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Synthesis of Gold(III) Complexes with Bidentate Amino-Thiolate Ligands as Precursors of Novel Bifunctional Acyclic Diaminocarbenes

Two neutral bis(pentafluorophenyl)thiolate gold(III) complexes with the unsymmetrical S^N ligands 2-aminothiophenol or cysteamine have been synthesized and their reactivity has been studied. Homo- and heterodinuclear compounds were obtained by their coordination to gold(I) or silver(I) derivatives through the sulfur atom. Interestingly, a tetranuclear derivative bearing short gold(I)···gold(I) and the more unusual gold(I)···gold(III) interactions has been prepared. These amino-thiolate derivatives can be used as precursors for the synthesis of novel gold(III) acyclic diaminocarbene complexes by reaction with isocyanides CNR. The nucleophilic attack of the amino group to isocyanide molecules affords the synthesis of unprecedented bidentate C^S acyclic diaminocarbene ligands. All of the complexes are air- and moisture-stable at room temperature and have been spectroscopically and structurally characterized.


■ INTRODUCTION
The chemistry of gold has undergone a big development in the last decades mainly because of the great range of applications presented by its complexes. However, this is really true for gold(I) derivatives. The chemistry of gold(III) is an active area but has been less explored than gold(I) chemistry probably because of the instability of gold(III) species to reduction. 1 Consequently, the synthesis of gold(III) derivatives has been the subject of increasing interest mainly because of its versatile applications as catalysts, 2 as luminescent materials, 3 or as antitumor or antiviral agents. 4 Gold trichloride was one of the first gold catalyst used, and from then on, several gold(III) complexes bearing bidentate ligands have been reported as excellent catalysts in some organic transformations. 5 In addition, excellent photophysical properties have been found in tridentate cyclometallated gold(III) complexes bearing ancillary ligands such as N-heterocyclic carbenes, alkynyls, amides, or thiolates. 6 Biological studies of gold(III) derivatives have been developed in part because they are isostructural and isoelectronic to platinum(II) complexes. It was supposedly a cytotoxic activity similar to that of cisplatin, the most wide metal-based antitumor drug. However, in physiological conditions, gold(III) can be reduced to gold(I). For this reason, the election of suitable ligands to stabilize the gold(III) complexes to prevent their reduction is important. For example, metallacyclic gold(III) complexes 7 or chelated gold(III) derivatives 7 with multidentate ligands have been stablished as far more stable under physiological conditions than any other, and some of them have been identified as good antitumor agents. 7 Gold(III) thiolate derivatives are less represented than the related gold(I) species probably because of the ability of thiolate groups to reduce gold(III) to gold(I) 8 although, for example, some tetrathiolate gold(III) compounds with highly electron-deficient thiols (highly fluorinated), that may be less capable of reducing gold(III), were synthesized by Bachman et al.,9 and some others with pentafluorophenyl groups have been described. 10 Moreover, an important number of metallacyclic gold(III) complexes with thiolate ligands have been reported, and some of them have been identified as good antitumor agents. 11 In this work, we were aiming at preparing stable gold(III) derivatives bearing bidentate S^N and S^C ligands. Mono-and binuclear thiolate gold(III) derivatives with potential medicinal properties have been prepared. Two heterofunctional ligands, 2-aminothiophenol and cysteamine, have been used to synthesize the corresponding bis(pentafluorophenyl)-(thiolate)gold(III) derivatives. We have chosen both ligands because of their different functional groups, the thiolate sulfur atom, that provide stability to the compound in addition to provide further reactivity by coordination of other metals, and the amino group that is a reactive group can be further functionalized. Thus, the bis(pentafluorophenyl)(thiolate)gold(III) complexes can act as metalloligands through the donor sulfur atom to give homo-and hetero-bimetallic complexes. Moreover, the amine nitrogen (NH 2 ) of the ligands can react with isocyanide groups to give the corresponding gold(III) derivatives with unprecedented bidentate S^C acyclic diaminocarbenes. These ligands, similar to the widely studied N-heterocyclic carbenes, are being the subject of a great attention because of their excellent possibilities to modulate both steric and electronic properties, as well as the easier mode to obtain chiral derivatives compared to the N-heterocyclic carbenes. 12 The reactivity of gold−amine complexes with isocyanide molecules or gold isocyanide compounds with amines to give the corresponding acyclic diaminocarbene complexes has been stablished for gold(I) and gold(III) derivatives. 13 Most of the acyclic diaminocarbenes described are mono (Figure 1a) 13b,c or dicarbene ( Figure   1b) 13d gold(III) species, but we have previously reported functionalized cyclic diaminocarbenes, originating from the reaction of cyclometalled complexes containing an amine group with isocyanides ( Figure 1c). 13g Following this strategy of using bidentate heterofunctional amine ligands bonded to a gold(III) center, we have chosen aminothiolates because they underwent a reaction with isocyanide ligands in the gold coordination sphere, without reduction or decomposition, allowing the synthesis of a novel bidentate-chelated C^S acyclic aminocarbene ligands.

■ RESULTS AND DISCUSSION
The gold(III) complexes have been prepared starting from the cis-[Au(C 6 F 5 ) 2 (OEt 2 ) 2 ]ClO 4 precursor which has two labile diethyl ether molecules. In this work, two functionalized amines, 2-aminothiophenol and cysteamine, were used to prepare the uncharged starting materials 1 and 2, respectively, (Scheme 1) as yellow solids that are air-and moisture-stable solids. These derivatives, as well as the following derivatives, have been characterized by means of infrared (IR), elemental analysis, NMR spectroscopy, and mass spectrometry. Assignments of the 1 H NMR and 13 C NMR signals were made on the basis of two-dimensional (2D) correlation spectroscopy and heteronuclear single-quantum correlation spectra.
The IR spectra of 1 and 2 present, apart from other absorptions, the vibrations because of the pentafluorophenyl groups bonded to gold(III) at 1503 (s), 952 (s), 801 (s), and 792 (s) cm −1 for 1 or 1507 (s), 960 (s), 811 (m), and 797 (m) cm −1 for 2. 1 H NMR spectra show the expected resonances for the ligands with a different chemical shift. The 19 F NMR spectrum of each compound presents six resonances, two for the para fluorines consistent with two different C 6 F 5 and two for both the ortho and the meta fluorines. This indicates that the pentafluorophenyl rings can rotate around the gold− carbon bond at room temperature. In the ESI + mass spectra, the fragments [M + H] + appear at m/z = 656 (15%) (1) and 608 (76%) (2).
Complexes 1 and 2 were used as metalloligands through the electronically rich sulfur atom, which has lone electron pairs that can be donated to metal cations. Then, the treatment of 1 with equimolecular amounts of [Au(OTf)(PPh 3 )] or AgOTf gave the bimetallic Au(III)−Au(I) (3) or Au(III)−Ag(I) (4) complexes as yellow or white, respectively, air-and moisturestable solids (Scheme 2).
The IR spectra of 3 and 4 show the absorption for the anion trifluoromethanesulphonate around 1265, 1230, 1170, and 1023 cm −1 . The typical absorption of the pentafluorophenyl groups appear around 1500 (s), 965 (s), 813 (m), and 800 (m) cm −1 . The 1 H NMR spectrum of 3 displays resonances for the 2-aminothiophenol ligand and phenyl rings in the appropriate ratio. The 31 P{ 1 H} NMR spectrum of 3 shows a single resonance for the phosphorus of the triphenylphosphine group. Two different pentafluorophenyl moieties, with free rotation in the ring, can be identified in the 19 F NMR spectra of 3 and 4.
The reaction of complex 2 with the gold(III) derivative [Au(C 6 F 5 ) 3 (tht)] (tht = tetrahydrothiophene) afforded the unexpected binuclear gold(III)−gold(I) complex 5 as a yellow air-and moisture-stable solid (Scheme 3). The gold(III) of the starting material, [Au(C 6 F 5 ) 3 (tht)], has been reduced to gold(I), and the oxidation of pentafluorophenyl with the formation of decafluorobiphenyl has taken place. The latter compound has been easily identified in the 19 F NMR spectrum of complex 5. Additionally, this compound can be prepared by reaction of the starting complex 2 with [Au(C 6 F 5 )(tht)].
The IR spectrum of complex 5 shows the absorptions of pentafluorophenyl groups bonded to gold(I) at 1485, 948, and 784 cm −1 and those bonded to Au(III) at 1505, 959, 815, and 794 cm −1 . The 1 H NMR spectrum shows the expected resonances for the ligand with a different chemical shift. In the 19 F NMR spectrum, the three signals corresponding to the gold(I) fragment and the six signals corresponding to the gold(III) fragment were observed in an appropriate ratio.
The crystal structure of complex 5 has been determined by an X-ray diffraction study ( Figure 2). Two different crystals in a 95.5:4.5 ratio were identified in compound 5. Only four gold atoms of the minority crystal could be detected. Several attempts to crystallize a single crystal were unfruitful; in all of the cases, a similar twinning was observed. The complex crystallizes in the triclinic P1̅ space group as a tetramer formed by an intermolecular gold(I)−gold(I) interaction of 3.054(1) Å. Moreover, there are short intramolecular gold(I)−gold(III) distances of 3.175(1) and 3.214(1) Å which indicate a high degree of metal−metal interaction. These distances are shorter than those found in other multinuclear gold(I)−gold(III) complexes, for example, the tetranuclear complex [(C 6 F 5 ) 3 Au-(μ 2 -2-SC 6 H 4 NH 2 )(AudppmAu)(μ 2 -2-SC 6 H 4 NH 2 )Au(C 6 F 5 ) 3 ] (dppm = PPh 2 CH 2 PPh 2 ) with the 2-aminothiophenol ligand [Au(III)−Au(I) from 3.2812(7) to 3.4052(7) Å], 8f or with the bridging sulfido ligands in [(C 6 F 5 ) 2 Au{μ-(S(Au 2 dppf)} 2 ]OTf for which the shortest distance found is 3.2195(8) Å. 14 Ignoring metal−metal interactions, the gold atoms show in 5 the characteristic geometry of each oxidation number, that is, square planar for gold(III) and linear for gold(I) atoms.
The reactivity of gold−amine complexes with isocyanide molecules to give the corresponding acyclic diaminocarbene complexes has been established for amine gold(I) and gold(III) derivatives. 13 In this work, the reaction of 1 or 2 with an equimolecular amount of the corresponding isocyanide CNR (R = cyclohexyl, 2-naphthyl) gives complexes 6−8 in which the nucleophilic attack of the amine to the isocyanide carbon produces the formation of unprecedented bidentate S^C acyclic diaminocarbenes (Scheme 4). Compounds 6−8 are synthesized as off-white air-and moisture-stable solids. Their 1 H NMR spectra show the resonances assigned to the protons of the thiolate ligands and the signals characteristic of the substituents of the former isocyanide group in the appropriate ratio. The 19 F NMR spectra of complexes indicate that the pentafluorophenyl rings can rotate at room temperature. In the ESI + mass spectra, the fragments [M + Na] + (6) and [M + H] + (8) appear at m/z (%) = 787 (51) and 717 (100), respectively.
The structure of complex 8 in the solid state has been solved by an X-ray diffraction study (Figure 3). It crystallizes in the monoclinic P2(1)/n space group with one molecule in the asymmetric unit. The gold(III) center is in a distorted squareplanar geometry. The mean deviation from the plane formed by the four donor atoms of the gold center is 0.0475 Å (S1, C29, C11, and C21). The angles around the gold(III) atom range from 84.40(16)°to 93.39(15)°. The six-membered AuC 3 SN chelate ring adopts a boat conformation, as shown in Figure 3, with the Au atom and the methylene carbon lying on the same side of the plane of the other four atoms, C 2 SN, which are almost coplanar (similar boat conformations were observed for some of us in the bidentate C ∧ N gold(III) acyclic carbene derivatives reported in ref 13g).

■ CONCLUSIONS
In summary, new gold(III) complexes with aminothiolate ligands have been synthesized. These compounds are very  stable and have allowed the preparation of polynuclear species by reaction with gold(I) or silver(I) moieties, in which these metals coordinate to the thiolate sulfur atom. Interestingly, the reaction with other gold(III) centers in the form of a tris(pentafluorophenyl) derivative produces reduction to gold(I) and oxidation of the two pentafluorophenyl units to form decafluorobiphenyl. In this case, it is probable that bulky aryl groups preclude the formation of the corresponding thiolate ligand bridging to bulky gold(III) fragments. An interesting tetranuclear species is formed which shows the presence of short gold(I)···gold(I) and also unusually short gold(I)···gold(III) interaction contacts. In addition, these heterofunctional amine−thiolate complexes serve as excellent platforms to form unprecedented S^C bidentate acyclic diaminocarbenes by reaction with isocyanides. These complexes are very stable and may be adequate for biological studies.  17 with Ag(OTf) in dichloromethane and used in situ. All other reagents were commercially available. Solvents were used as received without purification or drying.
Caution: Perchlorate salts with organic cations might be explosive.
Complex 6. Yield: 0.134 g, 58%. Anal. Calcd for C 25 H 17 AuF 10 N 2 S (764.43): C,39.28;H,2.24;N,3.66;S,4.19. Found: C,38.97;H,2.26;N,3.79;S,4.32 Crystallography. Data were registered on a Bruker SMART 1000 CCD diffractometer. The crystals were mounted on glass fibers using inert oil and transferred to the cold gas stream of the diffractometer. Data were collected using monochromated MoKα radiation (λ = 0.71073) in ω scans. Absorption corrections based on multiple scans were applied with the program SADABS. The structures were solved by direct methods and refined on F 2 using the program SHELXL-2016. 18 All nonhydrogen atoms were refined anisotropically. Hydrogen atoms were included using a riding model. Two different crystals in a 95.5:4.5 ratio were identified in compound 5. Only the four gold atoms of the minority crystal could be detected. Structure was refined as two fragments with the Part instruction. CCDC deposition numbers 1846294 (5) and 1846295 (8)

■ ACKNOWLEDGMENTS
This work is dedicated to Professor Ernesto Carmona in recognition of his outstanding contribution to modern organometallic chemistry. Authors thank the Ministerio de Economía y Competitividad (MINECO/FEDER CTQ2016-75816-C2-1-P and Gobierno de Aragoń-Fondo Social Europeo (E07-17R) for the financial support of our research.