spectra of HL acPz and HL acPzMe in CDCl 3 suggest the presence of the keto form in solution.In the 1 H-NMR spectrum of 1, the 3-CH and 4-CH protons of pyrazole ring are present at 7.50 and 6.22 ppm, respectively.The 5-CH of pyrazole and the CH aromatic protons of the phenyl ring are present in the range 7.32-7.41ppm.The α-CH and γ-CH protons are present at 5.32 (J = 11.28Hz) and 6.01 ppm (J = 11.28Hz).The singlets at 2.03 and 2.22 ppm are attributable to the methyl groups bonded to the β-dicarbonyl moieties.In the 13 C-NMR spectrum in CDCl 3 , the C=O signals are detectable at about 200.0 ppm, while the α-CH and γ-CH carbons are visible at 72.6 and 64.2 ppm; the 4-CH of the pyrazole ring and the CH 3 carbons are present at 106.1 and 29.9-30.9ppm, respectively.In the 1 H-NMR spectrum of 2 recorded in CDCl 3 solution, the CH aromatic protons are present in the range 7.28-7.37ppm and the α-CH and γ-CH proton are present at 5.82 ppm (J = 11.13Hz) and 5.41 ppm (J = 11.11Hz), respectively The singlets in the range 2.00-2.22ppm are attributable to the methyl groups bonded to the β-dicarbonyl moieties and to the 3-and 5-CH 3 of pyrazole, while the 4-CH proton is present as a singlet at 5.75 ppm.In the 13 C-NMR spectrum, the C=O signals are detectable at 199.9 and 200.9 ppm, while the αand γ-CH are at 72.4, and 60.6 ppm.The 4-CH carbon of the pyrazole ring is detectable at 105.6 ppm, while the 3-and 5-CH 3 of the pyrazole and the CH 3 of the β-dicarbonyl moieties are present at 10.9-13.6 and 30.3-31.6, respectively.The ESI-MS study has been performed by dissolving 1 and 2 in CH 3 CN and recording the spectra in the positive-and negative-ion modes.The molecular structure of 1 has been confirmed by the presence of the molecular peaks at m/z 257 and 279, respectively, attributable to the [HL acPz + H] + and [HL acPz + Na] + species.Analogously, in the positive-ion spectrum of 2 peaks at m/z 285 and 307, respectively, are attributable to the [HL acPzMe + H] + and [HL acPzMe + Na] + species.The Cu(I) complex [Cu(HL acPz )(PPh 3 ) 2 ]PF 6 (3) was prepared from the reaction of PPh 3 , Cu(CH 3 CN) 4 PF 6 and the ligand 1, in CH 3 CN solution.Complex 3 is soluble in CHCl 3 , CH 3 CN, DMSO and acetone.Compound 3 was fully characterized by multinuclear NMR spectroscopy, FT-IR, ESI-MS and elemental analysis and a batch of good quality crystals, suitable for X-ray analysis, was obtained by slow evaporation of an acetone/ethyl acetate solution.The IR spectrum carried out on a solid sample of 3 shows all the expected bands for the β-diketone ligand and the triphenylphosphine co-ligand.The absorptions due to the C=O stretching are at 1687-1727 cm −1 ; they do not significantly vary with respect to the same absorptions of the carbonyl group detectable in the spectrum of the free ligand (1699-1732 cm −1 ).In a lower-frequency region, complex 3 shows a broad strong band at 831 cm −1 due to the stretching vibrations of the PF 6 − anion.The δ(PF 6 ) bending vibration is observed as a narrow strong band at 560 cm −1 .In the 1 H-NMR spectra of 3, recorded in acetone-d 6 solution at room temperature, the 3-CH and 4-CH protons of the pyrazole ring are present at 7.72 and 6.21 ppm, while the 5-CH proton of the pyrazole ring and the CH aromatic protons of the phenyl rings are present in the range 7.33-7.57ppm.The α-CH and γ-CH bridging protons are present at 5.53 ppm (J = 11.40Hz) and 6.10 ppm (J = 11.42Hz).The singlets at 2.19 and 2.84 ppm are attributable to the methyl groups of the acetylacetone fragment; the signal at 2.84 is shifted with respect to the signal of the free ligand in the same solvent.In the 13 C-NMR spectrum in acetone-d 6 , the C=O signals, are detectable at about 200 ppm.The 31 P{H}-NMR spectrum of the Cu(I) complex 3, recorded in CDCl 3 solution at room temperature, gave a broad singlet at −0.86 ppm downfield shifted with respect to the value of the free phosphane (δ = −5.36ppm).In the spectrum, the characteristic septet centered at −144.21 ppm is due to the PF 6 − counterion.Compound [Cu(HL acPzMe )(PPh 3 ) 2 ]PF 6 . 2CH 3 CN (5) was prepared similarly to compound 4 from the reaction of PPh 3 , Cu(CH 3 CN) 4 PF 6 and the ligand 2, in CH 3 CN solution and it was fully characterized.Complex 5 is soluble in CHCl 3 , CH 2 Cl 2 , CH 3 CN, ethyl acetate, THF, DMSO and acetone.The IR spectrum carried out on a solid sample of 5 shows all the expected bands for the β-diketone ligand and the triphenylphosphine co-ligand.The absorptions due to the C=O stretching are at 1700-1730 cm −1 ; they do not significantly vary with respect to the same absorptions of the carbonyl group detectable in the spectrum of the free ligand (1699-1729 cm −1 ).Very strong bands at 832 and 557 cm −1 are due to the stretching vibrations and the δ(PF 6 ) bending vibrations, respectively, of the PF 6 − anion.In the 1 H-NMR spectra of 5, recorded in CDCl 3 solution at room temperature, the 3-and 5-CH 3 protons of the pyrazole ring are present at 2.21 ppm, while the 4-CH proton of the pyrazole ring and the CH aromatic protons of the phenyl rings are present at 5.86 and at in the range 7.19-7.41ppm, respectively.The α-CH and γ-CH bridging protons are present at 5.44 and 5.77 ppm.The singlets at 2.19 and 2.84 ppm are attributable to the methyl groups of the acetylacetone fragment; the signal at 2.84 is shifted with respect to the signal of the free ligand in the same solvent.In the 13 C-NMR spectrum in CDCl 3 , the C=O signals, are detectable at about 200 ppm.The 31 P{H}-NMR spectrum of 5, recorded in CDCl 3 solution at room temperature, gave a singlet at −0.12 ppm downfield shifted with respect to the value of the free phosphane.In the spectrum, the characteristic septet centered at −144.21 ppm is due to the PF 6 − counterion.The ESI-MS study was performed by dissolving 3 and 5 in CH 3 CN and recording the spectra in the positive-and negative-ion modes.The molecular structure of 3 was confirmed by the presence of the peak at m/z 865, attributable to the molecular peak [Cu(L acPz )(PPh 3 ) 2 + Na] + ; in addition, peaks at m/z 581 and 603 are attributable to the [Cu(HL acPz )(PPh 3 )] + and [Cu(L acPz )(PPh 3 ) + Na] + species, being positive fragments of the dissociation of the PPh 3 coligand from the complex.In both the compounds, the peaks at m/z 587 are due to the fragments of the dissociation of the ligand [Cu(PPh 3 ) 2 ] + .The ESI-MS spectra of 3 and 5 in CH 3 CN recorded in the negative-ion mode show peaks at m/z 145 attributable to the PF 6 − aggregate, confirming the presence of the counterion (PF 6 − ).The copper(II) complexes [Cu(HL acPz ) 2 (L acPz ) 2 ] (4) and [Cu(HL acPzMe ) 2 (L acPzMe ) 2 ] (6) were prepared from the reaction of Cu(CH 3 CO 2 ) 2 •H 2 O with HL acPz (1) and HL acPzMe (2), respectively, in methanol solution at room temperature, starting from a 1:4 stoichiometric ratio between metal and ligands.The syntheses were also performed starting from a 1:2 stoichiometric ratio obtaining the same products.The Cu(II) compounds 4 and 6 are soluble in Et 2 O, CH 2 Cl 2 , CHCl 3 , EtOAc, MeCN, DMSO, acetone and are air stable even as solutions; compound 6 is soluble in methanol too.The authenticity of compounds 4 and 6 was confirmed by elemental analysis, IR spectroscopy and electrospray mass spectra.The infrared spectra showed all the bands required by the presence of the chelating donors.In the spectra of compounds 4 and 6, weak absorptions due to the CH stretching were observed at 2916-3107 cm −1 .The carbonylic asymmetric stretching of 4 and 6 is detectable as strong absorptions at 1700-1734 cm −1 , together with medium signals at 1667 and 1659 cm −1 , respectively, in the typical range of β-diketonate systems [91].The ESI-MS study was conducted by dissolving the Cu(II) complex compounds in acetonitrile, and recording the spectra in the positive-and negative-ion modes.In the positive-ion spectrum of 4, it is possible to detect peaks at m/z 318 and 360 attributable to the [Cu(L acPz )]+ and [Cu(L acPz ) + CH 3 CN] + species, confirming the complex formation.
in the negative-ion mode show peaks at m/z 145 attributable to the PF6 -aggregate, confirming the presence of the counterion (PF6 -).
The copper(II) complexes [Cu(HL acPz )2(L acPz )2] ( 4) and [Cu(HL acPzMe )2(L acPzMe )2] (6) were prepared from the reaction of Cu(CH 3 CO 2 ) 2 •H 2 O with HL acPz (1) and HL acPzMe (2), respectively, in methanol solution at room temperature, starting from a 1:4 stoichiometric ratio between metal and ligands.The syntheses were also performed starting from a 1:2 stoichiometric ratio obtaining the same products.The Cu(II) compounds 4 and 6 are soluble in Et 2 O, CH 2 Cl 2 , CHCl 3 , EtOAc, MeCN, DMSO, acetone and are air stable even as solutions; compound 6 is soluble in methanol too.The authenticity of compounds 4 and 6 was confirmed by elemental analysis, IR spectroscopy and electrospray mass spectra.The infrared spectra showed all the bands required by the presence of the chelating donors.In the spectra of compounds 4 and 6, weak absorptions due to the CH stretching were observed at 2916-3107 cm −1 .The carbonylic asymmetric stretching of 4 and 6 is detectable as strong absorptions at 1700-1734 cm −1 , together with medium signals at 1667 and 1659 cm −1 , respectively, in the typical range of β-diketonate systems [91].The ESI-MS study was conducted by dissolving the Cu(II) complex compounds in acetonitrile, and recording the spectra in the positive-and negative-ion modes.In the positive-ion spectrum of 4, it is possible to detect peaks at m/z 318 and 360 attributable to the [Cu(L acPz )]+ and [Cu(L acPz ) + CH3CN] + species, confirming the complex formation.
Both α-unsubstituted and α-monosubstituted β-diketones are well studied in retro-Claisen reactions [54,[92][93][94][95][96][97].The retro-Claisen reactions of β-diketones are extremely attractive, not only because these reactions are distributed widely in biological chemistry [7,98] but also because this C−C bond cleavage protocol provided efficient access to synthetically useful ester and ketone compounds, simultaneously [99][100][101][102].In ethanol solution, HL acPz and HL acPzMe react with strong bases such as NaOH or t-BuOK by the retro-Claisen C−C bond cleavage reaction, giving rise to the formation of the species 4-phenyl-4-(1H-pyrazol-1-yl)butan-2-one, PhPz MEK ( 7) and 4-(3,5-dimethyl-1H-pyrazol-1-yl)-4phenylbutan-2-one, PhPzMe2 MEK (8) (Scheme 3).The reactions presumably proceed by the nucleophilic addition of bases to keto carbonyl group furnishing the key tetrahedral intermediate as a hemiketal anion, which might introduce C−C bond cleavage, leading to the retro-Claisen reaction, where an enolate anion intermediate is potentially involved in the reaction process [54].The reaction was found to be highly dependent on the basicity of the base.Weak bases (such as Et3N) gave poor yield or even no reaction, while strong bases afforded a complete transformation.It is interesting to note that compound 7 was obtained in ethanol solution by the reaction of HL acPz with strong bases only in small amounts, in the presence of unreacted ligand.Compounds 7 and 8 were fully characterized by multinuclear NMR spectroscopy, FT-IR, ESI-MS and elemental analysis and in addition a batch of good quality crystals of 8, suitable for X-ray analysis, was obtained by slow evaporation of a diethyl ether/n-hexane solution.The reaction was found to be highly dependent on the basicity of the base.Weak bases (such as Et 3 N) gave poor yield or even no reaction, while strong bases afforded a complete transformation.It is interesting to note that compound 7 was obtained in ethanol solution by the reaction of HL acPz with strong bases only in small amounts, in the presence of unreacted ligand.Compounds 7 and 8 were fully characterized by multinuclear NMR spectroscopy, FT-IR, ESI-MS and elemental analysis and in addition a batch of good quality crystals of 8, suitable for X-ray analysis, was obtained by slow evaporation of a diethyl ether/n-hexane solution.
The IR spectrum of 7 and 8 have been carried out on solid samples and show all the expected absorption bands.Weak bands in the region 2833-3106 cm −1 are assigned to C-H stretching vibrations, while the presence of only one strong band at about 1715 cm −1 , due to the stretching vibration of the carbonyl group, confirms the deacetylation of 1 and 2 by the retro-Claisen reaction.In the 1 H-NMR spectrum of 7 and 8 recorded in CDCl 3 solution, the CH aromatic protons are present in the range 7.17-7.34,the singlets at 2.19 and 2.26 ppm are attributable to the methyl bonded to the carbonyl group, respectively in 7 and 8.The CH bridging proton is present as a double doublet at 5.73-5.89ppm.The diasterotopic protons of the methylene are detectable as double doublets at 3.05-3.11ppm and 3.93-3.99ppm.In the 13 C-NMR spectra of 7 and 8, recorded in CDCl 3 the diagnostic CH 2 signals, are detectable at 48.7 and 49.0 ppm, respectively.In the ESI-MS spectra of 7 and 8, recorded in acetonitrile in the positive-ion mode, it is possible to detect the molecular peaks at m/z 215 and 243 attributable to the protonated species [ PhPz MEK + H] + and [ PhPzMe2 MEK + H] + , respectively.

X-ray Crystallography
A summary of the data collection parameters and crystal data for the HL acPz (1) and HL acPzMe (2) ligands, the PhPzMe2 MEK molecule (8) and the [Cu(PPh 3 ) 2 (HL acPz )]PF 6 complex (3) are reported in Table 1.Tables 2-5 list a selection of bond lengths and angles of these compounds, while ORTEP [103] representations of the pertinent molecular structures are shown in Figures 1-4.The selected specimens of 1, 2 and 8 (Table 1) were all found to belong to the monoclinic crystal system; compound 8 was crystallized as a non-merohedral, two-component twin, with the two components having the same cell parameters.The twin data finalization showed that the whole reflection dataset was unequally divided into a major and a minor component (0.7761/0.2239 ratio).The R int values for the two sets of reflections were significantly different, with the R int value for the data of the minor component significantly worse.Accordingly, the molecular structure of 8 has been solved analyzing only data pertaining to the major component.Compounds 1, 2 and 8 share a common 4-phenyl-4-(1H-pyrazol-1-yl)butan-2-one moiety and their structures can be discussed together.An examination of the CCDC repository [104,105] shows that the above fragment has not yet been documented, so, to the best of our knowledge, these molecules and complex 3 below are the first examples of structures containing this rather unusual synthon, while only few compounds show only some degree of similarity with those described here.Among these, ethyl N-(2-acetyl-3-oxo-1-phenylbutyl)carbamate [106] incorporates the 3-phenylmethyl-2,4-pentanedione moiety bound to a sp 2 nitrogen that is also present in the 1 and 2 ligands, while few [107][108][109] bis-pyrazolyl derivatives show the pyrazole ring bound to a short alkyl-carbonyl chain.1, 2 and 8 are optically active molecules, because the C1 atom of all compounds shows four different substituent groups.
The X-ray experiments for 1 (Figure 1) and 8 (Figure 3) reveal that the asymmetric unit of these compounds is made of a single molecule, in which C1 has an S configuration.The asymmetric unit of compound 2 (Figure 2) shows instead two independent molecules, defining an enantiomeric pair, with C1 and C1A atoms showing, respectively, S and R configurations.The atoms common to 1, 2 and 8 are reasonably superimposable (RMS value within 0.315-0.489Å, making allowance for the inversion of the R enantiomer of 2) by using the overlay routine in Mercury [110].In 1 and 2, the two -C(O)-CH 3 groups branching from C5 have a nearly eclipsed reciprocal arrangement.In all compounds, the carbonyl oxygen atoms are always syn-placed with respect to the C1 methine hydrogen and the molecular pucker brings the mean planes encompassing the phenyl and the pyrazolyl moieties to form similar angles with each other; 73.8 • in 1, 71.8 and 67.5 • in the two enantiomers of 2 and 61.6 • in 8.In the latter, the propan-2-one chain bound to C1 is also planar and makes angles of 87.7 and 54.1 • , respectively, with the mean planes of the pyrazolyl and phenyl moieties.A comparison (Tables 2-5) of the selected structural parameters in the common fragments of the three molecules indicate that the distribution of the bond lengths in the pyrazolyl rings and in the 2,4-pentanedione/propan-2-one chains is comparable, and it is also comparable with those reported for the few molecules [106][107][108][109] sharing some similarities with the compounds described here.In particular, the C=O bonds (mean length of 1.199 Å) have clear double bond character and the bonds made by the C1 atom (mean length of 1.526 Å) have single-bond character.Likewise, the distribution of the average bond lengths about the pyrazolyl rings (1.356, 1.332, 1.384, 1.368 and 1.465 Å for, respectively, N1-N2, N1-C2, C2-C3, C3-C4, N2-C4 distances) matches those found in reported [107][108][109] compounds (1.366, 1.334, 1.394, 1.367, 1.357 and 1.462 Å), thus suggesting that there is not conjugation outside the ring and that N1-C2 and C3-C4 distances have the greater double-bond character.As for the above compounds, the exploration of the CCDC database reveals only one bis-triphenylphosphine copper(I) complex having some similarity with the one presented here [111].matches those found in reported [107][108][109] compounds (1.366, 1.334, 1.394, 1.367, 1.357 and 1.462 Å), thus suggesting that there is not conjugation outside the ring and that N1-C2 and C3-C4 distances have the greater double-bond character.As for the above compounds, the exploration of the CCDC database reveals only one bistriphenylphosphine copper(I) complex having some similarity with the one presented here [111].1.368 and 1.465 Å for, respectively, N1-N2, N1-C2, C2-C3, C3-C4, N2-C4 distances) matches those found in reported [107][108][109] compounds (1.366, 1.334, 1.394, 1.367, 1.357 and 1.462 Å), thus suggesting that there is not conjugation outside the ring and that N1-C2 and C3-C4 distances have the greater double-bond character.As for the above compounds, the exploration of the CCDC database reveals only one bistriphenylphosphine copper(I) complex having some similarity with the one presented here [111].The complex 3 crystallizes in the orthorhombic crystal system; in its structure, the Cu(I) ion is surrounded by two unidentate PPh 3 molecules and one bidentate HL acPz neutral ligand, which attacks the copper ion by means of its N1, O1 atoms.The resulting complex [Cu(PPh 3 ) 2 (HL acPz )] + is cationic and crystallizes with the help of a (disordered) hexafluorophosphate anion.The central metal has a distorted tetrahedral environment (τ 4 and τ 4 ′ indexes values of 0.794 and 0.768, respectively [112,113]), dominated at one side by the large P1-Cu1-P2 angle of 128.25(4), to make allowance for the bulky triphenylphosphine ligands and at the other side by the narrow N1-Cu1-O1 chelation angle of 87.81 (13).Notably, upon coordination, the HL acPz ligand forms a seven-membered metallacycle, in which, in addition to C1, also C5 becomes optically active, with both centers having an R configuration.In its bound form, only the O6 atoms remains syn-oriented with respect to the methine C1 hydrogen, while O5 becomes anti-oriented.Accordingly, the two -C(O)-CH 3 groups branching from C5 are also reciprocally anti-oriented with respect to the C5 atom.The atoms participating in the seven-membered ring, in addition to Cu1, O1 and N1, are N2, C1, C5 and C6.The ring has a distorted boat (C s ) arrangement, due to the unequal Cu1-O1, Cu1-N1 distances as well as to the constraints imposed by the pyrazolyl ring.The Cu1, N1, O1 and C6 atoms are coplanar within 0.06 Å; another plane encompasses N1, N2, C5 and C6, coplanar within 0.02 Å, with C1 out of this last plane by 0.78 Å.The mean planes passing through the phenyl and the pyrazolyl rings in 3 make with each other a dihedral angle of 70.2 • (compared with 73.8 • in the free ligand), so the HL acPz ligand satisfies the copper coordination needs by properly adjusting only its 2,4-pentanedionato moiety.The two triphenylphosphine ligands have the expected propeller shape, with the planes of the three phenyl rings making with each other angles of 64.2, 73.4,88.1 • for the rings branching from P1 and 78.1, 82.8, 87.3 • for the rings branching from P2, respectively.Notably, the atoms of the C22/C27 ring, P1 and Cu1 are also coplanar within 0.03 Å.The C6-O1 and N1-N2 bond distances (Table 5) slightly elongate upon coordination (+0.008 and +0.006 Å, respectively), while the N1-C2 and C3-C4 distances shrink a bit, slightly increasing their double-bond character (−0.010 and −0.008 Å, respectively).The complex 3 crystallizes in the orthorhombic crystal system; in its structure, the Cu(I) ion is surrounded by two unidentate PPh3 molecules and one bidentate HL acPz neutral ligand, which attacks the copper ion by means of its N1, O1 atoms.The resulting complex [Cu(PPh3)2(HL acPz )] + is cationic and crystallizes with the help of a (disordered) hexafluorophosphate anion.The central metal has a distorted tetrahedral environment (τ4 and τ4′ indexes values of 0.794 and 0.768, respectively [112,113]), dominated at one side by the large P1-Cu1-P2 angle of 128.25(4), to make allowance for the bulky triphenylphosphine ligands and at the other side by the narrow N1-Cu1-O1 chelation angle of 87.81 (13).Notably, upon coordination, the HL acPz ligand forms a seven-membered metallacycle, in which, in addition to C1, also C5 becomes optically active, with both centers having an R configuration.In its bound form, only the O6 atoms remains synoriented with respect to the methine C1 hydrogen, while O5 becomes anti-oriented.Accordingly, the two -C(O)-CH3 groups branching from C5 are also reciprocally antioriented with respect to the C5 atom.The atoms participating in the seven-membered ring, in addition to Cu1, O1 and N1, are N2, C1, C5 and C6.The ring has a distorted boat (Cs) arrangement, due to the unequal Cu1-O1, Cu1-N1 distances as well as to the constraints imposed by the pyrazolyl ring.The Cu1, N1, O1 and C6 atoms are coplanar within 0.06 Å; another plane encompasses N1, N2, C5 and C6, coplanar within 0.02 Å, with C1 out of this last plane by 0.78 Å.The mean planes passing through the phenyl and the pyrazolyl rings in 3 make with each other a dihedral angle of 70.2° (compared with 73.8° in the free ligand), so the HL acPz ligand satisfies the copper coordination needs by properly adjusting only its 2,4-pentanedionato moiety.The two triphenylphosphine ligands have the expected propeller shape, with the planes of the three phenyl rings making with each other angles of 64.2, 73.4,88.1° for the rings branching from P1 and 78.1, 82.8, 87.3° for the rings branching from P2, respectively.Notably, the atoms of the C22/C27 ring, P1 and Cu1 are also coplanar within 0.03 Å.The C6-O1 and N1-N2 bond distances (Table 5) slightly elongate upon coordination (+0.008 and +0.006 Å, respectively), while  By examining the metrical data of the above noted (1H-pyrazole-3,5-dicarboxylato)bis(triphenylphosphine)-copper(I) [111], we note that Cu-P distances in 3,  By examining the metrical data of the above noted (1H-pyrazole-3,5-dicarboxylato)bis(triphenylphosphine)-copper(I) [111], we note that Cu-P distances in 3, (2.2385(9)/2.2578(9)Å) compare quite well with those in the reported complex (2.226/2.265Å) and are little shorter than the average of 2.272 Å for 950 bis-triphenylphosphine copper(I) complexes in the CCDC repository.On the other side, Cu-N (2.039(3) Å) and Cu-O (2.307(3) Å) distances are instead shorter and longer (−0.05 and +0.147 Å, respectively) than the corresponding ones [111] and also appreciably longer (+0.104 and +0.127 Å) of the known means for Cu(I) complexes showing Cu-N(pyrazolyl) and Cu-O=C bonds (1.935 Å/290 compounds and 2.180 Å/260 compounds, respectively).The longer Cu-N and Cu-O bonds (compared to averages for known compounds) may hint in part to a lesser donating ability of the N1 and especially O6 atoms, as well as to the steric hindrance brought by the bulky triphenylphosphine ligands.With respect to the nonbonding contacts, a list of the tightest interactions for the compounds described in this work is given in Table 6 (involved distances equal sum of the pertinent van der Waals radii minus 0.05 Å and almost all of them fall below 2.7 Å).An inspection of the packing diagrams of the compounds 1 and 8 shows a similar contact network.In 1, the two noticeable contacts involve O1 and N1 that binds, respectively the H15 and H11 atoms of two different nearby molecules.(at x, 1 − y, -1/2 + z and x, 1 − y, 1/2 + z).The two contacts help to consolidate a one-dimensional chain that propagates along the crystallographic c axis.In 8, the three shortest contacts (range: 2.55-2.66Å) all involve the O1 atom which binds, again, the H1/H15 and H14 of two different proximal molecules.The links with H1, H15 establish a dimeric couple, the third one (symmetry operation: 1 + x, y, z) in turn propagates a one-dimensional chain of the dimer along the crystallographic a axis.In 2, the two independent molecules in the asymmetric unit are bound through an O1A••••H7B link (2.53 Å); O1A is also involved in a contact with the H14A of another molecule (at 1 + x, y, z).Likewise, O1 establish two different contacts with the H7AC and H14 atoms 14 (at 1 + x, y, z and −1 + x, y, z) and all these links create again a one-dimensional chain propagating along the crystallographic a axis.This motif is also reinforced by an O2••••H16 contact that joins together two proximal chains.The more extended nonbonding contact network of complex 3 depends on the disordered PF 6 − anion.
In the latter, almost all the atoms of the alternate position of the anion establish contacts with several hydrogen atoms sustaining a full 3D network in which the hexafluorophosphate anions and the complex cations pile up in alternate layers along the crystallographic c axis.Among these contacts, that between C15 and H37 of another molecule (at 1 − x, 1/2 − y, 1/2 + z) of 2.79 Å is the longest one among those reported in Table 6 and also the only one that does not involve fluorine atoms; it creates a 1D chain propagating along the crystallographic a axis.Those involving F2 and F2A with H9B, F5A with H21 (all within the same unit) and F6A with H42 (at 1 − x, 1 − y, 1/2 + z) range between 2.51 and 2.57 Å and sustain a zigzag 1D chain that propagates along the crystallographic c axis (Table 6).This chain is crisscrossed by another chain, running along the −1, 1, 0 plane and originated by the contacts of F1A with H14 and H18 (at1/2 + x, 3/2 − y, z), F3 with H11, F4 with H5 and F4A with H38 (all of them at x, 1 + y, z, range: 2.44-2.56Å), which also intersects the motif originated by C15••••H37 contact.The articulate 3D network is finally completed by the contact (2.63 Å) established between F3 and H32 (at 1/2 − x, 1/2 + y, 1/2 + z), which also intersects the aforementioned zigzag motif, keeping together two proximal zigzag chains.The nonbonding interactions above described are also illustrated with a series of crystal packing diagrams that have been attached to the Supporting Information (Figures S1-S8), highlighting the different structural motifs as well as the pertinent distances and angles.

Materials and Instruments
All reagents were obtained from commercial suppliers and used as received.Melting Points (MP) were performed by an SMP3 Stuart Scientific Instrument (Bibby Sterilin Ltd., London, UK).Elemental Analyses (C, H, N, S) (EA) were performed with a Fisons Instruments EA-1108 CHNS-O Elemental Analyzer (Thermo Fisher Scientific Inc., Waltham, MA, USA).Fourier-Transform InfraRed (FT-IR) spectra were recorded from 4000 to 700 cm −1 on a PerkinElmer Frontier Instrument (PerkinElmer Inc., Waltham, MA, USA), equipped with the Attenuated Total Reflection (ATR) unit using universal diamond top-plate as sample holder.Abbreviation used in the analyses of the FT-IR spectra: br = broad, m = medium, mbr = medium broad, s = strong, sbr = strong broad, vs. = very strong, w = weak, and wbr = weak broad.Nuclear Magnetic Resonance (NMR) spectra for the nuclei 1 H, 13 C and 31 P were recorded with a Bruker 500 Ascend Spectrometer (Bruker BioSpin Corporation, Billerica, MA, USA; 500.13MHz for 1 H, 125.78 MHz for 13 C, 202.46 MHz for 31 P and 470.59 MHz for 19 F).Tetramethylsilane (SiMe 4 ) was used as external standard for the 1 H-and 13 C-NMR spectra, while 85% H 3 PO 4 was used for the 31 P-NMR spectra.The chemical shifts (δ) are reported in ppm, and coupling constants (J) are reported in hertz (Hz).Abbreviation used in the analyses of the NMR spectra: br = broad, d = doublet, dbr = broad doublet, dd = doublet of doublets, m = multiplet, s = singlet, sbr = broad singlet, and t = triplet.Electrospray ionization mass spectra (ESI-MS) were recorded in the positive-(ESI-MS(+)) or negative-ion (ESI-MS(−)) modes on a Waters Micromass ZQ Spectrometer equipped with a single quadrupole (Waters Corporation, Milford, MA, USA), using methanol or acetonitrile mobile phase.The compounds were added to reagent grade methanol or acetonitrile to give approximately 0.1 mM solutions.These solutions were injected (1 µL) into the spectrometer fitted with an autosampler.The pump delivered the solutions to the mass spectrometer source at a flow rate of 200 µL/min and nitrogen was employed both as a drying and nebulizing gas.Capillary voltage was typically 2500 V.The temperature of the source was 100 • C, while the temperature of the desolvation was 400 • C. In the analyses of ESI-MS spectra, the confirmation of major peaks was supported by comparison of the observed and predicted isotope distribution patterns, the latter calculated using the IsoPro 3.1 computer software (T-Tech Inc., Norcross, GA, USA).

Crystallographic Data Collection and Refinement
Single crystals suitable for the X-ray experiment of the compounds 1, 2, 8 were obtained by slow evaporation of n-hexane or diethyl ether/n-hexane solutions; likewise, crystals of the complex 3 were obtained by slow evaporation of an acetone/ethyl acetate solution.In all cases, several specimens were screened before selecting the most appropriate items, which were picked up with a nylon loop and mounted on the top of the goniometer head of a Rigaku-OD Gemini E diffractometer, equipped with a 2K × 2K EOS CCD area detector and sealed tube to enhance the Cu X-ray source.The raw diffraction data for all compounds were collected at room temperature [range: 298(1)-299.4(8)K] by means of the ω-scan technique, using graphite-monochromated Cu Kα radiation (λ = 1.54184Å) in a 1024 × 1024-pixel mode and 2 × 2-pixel binning.Data collection, reduction, and finalization were performed using the CrysAlisPro software, Versions 1.171.41.123a (1) and 1.171.42.49(2, 3, 8) [114].Data collections were usually planned to allow for a certain degree of redundancy, except for compound 8, where reflection intensities were low and the time for the experiment would have been exceedingly long.The raw data were corrected for Lorentz/polarization effects.An empirical absorption correction was also performed by means of a multiscan approach, with the scaling algorithm SCALE3 ABSPACK, using equivalent reflections.Accurate unit cell parameters were obtained by the least-squares refinement of 8464 (1), 19353 (2), 23975 (3), 2282 (8) strongest reflections chosen throughout the whole data collection.The crystal and equipment stability were checked by monitoring two reference frames every 50 frames for all compounds.A manual data reduction was performed at the end of the data collection in order to appropriately account for limited sample wobbling, but no significant change in peak intensities were observed during all experiments.
The structures were solved by direct phasing and refined by full-matrix least squares based on F o 2 with the SHELXT [115] and SHELXL [116] programs through the OLEX2 program interface [117].For all compounds, non-H atoms were allowed to vibrate anisotropically in the last cycles of refinement.In compounds 1, 2 and 8, the positions of the H atoms were obtained by difference Fourier maps; in complex 3, H atoms were placed in calculated positions and refined as a riding model, with their displacement parameters calculated as 1.2 (or 1.5 for the methyl groups) times the U eq of the pertinent carrier carbon atom.The asymmetric unit of compound 2 contains two independent molecules which define an enantiomeric pair, with C1 and C1A atoms showing, respectively, S and R configurations.The cationic complex 3 crystallizes as an hexafluorophosphate salt.The PF 6 − anion is disordered over two positions, whose site occupation factors were constrained to sum to unity; finally refined sofs were 0.472/0.528for F1/F6 and F1A/F6A, respectively.The involved atoms have also been modelled introducing RIGU restraints.The analysis of the diffraction data of 8 showed that this compound crystallizes in the form of a non-merohedral two-component twin (second component individuated by a rotation of -179.992• about the [1.00 0.00 0.00] direction in the reciprocal space).The two components account, respectively, for 77.61% and 22.39% of the diffraction peaks.Twin data finalization [114] of this compound showed that the R int value of the data pertaining to the minor component was significantly worse than that of the major component; for this reason, the structure of 8 was solved using only the data of the major component.Full listings of atomic coordinates, bond lengths and angles, anisotropic thermal parameters are available as Supporting Information, in the form of .ciffiles; ORTEP [103] representations of all compounds (Figures 1-4) have been prepared using the Mercury program [110].CCDC 2326184 (8), 2326185 (1), 2326186 (3) and 2326187 (2) contain the supplementary crystallographic data for this paper, available free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
This study establishes a new and easily accessible class of copper compounds, provides new insights into the chemistry group 11 metal compounds, and opens new opportunities for further research in this field.

Figure 1 .
Figure 1.ORTEP representation of the HL acPz ligand (1), with the atomic numbering scheme.Ellipsoids drawn at the 50% probability level; H atoms not shown.

Figure 1 .
Figure 1.ORTEP representation of the HL acPz ligand (1), with the atomic numbering scheme.Ellipsoids drawn at the 50% probability level; H atoms not shown.

Figure 1 .
Figure 1.ORTEP representation of the HL acPz ligand (1), with the atomic numbering scheme.Ellipsoids drawn at the 50% probability level; H atoms not shown.

Figure 2 .
Figure 2. ORTEP representation of the two independent molecules in the asymmetric unit of the HL acPzMe ligand (2), with the atomic numbering scheme.Ellipsoids drawn at the 50% probability level; H atoms not shown.

Figure 2 .
Figure 2. ORTEP representation of the two independent molecules in the asymmetric unit of the HL acPzMe ligand (2), with the atomic numbering scheme.Ellipsoids drawn at the 50% probability level; H atoms not shown.

Figure 3 .
Figure 3. ORTEP representation of the PhPzMe2 MEK molecule (8), with the atomic numbering scheme.Ellipsoids drawn at the 50% probability level; H atoms not shown.

Figure 3 .
Figure 3. ORTEP representation of the PhPzMe2 MEK molecule (8), with the atomic numbering scheme.Ellipsoids drawn at the 50% probability level; H atoms not shown.

Table 1 .
Summary of data collection parameters and crystal data for compounds 1, 2, 3 and 8.
* Compound 2 with two independent molecules in an asymmetric unit.
* Atom to which the donor atom is bound.