Scott McIndoe

A combination of UV-Vis spectroscopy and electrospray ionization mass spectrometry is used for real-time monitoring of Pd 2 (dba) 3 activation with sulfonated versions of PPh 3 and Buchwald-type ligands. This provides insight into the effect of ligand and preparation conditions on activation and allows for establishment of rational activation protocols. Palladium-based catalysts are amongst the most important and widely used transition-metal complexes in catalysis and are used in numerous coupling reactions. 1 The active Pd catalyst is often obtained by in situ activation of a precatalyst with a triaryl phosphine. The outcome of the activation process can depend on the source of the precatalyst, 2 order of addition, and chosen reaction conditions. 3 Recently, several reports on the activation chemistry of Pd(II) precursors have appeared, 4 but investigations regarding the activation of zero valent Pd precursors remain limited. 5–12 Pd 2 (dba) 3 is the most frequently employed source of Pd(0), 13 but despite its popularity the actual nature of the catalytically relevant species and the influence of reaction conditions on its activation are incompletely understood. In situ activation is often carried out using a Pd 2 (dba) 3 solution which is either pre-heated or stirred for an extended period of time followed by addition of two equivalents (relative to Pd) of ligand of choice. 5–7,14 This general process is often portrayed as a simple ligand exchange (eqn (1)) but is actually more complicated, because the free dba remains in solution to compete for coordination to palladium. Pd 2 ðdbaÞ 3 þ 4L *) 2PdðZ 2-dbaÞL 2 þ 2dba (1) Depending on the ligand used and the reaction conditions chosen the activity of the catalyst varies significantly. 14,15 Reports on the effect of changes in parameters during activation are in some cases contradictory. 16 Heating of precatalyst and ligand prior to the addition of substrates has been suggested as a means to ensure reproducible reaction rates; 17–19 however, others question the benefits of this precaution. 2,3,20 Depending on the precatalyst and ligand used, long stirring times may be unnecessary or may even change catalyst speciation which further complicates the activation. A further complicating factor is the non-innocence of the dba ligand leading to the presence of Pd(dba) x L y type complexes. 5,8,21 The occurrence of such species in different solvents have not been investigated in detail and may play a significant role in the catalytic process. 22–24 On top of that, the choice of Pd 2 (dba) 3 supplier or storage may influence catalytic activity as minor impurities and the presence of nanoparticles in individual samples of Pd 2 (dba) 3 may further influence the activation and activity. 2,25 It is important to understand the activation of Pd 2 (dba) 3 under various conditions to get a clear picture of the process and to optimize the formation of active catalyst. Real-time monitoring of catalyst activation assists in the elucidation of the various species formed and pathways taken during this process. Electrospray ionization mass spectrometry (ESI-MS) has previously been shown to be a valuable tool in understanding catalytic reactions and charge-tagged phosphine ligands (vide infra) have been established as a useful means of enabling real-time ESI-MS investigations using a normally neutral catalyst. 26–30 Using only ESI-MS, neutral Pd 2 (dba) 3 and other neutral species cannot be observed. To overcome this limitation and obtain richer information we have paired ESI-MS with UV-Vis spectroscopy. This set up allows for monitoring of the complete activation and provides deeper understanding of the processes involved. The phosphine ligands used in this study were chosen because they can be seen as the charge-tagged derivatives of two commonly used neutral phosphine ligands (Fig. 1). The [PPN] + [TPPMS] À (1), was chosen as an analogue of triarylphospines (PAr 3); Na + [sSPhos] À (2) is a Buchwald-type ligand. In a typical reaction, a custom-made flask was equipped with a septum and fiber optic UV-Vis probe (see ESI †). The flask was evacuated and filled with degassed solvent that was fed into the ESI-MS using the pressurized sample infusion (PSI) methodology. 31,32

Electron ionization (EI) is a reliable mass spectrometric method for the analysis of the vast majority of thermally stable and volatile compounds. In direct EI-MS, the sample is placed into the probe and introduced to the source. For air-and moisture-sensitive organometallic complexes, the sample introduction step is critical. A small quantity must be briefly exposed to the atmosphere, during which time decomposition can occur. Here we present a simple tool that allows convenient analysis of air-and moisture-sensitive organometallic species by direct probe methods: a small purge-able glove chamber affixed to the front end of the mass spectrometer. Using the upgraded mass spectrometer, we successfully characterized a series of air-and moisture-sensitive organometallic complexes, ranging from mildly to very air-sensitive.

The use of hand-held 3D printing technology provides a unique and engaging approach to learning VSEPR theory by enabling students to draw three-dimensional depictions of different molecular geometries, giving them an appreciation of the shapes of the building blocks of complex molecular structures. Students are provided with 3D printing pens and two-dimensional templates which allows them to construct three-dimensional ABS models of the basic VSEPR shapes. We found that the learning curve associated with manipulating the pen accurately and the time required to draw a structure is sufficiently high that this exercise would need to be limited in a laboratory setting to students each being tasked with drawing a different molecule; however, in the correct setting, hand-held 3D printing pens are a potentially powerful tool for the teaching of VSEPR theory.

a department of Pure and industrial Chemistry, university of nigeria, nsukka, nigeria; b department of Chemistry and Biochemistry, university of notre dame, notre dame, in, usa; c department of mechanical engineering, university of nigeria, nsukka, nigeria; ABSTRACT The reactivity of the metalloligand [Pt 2 (μ-S) 2 (PPh 3) 4 ] with the boron-functionalized alkylating agents BrCH 2 (C 6 H 4)B(OR) 2 (R = H or C(CH 3) 2) was investigated by electrospray ionization mass spectrometry (ESI-MS) in real time using pressurized sample infusion (PSI). The macroscopic reaction of [Pt 2 (μ-S) 2 (PPh 3) 4 ] with one mole equivalent of alkylating agents BrCH 2 (C 6 H 4) B{OC(CH 3) 2 } 2 and BrCH 2 (C 6 H 4)B(OH) 2 gave the dinuclear monocationic μ-sulfide thiolate complexes [Pt 2 (μ-S){μ-SCH 2 (C 6 H 4)B{OC(CH 3) 2 } 2 }(PPh 3) 4 ] + and [Pt 2 (μ-S){μ-S + CH 2 (C 6 H 4)B(OH)(O −)}(PPh 3) 4 ]. The products were isolated as the [PF 6 ] − salt and zwitterion, respectively, and fully characterized by ESI-MS, IR, 1 H and 31 P NMR spectroscopy, and single-crystal X-ray structure determinations.

Continuous monitoring of catalyzed reactions using infrared spectroscopy (IR) measures the transformation of reactant into product, whereas mass spectrometry delineates the dynamics of the catalytically relevant species present at much lower concentrations, a holistic approach that provides mechanistic insight into the reaction components whose abundance spans 5 orders of magnitude. Probing reactions to this depth reveals entities that include precatalysts, resting states, intermediates, and also catalyst impurities and decomposition products. Simple temporal profiles that arise from this analysis aid discrimination between the different types of species, and a hydroacylation reaction catalyzed by a cationic rhodium complex is studied in detail to provide a test case for the utility of this methodology. C atalytic reactions are notoriously difficult to study directly under real reaction conditions, principally because the abundance of the catalyst is typically several orders of magnitude lower than that of the substrates. For example, a 1 mol % catalyst loading is at the limit of sensitivity for standard in situ NMR experiments. Although more sophisticated nuclear spin polarization methods can produce remarkable enhancements to signals (10 2 −10 4) in NMR spectroscopy, such techniques are generally equipment and/or catalyst system specific. 1 Few available, straightforward techniques are sensitive enough to determine the catalyst speciation while at the same time not being overwhelmed by the large quantities of substrate, products, and solvent present, though the combination of multiple methods is becoming an increasingly popular solution. 2 The high dynamic range of electrospray ionization mass spectrometry (ESI-MS) enables detection of otherwise-invisible, catalytically relevant species, 3 and pressurized sample infusion (PSI) provides a methodology to allow for continuous monitoring of catalytic reactions. 4 However, when using ESI-MS to monitor substrates and products, the catalytic species observed are for the most part the resting state and/or the most abundant on-cycle species. This does not utilize the full potential of ESI-MS to probe deeper into even less abundant species, because the concentration range employed does not exercise the sensitivity limits of the instrument. The ideal approach would be to co-opt some other, less sensitive, orthogonal technique to monitor overall reaction progress, while using the ESI-MS to focus exclusively on the low abundance, catalytically relevant species. Infrared spectroscopy (IR) is the perfect complementary tool for this (especially under flow conditions), but it comes with certain reaction design criteria for monitoring by flow IR/ESI-MS: (1) an IR spectroscopic handle in substrates/products; (2) a cationic catalyst, appropriate reaction times and catalysis concentrations (minutes to hours, catalyst at low mol % level; a charged catalyst circumvents the need for charge-tagging strategies); 5 (3) atom efficiency so products and substrates reciprocally track each other. The catalyzed hydroacylation reaction (the potentially 100% atom efficient C−H activation/C−C coupling between an aldehyde and olefin to form a ketone) offers an ideal platform to develop flow IR/ESI-MS as it is commonly catalyzed by well-defined cationic Rh−phosphine systems at low catalyst loadings (0.1−5 mol %), and has the benefit of an aldehyde to ketone transformation which have well-defined IR-reporter carbonyl groups. 6 Catalytic chemists have always had strong intuitions about the temporal evolution of various components of a reaction (Figure 1) and especially the temporal evolution of reactants and products. 7 They expect reactant to be consumed and product to be formed that follow zero-, first-, or second-order kinetics (and sometimes more complex kinetics). Many methods, spectroscopic and otherwise, exist to establish these data. 8 However, given that ESI-MS is able to probe temporal evolution of species at concentration levels several orders of magnitude lower than most other techniques, it is worth thinking about what behaviors might be expected to be observed of species directly or indirectly related to the precatalyst (Figure 1). The precatalyst itself might be expected to diminish at a rate related to the initiation period. Species that

Oligomeric phosphaalkenes are readily characterized using electrospray ionization mass spectrometry (ESI-MS). The high affinity of phosphines for silver ions permits the detection of the unadulterated polymer as [M + xAg] x+ ions (x = 2–3). When the oligomers are oxidized using H 2 O 2 , the resulting phosphine oxide polymer may be treated with sodium ions to produce [M + xNa] x+ ions (x = 2–3). Both methods predict a similar distribution of oligomers: M n values of 3450 ± 100 Da and a PDI of 1.09 ± 0.01 cover both analyses. This distribution represents oligomers of the general formula Me(PMesCPh 2) n H from n = 4–20, maximizing at n = 10. Résumé : Les phosphalcènes oligomériques peuvent être facilement caractérisés par spectrométrie de masse a ` ionisation par électronébulisation (ESI-MS). La forte affinité des phosphines pour les ions d'argent permet la détection du polymère intact sous la forme d'ions [M + xAg] x+ (x = 2 ou 3). Lorsque les oligomères sont oxydés par le peroxyde d'hydrogène (H 2 O 2), le polymère d'oxyde de phosphine résultant peut être traité a ` l'aide d'ions de sodium pour former des ions [M + xNa] x+ (x = 2 ou 3). Les deux méthodes permettent de prédire une distribution oligomérique similaire : les résultats correspondent a ` des valeurs de masse moléculaire moyenne (M n) de 3450 ± 100 Da et un indice de polydispersité de 1,09 ± 0,01. Cette distribution représente des oligomères de formule générale Me(PMesCPh 2) n H dans l'intervalle où n = 4 a ` 20, et atteint un maximum autour de n = 10. [Traduit par la Rédaction] Mots-clés : spectrométrie de masse, phosphore, polymère, ionisation par électronébulisation, oligomères.

Reactions of [Pt 2 (l-S) 2 (PPh 3) 4 ] with activated aliphatic bromoacyl alkylating agents BrCH 2 C(O)C(CH 3) 3 , BrCH 2 C(O)CH 2 CH 3 and BrCH 2 C(O)C(O)CH 2 Br, were investigated by electrospray ionization mass spec-trometry (ESI-MS) in real time using pressurized sample infusion (PSI). The laboratory scale reactions gave the mono-, dicationic and bridged, l-thiolate complexes [Pt 2 (l-S){l-SCH 2 C(O)C(CH 3) 3 }(PPh 3) 4 ] + , [Pt 2 {l-SCH 2 C(O)CH 2 CH 3 } 2 (PPh 3) 4 ] 2+ and [Pt 2 {l-SCH 2 C(O)C(O)CH 2 S}(PPh 3) 4 ] 2+. Sequential reactions of [Pt 2 (l-S) 2 (PPh 3) 4 ] with BrCH 2 C(O)C(CH 3) 3 and BrCH 2 C(O)CH 2 CH 3 yielded the heterodialkylated complex [Pt 2 {l-SCH 2 C(O)C(CH 3) 3 }{l-SCH 2 C(O)CH 2 CH 3 }(PPh 3) 4 ] 2+. The products were isolated as the [BPh 4 ] À or [PF 6 ] À salts and characterized by ESI-MS, IR, 1 H and 31 P NMR spectroscopy and single-crystal X-ray crystallography.

The mechanism of the Sonogashira reaction in methanol was studied in detail using pressurized sample infusion electrospray ionization mass spectrometry (PSI-ESI-MS). Several key intermediates were identified and their structures were assigned by MS/MS studies. Cationic and anionic charged-tagged substrates were employed to look into the mechanism of this reaction from variety of angles. A reverse kinetic isotope effect was observed in which the reaction rate is accelerated in deuterated solvents (k H /k D = 0.6). The reaction was found to be zero order with respect to the aryl iodide and first order with respect to the phenylacetylene. A Hammett parameter of ρ = 1.4 indicates that the reaction is more favorable for aryl iodides with para EWGs. No evidence of product inhibition, dimerization of palladium catalyst, or agglomeration were observed. However, catalyst decomposition was inferred from a non-zero intercept in the plot of catalyst loading versus reaction rate. Monitoring the reaction by PSI-ESI-(−)MS on neutral and negatively charged substrates at variety of concentrations and conditions did not reveal any detectable anionic palladium complexes. Likewise no evidence of carbopalladation and relevant intermediates in the absence of a base was observed.

Dynamic information can be obtained on in-progress reactions in real time using a balloon-pressurized Schlenk flask in combination with an electrospray ionization mass spectrometer. The apparatus can be set up on a Schlenk line or in a glovebox and transported to the spectrometer, to be initiated by addition of catalyst or reactant by syringe through a septum. The system is demonstrated on palladium-catalyzed oxidation of phosphines.

The position of the spray-head, the solvent, and a variety of additional instrumental parameters were independently adjusted during electrospray ionization mass spectrometric (ESI-MS) analysis of an equimolar mixture of two different ions. These parameters were found to have drastic effects on the distribution of signal intensity from one ion to another, and therefore the resulting usefulness of acquired spectra. The analytes studied were bis(triphenylphosphine)iminium (PPN) chloride and tetramethylam-monium (TMA) chloride, two chemically distinct ions. The use of these two ions in a test solution yielded information regarding ESI probe spatial effects for two very different analytes, while probing the issue of sampling efficiency. Each experimental parameter was individually adjusted prior to rastering the spray head across the operational plane in order to observe how adjustment to a particular parameter affects analyte signal in relation to the distance from the MS aperture. Following acquisition, the intensities of both ions were plotted as ion contour maps demonstrating the intensity change with respect to capillary position in relation to the mass spectrometer aperture. The sharp contrast in ion intensity, and even differential ion activity, with relatively minor instrument changes (such as temperature programming, gas flow rates and solvent choice) clearly demonstrates the importance of finding the " sweet spot " for the ESI spray head, especially when signal intensity and a quality analysis are key.

Real-time mass spectrometric monitoring of speciation in a catalytic reaction while it is occurring provides powerful insights into mechanistic aspects of the reaction, but cannot be expected to elucidate all details. However, mass spectrometers are not limited just to analysis: they can serve as reaction vessels in their own right, and given their powers of separation and activation in the gas phase, they are also capable of generating and isolating reactive intermediates. We can use these capabilities to help fill in our overall understanding of the catalytic cycle by examining the elementary steps that make it up. This article provides examples of how these simple reactions have been examined in the gas phase.

The cationic rhodium complex [Rh(P c Pr 3) 2 (η 6-PhF)] + [B-{3,5-(CF 3) 2 C 6 H 3 } 4 ] − (P c Pr 3 = triscyclopropylphosphine, PhF = fluo-robenzene) was used as a catalyst for the hydrogenation of the charge-tagged alkyne [Ph 3 P(CH 2) 4 C 2 H] + [PF 6 ] −. Pressurized sample infusion electrospray ionization mass spectrometry (PSI-ESI-MS) was used to monitor reaction progress. Experiments revealed that the reaction is first order in catalyst and first order in hydrogen, so under conditions of excess hydrogen the reaction is pseudo-zero order. Alkyne hydrogenation was 40 times faster than alkene hydrogenation. The turnover-limiting step is proposed to be oxidative addition of hydrogen to the alkyne (or alkene)-bound complex. Addition of triethylamine caused a dramatic reduction in rate, suggesting a deprotonation pathway was not operative. ■ INTRODUCTION Hydrogenation of alkynes and alkenes mediated by rhodium complexes is a classic catalytic organometallic reaction. 1 First introduced by Wilkinson, 2 the eponymous catalyst Rh-(PPh 3) 3 Cl has been widely employed, thanks to the mild conditions it operates under and its selectivity for C−C multiple bonds over other unsaturated sites. 3 The mechanism of the reaction has been studied by a wide range of approaches. 4 It may well be the most well-studied organo-metallic catalytic reaction. It is relatively complicated, with off-cycle equilibria between catalyst monomer and dimer (and hydrogenated versions thereof) and between di-and triphosphine species. Cationic rhodium complexes are known for the hydrogenation of alkynes from Schrock and Osborn's work, 5 and since then, these types of complexes have served as precursors in various studies of homogeneous catalysis. Bis(ditertiaryphosphine) chelate complexes of rhodium(I) were studied as catalytic hydrogenators of methylenesuccinic acid, and cationic and hydrido versions of the complex were found to be more active than corresponding chloro versions, with activity increasing with increasing chain length of the diphosphine. 6a Semihydrogenation of internal alkynes such as diphenylacetylene has also been developed with good selectivity with use of trinuclear cationic rhodium complexes. 6b Innately linked to cationic rhodium hydrogenation is catalytic asymmetric synthesis to produce enantiomerically pure compounds due to the possibility of introducing a degree of chirality in the ligands on the metal center. Extensive work has been done in this area with rhodium and more recently with iridium and ruthenium complexes. 7 The scope of [Rh(diene)-(PR 3) 2 ] + precursors 8 was further increased to the hydro-genation of imines, 9 and since then, the hydrogenations of prochiral imines for the production of a chiral amines has become a promising route for synthesis of chiral nitrogen-containing compounds. 10 DFT studies have become increasingly popular for the unravelling of mechanistic details of these systems. 11 We have examined rhodium-catalyzed hydrogenation previously using electrospray ionization mass spectrometry (ESI-MS), wherein we doped in substoichiometric quantities of a charged phosphine ligand, 12 [Ph 2 P(CH 2) 4 PPh 2 Bn] + [PF 6 ] − (Bn = benzyl), into a reaction mixture consisting of an alkene, hydrogen, and Wilkinson's catalyst, using chlorobenzene as a solvent. 13 We observed a large variety of rhodium complexes consistent with the known speciation of this reaction mixture. However, because ESI-MS operates only on ions, the overall progress of the reaction was not tracked, and therefore the concentration of metal−ligand intermediates cannot be matched to activity. As such, establishing whether or not an observed species is an intermediate, a resting state, or a decomposition product is not easy. We later reexamined the reaction, where we added a charged tag to the substrate (in this case an alkyne) rather than the catalyst. 14 This paper confirmed that the turnover-limiting step was ligand dissociation from the precatalyst to generate the unsaturated, 14-electron species Rh(PPh 3) 2 Cl. However, since all steps involving the alkyne on

A B S T R A C T A principal feature of electrospray ionization (ESI) is the transfer of ions in solution into the gas-phase for analysis by mass spectrometry. The electrospray process is intricate and therefore each stage of the process must be well-characterized in order to optimize the quality of the data obtained. The surface activity of a given ion is a substantial factor in its likelihood of evaporating from droplets formed by the electrospray, and leads to a differential response of one ion over another. Consequently, investigation of the response of a variety of ions in multiple solvents lends insight toward both desolvation processes and the surface activity of the ions studied in the chosen solvent. In the present work, a cationic ionic liquid, butyl methylimidazolium (BMIM), was paired with a counterion and mixed in various solvents. Subsequently, BMIM paired with a different counterion was added to the solution and analyzed by ESI mass spectrometry to determine the relative response ratio between two observable aggregates. The findings assist in the elucidation of differential surface activity of chemically distinct ions in ESI, with respect to changes in solvent. Furthermore, the results obtained suggest acetonitrile is an optimal solvent for the analysis of ions of this type due to a reduction in differential effects, whereas other common ESI solvents prove to enhance the surface activity of specific aggregate ions.

A range of cationic rhodium bisphosphine h 6-fluorobenzene (fluorobenzenes ¼ C 6 H 6Àn F n , n ¼ 1e3) and related complexes have been synthesized and characterized. These complexes act as useful organome-tallic precursors for catalysis or further synthetic elaboration. The relative binding affinity of the arene ligands has been investigated using Electrospray Ionisation Mass Spectrometry (ESIeMS) and two different collision-induced dissociation (CID) techniques. The influence of arene fluorination upon arene binding affinity is discussed as well as the comparison of different bisephosphine ligands with regard to bite angle and phosphine substitution. We show that this simple technique allows fast and easy comparison of the binding affinity of arene ligands to cationic organometallic fragments.

The conjugate addition of an alcohol to a butynoate ester using an organophosphine catalyst was monitored using pressurized sample infusion electrospray ionization mass spectrometry (PSI-ESI-MS), together with 31 P and 1 H NMR spectroscopy. The combination of methods allowed examination of the reaction progress from the perspective of reactants and products (1 H NMR) and insights into behaviors of the reaction intermediates and formation of byproducts (31 P NMR and MS). The resulting traces could be closely approximated through numerical modeling by appropriate selection of rate constants, and a sound understanding of the mechanism and the means by which oligomeric byproducts are formed allows a rational approach to experimental design.

The [Rh(xantphos)] + fragment acts as an effective catalyst for the hydroboration of the alkene TBE (tert-butyl ethene) using the amine–borane H 3 B·NMe 3 at low (0.5 mol%) catalyst loadings to give the linear product. Investigations into the mechanism using the initial rate method and labelling studies show that reductive elimination of the linear hydroboration product is likely the rate-limiting step at the early stages of catalysis, and that alkene and borane activation (insertion into a Rh–H bond and B–H oxidative addition) are reversible. The resting state of the system has also been probed using electrospray ionization mass spectrometry (ESI-MS) using the pressurised sample infusion (PSI) technique. This system is not as effective for hydroboration of other alkenes such as 1-hexene, or using phosphine borane H 3 B·PCy 3 , with decomposition or P–B bond cleavage occurring respectively.

A series of thioether-functionalised imidazolium salts have been prepared and characterized. Subsequent reaction of the thioether-functionalised imidazolium salts with iodomethane affords imidazolium–sulfonium salts composed of doubly charged cations and two different anions. Imid-azolium–sulfonium salts containing a single anion type are obtained either by a solvent extraction method or by anion exchange. The imidazolium–sulfonium salts undergo a methyl-transfer reaction on exposure to water, giving rise to a new, singly charged imidazolium salt with iodide introduced at the 2-position of the imidazolium ring. Crystal structures of some of the imidazolium–sulfonium salts were determined by X-ray crystallography providing the topology of the interactions between the dications and the anions. Electrospray ionization mass spectrometry and quantum-chemical calculations were used to rationalise the relative strength of these interactions.

Electrospray ionization mass spectrometry (ESI-MS) is a soft ionization technique commonly coupled with liquid or gas chromatography for the identification of compounds in a one-time view of a mixture (for example, the resulting mixture generated by a synthesis). Over the past decade, Scott McIndoe and his research group at the University of Victoria have developed various methodologies to enhance the ability of ESI-MS to continuously monitor catalytic reactions as they proceed. The power, sensitivity and large dynamic range of ESI-MS have allowed for the refinement of several homogenous catalytic mechanisms and could potentially be applied to a wide range of reactions (catalytic or otherwise) for the determination of their mechanis-tic pathways. In this special feature article, some of the key challenges encountered and the adaptations employed to counter them are briefly reviewed. Electrospray ionization mass spectrometry (ESI-MS) is a technique that at first blush seems ideally suited to the examination of catalytic reactions. It is a fast technique which possesses great sensitivity, [1] it can cope with mixtures intractable to many other techniques [2] and it has a high dynamic range. [3] These properties are all useful for analysis of complex reaction mixtures. The sensitivity allows for detection of trace intermediates. Its speed – one spectrum takes a second or less to acquire – enables dense data to be collected on reactions that are over in mere minutes, but can easily be extended to reactions lasting hours. [4] Catalytic reactions are almost by necessity a soup of reactants, products, byproducts, intermediates, resting states and decomposed material; intrinsic to the property of ESI-MS is that it produces well-separated and diagnostic signals for individual components, making it capable of dissecting such mixtures. Finally, a dynamic range across several orders of magnitude enables accurate measurement of abundant and traces components alike. [5] Accordingly, ESI-MS was earmarked as a promising technique for the analysis of catalytic reactions almost as soon as the first commercial machines appeared. The groundbreaking paper was the 1994 report by Canary, [6] detailing studying the mechanism of the Suzuki cross-coupling reaction. This paper introduced the idea of using a substrate that was especially amenable to the ESI-MS process, in this case a brominated pyridine. The pyridine, carrying as it did a peripheral basic site that was uninvolved in the reactivity but was easily protonated to provide [M + H] + ions, showed how the use of appropriate substrates for reactions would light up not only that species, but whatever intermediates, resting states and decomposition products that substrate was bound to. Canary used this property to take snapshots of the speciation of the reaction as it proceeded and obtained interesting insights into the nature of the reaction. However, despite the promising start, it is fair to say that progress has stuttered in the two decades following, with the vast majority of mechanistic studies still being conducted with other methods. The question of why ESI-MS was not a standard method for catalytic analysis was one we asked ourselves nearly ten years ago, and we've spent the intervening period finding out why, and developing solutions to the problems we encountered. Fortunately, we had the benefit of years of pioneering work by others, and the community has continued to inspire and innovate. This short review will, however, restrict itself to the approaches we employ to solve the problems and conclude with a short section on the information that can be obtained on catalytic reactions using these techniques. Many of the suggestions are simple precautions , tips and protocols which will be helpful for those looking to make better use of a technique available in most large research facilities and chemistry departments. Collectively, they can be used to enable researchers to gain insights that are beyond the capabilities of competing methods. Cross contamination Most spectroscopic methods do not need to concern themselves with what the previous user was examining. Provided the experiment uses clean apparatus, the only analyte being detected will be the intended one. However, ESI-MS has the notable feature that all samples pass through the same infusion system, and the sensitivity of the technique and variation in ionization response for different molecules and ions means that it is entirely plausible that an intense signal observed in a spectrum in fact originated from the previous user's sample. Safeguarding against such cross-contamination requires certain precautions. A. Minimize shared apparatus. It is always necessary to share the capillary from which the spray emerges (and depending on instrumental design, an internal capillary designed to

The rate of hydrodehalogenation of aryl iodides with a palladium catalyst in methanol exhibits a strong primary kinetic isotope effect from both CD 3 OD and CH 3 OD, suggesting that deprotonation plays a major role in the mechanism. The replacement of a C–X (X = halide) bond with a C–H bond (hydrodehalogenation) is a frequent competing reaction in palladium-catalyzed cross-coupling reactions, and is responsible for diminished yields and unwanted byproducts. An early mechanism for catalytic hydrodehalogenation of aryl halides was proposed by Zask, 1 and then extended by Nolan 2 involving oxidative addition of aryl halide (Ar–X) to a Pd(0) complex, followed by displacement of the halide ligand by methoxide, b-elimination of formaldehyde and reductive elimination of Ar–H to regenerate the Pd(0) species (Scheme 1). The same mechanism also was reported using Ni(0)/imidazolium chloride 3 and Ru(II) 4 catalysts. Oxidation of the alcohol solvent has been reported by Zhang 5 in homocoupling as well as hydrodehalogenation of aryl halides. Recently, another report 6 on equivalent oxidation of solvent during hydrodehalogenation also supports the involvement of beta hydride elimination as a key step in the reaction. Our interest in the reaction stemmed from our observation that hydrodehalogenation was the major side reaction in the copper-free Sonogashira reaction/Heck alkynation when conducted in methanol, 7 and we decided to study it in its own right by the simple expedient of leaving out the other coupling partner, the terminal alkyne. Hydrodehalogenation is slow in the presence of weak bases such as triethylamine, but is greatly accelerated by using the relatively strong base potassium tert-butoxide. Our approach to catalytic analysis is to use the continuous monitoring technique of pressurized sample infusion electrospray ionisation mass spectrometry (PSI-ESI-MS) 8 in conjunction with substrates tagged on the periphery of the molecule with a charged functional group. 9 The combination of charge-tagging and ESI-MS is an increasingly popular approach to establishing speciation in catalytic mixtures. 10 Examination of the reaction of the charge-tagged aryl iodide [Ph 3 PCH 2 C 6 H 4 I][PF 6 ] (ArI) in methanol using Pd(PPh 3) 4 as the catalyst and t BuOK as the base allowed us to follow the abundance of starting material, product, byproduct (in this case the biphenyl product of homocoupling) and all intermediates containing the charged tag that are present in reasonable abundance. The reaction was repeated in CH 3 OD and CD 3 OD. The reaction takes about 100 minutes to go to completion in CH 3 OH at a catalyst loading of 6 mol% under pseudo first-order kinetics (k = 0.0292 min À1). In addition to the product (ArH), the homo-coupling byproduct (ArAr) also forms in low yield (B2%). The main palladium-containing species observed over the course of the reaction are PdP 2 (Ar)(I), PdP 2 (Ar)(H), and PdP 2 (Ar) 2. Fig. 1 shows intensity vs. time traces for ArI, ArH, ArAr, PdP 2 (Ar)(I) and PdP 2 (Ar)(H) (the two Pd-containing species have been multiplied by 100 to get them on the same scale as the other species). Note that the behaviour of the PdP 2 (Ar) 2 is discussed in ESI; † the low yield of this byproduct means we have neglected it as contributing significantly to the overall process. Because two different plausible intermediates are observed, the reactions that consume these compounds are both relatively slow, and both reactions are likely to contribute to the overall rate of the reaction. Both of these species appear in the Scheme 1 A possible mechanism of hydrodehalogenation of aryl halides.

Continuous monitoring using electrospray ionisation mass spectrometry (ESI-MS) shows that Wilkinson's catalyst hydrogenates a charge-tagged alkyne to the corresponding alkene, and at only a marginally slower rate, to the alkane. No rhodium-containing intermediates were observed during the reaction, consistent with the established mechanism which points at the initial dissociation of triphenylphosphine from Rh(PPh 3) 3 Cl as being the key step in the reaction. A numerical model was constructed that the closely matched the experimental data, and correctly predicted the response of the reaction to the addition of excess PPh 3 .

The anionic transition metal carbonyl cluster [H 3 Ru 4 (CO) 12 ] − may be energized in the gas phase through collision-induced dissociation (CID), which results in sequential loss of hydrogen and carbon monoxide from the cluster. If this experiment is performed in the presence of iron pentacarbonyl gas, up to three equivalents of the iron complex add to the tetranuclear ruthenium complex to give nearly-saturated product clusters with cores containing five, six and seven metal atoms. Further CID reveals that the iron atoms become intimately incorporated into the cluster core, and thus this process represents a method for the gas-phase synthesis of mixed-metal clusters.

Electrospray ionization mass spectrometric studies of poly(methylaluminoxane) (MAO) in the presence of Cp 2 ZrMe 2 , octamethyltrisiloxane (OMTS), or [Bu 4 N]Cl in fluorobenzene solution are reported. The results concur with the hypothesis that MAO is partially ionized in sufficiently polar media, where the contact ion pairs are of the general formula [Me 2 Al][(MeAlO) x (AlMe 3) y Me]. A limited number of compositions of this type are detected; the most abundant has x = 23 and y = 7, where the cation [Me 2 Al(OMTS)] + (with m/z 293) and the anion (with m/z 1853) were detected in the presence of OMTS, which stabilizes the Me 2 Al cation. The results demonstrate that MAO ionizes Cp 2 ZrMe 2 by acting as a source of this electrophilic cation, giving rise to an ion pair featuring a large and weakly coordinating aluminoxanate counterion. E ver since its discovery by Sinn and Kaminsky, 1 MAO has been used extensively as an activator of single-site, olefin polymerization catalysts. 2 MAO is believed to activate single-site catalysts such as metallocene complexes by alkylation and ionization, as depicted in eqs 1 and 2. Although much is known about the chemistry of the cationic moiety, an alkylmetalloce-nium ion, 3 much less is known about the structure and composition of the counteranion. MAO is made by the controlled hydrolysis of trimethylalu-minum 4 or by reaction of AlMe 3 with, for example, CO compounds, 4b resulting in an oligomeric mixture that has defied definitive structural characterization. There are few diagnostic spectroscopic handles, and the MAO oligomers can inter-convert in the presence of free AlMe 3. Proton NMR studies have indicated that the empirical formula of the MAO repeat unit is [AlO 0.75−0.8 Me 1.4−1.5 ] n , 5 while multinuclear NMR studies confirm the presence of tetrahedral AlMe groups and pyramidal O. 6 The X-ray structures of discrete tert-butylaluminoxanes (TBAO) reveal cages featuring tetrahedral Al and pyramidal O, and some of these were used to activate metallocene complexes for olefin polymerization. 7 Analogous cage structures for MAO are supported by theoretical studies, 2c,8 while much larger, symmetrical cages have been studied for the parent aluminoxane (HAlO) n , 9 and it has been shown recently that extended structures, such as nanotubes, are favored over cages for MAO compared with TBAO. 10 The TBAO cages are known to undergo cleavage, due to " latent Lewis acidity " or ring strain, 7 to afford contact ion pairs on reaction with metallocene complexes. In the case of MAO, similar behavior has been invoked, 2c,8 with formation of more dissociated ion pairs, at sufficiently high Al:M ratios. The latter findings are based on extensive solution NMR, UV−vis, and other spectroscopic studies of the metallocenium ions formed in situ from metallocene complexes and MAO. 3,11 The hydrodynamic radius (r h) and MW (molecular weight) of MAO, as well as the ion pairs formed from MAO and Cp 2 ZrMe 2 , have been estimated by a number of techniques. 12 Values of r h between 7.5 and 9.7 Å and MW values between 0.5 and 3.0 kg mol −1 have been reported for MAO at ambient temperature. A larger value of r h = 12−12.5 Å has been reported for ion pairs derived from MAO. 12a The various, and disparate, estimates of MW vs size can be reconciled if the shape of MAO oligomers and the ion pairs derived from this material are not spherical. 10a In particular, for rigid-rod molecules with one long axis, r h will approximate the length of this axis as the molecule randomly tumbles in solution, while MW scales with r h instead of r h 3. 13 What is required is a measurement of absolute MW for MAO or these ion pairs in solution to shed further light on this issue. Electrospray ionization mass spectrometry (ESI-MS) is an obvious choice for detection of ions in MAO solutions, at least in polar media, but few MS studies of MAO have been reported. 14 Repo and co-workers have reported detection of MAO using ESI-MS in THF and found that the positive ion spectra consisted of oxidized material. 15 Analysis of metal-locenium ions by ESI-MS, initially by Chen 16 and later by Metzger, 17 has shed light on the reactivity of the metal complex, but these studies were not concerned with the identity of the anionic components of MAO. We report here the first systematic, negative and positive ion studies of MAO by ESI-MS in fluorobenzene (PhF).

Dedicated to Professor Brian K. Nicholson on the occasion of his 65th birthday Aryl halide complexes of palladium are interesting because of their intermediacy in many palladium-catalyzed cross-coupling reactions. [1] Their reactivity towards reagents such as alkyne derivatives , carbon monoxide, and isocyanide to give new orga-nopalladium or organic compounds has been studied extensively. [2] Despite much effort having been expended on the synthesis and reactivity of these complexes, [3] less attention has been paid to the mechanism by which they are formed. For example, the preparation of [Pd(PPh 3) 2 (Ar)(I)] from [Pd-(tmeda)(Ar)(I)] (Ar = aryl ligand, tmeda = tetramethylethylenedi-amine) has been described as proceeding " by replacement of the chelating N N ligand by PPh 3 and an isomerization process that is probably promoted by the great transphobia of the Ph 3 P/Ar ligand pair ". [4] The trans effect of a ligand is a measure of its ability to labilize the ligand coordinated on the opposite side of the metal complex to itself, and is most obvious in square planar complexes. [5] Ph À is a strong trans-effect ligand, and amines exert a relatively weakly trans effect, so it is reasonable to expect that the tmeda (trans to the aryl group) is activated in preference to I À (trans to a nitrogen donor of tmeda). A high-yielding, convenient synthesis of [Pd(PR 3) 2 (Ar)(I)] complexes is the oxidative addition of an aryl iodide to [Pd 0 (dba) 2 ] in the presence of tmeda, and subsequent displacement of tmeda by two equivalents of phosphine (a reaction that works well for aryl iodides, but not for the other halides). [1] We wanted to use this reaction to make a charge-tagged version of [Pd(PR 3) 2 (Ar)(I)], where a positive charge was appended to the aryl group, because this species is an often-seen intermediate when following cross-coupling reactions using electrospray ionization mass spectrometry (ESI-MS). [6] ESI-MS is an increasingly popular method for studying organometallic and catalytic reactions, [7] and charge-tagging [8] enables this approach because ESI-MS detects only ions preformed in solution. Our recent introduction of pressurized sample infusion allows us to monitor reaction solutions in real time in a wide variety of solvents and at temperatures up to reflux, simultaneously generating dense data on the abundance of reactants, products, by-products, and intermediates. [9] The synthesis of the charge-tagged analogue itself presented an opportunity to study a ligand substitution reaction in detail, because both the precursor, [Pd(tmeda)(Ar)(I)] + (1, Ar= C 6 H 4 CH 2 PPh 3 + PF 6 À , see Figure 1 for structure) and product, [Pd(PPh 3) 2 (Ar)(I)] + (4), are themselves charged. We expected a slow displacement of one of the tmeda donors by PPh 3 , and subsequent rapid displacement of the other tmeda donor with a second molecule of PPh 3 , with any isomerization that might occur which is invisible to our methods (as it does not involve a mass change). However, when we examined the reaction using PSI-ESI-MS in positive and negative ion modes, it was evident that the reaction proceeded quite differently; there was a very fast displacement of I À by PPh 3 to form [Pd-(tmeda)(Ar)(PPh 3)] 2 + (2), followed by a much slower displacement of tmeda and recoordination of I À to form the product (4). The formation of 2 (and I À) from 1 is fast under these conditions , and is complete in less time than it takes for the solution to move from reaction flask to mass spectrometer (% 10 sec). The reaction proceeds despite the fact that complex 1 is already cationic by virtue of the charged tag. Identical chemistry occurs for the neutral complex [Pd(tmeda)(Ph)(I)], though only intermediate [Pd(tmeda)(Ph)(PPh 3)] + is visible by ESI-MS (see the Supporting Information). Lowering the temperature and Figure 1. Reaction progress in methanol at 55 8C, as measured by positive-ion (traces for blue 1, red 2, and green 4) and negative-ion mode (orange I À , from a duplicate experiment)