Diarylplatinum(ii) Compounds as Versatile Metallating Agents in the Synthesis of Cyclometallated Platinum Compounds with N-donor Ligands

This review deals with the reactions of diarylplatinum(II) complexes with N-donor ligands to produce a variety of cycloplatinated compounds including endo-five-, endo-seven-, endo-six-or exo-five-membered platinacycles. The observed reactions result from a series of oxidative addition/reductive elimination processes taking place at platinum(II)/platinum(IV) species and involving C–X (X = H, Cl, Br) bond activation, arene elimination, and, in some cases, C aryl –C aryl bond formation.


The reactions of potentially tridentate
have been studied [60] in order to compare the results with those obtained when [Pt 2 Me 4 (μ-SMe 2 ) 2 ] was used as precursor.These reactions gave, in addition to cyclometallated platinum(II) and platinum(IV) compounds analogous to those described for the dimethylplatinum precursor, a new type of platinum(II) compound with a seven-membered metallacycle when X = Cl (Scheme 7).In agreement with previous results for the chemistry of dimethylplatinum analogues [41][42][43], a concerted mechanism is suggested for intramolecular C-X bond activation [61]; for X = Br a platinum(IV) compound is obtained at room temperature, while for X = H a platinum(II) compound is formed along with reductive elimination of benzene after refluxing in toluene the corresponding coordination compounds.Unexpectedly, under the conditions required for intramolecular activation of the C-Cl bond, a seven-membered metallacycle including a biaryl linkage is formed.Scheme 7. Synthesis of cyclometallated platinum(II) and platinum(IV) compounds from a diphenylplatinum(II) precursor [60].
It is interesting to point out that despite the involvement of triarylplatinum(IV) species in these processes and the known susceptibility of such compounds to undergo reductive elimination of two aryl ligands to release a free biaryl [56], no evidence of such reductive elimination of biphenyl was observed.
In order to gain insight into the different processes that might take place when diarylplatinum compounds are used as metallating substrates, the study of the reactions of cis-[Pt(4-MeC 6 H 4 ) 2 (μ-SEt 2 )] 2 with imines of general formula RCH=NCH 2 CH 2 NMe 2 in which the aryl group R may contain either Br, Cl, H or F in the ortho positions was undertaken [62].Dinuclear compound cis-[Pt(4-MeC 6 H 4 ) 2 (μ-SEt 2 )] 2 , previously used as metallating agent as stated above, was selected for this study since the presence of an electron-donor methyl substituent in the aryl ring could facilitate the activation of the ortho C-X bonds.In addition, the position of the methyl substituent in the final products is relevant in order to confirm the mechanism of the process.As shown in Scheme 8, the reactions proceed as expected, yielding as final products a cyclometallated platinum(IV) compound 3a (for X = Br), a cyclometallated platinum(II) compound 4c (for X = H) and a seven-membered platinum(II) compound 6b for X = Cl.In the latter case, it was possible to detect a platinum(IV) compound (3b) as a precursor of the seven membered platinacycle.In addition, the presence of the methyl substituent, initially para to platinum, in a meta position in compound 6b suggests that the C aryl -C aryl bond is formed in a reductive elimination reaction from the platinum(IV) compound.A subsequent cyclometallation process takes place through C aryl -H bond activation at the biaryl fragment and elimination of one molecule of toluene.Scheme 8. Synthesis of cyclometallated platinum(II) and platinum(IV) compounds from cis-[Pt(4-MeC 6 H 4 ) 2 (μ-SEt 2 )] 2 [62,63].
An initial attempt to produce a seven-membered platinacycle from the more inert bromide platinum(IV) compound [PtBr(4-MeC 6 H 4 ) 2 (C 6 H 4 CH=NCH 2 CH 2 NMe 2 )] was carried out in refluxing toluene and lead to a complex mixture of compounds in which the major component was surprisingly a five-membered platinacycle with an "exo C aryl -C aryl " bond (5a).To analyze the factors governing the selective formation of either five or seven-membered platinacycles from the corresponding cyclometallated platinum(IV) compounds, a kinetico-mechanistic study of these processes was carried out [63].Based on these studies, the mechanism depicted in Scheme 9 is proposed.In all cases, a common reductive elimination reaction occurs to form a non-cyclometallated intermediate containing a dangling biaryl moiety, which leads to the selective formation of five or seven-membered platinacycles through a trans (X, NMe 2 )-cis (X, NMe 2 ) isomers equilibrium.The trans form leads exclusively to the five-membered compound, as observed for X = Br.A fast trans to cis isomerization process takes place for X = Cl, and in the obtained cis isomer the steric hindrance forces a Z conformation of the imine, for which only formation of the seven-membered platinacycle is plausible.Along this work, using the reaction conditions extracted from the kinetic studies, both E-cis and E-trans intermediates could be detected and crystallographically characterized.
The reactions of diarylplatinum(II) substrates have been also tested with imine ligands containing a single nitrogen atom.Initial work was based on the reaction of [PtPh 2 (SMe 2 ) 2 ] with imine 2-BrC 6 H 4 CH=NCH 2 C 6 H 5 [64,65] [62].In these reactions, both intramolecular activation of C-Br or C-Cl bonds lead eventually to formation of seven-membered platinacycles.Scheme 9. Proposed mechanism for the formation of five and seven-membered platinacycles [63].
Although for these reactions the corresponding non-cyclometallated intermediates containing a dangling biaryl moiety were not detected, an analogous mechanism to that proposed for ligands containing two nitrogen donor atoms should operate.Accordingly, the cyclometallated platinum(IV) compound initially formed undergoes a process involving reductive elimination to form a biaryl that remains coordinated through the nitrogen atom to platinum(II), and this step is followed by C aryl -H bond activation and reductive elimination of arene (benzene or toluene) to yield a seven-membered platinum(II) metallacycle.Taking into account the results described above for ligands containing two nitrogen atoms, isomerization to the adequate isomer should be more facile for ligands containing one single nitrogen, thus allowing formation of seven-membered platinacycles even for the less prone bromo derivatives.
On the other hand, although intramolecular C-F bond activation has been achieved upon reaction of [Pt 2 Me 4 (μ-SMe 2 ) 2 ] with ligand C 6 F 5 CH=NCH 2 CH 2 NMe 2 [41][42][43] such process has not been observed for precursors cis-[PtPh 2 (SMe 2 ) 2 ] or cis-[Pt(4-MeC 6 H 4 ) 2 (μ-SEt 2 )] 2 .This result can be related with the strength of the C-F bond and the lower reactivity of the later substrates toward intramolecular activation of σ bonds.In order to achieve C aryl -C aryl coupling leading to a fluorinated biphenyl moiety, a new preparative strategy based on the reaction of cis-[Pt(C 6 F 5 ) 2 (SEt 2 ) 2 ] with imine 2-BrC 6 H 4 CH=NCH 2 (4-ClC 6 H 4 ) was tested.In this process, a five-membered metallacycle, in which the formed C aryl -C aryl is not included, was obtained.In this case, formation of a seven-membered platinacycle, which requires C-F bond activation, is not favored and indeed is not observed.The kinetico-mechanistic studies carried out for this system [66] indicate initial formation of platinum(IV) compound arising from the activation of the C-Br bond of the imine.This process is followed by a C aryl -C aryl reductive elimination and a final C aryl -H bond activation leading to a five-membered cyclometallated platinum(II) compound with elimination of pentafluorobenzene as shown in Scheme 10.In this case, 19 F NMR monitoring of the process allows the detection of all proposed intermediates.Scheme 10.An example of C aryl -C aryl reductive coupling leading to a fluorinated biphenyl moiety [66].

Six-versus Five-Membered and endo-versus exo-Platinacycles
In all cases reported above, the C aryl -C aryl coupling processes leading to either seven-or five-membered platinacycles involve formation of stable endo-metallacycles.In order to analyze whether formation of a biaryl linkage is also possible for N-benzylidenebenzylamines for which formation of less stable exo-metallacycles is preferred, the reactions of cis-[Pt(4-MeC 6 H 4 ) 2 (μ-SEt 2 )] 2 with imines containing a C-Br bond at an ortho position of the more flexible benzyl ring have been studied and are summarized in Scheme 11 [67,68].According to the obtained results, these reactions proceed through activation of the C-Br bond to produce a platinum(IV) compound with a five-membered exo-metallacycle, followed by C aryl -C aryl bond formation between the benzyl group of the imine ligand and one of the para-tolyl ligands leading to a biaryl linkage.The subsequent C aryl -H bond activation does not necessarily take place at the biaryl system; instead, a C aryl -H bond of the benzylidene group is activated to produce a five-membered endo-metallacycle with elimination of a toluene molecule (ligands 1d and 1e).For ligand 1f, the mesityl group was chosen in order to block the ortho positions of the benzylidene group and drive the reaction towards the benzyl group of the ligand.Instead, an aliphatic C-H bond of the mesityl group is activated to produce a six-membered endo-metallacycle.This result, analogous to those reported for cyclopalladation reactions [69,70] can be related to the higher stability of the endo versus exo-metallacycles (the so-called endo effect), which allows to overcome the low tendency to form six-membered rings and to activate a sp 3 C-H bond [18].For imine 2,6-F 2 C 6 H 3 CH=NCH 2 (2-BrC 6 H 4 ), the fluoro substituents block cyclometallation at the benzylidene ring, and drive the reaction towards formation of a five-membered exo-metallacycle (2g).As a whole, the obtained results indicate that intramolecular C-X bond activation at the saturated arm of N-benzylidene-benzylamines may promote formation of a biaryl linkage between one of the tolyl ligands and the benzyl group of the imine ligand.However, the biaryl linkage is not necessarily involved in the subsequent metallation process which leads to either endo-five, endo-six or exo-five-membered platinacycles as shown in Scheme 11.
Finally, it is interesting to point out that analogous processes from cyclometallated platinum(IV) complexes obtained from dimethylplatinum(II) precursors such as [PtMe 2 X{C 6 H 4 CH=NCH 2 R'}L] (X = Cl, Br; R' = aryl; L = SMe 2 , PPh 3 ) have been recently reported [71,72].In this case, C sp2 -C sp3 reductive elimination involving the metallated ring and one methyl ligand takes place and is followed by formation of five or six-membered platinacycles.

Conclusions
As a whole, several diarylplatinum(II) compounds displaying monomeric or dimeric structures in which the square-planar coordination of the platinum is completed with labile ligands such as dimethylsulfoxide or dialkylsulfides have been shown to be useful in the synthesis of several classes of platinacycles containing N-donor ligands.The observed reactions result from a series of oxidative addition/reductive elimination processes involving platinum(II)/platinum(IV) species.The initial coordination of the ligand takes place easily by substitution of the labile ligands and/or cleavage of the dinuclear structure and is followed by intramolecular C-X (X = Br, Cl, H) bond activation leading to cyclometallated platinum(IV) compounds.When C-H bond activation is involved, straightforward reductive elimination of a molecule of arene leads to formation of a cyclometallated platinum(II) compound.However, cyclometallated platinum(IV) compounds are formed for X = Br or Cl and subsequent reductive elimination from these species leads to C aryl -C aryl bond formation.When the formed biaryl moiety remains coordinated to the platinum through one or two nitrogen atoms, as for ligands RCH=NCH 2 R' or RCH=NCH 2 CH 2 NMe 2 , a further step involving C-H bond activation at either the formed biaryl fragment, or at other available aromatic or aliphatic positions produces a cyclometallated platinum(II) compound with reductive elimination of one molecule of arene.In this process, in addition to the more prevalent endo-five-membered platinacycles, other metallacycles such as endo-seven, endo-six or exo-five-membered can be obtained.In summary, a careful choice of the aryl groups in both the platinum precursor and the employed ligands allows the synthesis of a great variety of cycloplatinated compounds.