Cycloaurated Complexes Research Articles

2‐Pyridylmetallocenes, Part VII. Synthesis and Crystal Structures of Cycloaurated Pyridylmetallocenes

AbstractTreatment of the 2‐pyridylferrocenes [CpFe(C5H3R{C5H4N})] (R=H, Me) with HAuCl4 or NaAuCl4 in aqueous acetonitrile yields the cycloaurated complexes [CpFe(C5H2R{C5H4N}AuCl2)] (R=H, 2 a; Me, 2 b). Reaction of 2 a,b with phenylacetylene in the presence of CuI and NEt3 produces the monoalkynyl complexes [CpFe(C5H2R{C5H4N}AuI{CCPh})] (R=H, 3 a; Me, 3 b), while the reaction of 2 a with NaCN/ LiCl yields.the bis‐cyanide [CpFe(C5H3{C5H4N}Au{CN}2)] 4 a. The molecular structures of 2 a, 3 a, 3 b and 4 a were determined by X‐ray diffraction.

Cyclometallated gold(III) complexes against colon cancer. X-ray structure of [Au(C,NPhenylpyridine)(OAc)2

The discovery of cisplatin made a difference in the way that chemotherapy was understood. Since then, and in order to improve the effectiveness and the clinical problems related to this kind of metallodrugs, several metals have been investigated as an alternative to this therapy. Due to the chemical similarities with Pt(II), Au(III) is a promising metal for this purpose. Nevertheless, the stabilization of this oxidation state in physiological conditions is still a difficult goal to achieve. In this research, we have studied the cyclometallation as a strategy to make stable Au(III) complexes, and we have evaluated these compounds as candidates to be used in the treatment of colon cancer. To achieve our goals, we made a huge effort to design a general strategy to obtain cycloaurated complexes, without organomercurial compounds. Thus, we have synthesized the cyclometallated Au(III) derivatives from the corresponding [AuCl3(N–CH)] complex and we have tested some ADME-tox properties of these compounds. The partition coefficient showed that, although [AuCl3(N–CH)] were more water-soluble, cyclometallated species present a better balance between hydro- and lipophilicity. That is why cycloaurated complexes were modified by the coordination of O-donor ligands and studied as anticancer drugs for colon cancer (Caco-2/TC7 cell line). The precursors ([AuCl3(N–CH)]) and starting cyclometallated complexes did not present any effect on tumour or normal cell proliferation. However, complex [Au(Phe)(ppy)]Cl presents a better antiproliferative effect than cisplatin on tumour cells and a selectivity 9-times greater towards tumour cells than towards normal cells. Some interesting conclusions actually arise from these results for a better future structural design, and thus to achieve more active anticancer drugs.

Catalytic activity of cycloaurated complexes in the addition of 2‐methylfuran to methyl vinyl ketone

AbstractCycloaurated gold(III) complexes derived from cycloaurated iminophosphorane, triphenylphosphine sulfide or selenide, or pyridylsulfonamide ligands have been assessed for their catalytic activity in the addition of 2‐methylfuran to methyl vinyl ketone. Addition of AgBF4 was generally needed for high activity, although those with coordinated atoms of high trans influence showed some activity in the absence of added Ag+. Copyright © 2011 John Wiley & Sons, Ltd.

Cycloaurated triphenylphosphine-sulfide and -selenide

The first examples of cycloaurated phosphine sulfides and triphenylphosphine selenide have been synthesised; these complexes are fairly rare examples of gold(iii) complexes with potentially reducing sulfur- and selenium-donor ligands. The cycloaurated complex (AuCl(2)(2-C(6)H(4)P(S)Ph(2)) was synthesised in good yield by transmetallation of the organomercury precursor Hg(2-C(6)H(4)P(S)Ph(2))(2) with Me(4)N[AuCl(4)]. A route to the chloro-mercury analogue ClHg(2-C(6)H(4)P(S)Ph(2)) was developed by reaction of the cyclomanganated triphenylphosphine sulfide (CO)(4)Mn(2-C(6)H(4)P(S)Ph(2)) with HgCl(2); this mercury substrate was also used in the synthesis of AuCl(2)(2-C(6)H(4)P(S)Ph(2)). The cycloaurated triphenylphosphine selenide complex AuCl(2)(2-C(6)H(4)P(Se)Ph(2)) was synthesised by an analogous methodology using the new phosphine selenide Hg(2-C(6)H(4)P(Se)Ph(2))(2) [prepared from Hg(2-C(6)H(4)PPh(2))(2) and elemental Se under sonication]. The phosphonamidic analogue AuCl(2)(2-C(6)H(4)P(S)(NEt(2))(2)) has also been synthesised from PhP(S)(NEt(2))(2)via lithiation and mercuration. X-Ray crystal structures of several compounds are reported, and show the presence of puckered ring systems.

Synthesis and characterisation of isomeric cycloaurated complexes derived from the iminophosphorane Ph 3P [dbnd]NC(O)Ph

Using different organomercury substrates, two isomeric cycloaurated complexes derived from the stabilised iminophosphorane Ph 3P NC(O)Ph were prepared. Reaction of Ph 3P NC(O)Ph with PhCH 2Mn(CO) 5 gave the manganated precursor (CO) 4Mn(2-C 6H 4C(O)N PPh 3), metallated on the C(O)Ph substituent, which yielded the organomercury complex ClHg(2-C 6H 4C(O)N PPh 3) by reaction with HgCl 2 in methanol. Transmetallation of the mercurated derivative with Me 4N[AuCl 4] gave the cycloaurated iminophosphorane AuCl 2(2-C 6H 4C(O)N PPh 3) with an exo PPh 3 substituent. The endo isomer AuCl 2(2-C 6H 4Ph 2P NC(O)Ph) [aurated on a PPh 3 ring] was obtained by an independent reaction sequence, involving reaction of the diarylmercury precursor Hg(2-C 6H 4P( NC(O)Ph)Ph 2) 2 [prepared from the known compound Hg(2-C 6H 4PPh 2) 2 and PhC(O)N 3] with Me 4N[AuCl 4]. Both of the isomeric iminophosphorane derivatives were structurally characterised, together with the precursors (2-HgClC 6H 4)C(O)N PPh 3 and (CO) 4Mn(2-C 6H 4C(O)N PPh 3). The utility of 31P NMR spectroscopy in monitoring reaction chemistry in this system is described.

197Au Mössbauer Spectroscopic Study of Binuclear Cycloaurated Complexes Containing Bridging (2-Diphenylarsino-n-methyl)phenyl (n = 5 and 6)

Abstract 197Au Mössbauer spectra have been measured on a series of binuclear gold complexes containing a bridging As–C ligand. The plot of quadrupole splitting (Q.S.) against isomer shift (I.S.) indicates that the gold–arsenic bond in these complexes is less covalent than the gold–phosphorus bond in analogous P–C complexes.

Orthomercurated and cycloaurated derivatives of the iminophosphorane Ph 3P [dbnd]NPh

Ortho-lithiation of Ph 3P NPh followed by reaction with HgCl 2 gave good yields of [Hg{C 6H 4(PPh 2 NPh)-2}Cl], 3, which was characterised spectroscopically and by an X-ray crystal structure determination. This is an isomer of the product of direct mercuration of Ph 3P NPh which occurs on the N-bonded phenyl ring [J. Vicente, J.A. Abad, R. Clemente, J. Lopez-Serrano, M.C. Ramirez de Arellano, P.G. Jones, D. Bautista, Organometallics, 22 (2003) 4248]. Transmetallation of 3 with [AuCl 4] − gave the corresponding cycloaurated complex [Au{κ 2- C, N-C 6H 4(PPh 2 NPh)-2}Cl 2], with a five-membered metallocyclic ring incorporating four different elements.

Synthesis and reactivity of the five-membered cycloaurated complexes of 2-phenylthiazole

2-Phenylthiazole (Hphtz) reacted with H[AuCl 4]·4H 2O to give the salt [H(Hphtz)][AuCl 4] ( 1), while the reaction of Hphtz with Na[AuCl 4]·2H 2O or AuCl 3·4H 2O afforded the adduct [AuCl 3(Hphtz N)] ( 2). When the adduct 2 was heated in 1,2-dichloroethane in the presence of AgBF 4, cycloauration took place to produce [AuCl 2(phtz C 1, N)] [phtz=2-(2-thiazolyl)phenyl] ( 3). The reactivity of 3 towards Tl(acac) and PPh 3 was investigated.

Carbon−Carbon Coupling in Dinuclear Cycloaurated Complexes Containing Bridging 2-(Diphenylphosphino)phenyl or 2-(Diethylphosphino)phenyl. Role of the Axial Ligand and the Fine Balance between Gold(II)−Gold(II) and Gold(I)−Gold(III)

Reactions of the homovalent bis(benzoato)digold(II) complexes [AuII2(O2CPh)2(μ-2-C6H4PR2)2] (R = Ph (1a), Et (1b)) with the anions CH3-, C6F5-, and SCN- have been investigated. Dimethylmagnesium gives the stable heterovalent complexes [AuI(μ-2-C6H4PR2)2AuIII(CH3)2] (R = Ph (2a), Et (2b)), whereas (pentafluorophenyl)lithium gives the homovalent complexes [AuII2(C6F5)2(μ-2-C6H4PR2)2] (R = Ph (3a), Et (3b)). On prolonged heating in toluene, the latter rearrange to give predominantly dinuclear bis(pentafluorophenyl)digold(I) complexes of the corresponding (2,2‘-biphenylyl)bis(tertiary phosphines) [AuI2(C6F5)2(μ-2,2‘-R2PC6H4C6H4PR2)] (R = Ph (4a), Et (4b)), resulting from coupling of the C6H4PR2 units. Minor products of these rearrangements are the zwitterionic heterovalent complexes [(C6F5)2AuIII(μ-2-C6H4PR2)2AuI] (R = Ph (5a), Et (5b)). The structure of 5a differs from that of 2a by rotation of one of the bridging 2-C6H4PPh2 groups through 180°. Precursors to 4a/5a and 4b/5b have been detected by 31P NMR spe...

First intramolecular aromatic substitution by gold(III) of a ligand other than pyridine derivatives. Synthesis and crystal structure of the novel five-membered cycloaurated complex of 1-ethyl-2-phenylimidazole

Reactions of gold(III) compounds, AuCl3·4H2O and HAuCl4·4H2O, with 2-phenyl-1H-imidazole (Hpi) and 1-ethyl-2-phenylimidazole (Hepi) have been performed under various reaction conditions: Hpi afforded only the salt [H(Hpi)][AuCl4], while Hepi produced both the salt [H(Hepi)][AuCl4] and the adduct [AuCl3(Hepi)]. Cycloauration of Hepi, the first example of cycloauration of a substrate other than pyridine derivatives, has been established by the formation of [AuCl2(epi-C1,N)] [epi = 2-(1-ethyl-2-imidazolyl)phenyl] from the reaction between the adduct [AuCl3(Hepi)] and AgBF4. The cyclometallated structure of Hepi has been confirmed by the X-ray crystallographic study of a derivative [AuCl(epi-C1,N)(PPh3)]PF6.

Organogold(III) complexes derived from auration reactions of thienyl-substituted pyridine derivatives

2-(3-Thienyl)pyridine (3-Hthpy) and 2-(2-thienyl)pyridine (2-Hthpy) reacted with Na[AuCl4]·2H2O to afford the adducts [AuCl3(3-Hthpy)] 1a and [AuCl3(2-Hthpy)] 1b, respectively. The cycloaurated complex [AuCl2(3-thpy-C2,N)] [3-thpy = 3-(2-pyridyl)thiophen-2-yl] 2a was obtained by warming 1a at 80 °C in an acetonitrile–water (1∶5) mixed solvent, whereas the cycloaurated complex [AuCl2(2-thpy-C3,N)] [2-thpy = 2-(2-pyridyl)thiophen-3-yl] 2b was produced by the reaction of 1b with silver(I) tetrafluoroborate in refluxing dichloromethane. Moreover, when 1b was heated at reflux in dichloromethane in the absence of silver(I) tetrafluoroborate, the thiophene-C(5) metallated species [{Au(µ-Cl)Cl[(2-thpy-C 5)H]}2]Cl2 [2-thpy = 2-(2-pyridyl)thiophen-5-yl] 3b was formed. Thermal degradation of 3b in aqueous acetonitrile yielded 2-(5-chloro-2-thienyl)pyridine and 5,5′-bis(2-pyridyl)-2,2′-bithienyl. X-Ray structural analyses of [AuCl(3-thpy-C1,N)(PPh3)]BF4 4a and [AuCl(3-thpy-C1,N)(PPh3)]BF4 4b, which were obtained by the reactions of 2a and 2b with triphenylphosphine, have been performed.

X-ray photoelectron spectroscopic studies on binuclear gold(II) complexes

X-ray photoelectron spectroscopic (XPS) studies on the binuclear cycloaurated complexes [Au 2(μ- o-C 6H 4PPh 2) 2] (I), [Au 2I 2(μ- o-C 6H 4PPh 2) 2] (II) and [Au 2(O 2CPh) 2(μ- o-C 6H 4PEt 2) 2] (III) are presented. The increase in the formal oxidation state of the metal in complexes II and III as a result of gold–gold bond formation is clearly shown. In the benzoate complex (III) the charge transfer is suggested to occur from oxygen to gold. The charge distribution on all the atoms is calculated using a charge potential model is in conjunction with the XPS results.

Synthesis, structure and reactivity of a new six-membered cycloaurated complex of 2-benzoylpyridine [AuCl2(pcp-C 1,N )] [pcp = 2-(2-pyridylcarbonyl)phenyl]. Comparison with the cycloaurated complex derived from 2-benzylpyridine

A six-membered cycloaurated complex [AuCl2(pcp-C1,N)] [pcp = 2-(2-pyridylcarbonyl)phenyl] has been prepared by the reaction between the adduct [AuCl3(Hpcp)] (Hpcp = 2-benzoylpyridine) and AgO2CCF3, and its structure determined by X-ray diffraction. The boat-like conformation of the six-membered pcp–Au ring has been compared to that of the pmp–Au ring in [AuCl(pmp-C1,N)(PPh3)]BF4 [pmp = 2-(2-pyridylmethyl)phenyl] the structure of which has also been established by X-ray diffraction. The complex [AuCl2(pcp-C1,N)] reacts with PPh3 in a 1∶1 molar ratio to give a neutral complex [AuCl2(pcp)(PPh3)]. This is further converted into trans-[AuCl(pcp)(PPh3)2]BF4 and [Au(pcp-C1,N)2]BF4 by treating with PPh3 in the presence of NaBF4 and excess of AgBF4, respectively. This reactivity towards triphenylphosphine has been compared with that of the known cycloaurated complex [AuCl2(pmp-C1,N)]. Temperature-dependent 1H NMR spectra attributable to inversion of the six-membered pmp–Au ring have been observed and the rates of inversion measured by line shape analysis of the methylene protons in [AuCl(pmp-C1,N)(PPh3)]BF4.

Cycloauration of 2-substituted pyridine derivatives. Synthesis, structure and reactivity of six-membered cycloaurated complexes of 2-anilino-, 2-phenoxy- and 2-(phenylsulfanyl)-pyridine

At room temperature and in ethanol 2-anilinopyridine reacted with H[AuCl4]·4H2O as well as Na[AuCl4]·2H2O to give directly the six-membered cycloaurated complex [AuCl2(pap-C 1, N)] 1a [pap = 2-(2-pyridylamino)phenyl], whereas 2-phenoxypyridine (Hpop) and 2-(phenylsulfanyl)pyridine (Hptp) produced only the salts [H2pop][AuCl4] 2b and [H2ptp][AuCl4] 2c, respectively. The adducts [AuCl3(Hpop)] 3b and [AuCl3(Hptp)] 3c have separately been prepared by the reactions of Na[AuCl4]·2H2O with Hpop and Hptp, respectively, in an acetonitrile–water mixed solvent. The salts 2b and 2c can be converted into the corresponding adducts 3b and 3c when they are stirred in acetonitrile–water at room temperature. The cycloaurated complexes [AuCl2(pop-C 1, N)] [pop = 2-(2-pyridyloxy)phenyl] 1b and [AuCl2(ptp-C 1, N)] [ptp = 2-(2-pyridylsulfanyl)phenyl] 1c have been obtained by heating the salts or the adducts in acetonitrile–water. Moreover, complexes 1b and 1c have been synthesized directly by the reaction of H[AuCl4]·4H2O with Hpop and Hptp in refluxing acetonitrile–water, ethanol–water and propan-2-ol–water. The reaction of 1a with an equimolar amount of PPh3 in the presence of NaBF4 gave the cationic complex [AuCl(pap-C 1, N)(PPh3)]BF4 5a, while two equivalents of PPh3 or PEt3 afforded [AuCl(pap-C1)(PPh3)2]Cl 6a or [AuCl(pap-C1)(PEt3)2]Cl 7a where the pap ligand co-ordinates through only the carbon atom. On the other hand, the C–N chelates in 1b and 1c are easily cleaved with one equimolar amount of PPh3 to give [AuCl2(pop-C1)(PPh3)] 8b and [AuCl2(ptp-C1)(PPh3)] 8c, respectively. The boat-form structures of the three six-membered auracycles have been confirmed by X-ray diffraction studies of 1b, 1c and 5a. The crystal structure of 7a has also been determined.

Dinuclear Cycloaurated Complexes Containing Bridging (2-Diphenylphosphino)phenylphosphine and (2-Diethylphosphino)phenylphosphine, C6H4PR2 (R = Ph, Et). Carbon−Carbon Bond Formation by Reductive Elimination at a Gold(II)−Gold(II) Center

The digold(I) complexes Au2(μ-C6H4PR2)2 [R = Ph (1a), Et (1b)] obtained by treatment of AuBr(PEt3) with o-LiC6H4PR2 undergo addition with halogens or benzoyl peroxide to give metal−metal bonded dig...