Analysis of Anionic Palladium Complexes by Electrospray-Ionization Mass Spec-

Electrospray-Ionization Mass Spectrometry: Motivation and Preliminary Results

As mentioned above, anionic palladium complexes are discussed as important intermediates in a number of palladium-catalyzed transformations. However, these species are challenging in several ways when it comes to the choice of suitable analytical methods. In-situ formed palladate intermediates often have only limited lifetimes and/or display a high susceptibility against air and moisture, rendering the use of, for example, crystallographic techniques diffi-cult. Furthermore, they are not present as isolated species, but as part of a complex mixture, which poses a drawback to many spectroscopic methods. As the palladate anions of interest bear a charge by definition, the use of mass spectrometry is a straightforward approach in this case. Electrospray-ionization (ESI) mass spectrometry allows for the generation and analysis of gas-phase ions from susceptible analytes under mild ionization conditions and has been suc-cessfully applied for the characterization of reactive organometallic species in general and for the observation of palladium-catalyzed transformations in particular.^[26,34–38]

Leading up to the studies presented in this work, ESI mass spectrometry had been applied in preliminary experiments to analyze anionic palladium complexes [(PAr^F₃)nPdX]^– ((PAr^F₃) = tris-[3,5-bis(trifluoromethyl)phenyl]phosphine) and [(S – PHOS)PdR3]^– (chart 1).^[39,40]

OCH₃

Chart 1:Phosphine ligands PAr^F₃(left) and S-PHOS (right) used in preliminary ESI-mass spectrometric experiments.

ESI mass spectrometry of palladate complexes [(PAr^F₃)nPdX]^–

Anionic palladium(0) complexes can be assumed to have a very high electron density on the palladium center, which is expected to decrease their stability and thus reduce the chances for their detection by ESI mass spectrometry. Therefore, a catalyst bearing an electron-poor phosphine ligand was found suitable as a model system to allow for the formation of better stabilized palladate complexes. The chosen catalyst [Pd(PAr^F₃)₃] is known to be active in Heck and cross-coupling reactions.^[41,42] As anticipated, [Pd(PAr^F₃)3] showed the formation of pal-ladate complexes [(PAr^F₃)_nPdX]^–, with n= 2 and 3, in high signal intensities when combined

Analysis of Anionic Palladium Complexes by Electrospray-Ionization Mass Spectrometry:

Motivation and Preliminary Results

with lithium halides LiX in preliminary ESI-mass spectrometric experiments. The formation of palladates was further confirmed by conductivity studies of [Pd(PAr^F₃)₃] with various added salts (LiF, LiCl, LiBr, LiI, LiClO₄, NBu₄Cl) in tetrahydrofuran (THF) as well as by³¹P-NMR spectroscopic experiments.^[40] These results demonstrated that [Pd(PAr^F₃)3] was a very well-suited model catalyst for undertaking a more detailed analysis of the formation, stability, and reactivity of palladate(0) complexes bearing (pseudo)halide ligands.

ESI mass spectrometry of organopalladate complexes [(S – PHOS)PdR₃]^–

Previous results from ESI-mass spectrometric studies on the possibility of a transmetalation/

reductive elimination sequence for the reduction of palladium(II) precatalysts (section 1.3) showed that the transmetalation of a mixture of Pd(OAc)2and 2-dicyclohexylphosphino-2’,6’-dimethoxybiphenyl (S-PHOS) with a Grignard reagent RMgCl, with R = Ph and Bn, yielded triply substituted organopalladate complexes [PdBn₃]^– and [(S – PHOS)PdR₃]^– (figure 1.1 for the example of R = Ph).^[39] These complexes readily underwent reductive elimination in gas-phase fragmentation reactions, yielding the corresponding palladium(0) anions [(S – PHOS)PdR]^–and [PdBn]^–(figure 1.2 for the example of [(S – PHOS)PdPh₃]^–).

For both R = Ph and R = Bn, a minor fragmentation pathway was the loss of RH, which corre-sponded to a C – H activation reaction. The product ions of these reactions, [(S – PHOS)PdR₂– H]^–, were present already in the mass spectra without any additional frag-mentation, suggesting the loss of RH to be a relevant decomposition pathway also in so-lution. Furthermore, the collision-induced dissociation of [(S – PHOS)PdPh₂– H]^– produced [(S – PHOS)Pd – H]^– in a reductive elimination of Ph₂, indicating that the hydrogen atom in the dissociation of RH may also stem from the S-PHOS ligand.

Figure 1.1: Negative-ion mode ESI mass spec-trum of a solution of Pd(OAc)2 (3 mM), S-PHOS (6 mM), and PhMgCl (12 mM) in THF (a = [(S – PHOS)PdPh2– H]^–).^[43]

Figure 1.2: Mass spectrum of mass-selected [(S – PHOS)PdPh3]^– (b) and its fragment ions produced upon collision-induced dis-sociation (Acceleration energy ELAB= 8.0 eV, a = [(S – PHOS)PdPh2– H]^–).

10

Introduction In all cases, the organopalladate complexes of interest were obtained in relatively low signal intensities, pointing to their correspondingly low concentration in the sample solutions. Con-ducting the same reaction withn-BuMgCl did not lead to any detectable palladate complexes at first; the formation of [(S – PHOS)PdBu3]^– was only achieved when lithium chloride was added to the mixture to enhance the reactivity of the Grignard reagent.^[44] The transmetala-tion withn-BuLi, surprisingly, did not yield any detectable palladate complexes, despite the fact that organyllithium reagents had been found before to react with palladium(II) species to form palladates.^[22,23] Yet, it is possible that the chosen reaction conditions gave rise to follow-up reactions, or that palladate complexes were actually formed, but could not be de-tected due to the formation of contact-ion pairs with the lithium counterion. Control experi-ments with the palladium(0) precursor Pd(PPh₃)₄did not show any palladium-containing an-ions.

These first studies made clear that organopalladate(II) complexes are formed in transmetala-tion reactransmetala-tions and also show the reductive eliminatransmetala-tion under formatransmetala-tion of palladium(0) species as suggested in section 1.3, and that the considered anions can be probed by ESI-mass spectro-metric methods. Still, the present results raised several interesting questions regarding, for example, the influences of the nature of the phosphine ligands and the organic substituents R on the formation and reactivity of these palladate(II) complexes, which is why further investi-gations were required.

As the above-shown previous research and preliminary results demonstrate, ESI mass spec-trometry is a promising method to identify and characterize ionic intermediates in palladium-catalyzed reactions. Hence, it was applied as the primary analytical method in the studies pre-sented in this work, and will therefore be explained in more detail in the following.

2 Theoretical Background:

Electrospray-Ionization Mass Spectrometry

2.1 Setup of a Mass Spectrometer

Mass spectrometry is an analytical method that allows the generation and analysis of ions in the gas phase. Generally, any mass spectrometer consists of the same basic components (fig-ure 2.1).^[45]The analyte is transferred through the sample inlet into the ion source, where gas-phase ions are generated. The ions are then separated according to their mass-to-charge (m/z) ratio by the mass analyzer before they are allowed to pass into the detector. Depending on the instrument type, high vacuum or ultra-high vacuum conditions are applied for the generation and analysis of gas-phase ions in most cases. Ion guides like ion funnels or multipoles ensure an efficient transfer of the ions between the different parts of the mass spectrometer. A com-puter with a suitable software is used to control the instrument and to process the aquired data.

Mass spectra are prepared by plotting the obtained signal intensities against the respectivem/z ratio of the analyte ions.

Figure 2.1:Schematic representation of the general setup of a mass spectrometer.^[45]

Electrospray Ionization